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1,100 | 29,876,876 | Conclusion Caffeine can be used effectively as an ergogenic aid when taken in moderate doses , such as during sports when a small increase in endurance performance can lead to significant differences in placements as athletes are often separated by small margins | Background Caffeine is a widely used ergogenic aid with most research suggesting it confers the greatest effects during endurance activities .
Despite the growing body of literature around the use of caffeine as an ergogenic aid , there are few recent meta-analyses that quantitatively assess the effect of caffeine on endurance exercise .
Objectives To summarise studies that have investigated the ergogenic effects of caffeine on endurance time-trial performance and to quantitatively analyse the results of these studies to gain a better underst and ing of the magnitude of the ergogenic effect of caffeine on endurance time-trial performance . | Caffeine , an adenosine receptor antagonist , has shown to improve performance in normal ambient temperature , presumably via an effect on dopaminergic neurotransmission through the antagonism of adenosine receptors . However , there is very limited evidence from studies that administered caffeine and examined its effects on exercise in the heat . Therefore , we wanted to study the effects of caffeine on performance and thermoregulation in high ambient temperature . Eight healthy trained male cyclists completed two experimental trials ( in 30 ° C ) in a double-blind-r and omized crossover design . Subjects ingested either placebo ( 6 mg/kg ) or caffeine ( 6 mg/kg ) 1 h prior to exercise . Subjects cycled for 60 min at 55 % Wmax , immediately followed by a time trial to measure performance . The significance level was set at p < 0.05 . Caffeine did not change performance ( p = 0.462 ) . Rectal temperature was significantly elevated after caffeine administration ( p < 0.036 ) . Caffeine significantly increased B-endorphin plasma concentrations at the end of the time trial ( p = 0.032 ) . The present study showed no ergogenic effect of caffeine when administered 1 h before exercise in 30 ° C . This confirms results from a previous study that examined the effects of caffeine administration on a short ( 15 min ) time trial in 40 ° C . However , caffeine increased core temperature during exercise . Presumably , the rate of increase in core temperature may have counteracted the ergogenic effects of caffeine . However , other factors such as interindividual differences in response to caffeine and changes in neurotransmitter concentrations might also be responsible for the lack of performance improvement of caffeine in high ambient temperature This study compared the effects of a single and divided dose of caffeine on endurance performance and on postexercise urinary caffeine and plasma paraxanthine concentrations . Nine male cyclists and triathletes cycled for 90 min at 68 % of maximal oxygen uptake , followed by a self-paced time trial ( work equivalent to 80 % of maximal oxygen uptake workload over 30 min ) with three r and omized , balanced , and double-blind interventions : 1 ) placebo 60 min before and 45 min into exercise ( PP ) ; 2 ) single caffeine dose ( 6 mg/kg ) 60 min before exercise and placebo 45 min into exercise ( CP ) ; and 3 ) divided caffeine dose ( 3 mg/kg ) 60 min before and 45 min into exercise ( CC ) . Time trial performance was unchanged with caffeine ingestion ( P = 0.08 ) , but it tended to be faster in the caffeine trials ( CP : 24.2 min and CC : 23.4 min ) compared with placebo ( PP : 28.3 min ) . Postexercise urinary caffeine concentration was significantly lower in CC ( 3.8 micro g/ml ) compared with CP ( 6.8 micro g/ml ) . Plasma paraxanthine increased in a dose-dependent fashion and did not peak during exercise . In conclusion , dividing a caffeine dose provides no ergogenic effect over a bolus dose but reduces postexercise urinary concentration AIM The purpose of this work was to determine the effects of caffeine ingestion on cycling time trial ( TT ) performance in well trained male subjects . METHODS Eight males , with the following physical characteristics ( Mean + /- SD ) age 30.2+/-10.1 years , height 180.3+/-7.1 cm , mass 70.4+/-5.1 kg , VO2max 63.6+/-4.4 mL.kg(-1).min(-1 ) undertook three 1 h TT performances on a VelotronPro cycle ergometer , in a double blind , r and om fashion . The trials were Control ( C ) , Placebo ( Pl ) and Caffeine ( CAF ) . The CAF and Pl were given 60 min prior to exercise in a dose of 6 mg.kg(-1 ) body mass . Prior to ingestion , 60 min post ingestion , and at the end of the TT , subjects gave 10 mL of venous blood which was analysed for lactate , glucose , and free fatty acids . Expired air was collected throughout each test by indirect calorimetry . RESULTS The cyclists rode significantly further in CAF trial ( 28.11+/-1.32 km ) than they did in the C ( 26.69+/-1.5 km , P < 0.03 ) or Pl ( 27.0+/-1.5 km , P < 0.03 ) trials . No significant differences were seen between C and Pl trials ( P > 0.88 ) . No differences between C and Pl were seen in heart rate data throughout the TT ( p > 0.05 ) . The free fatty acid ( FFA ) concentrations were significantly higher in the CAF trials both post ingestion ( P < 0.005 ) and post exercise ( P < 0.0001 ) than either C or Pl trials . CONCLUSION We concluded that performance was improved possibly based upon a greater reliance on fat metabolism , as indicated by increased FFA and a lower respiratory exchange ratio ( RER ) This study analyzed the effect of caffeine ingestion on performance during a repeated- measures , 100-km , laboratory cycling time trial that included bouts of 1- and 4-km high intensity epochs ( HIE ) . Eight highly trained cyclists participated in 3 separate trials ' placebo ingestion before exercise with a placebo carbohydrate solution and placebo tablets during exercise ( Pl ) , or placebo ingestion before exercise with a 7 % carbohydrate drink and placebo tablets during exercise ( Cho ) , or caffeine tablet ingestion before and during exercise with 7 % carbohydrate ( Caf ) . Placebo ( twice ) or 6 mg.kg(-1 ) caffeine was ingested 60 min prior to starting 1 of the 3 cycling trials , during which subjects ingested either additional placebos or a caffeine maintenance dose of 0.33 mg.kg(-1 ) every 15 min to trial completion . The 100-km time trial consisted of five 1-km HIE after 10 , 32 , 52 , 72 , and 99 km , as well as four 4-km HIE after 20 , 40 , 60 , and 80 km . Subjects were instructed to complete the time trial and all HIE as fast as possible . Plasma ( caffeine ) was significantly higher during Caf ( 0.43 + /- 0.56 and 1.11 + /- 1.78 mM pre vs. post Pl ; and 47.32 + /- 12.01 and 72.43 + /- 29.08 mM pre vs. post Caf ) . Average power , HIE time to completion , and 100-km time to completion were not different between trials . Mean heart rates during both the 1-km HIE ( 184.0 + /- 9.8 Caf ; 177.0 + /- 5.8 Pl ; 177.4 + /- 8.9 Cho ) and 4-km HIE ( 181.7 + /- 5.7 Caf ; 174.3 + /- 7.2 Pl ; 175.6 + /- 7.6 Cho ; p < .05 ) was higher in Caf than in the other groups . No significant differences were found between groups for either EMG amplitude ( IEMG ) or mean power frequency spectrum ( MPFS ) . IEMG activity and performance were not different between groups but were both higher in the 1-km HIE , indicating the absence of peripheral fatigue and the presence of a central ly-regulated pacing strategy that is not altered by caffeine ingestion . Caffeine may be without ergogenic benefit during endurance exercise in which the athlete begins exercise with a defined , predetermined goal measured as speed or distance Purpose Many studies have examined the effect of caffeine on exercise performance , but findings have not always been consistent . The objective of this study was to determine whether variation in the CYP1A2 gene , which affects caffeine metabolism , modifies the ergogenic effects of caffeine in a 10-km cycling time trial . Methods Competitive male athletes ( n = 101 ; age = 25 ± 4 yr ) completed the time trial under three conditions : 0 , 2 , or 4 mg of caffeine per kilogram body mass , using a split-plot r and omized , double-blinded , placebo-controlled design . DNA was isolated from saliva and genotyped for the −163A > C polymorphism in the CYP1A2 gene ( rs762551 ) . Results Overall , 4 mg·kg−1 caffeine decreased cycling time by 3 % ( mean ± SEM ) versus placebo ( 17.6 ± 0.1 vs 18.1 ± 0.1 min , P = 0.01 ) . However , a significant ( P < 0.0001 ) caffeine – gene interaction was observed . Among those with the AA genotype , cycling time decreased by 4.8 % at 2 mg·kg−1 ( 17.0 ± 0.3 vs 17.8 ± 0.4 min , P = 0.0005 ) and by 6.8 % at 4 mg·kg−1 ( 16.6 ± 0.3 vs 17.8 ± 0.4 min , P < 0.0001 ) . In those with the CC genotype , 4 mg·kg−1 increased cycling time by 13.7 % versus placebo ( 20.8 ± 0.8 vs 18.3 ± 0.5 min , P = 0.04 ) . No effects were observed among those with the AC genotype . Conclusion Our findings show that both 2 and 4 mg·kg−1 caffeine improve 10-km cycling time , but only in those with the AA genotype . Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg·kg−1 in those with the CC genotype . CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance PURPOSE To determine the effects of ingesting caffeine ( CAFF ) and sodium bicarbonate ( SB ) , taken individually and simultaneously , on 3-km cycling time-trial ( TT ) performance . METHOD Ten well-trained cyclists , age 24.2 ± 5.4 yr , participated in this acute-treatment , double-blind , crossover study that involved four 3-km cycling TTs performed on separate days . Before each TT , participants ingested either 3 mg/kg body mass ( BM ) of CAFF , 0.3 g · kg⁻¹ · BM⁻¹ of SB , a combination of the two ( CAFF+SB ) , or a placebo ( PLAC ) . They completed each 3-km TT on a laboratory-based cycle ergometer , during which physiological , perceptual , and performance measurements were determined . For statistical analysis , the minimal worthwhile difference was considered ~1 % based on previous research . RESULTS Pretrial pH and HCO₃ were higher in SB and CAFF+SB than in the CAFF and PLAC trials . Differences across treatments for perceived exertion and gastric discomfort were mostly unclear . Compared with PLAC , mean power output during the 3-km TT was higher in CAFF , SB , and CAFF+SB trials ( 2.4 % , 2.6 % , 2.7 % respectively ) , result ing in faster performance times ( -0.9 , -1.2 , -1.2 % respectively ) . Effect sizes for all trials were small ( 0.21 - 0.24 ) . CONCLUSIONS When ingested individually , both CAFF and SB enhance high-intensity cycling TT performance in trained cyclists . However , the ergogenic effect of these 2 popular supplements was not additive , bringing into question the efficacy of coingesting the 2 supplements before short- duration high-intensity exercise . In this study there were no negative effects of combining CAFF and SB , 2 relatively inexpensive and safe supplements BACKGROUND The ingestion of either caffeine ( C ) or ephedrine ( E ) has been shown to improve performance during high-intensity aerobic activity lasting 10 - 20 min , with an additive effect being found when the combination ( C + E ) was ingested . It was the purpose of this study to determine if the addition of E to C would improve performance in activity lasting longer than 20 min . METHODS One and one half hours after ingesting a placebo ( P ) , C ( 4 mg/kg ) , E ( 0.8 mg/kg ) , or C + E , 12 subjects performed a 10-km run while wearing a helmet and backpack weighing 11 kg . The trials were performed in a climatic suite at 12 - 13 degrees C , on a treadmill where the speed was regulated by the subject . VO(2 ) , VCO(2 ) , V(E ) , heart rate ( HR ) , and rating of perceived exertion ( RPE ) were measured during the run at 15 and 30 min , and again when the individual reached 9 km . Blood was sample d at 15 and 30 min and again at the end of the run and assayed for lactate , glucose , and catecholamines . RESULTS Run times ( mean + /- SD ) , in minutes , were for C ( 46.0 + /- 2.8 ) , E ( 45.5 + /- 2.9 ) , C + E ( 45.7 + /- 3.3 ) , and P ( 46.8 + /- 3.2 ) . The run times for the E trials ( E and C + E ) were significantly reduced compared with the non-E trials ( C and P ) . Pace was increased for the E trials compared with the non-E trials over the last 5 km of the run . VO(2 ) was not affected by drug ingestion . HR was elevated for the ephedrine trials ( E and C + E ) . RPE remained similar for all trails . Caffeine increased the epinephrine and norepinephrine response associated with exercise and also increased blood lactate , glucose , and glycerol levels . Ephedrine reduced the epinephrine response but increased dopamine and FFA levels . CONCLUSION The previously seen additive nature of E and C was not evident in this study , with the primary ergogenic effect being attributed to OBJECTIVES To investigate whether coinciding peak serum caffeine concentration with the onset of exercise enhances subsequent endurance performance . DESIGN R and omised , double-blind , crossover . METHODS In this r and omised , placebo-controlled , double-blind crossover study , 14 male trained cyclists and triathletes ( age 31±5year , body mass 75.4±5.7 kg , VO₂max 69.5±6.1 mL kg⁻¹ min⁻¹ and peak power output 417±35W , mean±SD ) consumed 6 mg kg(-1 ) caffeine or a placebo either 1h ( C(1h ) ) prior to completing a 40 km time trial or when the start of exercise coincided with individual peak serum caffeine concentrations ( C(peak ) ) . C(peak ) was determined from a separate ' caffeine profiling ' session that involved monitoring caffeine concentrations in the blood every 30 min over a 4h period . RESULTS Following caffeine ingestion , peak serum caffeine occurred 120 min in 12 participants and 150 min in 2 participants . Time to complete the 40 km time trial was significantly faster ( 2.0 % ; p=0.002 ) in C(1h ) compared to placebo . No statistically significant improvement in performance was noted in the C(peak ) trial versus placebo ( 1.1 % ; p=0.240 ) . Whilst no differences in metabolic markers were found between C(peak ) and placebo conditions , plasma concentrations of glucose ( p=0.005 ) , norepinephrine and epinephrine ( p≤0.002 ) were higher in the C(1h ) trial 6 min post-exercise versus placebo . CONCLUSIONS In contrast to coinciding peak serum caffeine concentration with exercise onset , caffeine consumed 60 min prior to exercise result ed in significant improvements in 40 km time trial performance . The ergogenic effect of caffeine was not found to be related to peak caffeine concentration in the blood at the onset of endurance exercise Background The objective of this study was to analyze the effect of caffeine ingestion on the performance and physiological variables associated with fatigue in 20-km cycling time trials . Methods In a double-blind placebo-controlled crossover study , 13 male cyclists ( 26–10 y , 71–9 kg , 176–6 cm ) were r and omized into 2 groups and received caffeine ( CAF ) capsules ( 6 mg.kg–1 ) or placebo ( PLA ) 60 min before performing 20-km time trials . Distance , speed , power , rpm , rating of perceived exertion ( RPE ) , electromyography ( EMG ) of the quadriceps muscles and heart rate ( HR ) were continuously measured during the tests . In addition , BRUMS question naire was applied before and after the tests . Results Significant interactions were found in power and speed ( P=0.001 ) , which were significantly higher at the end of the test ( final 2 km ) after CAF condition . A main effect of time ( P=0.001 ) was observed for RPE and HR , which increased linearly until the end of exercise in both conditions . The time taken to complete the test was similar in both conditions ( PLA=2191–158 s vs. CAF=2181–194 s , P=0.61 ) . No significant differences between CAF and PLA conditions were identified for speed , power , rpm , RPE , EMG , HR , and BRUMS ( P>0.05 ) . Conclusion The results suggest that caffeine intake 60 min before 20-km time trials has no effect on the performance or physiological responses of cyclists Background The purpose of this study was to examine the ergogenic benefits of Turkish coffee consumed an hour before exercise . In addition , metabolic , cardiovascular , and subjective measures of energy , focus and alertness were examined in healthy , recreationally active adults who were regular caffeine consumers ( > 200 mg per day ) . Methods Twenty males ( n = 10 ) and females ( n = 10 ) , age 24.1 ± 2.9 y ; height 1.70 ± 0.09 m ; body mass 73.0 ± 13.0 kg ( mean ± SD ) , ingested both Turkish coffee [ 3 mg · kg−1 BW of caffeine , ( TC ) ] , and decaffeinated Turkish coffee ( DC ) in a double-blind , r and omized , cross-over design . Performance measures included a 5 km time trial , upper and lower body reaction to visual stimuli , and multiple object tracking . Plasma caffeine concentrations , blood pressure ( BP ) , heart rate and subjective measures of energy , focus and alertness were assessed at baseline ( BL ) , 30-min following coffee ingestion ( 30 + ) , prior to endurance exercise ( PRE ) and immediately-post 5 km ( IP ) . Metabolic measures [ VO2 , VE , and respiratory exchange rate ( RER ) ] were measured during the 5 km . Results Plasma caffeine concentrations were significantly greater during TC ( p < 0.001 ) at 30 + , PRE , and IP compared to DC . Significantly higher energy levels were reported at 30 + and PRE for TC compared to DC . Upper body reaction performance ( p = 0.023 ) and RER ( p = 0.019 ) were significantly higher for TC ( 85.1 ± 11.6 “ hits , ” and 0.98 ± 0.05 respectively ) compared to DC ( 81.2 ± 13.7 “ hits , ” and 0.96 ± 0.05 , respectively ) . Although no significant differences ( p = 0.192 ) were observed in 5 km run time , 12 of the 20 subjects ran faster ( p = 0.012 ) during TC ( 1662 ± 252 s ) compared to DC ( 1743 ± 296 s ) . Systolic BP was significantly elevated during TC in comparison to DC . No other differences ( p > 0.05 ) were noted in any of the other performance or metabolic measures . Conclusions Acute ingestion of TC result ed in a significant elevation in plasma caffeine concentrations within 30-min of consumption . TC ingestion result ed in significant performance benefits in reaction time and an increase in subjective feelings of energy in habitual caffeine users . No significant differences were noted in time for the 5 km between trials , however 60 % of the participants performed the 5 km faster during the TC trial and were deemed responders . When comparing TC to DC in responders only , significantly faster times were noted when consuming TC compared to DC . No significant benefits were noted in measures of cognitive function Caffeine ( CAF ) ingestion may enhance endurance exercise by lowering perceived exertion ( RPE ) and muscle pain . However , exercise in the heat may be detrimental to performance by increasing RPE and pain . The purpose of this study was to examine if caffeine affects pain and related perceptual responses differently in cool and hot ambient conditions . Eleven male cyclists ( mean ± SD ; age , 25 ± 6 years ; mass , 72.6 ± 8.1 kg ; VO(2max ) , 58.7 ± 2.9 ml kg(-1 ) min(-1 ) ) completed four trials in a r and omized , double blind design . While remaining euhydrated , subjects cycled for 90 min at 65 ± 7 % VO(2max ) followed by a 15-min performance trial . Subjects ingested 3 mg kg(-1 ) of encapsulated caffeine ( CAF ) or placebo ( PLA ) 60 min before and 45 after beginning exercise in 12 ° C and 33 ° C ( i.e. , 12-CAF , 33-CAF , 12-PLA , and 33-PLA trials ) . Central , local , and overall perceived exertion ( C- , L- , and O-RPE ) and pain were measured throughout exercise . Throughout submaximal exercise C- , L- , and O-RPE were significantly greater in 33 ° C ( P<0.05 ) but were not affected by CAF ( P>0.05 ) . Using area-under-the-curve analysis , pain in 33-PLA was increased by 74 % vs 12-PLA ( P<0.05 ) . CAF did not reduce pain in 12 ° C ( P=0.542 ) , but in 33 ° C , CAF reduced pain by 27 % ( P=0.032 ) . Despite this apparent advantage , CAF improved performance independent of ambient temperature ( i.e. , non-significant interaction ; P=0.662 ) . This study found that , although caffeine improves exercise capacity , its effect on leg muscle pain is dependent on ambient temperature . Although exercise in the heat increases muscle pain compared to a cooler environment , caffeine reduces this pain Purpose In athletes , caffeine use is common although its effects on sleep have not been widely studied . This r and omised , double-blind , placebo-controlled crossover trial investigated the effects of late-afternoon caffeine and carbohydrate-electrolyte ( CEB ) co-ingestion on cycling performance and nocturnal sleep . Methods Six male cyclists/triathletes ( age 27.5 ± 6.9 years ) completed an afternoon training session ( TS ; cycling 80 min ; 65 % VO2max ) followed by a 5 kJ kg−1 cycling time trial ( TT ) . Caffeine ( split dose 2 × 3 mg kg−1 ) or placebo was administered 1 h prior and 40 min into the TS . A 7.4 % CEB ( 3 ml kg−1 every 15 min ) was administered during the TS , followed 30 min after by a st and ardised evening meal . Participants retired at their usual bedtime and indices of sleep duration and quality were monitored via polysomnography . Data : mean ± SD . Results All participants performed better in the caffeine TT ( caffeine 19.7 ± 3.3 ; placebo 20.5 ± 3.5 min ; p = 0.006 ) , while ratings of perceived exertion ( caffeine 12.0 ± 0.6 ; placebo 12.9 ± 0.7 ; p = 0.004 ) and heart rate ( caffeine 175 ± 6 ; placebo 167 ± 11 bpm ; p = 0.085 ) were lower in the caffeine TS . Caffeine intake induced significant disruptions to a number of sleep indices including increased sleep onset latency ( caffeine 51.1 ± 34.7 ; placebo 10.2 ± 4.2 min ; p = 0.028 ) and decreased sleep efficiency ( caffeine 76.1 ± 19.6 ; placebo 91.5 ± 4.2 % ; p = 0.028 ) , rapid eye movement sleep ( caffeine 62.1 ± 19.6 ; placebo 85.8 ± 24.7 min ; p = 0.028 ) and total sleep time ( caffeine 391 ± 97 ; placebo 464 ± 49 min ; p = 0.028 ) . Conclusions This study supports a performance-enhancing effect of caffeine , although athletes ( especially those using caffeine for late-afternoon/evening training and competition ) should consider its deleterious effects on sleep The purpose of the present study was to investigate the effects of caffeine ingestion on pacing strategy and energy expenditure during a 4000-m cycling time-trial ( TT ) . Eight recreationally-trained male cyclists volunteered and performed a maximal incremental test and a familiarization test on their first and second visits , respectively . On the third and fourth visits , the participants performed a 4000-m cycling TT after ingesting capsules containing either caffeine ( 5 mg.kg−1 of body weight , CAF ) or cellulose ( PLA ) . The tests were applied in a double-blind , r and omized , repeated- measures , cross-over design . When compared to PLA , CAF ingestion increased mean power output [ 219.1±18.6 vs. 232.8±21.4 W ; effect size ( ES ) = 0.60 ( 95 % CI = 0.05 to 1.16 ) , p = 0.034 ] and reduced the total time [ 419±13 vs. 409±12 s ; ES = −0.71 ( 95 % CI = −0.09 to −1.13 ) , p = 0.026 ] . Furthermore , anaerobic contribution during the 2200- , 2400- , and 2600-m intervals was significantly greater in CAF than in PLA ( p<0.05 ) . However , the mean anaerobic [ 64.9±20.1 vs. 57.3±17.5 W ] and aerobic [ 167.9±4.3 vs. 161.8±11.2 W ] contributions were similar between conditions ( p>0.05 ) . Similarly , there were no significant differences between CAF and PLA for anaerobic work ( 26363±7361 vs. 23888±6795 J ) , aerobic work ( 68709±2118 vs. 67739±3912 J ) , or total work ( 95245±8593 vs. 91789±7709 J ) , respectively . There was no difference for integrated electromyography , blood lactate concentration , heart rate , and ratings of perceived exertion between the conditions . These results suggest that caffeine increases the anaerobic contribution in the middle of the time trial , result ing in enhanced overall performance Abstract There is little published data in relation to the effects of caffeine upon cycling performance , speed and power in trained cyclists , especially during cycling of ∼60 s duration . To address this , eight trained cyclists performed a 1 km time-trial on an electronically braked cycle ergometer under three conditions : after ingestion of 5 mg · kg−1 caffeine , after ingestion of a placebo , or a control condition . The three time-trials were performed in a r and omized order and performance time , mean speed , mean power and peak power were determined . Caffeine ingestion result ed in improved performance time ( caffeine vs. placebo vs. control : 71.1 ± 2.0 vs. 73.4 ± 2.3 vs. 73.3 ± 2.7 s ; P = 0.02 ; mean ± s ) . This change represented a 3.1 % ( 95 % confidence interval : 0.7–5.6 ) improvement compared with the placebo condition . Mean speed was also higher in the caffeine than placebo and control conditions ( caffeine vs. placebo vs. control : 50.7 ± 1.4 vs. 49.1 ± 1.5 vs. 49.2 ± 1.7 km · h−1 ; P = 0.0005 ) . Mean power increased after caffeine ingestion ( caffeine vs. placebo vs. control : 523 ± 43 vs. 505 ± 46 vs. 504 ± 38 W ; P = 0.007 ) . Peak power also increased from 864 ± 107 W ( placebo ) and 830 ± 87 W ( control ) to 940 ± 83 W after caffeine ingestion ( P = 0.027 ) . These results provide support for previous research that found improved performance after caffeine ingestion during short- duration high-intensity exercise . The magnitude of the improvements observed in our study could be due to our use of sport-specific ergometry , a tablet form and trained participants Abstract It is not known if ergogenic effects of caffeine ingestion in athletic groups occur in the sedentary . To investigate this , we used a counterbalanced , double-blind , crossover design to examine the effects of caffeine ingestion ( 6 mg · kg−1 body-mass ) on exercise performance , substrate utilisation and perceived exertion during 30 minutes of self-paced stationary cycling in sedentary men . Participants performed two trials , one week apart , after ingestion of either caffeine or placebo one hour before exercise . Participants were instructed to cycle as quickly as they could during each trial . External work ( J · kg−1 ) after caffeine ingestion was greater than after placebo ( P = 0.001 , effect size [ ES ] = 0.3 ) . Further , heart rate , oxygen uptake and energy expenditure during exercise were greater after caffeine ingestion ( P = 0.031 , ES = 0.4 ; P = 0.009 , ES = 0.3 and P = 0.018 , ES = 0.3 ; respectively ) , whereas ratings of perceived exertion and respiratory exchange ratio values did not differ between trials ( P = 0.877 , ES = 0.1 ; P = 0.760 , ES = 0.1 ; respectively ) . The ability to do more exercise after caffeine ingestion , without an accompanying increase in effort sensation , could motivate sedentary men to participate in exercise more often and so reduce adverse effects of inactivity on health This study investigated the ergogenic effects of a commercial energy drink ( Red Bull ) or an equivalent dose of anhydrous caffeine in comparison with a noncaffeinated control beverage on cycling performance . Eleven trained male cyclists ( 31.7 ± 5.9 y 82.3 ± 6.1 kg , VO2max = 60.3 ± 7.8 mL · kg-1 · min-1 ) participated in a double-blind , placebo-controlled , crossover- design study involving 3 experimental conditions . Participants were r and omly administered Red Bull ( 9.4 mL/kg body mass [ BM ] containing 3 mg/kg BM caffeine ) , anhydrous caffeine ( 3 mg/kg BM given in capsule form ) , or a placebo 90 min before commencing a time trial equivalent to 1 h cycling at 75 % peak power output . Carbohydrate and fluid volumes were matched across all trials . Performance improved by 109 ± 153 s ( 2.8 % , P = .039 ) after Red Bull compared with placebo and by 120 ± 172 s ( 3.1 % , P = .043 ) after caffeine compared with placebo . No significant difference ( P > .05 ) in performance time was detected between Red Bull and caffeine treatments . There was no significant difference ( P > .05 ) in mean heart rate or rating of perceived exertion among the 3 treatments . This study demonstrated that a moderate dose of caffeine consumed as either Red Bull or in anhydrous form enhanced cycling time-trial performance . The ergogenic benefits of Red Bull energy drink are therefore most likely due to the effects of caffeine , with the other ingredients not likely to offer additional benefit PURPOSE To determine whether a dose-response relationship exists between caffeine and 2000-m rowing performance . METHODS In this r and omized , placebo-controlled , double-blind crossover study , 10 competitive male rowers ( mean + /- SD : age = 20.6 + /- 1.4 yr , body mass = 87.7 + /- 10.5 kg , height = 186.8 + /- 6.8 cm , (.)VO2peak = 5.1 + /- 0.6 L x min(-1 ) ) consumed 2 , 4 , or 6 mg x kg(-1 ) caffeine or a placebo 60 min before completing a 2000-m time trial on a rowing ergometer . The trials were preceded by a 24-h st and ardized diet ( including a light preexercise meal of 2 g x kg(-1 ) CHO ) , and subjects were tested preexercise for hydration , caffeine abstinence , and blood glucose concentrations . RESULTS Time trial performance was not significantly different across the three caffeine doses or placebo ( P = 0.249 ) . After the three caffeine trials , postexercise plasma glucose and lactate concentrations were higher compared with the placebo trial ( P < 0.05 ) . Plasma caffeine concentrations after 60 min of ingestion were lower than the values reported previously by others following the same dose , and there was considerable interindividual variation in plasma caffeine concentrations in response to the various caffeine doses . CONCLUSIONS The large interindividual response to the caffeine doses suggests that individual characteristics need to be considered when administering caffeine for performance enhancement . In addition , preexercise feeding may significantly affect plasma caffeine concentrations and the potential for caffeine to improve performance PURPOSE To investigate the effect of caffeine ingestion on short-term endurance performance in competitive rowers . METHODS In this r and omized double-blind crossover study , eight competitive oarsmen ( peak oxygen uptake [ VO2peak ] 4.7+/-0.4 L x min(-1 ) , mean + /- SD ) performed three familiarization trials of a 2000-m rowing test on an air-braked ergometer , followed by three experimental trials at 3- to 7-d intervals , each 1 h after ingesting caffeine ( 6 or 9 mg x kg(-1 ) body mass ) or placebo . Trials were preceded by a st and ardized warm-up ( 6 min at 225+/-39 W ; 75+/-7.7 % VO2peak ) . RESULTS Urinary caffeine concentration was similar before ingestion ( approximately 1 mg x L(-1 ) ) but rose to 6.2+/-3.6 and 14.5+/-7.0 mg x L(-1 ) for the low and high caffeine doses , respectively . Plasma free fatty acid concentration before exercise was higher after caffeine ingestion ( 0.29+/-0.17 and 0.39+/-0.20 mM for 6 and 9 mg x kg(-1 ) , respectively ) than after placebo ( 0.13+/-0.05 mM ) . Respiratory exchange ratio during the warm-up was also substantially lower with caffeine ( 0.94+/-0.09 and 0.93+/-0.06 for the low and high dose ) than with placebo ( 0.98+/-0.12 ) . Subjects could not distinguish between treatments before or after the exercise test . Both doses of caffeine had a similar ergogenic effect relative to placebo : performance time decreased by a mean of 1.2 % ( 95 % likely range 0.4 - 1.9 % ) ; the corresponding increase in mean power was 2.7 % ( 0.4 - 5.0 % ) . Performance time showed some evidence of individual differences in the effect of caffeine ( SD 0.9 % ; 95 % likely range 1.5 to -0.9 % ) . CONCLUSIONS Ingestion of 6 or 9 mg x kg(-1 ) of caffeine produces a worthwhile enhancement of short-term endurance performance in a controlled laboratory setting It is well established that caffeine ingestion during exercise enhances endurance performance . Conversely , the physiological and psychological strain that accompanies increased ambient temperature decreases endurance performance . Little is known about the interaction between environmental temperature and the effects of caffeine on performance . The purpose of this study was to compare the effects of ambient temperature ( 12 and 33 ° C ) on caffeine ergogenicity during endurance cycling exercise . Eleven male cyclists ( mean ± SD ; age , 25 ± 6 years ; $ $ { \dot V \text{O}}_{2\max } , $ $ 58.7 ± 2.9 ml kg−1 min−1 ) completed four exercise trials in a r and omized , double blind experimental design . After cycling continuously for 90 min ( average 65 ± 7 % $ $ { \dot V \text{O}}_{2\max } $ $ ) in either a warm ( 33 ± 1 ° C , 41 ± 5%rh ) or cool ( 12 ± 1 ° C , 60 ± 7%rh ) environment , subjects completed a 15-min performance trial ( PT ; based on total work accumulated ) . Subjects ingested 3 mg kg−1 of encapsulated caffeine ( CAF ) or placebo ( PLA ) 60 min prior to and after 45 min of exercise . Throughout exercise , subjects ingested water so that at the end of exercise , independent of ambient temperature , their body mass was reduced 0.55 ± 0.67 % . Two-way ( temperature × treatment ) repeated- measures ANOVA were conducted with alpha set at 0.05 . Total work ( kJ ) during the PT was greater in 12 ° C than 33 ° C [ P < 0.001 , η2 = 0.804 , confidence interval ( CI ) : 30.51–62.30 ] . When pooled , CAF increased performance versus PLA independent of temperature ( P = 0.006 , η2 = 0.542 CI : 3.60–16.86 ) . However , performance differences with CAF were not dependent on ambient temperature ( i.e. , non-significant interaction ; P = 0.662 ) . CAF versus PLA in 12 and 33 ° C result ed in few differences in other physiological variables . However , during exercise , rectal temperature ( Tre ) increased in the warm environment ( peak Tre ; 33 ° C , 39.40 ± 0.45 ; 12 ° C , 38.79 ± 0.42 ° C ; P < 0.05 ) but was not different in CAF versus PLA ( P > 0.05 ) . Increased ambient temperature had a detrimental effect on cycling performance in both the CAF and PLA conditions . CAF improved performance independent of environmental temperature . These findings suggest that caffeine at the dosage utilized ( 6 mg/kg body mass ) is a , legal drug that provides an ergogenic benefit in 12 and 33 ° C PURPOSE Caffeine ( CAF ) improves performance in both short- and long- duration running and cycling where performance relies on power output and endurance capacity of leg muscles . No studies have so far tested the effects of CAF while using the double-poling ( DP ) technique in cross-country skiing . When using the DP technique , arm muscles provide the speed-generating force and therefore play an important role in performance outcome . The metabolism of arm muscles differs from that of leg muscles . Thus , results from studies on leg muscles and CAF may not be directly applicable to exercises while using the DP technique in cross-country skiing . The purpose of our study was therefore to investigate the effects of CAF on exercise performance in DP . METHOD Ten highly trained male cross-country skiers ( V·O 2max running , 69.3 ± 1.0 mL · kg · min(-1 ) ) performed a placebo ( PLA ) and CAF trial using a r and omized , double-blind , crossover design . Performance was assessed by measuring the time to complete an 8-km cross-country DP performance test ( C-PT ) . CAF ( 6 mg · kg(-1 ) ) or PLA was ingested 75 min before the C-PT . RESULTS CAF ingestion reduced the time to complete the 8-km C-PT from 34:26 ± 1:25 to 33:01 ± 1:24 min ( P < 0.05 ) . The subjects maintained higher speed and HR throughout the C-PT , and lactate was higher immediately after the C-PT with CAF exposure compared with PLA . Subjects reported lower RPE at submaximal intensities during CAF compared with PLA , although HR was similar . CONCLUSION CAF intake enhances endurance performance in an 8-km C-PT , where arm muscles limit performance . CAF ingestion allowed the participants to exercise with a higher HR and work intensity possibly by reducing perception of effort or facilitating motor unit recruitment A hot and humid environment can be detrimental to race performance . Caffeine , on the other h and , has been shown to be an ergogenic aid for improving endurance performance . To examine the influence of caffeine ingestion on race performance during high heat stress , seven endurance trained competitive road racers aged between 23 and 51 years ( five men , two women ) performed three maximal effort 21-km road races outdoors in hot and humid conditions . The caffeine dose , r and omly assigned in a double-blind fashion , consisted of either 0 , 5 , or 9 mg · kg−1 body mass . During each run , the subjects were allowed to drink waterad libitum at each 5-km point . Blood sample s were obtained immediately before and after each run and analysed for changes in concentrations of Na+ , K+ , glucose , lactate , and hematocrit . Pre and postrun data were also collected for body mass and tympanic membrane temperature . Race times were not significantly different among the races or caffeine doses , with the average times within 1.1 % of each other . In addition , none of the other variables measured varied significantly among the races or caffeine doses . In summary , caffeine intake did not affect race performance . Therefore it was concluded from our study that caffeine is not of ergogenic benefit in endurance races during high heat stress The purpose of this study was to evaluate the potential ergogenic benefit of caffeine in the performance of a 1,500-meter swim . Caffeine ( 6 mg.kg-1 ) or placebo was administered 2 - 1/2 hrs prior to the swim trial in a double-blind crossover design . Caffeine result ed in a significantly lower perceived exertion for 100-m warm-up swims . Subjects swam significantly ( p < 0.05 ) faster with caffeine ( 20:58.8 + /- 0:36.4 , mean + /- SEM ) than without ( 21:21.8 + /- 0:38 ) . Plasma potassium was significantly lower prior to the swim with caffeine , and blood glucose was higher after that swim . Caffeine provides an ergogenic benefit for a 1,500-meter swim , an event that is completed in less than 25 min . Lower plasma potassium concentration prior to exercise and higher blood glucose following the trial suggest that electrolyte balance and glucose availability may be important aspects of the ergogenic effects of caffeine The purpose of this study was to investigate if caffeine ingestion improves 5-km time-trial performance in well-trained and recreational runners . Using a double-blind placebo-controlled design , 15 well-trained and 15 recreational runners completed two r and omized 5-km time-trials , after ingestion of either 5mgkg(-1 ) of caffeine or a placebo . Caffeine ingestion significantly improved 5-km running performance in both the well-trained and recreational runners . In comparison to the placebo trial , the caffeine trial result ed in 1.1 % ( 90 % CI 0.4 - 1.6 ) and 1.0 % ( 0.2 - 2 % ) faster times for the well-trained and recreational runners . Reliability testing of the recreational runners indicated a test-retest error of measurement of 1.4 % . We conclude that caffeine ingestion is likely to produce small but significant gains in 5-km running performance for both well-trained and recreational runners 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 . There is limited research on the physiological effects of caffeine ( CAF ) ingestion on exercise performance during acute hypoxia . The aim of the present study was therefore to test the effect of placebo ( PLA ) and CAF ( 4.5 mg/kg ) on double poling ( DP ) performance during acute hypoxia . Thirteen male subelite cross-country skiers ( V̇o2max 72.6 ± 5.68 ml·kg(-1)·min(-1 ) ) were included . Performance was assessed as 1 ) an 8-km cross-country DP time-trial ( C-PT ) , and 2 ) time until task failure at a set workload equal to ∼90 % of DP V̇o2max . Testing was carried out in a hypobaric chamber , at 800 mbar ( Pio2 : ∼125 mmHg ) corresponding to ∼2,000 m above sea level in a r and omized double-blinded , placebo-controlled , cross-over design . CAF improved time to task failure from 6.10 ± 1.40 to 7.22 ± 1.30 min ( P < 0.05 ) and velocity the first 4 km ( P < 0.05 ) but not overall time usage for the 8-km C-PT . During submaximal exercise subjects reported lower pain in arms and rate of perceived exertion ( RPE ) following CAF ingestion . Throughout C-PTs similar RPE and pain was shown between treatments . However , higher heart rate was observed during the CAF 8 km ( 187 ± 7 vs. 185 ± 7 ; P < 0.05 ) and 90 % C-PT ( 185 ± 7 vs. 181 ± 9 ) associated with increased ventilation , blood lactate , glucose , adrenaline , decreased pH , and bicarbonate . The present study demonstrates for the first time that CAF ingestion improves DP time to task failure although not consistently time trial performance during acute exposure to altitude . Mechanisms underpinning improvements seem related to reduced pain RPE and increased heart rate during CAF C-PTs OBJECTIVE The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation . METHODS This was a double blind , parallel , r and omized , seven treatment study . The treatment groups were : 50 , 100 , and 200 mg gum , 50 , 100 , and 200 mg capsule , and a placebo . Subjects consisted of 84 ( n=12 per group ) ; healthy , non-smoking , males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were r and omly assigned to the treatment groups . Blood sample s were collected pre-dose and at 5 , 15 , 25 , 35 , 45 , 55 , 65 , 90 min and 2 , 3 , 4 , 6 , 8 , 12 , 16 and 29 h post administration . Plasma caffeine levels were analyzed by a vali date d UV-HPLC method . RESULTS Mean Tmax for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0 - 120.0 min for the capsule groups . The Tmax , for the pooled data was significantly lower ( P<0.05 ) for the gum groups as compared with the capsule groups . Differences in Tmax were significant for the 200 mg capsule versus 200 mg gum ( P<0.05 ) . The mean ka values for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged from 1.29 to 2.36 h-1 . Relative bioavailability of the gum formulation after the 50 , 100 and 200 mg dose was 64 , 74 and 77 % , respectively . When normalized to the total drug released from the gum ( 85 % ) , the relative bioavailability of the 50 , 100 and 200 mg dose were 75 , 87 , and 90 % , respectively . No statistical differences were found for Cmax and AUCinf for comparisons of the gum and capsule formulations at each dose . Within each dose level , there were no significant formulation related differences in Cmax . No significant differences were observed in the elimination of caffeine after the gum or capsule . CONCLUSIONS The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa . In addition , for the 100 and 200 mg groups , the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation . These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation , which is advantageous in situations where the rapid reversal of alertness and performance deficits result ing from sleep loss is desirable The primary aim of this study was to determine the repeatability of caffeine 's ergogenic effects on cycling performance . It was hypothesized that improvements in performance would be similar when caffeine was ingested on 2 separate days . Nine endurance-trained men and women ( mean age and maximal oxygen uptake , 27.4 ± 5.9 years and 57.5 ± 3.9 mL kg⁻¹ min⁻¹ ) initially completed 2 familiarization trials . During 3 subsequent sessions separated by at least 48 hours , the subjects completed a 10-km cycling time trial preceded by ingestion of a drink containing caffeine ( 5 mg/kg ) or placebo . Treatments were ingested using a r and omized , single-blind , crossover design , and the subjects were deceived as to the specific content of all drinks . During exercise , heart rate , rating of perceived exertion , and time were recorded every 1.6 km . Repeated- measures analysis of variance was used to compare the differences in variables across distance and treatment . In both caffeine trials , caffeine increased ( P = .02 ) cycling performance by 1.6 % and 1.9 % vs placebo ( 16.98 ± 0.96 and 16.92 ± 0.97 minutes with caffeine vs 17.25 ± 0.96 minutes in placebo ) , and 7 of 9 subjects revealed improved performance . The mean performance improvement in the caffeine trials was similar ( P = .35 ; -0.27 and -0.32 minutes , respectively ) across days . Heart rate during exercise was higher ( P b .001 ) with caffeine vs placebo , although the rating of perceived exertion was similar ( P = .65 ) . Data reveal that caffeine 's ergogenic effects on cycling performance are repeatable across days , yet some individuals did not exhibit improved performance with caffeine This study examined the ergogenic effects in a 6 min maximal performance test ( PT ) on 12 elite rowers : 6 open-weight ( mean ± SD ; 25 ± 1 years , and 92 ± 3 kg ) and 6 light-weight ( 25 ± 3 years , and 73 ± 6 kg ) , following supplementation with caffeine ( CAF ) , sodium bicarbonate ( SB ) , and the combination of both , in a double-blind r and omized placebo ( PLA ) controlled design . PT was executed on 4 occasions , on separate days within a week , and in a non-fasted state , with st and ardized training being performed the day before PT . Protocol s were as follows : ( i ) CAF , 3 mg/kg , 45 min prior to PT + calcium as SB-PLA ; ( ii ) SB , 0.3 g/kg , 75 min prior to PT + dextrose as CAF-PLA ; ( iii ) CAF + SB ; and ( iv ) PLA ; CAF-PLA + SB-PLA . The total distance in the CAF ( 1878 ± 97 m ) and CAF + SB ( 1877 ± 97 m ) was longer than in the PLA ( 1865 ± 104 m ; P < 0.05 ) and SB ( 1860 ± 96 m ; P < 0.01 ) . The mean power in CAF ( 400 ± 58 W ) and CAF + SB ( 400 ± 58 W ) was higher than the PLA ( 393 ± 61 W ; P < 0.05 ) and SB ( 389 ± 57 W ; P < 0.01 ) . In CAF and CAF + SB , power was higher ( P < 0.05 ) relative to PLA in the last half ( 4 - 6 min ) of PT . Trials with CAF were more effective in light-weight rowers ( 1.0 % ± 0.8 % improvement in distance ; P < 0.05 ) than in open-weight rowers ( 0.3 % ± 0.8 % ; P > 0.05 ) . No difference between interventions was observed for readiness and stomach comfort before PT and perceived exertion during PT . This study demonstrates that caffeine ingestion does improve performance in elite rowing . In contrast sodium bicarbonate does not appear to be ergogenic , but it does not abolish the ergogenic effect of caffeine The ergogenic effect of caffeine on endurance exercise is commonly accepted . We aim ed to eluci date realistically the effect of caffeine on triathlon event performance using a field study design , while allowing investigation into potential mechanisms at play . A double-blind , r and omized , crossover field trial was conducted . Twenty-six triathletes ( 14 males and 12 females ; mean ± SD : age = 37.8 ± 10.6 years , habitual caffeine intake = 413 ± 505 mg/day , percentage body fat = 14.5 ± 7.2 % , and training/week = 12.8 ± 4.5 hr ) participated in this study . Microencapsulated caffeine ( 6 mg/kg body weight ) was supplemented 60 min pretrial . Performance data included time to completion , rating of perceived exertion , and profile of mood states . Blood sample s taken before , during , and postrace were analyzed for cortisol , testosterone , and full blood count . Capillary blood lactate concentrations were assessed prerace , during transitions , and 3 , 6 , 9 , 12 , and 15 min after triathlons . Caffeine supplementation result ed in a 3.7 % reduction in swim time ( 33.5 ± 7.0 vs. 34.8 ± 8.1 min , p < .05 ) and a 1.3 % reduction in time to completion ( 149.6 ± 19.8 vs. 151.5 ± 18.6 min , p < .05 ) for the whole group . Gender differences and individual responses are also presented . Caffeine did not alter the rating of perceived exertion significantly , but better performance after caffeine supplementation suggests a central effect result ing in greater overall exercise intensity at the same rating of perceived exertion . Caffeine supplementation was associated with higher postexercise cortisol levels ( 665 ± 200 vs. 543 ± 169 nmol/L , p < .0001 ) and facilitated greater peak blood lactate accumulation ( analysis of variance main effect , p < .05 ) . We recommend that triathlon athletes with relatively low habitual caffeine intake may ingest 6 mg/kg body weight caffeine , 45 - 60 min before the start of Olympic-distance triathlon to improve their performance Gastrointestinal ( GI ) complaints are frequently experienced during running . Sports drinks to prevent dehydration and hypoglycemia during exercise are generally used . The aim was to investigate the effect of 3 different drinks on GI complaints and performance during competitive running in a controlled field study . Ninety-eight well-trained subjects ( 90 M , 8 F , age 41 + /- 8 y ) performed a competitive 18-km run three times within 8 days . The study was a controlled , st and ardized field experiment following a r and omized , crossover design . Three different drinks were compared : water , a sports drink ( CES ) , and a sports drink with added 150 mg/l caffeine ( CAF ) . The incidence of GI complaints and the effect of the drinks on performance was studied . Each subject consumed 4 times 150 ml as follows : at the start , after 4.5 km , 9 km , and 13.5 km . Fluid intake was controlled . Incidence and intensity of GI complaints during the run were determined using a 10 points scale question naire . There were no significant differences in performance between the 3 drinks . Run time ( 18 km , mean + /- SD ) : WAT 1 : 18 : 03 + /- 08 : 30 , CES 1 : 18 : 23 + /- 08 : 47 , CAF 1 : 18 : 03 + /- 08 : 42 . The use of carbohydrate-containing sports drinks led to higher incidences of all types of GI complaints compared to water . Significant differences ( p < 0.05 ) were reached for flatulence ; incidence : WAT 17.9 % , CES 28.6 % , CAF 30.6 % , and reflux ; incidence : WAT 55.7 % , CES 78.6 % , CAF 72.5 % . There were no significant differences in intensity of the GI complaints . Addition of caffeine to CES had no effect on GI complaints , compared to CES alone . We conclude that sports drinks used during an 18-km run in cool environmental conditions do not support the performance better than mineral water . The use of sports drinks during an 18-km run leads to a higher incidence of both upper and lower GI complaints compared to water . Addition of caffeine to the sports drink has no effect on either running performance or GI complaints Abstract Glaister , M , Pattison , JR , Muniz-Pumares , D , Patterson , SD , and Foley , P. Effects of dietary nitrate , caffeine , and their combination on 20-km cycling time trial performance . J Strength Cond Res 29(1 ) : 165–174 , 2015—The aim of this study was to examine the acute supplementation effects of dietary nitrate , caffeine , and their combination on 20-km cycling time trial performance . Using a r and omized , counterbalanced , double-blind Latin-square design , 14 competitive female cyclists ( age : 31 ± 7 years ; height : 1.69 ± 0.07 m ; body mass : 61.6 ± 6.0 kg ) completed four 20-km time trials on a racing bicycle fitted to a turbo trainer . Approximately 2.5 hours before each trial , subjects consumed a 70-ml dose of concentrated beetroot juice containing either 0.45 g of dietary nitrate or with the nitrate content removed ( placebo ) . One hour before each trial , subjects consumed a capsule containing either 5 mg·kg−1 of caffeine or maltodextrin ( placebo ) . There was a significant effect of supplementation on power output ( p = 0.001 ) , with post hoc tests revealing higher power outputs in caffeine ( 205 ± 21 W ) vs. nitrate ( 194 ± 22 W ) and placebo ( 194 ± 25 W ) trials only . Caffeine-induced improvements in power output corresponded with significantly higher measures of heart rate ( caffeine : 166 ± 12 b·min−1 vs. placebo : 159 ± 15 b·min−1 ; p = 0.02 ) , blood lactate ( caffeine : 6.54 ± 2.40 mmol·L−1 vs. placebo : 4.50 ± 2.11 mmol·L−1 ; p < 0.001 ) , and respiratory exchange ratio ( caffeine : 0.95 ± 0.04 vs. placebo : 0.91 ± 0.05 ; p = 0.03 ) . There were no effects ( p ≥ 0.05 ) of supplementation on cycling cadence , rating of perceived exertion , , or integrated electromyographic activity . The results of this study support the well-established beneficial effects of caffeine supplementation on endurance performance . In contrast , acute supplementation with dietary nitrate seems to have no effect on endurance performance and adds nothing to the benefits afforded by caffeine supplementation Eight competitive oarswomen ( age , 22 + /- 3 years ; mass , 64.4 + /- 3.8 kg ) performed three simulated 2,000-m time trials on a rowing ergometer . The trials , which were preceded by a 24-hour dietary and training control and 72 hours of caffeine abstinence , were conducted 1 hour after ingesting caffeine ( 6 or 9 mg á kg-1 body mass ) or placebo . Plasma free fatty acid concentrations before exercise were higher with caffeine than placebo ( 0.67 + /- 0.34 vs. 0.72 + /- 0.36 vs. 0.30 + /- 0.10 mM for 6 and 9 mg á kg-1 caffeine and placebo , respectively ; p < .05 ) . Performance time improved 0.7 % ( 95 % confidence interval [ CI ] 0 to 1.5 % ) with 6 mg á kg-1 caffeine and 1 . 3 % ( 95 % CI 0.5 to 2.0 % ) with 9 mg á kg-1 caffeine . The first 500 m of the 2,000 m was faster with the higher caffeine dose compared with placebo or the lower dose ( 1.53 + /- 0.52 vs.1.55 + /- 0.62 and 1 . 56 + /- 0.43 min ; p = .02 ) . We concluded that caffeine produces a worthwhile enhancement of performance in a controlled laboratory setting , primarily by improving the first 500 m of a 2,000-m row Abstract This study investigated the effects of two different doses of caffeine on endurance cycle time trial performance in male athletes . Using a r and omised , placebo-controlled , double-blind crossover study design , sixteen well-trained and familiarised male cyclists ( Mean ± s : Age = 32.6 ± 8.3 years ; Body mass = 78.5 ± 6.0 kg ; Height = 180.9 ± 5.5 cm [Vdot]O2peak = 60.4 ± 4.1 ml · kg−1 · min−1 ) completed three experimental trials , following training and dietary st and ardisation . Participants ingested either a placebo , or 3 or 6 mg · kg−1 body mass of caffeine 90 min prior to completing a set amount of work equivalent to 75 % of peak sustainable power output for 60 min . Exercise performance was significantly ( P < 0.05 ) improved with both caffeine treatments as compared to placebo ( 4.2 % with 3 mg · kg−1 body mass and 2.9 % with 6 mg · kg−1 body mass ) . The difference between the two caffeine doses was not statistically significant ( P = 0.24 ) . Caffeine ingestion at either dose result ed in significantly higher heart rate values than the placebo conditions ( P < 0.05 ) , but no statistically significant treatment effects in ratings of perceived exertion ( RPE ) were observed ( P = 0.39 ) . A caffeine dose of 3 mg · kg−1 body mass appears to improve cycling performance in well-trained and familiarised athletes . Doubling the dose to 6 mg · kg−1 body mass does not confer any additional improvements in performance Research ers have long been investigating strategies that can increase athletes ' ability to oxidize fatty acids and spare carbohydrate , thus potentially improving endurance capacity . Green-tea extract ( epigallocatechin-3-gallate ; EGCG ) has been shown to improve endurance capacity in mice . If a green-tea extract can stimulate fat oxidation and as a result spare glycogen stores , then athletes may benefit through improved endurance performance . Eight male cyclists completed a study incorporating a 3-way crossover , r and omized , placebo-controlled , double-blinded , diet-controlled research design . All participants received 3 different treatments ( placebo 270 mg , EGCG 270 mg , and placebo 270 mg + caffeine 3 mg/kg ) over a 6-day period and 1 hr before exercise testing . Each participant completed 3 exercise trials consisting of 60 min of cycling at 60 % maximum oxygen uptake ( VO2(max ) ) immediately followed by a self-paced 40-km cycling time trial . The study found little benefit in consuming green-tea extract on fat oxidation or cycling performance , unlike caffeine , which did benefit cycling performance . The physiological responses observed during submaximal cycling after caffeine ingestion were similar to those reported previously , including an increase in heart rate ( EGCG 147 + /- 17 , caffeine 146 + /- 19 , and placebo 144 + /- 15 beats/min ) , glucose at the 40-min exercise time point ( placebo 5.0 + /- 0.8 , EGCG 5.4 + /- 1.0 , and caffeine 5.8 + /- 1.0 mmol/L ) , and resting plasma free fatty acids and no change in the amount of carbohydrate and fat being oxidized . Therefore , it was concluded that green-tea extract offers no additional benefit to cyclists over and above those achieved by using caffeine Caffeine has been reported to alter perceptions of exertion , muscle pain , and mood , yet the majority of existing data were obtained in resting volunteers or during steady-state exercise . The primary aim of this study was to examine the effects of caffeine on rating of perceived exertion ( RPE ) and perceptions of leg pain , arousal , and pleasure/displeasure during a simulated cycling time trial . Endurance-trained ( n=8 , VO(2)max=57.5±3.9 mL/kg/min ) and active ( n=8 , VO(2)max=46.5±6.3 mL/kg/min ) men initially completed two familiarization trials separated by at least 48 h. Over the next three trials , they completed a 10 km time trial preceded by ingestion of drinks containing caffeine ( 5 mg/kg ingested on 2 separate days ) or placebo . Treatments were ingested using a single-blind , crossover design , and participants were deceived as to the content of all drinks . During exercise , RPE ( 6 - 20 scale ) , leg pain ( 0 - 10 scale ) , arousal ( Felt Arousal Scale ) , and pleasure/displeasure ( Feeling Scale ) were recorded using various categorical scales . Repeated measures analysis of variance was used to assess differences in all variables across time and treatments , with fitness level used as a between-subjects variable . Pleasure/displeasure was altered ( p<0.05 , partial eta-squared ( η(2))=0.23 ) with caffeine compared to placebo , although leg pain , RPE , and arousal were similar ( p>0.05 ) across treatments . Caffeine increased ( p<0.05 , η(2)=0.27 ) cycling performance by 0.3 - 2.0 % versus placebo , with no effect ( p>0.05 ) of fitness level . Only in trained men ; however , was there a significant caffeine-mediated improvement in cycling performance , which was consequent with diminished mood in trained and improved mood in active individuals Abstract The aim of this study was to assess the effect of caffeine ingestion on 8 km run performance using an ecologically valid test protocol . A r and omized double-blind crossover study was conducted involving eight male distance runners . The participants ran an 8 km race 1 h after ingesting a placebo capsule , a caffeine capsule ( 3 mg · kg−1 body mass ) or no supplement . Heart rate was recorded at 5 s intervals throughout the race . Blood lactate concentration and ratings of perceived exertion were recorded after exercise . A repeated- measures analysis of variance ( ANOVA ) identified a significant treatment effect for 8 km performance time ( P < 0.05 ) ; caffeine result ed in a mean improvement of 23.8 s ( 95 % confidence interval [ CI ] = 13.1 to 34.5 s ) in 8 km performance time ( 1.2 % improvement , 95 % CI = 0.7 to 1.8 % ) . In addition , a two-way ( time × condition ) repeated- measures ANOVA identified a significantly higher blood lactate concentration 3 min after exercise during the caffeine trial ( P < 0.05 ) . We conclude that ingestion of 3 mg · kg−1 body mass of caffeine can improve absolute 8 km run performance in an ecologically valid race setting |
1,101 | 30,272,196 | Conclusions The combination of transarterial chemoembolizaiton and sorafenib significantly improves outcomes of unresectable hepatocellular carcinoma compared with transarterial chemoembolization monotherapy , especially in Asian region | Background The effectiveness of combination therapy of transarterial chemoembolization and sorafenib for unresectable hepatocellular carcinoma are controversial in some studies .
This meta- analysis aims to compare efficacy and safety , as well as regional disparities , between transarterial chemoembolization plus sorafenib and transarterial chemotherapy alone for hepatocellular carcinoma . | Objective To compare the treatment outcomes of sorafenib plus transarterial chemoembolization ( TACE ) vs TACE alone in patients with hepatocellular carcinoma ( HCC ) and hepatic vein tumor thrombus ( HVTT ) . Methods Twenty patients who were initially diagnosed with HCC and HVTT and received TACE combined with sorafenib during February 2009 to October 2013 were included in the study . To minimize selection bias , these patients were compared with 60 case-matched controls selected from a pool of 81 patients ( in a 1:3 ratio ) who received TACE alone during the same period . The primary end point was overall survival ( OS ) . The secondary end points were time to progression , disease control rate , and adverse events . Results After a median follow-up period of 12.5 months ( range , 1.03–44.23 months ) , the OS of the combined group was found to be significantly higher compared with the monotherapy group ( 14.9 vs 6.1 months , P=0.010 ) . The time to progression was found to be significantly longer in the combined group ( 4.9 vs 2.4 months , P=0.016 ) . Univariate and multivariate analyses revealed that the treatment allocation was an independent predictor of OS . Conclusion Sorafenib plus TACE was well tolerated and was more effective in treating patients with advanced HCC and HVTT . Future trials with prospect i ve larger sample s are required to vali date these results BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) . HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses BACKGROUND AND OBJECTIVES To compare the impact of concurrent TACE + sorafenib versus TACE alone on overall survival ( OS ) and time to progression ( TTP ) in patients with unresectable hepatocellular carcinoma ( uHCC ) . A secondary goal was to determine if sorafenib use increases the interval between courses of TACE . METHODS This study enrolled 150 patients with uHCC from June 2011 to June 2014 , including 50 treated with TACE + sorafenib and 100 treated with TACE alone . Factors associated with OS and TTP were identified by univariate and multivariate Cox-regression model analyses . Average TACE interval was defined as TTP/TACE frequency . RESULTS The median OS ( 21.7 vs. 11.5 months ) and TTP ( 10.2 vs. 6.7 months ) were longer in the TACE + sorafenib group compared to the TACE group . Patients receiving combination therapy had higher survival rate ( P < 0.032 ) and longer average interval to TACE ( P < 0.001 ) , but lower progression rate ( P < 0.001 ) . TACE + sorafenib therapy was associated with improved OS ( P ≤ 0.009 ) and TTP ( P ≤ 0.021 ) . The majority of AEs identified in patients receiving the combination therapy were classified as Grade s 1 and 2 , and skin-related reactions and fatigue were the most common . CONCLUSION Concurrent sorafenib with TACE provides survival benefits over TACE monotherapy , which may be related to a prolonged interval between subsequent TACE courses . J. Surg . Oncol . 2016;113:672 - 677 . © 2016 Wiley Periodicals , BACKGROUND & AIMS Transarterial chemoembolization with doxorubicin-eluting beads ( DC Bead ® ; DEB-TACE ) is effective in patients with Barcelona clinic liver cancer stage B hepatocellular carcinoma ( HCC ) . The multikinase inhibitor sorafenib enhances overall survival ( OS ) and time-to-tumor progression ( TTP ) in patients with advanced HCC . This exploratory phase II trial tested the efficacy and safety of DEB-TACE plus sorafenib in patients with intermediate stage HCC . METHODS Patients with intermediate stage multinodular HCC without macrovascular invasion ( MVI ) or extrahepatic spread ( EHS ) were r and omized 1:1 to DEB-TACE ( 150 mg doxorubicin ) plus sorafenib 400 mg twice daily or placebo . The primary endpoint was TTP by blinded central review . Secondary endpoints included time to MVI/EHS , OS , overall response rate ( ORR ) using modified response evaluation criteria in solid tumors , disease control rate ( DCR ) , time to unTACEable progression ( TTUP ) , and safety . RESULTS Of 307 patients r and omized , 154 received sorafenib and 153 received placebo . Median TTP for subjects receiving sorafenib plus DEB-TACE or placebo plus DEB-TACE was similar ( 169 vs. 166 days , respectively ; hazard ratio ( HR ) 0.797 , p=0.072 ) . Median time to MVI/EHS ( HR 0.621 , p=0.076 ) and OS ( HR 0.898 , p=0.29 ) had not been reached . The ORRs for patients in the sorafenib and placebo groups with post-baseline scans were 55.9 % and 41.3 % , respectively , and the DCRs were 89.2 % and 76.1 % , respectively . TTUP was lower with sorafenib than with placebo ( HR 1.586 ; 95 % confidence intervals , 1.200 - 2.096 ; median 95 vs. 224 days ) . No unexpected adverse events related to sorafenib were observed . CONCLUSION Sorafenib plus DEB-TACE was technically feasible , but the combination did not improve TTP in a clinical ly meaningful manner compared with DEB-TACE alone This prospect i ve non‐r and omized controlled trial aim ed to compare the efficacy of sorafenib in combination with transarterial chemoembolization ( TACE ) vs TACE alone for the treatment of patients with unresectable intermediate or advanced hepatocellular carcinoma PURPOSE To determine the safety and efficacy of transarterial chemoembolization ( TACE ) combined with sorafenib ( hereafter , TACE-sorafenib ) in patients with hepatocellular carcinoma ( HCC ) and portal vein tumor thrombus ( PVTT ) . MATERIAL S AND METHODS This study was approved by the institutional review board , and the requirement for informed consent was waived . The medical records of consecutive patients with HCC and PVTT who underwent TACE-sorafenib or TACE alone from January 2010 to December 2012 were retrospectively evaluated . Sorafenib ( 400 mg ) was administered twice daily . Outcomes of patients who underwent TACE-sorafenib were compared with outcomes of patients who underwent TACE by using the Kaplan-Meier method according to types of PVTT : PVTT in the main portal vein ( type A ) , PVTT in the first-order portal vein branch ( type B ) , and PVTT in second- or lower-order portal vein branches ( type C ) . RESULTS Ninety-one patients were included in the analysis ; 46 patients underwent TACE-sorafenib and 45 underwent TACE . TACE-sorafenib showed significant survival benefits compared with TACE in patients with type B ( median survival , 13 months vs 6 months ; P = .002 ) or type C ( median survival , 15 months vs 10 months ; P = .003 ) PVTT . TACE-sorafenib and main PVTT were the independent prognostic factors for survival at uni- and multivariate analysis . Liver function after TACE-sorafenib worsened only in patients with main PVTT . Sorafenib-related adverse events of grade 3 or higher occurred in 16 patients ( 35 % ) . CONCLUSION TACE-sorafenib side effects were acceptable , and this treatment may improve overall survival in patients with HCC with first-order or lower-branch PVTT when compared with patients who underwent TACE alone The oncologic community is faced with a steady increase in the incidence of hepatocellular carcinoma ( HCC ) [ 1 ] . Liver cancer represents the sixth most common cancer in the world ( 749 000 new cases ) and the third cause of cancer-related death ( 692 000 cases ) . The incidence varies from 3 out of 100 000 in Western countries , to more than 15 out of 100 000 in certain areas of the world , mapping the geographical distribution of viral hepatitis B ( HBV ) and hepatitis C ( HCV ) , the most important causes of chronic liver disease and HCC [ 2 ] . Most cases arise in those regions with limited re sources . The incidence of HCC increases progressively with advancing age in all population s , with a strong male preponderance . The association of chronic liver disease and HCC represents the basis for preventive strategies , including universal vaccination at birth against hepatitis B , programs to stop transmission and early antiviral eradication of viral hepatitis B and C [ III , A ] . It is unclear whether HBV vaccination will result in a decline in HCC as was seen in Taiwan , given the importance of other risk factors in Europe , such as alcoholic and non-alcoholic fatty liver disease . The control of other risk factors for chronic liver disease and cancer is more difficult to implement , such as cutting down on the consumption of alcohol and programs aim ing at a healthier lifestyle in the light of the obesity p and emic [ 3 , 4 ] . In Africa , reduction of exposure to aflatoxin B1 , especially in HBV-infected individuals , may lower the risk of HCC . HCC may evolve from subclasses of adenomas , and in < 10 % of cases HCC occurs in a normal liver . Surveillance of HCC involves the repeated application of screening tools in patients at risk for HCC and aims for the reduction in mortality of this patient population . The success of surveillance is influenced by the incidence of HCC in the target population , the availability and acceptance of efficient diagnostic tests and the availability of effective treatment . Costeffectiveness studies suggest surveillance of HCC is warranted in cirrhotic patients irrespective of its etiology [ 5 ] . Surveillance of non-cirrhotic patients is also advocated , especially in HBV carriers with serum viral load > 10 000 copies/ml [ 6 ] or HCVinfected patients with bridging fibrosis ( F3 ) [ III , A ] . Patients with HCV infection and advanced fibrosis remain at risk for HCC even after achieving sustained virological response following antiviral treatment [ III , A ] . Japanese cohort studies have shown that surveillance by abdominal ultrasound result ed in an average size of the detected tumors of 1.6 ± 0.6 cm , with < 2 % of the cases exceeding 3 cm [ 7 ] . In the Western world and in less experienced centers , sensitivity of finding early-stage HCC by ultrasound is considerably less effective [ 8 ] . There are no data to support the use of contrast-enhanced computed tomography ( CT ) or magnetic resonance imaging ( MRI ) for surveillance . In many centers , ultrasound surveillance is complemented with the determination of serum alphafetoprotein ( AFP ) , which can lead to a 6%–8 % gain in the tumor detection rate but at the price of false-positive results . A r and omized , controlled trial ( RCT ) of Chinese patients with chronic hepatitis B infection compared surveillance ( ultrasound and serum AFP measurements every 6 months ) versus no surveillance [ 9 ] . Despite low compliance with the surveillance program ( 55 % ) , HCC-related mortality was reduced by 37 % in the surveillance arm . Considering the most appropriate surveillance interval , a r and omized study comparing a 3versus 6-month based schedule failed to detect any differences [ 10 ] . Therefore , surveillance of patients at risk for HCC should be carried out by abdominal ultrasound every 6 months [ I , A ] BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group ( hazard ratio in the sorafenib group , 0.69 ; 95 % confidence interval , 0.55 to 0.87 ; P<0.001 ) . There was no significant difference between the two groups in the median time to symptomatic progression ( 4.1 months vs. 4.9 months , respectively , P=0.77 ) . The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( P<0.001 ) . Seven patients in the sorafenib group ( 2 % ) and two patients in the placebo group ( 1 % ) had a partial response ; no patients had a complete response . Diarrhea , weight loss , h and -foot skin reaction , and hypophosphatemia were more frequent in the sorafenib group . CONCLUSIONS In patients with advanced hepatocellular carcinoma , median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo . ( Clinical Trials.gov number , NCT00105443 . BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma BACKGROUND Transarterial chemoembolisation ( TACE ) is the st and ard of care for patients with intermediate stage hepatocellular carcinoma , while the multikinase inhibitor sorafenib improves survival in patients with advanced disease . We aim ed to determine whether TACE with sorafenib improves progression-free survival versus TACE with placebo . METHODS We did a multicentre , r and omised , placebo-controlled , phase 3 trial ( TACE 2 ) in 20 hospitals in the UK for patients with unresectable , liver-confined hepatocellular carcinoma . Patients were eligible if they were at least aged 18 years , had Eastern Cooperative Oncology Group performance status of 1 or less , and had Child-Pugh A liver disease . Patients were r and omised 1:1 by computerised minimisation algorithm to continuous oral sorafenib ( 400 mg twice-daily ) or matching placebo combined with TACE using drug-eluting beads ( DEB-TACE ) , which was given via the hepatic artery 2 - 5 weeks after r and omisation and according to radiological response and patient tolerance thereafter . Patients were stratified according to r and omising centre and serum α-fetoprotein concentration ( < 400 ng/mL and ≥400 ng/mL ) . Only the trial coordinator was unmasked to treatment allocation before patient progression during the study . The primary endpoint was progression-free survival defined as the interval between r and omisation and progression according to Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) or death due to any cause , and was analysed by intention-to-treat . Safety was analysed by intention-to-treat . The trial has been completed and the final results are reported . The trial is registered at EudraCT , number 2008 - 005073 - 36 , and IS RCT N , number IS RCT N93375053 . FINDINGS Between Nov 4 , 2010 , and Dec 7 , 2015 , the trial enrolled 399 patients and was terminated after a planned interim futility analysis . 86 patients failed screening and 313 remaining patients were r and omly assigned : 157 to sorafenib and 156 to placebo . The median daily dose was 660 mg ( IQR 389·2 - 800·0 ) sorafenib versus 800 mg ( 758·2 - 800·0 ) placebo , and median duration of therapy was 120·0 days ( IQR 43·0 - 266·0 ) for sorafenib versus 162·0 days ( 70·0 - 323·5 ) for placebo . There was no evidence of difference in progression-free survival between the sorafenib group and the placebo group ( hazard ratio [ HR ] 0·99 [ 95 % CI 0·77 - 1·27 ] , p=0·94 ) ; median progression-free survival was 238·0 days ( 95 % CI 221·0 - 281·0 ) in the sorafenib group and 235·0 days ( 209·0 - 322·0 ) in the placebo group . The most common grade 3 - 4 adverse events were fatigue ( 29 [ 18 % ] of 157 patients in the sorafenib group vs 21 [ 13 % ] of 156 patients in the placebo group ) , abdominal pain ( 20 [ 13 % ] vs 12 [ 8 % ] ) , diarrhoea ( 16 [ 10 % ] vs four [ 3 % ] ) , gastrointestinal disorders ( 18 [ 11 % ] vs 12 [ 8 % ] ) , and h and -foot skin reaction ( 12 [ 8 % ] and none ) . At least one serious adverse event was reported in 65 ( 41 % ) of 157 patients in the sorafenib group and 50 ( 32 % ) of 156 in the placebo group , and 181 serious adverse events were reported in total , 95 ( 52 % ) in the sorafenib group and 86 ( 48 % ) in the placebo group . Three deaths occurred in each group that were attributed to DEB-TACE . Four deaths were attributed to study drug ; three in the sorafenib group and one in the placebo group . INTERPRETATION The addition of sorafenib to DEB-TACE does not improve progression-free survival in European patients with hepatocellular carcinoma . Alternative systemic therapies need to be assessed in combination with TACE to improve patient outcomes . FUNDING Bayer PLC and BTG PLC BACKGROUND Recurrence of hepatocellular carcinoma ( HCC ) is a major problem after surgical or ablative treatments . The aim of this prospect i ve , single-center , placebo-controlled , r and omized , double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization ( TACE ) combined with sorafenib as a sequential treatment regimen in delaying time to progression ( TTP ) of intermediate-stage HCC in patients with chronic hepatitis C virus ( HCV ) infection . MATERIAL AND METHODS Between October , 2007 and January , 2011 , 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure . All had Child-Pugh class A disease . They were r and omized 1:1 to receive sorafenib at a dose of 400 mg twice daily or placebo . Endpoints were the TTP and the rates of adverse events and toxicity . RESULTS Sixty-two of 80 patients ( 77 % ) , 31 in the sorafenib group and 31 in the control group , completed the study . The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group ( hazard ratio , 2.5 ; 95 % confidence interval , 1.66 - 7.56 ; p < .001 ) . Metachronous , multicentric HCC progression occurred less frequently in sorafenib-treated patients ( p < .05 ) . Adverse reactions to sorafenib caused withdrawal from the study of 9 ( 22 % ) patients . CONCLUSION A conventional TACE procedure followed by sorafenib treatment result ed in a significantly longer TTP in patients with intermediate-stage HCV-related HCC , with no unexpected side effects Background Liver Transplantation ( LT ) is treatment of choice for patients with hepatocellular carcinoma ( HCC ) within MILAN Criteria . Tumour progression and subsequent dropout from waiting list have significant impact on the survival . Transarterial chemoembolization ( TACE ) controls tumour growth in the treated HCC nodule , however , the risk of tumour development in the untreated liver is increased by simultaneous release of neo-angiogenic factors . Due to its anti-angiogenic effects , Sorafenib delays the progression of HCC . Aim of this study was to determine whether combination of TACE and Sorafenib improves tumour control in HCC patients on waiting list for LT . Methods Fifty patients were r and omly assigned on a 1:1 ratio in double-blinded fashion at four centers in Germany and treated with TACE plus either Sorafenib ( n = 24 ) or placebo ( n = 26 ) . The end of treatment was development of progressive disease according to mRECIST criteria or LT . The primary endpoint of the trial was the Time-to-Progression ( TTP ) . Other efficacy endpoints were Tumour Response , Progression-free Survival ( PFS ) , and Time-to-LT ( TTLT ) . Results The median time of treatment was 125 days with Sorafenib and 171 days with the placebo . Fourteen patients ( seven from each group ) developed tumour progression during the course of the study period . The Hazard Ratio of TTP was 1.106 ( 95 % CI : 0.387 , 3.162 ) . The results of the Objective Response Rate , Disease Control Rate , PFS , and TTLT were comparable in both groups . The incidence of AEs was comparable in the placebo group ( n = 23 , 92 % ) and in the Sorafenib group ( n = 23 , 96 % ) . Twelve patients ( 50 % ) on Sorafenib and four patients ( 16 % ) on placebo experienced severe treatment-related AEs . Conclusion The TTP is similar after neo-adjuvant treatment with TACE and Sorafenib before LT compared to TACE and placebo . The Tumour Response , PFS , and TTLT were comparable . The safety profile of the Sorafenib group was similar to that of the placebo group . Trial registration IS RCT |
1,102 | 31,015,816 | In light of its proven effectiveness in other setting s , there is no compelling evidence to stop using good h and hygiene practice to reduce the risk of influenza infection and transmission in the community setting | Background H and hygiene is known to be an effective infection prevention and control measure in health care setting s. However , the effectiveness of h and hygiene practice s in preventing influenza infection and transmission in the community setting is not clear .
Objective To identify , review and synthesize available evidence on the effectiveness of h and hygiene in preventing laboratory-confirmed or possible influenza infection and transmission in the community setting . | Rationale There is little evidence for the efficacy of h and washing for prevention of influenza transmission in re source -poor setting s. We tested the impact of intensive h and washing promotion on household transmission of influenza-like illness and influenza in rural Bangladesh . Methods In 2009–10 , we identified index case- patients with influenza-like illness ( fever with cough or sore throat ) who were the only symptomatic person in their household . Household compounds of index case- patients were r and omized to control or intervention ( soap and daily h and washing promotion ) . We conducted daily surveillance and collected oropharyngeal specimens . Secondary attack ratios ( SAR ) were calculated for influenza and ILI in each arm . Among controls , we investigated individual risk factors for ILI among household contacts of index case- patients . Results Among 377 index case- patients , the mean number of days between fever onset and study enrollment was 2.1 ( SD 1.7 ) among the 184 controls and 2.6 ( SD 2.9 ) among 193 intervention case- patients . Influenza infection was confirmed in 20 % of controls and 12 % of intervention index case- patients . The SAR for influenza-like illness among household contacts was 9.5 % among intervention ( 158/1661 ) and 7.7 % among control households ( 115/1498 ) ( SAR ratio 1.24 , 95 % CI 0.92–1.65 ) . The SAR ratio for influenza was 2.40 ( 95 % CI 0.68–8.47 ) . In the control arm , susceptible contacts < 2 years old ( RRadj 5.51 , 95 % CI 3.43–8.85 ) , those living with an index case-patient enrolled ≤24 hours after symptom onset ( RRadj 1.91 , 95 % CI 1.18–3.10 ) , and those who reported multiple daily interactions with the index case-patient ( RRadj 1.94 , 95 % CI 1.71–3.26 ) were at increased risk of influenza-like illness . Discussion H and washing promotion initiated after illness onset in a household member did not protect against influenza-like illness or influenza . Behavior may not have changed rapidly enough to curb transmission between household members . A reactive approach to reduce household influenza transmission through h and washing promotion may be ineffective in the context of rural Bangladesh . Trial Registration Clinical Trials.gov Please cite this paper as : Simmerman et al. ( 2011 ) Findings from a household r and omized controlled trial of h and washing and face masks to reduce influenza transmission in Bangkok , Thail and . Influenza and Other Respiratory Viruses 5(4 ) , 256–267 Background Evidence is needed on the effectiveness of non‐pharmaceutical interventions ( NPIs ) to reduce influenza transmission . Methodology We studied NPIs in households with a febrile , influenza‐positive child . Households were r and omized to control , h and washing ( HW ) , or h and washing plus paper surgical face masks ( HW + FM ) arms . Study nurses conducted home visits within 24 hours of enrollment and on days 3 , 7 , and 21 . Respiratory swabs and serum were collected from all household members and tested for influenza by RT‐PCR or serology . Principal Findings Between April 2008 and August 2009 , 991 ( 16·5 % ) of 5995 pediatric influenza‐like illness patients tested influenza positive . Four hundred and forty‐two index children with 1147 household members were enrolled , and 221 ( 50·0 % ) were aged < 6 years . Three hundred and ninety‐seven ( 89·8 % ) households reported that the index patient slept in the parents ’ bedroom . The secondary attack rate was 21·5 % , and 56/345 ( 16·3 % ; 95 % CI 12·4–20·2 % ) secondary cases were asymptomatic . H and ‐washing subjects reported 4·7 washing episodes/day , compared to 4·9 times/day in the HW + FM arm and 3·9 times/day in controls ( P = 0·001 ) . The odds ratios ( ORs ) for secondary influenza infection were not significantly different in the HW arm ( OR = 1·20 ; 95 % CI 0·76–1·88 ; P‐0.442 ) , or the HW + FM arm ( OR = 1·16 ; 95 % CI .0·74–1·82 ; P = 0.525 ) . Conclusions Influenza transmission was not reduced by interventions to promote h and washing and face mask use . This may be attributable to transmission that occurred before the intervention , poor facemask compliance , little difference in h and ‐washing frequency between study groups , and shared sleeping arrangements . A prospect i ve study design and a careful analysis of sociocultural factors could improve future NPI studies 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 economical impact of absenteeism and reduced productivity due to acute infectious respiratory and gastrointestinal disease is normally not in the focus of surveillance systems and may therefore be underestimated . However , large community studies in Europe and USA have shown that communicable diseases have a great impact on morbidity and lead to millions of lost days at work , school and university each year . H and disinfection is acknowledged as key element for infection control , but its effect in open , work place setting s is unclear . Methods Our study involved a prospect i ve , controlled , intervention-control group design to assess the epidemiological and economical impact of alcohol-based h and disinfectants use at work place . Volunteers in public administrations in the municipality of the city of Greifswald were r and omized in two groups . Participants in the intervention group were provided with alcoholic h and disinfection , the control group was unchanged . Respiratory and gastrointestinal symptoms and days of work were recorded based on a monthly question naire over one year . On the whole , 1230 person months were evaluated . Results H and disinfection reduced the number of episodes of illness for the majority of the registered symptoms . This effect became statistically significant for common cold ( OR = 0.35 [ 0.17 - 0.71 ] , p = 0.003 ) , fever ( OR = 0.38 [ 0.14 - 0.99 ] , p = 0.035 ) and coughing ( OR = 0.45 [ 0.22 - 0.91 ] , p = 0.02 ) . Participants in the intervention group reported less days ill for most symptoms assessed , e.g. colds ( 2.07 vs. 2.78 % , p = 0.008 ) , fever ( 0.25 vs. 0.31 % , p = 0.037 ) and cough ( 1.85 vs. 2.00 % , p = 0.024 ) . For diarrhoea , the odds ratio for being absent became statistically significant too ( 0.11 ( CI 0.01 - 0.93 ) . Conclusion H and disinfection can easily be introduced and maintained outside clinical setting s as part of the daily h and hygiene . Therefore it appears as an interesting , cost-efficient method within the scope of company health support programmes . Trial registration numberIS RCT N : IS RCT Background There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza . We implemented a study of the feasibility and efficacy of face masks and h and hygiene to reduce influenza transmission among Hong Kong household members . Methodology /Principal Findings We conducted a cluster r and omized controlled trial of households ( composed of at least 3 members ) where an index subject presented with influenza-like-illness of < 48 hours duration . After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test , the household of the index subject was r and omized to 1 ) control or 2 ) surgical face masks or 3 ) h and hygiene . Households were visited within 36 hours , and 3 , 6 and 9 days later . Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture . The primary outcome measure was laboratory culture confirmed influenza in a household contact ; the secondary outcome was clinical ly diagnosed influenza ( by self-reported symptoms ) . We r and omized 198 households and completed follow up home visits in 128 ; the index cases in 122 of those households had laboratory-confirmed influenza . There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6 % . Clinical secondary attack ratios varied from 5 % to 18 % depending on case definitions . The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms . Adherence to interventions was variable . Conclusions / Significance The secondary attack ratios were lower than anticipated , and lower than reported in other countries , perhaps due to differing patterns of susceptibility , lack of significant antigenic drift in circulating influenza virus strains recently , and /or issues related to the symptomatic recruitment design . Lessons learnt from this pilot have informed changes for the main study in 2008 . Trial Registration Clinical Trials.gov NCT00425893 HK Clinical Trials.com The objective of this study was to identify possible hygiene behaviors associated with the incidence of ILI among adults in Beijing . In January 2011 , we conducted a multi-stage sampling , cross-sectional survey of adults living in Beijing using self-administered anonymous question naires . The main outcome variable was self-reported ILI within the past year . Multivariate logistic regression was used to identify factors associated with self-reported ILI . A total of 13003 participants completed the question naires . 6068 ( 46.7 % ) of all participants reported ILI during the past year . After adjusting for demographic characteristics , the variables significantly associated with a lower likelihood of reporting ILI were regular physical exercise ( OR 0.80 ; 95 % CI 0.74–0.87 ) , optimal h and hygiene ( OR 0.87 ; 95 % CI 0.80–0.94 ) , face mask use when going to hospitals ( OR 0.87 ; 95 % CI 0.80–0.95 ) , and not sharing of towels and h and kerchiefs ( OR 0.68 ; 95 % CI 0.63–0.73 ) . These results highlight that personal hygiene behaviors were potential preventive factors against the incidence of ILI among adults in Beijing , and future interventions to improve personal hygiene behaviors are needed in Beijing BACKGROUND Minimal research has been published evaluating the effectiveness of h and hygiene delivery systems ( ie , rubs , foams , or wipes ) at removing viruses from h and s. The purpose s of this study were to determine the effect of several alcohol-based h and sanitizers in removing influenza A ( H1N1 ) virus , and to compare the effectiveness of foam , gel , and h and wipe products . METHODS H and s of 30 volunteers were inoculated with H1N1 and r and omized to treatment with foam , gel , or h and wipe applied to half of each volunteer 's finger pads . The log(10 ) count of each subject 's treated and untreated finger pads were averaged . Log(10 ) reductions were calculated from these differences and averaged within treatment group . Between-treatment analysis compared changes from the untreated finger pads using analysis of covariance with treatment as a factor and the average log(10 ) untreated finger pads as the covariate . RESULTS Log(10 ) counts on control finger pads were 2.7 - 5.3 log(10 ) of the 50 % infectious dose for tissue culture ( TCID(50)/0.1 mL ) ( mean , 3.8 ± 0.5 log(10 ) TCID(50)/0.1 mL ) , and treated finger pad counts for all test products were 0.5 - 1.9 log(10 ) TCID(50)/0.1 mL ( mean , 0.53 ± 0.17 log(10 ) TCID(50)/0.1 mL ) . Treatments with all products result ed in a significant reduction in viral titers ( > 3 logs ) at their respective exposure times that were statistically comparable . CONCLUSIONS All 3 delivery systems ( foam , gel , and wipe ) produced significantly reduced viral counts on h and BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application BACKGROUND H and washing to prevent transmission of respiratory tract infections ( RTIs ) has been widely advocated , especially during the H1N1 p and emic . However , the role of h and washing is debated , and no good r and omised evidence exists among adults in non-deprived setting s. We aim ed to assess whether an internet-delivered intervention to modify h and washing would reduce the number of RTIs among adults and their household members . METHODS We recruited individuals sharing a household by mailed invitation through general practice s in Engl and . After consent , participants were r and omised online by an automated computer-generated r and om number programme to receive either no access or access to a bespoke automated web-based intervention that maximised h and washing intention , monitored h and washing behaviour , provided tailored feedback , reinforced helpful attitudes and norms , and addressed negative beliefs . We enrolled participants into an additional cohort ( r and omised to receive intervention or no intervention ) to assess whether the baseline question naire on h and washing would affect h and washing behaviour . Participants were not masked to intervention allocation , but statistical analysis comm and s were constructed masked to group . The primary outcome was number of episodes of RTIs in index participants in a modified intention-to-treat population of r and omly assigned participants who completed follow-up at 16 weeks . This trial is registered with the IS RCT N registry , number IS RCT N75058295 . FINDINGS Across three winters between Jan 17 , 2011 , and March 31 , 2013 , we enrolled 20,066 participants and r and omly assigned them to receive intervention ( n=10,040 ) or no intervention ( n=10,026 ) . 16,908 ( 84 % ) participants were followed up with the 16 week question naire ( 8241 index participants in intervention group and 8667 in control group ) . After 16 weeks , 4242 individuals ( 51 % ) in the intervention group reported one or more episodes of RTI compared with 5135 ( 59 % ) in the control group ( multivariate risk ratio 0·86 , 95 % CI 0·83 - 0·89 ; p<0·0001 ) . The intervention reduced transmission of RTIs ( reported within 1 week of another household member ) both to and from the index person . We noted a slight increase in minor self-reported skin irritation ( 231 [ 4 % ] of 5429 in intervention group vs 79 [ 1 % ] of 6087 in control group ) and no reported serious adverse events . INTERPRETATION In non-p and emic years , an effective internet intervention design ed to increase h and washing could have an important effect in reduction of infection transmission . In view of the heightened concern during a p and emic and the likely role of the internet in access to advice , the intervention also has potential for effective implementation during a p and emic . FUNDING Medical Research Council |
1,103 | 31,024,935 | HR increase and age were inversely correlated at high stress intensities .
Conclusion : This systematic review and meta- analysis presents pooled hemodynamic changes under light , moderate and high intensity exercise and pharmacological stress , while considering the potential influence of age . | Introduction : Exercise testing has become a diagnostic st and ard in the evaluation and management of heart disease .
While different methods of exercise and pharmacological stress testing exist , only little is known about their comparability .
We aim ed to assess hemodynamic changes during dynamic exercise , isometric exercise , and dobutamine stress testing at different stress intensities in healthy subjects and patients with aortic stenosis ( AS ) and aortic coa rct ation ( CoA ) . | AIMS Exercise limitation is common post-Fontan . Hybrid X-ray and magnetic resonance imaging ( XMR ) catheterization allows haemodynamic assessment by means of measurement of ventricular volumes and flow in major vessels with simultaneous invasive pressures . We aim to assess haemodynamic response to stress in patients with hypoplastic left heart syndrome ( HLHS ) post-Fontan . METHODS AND RESULTS Prospect i ve study of 13 symptomatic children ( NHYA 2 ) with HLHS post-Fontan using XMR catheterization . Three conditions were applied : baseline ( Stage 1 ) , dobutamine at 10 µg/kg/min ( Stage 2 ) , and dobutamine at 20 µg/kg/min ( Stage 3 ) . Seven consecutive patients received inhaled nitric oxide ( iNO ) at peak stress . Control MRI data were from normal healthy adults . In the HLHS patients , baseline mean pulmonary vascular resistance ( PVR ) was 1.51 ± 0.59 WU m(2 ) and aortopulmonary collateral flow was 17.7 ± 13.6 % of systemic cardiac output . Mean right ventricular end-diastolic pressure was 6.7 ± 2.5 mmHg which did not rise with stress . Cardiac index ( CI ) increased at Stage 2 in HLHS ( 40 % ) and controls ( 61 % ) but continued to increase at Stage 3 only in controls ( 19 % ) but not in HLHS . The blunted rise in CI in HLHS was due to a continuing fall in end-diastolic volume throughout stress , with no significant change in PVR or CI at peak stress in response to iNO . CONCLUSION Cardiac output post-Fontan in HLHS at peak stress is blunted due to a limitation in preload which is not responsive to inhaled pulmonary vasodilators in the setting of normal PVR Introduction The aim of this multicenter , prospect i ve study was to evaluate the long-term prognostic value of low-dose dobutamine stress echocardiography ( LDDSE ) in patients with aortic stenosis ( AS ) and depressed left ventricular ( LV ) function . Material and methods The study group comprised 39 patients ( 34 male , mean age 59 ±13 years ) with AS ( peak gradient > 25 mm Hg ) , LV ejection fraction ( LVEF ) ≤ 45 % and low transaortic gradient ( peak gradient ≤ 45 mm Hg , mean gradient ≤ 35 mm Hg ) . The qualification for subsequent therapeutic procedures was based on generally accepted indications . All patients underwent LDDSE and coronary angiography . Twelve months after LDDSE patients underwent control resting echocardiography and clinical evaluation . Results Twenty-seven ( 69.2 % ) patients had preserved contractile reserve . In this subgroup , true-severe AS was diagnosed in 12 patients , whereas pseudo-severe AS was found in 15 patients . Nine patients with true-severe AS , 2 patients with pseudo-severe AS and 7 patients without contractile reserve were referred for surgical treatment . The independent risk factors of death during follow-up were : aortic valve area ( AVA ) at peak stress < 0.8 cm2 ( OR 1.4 ; p = 0.003 ) and LVEF at rest < 35 % ( OR 6.8 ; p = 0.05 ) . The independent risk factors of composite end-point ( death or myocardial infa rct ions or pulmonary edema ) were : AVA at stress < 0.8 cm2 ( OR 4.0 ; p = 0.03 ) , absence of AVA increase during LDDSE ( OR 5.7 ; p = 0.005 ) , absence of contractile reserve ( OR 4.5 ; p = 0.01 ) and presence of significant CAD ( OR 6.9 ; p = 0.02 ) . Conclusions In patients with AS and depressed LVEF , LDDSE is a useful tool for long-term risk stratification Background The prognostic value of dobutamine stress hemodynamic data in the setting of low‐gradient aortic stenosis has been addressed in small , single‐center studies . Larger studies are needed to define the criteria for selecting the patients who will benefit from valve replacement . Methods and Results Six centers prospect ively enrolled 136 patients with aortic stenosis ( 96 men ; median age , 72 years [ range , 65 to 77 years ] ; median aortic valve area , 0.7 cm2 [ range , 0.6 to 0.8 ] ; mean transaortic gradient , 29 mm Hg [ range , 23 to 34 mm Hg ] ; cardiac index , 2.11 L min‐1 m‐2 [ range , 1.75 to 2.55 L min‐1 m‐2 ] ) . Left ventricular contractile reserve on the dobutamine stress Doppler study was present in 92 patients ( group I ) and absent in 44 patients ( group II ) . Operative mortality was 5 % ( 3 of 64 patients ) in group I compared with 32 % ( 10 of 31 patients ) in group II ( P=0.0002 ) . Predictors for operative mortality were the lack of contractile reserve ( odds ratio , 10.9 ; 95 % confidence interval [ CI ] , 2.6 to 43.4 ; P=0.001 ) and a mean transaortic gradient ≤20 mm Hg ( odds ratio , 4.7 ; 95 % CI , 1.1 to 21.0 ; P=0.04 ) . Predictors for long‐term survival were valve replacement ( hazard ratio , 0.30 ; 95 % CI , 0.17 to 0.53 ; P=0.001 ) and left ventricular contractile reserve ( hazard ratio , 0.40 ; 95 % CI , 0.23 to 0.69 ; P=0.001 ) . Conclusions In the setting of low‐gradient aortic stenosis , surgery seems beneficial for most of the patients with left ventricular contractile reserve . In contrast , the postoperative outcome of patients without reserve is compromised by a high operative mortality . Thus , dobutamine stress Doppler hemodynamics may be factored into the risk‐benefit analysis for each patient . ( Circulation . 2003;108:319‐324 . PURPOSE This study compared cardiac hemodynamics during supine cycle ergometry and dobutamine stress . METHODS Thirty-two healthy volunteers ( 19 female , 13 male , 23.5 + /- 3.5 yr old ) completed respective tests on separate days and in r and om order . Heart rate , blood pressure , and cardiac output were recorded at baseline and peak stress . Echocardiographic measures included left ventricular end-diastolic dimension , fractional shortening , heart rate corrected velocity of circumferential fiber shortening , end-systolic wall stress , and the difference between measured and predicted fiber shortening for measured wall stress . RESULTS Compared with peak exercise , dobutamine infusion result ed in lower cardiac output ( 12 + /- 2 vs 16 + /- 4 l x min(-1 ) , P < 0.0001 ) , heart rates ( 163 + /- 7 vs 175 + /- 12 beats x min(-1 ) , P < 0.0001 ) , and systolic blood pressure ( 160 + /- 22 vs 185 + /- 20 mm Hg , P < or = 0.0001 ) . Echocardiography demonstrated smaller left ventricular end-diastolic dimension ( 4.2 + /- 0.7 vs 4.5 + /- 0.7 cm , P = 0.013 ) , higher fractional shortening ( 0.55 + /- 0.07 vs 0.50 + /- 0.06 % , P < 0.001 ) , higher VCFc ( 2.07 + /- 0.36 vs 1.54 + /- 0.20 circs x s(-1 ) , P < 0.001 ) higher VCFdiff ( 0.94 + /- 0.35 vs 0.48 + /- 0.20 circs x s(-1 ) , P < 0.001 ) , and lower end-systolic wall stress ( 25 + /- 11 vs 42 + /- 16 g x cm(-2 ) , P < 0.001 ) . The stress-velocity relationship during dobutamine demonstrated higher y-intercept and steeper slope , indicating greater load-independent contractility . CONCLUSION The cardiovascular adaptation to exercise and dobutamine stress differ significantly . Cardiac output during peak exercise is greater than during peak dobutamine secondary to increased heart rate and stroke volume . Despite a greater increase in contractility and decrease in afterload , a smaller increase in cardiac output during dobutamine stress may be secondary to limited ventricular preload 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 Exercise testing has an established role in the evaluation of patients with valvular heart disease and can aid clinical decision making . Because symptoms may develop slowly and indolently in chronic valve diseases and are often not recognized by patients and their physicians , the symptomatic , blood pressure , and electrocardiographic responses to exercise can help identify patients who would benefit from early valve repair or replacement . In addition , stress echocardiography has emerged as an important component of stress testing in patients with valvular heart disease , with relevant established and potential applications . Stress echocardiography has the advantages of its wide availability , low cost , and versatility for the assessment of disease severity . The versatile applications of stress echocardiography can be tailored to the individual patient with aortic or mitral valve disease , both before and after valve replacement or repair . Hence , exercise-induced changes in valve hemodynamics , ventricular function , and pulmonary artery pressure , together with exercise capacity and symptomatic responses to exercise , provide the clinician with diagnostic and prognostic information that can contribute to subsequent clinical decisions . Nevertheless , there is a lack of convincing evidence that the results of stress echocardiography lead to clinical decisions that result in better outcomes , and therefore large-scale prospect i ve r and omized studies focusing on patient outcomes are needed in the future To clarify the influence of body position on exercise prescription , 14 men ( mean age + /- st and ard deviation 60.0 + /- 6.1 years ) with coronary artery disease who underwent r and omized recumbent and upright cycle ergometer tests to volitional fatigue were studied . At 100 watts , heart rate ( HR ) , systolic blood pressure , oxygen consumption ( VO2 ) , rate pressure product and rating of perceived exertion were greater ( p less than 0.05 ) in the upright than in the recumbent position . At peak exercise , however , these variables were not significantly different . Regressions of relative HR versus VO2 for recumbent and upright cycle ergometry were comparable : y = 1.24x - 32.7 and y = 1.26x - 31.5 , respectively , where y = % maximal VO2 , and x = % maximal HR . These findings indicate that recumbent exercise prescriptions may be based on the peak HR and VO2 values obtained during upright cycle ergometry , and vice versa . However , differences in the cardiorespiratory responses at submaximal exercise preclude the interchangeability of upright and recumbent training work rates INTRODUCTION Despite high error ranges , age-predicted maximal heart rate ( APMHR ) is frequently used to gauge the achievement of adequate effort during an exercise test . The current analysis revisits this issue using the Fitness Registry and the Importance of Exercise : National Data base ( FRIEND Registry ) . METHODS A total of 4,796 ( 63 % male ) apparently healthy subjects underwent a maximal cardiopulmonary exercise test on a treadmill . The mean age , maximal heart rate ( HR ) , and maximal aerobic capacity of the cohort were 43 ± 12 years , 178 ± 15 beats per minute , and 36.1 ± 10.6 mlO2 · kg(-1 ) · min(-1 ) , respectively . All subjects reached or surpassed a peak respiratory exchange ratio of 1.10 . A linear regression equation using age to predict maximal HR was vali date d in 3,796 subjects and cross-vali date d in the remaining 1,000 ( r and omly assigned ) . RESULTS The APMHR equation in the validation cohort was as follows : 209.3 - 0.72(age ) . The r value and st and ard error of estimate for this regression was 0.61 ( P < .001 ) and 11.35 beats/min , respectively . A 1- sample t test revealed that the mean difference between actual maximal HR and APMHR was not significantly different from 0 ( mean difference = 0.32 , P = .43 ) . However , Bl and -Altman revealed high limits of agreement ( upper 25.31 and lower -24.67 ) and a significant proportional bias . DISCUSSION The APMHR equation derived from this analysis included a large cohort of apparently healthy individuals with maximal exercise effort vali date d by the criterion st and ard ( ie , peak respiratory exchange ratio ) . Using APMHR in this capacity should be discouraged , and new approaches to gauging an individual 's exercise effort should be explored We assessed the haemodynamic changes after a propofol infusion at two rates in low‐risk unpremedicated patients ( ASA I – II ) . To determine contractility changes and loading conditions , we measured the ejection fraction , end‐systolic quotient and fractional shortening on transthoracic echocardiograms . We studied 40 patients undergoing peripheral neurosurgical procedures under general anaesthesia induced by propofol alone ( total dose 2.5 mg.kg−1 ) . Patients were r and omly assigned to receive propofol at an infusion rate of 10 mg.s−1 ; or 2 mg.s−1 . Haemodynamic data were recorded simultaneously immediately before propofol infusion , at the end of infusion , and 5 and 10 min after the infusion ended . The higher infusion rate induced a larger decrease in mean arterial pressure than the lower infusion rate ( − 20 % vs. − 10 % from baseline , p = 0.01 ) . In both groups , global and segmental ventricular function remained unchanged throughout the study . In both groups , there were markedly reduced end‐systolic quotients – presumably related to diminished afterload , and in the higher infusion‐rate group a significant reduction in fractional shortening – presumably related principally to diminished preload |
1,104 | 31,511,292 | Thechanges of serum creatinine ( Scr ) was not significantly different between eachtreatments of immunosuppressive agents and the control , except for STE whichhas the possibility of increasing Scr ( SMD , 1.00 ( 95 % CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse .
Infection , gastrointestinal symptoms , and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies .
This study demonstrates that TAC+TW , TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP .
Moreover , they are all at risk of infection , gastrointestinal symptoms , and myelosuppression .
Furthermore , TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus .
Conversely , STE alone , LEF and MZB seem to have little advantage in clinical treatment of IMN . | OBJECTIVES This study aim ed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy ( IMN ) in adults with nephrotic syndrome . | Although idiopathic membranous nephropathy ( IMN ) is the most common cause of adult-onset nephrotic syndrome , the management of IMN remains controversial . The aim of this prospect i ve study was to compare the efficacy and drug safety of tacrolimus with that of cyclophosphamide ( CTX ; control group ) in IMN patients receiving corticosteroid therapy . A total of 100 IMN patients with nephrotic syndrome were r and omly assigned to receive a combination of corticosteroid therapy and either CTX or tacrolimus . During a follow-up period of at least 18 months , the remission rate after 2 months in the tacrolimus group was 65.1 % , which was higher than that of the CTX group ( 44.2 % ) ( p = 0.02 ) . The mean time to partial or complete remission was 2.20 months in the tacrolimus group and 3.92 months in the CTX group ( p < 0.001 ) . We also found significantly greater improvements in the serum albumin levels in the tacrolimus group compared with the CTX group at the 2-month ( p = 0.003 ) and 3-month time points ( p = 0.01 ) . The serum creatinine levels remained stable in both groups . Although remission was quicker and more common in the tacrolimus group ( compared with the CTX group ) before 3 months , there was no superiority of tacrolimus after 6 months . Glucose intolerance , urinary tract infections , and pneumonia were the major side effects observed in this study . All of the side effects were mild and controlled , and there were fewer side effects in the tacrolimus group compared with the CTX group , indicating a better treatment tolerance in the tacrolimus group To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy , we compared two regimens based on a 6-mo treatment , alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide . Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were r and omized to be given methylprednisolone ( 1 g intravenously for 3 consecutive days followed by oral methylprednisolone , 0.4 mg/kg per d for 27 d ) alternated every other month either with chlorambucil ( 0.2 mg/kg per d for 30 d ) or cyclophosphamide ( 2.5 mg/kg per d for 30 d ) . The whole treatment lasted 6 mo ; 3 mo with corticosteroids and 3 mo with one cytotoxic drug . Among 87 patients followed for at least 1 yr , 36 of 44 ( 82 % ; 95 % confidence interval [ CI ] , 67.3 to 91.8 % ) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome , versus 40 of 43 ( 93 % ; 95 % CI , 80.9 to 98.5 % ) assigned to methylprednisolone and cyclophosphamide ( P = 0.116 ) . Of patients who attained remission of the nephrotic syndrome , 11 of 36 in the chlorambucil group ( 30.5 % ) and 10 of 40 in the cyclophosphamide group ( 25 % ) had a relapse of the nephrotic syndrome between 6 and 30 mo . The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups ( P < 0.01 ) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr . Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects . Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster . One patient per group developed cancer . It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr BACKGROUND Evidence regarding the optimal dose of tacrolimus ( TAC ) in treatment of idiopathic membranous nephropathy ( IMN ) remains inconclusive . The objective of this study was to evaluate the efficacy and safety of low-dose TAC combined with prednisone for patients with IMN . METHODS We conducted a r and omized prospect i ve cohort study in IMN patients : 28 patients received oral TAC ( target whole blood concentration of 2 - 4 ng/mL ) plus prednisone for 12 months , and 28 patients received prednisone combined with intravenous cyclophosphamide ( CYC ) ( 750 mg/m2 body surface ) once every 4 weeks for 24 weeks . RESULTS Of the 56 patients who completed the 12-month treatment , complete remission ( CR ) occurred in 8 ( 28.6 % ) of the CYC group and 18 ( 64.3 % ) of the TAC group ; partial remission ( PR ) occurred in 10 ( 35.7 % ) of the CYC group and 7 ( 25.0 % ) of the TAC group . The probability of remission ( either CR or PR ) was higher in the TAC group than in the CYC group ( p = 0.0439 , by log-rank test ) . Furthermore , a significantly greater improvement in proteinuria and serum albumin levels was observed in the TAC group compared with the CYC group . Patients treated with TAC can often show a rapid increase in their serum albumin levels before any obvious reduction of urinary protein excretion . Side effects were mild and transitory in both groups . CONCLUSION The results demonstrated that the combined therapy of low-dose TAC and prednisone is an effective and safe therapeutic method for Chinese adults with IMN . Low-dose TAC accompanied by prednisone is enough to induce remission in the majority of patients with IMN BACKGROUND We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome . METHODS To vali date the hypothesis that the 2 treatments were equivalent , patients with biopsy-proven membranous nephropathy and nephrotic syndrome were r and omly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months ( group A ) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year ( group B ) . RESULTS The primary outcome measure is cumulative number of remissions as a first event . Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event . After a median follow-up of 24 months ( interquartile range , 15 to 25 months ) , there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d ( interquartile range , 4.0 to 7.3 g/d ) to 2.1 g/d ( interquartile range , 0.4 to 3.8 g/d ; P = 0.004 ) in group A and 6.0 g/d ( interquartile range , 4.4 to 8.5 g/d ) to 0.3 g/d ( interquartile range , 0.2 to 1.9 g/d ; P = 0.049 ) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy . CONCLUSION Most nephrotic patients with membranous nephropathy responded to either treatment . Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone , without significant differences between these 2 therapies Background Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy ( MN ) remains controversial . The effect of mycophenolate mofetil ( MMF ) versus cyclosporine ( CsA ) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center r and omized trial ( NCT01282073 ) . Methods A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were r and omly assigned to receive MMF combined with low-dose corticosteroids ( MMF group ) versus CsA combined with low-dose corticosteroids ( CsA group ) , respectively , and followed up for 48 weeks . Complete or partial remission rate of proteinuria and estimated glomerular filtration rate ( eGFR ) at 48 weeks were compared . Results The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day , respectively , in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day , respectively , in the CsA group . In total , 76.1 % of the MMF group and 66.7 % of the CsA group achieved remission at 48 weeks ( 95 % confidence interval , −0.18 to 0.38 ) . There was no difference in eGFR between the two groups . Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group ( P = 0.001 ) , but were unchanged in the no-response group . There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks . Conclusion In combination with low-dose corticosteroids , the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN , with similar adverse effects including gastrointestinal symptoms . Trial Registration Clinical Trials.gov Identifier : R and omized trials of rituximab in primary membranous nephropathy ( PMN ) have not been conducted . We undertook a multicenter , r and omized , controlled trial at 31 French hospitals ( NCT01508468 ) . Patients with biopsy-proven PMN and nephrotic syndrome after 6 months of nonimmunosuppressive antiproteinuric treatment ( NIAT ) were r and omly assigned to 6-month therapy with NIAT and 375 mg/m2 intravenous rituximab on days 1 and 8 ( n=37 ) or NIAT alone ( n=38 ) . Median times to last follow-up were 17.0 ( interquartile range , 12.5 - 24.0 ) months and 17.0 ( interquartile range , 13.0 - 23.0 ) months in NIAT-rituximab and NIAT groups , respectively . Primary outcome was a combined end point of complete or partial remission of proteinuria at 6 months . At month 6 , 13 ( 35.1 % ; 95 % confidence interval [ 95 % CI ] , 19.7 to 50.5 ) patients in the NIAT-rituximab group and eight ( 21.1 % ; 95 % CI , 8.1 to 34.0 ) patients in the NIAT group achieved remission ( P=0.21 ) . Rates of antiphospholipase A2 receptor antibody ( anti-PLA2R-Ab ) depletion in NIAT-rituximab and NIAT groups were 14 of 25 ( 56 % ) and one of 23 ( 4.3 % ) patients at month 3 ( P<0.001 ) and 13 of 26 ( 50 % ) and three of 25 ( 12 % ) patients at month 6 ( P=0.004 ) , respectively . Eight serious adverse events occurred in each group . During the observational phase , remission rates before change of assigned treatment were 24 of 37 ( 64.9 % ) and 13 of 38 ( 34.2 % ) patients in NIAT-rituximab and NIAT groups , respectively ( P<0.01 ) . Positive effect of rituximab on proteinuria remission occurred after 6 months . These data suggest that PLA2R-Ab levels are early markers of rituximab effect and that addition of rituximab to NIAT does not affect safety Idiopathic membranous nephropathy is a common cause of nephrotic syndrome whose pathogenesis may involve B-cell functions . Rituximab is a monoclonal antibody that binds to the CD20 antigen on B cells thereby deleting them . We conducted an open-label pilot trial of rituximab treatment in 15 severely nephrotic patients with proteinuria refractory to angiotensin-converting enzyme inhibition and /or receptor blockade but with adequately controlled blood pressure . Rituximab was given 2 weeks apart and , at 6 months , patients who remained proteinuric but had recovered B-cell counts were given a second course of treatment . Proteinuria was significantly decreased by about half at 12 months . Of the 14 patients who completed follow-up , full remission was achieved in two and partial remission in six patients based upon the degree of proteinuria . Side effects were minor ; however , we found no relationship between the response and number of B cells in the blood , CD20 cells in the kidney biopsy , degree of tubulointerstitial fibrosis , starting proteinuria or creatinine values . Rituximab appears effective in reducing proteinuria in some patients with idiopathic membranous nephropathy but prospect i ve identification of responsive patients was not possible Controlled trial of cyclophosphamide in idiopathic membranous nephropathy . We evaluated cyclophosphamide treatment in a controlled prospect i ve study of 22 adult patients with clinical ly and histologically defined idiopathic membranous nephropathy . By r and om assignment , 11 patients received no drug and 11 patients received cyclophosphamide orally , 1.5 to 2.5 mg/kg/day ( mean , 1.8 ) , for one year . Before treatment , the two groups were similar in age and sex distributions , duration of illness , blood pressure , degree of proteinuria , renal function and histologic staging . After treatment , a downward trend in proteinuria was noted , with no significant difference in the quantity and rate of decrease between groups . Renal function ( C in and C PAH ) was stable in all patients , with no difference between groups . On comparing pretreatment and one-year renal biopsy specimens in eight patients in each group , regardless of treatment or clinical outcome , the appearance of the renal lesions remained the same or progressed in terms of basement membrane thickening and incorporation of subepithelial deposits , and immunofluorescence with IgG and C3 remained positive in glomerular capillaries . Cyclophosphamide dosage was decreased in five patients because of recurrent leukopenia ; no other major toxicity was observed . Beyond one year of treatment , renal function has decreased in two of eight patients in the no-drug group and in one of seven patients in the cyclophosphamide-treated group . We conclude that treatment with cyclophosphamide for one year did not have a favorable effect on proteinuria , renal function or morphologic aspects of the glomerular lesion . Essai controle du cyclophosphamide dans la nephropathie membraneuse idiopathique . Nous avons evalue le traitement par le cyclophosphamide dans une etude prospect i ve controlee de 22 malades adultes atteints de nephropathie membraneuse idiopathique cliniquement et anatomiquement definie . Au hasard , onze malade n'ont recu aucun traitement et onze autres ont eu du cyclophosphamide par voie orale a raison de 1,5 a 2,5 mg/kg par jour ( 1,8 en moyenne ) pendant un an . Avant le traitement les deux groupes etaient semblables en distribution d'âge et de sexe , duree de la maladie , pression arterielle , importance de la proteinurie , fonction renale et etat histologique . Apres traitement , une tendance a la diminution de la proteinurie a ete observee sans difference significative entre les groupes dans le debit de proteine ou la vitesse de diminution . La fonction renale ( C in et C PAH ) etait stable chez tous les malades , sans difference entre les groupes . La comparaison des biopsies avant traitement et apres un an chez huit malades de chaque groupe , independamment du traitement ou de l'evolution clinique , a montre que les lesions renales sont restees les memes ou ont progresse , sous la forme d'un epaississement de la membrane basale et de l'incorporation de depots sous-epitheliaux , et que l'immunofluorescence avec IgG et C3 reste positive dans les capillaires glomerulaires . La posologie du cyclophosphamide a ete diminuee chez cinq malades en raison d'une leucopenie recidivante ; aucune autre toxicite majeure n'a ete observee . Au-dela d'un an de traitement , la fonction renale a diminue chez deux des huit malades du groupe ne recevant pas de medicament et chez l'un des sept malades du groupe traite par le cyclophosphamide . Nous concluons que le traitement par le cyclophosphamide pendant un an n'a pas eu d'effet favorable sur la proteinurie , la fonction renale ou les lesions histologiques glomerulaires Summary Background Membranous nephropathy leads to end-stage renal disease in more than 20 % of patients . Although immunosuppressive therapy benefits some patients , trial evidence for the subset of patients with declining renal function is not available . We aim ed to assess whether immunosuppression preserves renal function in patients with idiopathic membranous nephropathy with declining renal function . Methods This r and omised controlled trial was undertaken in 37 renal units across the UK . We recruited patients ( 18–75 years ) with biopsy-proven idiopathic membranous nephropathy , a plasma creatinine concentration of less than 300 μmol/L , and at least a 20 % decline in excretory renal function measured in the 2 years before study entry , based on at least three measurements over a period of 3 months or longer . Patients were r and omly assigned ( 1:1:1 ) by a r and om number table to receive supportive treatment only , supportive treatment plus 6 months of alternating cycles of prednisolone and chlorambucil , or supportive treatment plus 12 months of ciclosporin . The primary outcome was a further 20 % decline in renal function from baseline , analysed by intention to treat . The trial is registered as an International St and ard R and omised Controlled Trial , number 99959692 . Findings We r and omly assigned 108 patients , 33 of whom received prednisolone and chlorambucil , 37 ciclosporin , and 38 supportive therapy alone . Two patients ( one who received ciclosporin and one who received supportive therapy ) were ineligible , so were not included in the intention-to-treat analysis , and 45 patients deviated from protocol before study end , mostly as a result of minor dose adjustments . Follow up was until primary endpoint or for minimum of 3 years if primary endpoint was not reached . Risk of further 20 % decline in renal function was significantly lower in the prednisolone and chlorambucil group than in the supportive care group ( 19 [ 58 % ] of 33 patients reached endpoint vs 31 [ 84 % ] of 37 , hazard ratio [ HR ] 0·44 [ 95 % CI 0·24–0·78 ] ; p=0·0042 ) ; risk did not differ between the ciclosporin ( 29 [ 81 % ] of 36 ) and supportive treatment only groups ( HR 1·17 [ 0·70–1·95 ] ; p=0·54 ) , but did differ significantly across all three groups ( p=0·003 ) . Serious adverse events were frequent in all three groups but were higher in the prednisolone and chlorambucil group than in the supportive care only group ( 56 events vs 24 events ; p=0·048 ) . Interpretation For the subset of patients with idiopathic membranous nephropathy and deteriorating excretory renal function , 6 months ' therapy with prednisolone and chlorambucil is the treatment approach best supported by our evidence . Ciclosporin should be avoided in this subset . Funding Medical Research Council , Novartis , Renal Association , Kidney Research UK BACKGROUND Retrospective and anecdotal data suggest that mycophenolate mofetil ( MMF ) might be effective when given as rescue therapy for membranous nephropathy ( MN ) . Prospect i ve controlled data on MMF and prednisolone as primary therapy are lacking . METHODS A prospect i ve , r and omized , controlled , open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome . MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients , with follow up of 15 months . RESULTS MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction , despite a lower cumulative prednisolone dose in the MMF group ( 3.80 + /- 0.28 vs 9.93 + /- 0.25 g , P < 0.001 ) . Remission ( composite of ' complete ' and ' partial ' ) rates were 63.6 % and 66.7 % in the MMF group and control group , respectively ( P = 1.000 ) . Serum creatinine and creatinine clearance remained stable during follow up . Cumulative relapse rate was 23.1 % at 2 years . Chlorambucil result ed in more leucopenia compared with MMF . CONCLUSION Data from this pilot study indicate that more than 60 % of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment , and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents Background Idiopathic membranous nephropathy ( IMN ) is a major cause of nephrotic syndrome among adults . Considering the natural course of IMN , when to treat and with which immunosuppressive treatment need to be carefully considered in such patients . A combination of tripterygium wilfordii multiglycosides ( TWG ) and prednisone may be an effective option for treating patients with IMN . Methods In this prospect i ve cohort study , we enrolled patients with biopsy-proven IMN at our kidney centre . One cohort received TWG combined with prednisone , whereas another cohort received tacrolimus ( TAC ) combined with prednisone , for 36 weeks . The primary outcome was the remission rate , whereas the secondary outcomes included the time to remission , relapse rate , changes in serum albumin levels and daily urinary protein levels , estimated glomerular filtration rate , and adverse events . Results A total of 53 patients with IMN met the criteria for enrolment , and all patients completed the therapy . At the end of the 36-week therapy , remission ( either partial remission [ PR ] or complete remission [ CR ] ) was observed in 20 patients ( 86.9 % ) receiving TWG and in 27 patients ( 90.0 % ) receiving TAC ( p > 0.05 ) , whereas CR was noted in 12 patients ( 52.2 % ) receiving TWG and 14 patients ( 46.7 % ) receiving TAC ( p > 0.05 ) . The probability of remission was similar for both the TWG and TAC groups ( p > 0.05 , by log-bank test ) . The mean time for achieving remission was 11.8 ± 12.5 weeks in the TWG group and 8.5 ± 9.1 weeks in the TAC group ( p > 0.05 ) . Conclusions The combination of TWG and predisone is an effective and safe therapy for IMN BACKGROUND The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy ( MN ) and focal segmental glomerulosclerosis ( FSGS ) are based on steroids and /or cytotoxic agents . Data on the effect of mycophenolate mofetil ( MMF ) for these conditions are scarce and confounding . METHODS We compared the efficacy of an MMF-based therapy with st and ard therapies in inducing remission in adult nephrotics with MN and FSGS in a r and omized pilot study . MMF was given at 2 g/day for 6 months along with prednisolone at 0.5 mg/kg/day for 2 - 3 months . Conventional therapy was prednisolone 1 mg/kg/day for 3 - 6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN . The primary end point was change in urinary protein/creatinine ratio . RESULTS A total of 54 patients ( 21 MN and 33 FSGS ) were recruited ; 28 were r and omized to receive MMF ( group A ) and 26 were on conventional treatment ( group B ) . There was no difference in the proportion of patients achieving remission in two groups ( 64 and 80 % in MN and 70 and 69 % in FSGS ) . The frequency of relapses and incidence of infections was also similar . FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose . CONCLUSIONS A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term . It induces remission faster and reduces steroid exposure in FSGS patients . Studies with more cases and longer follow-up are required to evaluate its impact on preservation of kidney function The natural course of idiopathic membranous nephropathy is variable , with some patients slowly progressing to renal failure while others maintain normal renal function over the entire time . Whether to treat this disease or not is controversial due to the lack of controlled data about the long-term effects of treatment . We up date d at 10 years the results of a controlled trial in which 81 patients with idiopathic membraneous nephropathy and nephrotic syndrome were r and omly assigned to receive symptomatic therapy ( 39 patients ) or a treatment of six months with methylprednisolone and chlorambucil ( 42 patients ) . The probability of surviving without developing end-stage renal disease at 10 years was 92 % in patients given methylprednisolone and chlorambucil versus 60 % in controls ( P = 0.0038 ) . The slope of the reciprocal of plasma creatinine up to 10 years was significantly better in treated patients than in controls ( P = 0.035 ) . The probability of having a complete or partial remission of the nephrotic syndrome was significantly higher in treated patients ( P = 0.000 ) . Patients assigned to therapy spent significantly longer time without nephrotic syndrome than untreated patients ( P = 0.0001 ) . Four patients had to stop treatment because of reversible side-effects . In the long-term one treated patient developed diabetes and another one became obese . In conclusion , a six-month therapy with methylprednisolone and chlorambucil increases the probability of remission of proteinuria and protects from renal function deterioration even in the long-term . This treatment may avoid dialysis or death within 10 years to about one third of nephrotic patients with membranous nephropathy Membranous nephropathy is a common cause of nephrotic syndrome in adults . Although some patients with membranous nephropathy achieve a spontaneous remission , renal function continues to deteriorate in others . We conducted a prospect i ve r and omized trial evaluating monotherapy with tacrolimus to achieve complete or partial remission in patients with biopsy-proven membranous nephropathy . Twenty-five patients received tacrolimus ( 0.05 mg/kg/day ) over 12 months with a 6-month taper , whereas 23 patients were in the control group . The probability of remission in the treatment group was 58 , 82 , and 94 % after 6 , 12 , and 18 months but only 10 , 24 , and 35 % , respectively in the control group . The decrease in proteinuria was significantly greater in the treatment group . Notably , six patients in the control group and only one in the treatment group reached the secondary end point of a 50 % increase in their serum creatinine . No patient in the tacrolimus group showed a relapse during the taper period . Nephrotic syndrome reappeared in almost half of the patients who were in remission by the 18th month after tacrolimus withdrawal . We conclude that tacrolimus is a very useful therapeutic option for patients with membranous nephropathy and preserved renal function . The majority of patients experienced remission with a significant reduction in the risk for deteriorating renal function A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy ( MGN ) was carried out to determine whether cyclosporine ( D ) would be more effective than placebo ( P ) in reducing the rate of deterioration in renal function . Patients ( N = 64 ) with MGN were placed on a restricted protein diet ( < or = 0.9 g/kg ) and followed closely for 12 months ( Part 1 ) . Patients at high risk of progression based on an absolute loss in creatinine clearance ( CCr ) of > or = 8 ml/min and persistent nephrotic range proteinuria ( Pr ) were selected and r and omly assigned to either ( D ) ( N = 9 ) or ( P ) ( N = 8) for 12 months ( Part 2 ) . No differences in the two groups were noted at entry . After 12 months , the improvement in CCr slope in ml/min/month was significantly greater in the D patients ( D + 2.1 vs. P + 0.5 , mean difference 1.6 ; 95 % CI 0.3 to 3.0 , P < 0.02 ) . This improvement was maintained in six of eight D ( 75 % ) over a mean follow-up period of 21 months . Daily Pr also improved with D ( by month 3 , D - 4.5 g/day vs. P + 0.7 g/day , P = 0.02 ) and was sustained in six of eight ( 75 % ) D patients . When Pr was expressed as a function of their concurrent CCr , the D versus P patients ' time to halving was faster ( P = 0.02 ) and absolute number higher ( 4/9 D vs 0/8 P ) . In the D group a trend towards worse hypertension and an increase in the number of transient rises in serum creatinine were noted . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND / PURPOSE Immunosuppressive therapy plays an important role in patients with high-risk idiopathic membranous nephropathy ( IMN ) , but the therapeutic modality is still controversial . METHODS Corticosteroid combined with oral tacrolimus ( TAC , target trough blood concentration of 4 - 8 ng/mL ) , intravenous cyclophosphamide ( CYC , 750 mg/m(2)/mo , or oral mycophenolate mofetil ( MMF , 1.5 - 2.0 g/d ) were r and omly administered for 9 months to 90 patients with IMN proved with renal biopsy with severe proteinuria ( > 8 g/d ) . RESULTS Eighty-six of the 90 patients completed the study . The total remission ( TR ) rates in the TAC group were significantly higher than those in the CYC group at 1 and 2 months ( p < 0.01 ) and the MMF group at 1 - 4 months ( p < 0.01 ) . The TR rates were 83.3 % , 73.3 % , and 70.0 % in the TAC , CYC , and MMF groups at 9 months ( p = 0.457 ) , and there were no significant differences between the three groups from 5 to 9 months . Furthermore , TAC reduced proteinuria and ameliorated hypoalbuminemia more quickly and effectively than CYC and MMF . We observed no severe adverse events in the three groups . CONCLUSION Tacrolimus combined with corticosteroid had tolerable adverse effects and induced the remission of IMN more effectively and more rapidly . This is the first prospect i ve r and omized cohort study to compare three different therapies in patients at high risk for IMN . It provides strong evidence for choosing optimal treatment for patients with IMN . The long-term efficacy of this treatment strategy should be investigated further in future studies AIM Membranous nephropathy remains the most common form of the nephrotic syndrome in adults . The combination therapy of steroid and cyclophosphamide has routinely been used . Although satisfactory therapeutic efficacy can be achieved , its side effect on reproductive system has been a concern . Mizoribine is an imidazole nucleoside and a novel immunosuppressant that has been used to treat other immune-related diseases . In this study we examine if the combined regimen of mizoribine and steroid would be advantageous over the use of cyclophosphamide and steroid in treating adult membranous nephropathy . METHODS There were total of fifty-five patients completed the study . These patients had membranous nephropathy with presentation of proteinuria . They were treated with combined regimen of mizoribine and steroid or cyclophosphamide and steroid , and were followed up for one year to monitor safety and efficacy . RESULTS We found the condition of proteinuria was significantly improved in the mizoribine group and the improvement was comparable to the patients treated with cyclophosphamide . These patients also exhibited an increase of serum albumin . There was no significant increase of adverse events with the use of mizoribine-based therapy , suggesting the tolerability of mizoribine in adult patients with membranous nephropathy . CONCLUSION In conclusion , the results indicated the satisfactory safety and efficacy of the combination regiment of mizoribine and steroid in treating adult patients with membranous nephropathy Introduction Both cCTX/GCs and CNIs are recommended as first-line agents in the management of PMN . The present study is an extended report of patients r and omized to receive TAC/GCs or cCTX/GCs at 2 years post r and omization . Methods Seventy patients enrolled in the clinical trial Tacrolimus Combined With Corticosteroids Versus Modified Ponticelli Regimen in Treatment of Idiopathic Membranous Nephropathy : R and omized Control Trial were followed quarterly between 12 and 24 months . At the end of 24 months , 3 patients were lost to follow-up . Results At 18 months , 66 % and 89 % ( P = 0.04 ) were in remission in TAC/GCs and cCTX/GCs groups , respectively . At 18 and 24 months , 60 % and 86 % ( P = 0.03 ) of cases were in remission in the TAC/GCs and cCTX/GCs groups , respectively . At 18 months , 57 % and 83 % ( P = 0.03 ) of the patients in TAC/GCs and cCTX/GCs groups were in remission without need of any additional immunosuppression ( persistent remission ) and , at 24 months , 43 % and 80 % ( P = 0.002 ) were in persistent remission in TAC/GCs and cCTX/GCs groups , respectively . Relapse rate after any remission was 40 % and 6.7 % in TAC/GCs and cCTX/GCs groups , respectively ( P = 0.007 ) . There was an association of aPLA2R titers with remission or resistance ( P = 0.006 ) in relapsing PMN . The significant decrease in eGFR after 12 months of TAC/GCs therapy normalized at 18 and 24 months . Discussion At 2 years after r and omization , relapse rates are higher for TAC/GCs compared with cCTX/GCs in PMN patients . Thus , cCTX/GCs are better than TAC/GCs in the longer term in PMN patients In this prospect i ve r and omized trial , we compared the effects of cyclosporine- and cyclophosphamide-based treatment regimens in patients with idiopathic membranous nephropathy . Twenty-eight patients were r and omized to receive treatment with one of the three therapeutic regimens : cyclosporine with methylprednisolone , cyclophosphamide with methylprednisolone or lisinopril ( control ) . Renal function and nephrotic syndrome parameters were determined at baseline and during a 9-month treatment period . At the end of the study period , renal function improved significantly in the cyclophosphamide and deteriorated significantly in the cyclosporine group . Serum albumin levels increased significantly in the cyclosporine and cyclophosphamide group . Total cholesterol levels and proteinuria were significantly reduced in all groups . In the comparison between the groups , serum albumin levels were significantly lower in the control group and there were no differences in the rest of the studied parameters at the end of the study . Six patients from the cyclosporine group ( 1/10 complete and 5/10 partial ) , all cyclophosphamide-treated ( 4/8 complete and 4/8 partial ) and all 10 lisinopril-treated patients ( 10/10 partial ) were on remission at the end of the study . In conclusion , cyclosporine-based regimens are not inferior to cyclophosphamide-based regimens . Cyclophosphamide is associated with more complete remissions after 9 months of treatment . Lisinopril is associated with a significant proteinuria reduction and without inducing any complete remissions BACKGROUND Treatment of patients with membranous glomerulonephritis ( MGN ) is controversial because of the lack of clear benefit of the immunosuppressive regimens on patient or renal survival . The objective of this study is to evaluate the efficacy and safety of mycophenolate mofetil ( MMF ) for patients with MGN . STUDY DESIGN 1-year prospect i ve , r and omized , and controlled clinical trial . SETTING & PARTICIPANTS 36 patients with biopsy-proven idiopathic MGN and nephrotic syndrome . INTERVENTION 19 patients received MMF ( 2 g/d ) for 12 months and 17 patients were in the control group . All patients had the same conservative treatment based on renin-angiotensin blockers , statins , low-salt and low-protein diet , and diuretics in case of edema . OUTCOMES & MEASUREMENTS End points were the mean proteinuria over creatinuria ratio in mg/g throughout the study and numbers of complete and partial remissions at 1 year ( month 12 ) . Data were analyzed on an intention-to-treat analysis . RESULTS Mean proteinuria over creatinuria ratio was stable in both groups throughout the study ( P = 0.1 ) . Mean proteinuria over creatinuria ratio was 4,690 + /- 2,212 mg/g in the MMF group and 6,548 + /- 4,601 mg/g in the control group ( 95 % confidence interval of the difference , -619 to + 4,247 ; P = 0.1 ) . Remission was complete in 3 patients ( 1 in the MMF group , 2 in the control group ; P = 0.5 ) and partial in 11 patients ( 6 in the MMF group , 5 in the control group ; P = 0.9 ) . The probability of complete or partial remission did not differ between the 2 groups after 12 months ( relative risk , 0.92 ; 95 % confidence interval , 0.48 to 1.75 ; P = 0.7 ) . Kidney function was stable in the 2 groups according to estimated glomerular filtration rate and serum creatinine level . LIMITATIONS The small number of patients and short follow-up prevent generalizations . CONCLUSIONS A 12-month regimen of MMF did not decrease mean proteinuria over creatinuria ratio or increase partial and complete remissions . Serious adverse effects were observed in 4 patients ( 20 % ) receiving MMF Sixty-seven adults with idiopathic membranous nephropathy and the nephrotic syndrome were r and omly assigned to symptomatic treatment only or to a six-month course of methylprednisolone alternated with chlorambucil every other month . Patients were followed for one to seven years . At the end of follow-up ( mean of 31.4 + /- 18.2 months for the treated group and 37.0 + /- 22.0 for the control group ) 23 of 32 treated patients were in complete or partial remission , as compared with 9 of 30 control patients ( P = 0.001 ) . Twelve of the treated patients were in complete remission , as compared with only two of the controls . In the treated group there were no changes in renal function during follow-up , whereas in the control group the reciprocal of the plasma creatinin level , which is proportional to the creatinine clearance , decreased significantly ( P = 0.00017 ) after two years of follow-up . Side effects were minimal in all treated patients except two , who were dropped from the study because of peptic ulcer and gastric intolerance to chlorambucil . We conclude that steroid and chlorambucil treatment for six months favors remission of the nephrotic syndrome in adults with idiopathic membranous nephropathy and can preserve renal function for at least some years Seventy-two adults with the nephrotic syndrome without renal insufficiency had a membranous type of renal histology on biopsy . These patients were r and omly allocated to at least eight weeks of alternate-day treatment with prednisone or placebo in a multicenter study . Deterioration of glomerular filtration rate was significantly more rapid in placebo-treated than in prednisone-treated patients , and ultimately 10 of 38 given placebo but only one of 34 given prednisone were in renal failure ( creatinine more than 5 mg per deciliter [ 440 mumol per liter ] ) or dead ( P less than 0.02 ) . In male patients and in those with nonselective initial proteinuria , there was a trend ( not reaching statistical significance ) toward more rapid deterioration of renal function . Age , admission blood pressure , serum creatinine , daily total protein excretion , and severity of histologic changes did not predict the subsequent course . We conclude that a short course of alternate-day prednisone therapy was beneficial in our group of patients with idiopathic membranous nephropathy OBJECTIVE To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy . DESIGN R and omized , controlled treatment trial . Patients were followed for a mean of 29.2 + /- 17.1 months . SETTING Collaborative network of 120 university and private- practice nephrologists . PARTICIPANTS Patients with membranous glomerulopathy whose renal function deteriorated ( as evidence d by doubling of the serum creatinine level , a 50 % fall in the glomerular filtration rate , or a sustained serum creatinine level of greater than 2.0 mg/dL [ reciprocal creatinine value , 0.5 ] , or whose nephrotic range proteinuria persisted in association with morbid complications . Of 156 patients with biopsy-proven membranous glomerulopathy , 36 became eligible for r and omization . Twenty-six of these 36 patients were r and omly assigned to receive one of the two treatments . INTERVENTIONS Pulse methylprednisolone , oral corticosteroids , and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone . MAIN RESULTS At entry , no statistical differences were found between the treatment groups in duration of renal disease , age , gender , serum creatinine level , 24-hour urine protein excretion , or biopsy stage . The groups showed no difference in mean arterial blood pressure during follow-up . Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up . Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point . The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment . The power to detect a substantial improvement in renal function , defined as a doubling of the reciprocal of the serum creatinine , at the 0.05 significance level was 0.92 . CONCLUSIONS Combination therapy with intravenous cyclophosphamide and corticosteroids , when compared with corticosteroid therapy alone , does not improve renal function in patients with progressive membranous glomerulopathy AIM There have been very few studies comparing cyclophosphamide ( CTX ) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy ( NIST ) resistant idiopathic membranous nephropathy ( IMN ) . The present study was aim ed at comparing the efficacy and safety of tacrolimus (TAC)/steroids with cyclical CTX/steroids ( Modified Ponticelli regimen ( MPR ) ) in patients with IMN . METHODS Idiopathic membranous nephropathy patients ( n = 70 ) with persistent nephrotic syndrome after at least 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally r and omized to receive TAC with oral prednisolone ( TAC * ) or MPR . Antibodies against m-type phospholipase A2 receptor ( PLA2R Ab ) were tested for at baseline and , at 6 and 12 months after the start of therapy . The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups . RESULTS Intention-to-treat analysis showed that remissions at the end of 6 ( 74 % with TAC * vs. 60 % with MPR ; P = 0.30 ) and 12 months ( 71 % with TAC * vs. 77 % with MPR ; P = 0.78 ) were comparable . PLA2R Ab titres at 6/12 months correlated with urine protein ( r 0.54/0.58 ) and serum albumin ( r -0.49/-0.53 ) at the end of therapy . Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity . CONCLUSION In NIST refractory IMN , both TAC * and MPR are comparable , but with different adverse effect profile . PLA2 R Ab has a very good association with proteinuria , and should be regularly monitored on clinical follow-up We conducted a controlled trial to investigate the long-term effects of treatment with methylprednisolone and chlorambucil in patients with idiopathic membranous nephropathy . We have previously reported that after a mean of 31 months , treated patients did better . We now report the results of a longer follow-up . Eighty-one patients with proteinuria ( greater than or equal to 3.5 g per day ) and biopsy-proved membranous nephropathy were r and omly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil ( 0.2 mg per kilogram of body weight per day ) every other month . Methylprednisolone was first given intravenously in three pulses ( 1 g per day ) and was then given orally ( 0.4 mg per kilogram per day ) for 27 days . The patients were followed for 2 to 11 years ( median , 5 ) . Two patients in the control group and one in the treatment group died . At the last follow-up visit , 9 of 39 patients assigned to the control group ( 23 percent ) and 28 of 42 patients assigned to the treatment group ( 67 percent ) did not have the nephrotic syndrome . At five years there were more remissions of the nephrotic syndrome in treated patients than in controls ( 22 of 30 vs. 10 of 25 ; P = 0.026 ) . Compared with base-line values , the mean reciprocal of the plasma creatinine level declined significantly in the control group ( 33 percent ; P = 0.0002 ) but not in the treatment group ( 6 percent ; P not significant ) . Plasma creatinine increased by 50 percent or more in 19 controls ( 49 percent ) and in 4 treated patients ( 10 percent ) . We conclude that a six-month course of methylprednisolone and chlorambucil can bring about sustained remission of the nephrotic syndrome and help to preserve renal function in patients with idiopathic membranous nephropathy BACKGROUND A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy ( MGN ) was conducted . Although MGN remains the most common cause of adult-onset nephrotic syndrome , its management is still controversial . Cyclosporine has been shown to be effective in cases of progressive MGN , but it has not been used in controlled studies at an early stage of the disease . METHODS We conducted a r and omized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone . All patients were followed for an average of 78 weeks , and the short- and long-term effects on renal function were assessed . RESULTS Seventy-five percent of the treatment group versus 22 % of the control group ( P < 0.001 ) had a partial or complete remission of their proteinuria by 26 weeks . Relapse occurred in 43 % ( N = 9 ) of the cyclosporine remission group and 40 % ( N = 2 ) of the placebo group by week 52 . The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study ( cyclosporine 39 % , placebo 13 % , P = 0.007 ) . Renal function was unchanged and equal in the two groups over the test medication period . In the subsequent follow-up , renal insufficiency , defined as doubling of baseline creatinine , was seen in two patients in each group , but remained equal and stable in all of the other patients . CONCLUSION This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN . Although a high relapse does occur , 39 % of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment , with no adverse effect on filtration function BACKGROUND AND METHODS Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy . To determine whether similar results might be obtained with methylprednisolone alone , we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy . The patients were r and omly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months ( group 1 ) or methylprednisolone alone for six months at the same cumulative dosage ( group 2 ) . RESULTS Four of the 45 patients in group 1 ( 9 percent ) and 1 of the 47 in group 2 ( 2 percent ) stopped treatment because of side effects . At one , two , and three years , the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1 than in group 2 . It was 58 , 54 , and 66 percent , respectively , in group 1 , as compared with 26 , 32 , and 40 percent in group 2 ( P = 0.002 , 0.029 , and 0.011 ) . By year 4 , the difference was no longer statistically significant : 62 percent of the patients in group 1 and 42 percent of those in group 2 did not have the nephrotic syndrome ( P = 0.102 ) . The patients in group 1 were in remission longer than those in group 2 ( P = 0.008 ) . CONCLUSIONS In patients with the nephrotic syndrome caused by idiopathic membranous nephropathy , treatment with methylprednisolone and chlorambucil for six months induces an earlier remission of the nephrotic syndrome than methylprednisolone alone , but the difference may diminish with time The behavior of T lymphocyte subsets was studied in 39 Italian patients with nephrotic syndrome due to idiopathic membranous nephropathy . They took part in a long-term prospect i ve and r and omized therapeutic trial based on the 6-month administration of methylprednisolone and chlorambucil . The lymphocyte subsets were evaluated by monoclonal antibodies at the beginning of the trial and at the end of the follow-up period in 23 treated and in 16 untreated patients . Our data seem to suggest that a higher helper-inducer/suppressor-cytotoxic cell ratio before therapy may be a good prognostic index of improved proteinuria . Moreover , the therapeutic schedule does not seem to induce a long-lasting abnormality in cellular immunity BACKGROUND To compare the safety and efficacy of the traditional Chinese medicine Shenqi particle and st and ard therapy with prednisone and cyclophosphamide ( control ) in adult patients with idiopathic membranous nephropathy ( IMN ) . STUDY DESIGN Open-label , multicenter , parallel , r and omized , controlled clinical trial . SETTING & PARTICIPANTS From April 2008 to February 2011 , a total of 190 patients with biopsy-proven IMN from 7 hospitals in China participated in the study . All patients had nephrotic syndrome with estimated glomerular filtration rate ( eGFR ) > 30 mL/min/1.73 m(2 ) . INTERVENTION Shenqi particle ( 9.6 g 3 times per day ) or prednisone ( 1 mg/kg/d tapering to 0.17 mg/kg/d ) and cyclophosphamide ( total dose of 9 - 12 g per square meter of body surface area ) for 48 weeks . OUTCOMES Primary outcomes included complete remission , defined as proteinuria ( 24-hour urine protein excretion ) ≤0.3 g/d , or partial remission , defined as proteinuria with protein excretion > 0.3-<3.5 g/d and a 50 % reduction from its peak value at 48 weeks . Secondary outcomes included serum albumin level , eGFR , doubling of serum creatinine level , end-stage renal disease , and death . RESULTS Baseline values for proteinuria and eGFR were 5.34 ± 2.74 g/d and 84.0 ± 27.4 mL/min/1.73 m(2 ) for the Shenqi particle group and 5.33 ± 2.47 g/d and 83.8 ± 24.9 mL/min/1.73 m(2 ) for the control group , respectively . 132 patients ( 63 Shenqi particle group , 69 control group ) completed the study . Change in urinary protein excretion in the Shenqi particle group was -3.01 ( 95 % CI , -3.68 to -2.34 ) g/d , and in the control group , -3.28 ( 95 % CI , -3.98 to -2.58 ) g/d ; the mean difference between groups was 0.27 ( 95 % CI , -0.70 to 1.23 ) g/d ( P = 0.6 ) . Changes in eGFR were 12.3 ( 95 % CI , 4.99 to 19.6 ) mL/min/1.73 m(2 ) in the Shenqi particle group and -2.8 ( 95 % CI , -10.32 to 4.77 ) mL/min/1.73 m(2 ) in the control group ; the mean difference between groups was 15.1 ( 95 % CI , 4.56 to 25.55 ) mL/min/1.73 m(2 ) ( P = 0.005 ) . Severe adverse events occurred in only the control group ( 14.5 % ) and included lung infection , liver injury , and pneumonia . LIMITATIONS High rate of loss to follow-up and lack of observation period prior to the study . CONCLUSIONS Shenqi particle may be a promising alternative therapy for adults with IMN and nephrotic syndrome Idiopathic membranous nephropathy ( IMN ) is the most common cause of nephrotic syndrome in adults . Universal consensus regarding the need for and the modality of therapy has not been formed because of a lack of controlled trials of sufficient size , quality , and duration . This study compared the effect of a 6-mo course of alternating prednisolone and cyclophosphamide with supportive treatment in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine , development of ESRD , and quality of life in a r and omized , controlled trial . Patients were followed up for 10 yr . Data were analyzed on an intention-to-treat basis . A total of 93 patients completed the study . Of the 47 patients who received the experimental protocol , 34 achieved remission ( 15 complete and 19 partial ) , compared with 16 ( five complete , 11 partial ) of 46 in the control group ( P < 0.0001 ) . The 10-yr dialysis-free survival was 89 and 65 % ( P = 0.016 ) , and the likelihood of survival without death , dialysis , and doubling of serum creatinine were 79 and 44 % ( P = 0.0006 ) in the two groups . Treated patients exhibited significantly lower prevalence of edema , hypertension , hypoalbuminemia , hyperlipidemia that required therapy , angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use , and better quality of life on follow-up . The incidence of infections was similar in the two groups . In conclusion , untreated IMN with nephrotic syndrome is associated with a high risk for deterioration of renal function . A 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion , arrests progression of renal insufficiency , and improves quality of life In a controlled double-blind trial five patients with the nephrotic syndrome due to idiopathic membranous glomerulonephritis received azathioprine , 2.5 mg/kg-d , while four others received placebo . After 1 year of treatment there was no significant difference between the two groups with regard to the changes in leukocyte count , values for hemoglobin , serum creatinine , blood urea nitrogen or serum albumin , 24-hour excretion of protein in the urine , or creatinine clearance . In this study azathiprine appeared not to be useful in the treatment of idiopathic membranous glomerulonephritis We treated patients with idiopathic membranous nephropathy ( iMGN ) and renal insufficiency , using : ( i ) ( n = 15 ) monthly cycles of steroids ( 1 g methyl-prednisolone i.v . on three consecutive days , followed by oral prednisone 0.5 mg/kg/day months 1 , 3 and 5 ) and chlorambucil ( 0.15 mg/kg/day months 2 , 4 and 6 ) ; or ( ii ) ( n = 17 ) oral cyclophosphamide ( 1.5 - 2.0 mg/kg/day for 1 year ) and steroids in a comparable dose . The groups were comparable in age , renal function and levels of proteinuria . During the 6 months preceding treatment , serum creatinine levels increased from 148 + /- 50 to 219 + /- 73 mumol/l in the chlorambucil group and from 164 + /- 86 to 274 + /- 126 mumol/l in the cyclophosphamide group . Median ( range ) follow-ups were : chlorambucil 38 months ( 8 - 71 ) ; cyclophosphamide 26 months ( 5 - 68 ) ( NS ) . Renal function improved in both groups , but the improvement was short-lived in the chlorambucil group ; 12 months after starting treatment , mean serum creatinine was 6.3 mumol/l lower in the chlorambucil group and 121 mumol/l lower in the cyclophosphamide group ( p < 0.01 ) . Four chlorambucil-treated patients developed ESRD , and five needed a second course of therapy , whereas only one cyclophosphamide-treated patient developed ESRD ( p < 0.05 ) . Remissions of proteinuria occurred more frequently after cyclophosphamide treatment ( 15/17 vs. 5/15 ; p < 0.01 ) . Side-effects necessitated interruption of treatment in six patients on cyclophosphamide and in 11 on chlorambucil ( p < 0.05 ) . In our patients , oral cyclophosphamide was better tolerated than oral chlorambucil . The suggested greater efficacy of the oral cyclophosphamide regimen needs to be ascertained by longer follow-up Background : Idiopathic membranous nephropathy ( IMN ) , a common cause of nephrotic syndrome in adults , is usually treated with corticosteroids in combination with cyclophosphamide or cyclosporine . A recent placebo-controlled study suggested that tacrolimus monotherapy was effective in IMN . However , the effectiveness of tacrolimus versus classic regimen and its potential nephrotoxicity remain inconclusive . This study evaluated the efficacy and safety of tacrolimus plus prednisone in patients with nephrotic IMN . Methods : Seventy-three patients with nephrotic IMN were recruited in this multicenter r and omized controlled trial , 39 receiving tacrolimus and prednisone , while 34 receiving cyclophosphamide and prednisone . Tacrolimus was given at 0.1 mg/kg/d initially and adjusted to a blood trough level at 5 to 10 ng/mL for 6 months and then reduced to 2 to 5 ng/mL in the subsequent 3 months . Results : Intention-to-treat analysis suggested that the remission rate at the end of the sixth month was significantly higher in tacrolimus group than that in cyclophosphamide group ( 85 % versus 65 % , P < 0.05 ) . The decrease of proteinuria was significantly greater in tacrolimus group . At the end of the 12th month , the remission rates were comparable between these 2 groups . Patients treated with tacrolimus were more likely to develop glucose intolerance ( or diabetes mellitus ) , infection , and hypertension . No obvious nephrotoxicity of calcineurin inhibitor was found in repeat renal biopsy . Conclusions : Tacrolimus plus corticosteroids is an alternative therapeutic regimen for nephrotic IMN . The short-term efficacy might be better than cyclophosphamide plus prednisone |
1,105 | 31,804,617 | Thus , intradialytic exercise protocol s can improve cardiopulmonary function , exercise tolerance and ventilatory efficiency in chronic kidney disease patients | Patients with chronic kidney disease show poorer functional and cardiorespiratory capacity than healthy individuals , and these impairments result in sedentarism .
The aim of this study was to conduct a systematic review and meta- analysis of r and omized clinical trials on the effects of different intradialytic exercise protocol s on cardiopulmonary capacity in chronic kidney disease patients . | INTRODUCTION Hemodialysis contributes to increased oxidative stress and induces transitory hypoxemia . Compartmentalization decreases the supply of solutes to the dialyzer during treatment . The aim of this study was to investigate the acute effects of intradialytic aerobic exercise on solute removal , blood gases and oxidative stress in patients with chronic kidney disease during a single hemodialysis session . METHODS Thirty patients were r and omized to perform aerobic exercise with cycle ergometer for lower limbs during 30 minutes with intensity between 60 - 70 % of maximal heart rate , or control group ( CG ) . Blood sample s were collected prior to and immediately after exercise or the equivalent time in CG . Analysis of blood and dialysate biochemistry as well as blood gases were performed . Mass removal and solute clearance were calculated . Oxidative stress was determined by lipid peroxidation and by the total antioxidant capacity . RESULTS Serum concentrations of solutes increased with exercise , but only phosphorus showed a significant elevation ( p = 0.035 ) . There were no significant changes in solute removal and in the acid-base balance . Both oxygen partial pressure and saturation increased with exercise ( p = 0.035 and p = 0.024 , respectivelly ) , which did not occur in the CG . The total antioxidant capacity decreased significantly ( p = 0.027 ) . CONCLUSION The acute intradialytic aerobic exercise increased phosphorus serum concentration and decreased total antioxidant capacity , reversing hypoxemia result ing from hemodialysis . The intradialytic exercise did not change the blood acid-base balance and the removal of solutes BACKGROUND Individuals on hemodialysis have low physical function and activity levels . Clinical trials have shown improvements in these parameters with exercise programming . Pedometers have not been extensively evaluated in individuals on hemodialysis . This r and omized clinical trial compared the effects of intradialytic cycling versus a pedometer program on physical function , physical activity and quality of life . METHODS Sixty patients were r and omly assigned to two study groups . The ergometer group cycled during each hemodialysis session for 24 weeks . Pedometer participants followed a home-based walking program for 24 weeks . The primary outcome was aerobic capacity [ VO2peak and 6-minute walk ( 6MW ) test ] . Secondary outcomes included lower extremity strength [ sit-to-st and ( SS ) test ] , flexibility [ sit- and -reach ( SR ) test ] , physical activity ( accelerometer ) and health-related quality of life . Measurements were collected at baseline and at 12 and 24 weeks . RESULTS At 12 and 24 weeks , there was no significant change in the VO2peak or 6MW test between or within study groups . SS testing in the ergometer group improved from 10.2 ( SD 3.4 ) to 11.4 ( SD 2.5 ) cycles from baseline to 24 weeks ( P < 0.005 ) . Similarly , in the pedometer group , SS cycles improved from 10.1 ( SD 3.3 ) to 12.2 ( SD 3.5 ) ( P < 0.005 ) . The SR test also significantly improved over time in both the study groups . No significant changes were noted for other secondary outcomes . CONCLUSIONS Both intradialytic cycling and pedometer programming improved aspects of physical function . Neither intervention had a significant effect on aerobic capacity . No significant differences in any outcomes were identified between interventions groups OBJECTIVES The purpose of this study is to determine whether a low-to-moderate intensity pre-conditioning exercise programme linked with exercise counselling could improve behavioural change , physical fitness , physiological condition and health-related quality of life of sedentary haemodialysis patients in The Netherl and s. METHODS Ninety-six haemodialysis patients of the Groningen Dialysis Center were r and omized into an exercise group ( n = 53 ) and a control group ( n = 43 ) . The exercise programme consists of cycling during dialysis together with a pre-dialysis strength training programme lasting 12 weeks . The intensity of the exercise programme is condition level 12 - 16 according to the rate of perceived exertion ( RPE ) . Motivational interviewing techniques were used for exercise counselling . Before and after the intervention , both groups were tested on behavioural change and physical fitness components such as reaction time , manual dexterity , lower extremity muscle strength and VO2 peak . Physiological conditions such as weight , blood pressure , haemoglobin and haematocrit values , cholesterol and Kt/V were obtained from the medical records . Health-related quality of life assessment included R AND -36 scores , symptoms and depression . RESULTS A group x time analysis with MANOVA ( repeated measures ) demonstrates that participation in a low-to-moderate intensity exercise programme linked with exercise counselling yields a significant increase in behavioural change , reaction time , lower extremity muscle strength , Kt/V and three components of quality of life , and no significant effects in the control group . CONCLUSION Participating in a low-to-moderate intensity pre-conditioning exercise programme showed beneficial effects on behavioural change , physical fitness , physiological conditions and health-related quality of life In chronic kidney disease ( CKD ) , oxidative stress ( OS ) plays a central role in the development of cardiovascular diseases . This pilot program aim ed to determine whether an intradialytic aerobic cycling training protocol , by increasing physical fitness , could reduce OS and improve other CKD-related disorders such as altered body composition and lipid profile . Eighteen hemodialysis patients were r and omly assigned to either an intradialytic training ( cycling : 30 min , 55%-60 % peak power , 3 days/week ) group ( EX ; n = 8) or a control group ( CON ; n = 10 ) for 3 months . Body composition ( from dual-energy X-ray absorptiometry ) , physical fitness ( peak oxygen uptake and the 6-minute walk test ( 6MWT ) ) , lipid profile ( triglycerides ( TG ) , total cholesterol , high-density lipoprotein , and low-density lipoprotein ( LDL ) ) , and pro/antioxidant status ( 15-F2α-isoprostanes ( F2-IsoP ) and oxidized LDL in plasma ; superoxide dismutase , glutathione peroxidase , and reduced/oxidized glutathione in erythrocytes ) were determined at baseline and 3 months later . The intradialytic training protocol did not modify body composition but had significant effects on physical fitness , lipid profile , and pro/antioxidant status . Indeed , at 3 months : ( i ) performance on the 6MWT was increased in EX ( + 23.4 % , p < 0.001 ) but did not change in CON , ( ii ) plasma TG were reduced in EX ( -23 % , p < 0.03 ) but were not modified in CON , and ( iii ) plasma F2-IsoP concentrations were lower in EX than in CON ( -35.7 % , p = 0.02 ) . In conclusion , our results show that 30 min of intradialytic training , 3 times per week for 3 months , are enough to exert beneficial effects on the most sensitive and reliable marker of lipid peroxidation ( IsoP ) while improving CKD-associated disorders ( lipid profile and physical fitness ) . Intradialytic aerobic cycling training represents a useful and easy strategy to reduce CKD-associated disorders . These results need to be confirmed with a larger r and omized study AimS keletal muscle atrophy and dysfunction with associated weakness may involve the respiratory muscles of dialysis patients . We evaluated the effect of moderate-intensity exercise on lung function and respiratory muscle strength . Methods Fifty-nine patients ( 25 F , aged 65 ± 13 years ) from two centers participating in the multicenter r and omized clinical trial EXerCise Introduction To Enhance Performance in Dialysis ( EXCITE ) were studied . Subjects were r and omized into a prescribed exercise group ( E ) , wherein subjects performed two 10-min walking sessions every second day at an intensity below the self-selected speed , or a control group ( C ) with usual care . Physical performance was assessed by the 6-min walk test ( 6MWT ) . Patient lung function and respiratory muscle strength were evaluated by spirometry and maximal inspiratory pressure ( MIP ) , respectively . Results Forty-two patients ( 14 F ) completed the study . At baseline , the groups did not differ in any parameters . In total , 7 patients ( 4 in E ; 3 in C ) showed an obstructive pattern . The pulmonary function parameters were significantly correlated with 6MWT but not with any biochemical measurements . Group E safely performed the exercise program . At follow-up , the spirometry parameters did not change in either group . A deterioration of MIP ( −7 % ; p = 0.008 ) was observed in group C , but not in group E ( + 3.3 % , p = ns ) . In E , an increase of 6MWT was also found ( + 12 vs. 0 % in C ; p = 0.038 ) . Conclusion In dialysis patients , a minimal dose of structured exercise improved physical capacity and maintained a stable respiratory muscle function , in contrast to the control group where it worsened OBJECTIVE To investigate if high-intensity constant work rate ( CWR ) would constitute a more appropriate testing strategy compared with incremental work rate ( IWR ) to assess the effectiveness of intradialytic aerobic training in patients with end-stage renal disease ( ESRD ) . DESIGN R and omized controlled trial . SETTING Nephrology unit at the university hospital . PARTICIPANTS Patients ( N=28 ; 47.0±11.9y ) under hemodialysis ( 4.4±4.3y ) were r and omly assigned to exercise and control groups . INTERVENTION Patients included in the exercise group underwent a moderate-intensity intradialytic aerobic training program 3 times per week for 12 weeks . MAIN OUTCOME MEASURES Cardiopulmonary and perceptual responses were obtained during an IWR and a high-intensity CWR test to the limit of tolerance on a cycle ergometer . RESULTS Training-induced increases in peak oxygen uptake ( Vo(2)peak ) and time to exercise intolerance ( Tlim ) . Mean improvement in Tlim ( 97.4%±75.6 % ) was significantly higher than increases in Vo(2)peak ( 12%±11.3 % ) ( P<.01 ) ; in fact , while Tlim improved 50 % to 200 % in 9 of 12 patients , Vo(2)peak increases were typically in the 15 % to 20 % range . CWR test revealed lower metabolic , ventilatory , cardiovascular , and subjective stresses at isotime ; in contrast , submaximal responses during the incremental work rate ( at the gas exchange threshold ) remained unaltered after training . CONCLUSIONS A laboratory-based measure of endurance exercise capacity ( high-intensity CWR test to Tlim ) was substantially more sensitive than oxygen uptake at the peak IWR test to unravel the physiologic benefits of an intradialytic aerobic training program in mildly impaired patients with ESRD Introduction Literature shows that patients undergoing hemodialysis present poor physical conditioning and low tolerance to exercise . They may also suffer from respiratory dysfunctions . The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation on pulmonary function and functional capacity of patients with chronic kidney disease on hemodialysis . Methods Forty adult patients with chronic kidney disease on hemodialysis were prospect ively studied and r and omized into two groups ( control n = 20 and treatment n = 20 ) . The treatment group underwent bilateral femoral quadriceps muscles electrical stimulation for 30 minutes during hemodialysis , three times per week , for two months . The patients were evaluated by pulmonary function test , maximum respiratory pressures , maximum one-repetition test , and six-minute walk test ( 6MWT ) , before and after the treatment protocol . Results The treatment group presented increased maximum inspiratory ( MIP ) ( p = 0.02 ) and expiratory pressures ( MEP ) ( p < 0.0001 ) , muscular strength in maximum one-repetition test ( p < 0.001 ) , and distance covered in the 6MWT ( p = 0.03 ) , and decreased systolic blood pressure ( p < 0.001 ) and respiratory frequency ( p < 0.001 ) when compared with the control group . Conclusion Electrical neuromuscular stimulation had a positive impact on pulmonary function and functional capacity , leading to better physical performance in patients on hemodialysis Functional capacity of end-stage renal disease patients is dramatically impaired . Although exercise training programs appear to have beneficial morphological , functional and psychosocial effects in end-stage renal disease patients on hemodialysis ( HD ) , the adherence rate is high . The purpose of this study was to compare the effects of three modes of exercise training on aerobic capacity and to identify the most favourable , efficient and preferable to patients on HD with regard to functional improvements and participation rate in the programs . Fifty-eight volunteer patients were screened for low-risk status and selected from the dialysis population . The 48 patients who completed the study protocol were r and omly assigned either to one of the three training groups or to a control group . Sixteen of them ( Group A - mean age 46.4+/-13.9 years ) completed a 6-month supervised outpatient exercise renal rehabilitation program consisting of three weekly sessions of aerobic and strengthening training on the non-dialysis days ; 10 ( Group B - mean age 48.3+/-12.1 years ) completed a 6-month exercise program during HD ; 10 ( Group C - mean age 51.4+/-12.5 years ) followed an unsupervised moderate exercise program at home , and 12 patients ( Group D-mean age 50.2+/-7.9 years ) were used as patient controls . The level of anemia , the medications and the HD prescription remained stable during the study . Fifteen sex- and age-matched sedentary individuals ( Group E - mean age 46.9+/-6.4 years ) comprised a healthy control group for baseline data . All subjects at the beginning and end of the study underwent clinical examination , laboratory tests and a treadmill exercise test to fatigue endpoints with direct measurement of aerobic capacity . Group A had a higher dropout rate ( 24 % ) compared to groups B ( 17 % ) and C ( 17 % ) . Peak oxygen consumption ( VO2 peak ) increased by 43 % ( p < 0.05 ) , anaerobic threshold ( VO2AT ) by 37 % ( p < 0.05 ) and exercise time by 33 % ( p < 0.05 ) after training in Group A ; by 24 % ( p < 0.05 ) , 18 % ( p < 0.05 ) and 22 % ( p < 0.05 ) , respectively , in B ; and by 17 % ( p < 0.05 ) , 8 % ( p < 0.05 ) and 14 % ( p < 0.05 ) , respectively , in C ; while both remained almost unchanged in Group D. These results demonstrate that intense exercise training on non-dialysis days is the most effective way of training , whereas exercise during HD is also effective and preferable The limitation to exercise capacity in hemodialysis patients has been attributed to anemia . We report the effects of normalization of hematocrit levels by using r-hu-recombinant erythropoietin and exercise training on exercise capacity and self-reported physical functioning in hemodialysis patients . Sixty-five patients were r and omized into 1 of 4 groups : usual hematocrit ( 30%-33 % ) with no exercise training ( UH ) ; usual hematocrit ( 30%-33 % ) plus exercise training ( UHX ) ; normalized hematocrit ( 40%-42 % ) with no exercise training ( NH ) ; and normalized hematocrit ( 40%-42 % ) plus exercise training ( NHX ) . Treadmill exercise testing was conducted at baseline and at 5 months after the initiation of the interventions . Analysis was performed on the data collapsed for 48 patients who met the criteria for hematocrit and exercise adherence and completed both baseline and post intervention ( 5.6 + /- 1.6 months ) testing . Significant effects of exercise were found in peak oxygen uptake measurements ( P = 0.03 ) and in self-reported physical functioning as measured by the Short Form-36 question naire ( P = 0.01 ) . There was a significant effect of hematocrit on the General Health scale on the SF-36 ( P = 0.03 ) . The changes in peak oxygen uptake with exercise training were small and levels remained lower than age-predicted values at the end of the study . These results indicate that there are other physiologic limitations to exercise capacity that are not overcome by exercise training or normalization of hematocrit . The effects of exercise training on self-reported physical functioning may be of clinical importance because these scores have been shown to be highly predictive of outcomes such as hospitalizations and mortality in hemodialysis patients The aim was to assess the effects of exercise training on aerobic and functional capacity of patients with end‐stage renal disease ( ESRD ) . Patients completed an incremental exercise test on a cycle ergometer to determine VO2 peak and VO2 at ventilatory threshold ( VT ; V‐slope ) . On a separate day they performed two constant load exercise tests on a cycle ergometer at 90 % of VT and at a workload of 33 W , to determine VO2 kinetics . Functional capacity was assessed using measurements of sit‐to‐st and s ( STS‐5 , STS‐60 ) and a walk test . Dialysis patients were r and omly allocated to an exercise ( ET : n=18 , age=57·3 years ) or control ( C : n=15 , age=50·5 years ) group . The ET group participated in an exercise training programme involving cycling for 3 months . Repeated measures ANOVA revealed significant time by group interactions ( P < 0·05 ) following training for VO2 peak ( ET : 17 ± 6·1 versus 19·9 ± 6·3 , C : 19·5 ± 4·7 versus 18·8 ± 4·9 ml kg min–1 ) and VO2–VT ( ET : 10·7 ± 3·5 versus 11·8 ± 3·3 , C:12·9 ± 3·2 versus 11·9 ± 3·5 ml kg min–1 ) . VO2 kinetics remained unchanged in both groups at 90 % ‐VT , but a trend ( P=0·059 ) towards faster kinetics at the 33 W was observed ( ET : 49·6 ± 19·5 versus 37·8 ± 12·7 , C : 42·8 ± 13 versus 49·4 ± 20·2 s ) . Significant time by group interactions ( P < 0·05 ) were also observed for STS‐5 ( ET : 14·7 ± 6·2 versus 11·0 ± 3·3 , C : 12·8 ± 4·4 versus 12·7 ± 4·8 s ) and STS‐60 measurements ( ET : 21·2 ± 7·2 versus 26·9 ± 6·2 , C : 23·7 ± 6·8 versus 24·1 ± 7·2 ) . Three months of exercise rehabilitation significantly improves peak exercise capacity of patients with ESRD . Measurements of VO2 kinetics and functional capacity suggest that longer time might be needed to induce peripheral adaptations BACKGROUND AND OBJECTIVES Patients with CKD have a high prevalence of cardiovascular disease associated with or exacerbated by inactivity . This r and omized , controlled study investigated whether a renal rehabilitation exercise program for patients with stages 3 or 4 CKD would improve their physical function and quality of life . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In total , 119 adults with CKD stages 3 and 4 were r and omized , and 107 of these patients proceeded to usual care or the renal rehabilitation exercise intervention consisting of usual care plus guided exercise two times per week for 12 weeks ( 24 sessions ) . Physical function was determined by three well established performance-based tests : 6-minute walk test , sit-to-st and test , and gait-speed test . Health-related quality of life was assessed by the R AND 36-Item Short Form Health Survey . RESULTS At baseline , no differences in self-reported level of activity , 6-minute walk test , and sit-to-st and test scores were observed between the usual care ( n=48 ) and renal rehabilitation exercise ( n=59 ) groups , although baseline gait-speed test score was higher in the renal rehabilitation exercise group ( P<0.001 ) . At follow-up , the renal rehabilitation exercise group but not the usual care group showed significant improvements in the 6-minute walk test ( + 210.4±266.0 ft [ 19 % improvement ] versus -10±219.9 ft ; P<0.001 ) , the sit-to-st and test ( + 26.9±27 % of age prediction [ 29 % improvement ] versus + 0.7±12.1 % of age prediction ; P<0.001 ) , and the R AND -36 physical measures of role functioning ( P<0.01 ) , physical functioning ( P<0.01 ) , energy/fatigue levels ( P=0.01 ) , and general health ( P=0.03 ) and mental measure of pain scale ( P=0.04 ) . The renal rehabilitation exercise regimen was generally well tolerated . CONCLUSIONS A 12-week/24-session renal rehabilitation exercise program improved physical capacity and quality of life in patients with CKD stages 3 and 4 . Longer follow-up is needed to determine if these findings will translate into decreased mortality rates |
1,106 | 23,303,472 | Cossins et al. , ( 2012 ) conclude that there is strong evidence that a number of treatments are effective .
Further , where statistically significant results are robust , the true treatment effect may still be clinical ly trivial .
For example , the authors conclude that there is strong evidence that repetitive transcranial magnetic stimulation ( rTMS ) is effective .
Indeed , generally , in chronic pain , there is reason to doubt that rTMS delivers clinical ly meaningful reductions in pain ( O’Connell et al. , 2010 ) .
In our view , while some treatments hold promise , there is currently no intervention for CRPS that can be considered to be supported by strong evidence of efficacy ; although we agree that the evidence is strong that intravenous regional blockade with guanethidine is ineffective . | In this issue , you will find a paper by Cossins et al. , ( 2012 ) entitled ‘ Treatment of complex regional pain syndrome [ CRPS ] in adults : A systematic review of r and omised controlled trials published from June 2000 to February 2012 ’ .
The aim of this review was to provide an up date d summary of the evidence of effectiveness for all treatments for CRPS .
This is an important task as considerable uncertainty persists regarding the optimal management of this condition .
It is also a difficult one .
Heterogeneity in interventions , dose , delivery method , diagnostic criteria and stage of the disease are frequently compounded by incomplete reporting in the original trials . | A number of pharmacologic treatments examined in recent r and omized clinical trials ( RCTs ) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated . Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies , such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ( “ assay sensitivity ” ) . Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development . Therefore , an Initiative on Methods , Measurement , and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was review ed and discussed . On the basis of this meeting and subsequent discussion s , the authors recommend consideration of a number of patient , study design , study site , and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments . Increased attention to and research on method ological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence ‐based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety In complex regional pain syndrome ( CRPS ) many clinical symptoms suggest involvement of the central nervous system . Neuropathic pain as the leading symptom is often resistant to therapy . In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation ( rTMS ) applied to the motor cortex contralateral to the CRPS-affected side . Seven out of ten patients reported decreased pain intensities . Pain relief occurred 30 s after stimulation , whereas the maximum effect was found 15 min later . Pain re-intensified increasingly 45 min after rTMS . In contrast , sham rTMS did not alter pain perception . These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation 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 |
1,107 | 10,796,307 | MAIN RESULTS Nasal CPAP , when applied to preterm infants being extubated following IPPV , reduces the incidence of adverse clinical events ( apnea , respiratory acidosis and increased oxygen requirements ) indicating the need for additional ventilatory support .
A reduction in the incidence of chronic lung disease at 28 days of age is also seen in the group extubated to NCPAP .
REVIEW ER 'S CONCLUSIONS IMPLICATION S FOR PRACTICE nasal CPAP is effective in preventing failure of extubation and reducing oxygen use at 28 days of life in preterm infants following a period of endotracheal intubation and IPPV . | BACKGROUND Preterm infants being extubated following a period of intermittent positive pressure ventilation via an endotracheal tube are at risk of developing respiratory failure as a result of apnea , respiratory acidosis and hypoxia .
Nasal continuous positive airway pressure appears to stabilise the upper airway , improve lung function and reduce apnea and may therefore have a role in facilitating extubation in this population .
OBJECTIVES In preterm infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation ( IPPV ) , does management with nasal continuous positive airways pressure ( NCPAP ) lead to an increased proportion remaining free of additional ventilatory support , compared to extubation directly to headbox oxygen ? | OBJECTIVE The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure ( CPAP ) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight ( VLBW ) infants . STUDY DESIGN We studied prospect ively 87 preterm infants ( mean + /- SD ; birth weight : 1078 + /- 188 g ; gestational age : 28.8 + /- 2.2 weeks ) who were in the process of being weaned from intermittent m and atory ventilation ( IMV ) . Infants were assigned by systematic sampling to one of the following three treatment groups : ( 1 ) direct extubation from IMV ( D.EXT ) ( n = 30 ) ; ( 2 ) preextubation endotracheal CPAP ( ET-CPAP ) for 12 - 24 hr ( n = 28 ) ; or ( 3 ) postextubation nasopharyngeal CPAP ( NP-CPAP ) for 12 - 24 hr ( n = 29 ) . Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and /or respiratory failure ( pH < 7.25 , PaCO2 > 60 mm Hg , and /or requirement for oxygen FiO2 > 60 % ) . RESULTS There were no significant differences in failure rates among the three procedures . Failures were 2/30 ( 7 % ) in D.EXT ; 4/28 ( 14 % ) in ET-CPAP ; and 7/29 ( 24 % ) in the NP-CPAP . There were also no differences in FiO2 , PaO2 , and respiratory rates before and after discontinuation of IMV among the three groups . PaCO2 values were slightly higher in the NP-CPAP group 12 - 24 hr after weaning from IMV . CONCLUSION We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low-rate IMV in VLBW infants AIM To determine whether extubation to nasal continuous airway pressure ( NCPAP ) results in a greater proportion of infants remaining free of additional ventilatory support for one week after extubation compared with those extubated directly to headbox oxygen . METHODS A r and omised , controlled , clinical trial was conducted at the neonatal intensive care unit of the Royal Women ’s Hospital , Melbourne , of infants with birthweights between 600 and 1250 g , ventilated via an endotracheal tube for more than 12 hours , requiring less than 50 % oxygen , a ventilator rate ⩽ 20/minute , considered by the clinical management team to be ready for extubation . Infants were r and omly allocated either to NCPAP or to oxygen administered via a headbox . Success was defined by no requirement for additional ventilatory support over the week following extubation . Failure criteria were ( i ) apnoea ; ( ii ) absolute increase in oxygen requirement greater than 15 % above that required before extubation ; or ( iii ) respiratory acidosis ( pH<7.25 with pCO2 > 6.67 kPa ) . RESULTS Thirty one of 47 ( 66 % ) infants were successfully extubated to NCPAP compared with 18 of 45 ( 40 % ) for headbox oxygen . The increase in failure rate in the headbox group was due primarily to increased oxygen requirements in this group . Of the 27 who failed headbox oxygen , 26 were given a trial of NCPAP and 13 did not require endotracheal reintubation . There was no significant difference between the groups in the total number of days of assisted ventilation or the duration of inpatient stay . CONCLUSIONS NCPAP applied prophylactically after endotracheal extubation reduces the incidence of adverse clinical events that lead to failure of extubation in the seven days after extubation . This reduction is clinical ly important . The benefits of NCPAP do not seem to be associated with an increased incidence of unwanted side effects Sixty infants ( median gestational age 29 weeks ) with acute and 60 infants ( median gestational age 25 weeks ) with chronic respiratory distress were r and omised to be extubated either directly into a headbox or onto 3 cm H2O nasal continuous positive airway pressure ( CPAP ) . Our aim was to test the hypothesis that extubation onto nasal CPAP rather than directly into a headbox was more likely to be associated with successful extubation in infants with acute rather than chronic respiratory distress . Overall the failure rate of extubation was approximately 33 % , with no significant difference between the infants with acute and chronic respiratory distress . There was no significant difference in the failure rate of extubation among infants r and omised to receive nasal CPAP or headbox oxygen in either the acute or chronic respiratory distress groups We conducted a prospect i ve , r and omized controlled trial to determine whether extubation of very low birth weight infants was facilitated by the use of nasopharyngeal continuous positive airway pressure ( CPAP ) . Eligible infants included patients weighing 600 to 1500 gm at birth who required tracheal intubation within 48 hours of birth and who met specific predetermined criteria for extubation by day 14 of life . We also sought to determine whether varying the duration of nasopharyngeal CPAP influenced the likelihood of successful extubation . Infants underwent r and om assignment to receive nasopharyngeal CPAP until resolution of lung disease ( n = 40 ) , 6 hours of nasopharyngeal CPAP ( n = 42 ) , or oxygen supplementation delivered by hood ( n = 42 ) . Extubation failure was predefined as a requirement for > or = 80 % oxygen , pH < or = 7.20 , severe apnea , or predefined clinical deterioration , and extubation success was predefined as the ability to remain free of a requirement for mechanical ventilation for 7 days and a 66 % reduction in the need for supplemental oxygen . Each group was similar with regard to race , sex , and birth weight . Extubation was successful in 62 % , 61 % , and 60 % of infants . After stratification by birth weight , there were no significant differences in the rates of successful extubation among the treatment groups . We conclude that nasopharyngeal CPAP does not improve the likelihood of successful extubation of very low birth weight infants who are ready for extubation within the first 2 weeks of life AIM To determine if a weaning regimen on flow driver continuous positive airway pressure ( CPAP ) would decrease the number of ventilator days but increase the number of CPAP days when compared with a rescue regimen . METHODS Fifty eight babies of 24–32 weeks gestation with respiratory distress syndrome ( RDS ) were studied prospect ively . After extubation they were r and omly allocated to receive CPAP for 72 hours ( n=29 ) according to a weaning regimen , or were placed in headbox oxygen and received CPAP only if preset “ start CPAP ” criteria were met ( n=29 , rescue group ) . RESULTS There was no difference in successful extubation at 72 hours , 1 and 2 weeks , between the groups in terms of the number of reventilation episodes , reventilation days , or in total days of CPAP . Birthweight , gestational age , race , day of first extubation , antenatal or postnatal steroids , patent ductus arteriosus status and maximal mean airway pressure used were of no value in predicting success or failure at 72 hours , 1 , or 2 weeks . CONCLUSION The weaning regimen did not decrease the number of ventilator days or days on CPAP compared with the rescue regimen . The rescue regimen on flow driver CPAP seems to be a safe and effective method of managing a baby of 24–32 weeks gestation who has been ventilated for RDS or immature lung disease Using a preset protocol for early extubation , 50 babies were r and omly selected to post-extubation headbox or post-extubation nasal continuous positive airway pressure ( N-CPAP ) . All infants weighed less than 1500 g , had a gestational age of less than 34 weeks , and had been weaning from mechanical ventilation within seven days of life . The criteria for extubation included stable condition , fraction of inspired oxygen ( FIO2 ) of < or = 35 % , peak inspiratory pressure ( PIP ) of < or = 15 cm H2O ( 1.47 kPa ) , and ventilator rate of 6/minute . Before extubation , a loading dose of aminophylline was given followed by maintenance treatment . If reintubation was not required within 72 hours of the initial extubation the procedure was considered successful . The reintubation criteria included FIO2 > or = 70 % to maintain arterial oxygen tension ( PaO2 ) of > or = 50 mm Hg ( 6.67 kPa ) or pulse oximetry between 90 - 96 % and pH of < 7.25 , and arterial carbon dioxide tension ( PACO2 ) of > 60 mm Hg ( 8.00 kPa ) and severe or recurring apnoea . The overall success rate of early extubation was 66 % ( 33/50 ) . The individual successful extubation rate of post-extubation in the N-CPAP group and the post-extubation headbox group were 84 % ( 21/25 ) and 48 % ( 12/25 ) , respectively ( p = 0.017 ; chi 2 ) . There were no significant differences in clinical characteristics between the two groups . The most common cause of failure in early extubation was apnoea , and most occurred in the headbox group ( 9/12 ) . These results suggest that application of N-CPAP to a preset protocol for extubation can achieve a better success rate of early extubation in very low birthweight ( VLBW ) infants Nasal continuous positive airway pressure ( N-CPAP ) , applied immediately after extubation , was prospect ively evaluated in 18 neonates recovering from respiratory distress syndrome . Patients were r and omly assigned to N-CPAP ( group 1 , N=9 ) or a control group given oxygen by hood ( group 2 , N=9 ) . Groups were comparable in birth weight and duration of intubation . In the 24-hour period following extubation , group 1 showed a significantly lower mean respiratory rate ( 46 + /- 2 vs 74 + /- 4 ) , alveolar-arterial oxygen gradient ( 94 + /- 9 vs 134 + /- 12 mm Hg ) , PCO2 ( 45 + /- 1 vs 50 + /- 1 mm Hg ) , higher pH ( 7.33 + /- 0.01 vs 7.30 + /- 0.01 ) , and less atelectasis by roentgenographic scores . This was associated with considerably better clinical courses in group 1 when compared with group 2 , in which six patients required a late trial of N-CPAP because of respiratory deterioration and two patients needed reintubation . Postextubation N-CPAP has a striking beneficial effect on respiratory function and prevention of atelectasis A prospect i ve r and omized trial was performed in 58 neonates comparing nasal continuous positive airway pressure ( NCPAP ) vs oxyhood following extubation of neonates weighing less than 1 kg . All neonates had been ventilated for the treatment of respiratory distress syndrome for at least 24 hours and weighed less than 1 kg at the time of extubation . Clinical criteria for elective extubation included improving pulmonary status , fraction of inspired oxygen ( FIO2 ) less than or equal to 0.35 , mean airway pressure less than or equal to 7 cm H2O , ventilator rate less than or equal to 20 breaths per minute , and weight at least 80 % of birth weight . Informed consent was obtained and neonates were r and omized to NCPAP or oxyhood following extubation . Success was defined as remaining free of additional ventilatory support for at least 5 days . Failure criteria included FIO2 greater than or equal to 0.60 to maintain pulse oximetry greater than or equal to 93 % , PaCO2 greater than or equal to 60 mm Hg , pH less than or equal to 7.23 , or moderate to severe apnea . Results demonstrate that 22 ( 76 % ) of 29 neonates were successfully extubated to NCPAP while only 6 ( 21 % ) of 29 were successfully extubated to oxyhood ( P less than .0001 ) . There were no differences in baseline characteristics between the two groups . Of the 23 neonates who failed oxyhood , 21 were then given a trial of NCPAP and 58 % ( 12/21 ) remained extubated . Data indicate that using selected clinical criteria for elective extubation of neonates weighing less than 1 kg , NCPAP facilitates successful extubation |
1,108 | 28,727,510 | The main findings indicated that perspectives of pre- and in-service teachers and studies of attitudes still dominate the research contributions . | This systematic review examines research published from 2009 to 2015 on inclusion of children with disabilities in physical education according to the PRISMA guidelines . | With an increase in the presence of students with autism spectrum disorder ( ASD ) in the general physical education ( GPE ) classroom , underst and ing the current state of GPE teachers ' beliefs and behaviors for including these students is warranted . The current study aim ed to examine the beliefs and self-reported behaviors of GPE teachers ' inclusion of students with ASD . In addition , the study examined potential factors affecting their inclusion behaviors . Using a national stratified r and om sample , participants were 142 current GPE teachers who su bmi tted surveys anonymously online . Results from a regression analysis indicate that teachers ' experience , graduate coursework in adapted physical education ( APE ) , and perceptions of strength in undergraduate training in APE significantly predicted their self-reported behavior for including students with ASD . Although the participant response rate is considerably low , this study provides some support toward the importance of teacher education programs for inclusion training The study investigated the effects of a Special Olympics ( SO ) Unified Sport ( UNS ) soccer program on anthropometry , physical fitness and soccer skills of male youth athletes with and without intellectual disabilities ( ID ) who participated in a training group ( TRG ) and in a comparison group ( CG ) without specific training . Youth with ID ( WID ) were r and omly selected out of all the students between the ages 12 and 15 , with a diagnosis of educable mental retardation and no secondary disabilities , who were attending a special education school . Participants without ID ( WoID ) were r and omly selected from a regular secondary school out of the same age groups of male students . All participants were given permission by their parents or guardians to participate in the study . Participants in the TRG included 23 youth WID and 23 youth WoID . Mean ages were = 14.1 ( SD = 1.1 ) and 13.2 ( SD = 0.79 ) respectively . Fifteen WID , and 15 WoID comprised the CG . Mean ages were 14.51 ( SD = 0.81 ) and 13.78 ( SD = 0.49 ) respectively . Prior to and following the program measurements were conducted , and data were collected on students ' anthropometric and fitness components of the Brockport physical fitness test as well as a soccer skill performance based on the SO soccer skill test . Participants in the TRG trained 8 weeks , 1.5h per session , three times per week , in an after-school soccer program . CG did not participate in any sports program outside of the school physical education class . Dependent t tests and effect size calculations revealed that SO athletes and non-disabled partners scored significantly higher with regard to physical fitness and football skills in most variables compared with their CG . This Unified Program was successful in increasing fitness and soccer skill performance of youth WID as well as of those WoID The purpose of this study was to explore the effect of two awareness programs ( 6-day vs. 1-day programs ) on children 's attitudes toward peers with a visual impairment . Three hundred and forty-four Spanish physical education students ( 164 girls and 180 boys ) aged 10–15 years , took part in the study . A modified version of the Attitudes Toward Disability Question naire ( ATDQ ) was used , which includes three sub-scales : ( i ) cognitive perceptions , ( ii ) emotional perception , and ( iii ) behavioral readiness to interact with children with disabilities . The question naire was filled out during the regular physical education class before and immediately after the awareness activity . The 6-day didactical unit included a lecture on visual impairments and a video describing visual impairments and the game of 5-a-side soccer ( first lesson ) , sensibilization activities toward visual impairment ( second and third lessons ) , training and competitive 5-a-side soccer tasks using blindfolded goggles ( fourth and fifth lessons ) , and a sport show and chat with soccer players with a visual impairment ( sixth lesson ) . The 1-day awareness unit only included the final session of the didactical activity . Repeated measures analysis of variance revealed significant time effects in the cognitive , emotional , and behavioral subscales . Sex also was found to demonstrate significant effects , in which women showed more favorable results than men . A time-by-group intervention effect was only demonstrated in the cognitive sub-scale , and the 6-day didactic intervention was more effective than the 1-day awareness unit . Zweck dieser Studie war die Untersuchung der Wirkung von zwei Bewusstseinsschulungen ( 6-Tage-Schulung ggü . 1-Tages-Schulung ) auf die Haltung von Kindern gegenüber sehbehinderten Gleichaltrigen . An der Studie nahmen insgesamt 344 spanische Sportstudenten ( 164 Mädchen und 180 Jungen ) i m Alter von 10–15 Jahren teil . Dazu wurde eine modifizierte Version des ATDQ-Fragebogens ( Haltungen gegenüber Behinderungen ) zu Hilfe gezogen , die die folgenden drei Subskalen umfasst : ( i ) kognitive Wahrnehmung , ( ii ) emotionale Wahrnehmung und ( iii ) intendiertes Verhalten bei der Kommunikation mit Kindern mit Behinderungen . Der Fragebogen wurde i m Rahmen des üblicherweise stattfindenden Sportunterrichts vor und unmittelbar nach der Bewusstseinsaktivität ausgefüllt . Die 6-tägige Didaktikschulung umfasste einen Vortrag über Sehbehinderungen und ein Video mit Erklärungen zu Sehbehinderungen sowie 5er Fußball ( erste Stunde ) , Sensibilisierungsaktivitäten speziell bei Sehbehinderungen ( zweite und dritte Stunde ) , Training und 5er Fußballturnier mit lichtundurchlässiger Brille ( vierte und fünfte Stunde ) und eine Sportshow und ein Gespräch mit sehbehinderten Fußballspielern ( sechste Stunde ) . Die 1-tägige Bewusstseinsschulung umfasste nur die letzte Stunde der Didaktikaktivität . Varianzanalysen für Messwiederholungen deckten signifikante Zeitwirkungen in den kognitiven , emotionalen und verhaltensgesteuerten Subskalen auf . Sex wies auch signifikante Wirkungen auf , wobei Frauen positivere Ergebnisse aufwiesen als Männer . Ein Interventions effekt ( Zeit x Gruppe ) konnte nur in der kognitiven Subskala nachgewiesen werden , und die 6-tägige Didaktikintervention erwies sich als effektiver als die 1-tägige Bewusstseinsschulung . El objetivo de este trabajo es analizar el efecto de dos programas educativos ( 6 vs. 1 día ) sobre las actitudes hacia compañeros con discapacidad visual . Participaron 344 estudiantes españoles de educación física ( 164 chicas y 189 chicos ) , con edades comprendidas entre los 10 y 15 años . Se empleó una versión modificada del Cuestionario de Actitudes hacia la Discapacidad , el cual incluye tres sub-escalas : ( i ) idea , ( ii ) emoción , y ( iii ) predisposición a la acción para interactuar con personas con discapacidad . Los cuestionarios fueron cumplimentados durante las clases de educación física , antes y después del inicio de cada uno de los programas desarrollados . La unidad didáctica de 6 sesiones incluye una charla informativa acerca de la discapacidad visual y una videoproyección de fútbol a 5 ( 1a sesión ) , actividades de sensibilización hacia la discapacidad visual ( sesiones 2 y 3 ) , juegos de entrenamiento y aprendizaje del fútbol a 5 con gafas de privación sensorial ( sesiones 4 y 5 ) , y una demostración del deporte con una charla posterior con los jugadores asistentes ( 6a sesión ) . La actividad docente de 1 día incluye sólo la última de las sesiones indicadas . El análisis ANOVA de medidas repetidas muestra mejoras en los tres componentes de la actitud tras la aplicación de los programas . También se han encontrado diferencias en función del sexo de los alumnos , con actitudes más favorables por parte de las chicas . El análisis intra-grupo por género mostró efectos en el componente de idea , demostr and o que el programa de 6 sesiones era más efectivo que el de 1 día . Cette étude avait pour objet d'explorer l'effet de deux programmes de sensibilisation ( programmes de 6 jours et d'1 jour ) à l'attitude des enfants vis-à-vis de leurs pairs souffrant de déficience visuelle . Trois cent quarante-quatre élèves espagnols en classes d'éducation physique ( 164 filles et 180 garçons ) âgés de 10 à 15 ans ont participé à l'étude . Une version modifiée du question naire d'attitude à l'égard des personnes h and icapées ( ATDQ ) a été utilisée , qui comprenait trois sous-échelles : ( i ) les perceptions cognitives , ( ii ) la perception des émotions , et ( iii ) la volonté comportementale d'interagir avec les enfants h and icapés . Le question naire a été rempli durant les classes d'éducation physique régulières avant et immédiatement après l'activité de sensibilisation . L'unité didactique de 6 jours comprenait une conférence sur les déficiences visuelles et une vidéo décrivant les déficiences visuelles et le jeu de football à 5 ( première leçon ) , des activités de sensibilisation aux déficiences visuelles ( deuxième et troisième leçons ) , un entraînement et des activités de football à 5 compétitives avec des lunettes bloquant la vue ( quatrième et cinquième leçons ) , et une démonstration sportive et un débat avec des joueurs de football souffrant de déficiences visuelles ( sixième leçon ) . L'unité de sensibilisation d'1 journée incluait seulement la dernière séance de l'activité didactique . Des analyses de variance répétées des mesures ont révélé des effets temporels significatifs sur les sous-échelles cognitives , émotionnelles et comportementales . Le sexe s'est révélé un facteur déterminant , les filles présentant des résultats plus favorables que les garçons . Un effet d'intervention de temps par groupe n'a été démontré que sur la sous-échelle cognitive , et l'intervention didactique de 6 jours a été plus efficace que l'unité de sensibilisation d'1 journée |
1,109 | 11,040,173 | On the other h and , enteral feeding ( with milk , not water2 ) in the first five days of life promotes endocrine adaptation and the maturation of motility patterns,3 provides luminal nutrient , and probably benefits immune function.4Potential clinical benefits are therefore earlier tolerance of enteral feeds , reduced risk of infection , and earlier discharge .
A systematic review of studies published to 1997 concluded that it reduced | Questions about when , how , and what to feed the preterm baby elicit many different answers .
Balancing the risks of enteral feeding with those of parenteral nutrition is not easy .
In contrast with the sophistication of clinical cardiorespiratory monitoring , the day to day assessment of gastrointestinal function is still largely dependent on clinical observation .
Moreover the population at risk is extremely heterogeneous with respect to both the prevalence of comorbidity and developmental stage , particularly , in this context , the maturation of intestinal motility .
Enteral feeding involves many potentially confounding interventions : route chosen , postnatal or postconceptional age at initiation , frequency of administration , amount given , rate of advancement , and , not least , choice between human milk and formula .
The spectre of necrotising enterocolitis ( NEC ) is the dominant argument for postponing enteral feeding , yet NEC can occur in babies fed parenterally .
The risk of sepsis and other complications during total parenteral nutrition ( TPN ) is high and may more than offset any reduction in the risk of NEC.1 TPN also provides certain important nutrients less effectively , notably vitamin A , glutamine , calcium , and phosphorus . | AIMS To determine the effect of trophic feeding on clinical outcome in ill preterm infants . METHODS A r and omised , controlled , prospect i ve study of 100 preterm infants , weighing less than 1750 g at birth and requiring ventilatory support and parenteral nutrition , was performed . Group TF ( 48 infants ) received trophic feeding from day 3 ( 0.5–1 ml/h ) along with parenteral nutrition until ventilatory support finished . Group C ( 52 infants ) received parenteral nutrition alone . “ Nutritive ” milk feeding was then introduced to both groups . Clinical outcomes measured included total energy intake and growth over the first six postnatal weeks , sepsis incidence , liver function , milk tolerance , duration of respiratory support , duration of hospital stay and complication incidence . RESULTS Groups were well matched for birthweight , gestation and CRIB scores . Infants in group TF had significantly greater energy intake , mean difference 41.4 ( 95 % confidence interval 9 , 73.7 ) kcal/kg p=0.02 ; weight gain , 130 ( CI 1 , 250 ) g p = 0.02 ; head circumference gain , mean difference 0.7 ( CI 0.1 , 1.3 ) cm , p = 0.04 ; fewer episodes of culture confirmed sepsis , mean difference −0.7 ( −1.3 , −0.2 ) episodes , p = 0.04 ; less parenteral nutrition , mean difference −11.5 ( CI −20 , −3 ) days , p = 0.03 ; tolerated full milk feeds ( 165 ml/kg/day ) earlier , mean difference −11.2 ( CI −19 , −3 ) days , p = 0.03 ; reduced requirement for supplemental oxygen , mean difference −22.4 ( CI−41.5 , −3.3 ) days , p = 0.02 ; and were discharged home earlier , mean difference −22.1 ( CI −42.1 , −2.2 ) days , p = 0.04 . There was no significant difference in the relative risk of any complication . CONCLUSIONS Trophic feeding improves clinical outcome in ill preterm infants requiring parenteral nutrition . Key messages Timing of the introduction of milk feeds in sick low birthweight infants is controversial . Almost all infants with non-surgical illness can tolerate at least some milk as trophic feeds . Trophic feeding leads to improved energy intake , weight gain , milk tolerance , less sepsis and earlier hospital discharge . No increase in major complication rate is seen following trophic feeding A study was performed to determine if the addition of a fortifier to expressed breast milk ( EBM ) affected gastric emptying in low birthweight infants . Using ultrasonography , the gastric emptying of EBM alone was compared with that containing a fortifier , in a blind , crossover study . Twenty two low birthweight infants were studied : median ( range ) gestation 31.5 weeks ( 28 - 37 ) ; birthweight 1495 g ( 1000 - 2480 g ) . The gastric antral cross-sectional area ( ACSA ) was measured by ultrasonography before each feed and then sequentially after its completion until the ACSA returned to its pre-feed value . The half emptying time was calculated as the time taken for the ACSA to decrease to half the maximum increment . The mean difference ( st and ard error ) between half emptying times for EBM alone and for EBM with added fortifier was not significant : 1.48 ( 4.9 ) minutes . These data show that fortifying breast milk does not affect gastric emptying and suggests that the practice is unlikely to affect feed tolerance in low birthweight infants BACKGROUND Preterm children are at high risk of poor growth performance . In 2 r and omized trials , preterm infants fed preterm formula grew better in the neonatal period than those fed banked donor breast milk or st and ard term formula . OBJECTIVE Our objective was to test the hypothesis that for preterm infants , the neonatal period is a critical one for programming growth performance and that early diet influences long-term growth . DESIGN A total of 926 preterm infants were recruited into 2 parallel , r and omized trials of neonatal diet . In trial 1 , infants were fed either banked donor breast milk or preterm formula whereas in trial 2 , infants were fed either st and ard term formula or preterm formula . Within each trial , the allocated milk was the sole diet for some infants ( study A ) , whereas for others it was a supplement to maternal breast milk , given when not enough expressed breast milk was available ( study B ) . We followed up 781 of 833 survivors ( 94 % ) to age 7.5 - 8 y. Trained assessors obtained anthropometric measurements according to a st and ard protocol . RESULTS Despite significantly better neonatal growth performance in infants fed preterm formula ( compared with either banked donor breast milk or st and ard formula ) , early diet had no influence on weight , height , head circumference , or skinfold thicknesses at 9 or 18 mo postterm or at age 7.5 - 8 y. CONCLUSIONS These findings suggest that the preterm period is not a critical window for nutritional programming of growth , which contrasts with evidence from these trials showing that early diet influences later neurodevelopment Despite potential benefits , human milk may fail to meet preterm infants ' nutrient requirements . We tested the hypothesis that fortified breast milk , fed alone or with preterm formula , would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences . Two hundred seventy-five preterm infants from two medical centers ( birth weight < 1850 g ; mean gestation 29.8 + /- 2.7 wk ) whose mothers chose to provide breast milk were r and omly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins . Breast milk comprised 47.6 % and 46.4 % of enteral intake in fortified and control groups , respectively ; preterm formula supplements were used when insufficient breast milk was available . Overall , there were no significant growth advantages with fortification ; although , when breast milk exceeded 50 % of intake , fortification promoted faster weight gain ( an advantage of 1.6 g.kg-1.d-1 ; 95 % CI : 0.1 , 3.1 ; P < 0.05 ) . Compared with control infants , the fortified group showed 1 ) higher plasma urea from week 2 ( P = 0.04 ) , 2 ) higher plasma calcium ( mean 2.34 + /- 0.01 compared with 2.27 + /- 0.02 mmol/L ; P = 0.003 ) , 3 ) a greater rise in alkaline phosphatase by week 6 ( P = 0.04 ) , 4 ) more clinical infections ( suspected plus proven ; 43 % compared with 31 % , P = 0.04 ) , 5 ) a nonsignificantly increased incidence of necrotizing enterocolitis ( 5.8 % compared with 2.2 % , P = 0.12 ) , and 6 ) higher white cell and platelet counts . Developmental scores at 18 mo were slightly but not significantly higher in the fortified group . This study confirmed that breast milk fortifiers can improve short-term growth ( when breast milk intakes are high ) ; but beneficial effects on long-term development remained unproven . Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies OBJECTIVE To compare the effects of continuous versus intermittent feedings on physical growth , gastrointestinal tolerance , and macronutrient retention in very low birth weight infants ( < 1500 gm ) . STUDY DESIGN Very low birth weight neonates stratified by birth weight were r and omly assigned to either continuous ( 24-hour ) or intermittent ( every 3 hours ) nasogastric feedings . Feedings with half-strength Similac Special Care formula were initiated between day 2 and 3 and were advanced isoenergetically to goal . Daily weights , volume/caloric intakes , weekly anthropometric and dynamic skin-fold thickness measurements , and data on feeding milestones and clinical complications were collected . Nitrogen , carbohydrate , and fat balance studies were performed on a subset of male subjects . RESULTS Eighty-two neonates with birth weights between 750 and 1500 gm who were born between 27 and 34 weeks of gestation were r and omly assigned to continuous ( n = 42 ) and intermittent ( n = 40 ) feeding groups . There were no significant differences in baseline demographics and severity of respiratory distress between groups . There were no significant differences in days to regain birth weight , days to full enteral feedings , days to discharge , and discharge anthropometric measurements between continuously fed and intermittently fed infants , both when evaluated together and according to 250 gm weight intervals . Retention rates of nitrogen , fat , total carbohydrate , and lactose were comparable in the continuously fed ( n = 17 ) and intermittently fed ( n = 13 ) male neonates . Very low birth weight neonates who were fed continuously did not have feeding-related complications . CONCLUSION Very low birth weight infants achieve similar growth and macronutrient retention rates and have comparable lengths of hospital stay whether they are fed with continuous or intermittent feedings OBJECTIVE To test the hypothesis that very low birth weight infants fed by continuous nasogastric gavage ( CNG ) would achieve full enteral feedings ( 100 kcal/kg/d ) at an earlier postnatal age and have less feeding intolerance ( FI ) than infants fed by intermittent bolus gavage ( IBG ) . METHODS Eighty infants were stratified by birth weight ( 700 to 1000 g and 1001 to 1250 g ) and r and omized into CNG or IBG feeding groups . CNG infants were comparable with IBG in birth weight , gestational age , sex , race , and day of onset of feeding ( 5.7 + /- 2.1 days vs 5.6 + /- 2.2 days , respectively ) . Feedings were given as undiluted Similac Special Care formula ( Ross Laboratories , Columbus , OH ) via a specific protocol design ed for each 50 to 100 g birth weight category . Feedings were advanced isoenergetically by a maximum of 25 mL/kg/d until an endpoint of 100/kcal/kg/d for at least 48 hours was reached . An infant whose feedings were withheld for > 12 hours based on predetermined criteria was considered to have an episode of FI . RESULTS Infants in the CNG group reached full enteral feeding at 17.1 + /- 8.9 days compared with 15.5 + /- 5.5 days in the IBG group ; these were not statistically different . Secondary outcome variables such as days to regain birth weight ( CNG , 12.6 + /- 5 days vs IBG , 12.5 + /- 3.7 days ) , days to reach discharge weight of 2040 g ( CNG , 60 + /- 13.4 days vs IBG , 62 + /- 13.6 days ) , and number of episodes of FI were not significantly different between feeding methods . FI was primarily associated with birth weight < /=1000 g ( 71 % ) vs 1001 to 1250 g ( 38 % ) . CONCLUSION Feeding methods are associated with similar outcomes when feeding regimens are comparable Forty three infants under 1400 g were fed by a bolus nasogastric , continuous nasogastric , or transpyloric route . There were more complications with transpyloric feeding and no identifiable benefits in the growth rate , oral energy input , or chosen biochemical indices of nutrition . Bolus or continuous nasogastric feeds rather than transpyloric are better routine methods in infants of low birth weight In a prospect i ve multicentre study on 926 preterm infants formally assigned to their early diet , necrotising enterocolitis developed in 51 ( 5.5 % ) . Mortality was 26 % in stringently confirmed cases . In exclusively formula-fed babies confirmed disease was 6 - 10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk . Pasteurised donor milk seemed to be as protective as raw maternal milk . Among babies born at more than 30 weeks ' gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk ; it was 20 times more common in those fed formula only . Other risk factors included very low gestational age , respiratory disease , umbilical artery catheterisation , and polycythaemia . In formula-fed but not breast-milk-fed infants , delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis . With the fall in the use of breast milk in British neonatal units , exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year . About 100 of these infants would die Whether breast milk influences later neurodevelopment has been explored in non-r and omised studies , potentially confounded by social and demographic differences between feed groups . Here in a strictly r and omised prospect i ve multicentre trial , Bayley psychomotor and mental development indices ( PDI and MDI ) were assessed at 18 months postterm in survivors of 502 preterm infants assigned to receive , during their early weeks , mature donor breast milk or a preterm formula . These diets were compared as sole enteral feeds or as supplements to the mother 's expressed breast milk . No differences in outcome at 18 months were seen between the two diet groups despite the low nutrient content of donor milk in relation to the preterm formula and to the estimated needs of preterm infants . These results contrast with those reported from our parallel two centre study that compared infants r and omly assigned a st and ard term formula or the preterm formula during their early weeks ; those fed st and ard formula , now regarded as nutritionally insufficient for preterm infants , were substantially disadvantaged in PDI and MDI at 18 months post-term . It is shown here that infants from that study fed solely on st and ard formula had significantly lower developmental scores at 18 months than those fed on donor breast milk in the present study ; yet the st and ard formula had a higher nutrient content than the donor milk . Thus , donor milk feeding was associated with advantages for later development that may have offset any potentially deleterious effects of its low nutrient content for preterm infants . As these outcome advantages were not confounded by the social and educational biases usually associated with mothers ' choice to breast feed , our data add significant support to the view that breast milk promotes neurodevelopment To determine the response of the preterm infant 's intestine to entire feedings at different postnatal ages , we recorded results of manometry of the gastroduodenum and determined fasting plasma concentrations of gastrin , gastric inhibitory peptide , neurotensin , and peptide YY three times in each of two groups : 27 preterm infants were r and omly assigned to receive hypocaloric enteral nutrition on postnatal days 3 to 5 ( early feeding ) or on days 10 to 14 ( late feeding ) . Initial observations ( study 1 ) were performed by the fifth postnatal day ; study 2 was performed on days 10 to 14 , and study 3 on days 24 to 28 . Early-fed infants received hypocaloric feedings immediately after study 1 ; late-fed infants did not receive enteral feedings until the completion of study 2 . Although motor activity and fasting gastrointestinal peptide concentrations did not differ between groups at study 1 , at study 2 early-fed infants had significantly more mature motor patterns than did babies not being fed . Early-fed infants also had significantly higher plasma concentrations of gastrin and gastric inhibitory peptide than did late-fed infants ; neurotensin and peptide YY values were similar in both groups . By the time of study 3 , when late-fed infants had also received enteral feedings , gut development was not different in the two groups . However , early-fed infants were able to tolerate full oral nutrition sooner , had fewer days of feeding intolerance , and had shorter hospital stays . Thus the provision of early hypocaloric nutrition was associated with earlier nutrition of preterm infants ' intestinal function and result ed in improved feeding tolerance . These findings support the use of early feedings in preterm infants NECROTIZING ENTEROCOLITIS is a serious disorder of the newborn infant that rarely occurs before the institution of oral feedings . ' -3 Various feeding practice s have been shown to be important in the pathogenesis of the disease . Low-birth-weight infants fed a hyperosmolar , 650 mOsm/1 , elemental formula have an increased incidence of NEC when compared to low-birth-weight infants fed a cow milk formula . 4 It has also been suggested that cow milk feedings themselves or the exclusion of breast milk from the diet of small newborn infants may be predisposing factors ? The quantity of feedings in the first weeks of life may also be important , and Krouskop and associates ~ have associated the development of NEC with early institution of oral feedings . In another retrospective study , however , there were no differences between the volume of formula offered NEC patients at the time symptoms developed and infants of similar size and age who did not develop NEC . 1 Conflicting opinions therefore exist regarding the relationship of oral feeding to the development of NEC ; there have been no r and omized , prospect i ve , clinical trials dealing with this issue . The purpose s of this paper are to report the relationship of different feeding practice s in the Intermountain Newborn Intensive Care Center to the incidence of NEC , and the results of a prospect i ve controlled investigation comparing two different feeding schedules in low-birth-weight infants OBJECTIVE To determine whether the rate of feed advancement affects the incidence of necrotizing enterocolitis ( NEC ) . STUDY DESIGN Prospect i ve r and omized controlled trial involving 185 formula-fed infants with birth weight 501 to 1500 g and gestational age < /=34 weeks . Infants were r and omized into 2 groups : " slow " ( n = 98 ) , who received 15 cc/kg/d increments ( a 10-day schedule to full feeds ) and " fast " ( n = 87 ) , who received 35 cc/kg/d increments ( a 5-day schedule to full feeds ) of Similac Special Care 20 cal/oz . Feeds were increased only if well tolerated as defined by a protocol . RESULTS The incidence of NEC ( Bell stage > /=II ) was similar in both groups ( slow 13 % and fast 9 % , P = .5 ) . The incidence of perforation ( Bell stage III ) was also similar in both groups ( slow 4 % and fast 2 % , P = .8 ) . Feeds were started at a comparable postnatal age in both groups ( median age : slow 5 days and fast 4 days , P = .9 ) . Although the neonates in the fast group attained full enteral intake earlier ( median days [ 25th and 75th percentiles ] : slow 15 [ 12 , 21 ] and fast 11 [ 8 , 15 ] , P < .001 ) and regained their birth weight earlier ( slow 15 [ 11 , 20 ] and fast 12 [ 8 , 15 ] , P < .05 ) , their ages at discharge were not statistically different ( slow 47 [ 31 , 67 ] and fast 43 [ 29 , 62 ] , P = .3 ) CONCLUSIONS A greater than twofold difference in the rate of feed advancement from 15 cc/kg/d to 35 cc/kg/d did not affect the incidence of NEC > /= stage II . Factors other than feed advancement appear to be more important in the pathogenesis or progression of NEC BACKGROUND Data on enteral feeding management of premature infants are limited and often not the subject of r and omized clinical trials . Several small studies suggest benefits from the early initiation of feeding , but do not assess the combined effects of time of initiation of feeding , tube-feeding method , and type of milk used . Either singly or in combination , these treatments may affect growth , bone mineralization , biochemical measures of nutritional status , and feeding tolerance , and , ultimately , the duration of hospitalization . METHODS A total of 171 premature infants , stratified by gestational age ( 26 to 30 weeks ) and diet ( human milk or preterm formula ) were assigned r and omly among four treatment combinations in a balanced two-way design comparing the presence or absence of gastrointestinal ( GI ) priming for 10 days and continuous infusion versus intermittent bolus tube-feeding . RESULTS The major outcome , time required for infants to attain full oral feeding , was similar among treatments . GI priming was not associated with any measured adverse effect and was associated with better calcium and phosphorus retention , higher serum calcium and alkaline phosphatase activity , and shorter intestinal transit times . The bolus tube-feeding method was associated with significantly less feeding intolerance and greater rate of weight gain than the continuous method . In addition , the greater the quantity of human milk fed , the lower the morbidity . CONCLUSIONS Early GI priming with human milk , using the bolus tube-feeding method , may provide the best advantage for the premature infant In a prospect i ve r and omized trial , we studied the effects of early hypocaloric enteral feedings ( PO ) begun at 48 hours of age in 19 infants compared with 20 infants who received no enteral feedings ( NPO ) for at least the first 9 days of life . Both groups initially received the majority of their calories by parenteral alimentation . The groups were similar with respect to birth weight , gestational age , sex , Apgar score , and major neonatal diagnoses . The early enteral feeds proved to be significantly beneficial without an increased incidence of complications . The PO group reached full enteral feedings faster than the NPO group ( 31.2 vs 47.3 days ) . The PO group had a greater decline in serum bilirubin concentration over the first 2 weeks of life and spent less time under phototherapy ( 6.8 vs 9.5 days ) . Less cholestasis was observed among the PO infants ( 6.7 % vs 33 % ) , and peak direct bilirubin levels were also lower ( 0.7 vs 2.5 mg/dL ) . Osteopenia of prematurity , manifested by significantly lower alkaline phosphatase activity , was also decreased in the PO group , perhaps because of greater calcium intake during the first month among PO infants ( 1.3 vs 0.8 g ) . Compared with complete bowel rest , early onset of hypocaloric enteral feedings has beneficial effects on indirect hyperbilirubinemia , cholestatic jaundice , and metabolic bone disease of very low birth weight infants The purpose of this study was to examine whether premature infants have higher rates of energy expenditure and diet-induced thermogenesis during intermittent feeding compared with continuous feeding . Using open-circuit respiratory calorimetry , we measured energy expenditure in 11 premature newborn infants on 2 successive days for 5 to 7 hours during and after either intermittent or continuous feeding . Infants were fed the same quantity of formula each day , either for 5 minutes or by continuous drip for 2 to 3 hours . The order of feeding type was r and omized . No response of diet-induced thermogenesis to continuous feeding was found , whereas a peak increase of 15 % over baseline was observed after intermittent feeding . Overall energy expenditure during the study period was significantly greater after intermittent compared with continuous feeding ( 2.18 + /- 0.07 kcal/kg per hour vs 2.09 + /- 0.05 kcal/kg per hour ; p less than 0.05 ) . Thus there was a mean 4 % difference ( range up to 17 % ) in energy expenditure between the two feeding modes . These results are similar to those obtained with adults and support the concept of the increased energy efficiency of continuous feeding . Further study will be necessary to document whether the increased energy efficiency provided by continuous feeding may be clinical ly significant |
1,110 | 21,949,893 | In 10 reports meeting study criteria , improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection .
/ SIGNIFICANCE Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation , there are incremental benefits to this approach at an estimated cost of $ 153 ( S. mansoni)-$211 ( S. haematobium ) per additional lifetime QALY gained by double treatment in school-based programs .
More rapid reduction of infection-related disease may improve program adherence , and if , as an externality of the program , transmission can be reduced through more effective coverage , significant additional benefits are expected to accrue in the targeted communities | BACKGROUND Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities .
In a systematic review of published studies , we examined evidence for incremental benefits from repeated praziquantel dosing , given 2 to 8 weeks after an initial dose , in Schistosoma-endemic areas of Africa . | OBJECTIVE We aim ed to assess the health impact of a national control programme targeting schistosomiasis and intestinal nematodes in Ug and a , which has provided population -based anthelmintic chemotherapy since 2003 . METHODS We conducted longitudinal surveys on infection status , haemoglobin concentration and clinical morbidity in 1871 r and omly selected schoolchildren from 37 schools in eight districts across Ug and a at three time points - before chemotherapy and after one year and two years of annual mass chemotherapy . FINDINGS Mass treatment with praziquantel and albendazole led to a significant decrease in the intensity of Schistosoma mansoni - 70 % ( 95 % confidence interval ( CI ) : 66 - 73 % ) after one year and 82 % ( 95 % CI : 80 - 85 % ) after two years of treatment . Intensity of hookworm infection also decreased ( 75 % and 93 % ; unadjusted ) . There was a significant increase in haemoglobin concentration after one ( 0.135 g/dL ( 95 % CI : 0.126 - 0.144 ) ) and two years ( 0.303 g/dL ( 95 % CI : 0.293 - 0.312 ) ) of treatment , and a significant decrease in signs of early clinical morbidity . The impact of intervention on S. mansoni prevalence and intensity was similar to that predicted by mathematical models of the impact of chemotherapy on human schistosomiasis . Improvements in haemoglobin concentration were greatest among children who were anaemic or harbouring heavy S. mansoni infection at baseline . CONCLUSION Anthelmintic treatment delivered as part of a national helminth control programme can decrease infection and morbidity among schoolchildren and improve haemoglobin concentration OBJECTIVE To study the role of health education and community participation for the provision of facilities necessary for the control of urinary schistosomiasis in southern Ghana . HYPOTHESIS Health education facilitates community participation in the provision of facilities for the control of bilharzia . STUDY AREA Three rural communities drained by the Densu river in southern Ghana . PARTICIPANTS Individuals aged 14 years and above formed groups of 10 - 12 persons by age , sex , ethnic and educational background ; 15 - 16 groups were formed . INTERVENTIONS Based on existing structures , one community received active , another passive health education and the third had no education . All three communities received chemotherapy . DESIGN Study was carried out in three phases : pre-intervention phase -- during which baseline data on residents ' knowledge , attitude , beliefs and perception about bilharzia were collected using focus group discussion s ( FGD ) prior to the second phase , intervention . Another FGD was held after 18 months to evaluate the intervention -- third phase . RESULTS This study suggests that most community members were aware of schistosomiasis but not as a disease . Before the health education , some residents believed bilharzia was a sign of manhood while others attributed the red colour of the urine to the red colour of a variety of sugar cane eaten in the area . After the health education , residents in the three areas constructed h and -dug wells . In addition , those who received active health education constructed two toilets for the schools and weeded the banks of the rivers . Residents also associated the disease with the water snail . CONCLUSION Health education was useful in changing community perception on bilharzia The aim of the study was to assess the efficacy and side effects following single and repeated ( 6 weeks apart ) praziquantel treatment ( 40 mg/kg ) in a Schistosoma mansoni-endemic focus with long-st and ing transmission at Lake Albert in Ug and a between December 1996 and January 1997 . The results were based on 482 individuals , r and omly representing all age and both gender groups . The cure rate following the first and second treatments was 41.9 % and 69.1 % , respectively . The cure rate was higher in adults than in children , irrespective of intensity of infection . In addition , the cure rate declined markedly with increasing intensity of infection . The reduction in intensity of infection was marked , being 97.7 % and 99.6 % after the first and second treatments , respectively . A pre- and post-treatment symptom question naire revealed a broad range of side effects , including abdominal pain and diarrhoea . However , no serious or long-lasting complications affecting compliance were observed . The marked reductions in faecal egg excretion and the acceptable level of side effects point to a single praziquantel treatment ( 40mg/kg ) as the strategy of choice in such a highly endemic S. mansoni focus To determine the effect of targeted field administration of oral chemotherapeutic agents on the prevalence , intensity , and morbidity of Schistosoma haematobium infections , we initiated a long-term school-based program in the Msambweni area of Kwale District , Coast Province , Kenya . Prior to treatment , 69 % of the children examined ( ages 4 - 21 , n = 2,628 ) were infected ; 34 % had moderate or heavy infections ( greater than 100 eggs/10 ml urine ) . Infected individuals were r and omized to receive , during one year , either metrifonate ( 10 mg/kg x 3 doses ) or praziquantel , ( 40 mg/kg x 1 dose ) . At the end of the first year , prevalence of infection fell to 19 % ; only 2 % of the pupils remained in the moderately and heavily infected groups . Corresponding decreases in the prevalence of hematuria ( 54 % in 1984 vs. 16 % in 1985 ) and proteinuria ( 56 % in 1984 vs. 26 % in 1985 ) were noted . These were associated with significant declines in bladder thickening and irregularities noted during ultrasound examinations , but not with decreases in hydronephrosis . There was no significant difference in the post-treatment prevalence or intensity of infection after treatment with metrifonate as compared with praziquantel . These results demonstrate that field-applied chemotherapy with either agent offers a practical strategy for the control of S. haematobium infection and its associated morbidity BACKGROUND In sub-Saharan Africa , 112 million people are infected with Schistosoma haematobium , with the most intense infections in children 5 - 15 years old . METHODS We describe a longitudinal epidemiological study that evaluates the relationship between S. haematobium infection and associated morbidity in children before and after the large-scale administration of praziquantel for schistosomiasis and albendazole for soil-transmitted helminths . RESULTS At baseline , higher intensities of S. haematobium infection were observed in children with anemia and /or severe microhematuria , but there was no apparent association between the risk of undernutrition and intensity of S. haematobium infection . Significant reductions in the prevalence and intensity of S. haematobium infection 1 year after treatment were , however , observed . Children who benefited the most from anthelmintic treatment in terms of increased hemoglobin concentrations were those who had anemia at baseline and those with highly positive microhematuria scores at baseline . CONCLUSIONS This study suggests that even a single round of mass chemotherapy can have a substantial impact on S. haematobium infection and its associated morbidity in children To determine the effect of repeated , annual , age-targeted therapy on prevalence and intensity of Schistosoma haematobium infection in an endemic area , we treated all available , infected , school-age children ( n = 2 , 493 ) in the Msambweni area of Coast Province , Kenya with a r and omized protocol of oral metrifonate ( 10 mg/kg for three doses each year ) or praziquantel therapy ( 40 mg/kg as a single dose each year ) for a period of one to three years . During 1984 - 1987 , 1 , 101 children completed three years of therapy , 550 received two years , and 842 received a single year . Annual followup revealed significant long-term suppression of S. haematobium infection in the targeted school-age population . Both cross-sectional analysis and study of individual outcomes suggested maximal suppression of infection after two years of therapy . Suppression lasted more than two years after cessation of treatment , and was associated with reduced community transmission ( gauged by decreased prevalence among new study entrants and decreasing negative-to-positive conversion on annual parasitologic examinations ) . Comparison of metrifonate and praziquantel outcomes indicated greater suppression of infection and longer infection-free intervals for some subgroups given praziquantel . We conclude that annual population -based therapy targeted to schoolchildren has direct and indirect beneficial effects for endemic communities . In some specific situations , repeat therapy may not suppress transmission , and reduced drug efficacy may be observed after one to three years , suggesting the need for additional non-drug control measures in highly endemic villages Severity of urinary tract morbidity increases with intensity and duration of Schistosoma haematobium infection . We assessed the ability of yearly drug therapy to control infection intensity and reduce S. haematobium-associated disease in children 5 - 21 years old in an endemic area of Kenya . In year 1 , therapy result ed in reduced prevalence ( 66 % to 22 % , P < 0.001 ) and intensity of S. haematobium infection ( 20 to 2 eggs/10 mL urine ) , with corresponding reductions in the prevalence of hematuria ( 52 % to 19 % , P < 0.001 ) . There was not , however , a significant first-year effect on prevalence of urinary tract abnormalities detected by ultrasound . Repeat therapy in years 2 and 3 result ed in significant regression of hydronephrosis and bladder abnormalities ( 41 % to 6 % prevalence , P < 0.01 ) , and further reductions in proteinuria . Repeat age-targeted therapy was associated with decreased prevalence of infection among young children ( < 5 yr ) entering into the targeted age group . Two years after discontinuation of therapy , intensity of S. haematobium infection and ultrasound abnormalities remained suppressed , but hematuria prevalence began to increase ( to 33 % in 1989 ) . Reinstitution of annual therapy in 1989 and 1990 reversed this trend . We conclude that annual oral therapy provides an effective strategy for control of morbidity due to S. haematobium on a population basis , both through regression of disease in treated individuals , and prevention of infection in untreated subjects Chemotherapy with praziquantel is the cornerstone of schistosomiasis control . In view of recent concern about tolerance or resistance to praziquantel , monitoring its efficacy in different epidemiological setting s is required . We report a study among 253 schoolchildren in an area highly endemic for Schistosoma mansoni in western Côte d'Ivoire . After examining four consecutive stool specimens from each child , the first praziquantel treatment at 60 mg/kg divided into two doses was administered . Four weeks later , stool specimens were again screened over 4 consecutive days and revealed a cure rate of 71.6 % and an egg reduction rate of 79.9 % . There was a significant association between cure rate and intensity of infection prior to treatment with highest cure rates observed in light infections ( P < 0.01 ) . Praziquantel , at a single dose of 40 mg/kg , was again administered 35 days after the first treatment . The overall cure and egg reduction rates increased considerably . The association between cure rate and intensity of infection prior to the second treatment was significant but less pronounced . Twenty-two children remained S. mansoni positive after the two chemotherapy campaigns , and interestingly , many of these were only identified after repeated stool examinations . We argue that pre-patent infections may account for some of these ' treatment failures ' . However , further studies in other endemic setting s are needed , with parasitological diagnoses having a high sensitivity The aim of this study was to assess the effect of two doses of 40 mg/kg praziquantel with 2 weeks interval versus a st and ard single dose of 40 mg/kg on cure rates , egg reduction , intensity of infection , and micro-haematuria in Schistosoma haematobium infections . A r and omised controlled intervention study was carried out among school-aged children in two different endemic setting s with follow-up at 3 , 6 and 18 months following drug administration . Differences in cure rates between the two treatment regimens were not significant . However , in high transmission areas , the double treatment regimen was more effective in egg reduction than single treatment regimen and the difference in egg reduction between the two treatments was significant at 3 months ( P<0.005 ) , 6 months ( P<0.0001 ) and 18 months ( P<0.003 ) after treatment . There was a significant difference in the effect of the two treatments on prevalence of micro-haematuria at 18-month follow-up in both Koulikoro ( P<0.001 ) and Selingue ( P<0.003 ) . The study shows that although no significant difference could be observed in the overall cure-rates between the two treatment regimens , the effect of double treatment was a significant reduction in infection intensity as well as micro-haematuria which may have a great impact in reducing subtle morbidity A study was performed to determine the efficacy of praziquantel ( PZQ ) against Schistosoma haematobium . Children ( n = 592 ) infected with S. haematobium received either a single treatment with PZQ ( 40 mg/kg ) or two or three treatments with PZQ at three-week intervals after the initial treatment and efficacy was monitored for nine weeks . Cure rates at three-weeks post-treatment were low ( < 50 % ) , suggesting either that worms are killed very slowly or , more likely , that eggs continue to be released from tissues after worm death . Interestingly , a single dose of PZQ showed high efficacy ( cure rate > 83 % and egg reduction rate > 98 % ) when assessed from six weeks post-treatment onward . There were no significant differences in cure rates or intensity of infection between the three cohorts at any point in the study , despite the different treatment regimens . Since children were in contact with transmission sites during the study period , the results suggest good efficacy of PZQ against all stages of S. haematobium , including the immature worms |
1,111 | 23,391,670 | Telestroke technology is now part of mainstream clinical stroke practice in North America and internationally . | BACKGROUND The use of 2-way audiovisual ( AV ) technology for delivery of acute stroke evaluation and management , termed " telestroke , " is supported by a rapidly growing literature base .
A systematic review that provides a comprehensive , easily digestible overview of telestroke science and practice is lacking .
PURPOSE To conduct a systematic review of the published literature on telemedical consultation for the purpose s of providing acute stroke evaluation and management . | BACKGROUND AND PURPOSE Telemedicine can disseminate vascular neurology expertise and optimize recombinant tissue plasminogen activator ( rt-PA ) use for acute ischemic stroke in rural underserved communities . The purpose of this study was to prospect ively assess whether telemedicine or telephone was superior for decision-making . METHODS The study design is a pooled analysis of two identically design ed r and omized controlled trials conducted in a multistate hub and spoke telestroke network setting with acute stroke syndrome patients , comparing telemedicine versus telephone-only consultations . From each trial , common data elements were pooled to assess , principally , for correctness of thrombolysis decision-making . Secondary outcomes included rt-PA use rate , 90-day functional outcome , post-thrombolysis intracranial hemorrhage , and data completeness . RESULTS Two hundred seventy-six pooled patients were evaluated . Correct thrombolysis eligibility decisions were made more often with telemedicine ( 96 % telemedicine , 83 % telephone ; odds ratio [ OR ] 4.2 ; 95 % confidence interval [ CI ] 1.69 - 10.46 ; p=0.002 ) . Intravenous rt-PA usage was 26 % ( 29 % telemedicine , 24 % telephone ; OR 1.27 ; 95 % CI 0.71 - 2.25 ; p=0.41 ) . Ninety-day outcomes were not different for Barthel Index , modified Rankin Scale , or mortality . There was no difference in post-thrombolysis intracranial hemorrhage ( 8 % telemedicine , 6 % telephone ; p>0.999 ) . CONCLUSIONS This pooled analysis supports the hypothesis that stroke telemedicine consultations , compared with telephone-only , result in more accurate decision-making . Together with high rt-PA utilization rate , low post-rt-PA intracranial hemorrhage rate , and acceptable patient outcome , the results confirm that telemedicine is a viable consultative tool for acute stroke . The replication of the hub and spoke network infrastructure supports the generalizability of telemedicine when used in broader setting Background and Purpose — Telemedicine techniques can be used to address the rural – metropolitan disparity in acute stroke care . The Stroke Team Remote Evaluation Using a Digital Observation Camera ( STRokE DOC ) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use , improved data collection , low risk of complications , low technical complications , and favorable assessment times . The main objective of the STRokE DOC Arizona TIME ( The Initial Mayo Clinic Experience ) trial was to determine the feasibility of establishing , de novo , a single-hub , multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol . Methods — Methods included prospect i ve , single-hub , 2-spoke , r and omized , blinded , controlled trial of a 2-way , site-independent , audiovisual telemedicine system design ed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis . The primary outcome measure was whether the decision to give thrombolysis was correct . Secondary outcomes were rate of thrombolytic use , 90-day functional outcomes , incidence of intracerebral hemorrhages , and technical observations . Results — From December 2007 to October 2008 , 54 patients were assessed , 27 of whom were r and omized to each arm . Mean National Institutes of Health Stroke Scale score at presentation was 7.3 ( SD 6.2 ) points . No consultations were aborted ; however , technical problems ( 74 % ) were prevalent in the telemedicine arm . Overall , the correct treatment decision was established in 87 % of the consultations . Both modalities , telephone ( 89 % correct ) and telemedicine ( 85 % correct ) , performed well . Intravenous thrombolytic treatment was used in 30 % of the telemedicine and telephone consultations . Good functional outcomes at 90 days were not significantly different . There were no statistically significant differences in mortality ( 4 % in telemedicine and 11 % in telephone ) or rates of intracerebral hemorrhage ( 4 % in telemedicine and 0 % in telephone ) . Conclusions — It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub , multispoke rural hospital telestroke research network in Arizona . The trial was not design ed to have sufficient power to detect a difference between the 2 consultative modes : telemedicine and telephone-only . Whether by telemedicine or telephone consultative modalities , there were appropriate treatment decisions , high rates of thrombolysis use , improved data collection , low rates of intracerebral hemorrhage , and equally favorable time requirements . The learning curve was steep for the hub and spoke personnel of the new telestroke network , as reflected by frequent technical problems . Overall , the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise Background and Purpose — Despite Food and Drug Administration approval of tissue-type plasminogen activator for stroke , obstacles in the US healthcare system prevent its widespread use . The Remote Evaluation for Acute Ischemic Stroke ( REACH ) program was developed to address these issues in rural setting s. A key component of stroke assessment in the REACH system is the National Institutes of Health Stroke Scale ( NIHSS ) evaluation . We sought to determine whether , using the REACH system , NIHSS values of bedside and remote evaluators would correspond . Methods — Twenty patients were recruited . On obtaining consent , a neurologist performed a bedside NIHSS evaluation on each patient . Within 1 hour , using any broadb and -connected workstation — either office or home personal computer and a l and line phone to speak with the patient — a second neurologist remotely evaluated the patient through the REACH system . Paired t tests and Pearson correlation coefficients were used to examine NIHSS reliability performed bedside and remotely . Results — NIHSS ranged from 1 to 24 . Correlations between bedside and remote locations ( r = 0.9552 , P = 0.0001 ) were very strong , and t tests indicate that the means were not different . Conclusions — The NIHSS can be reliably performed over the REACH system . This supports our endeavor to bring stroke expertise to rural community hospitals OBJECTIVE Patients with ischemic stroke treated with tissue plasminogen activator ( rt-PA ) have better outcomes when treated closer to the time of symptom onset and within the 3-hour window . We previously demonstrated the clinical use of TeleBAT , a mobile telemedicine system for stroke . We tested the impact of that system on time to treatment for patients with acute stroke . METHODS Validity and reliability were tested by comparing neurologic examination scores obtained using our wireless system , which transmits video of a patient from a moving ambulance to desktop computers , with those obtained using the National Institute of Neurological Disorders and Stroke training videotape . TeleBAT validity and good interrater reliability were defined a priori as a kappa statistic of r > 0.5 . We compared the average time to treatment for our TeleBAT-evaluated intervention group with that for our control group . The intervention group consisted of two actor patients with stroke mimicking 12 stroke scenarios and evaluated using TeleBAT . The control group consisted of patients with stroke evaluated and treated with rt-PA on arrival to the emergency department . Data were analyzed using st and ard t test . RESULTS National Institutes of Health Stroke Scale items calculated by the neurologists suggest TeleBAT is valid for assessing patients with stroke remotely . Interrater reliability was high : the neurologists gleaned the same information from TeleBAT transmissions . Kappa values for both validity and reliability exceeded 0.5 . The mean time to treatment for patients assessed by TeleBAT was 17 + /- 4 minutes compared with 33 + /- 17 minutes for our control group ( P = .0033 ) . CONCLUSION TeleBAT seems to be a valid and reliable means of evaluating stroke neurologic deficits . Time to treatment was shortened using ambulance transport time to evaluate patients as c and i date s for thrombolytic therapy . Future studies should use a r and omized design with patients with acute stroke BACKGROUND Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials . We performed a r and omized , double-blind trial of intravenous recombinant tissue plasminogen activator ( t-PA ) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke . METHODS The trial had two parts . Part 1 ( in which 291 patients were enrolled ) tested whether t-PA had clinical activity , as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale ( NIHSS ) or the resolution of the neurologic deficit within 24 hours of the onset of stroke . Part 2 ( in which 333 patients were enrolled ) used a global test statistic to assess clinical outcome at three months , according to scores on the Barthel index , modified Rankin scale , Glasgow outcome scale , and NIHSS : RESULTS In part 1 , there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours , although a benefit was observed for the t-PA group at three months for all four outcome measures . In part 2 , the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed ( global odds ratio for a favorable outcome , 1.7 ; 95 percent confidence interval , 1.2 to 2.6 ) . As compared with patients given placebo , patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales . Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo ( P < 0.001 ) . Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group ( P = 0.30 ) . CONCLUSIONS Despite an increased incidence of symptomatic intracerebral hemorrhage , treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months Objective : VA Stroke Study ( VASt ) data were analyzed to determine whether neurologist management affected the process and outcome of care of patients with ischemic stroke . Methods : VASt prospect ively identified patients with stroke admitted to nine VA hospitals ( April 1995 to March 1997 ) . Demographics , stroke severity ( Canadian Neurologic Score ) , stroke subtype ( Trial of ORG 10172 in Acute Stroke Treatment [ TOAST ] classification ) , tests/ procedures , and discharge status ( independent , Rankin ≤ 2 , vs dead or dependent , Rankin 3 through 5 ) were compared between patients who were or were not cared for by a neurologist . Results : Of 1,073 enrolled patients , 775 ( neurologist care , n = 614 ; non-neurologist , n = 161 ) with ischemic stroke were admitted from home . Stroke severity ( Canadian Neurologic Score 8.7 ± 0.1 vs 8.4 ± 0.2 ; p = 0.44 ) , TOAST subtype ( p = 0.55 ) , and patient age ( 71.4 ± 0.4 vs 72.4 ± 0.7 ; p = 0.23 ) were similar for neurologists and non-neurologists . Neurologists more frequently obtained MRI ( 44 % vs 16 % ; p < 0.001 ) , transesophageal echocardiograms ( 12 % vs 2 % ; p < 0.001 ) , carotid ultrasounds ( 65 % vs 57 % ; p = 0.05 ) , cerebral angiography ( 8 % vs 1 % ; p = 0.001 ) , speech ( 35 % vs 18 % ; p < 0.001 ) , and occupational therapy ( 46 % vs 33 % ; p = 0.005 ) evaluations . Brain CT , transthoracic echocardiogram , 24-hour ambulatory ECG use , and hospitalization duration s ( 18.2 ± 0.8 vs 19.7 ± 4.1 days ; p = 0.725 ) were similar . Neurologists ’ patients were less likely to be dead ( 5.6 % vs 13.5 % ; OR = 0.38 ; 95 % CI 0.22 , 0.68 ; p = 0.001 ) and less likely to be dead or dependent ( 46.1 % vs 57.1 % ; OR = 0.64 ; 95 % CI 0.45 , 0.92 ; p = 0.019 ) at the time of discharge . The benefit remained after controlling for stroke severity and comorbidity ( OR = 0.63 ; 95 % CI 0.42 , 0.94 ; p = 0.025 ) . Conclusion : Neurologist care was associated with more extensive testing , but similar lengths of hospitalization and improved outcomes BACKGROUND To increase the effective use of thrombolytics for acute stroke , the expertise of vascular neurologists must be disseminated more widely . We prospect ively assessed whether telemedicine ( real-time , two-way audio and video , and digital imaging and communications in medicine [ DICOM ] interpretation ) or telephone was superior for decision making in acute telemedicine consultations . METHODS From January , 2004 , to August , 2007 , patients older than 18 years who presented with acute stroke symptoms at one of four remote spoke sites were r and omly assigned , through a web-based , permuted blocks system , to telemedicine or telephone consultation to assess their suitability for treatment with thrombolytics , on the basis of st and ard criteria . The primary outcome measure was whether the decision to give thrombolytic treatment was correct , as determined by central adjudication . Secondary outcomes were the rate of thrombolytic use , 90-day functional outcomes ( Barthel index [ BI ] and modified Rankin scale [ mRS ] ) , the incidence of intracerebral haemorrhages , and technical observations . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00283868 . FINDINGS 234 patients were assessed prospect ively . 111 patients were r and omised to telemedicine , and 111 patients were r and omised to telephone consultation ; 207 completed the study . Mean National Institutes of Health stroke scale score at presentation was 9.5 ( SD 8.1 ) points ( 11.4 [ 8.7 ] points in the telemedicine group versus 7.7 [ 7.0 ] points in the telephone group ; p=0.002 ) . One telemedicine consultation was aborted for technical reasons , although it was included in the analyses . Correct treatment decisions were made more often in the telemedicine group than in the telephone group ( 108 [ 98 % ] vs 91 [ 82 % ] , odds ratio [ OR ] 10.9 , 95 % CI 2.7 - 44.6 ; p=0.0009 ) . Intravenous thrombolytics were used at an overall rate of 25 % ( 31 [ 28 % ] telemedicine vs 25 [ 23 % ] telephone , 1.3 , 0.7 - 2.5 ; p=0.43 ) . 90-day functional outcomes were not different for BI ( 95 - 100 ) ( 0.6 , 0.4 - 1.1 ; p=0.13 ) or for mRS score ( 0.6 , 0.3 - 1.1 ; p=0.09 ) . There was no difference in mortality ( 1.6 , 0.8 - 3.4 ; p=0.27 ) or rates of intracerebral haemorrhage after treatment with thrombolytics ( 2 [ 7 % ] telemedicine vs 2 [ 8 % ] telephone , 0.8 , 0.1 - 6.3 ; p=1.0 ) . However , there were more incomplete data in the telephone group than in the telemedicine group ( 12%vs 3 % , 0.2 , 0.1 - 0.3 ; p=0.0001 ) . INTERPRETATION The authors of this trial report that stroke telemedicine consultations result in more accurate decision making compared with telephone consultations and can serve as a model for the effectiveness of telemedicine in other medical specialties . The more appropriate decisions , high rates of thrombolysis use , improved data collection , low rate of intracerebral haemorrhage , low technical complications , and favourable time requirements all support the efficacy of telemedicine for making treatment decisions , and might enable more practitioners to use this medium in daily stroke care Background and Purpose — ResolutionMD mobile application runs on a Smartphone and affords vascular neurologists access to radiological images of patients with stroke from remote sites in the context of a telemedicine evaluation . Although reliability studies using this technology have been conducted in a controlled environment , this study is the first to incorporate it into a real-world hub and spoke telestroke network . The study objective was to assess the level of agreement of brain CT scan interpretation in a telestroke network between hub vascular neurologists using ResolutionMD , spoke radiologists using a Picture Archiving and Communications System , and independent adjudicators . Methods — Fifty-three patients with stroke at the spoke hospital consented to receive a telemedicine consultation and participate in a registry . Each CT was evaluated by a hub vascular neurologist , a spoke radiologist , and by blinded telestroke adjudicators , and agreement over clinical ly important radiological features was calculated . Results — Agreement ( & kgr ; and 95 % CI ) between hub vascular neurologists using ResolutionMD and ( 1 ) the spoke radiologist ; and ( 2 ) independent adjudicators , respectively , were : identification of intracranial hemorrhage 1.0 ( 0.92–1.0 ) , 1.0 ( 0.93–1.0 ) , neoplasm 1.0 ( 0.92–1.0 ) , 1.0 ( 0.93–1.0 ) , any radiological contraindication to thrombolysis 1.0 ( 0.92–1.0 ) , 0.85 ( 0.65–1.0 ) , early ischemic changes 0.62 ( 0.28–0.96 ) , 0.58 ( 0.30–0.86 ) , and hyperdense artery sign 0.40 ( 0.01–0.80 ) , 0.44 ( 0.06–0.81 ) . Conclusions — CT head interpretations of telestroke network patients by vascular neurologists using ResolutionMD on Smartphones were in excellent agreement with interpretations by spoke radiologists using a Picture Archiving and Communications System and those of independent telestroke adjudicators using a desktop viewer . Clinical Trial Registration Information— www . clinical trials.gov unique identifier NCT00829361 Rationale Time from symptom onset to treatment is closely associated with the effectiveness of intravenous thrombolysis in acute ischemic stroke patients . Hospitals are encouraged to take every effort to shorten delay of treatment . Despite combined efforts to streamline procedures in hospitals to provide treatment as soon as possible , most patients receive tissue plasminogen activator with considerable delay and very few of them within 90 mins . Germany has an internationally acknowledged prehospital emergency care system with specially trained doctors on ambulances . We developed an ambulance equipped with a Computed Tomography ( CT ) scanner , point-of-care laboratory , teleradiological support , and an emergency-trained neurologist on board . In the Pre-Hospital Acute Neurological Therapy and Optimization of Medical care in Stroke Patients study , we aim at a reduction of the current alarm-to-needle time by prehospital use of tissue plasminogen activator in an ambulance . Aims We hypothesized that compared with regular care , we will reduce alarm-to-needle time by a minimum of 20 mins by implementation of the stroke emergency mobile unit . Design Prospect i ve study comparing r and omly allocated periods with and without stroke emergency mobile unit availability . Study Outcomes Primary end point of the study is alarm-to-needle time . Secondary outcomes include thrombolysis treatment rates , modified Rankin scale after three-months , and alarm-to-imaging or alarm-to-laboratory time ; safety aspects to be evaluated are mortality and rates of ( symptomatic ) intracerebral hemorrhage |
1,112 | 26,333,525 | Authors ' conclusions Material incentives and enablers may have some positive short term effects on clinic attendance , particularly for marginal population s such as drug users , recently released prisoners , and the homeless , but there is currently insufficient evidence to know if they can improve long term adherence to TB treatment | Background Patient adherence to medications , particularly for conditions requiring prolonged treatment such as tuberculosis ( TB ) , is frequently less than ideal and can result in poor treatment outcomes .
Material incentives to reward good behaviour and enablers to remove economic barriers to accessing care are sometimes given in the form of cash , vouchers , or food to improve adherence .
Objectives To evaluate the effects of material incentives and enablers in patients undergoing diagnostic testing , or receiving prophylactic or curative therapy , for TB . | Background Poverty undermines adherence to tuberculosis treatment . Economic support may both encourage and enable patients to complete treatment . In South Africa , which carries a high burden of tuberculosis , such support may improve the currently poor outcomes of patients on tuberculosis treatment . The aim of this study was to test the feasibility and effectiveness of delivering economic support to patients with pulmonary tuberculosis in a high-burden province of South Africa . Methods This was a pragmatic , unblinded , two-arm cluster-r and omized controlled trial , where 20 public sector clinics acted as clusters . Patients with pulmonary tuberculosis in intervention clinics ( n = 2,107 ) were offered a monthly voucher of ZAR120.00 ( approximately US$ 15 ) until the completion of their treatment . Vouchers were redeemed at local shops for foodstuffs . Patients in control clinics ( n = 1,984 ) received usual tuberculosis care . Results Intention to treat analysis showed a small but non-significant improvement in treatment success rates in intervention clinics ( intervention 76.2 % ; control 70.7 % ; risk difference 5.6 % ( 95 % confidence interval : -1.2 % , 12.3 % ) , P = 0.107 ) . Low fidelity to the intervention meant that 36.2 % of eligible patients did not receive a voucher at all , 32.3 % received a voucher for between one and three months and 31.5 % received a voucher for four to eight months of treatment . There was a strong dose – response relationship between frequency of receipt of the voucher and treatment success ( P < 0.001 ) . Conclusions Our pragmatic trial has shown that , in the real world setting of public sector clinics in South Africa , economic support to patients with tuberculosis does not significantly improve outcomes on treatment . However , the low fidelity to the delivery of our voucher meant that a third of eligible patients did not receive it . Among patients in intervention clinics who received the voucher at least once , treatment success rates were significantly improved . Further operational research is needed to explore how best to ensure the consistent and appropriate delivery of such support to those eligible to receive it . Trial registration Current Controlled TrialsIS RCT Background Poverty undermines the adherence of patients to tuberculosis treatment . A pragmatic cluster r and omized controlled trial was conducted to investigate the extent to which economic support in the form of a voucher would improve patients ’ adherence to treatment , and their treatment outcomes . Although the trial showed a modest improvement in the treatment success rates of the intervention group , this was not statistically significant , due in part to the low fidelity to the trial intervention . A qualitative process evaluation , conducted in the final few months of the trial , explained some of the factors that contributed to this low fidelity . Methods In-depth interviews were conducted with patients who received vouchers , nurses in intervention clinics , personnel in shops who administered the vouchers , and managers of the TB Control Programme . These interviews were analyzed thematically . Results The low fidelity to the trial intervention can be explained by two main factors . The first was nurses ’ tendency to ‘ ration ’ the vouchers , only giving them to the most needy of eligible patients and leaving out those eligible patients whom they felt were financially more comfortable . The second was logistical issues related to the administration of the voucher as vouchers were not always available for patients on their appointed clinic date s , necessitating further visits to the clinics which they were not always able to make . Conclusions This process evaluation identifies some of the most important factors that contributed to the results of this pragmatic trial . It highlights the value of process evaluations as tools to explain the results of r and omized trials and emphasizes the importance of implementers as ‘ street level bureaucrats ’ who may profoundly affect the way an intervention is administered . Trial registration Current Controlled Trials IS RCT N50689131 , registered 21 April 2009.The trial protocol is available at the following web address : http://www.hst.org.za/publications/ study - protocol -economic-incentives-improving- clinical - outcomes - patients -tb-south-africa Objective To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis . Design Parallel group r and omised controlled trial . Setting Three primary care clinics in Dili , Timor-Leste . Participants 270 adults aged ≥18 with previously untreated newly diagnosed pulmonary tuberculosis . Main outcome measures Completion of treatment ( including cure ) . Secondary outcomes included adherence to treatment , weight gain , and clearance of sputum smears . Outcomes were assessed remotely , blinded to allocation status . Interventions Participants started st and ard tuberculosis treatment and were r and omly assigned to intervention ( nutritious , culturally appropriate daily meal ( weeks 1 - 8 ) and food package ( weeks 9 - 32 ) ( n=137 ) or control ( nutritional advice , n=133 ) groups . R and omisation sequence was computer generated with allocation concealment by sequentially numbered , opaque , sealed envelopes . Results Most patients with tuberculosis were poor , malnourished men living close to the clinics ; 265/270 ( 98 % ) contributed to the analysis . The intervention had no significant beneficial or harmful impact on the outcome of treatment ( 76 % v 78 % completion , P=0.7 ) or adherence ( 93 % for both groups , P=0.7 ) but did lead to improved weight gain at the end of treatment ( 10.1 % v 7.5 % improvement , P=0.04 ) . Itch was more common in the intervention group ( 21 % v 9 % , P<0.01 ) . In a subgroup analysis of patients with positive results on sputum smears , there were clinical ly important improvements in one month sputum clearance ( 85 % v 67 % , P=0.13 ) and completion of treatment ( 78 % v 68 % , P=0.3 ) . Conclusion Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste . Further studies in different setting s and measuring different outcomes are required . Trial registration Clinical Trials NCT0019256 BACKGROUND Drug users are at increased risk for latent tuberculosis infection ( LTBI ) and also at increased risk for noncompletion of medication regimens for treatment of LTBI or tuberculosis disease . Directly observed therapy ( DOT ) provided by outreach workers , the use of incentives , or both have been suggested as a means to increase adherence . OBJECTIVE To compare the independent and combined effects of monetary incentives and outreach worker provision of DOT for LTBI treatment in a sample of active drug users . METHODS The research design was a r and omized controlled trial in a community outreach program setting . Participants consisted of a volunteer sample of 163 active injection drug and crack cocaine users placed on twice weekly DOT . Condition 1 of the interventions consisted of provision of DOT by an outreach worker at a location chosen by the participant ( active outreach ) and a $ 5 per visit incentive . Condition 2 was comprised of active outreach with no monetary incentive , and Condition 3 , provision of DOT at the study community site and a $ 5 per visit incentive . The main outcome measures were percentage of medication taken as prescribed and completion of medication regimen . RESULTS The percentage of prescribed medication taken was higher for those who received incentives , either with ( 71 % ) or without ( 68 % ) active outreach , compared to those who received active outreach alone ( 13 % ) . Only 4 % of participants assigned to Condition 2 completed treatment , compared to 53 % of Condition 1 participants , and 60 % of Condition 3 participants . CONCLUSIONS Monetary incentives were clearly superior to active outreach . Active outreach in combination with monetary incentives did not increase adherence over incentives alone SETTING Few studies have examined strategies for optimizing adherence to latent tuberculosis infection ( LTBI ) treatment programs in homeless population s. OBJECTIVES 1 ) To compare the effectiveness of an intervention program employing nurse case management and incentives ( NCMI ) vs. a control program with st and ard care and incentives on completion of LTBI treatment ; and 2 ) to compare the impact of the two programs on tuberculosis ( TB ) knowledge among participants . DESIGN A prospect i ve , two-group site-r and omized design conducted among 520 homeless adults residing in the Skid Row region of Los Angeles from 1998 to 2003 , assessing completion rates of a 6-month isoniazid ( INH ) treatment program and change in TB knowledge . RESULTS Using intent-to-treat analysis , 62 % of participants in the intervention program , compared with 39 % of controls , completed the full 6-month course of LTBI treatment with INH . Logistic regression modeling revealed that intervention participants had three times greater odds of completing INH treatment than controls . TB knowledge improved in both programs , but the increase was greater among the intervention participants ( P < 0.001 ) . CONCLUSIONS Nurse case management combined with education , incentives , and tracking dramatically improves both adherence to LTBI treatment and TB knowledge in homeless persons compared to a st and ard approach of outreach and incentives OBJECTIVES To test 2 interventions to improve adherence to isoniazid preventive therapy for tuberculosis in homeless adults . We compared ( 1 ) biweekly directly observed preventive therapy using a $ 5 monetary incentive and ( 2 ) biweekly directly observed preventive therapy using a peer health adviser , with ( 3 ) usual care at the tuberculosis clinic . METHODS R and omized controlled trial in tuberculosis-infected homeless adults . Outcomes were completion of 6 months of isoniazid treatment and number of months of isoniazid dispensed . RESULTS A total of 118 subjects were r and omized to the 3 arms of the study . Completion in the monetary incentive arm was significantly better than in the peer health adviser arm ( P = .01 ) and the usual care arm ( P = .04 ) , by log-rank test . Overall , 19 subjects ( 44 % ) in the monetary incentive arm completed preventive therapy compared with 7 ( 19 % ) in the peer health adviser arm ( P = .02 ) and 10 ( 26 % ) in the usual care arm ( P = .11 ) . The median number of months of isoniazid dispensed was 5 in the monetary incentive arm vs 2 months in the peer health adviser arm ( P = .005 ) and 2 months in the usual care arm ( P = .04 ) . In multivariate analysis , independent predictors of completion were being in the monetary incentive arm ( odds ratio , 2.57 ; 95 % CI , 1.11 - 5.94 ) and residence in a hotel or other stable housing at entry into the study vs residence on the street or in a shelter at entry ( odds ratio , 2.33 ; 95 % CI , 1.00 - 5.47 ) . CONCLUSIONS A $ 5 biweekly cash incentive improved adherence to tuberculosis preventive therapy compared with a peer intervention or usual care . Living in a hotel or apartment at the start of treatment also predicted the completion of therapy SETTING Screening for active tuberculosis ( TB ) and providing isoniazid ( INH ) preventive therapy in jails are important control measures . In San Francisco , however , historical data showed that 62 % of inmates were released before completing preventive therapy , and of those only 3 % attended the TB Clinic for follow-up . OBJECTIVE AND DESIGN A r and omized clinical trial to compare a $ 5 cash incentive plus st and ardized TB education with st and ardized TB education alone in encouraging released inmates to make a first visit to the clinic . RESULTS Of 79 persons enrolled in the trial , 77.2 % were released before INH completion . Rates of first visit were not significantly different for those receiving + 5 plus st and ardized education ( 25.8 % ) versus st and ardized education alone ( 23.3 % ) , but were higher than rates seen in historical data for inmates not receiving st and ardized education . Age was an important predictor of completion of a first visit ( odds ratio 1.09 , 95 % confidence interval 1.02 - 1.16 , P = 0.017 ) . Other variables predicting adherence included intent to adhere , more previous time in jail , stable housing , and being partnered versus alone , although these were not statistically significant . CONCLUSION St and ardized education may be important in improving follow-up after release . Further work on the role of a financial incentive in this population is needed Background : The efficacy of a nurse case-managed intervention was evaluated in sub sample s of participants with one of the following characteristics : female gender , African American ethnicity , recruited from a homeless shelter , a history of military service , lifetime injection drug use , daily alcohol and drug use , poor physical health , and a history of poor mental health . Objective : To determine whether a vali date d nurse case-managed intervention with incentives and tracking would improve adherence to latent tuberculosis infection treatment in sub sample s of homeless persons with characteristics previously identified in the literature as predictive of nonadherence . Methods : A prospect i ve 2-group site-r and omized design was conducted with 520 homeless adults residing in 12 homeless shelters and residential recovery sites in the Skid Row region of Los Angeles from 1998 to 2003 . Results : Daily drug users , participants with a history of injection drug use , daily alcohol users , and persons who were not of African American race or ethnicity had particularly poor completion rates , even in the nurse case-managed intervention program ( 48 % , 55 % , 54 % , and 50 % , respectively ) . However , the intervention achieved a 91 % completion rate for homeless shelter residents and significantly improved latent tuberculosis infection treatment adherence in 9 of 12 subgroups tested ( odds ratios = 2.51 - 10.41 ) , including daily alcohol and drug users , when potential confounders were controlled using logistic regression analysis . Discussion : Nurse case management with incentives appears to be a good foundation for increasing adherence to 6-month isoniazid treatment in a variety of homeless subgroups and , in particular , for sheltered homeless population s. However , additional social-structural and environmental strategies are needed to address those at greatest risk of nonadherence The design , logic , and results of a two-year health education study directed at i m proving rates of patient adherence to antituberculosis medical regimens are presented . An incentive scheme to reward positive health behaviors plus targeted educational coun seling sessions was implemented in a r and omized clinical controlled trial . The 205 subjects who participated in the study are categorized according to patients with active tuberculosis ( n = 88 ) or preventive patients with no evidence of active disease ( n = 117 ) . Patients in each of these groups were r and omly assigned to a special intervention ( SI ) group or a usual care ( UC ) control group and were followed monthly throughout their treatment program . While SI patients with active tuberculosis demonstrated higher levels of ap pointment-keeping behavior and mean percent of medication taken compared to UC patients , no statistically significant differences between the two groups were found . Pre ventive therapy patients assigned to the SI group , however , were significantly more likely than UC patients to remain in care during their 12-month regimen ( 64 % vs 47 % ; p = .003 ) . Furthermore , SI patients had significantly higher levels of adherence to their medical regimen compared to UC patients ( 68 % vs 38 % ; p < .001 ) . These results demonstrate the positive effects of a structured health education program on the i m provement of continuity of care and adherence behavior among patients with tuberculosis . This study was funded by the Centers for Disease Control through contract # 200 - 85 - 0835 . The assistance of the Project Clerk , Sook Hee Treadwell , the Project Health Educators , Magda Fischer , Jennifer Adams , Nancy Murray , Fred Dominguez , and the clinic staff and patients who participated in this project are gratefully acknowledged . 1 . US Department of Health and Human Services , Public Health Service : The 1990 Health Objectives for the Nation : A Midcourse Review . Office of Disease Prevention and Health Promotion , 1986 . 2 . Centers for Disease Control . Tuberculosis — Provisional data —United States , 1986 . MMWR 36 : 254 - 255 , 1987 . 3 . Centers for Disease Control . Tuberculosis . Final Data —United States , 1986 . MMWR 36 : 817 - 820 , 1988 . 4 . County of Los Angeles , Department of Health Services , Public Health Programs : Communicable Disease Morbidity Report , County of Los Angeles , 1986 . 5 . Kopanoff DE , Snider DE , Johnson M : Recurrent tuberculosis : Why do patients develop disease again ? A United States Public Health Service Cooperative Survey . Am J Public Health 78 : 30 - 33 , 1988 . 6 . American Thoracic Society : Treatment of tuberculosis and tuberculosis infection in adults and children . Am Rev Respir Dis 134 : 355 - 363 , 1986 . 7 . Haynes RB : Introduction , in RB Haynes , DW Taylor , DL Sackett . ( eds ) : Compliance in Health Care . Baltimore , Johns Hopkins University Press , 1979 , pp 1 - 7 . 8 . Sackett DL , Haynes RB , editor : Compliance with Therapeutic Regimens . Baltimore , Johns Hopkins University Press , 1976 . 9 . Haynes RB , Taylor DW , Sackett DL , ed : Compliance in Health Care . Baltimore , Johns Hopkins University Press , 1979 . 10 . Meichenbaum D , Turk DC : Facilitating Treatment Adherence : A Practitioner 's Guidebook . Plenum Press , New York , 1987 . 11 . Addington WW : Patient compliance : The most serious remaining problem in the control of tuberculosis in the United States . Chest 76 (supp):741 - 743 , 1979 . 12 . Report of the Committee : A Strategic Plan for the Elimination of Tuberculosis in the United States . US Department of Health and Human Services , Centers for Disease Control , May 1988 . 13 . Comstock GW : New data on preventive treatment with isoniazid . Annals of Internal Medicine 98:663 - 665 , 1983 . 14 . Cross FS , Long MW , Banner AS , Snider DE Jr : Rifampin-isoniazid therapy of alcoholics and nonalcoholic tuberculosis patients in a U.S. Public Health Service cooperative trial . Am Rev Respir Dis 122:349 - 353 , 1980 . 15 . Snider DE Jr , . Improving Patient Compliance in Tuberculosis Treatment Programs . Atlanta , U.S. Department of Health and Human Services , Public Health Service , Centers for Disease Control , 1985 . 16 . Green LW , Kreuter MW , Deeds SG , Partridge KB : Health Education Planning : A Diagnostic Approach . Palo Alto , CA , Mayfield Publishing Company , 1980 . 17 . Hochbaum GM , Public Participation in Medical Science Programs : A Sociopsy chological Study . Washington , DC , United States Government Printing Office , PHS Publication No. 572 , 1958 . 18 . Rosenstock IM : What research in motivation suggests for public health . Am J Public Health 50:295 - 302 , 1960 . 19 . Becker MH : The health belief model and personal health behavior . Health Educ Monographs 2:324 - 473 , 1974 . 20 . Becker MH : Sociobehavioral determinants of compliance , in DL Sackett , RB Haynes ( eds ) : Compliance with Therapeutic Regimens . Baltimore , Johns Hopkins University Press , 1976 , pp 40 - 50 . 21 . Janz NK , Becker MH : The health belief model : A decade later . Health Education Quarterly 11:1 - 47 , 1984 . 22 . Sackett DL : Priorities and methods for future research , in DL Sackett , RB Haynes ( eds ) : Compliance with Therapeutic Regimens . Baltimore , Johns Hopkins University Press , 1976 , pp 169 - 189 . 23 . Dunbar JM , Stunkard AJ : Adherence to diet and drug regimen , in Levy RI , Rifkind B , Dennis B , Ernst N ( eds ) : Nutrition , Lipids , and Coronary Heart Disease . New York , Raven Press , 1979 , pp 391 - 423 . 24 . Svarstad BL : Physician-patient communication and patient conformity with medical advice , in Mechanie D ( ed ) : The Growth of Bureaucratic Medicine . New York , John Wiley and Sons , 1976 , pp 220 - 238 . 25 . Colcher IS , Bass JW : Penicillin treatment of streptococcal pharyngitis : A comparison of schedules and the role of specific counselling . JAMA 222:657 - 659 , 1972 . 26 . Sharpe TR , Mikeal RL : Patient compliance with antibiotic regimens . Am J Hospital Pharm 31:479 - 484 , 1974 . 27 . Swain MA , Steckel SB : Influencing adherence among hypertensives . Res Nursing and Health 4:213 - 222 , 1981 . 28 . Levine DM , Green LW , Russell RP , Morisky DE , Chwalow J , Benson P : Compliance in hypertension management : What the physician can do . Practical Cardiology 5:151- 160 , 1979 . 29 . DiMatteo MR , DiNicola DD , Achieving Patient Compliance : The Psychology of the Medical Practitioner 's Role . New York , Pergamon Press , 1982 . 30 . Eraker SA , Kirscht JP , Becker MH : Underst and ing and improving patient compli ance . Ann Intern Med 100:258 - 268 , 1984 . 31 . Waitzkin H , Stoeckle JD : Information control and the micro-politics of health care . Soc Sci Med 10:263 - 276 , 1976 . 32 . Minkler M : The use of incentives in family planning programmes : A study of com peting theories regarding their influence on attitude change . Int J Health Educ 19 (supplement):1 - 11 , 1976 . 33 . Sbarbaro JA : Compliance : Inducements and enforcements . Chest 76 ( supp ) : 750- 756 , 1979 . 34 . Snider DE Jr , And ers HM , Pozsik CJ : Incentives to take up health services . Lancet 2:812 , 1986 . 35 . Hull CH , Nie NH . Survival : Life Table Analysis . SPSS Up date 7 - 9 , McGraw-Hill , New York , 1981 PURPOSE Assess the costs and cost-effectiveness of an incentive-based tuberculosis ( TB ) program design ed to promote adolescents ' compliance with treatment for latent TB infection ( LTBI ) . METHODS R and omized controlled trial . Adolescents between the ages of 11 and 19 years who were referred to one of two participating clinics after being screened for TB and receiving a positive diagnosis indicating LTBI ( n = 794 ) were assigned to one of four groups : usual care , peer counseling , contingency contracting , and combined peer counseling/contingency contracting . Primary outcome variables were completion of isoniazid preventive therapy ( IPT ) , total treatment costs , and lifetime TB-related costs per quality -adjusted life year ( QALY ) in each of the four study groups ( three treatment , one control ) . Cost effectiveness was evaluated using a five-stage Markov model and a Monte Carlo simulation with 10,000 trials . RESULTS Average costs were 199 dollars for usual care ( UC ) , 277 dollars for peer counseling ( PC ) , 326 dollars for contingency contracting ( CC ) , and 341 dollars for PC + CC combined . The differences among these groups were all significant at the p = .001 level . Only the PC + CC group improved the rate of IPT completion ( 83.8 % ) relative to usual care ( 75.9 % ) ( p = .051 ) , with an overall incremental CE ratio of 209 dollars per QALY relative to usual care . CONCLUSION Incentives combined with peer counseling are a cost-effective strategy for helping adolescents to complete care when combined with peer counseling 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 PURPOSE To determine the effect of several interventions on adherence to tuberculosis preventive therapy . METHODS We conducted a r and omized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis . Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly ( Supervised group , n = 99 ) , daily self-administered isoniazid with peer counseling and education ( Peer group , n = 101 ) , or routine care ( Routine group , n = 100 ) . Patients within each arm were also r and omly assigned to receive an immediate or deferred monthly $ 10 stipend for maintaining adherence . The endpoints of the trial were completing 6 months of treatment , pill-taking as measured by self-report or observation , isoniazid metabolites present in urine , and bottle opening as determined by electronic monitors in a subset of patients . RESULTS Completion of therapy was 80 % for patients in the Supervised group , 78 % in the Peer group , and 79 % in the Routine group ( P = 0.70 ) . Completion was 83 % ( 125 of 150 ) among patients receiving immediate incentives versus 75 % ( 112 of 150 ) among patients with deferred incentives ( P = 0.09 ) . The proportion of patients who were observed or reported taking at least 80 % of their doses was 82 % for the Supervised arm of the study , compared with 71 % for the Peer arm and 90 % for the Routine arm . The proportion of patients who took 100 % of doses was 77 % for the Supervised arm ( by observation ) , 6 % for the Peer arm ( by report ) , and 10 % for the Routine arm ( by report ; P < 0.001 ) . Direct observation showed the median proportion of doses taken by the Supervised group was 100 % , while electronic monitoring in a subset of patients showed the Peer group ( n = 27 ) took 57 % of prescribed doses and the Routine group ( n = 32 ) took 49 % ( P < 0.001 ) . Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold st and ard . There were no significant differences in electronically monitored adherence by type of incentive . CONCLUSION Adherence to isoniazid preventive therapy by injection drug users is best with supervised care . Peer counseling improves adherence over routine care , as measured by electronic monitoring of pill caps , and patients receiving peer counseling more accurately reported their adherence . More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups BACKGROUND Adherence to treatment of persons with latent tuberculosis infection after release from jail has been poor . METHODS A r and omized controlled trial was conducted at the San Francisco City and County Jail , San Francisco , Calif. Subjects undergoing therapy for latent tuberculosis infection who spoke either English or Spanish were r and omly allocated to receive education every 2 weeks while in jail ; an incentive if they went to the San Francisco County Tuberculosis Clinic within 1 month of release ; or usual care . The main outcome measures were completion of a visit to the tuberculosis clinic within 1 month of release and completion of therapy . RESULTS Of 558 inmates enrolled , 325 were released before completion of therapy . Subjects in either intervention group were significantly more likely to complete a first visit than were control subjects ( education group , 37 % ; incentive group , 37 % ; and controls , 24 % ) ( adjusted odds ratio based on pooled results for the education and incentive groups , 1.85 ; 95 % confidence interval , 1.04 - 3.28 ; P = .02 ) . Those in the education group were twice as likely to complete therapy compared with controls ( adjusted odds ratio , 2.2 ; 95 % confidence interval , 1.04 - 4.72 ; P = .04 ) . Of those who went to the tuberculosis clinic after release , subjects in the education group were more likely to complete therapy ( education group , 65 % [ 24/37 ] ; incentive group , 33 % [ 14/42 ] ; and control group , 48 % [ 12/25 ] ; P = .02 ) . CONCLUSIONS Education or the promise of an incentive improved initial follow-up . Education was superior to an incentive for the completion of therapy . Fairly modest strategies provided in jail can improve adherence . Further links between jail health services and community care should be explored BACKGROUND In a prior study , we reported that monetary incentives were effective in increasing return for tuberculosis ( TB ) skin test reading . The purpose of this study was to compare the effects of monetary versus nonmonetary incentives and a theory-based educational intervention on return for TB skin test reading in a sample of newly recruited active injection and crack cocaine users , and to determine the prevalence of TB infection in this sample . METHODS Active injection drug and /or crack cocaine users ( n = 1,078 ) , recruited using street outreach techniques , were skin tested for TB . They were r and omly assigned to 1 of 5 experimental treatment conditions : $ 10 cash , grocery store coupons , bus tokens/fast-food coupons , motivational education , or usual encouragement to return . Nonmonetary incentives had a $ 10 value , and all incentives were provided at return for skin test reading . RESULTS Ninety-five percent of those who received $ 10 returned for skin test reading compared to 86 % of those who received grocery store coupons and 83 % of those who received either bus tokens or fast-food coupons . In contrast , only 47 % of those who received the educational session and only 49 % of those who received usual encouragement returned for skin test reading . The prevalence of a positive tuberculin test was 21 % , and was similar for crack cocaine and injection drug users . CONCLUSIONS Nonmonetary and monetary incentives dramatically increased the return rate for TB skin test reading among drug users who are at high risk of TB infection . Nonmonetary incentives were somewhat less effective than monetary incentives OBJECTIVES Activation of latent tuberculosis infection into tuberculosis disease ( TB ) , the primary killer among infectious diseases worldwide , can be prevented with six months of anti-TB medication . A large percentage of adolescents started on medication , however , fail to complete their treatment . The authors developed and tested the effects of innovative educational strategies on infected adolescents at two health centers serving ethnically diverse population s. METHODS The authors used a r and omized experimental four-group design to assess the independent and combined effects of peer counseling and a participant-parent contingency contract intervention . RESULTS A total of 794 adolescents were recruited into the study , for a 79 % participation rate . The overall rate of treatment completion was 79.8 % . Self-efficacy for medication-taking behavior at post-test correlated strongly with completion of care ( R = 0.367 , p = 0.002 ) . Participants r and omized to the peer counseling groups demonstrated significantly greater improvements in self-efficacy and mastery than the usual care control group . Based on the study results , continuing education seminars and workshops were implemented for TB control staff at the two health clinics and for all TB Control Division staff at the Los Angeles County Health Department . Educational material s and a training manual for enhancing completion of treatment of latent TB infection through tailored educational approaches were developed and disseminated to the clinics . CONCLUSIONS Health education and incentives are helpful adjuncts to the completion of treatment for latent tuberculosis infection in adolescents SETTING Community-based population of homeless adults living in San Francisco , California . OBJECTIVE To compare the effect of cash and non-cash incentives on 1 ) adherence to treatment for latent tuberculosis infection , and 2 ) length of time needed to look for participants who missed their dose of medications . DESIGN Prospect i ve , r and omized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive . All participants received directly observed preventive therapy and st and ardized follow-up per a predetermined protocol . Completion rates and amount of time needed to follow up participants was measured . RESULTS Of the 119 participants , 102 ( 86 % ) completed therapy . There was no difference between the cash and non-cash arms . Completion was significantly higher among males ( OR 5.65 , 95%CI 1.36 - 23.40 , P = 0.02 ) and persons in stable housing at study entry ( OR 4.86 , 95%CI 1.32 - 17.94 , P = 0.02 ) . No substance use or mental health measures were associated with completion . Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm ( P = 0.03 ) . In multivariate analysis , non-cash incentive , use of crack cocaine , and no prior preventive therapy were associated with more follow-up time . CONCLUSION Simple , low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults INTRODUCTION Wasting is the cardinal feature of tuberculosis , but not much documentary evidence supporting food supplements exists . This study was done to assess the effects of food supplements on body weight , physical function , quality of life and treatment outcomes in patients with tuberculosis and wasting . METHODS The study was conducted in 30 Anganwadi centres of 16 villages in the catchment area of Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation and the Gannavaram Directly Observed Treatment Short Course chemotherapy centre from August 2005 to December 2005 . A total of 100 patients participated in the study . Patients who were started on anti-tubercular therapy within the previous two weeks were r and omly assigned to either the control or the food supplement group . At the end of three months , their body weight was measured and physical function and quality of life were assessed . Treatment outcomes were assessed at the one-year follow-up for both groups . RESULTS Patients who received supplements had a significant increase in body weight ( 8.6 percent versus 2.6 percent , p-value less than 0.001 ) and maximum grip strength ( p-value less than 0.001 ) , a higher sputum conversion rate ( p-value is 0.039 ) , a higher treatment completion rate ( p-value is 0.031 ) and improvements in the quality of life scores . CONCLUSION Intake of food supplements result ed in a definitive increase in body weight and physical function in our study sample . Improvements can be observed in all areas , including psychologically , physiologically , socially and in the treatment outcomes OBJECTIVE To determine the most effective strategy to encourage adherence with tuberculosis test reading in a high-risk population . Design . Prospect i ve r and omized controlled trial . SETTING / PARTICIPANTS Consecutive sample of 627 children ages 1 to 12 years due for a tuberculosis ( TB ) test in an urban children 's hospital outpatient department . One child per family was enrolled . INTERVENTION All families received education regarding the importance of skin testing for TB and the need for follow-up , and written and verbal instructions regarding test reading . Families were r and omly assigned to one of five strategies for follow-up TB test reading at 48 to 72 hours : 1 ) routine verbal and written instructions , 2 ) reminder phone call , 3 ) transportation tokens and toy on return , 4 ) withholding of school forms until time of reading and need to repeat TB test if not timely read , 5 ) parents taught to read in duration with nurse home visit . Those who did not have tests read at 48 to 72 hours by a trained professional were phoned 1 week later . RESULTS The five groups did not differ with regard to TB risk factor score , maternal education , transportation source , or perceived importance of TB testing . Before the study the follow-up rate of TB test reading by a trained professional was 45 % . Reading rates in this study were 58 % , 70 % , 67 % , 70 % , and 72 % for groups 1 to 5 , respectively . In group 4 , only 39 % had school forms to be completed and their adherence rate was 84 % ( 53/63 ) . Compared to group 1 , the only statistically significant improvement was in group 4 , especially for those who needed school forms completed , and in group 5 . Those not adhering in groups 1 to 4 did not differ from returnees with regard to TB risk factors , maternal education , transportation , or perceived importance of testing . The most common reasons for failing to return included forgetfulness , transportation , and time constraints . Group 5 was stopped early because of difficulty with nurse visits ( N = 98 ) . When told of the nurse visit , 9 % ( 9/98 ) families could not find a time for the visit . Seventeen percent ( 17/98 ) were visited but the child was not home , and 7 % ( 7/98 ) were not visited because of a nurse scheduling problem . CONCLUSIONS In a high-risk population , adherence with TB test reading is poor . However , education and return of school forms at reading time can significantly improve adherence . Although requiring larger investment in re sources , visiting nurses may also aid in test reading OBJECTIVES This study assessed the independent and combined effects of different levels of monetary incentives and a theory-based educational intervention on return for tuberculosis ( TB ) skin test reading in a sample of active injection drug and crack cocaine users . Prevalence of TB infection in this sample was also determined . METHODS Active or recent drug users ( n = 1004 ) , recruited via street outreach techniques , were skin tested for TB . They were r and omly assigned to 1 of 2 levels of monetary incentive ( $ 5 and $ 10 ) provided at return for skin test reading , alone or in combination with a brief motivational education session . RESULTS More than 90 % of those who received $ 10 returned for skin test reading , in comparison with 85 % of those who received $ 5 and 33 % of those who received no monetary incentive . The education session had no impact on return for skin test reading . The prevalence of a positive tuberculin test was 18.3 % . CONCLUSIONS Monetary incentives dramatically increase the return rate for TB skin test reading among drug users who are at high risk of TB infection BACKGROUND Adherence to tuberculosis evaluation is poor in a high-risk population such as the homeless . OBJECTIVE To test two interventions aim ed at improving adherence to tuberculosis evaluation and to identify predictors of adherence . METHODS We conducted a r and omized clinical trial in shelters and food lines in the inner city of San Francisco , Calif. We r and omized 244 eligible subjects infected with tuberculosis to ( 1 ) peer health adviser ( assistance by a peer [ n = 83 ] ) , ( 2 ) monetary incentive ( $ 5 payment [ n = 82 ] ) , or ( 3 ) usual care ( referral slips and bus tokens only [ n = 79 ] ) . The primary outcome of the study was adherence to a first follow-up appointment at the tuberculosis clinic , where subjects were evaluated for active tuberculosis and the need for isoniazid prophylaxis . RESULTS Of the subjects assigned to a monetary incentive , 69 ( 84 % ) completed their first follow-up appointment , compared with 62 subjects ( 75 % ) assigned to a peer health adviser and 42 subjects ( 53 % ) assigned to usual care . Adherence was higher in the monetary incentive and peer health adviser groups than in the usual care group ( P < .001 and P = .004 , respectively ) . Patients not using intravenous drugs and patients 50 years of age or older were more likely to adhere to a first follow-up appointment ( odds ratios [ 95 % confidence intervals ] , 2.5 [ 1.3 to 5.0 ] and 3.3 [ 1.2 to 8.8 ] , respectively ) . Among the 173 tuberculosis-infected subjects who completed their appointment , isoniazid therapy was started for 72 individuals , and three cases of active tuberculosis were identified . CONCLUSION A monetary incentive or a peer health adviser is effective in improving adherence to a first follow-up appointment in homeless individuals infected with tuberculosis . A monetary incentive appears to be superior . Intravenous drug users and young individuals are at high risk for poor adherence to referral SETTING Intravenous drug users ( IDUs ) represent a high risk group for dual human immunodeficiency virus ( HIV ) and tuberculosis ( TB ) infection . Screening with TB skin testing has therefore been suggested in this group . Subjects ' compliance for returning to have TB skin test results read is a major problem . In the setting of a needle exchange program we evaluated the role of financial incentives to increase compliance . METHODS We evaluated the role of giving a small financial incentive of Can $ 5 to subjects if they returned to have their purified protein derivative ( PPD ) skin test read . IDUs who had previously been skin-tested were compared with IDUs drawn from a similar population who , prospect ively , were offered a financial incentive . RESULTS During the initial period 558 subjects were evaluated and no incentive was offered . During the second phase of the study 549 IDUs were assessed but were also offered Can $ 5 if they returned to have their skin test read . Use of incentives increased compliance from 43 % to 78 % ( P = 0.001 ) . During the same period three active cases of TB were also diagnosed . CONCLUSIONS We suggest that use of financial incentives can increase the return of IDUs to have their skin tests read . Further studies are required to assess the efficacy of follow-up interventions , especially the use of isoniazid chemoprophylaxis |
1,113 | 31,069,039 | Implant with rough surfaces were more favourable for plaque accumulation during short-term follow-up .
On a long-term , turned implants surfaces were associated with more plaque and higher peri-implant bone loss .
Conclusions Within the limitations of the present study , rough implant surface does not seem to increase the incidence of peri-implantitis in comparison to turned implants surface | Objectives Moderately-rough implant surface may improve implant therapy in terms of bone integration , but the increased surface roughness might affect the initiation and development of peri-implantitis .
The aim of the present review was to compare the prevalence of peri-implantitis in implants with rough and turned ( machined ) implant surfaces . | PURPOSE The aim of the study was to compare the differences in the long-term clinical and radiologic effects for three different treatment strategies with implant-supported overdentures in the edentulous m and ible , with a special emphasis on smoking . MATERIAL S AND METHODS In a r and omized- controlled clinical trial , 110 edentulous patients participated . Thirty-six patients were treated with an overdenture supported by two implants with ball attachments ( 2IBA ) , 37 patients with an overdenture supported by two implants with a bar ( 2ISB ) and 37 patients with an overdenture supported by four implants with a triple bar ( 4ITB ) . After a mean evaluation period of 8.3 years , the clinical and radiographic parameters were evaluated . RESULTS Ninety-four out of the original 110 patients ( = 85 % ) were evaluated . In the 2IBA group , the plaque index was significantly lower ( vs. 2ISB , P=0.013 ; vs. 4ITB , P=0.001 ) than in the other groups , but there was no correlation with the other peri-implant parameters . In the 4ITB group , the marginal bone loss was significantly higher than that in the two implant groups . The maximal probing depth was correlated with peri-implant bone loss ( P=0.011 ) . Smoking almost doubled marginal bone loss irrespective of the treatment strategy chosen . CONCLUSIONS Patients with two implants show less marginal bone loss than those with four implants . Smoking is a risk factor for the survival of dental implants in the long run AIM This 1-year prospect i ve RCT compared the outcome of minimally ( turned ) and moderately rough ( TiUnite ) implant surfaces . MATERIAL AND METHODS Two subgroups of patients were formed ; one group ( n = 10 ) where all teeth had been extracted due to severe periodontitis , another group ( n = 8) with teeth in the antagonistic jaw with a history of periodontitis and some remaining medium pockets ( 4 - 6 mm ) . Implants ( n = 85 , 43 turned & 42 TiUnite ) were installed r and omly in each patient . After 3 - 6 months of submerged healing , healing abutments were connected , followed by final abutments 2 weeks later , all with the same surface characteristics as the supporting implant . Peri-implant parameters and intra-oral radiographs were recorded up to 1 year after abutment connection . RESULTS Two turned implants failed in the partial edentulous group during the initial healing period ( CSR : 95 % ) and none of the TiUnite ( CSR : 100 % ) surface . No statistically significant differences in clinical parameters could be observed between both surfaces . The partial edentulous subgroup showed more bone loss compared to the full edentulous subgroup . CONCLUSION Moderately rough implants have a similar clinical outcome ( at 1 year of loading in periodontitis susceptible patients ) compared to minimally rough implants The aim of this prospect i ve longitudinal study of patients treated for generalized aggressive periodontitis ( GAP ) was the clinical , microbiologic , and radiologic longitudinal evaluation of implants placed into bone regenerated by the guided bone regeneration ( GBR ) technique . Ten patients with GAP who had lost either one or two maxillary incisors or premolars through periodontal disease and whose alveolar bone was neither high nor wide enough for implant placement were enrolled in the study . GBR was carried out in a two-stage procedure using titanium-reinforced extended polytetrafluoroethylene membranes and titanium screws . No bone graft or bone substitute material s were used . After 6 to 8 months , the membranes and supporting screws were removed , and a total of 15 implants ( Nobel Biocare ) were placed . The control group comprised 10 periodontally healthy patients who had a total of II implants ( Nobel Biocare ) placed in the maxilla ( incisor and premolar region ) without GBR because of aplasia , trauma , or endodontic lesions . All patients were examined 2 to 4 weeks before extraction of the nonretainable teeth ( baseline ) and again immediately after placement of the superstructure . Further examinations were performed within the framework of a 3-month recall schedule over a 3-year period . At each session , clinical parameters ( probing pocket depths , bleeding on probing , gingival recession , clinical attachment level , Gingival Index , and Plaque Index ) were recorded at teeth and implants , and the composition of the subgingival microflora was determined by dark-field microscopy and DNA probe . Intraoral radiographs were taken for control purpose s at baseline , immediately after insertion of the superstructure , and 1 and 3 years later . The GBR technique yielded a horizontal and vertical bone gain of 4.5 to 7.0 mm in the GAP patients . The clinical , microbiologic , and radiologic findings indicated healthy periodontal and periimplant conditions in both patient groups throughout the study . However , a slightly increased attachment loss ( 0.65 mm ) and bone loss ( 1.78 mm ) were recorded at the implants in the regenerated bone after 3 years of loading . The 3-year implant survival rate was 100 % in both groups . The possibility of continuous attachment loss and bone loss occurring at teeth and implants in regenerated bone can not be ruled out in patients treated for aggressive periodontitis . The prognosis for the retention of the teeth and implants is thus open to question The relationship between periodontitis and peri-implantitis remains a matter of debate . The present study compared , " within " r and omly chosen partially edentulous patients ( n=84 subjects , 97 jaws ) , the marginal bone loss around teeth and implants during 5 years ( range 3 to 11 years ) following the first year of bone remodelling . The patients had all been rehabilitated by means of screw-shape c.p . titanium implants with a machined surface ( Brånemark system ) . During the 5 years observation interval , periodontal parameters ( marginal bone and attachment loss , the latter for teeth only ) were collected together with data on confounding factors ( smoking , oral hygiene , tooth loss ) . Marginal bone loss was measured through long-cone intra-oral radiographs . The mean " interval " bone loss was significantly ( P=0.0001 ) higher around teeth ( 0.48+/-0.95 mm ) than around implants ( 0.09+/-0.28 mm ) . The corresponding data for the " worst " performing tooth ( 0.99+/-1.25 mm ) and implant ( 0.19+/-0.32 mm ) per subject showed the same tendency . Neither attachment nor bone loss around teeth correlated with marginal bone loss around implants . This study indicated that the rate of bone loss around screw-shape c.p . titanium implants with a machined surface ( Brånemark system implants ) was not influenced by the progression rate of periodontal destruction around the remaining teeth within the same jaw The roughness of intraoral hard surfaces plays an important role in bacterial adhesion and colonization . Earlier studies have shown that rough surfaces accumulate up to 25 times more subgingival plaque than do smooth sites . In the present study , the influence of surface smoothing was studied . In six partially edentulous patients waiting for a fixed prosthesis supported by endosseous titanium implants , four titanium abutments with different surface roughness were r and omly placed . After 1 month of intraoral exposure , subgingival plaque sample s from each abutment were compared within each patient by means of differential phase-contrast microscopy . After 3 months , supragingival and subgingival plaque sample s were taken from all abutments for differential phase-contrast microscopy and culturing . Probing depth , recession , and bleeding upon probing were scored at the same visit . Differential phase-contrast microscopy showed that subgingivally , only the two roughest abutments harbored spirochetes after 1 month . After 3 months , subgingivally , the composition of the flora showed little variation on the different abutment types , although spirochetes were only noticed around the roughest abutments . Anaerobic culturing result ed in comparable amounts of colony-forming units for all abutment types , both supragingivally and subgingivally . Subgingivally , the microbiologic composition did not show major interabutment differences . Clinical ly , small differences in probing depth were observed . The roughest abutment showed some attachment gain ( 0.2 mm ) during 3 months , whereas all other abutments had an attachment loss ranging from 0.8 to greater than 1 mm . The results indicate that a reduction in surface roughness ( less than a roughness of 0.2 micron ) had no major effect on the microbiologic composition , supragingivally or subgingivally . These observations indicate the existence of a threshold roughness below which no further impact on the bacterial adhesion and /or colonization should be expected . However , clinical evaluation seems to indicate that a certain surface roughness is necessary for increased resistance to clinical probing Bacterial adhesion to intra-oral , hard surfaces is firmly influenced by the surface roughness to these structures . Previous studies showed a remarkable higher subgingival bacterial load on rough surfaces when compared to smooth sites . More recently , the additional effect of a further smoothening of intra-oral hard surfaces on clinical and microbiological parameters was examined in a short-term experiment . The results indicated that a reduction in surface roughness below R(a ) = 0.2 microns , the so-called " thresholds R(a ) " , had no further effect on the quantitative/qualitative microbiological adhesion or colonisation , neither supra- nor subgingivally . This study aims to examine the long-term effects of smoothening intra-oral hard transgingival surfaces . In 6 patients expecting an overdenture in the lower jaw , supported by endosseus titanium implants , 2 different abutments ( transmucosal part of the implant ) : a st and ard machined titanium ( R(a ) = 0.2 microns ) and one highly polished and made of a ceramic material ( R(a ) = 0.06 microns ) were r and omly installed . After 3 months of intra-oral exposure , supra- and subgingival plaque sample s from both abutments were compared with each other by means of differential phase-contrast microscopy ( DPCM ) . Clinical periodontal parameters ( probing depth , gingival recession , bleeding upon probing and Periotest-value ) were recorded around each abutment . After 12 months , the supra- and subgingival sample s were additionally cultured in aerobic , CO2-enriched and anaerobic conditions . The same clinical parameters as at the 3-month interval were recorded after 12 months . At 3 months , spirochetes and motile organisms were only detected subgingivally around the titanium abutments . After 12 months , however , both abutment-types harboured equal proportions of spirochetes and motile organisms , both supra- and subgingivally . The microbial culturing ( month 12 ) failed to detect large inter-abutment differences . The differences in number of colony- forming units ( aerobic and anaerobic ) were within one division of a logarithmic scale . The aerobic culture data showed a higher proportion of Gram-negative organisms in the subgingival flora of the rougher abutments . From the group of potentially " pathogenic " bacteria , only Prevotella intermedia and Fusobacterium nucleatum were detected for anaerobic culturing and again the inter-abutment differences were negligible . Clinical ly , the smoothest abutment showed a slightly higher increase in probing depth between months 3 and 12 , and more bleeding on probing . The present results confirm the findings of our previous short-term study , indicating that a further reduction of the surface roughness , below a certain " threshold R(a ) " ( 0.2 microns ) , has no major impact on the supra- and subgingival microbial composition AIM This 3-year prospect i ve r and omized controlled trial compared the clinical , microbiological and biochemical outcome of minimally ( Turned , Tur ) and moderately rough ( TiUnite ( ® ) , TiU ) implant surfaces in a split-mouth design . MATERIAL AND METHODS The study population included 14 subjects : nine fully edentulous and five partially edentulous subjects with a history of periodontitis . Implants ( n = 78 , 39 Tur and 39 TiU ) were installed r and omly in each patient . Peri-implant clinical parameters and intra-oral radiographs were recorded after 3 years of loading . Subgingival plaque and peri-implant crevicular fluid sample s were collected and analysed using culture and quantitative polymerase chain reaction for the biofilm , and enzyme-linked immunosorbent assay for the concentration of osteoprotegerin and receptor activator of nuclear factor kappa-B lig and , respectively . RESULTS No statistically significant differences in clinical , microbiological and biochemical parameters could be observed when comparing the Tur and TiU implant surfaces . CONCLUSION After 3 years of loading , in periodontitis susceptible patients , the moderately rough , TiU implants demonstrated a similar clinical outcome compared with the smoother , turned implants . Longer follow-up and studies using different implant types are needed to confirm the statement that minimally and moderately rough implant surfaces perform similar , both from a clinical and from a microbiological point of view BACKGROUND Many longitudinal studies of different implant systems have been published but few controlled r and omized investigations have been reported . A 1-year report of a comparative study of ITI Dental Implant System implants ( Straumann AG , Waldenburg , Switzerl and ) and Brånemark System implants ( Nobel Biocare AB , Gothenburg , Sweden ) has been published by the present authors . This paper is a 3-year follow-up of that r and omized study . PURPOSE The aim of the study was to compare the outcome of fixed partial prostheses supported by ITI or Brånemark implants . The outcome was evaluated primarily in terms of survival rates and changes in marginal bone level . MATERIAL AND METHODS The study group comprised 28 patients with anterior residual dentition in the maxilla . The patients were provided with two to four implants on each side of the dentition and were r and omly allocated to Brånemark implants or ITI implants ; 77 ITI implants and 73 Brånemark implants were inserted . After 6 months abutment connections were made to both ITI and Brånemark implants . All patients were provided with fixed partial prostheses of gold-ceramic . The patients were followed up annually with clinical and radiographic examinations for 3 years RESULTS Two Brånemark implants and two ITI implants were lost . The Brånemark implants were lost before loading whereas the ITI implants were lost because of periimplantitis . The survival rate for both groups was 97.3 % . The mean marginal bone level of the Brånemark implants was situated 1.8 mm from the reference point at both the baseline and the 3-year examinations . The corresponding values for the ITI implants were 1.4 mm at baseline and 1.3 mm after 3 years . There was no significant difference between the implant systems with regard to bone level or bone level change . A steady state of the marginal bone level was calculated to have been reached after 3 years for 95.5 % of the Brånemark implants and 87.1 % of the ITI implants . Periimplantitis ( infection including pus and bone loss ) was observed with seven ITI implants but with none of the Brånemark implants . This difference was statistically significant . CONCLUSIONS No statistically significant differences were found between the implants studied , except for the frequency of periimplantitis , which was higher for the ITI implants . The survival rates were high , and the marginal bone loss was small for both systems BACKGROUND Most current implants have a moderately rough surface ( compared with older minimally rough " turned " implants ) to facilitate osseointegration . This r and omized controlled trial ( RCT ) , with split-mouth design , examined whether this increased surface roughness influenced the initial subgingival plaque formation . MATERIAL AND METHODS Ten fully edentulous and eight partially edentulous patients , all with a history of severe periodontitis , received 4 - 6 implants ( m and ible or maxilla ) . Per jaw , both minimally ( turned ) and moderately rough ( TiUnite ) implants ( MKIII ; Nobel Biocare ) were alternated . Also , the healing and final abutments had similar surface characteristics . Subgingival biofilm formation was followed up for 1 year , and sample s were analyzed by culture technique , qPCR and checkerboard RESULTS Over the entire period , no statistically significant differences could be detected in subgingival microbiota between the minimally and moderately rough surfaces . In partially edentulous patients , the biofilm matured to a higher concentration of pathogens when compared with fully edentulous patients . The subgingival implant composition and concentration in partially edentulous patients were comparable to the subgingival microbiota along teeth . CONCLUSION The roughness of the more modern implants did not influence the biofilm formation during the first year of implant loading In this prospect i ve study 47 edentulous patients were treated with m and ibular fixed prostheses supported by osseointegrated Brånemark implants and followed for 12 to 15 years . Three ( 1 % ) of the 273 inserted implants were lost , two before and one six years after placement of the fixed prosthesis . The cumulative success rate ( CSR ) of the implants was 98.9 % both after 10 and 15 years . None of the fixed prostheses was lost and at the last follow-up , all patients had stable fixed prostheses in function ( CSR 100 % ) . The marginal bone loss around the implants was small , on average 0.5 mm during the first post surgical year and thereafter about 0.05 mm annually . More bone was lost around the anterior implants than around the most posterior ones . Smoking and poor oral hygiene had significant influence on bone loss , while occlusal loading factors such as maximal bite force , tooth clenching and length of cantilevers were of minor importance . It is concluded that the long-term results of the m and ibular implant treatment were extremely successful , regarding both the fixed prostheses and implant stability . Bone resorption around the implants , albeit limited , was influenced by several factors , smoking and oral hygiene appeared to be most important INTRODUCTION Many studies have dealt with the clinical outcome of oral implants , yet none applied a r and omized split-mouth design for a long-term follow-up of similar implant systems . AIM To evaluate two oral implant systems with different surface characteristics in a r and omized split-mouth design and to radiologically analyse peri-implant bone level and density over an up to 16-year period . MATERIAL S AND METHODS The study comprised clinical and radiographic records of 18 partially edentulous patients treated with both implant types r and omly placed in either left or right jaw sides . Outcome was evaluated over time . RESULTS Clinical and radiographic parameters showed no significant differences over time for both systems . Ten years after implant placement , a significantly increasing peri-implant bone density was noted , while Periotest values were found to be significantly decreasing . Fifteen years after implant loading , mean bone loss was 0.02 mm ( range -1.15 to 1.51 ; SD 0.45 ) for Astra Tech ® implants ( n=24 ) and 0.31 mm ( range -0.98 to 2.31 ; SD 0.69 ) for Brånemark ® implants ( n=23 ) . CONCLUSIONS The study failed to demonstrate significant differences in the outcome of the peri-implant bone for two implant systems with different surface characteristics . The marginal bone level around oral implants changed < 0.5 mm after 15 years of loading BACKGROUND The mucosal attachment that forms to titanium implants , uncontaminated by bacterial plaque comprises , independent of the surface characteristics of the abutment , one barrier epithelium and one zone of connective tissue attachment . It was suggested that abutments with a rough surface may accumulate more plaque than abutments with a smooth surface and that such an enhanced rate of plaque build-up may favor the development of inflammatory lesions in the periimplant mucosa . OBJECTIVES The aim of the present experiment was to study some reactions of the periimplant mucosa to plaque accumulation on implant abutments design ed with either a rough or a smooth external surface . MATERIAL AND METHODS In five beagle dogs , four fixtures were placed and submerged in the premolar region . In a second stage procedure performed after 3 months , abutments with two different types of surface topography , one rough , acid-etched ( OA ) and one smooth , turned abutment ( TA ) , were installed in a r and om order . After 6 months of undisturbed plaque formation , the animals were sacrificed and biopsies obtained . Tissue sample s were prepared for light microscopy and exposed to histometric and morphometric measurements . RESULTS Six months of plaque accumulation result ed in the establishment of an inflammatory lesion ( pl-ICT ) in the connective tissue of the periimplant mucosa , the location , size and composition of which did not differ between OA and TA sites . In addition , most OA and TA sites harbored a second inflammatory cell infiltrate in the tissue lateral to the abutment/fixture junction ( ab-ICT ) . While pl-ICT was dominated by plasma cells and lymphocytes , ab-ICT contained a comparatively large number of polymorphonuclear leukocytes . CONCLUSION The different surface characteristics of abutment made of c.p . titanium failed to influence plaque formation and the establishment of inflammatory cell lesions in the periimplant mucosa BACKGROUND Concerns have been raised that use of surface-modified implants may result in peri-implant infection and marked marginal bone loss over time . PURPOSE The aim of this prospect i ve study was to evaluate the survival rate , marginal bone , and soft tissue conditions at surface-modified titanium dental implants after 10 years of function . MATERIAL AND METHODS Forty-six totally and partially edentulous patients were provided with 121 Brånemark oxidized implants ( TiUnite ™ , Nobel Biocare AB , Gothenburg , Sweden ) . Twenty-four ( 20 % ) implants were immediate loaded and 97 ( 80 % ) were placed using a two-stage procedure . A total of 22 single , 23 partial , and 7 total restorations were delivered . Clinical and radiographic checkups were carried out after 3 , 6 , 12 months , and thereafter annually up to 10 years . At these occasions , oral hygiene was evaluated and peri-implant mucosa examined by probing . If needed , patients were enrolled in an individual program for hygiene controls and professional cleaning . Marginal bone loss was evaluated in intraoral radiographs taken at baseline and after 1 , 5 , and 10 years of function . RESULTS One ( 0.8 % ) implant failed after 8 years giving a Survival Rate ( SR ) of 99.2 % after 10 years . A total of 11 sites ( 9.2 % ) showed bleeding on probing ( BP ) at the 10th annual checkup . The mean marginal bone loss was 0.7 ± 1.35 mm based on 106 readable pairs of radiographs from baseline and from the 10th annual examination . Twelve ( 11.3 % ) implants showed more than 2 mm bone loss , and five ( 4.7 % ) showed more than 3 mm of bone loss after 10 years . For the latter , all patients were smokers and had poor or acceptable oral hygiene . All five implants with > 3 mm bone loss showed BP and two ( 1.9 % ) showed suppuration from the pocket . For the remaining seven implants with more than 2 mm bone loss , no correlation to smoking , oral hygiene , bleeding , or pus could be seen . Time/marginal bone level plots of the 12 implants with more than 2 mm bone loss after 10 years , showed minor changes from the first annual checkup except for the two infected implants . CONCLUSIONS It is concluded that good long-term clinical outcomes can be obtained with oxidized titanium dental implants . Only 1.9 % of examined implants showed significant marginal bone loss together with bleeding and suppuration after 10 years of function PURPOSE The aim of the present study was to evaluate whether there was a difference between machined and TiO(2)-blasted implants regarding survival rate and marginal bone loss during a 5-year observation period . MATERIAL S AND METHODS A total of 133 implants ( Astra Tech Dental Implants ; Astra Tech AB , Mölndal , Sweden ) were placed in 50 patients at 6 centers in 4 Sc and inavian countries . Forty-eight implants were installed in the maxilla and 85 implants in the m and ible . A r and omization and a stratification were done , so that each fixed partial prosthesis was supported by at least 1 machined and 1 TiO(2)-blasted implant . The implant-supported fixed partial prostheses ( ISFPP ) were fabricated within 2 months after postoperative healing . A total of 52 ISFPP ( 17 maxillary , 35 m and ibular ) were inserted . The patients were clinical ly examined once a year for 5 years . At the annual follow-up , biological as well as technical complications were recorded . RESULTS Of the 133 implants placed , 3 were reported as failed after 5 years of follow-up , result ing in an overall cumulative survival rate of 97.6 % . The cumulative implant survival rates were 100 % for the TiO(2)-blasted implants and 95.1 % for the machined implants . No significant difference in survival was , however , found between the machined and TiO(2)-blasted implants after 5 years . The mean marginal bone loss in the maxilla was 0.21 + /- 0.83 mm ( SD ) for the machined implants and 0.51 + /- 1.11 mm ( SD ) for the TiO(2)-blasted implants during the 5-year observation period . In the m and ible , the mean marginal loss was 0.22 + /- 1.13 mm for the machined implants and 0.52 + /- 1.07 mm for the TiO(2)-blasted implants from baseline to the 5-year examination . No significant difference in marginal bone loss between the 2 surface groups was found during the 5-year observation period . CONCLUSIONS The present study shows good 5-year results with small ISFPP in the m and ible , as well as in the maxilla . No significant differences were found in failure rate and marginal bone loss around implants with a machined rather than a TiO(2)-blasted surface . J Prosthodont 2001;10:2 - 7 BACKGROUND Comparatively few studies with at least 5 years of follow-up are available that describe the use of implants in prosthetic rehabilitation of partially edentulous patients . R and omized , controlled clinical studies that evaluated the effect of different surface design s of screw-shaped implants on the outcome of treatment are also sparse . OBJECTIVE To determine , in a prospect i ve r and omized , controlled clinical trial , the outcome of restorative therapy in periodontitis-susceptible patients who , following basic periodontal therapy , had been restored with implants with either a machined- or a rough-surface topography . MATERIAL AND METHODS Fifty-one subjects ( mean age , 59.5 years ) , 20 males and 31 females who , following treatment of moderate-to-advanced chronic periodontitis , required implant therapy for prosthetic rehabilitation were recruited . Seventeen of the patients were current smokers . Following the active treatment , all subjects were included in an individually design ed maintenance program . A total of 56 fixed partial dentures ( FPDs ) and a total of 149 screw-shaped , and self-tapping implants ( Astra Tech implants ) -- 83 in the maxilla and 66 in the m and ible -- were installed in a two-stage procedure . Each patient received a minimum of two implants and by r and omization every second implant that was installed had been design ed with a machined surface and the remaining with a roughened Tioblast surface . Abutment connection was performed 3 - 6 months after implant installation . Clinical and radiographical examinations were performed following FPD connection and once a year during a 5-year follow-up period . The analysis of peri-implant bone-level alterations was performed on subject , FPD and implant levels . RESULTS Four patients and four FPDs were lost to the 5 years of monitoring . One implant ( machined surface ) did not properly integrate ( early failure ) , and was removed at the time of abutment connection . Three implants were lost during function and a further eight implants could not be accounted for at the 5-year follow-up examination . The overall failure rate at 5 years was 5.9 % ( subject level ) , 5.3 % ( FPD level ) and 2.7 % ( implant level ) . Radiographic signs of loss of osseointegration were not found at any of the implants during the 5-year observation period . During the first year in function there was on average 0.33 ( SD , 0.61 ) mm loss of peri-implant marginal bone on the subject and FPD levels and 0.31 ( 0.81 ) mm on the implant level . During the subsequent 4 years , the peri-implant bone-level alterations were small . The calculated annual change in peri-implant bone level was -0.02 ( 0.15 ) on subject and FPD levels and -0.03 ( 0.20 ) on the implant level . Thus , the mean total bone-level change over the 5-year interval amounted to 0.41 mm on all three levels of analysis . In the interval between baseline and 5 years , the machined and the Tioblast implants lost on average 0.33 and 0.48 mm , respectively ( p>0.05 ) . CONCLUSION The present r and omized , controlled clinical trial that included partially edentulous periodontitis-susceptible subjects demonstrated that bone loss ( i ) during the first year of function as well as annually thereafter was small and ( ii ) did not vary between implants with machined- or rough-surface design In a r and omized prospect i ve study , two implant systems were compared in forty consecutive patients treated for m and ibular edentulism . The patients were r and omly allotted for treatment by the Brånemark two-stage ( submerged ) system ( BRS ) , or the ITI(R ) one-stage ( non-submerged ) system . In all , 102 Brånemark selftapping implants and 106 ITI hollow screw implants were installed and all patients were treated with full bridges . Biological and prosthodontic parameters , complications , success rates , clinical efficacy , patient satisfaction and re source requirements were evaluated . No differences were found in plaque accumulation , bleeding or complications during the follow-up period . The BRS group showed deeper periimplant sulcus , less attached mucosa , larger bridge-mucosa distance and higher Periotest values . Prosthetic complications were not related to the configuration of the implant systems . After 3 years , the cumulative success rates were 97.9 % and 96.8 % for the Brånemark and ITI systems , respectively ( difference not statistically significant ) . One implant in the BRS group had failed to osseointegrate at the time of abutment connection , and another was lost after 2 years due to progressive breakdown of bone . In the ITI group , three implants showed progressive bone loss after 1 - 3 years associated with periimplant infection . All 40 bridges were intact and remained stable throughout the study . There was general patient satisfaction , but about half the Brånemark patients reported difficulty in coping with the surgical procedures . Treatment time was similar for the two systems . It is concluded that both systems meet the current requirements for dental implant systems in the treatment of m and ibular edentulism |
1,114 | 31,270,579 | There was no difference in mortality rate in ICU and hospital between the protocol ized intervention and control groups .
Conclusions Protocol ized family support intervention for enhanced communication and shared decision-making with the family reduced ICU LOS in critically ill patients without impacting mortality | Purpose This study aim ed to eluci date the impact of protocol ized family support intervention on length of stay ( LOS ) in the intensive care unit ( ICU ) through a systematic review and meta- analysis . | BACKGROUND Patients ' deaths in the ICU have been associated with a high burden of psychologic symptoms in families . This study identifies characteristics associated with psychologic symptoms in family members . METHODS Families of patients dying in the ICU or within 30 h of ICU discharge in 11 hospitals previously participated in a r and omized trial . In the current study , we assessed these families for symptoms of posttraumatic stress disorder ( PTSD ) and depression with follow-up surveys . Outcomes included vali date d measures of PTSD ( PTSD Checklist ) and depressive ( Patient Health Question naire ) symptoms . Predictors included family member mental-health history , involvement in decision making , and demographics . RESULTS Surveys were completed by 226 families . Response rate was 46 % in the original r and omized trial and 82 % in this study . Prevalence ( 95 % CI ) of PTSD and depressive symptoms were 14.0 % ( 9.7%-19.3 % ) and 18.4 % ( 13.5%-24.1 % ) , respectively . Family characteristics associated with increased symptoms included : female gender ( PTSD , P = .020 ; depression , P = .005 ) , knowing the patient for a shorter duration ( PTSD , P = .003 ; depression , P = .040 ) , and discordance between family members ' preferences for decision making and their actual decision-making roles ( PTSD , P = .005 ; depression , P = .049 ) . Depressive symptoms were also associated with lower educational level ( P = .002 ) . Families with psychologic symptoms were more likely to report that access to a counselor ( PTSD , P < .001 ; depression , P = .003 ) and information about spiritual services might have been helpful while the patient was in the ICU ( PTSD , P = .024 ; depression , P = .029 ) . CONCLUSIONS Families demonstrated a high prevalence of psychologic symptoms after a death in the ICU . Characteristics associated with symptoms may help target interventions to reduce these symptoms . TRIAL REGISTRATION clinical trials.gov ; Identifier : NCT00685893 OBJECTIVES To analyze the utilization of intensive care unit ( ICU ) days in a Canadian medical-surgical ICU and to identify ICU patients with prolonged ICU length of stay ( LOS ) . DESIGN Prospect i ve descriptive study . SETTING A Canadian tertiary care medical-surgical ICU . PATIENTS Consecutive patients admitted to an adult medical-surgical ICU . Neurosurgical , cardiac surgical , and coronary care unit patients were excluded . MEASUREMENTS For each ICU admission , patient demographics , diagnosis , Acute Physiology and Chronic Health Evaluation II ( APACHE II ) score , ICU LOS , and hospital mortality were collected . The patients ' risk of death was calculated using the APACHE II equation . Admissions were stratified by ICU LOS into four groups : 1 to 2 , 3 to 6 , 7 to 13 , and > or = 14 days . Among the four LOS groups , the number of ICU days and observed and predicted death rates were compared . Admissions were also stratified by risk of death into five probability range quintiles . Among the five risk groups , ICU LOS was compared between survivors and nonsurvivors . RESULTS A total of 1,960 admissions utilized 9,298 ICU days . ICU LOS ( mean + /- SEM ) was 4.74 + /- 0.2 ( median , 2 ; range , 1 to 178 ) days . Short-stay patients ( ICU LOS < or = 2 days ) accounted for 60.3 % of total admissions but consumed only 16.4 % of total ICU days . Long-stay patients ( ICU LOS > or = 14 days ) accounted for 7.3 % of total admissions but consumed 43.5 % of total ICU days . Among the long-stay patients , the most common reasons for admission were pneumonia , multiple trauma , neuromuscular weakness , and septic shock . The mortality for long-stay patients approached 50 % . When analyzed by patients ' mortality risks , those with a risk of death > 0.8 ( predicted to die ) or < 0.2 ( predicted to live ) whose outcomes were opposite to that predicted had twice the ICU LOS compared with patients whose outcomes were consistent with prediction . CONCLUSION In a Canadian medical-surgical ICU , patients with ICU LOS > or = 14 days accounted for 7.3 % of total admissions but consumed 43.5 % of total ICU days . Identification of patients with prolonged ICU LOS who would ultimately die in the ICU may lead to earlier withdrawal of therapy in these patients , result ing in a substantial reduction in suffering and cost savings . In our study population , outcome prediction using the APACHE II equation did not provide sufficient power to accurately discriminate between nonsurvivors and survivors Objective : To revise and up date the Acute Physiology and Chronic Health Evaluation ( APACHE ) model for predicting intensive care unit ( ICU ) length of stay . Design : Observational cohort study . Setting : One hundred and four ICUs in 45 U.S. hospitals . Patients : Patients included 131,618 consecutive ICU admissions during 2002 and 2003 , of which 116,209 met inclusion criteria . Interventions : None . Measurements and Main Results : The APACHE IV model for predicting ICU length of stay was developed using ICU day 1 patient data and a multivariate linear regression procedure to estimate the precise ICU stay for r and omly selected patients who comprised 60 % of the data base . New variables were added to the previous APACHE III model , and advanced statistical modeling techniques were used . Accuracy was assessed by comparing mean observed and mean predicted ICU stay for the excluded 40 % of patients . Aggregate mean observed ICU stay was 3.86 days and mean predicted 3.78 days ( p < .001 ) , a difference of 1.9 hrs . For 108 ( 93 % ) of 116 diagnoses , there was no significant difference between mean observed and mean predicted ICU stay . The model accounted for 21.5 % of the variation in ICU stay across individual patients and 62 % across ICUs . Correspondence between mean observed and mean predicted length of stay was reduced for patients with a short ( ≤1.7 days ) or long ( ≥9.4 days ) ICU stay and a low ( < 20 % ) or high ( > 80 % ) risk of death on ICU day 1 . Conclusions : The APACHE IV model provides clinical ly useful ICU length of stay predictions for critically ill patient groups , but its accuracy and utility are limited for individual patients . APACHE IV benchmarks for ICU stay are useful for assessing the efficiency of unit throughput and support examination of structural , managerial , and patient factors that affect ICU stay BACKGROUND Ten percent to 20 % of trauma patients admitted to the intensive care unit ( ICU ) will die from their injuries . Providing appropriate end-of-life care in this setting is difficult and often late in the patients ' course . Patients are young , prognosis uncertain , and conflict common around goals of care . We hypothesized that early , structured communication in the trauma ICU would improve end-of-life care practice . METHODS Prospect i ve , observational , prepost study on consecutive trauma patients admitted to the ICU before and after a structured palliative care intervention was integrated into st and ard ICU care . The program included part I , early ( at admission ) family bereavement support , assessment of prognosis , and patient preferences , and part II ( within 72 hours ) interdisciplinary family meeting . Data on goals of care discussion s , do-not-resuscitate ( DNR ) orders and withdrawal of life support ( W/D ) were collected from physician rounds , family meetings , and medical records . RESULTS Eighty-three percent of patients received part I and 69 % part II intervention . Discussion of goals of care by physicians on rounds increased from 4 % to 36 % of patient-days . During intervention , rates of mortality ( 14 % ) , DNR ( 43 % ) , and W/D ( 24 % ) were unchanged , but DNR orders and W/D were instituted earlier in hospital course . ICU length of stay was decreased in patients who died . CONCLUSIONS Structured communication between physician and families result ed in earlier consensus around goals of care for dying trauma patients . Integration of early palliative care alongside aggressive trauma care can be accomplished without change in mortality and has the ability to change the culture of care in the trauma ICU 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 STUDY OBJECTIVES To assess the impact of a proactive case finding approach to end-of-life care for critically ill patients experiencing global cerebral ischemia ( GCI ) after cardiopulmonary resuscitation and multiple organ system failure ( MOSF ) in comparison to historical control subjects . DESIGN Comparative study of retrospective and prospect i ve cohorts . SETTING Medical ICU of a university hospital . INTERVENTIONS Patterns of end-of life care for patients with MOSF and GCI obtained through a retrospective chart review were compared to proactive case finding facilitated by the inpatient palliative care service . Interventions included identification of patient 's advance directives or preferences about end-of life care , if any ; assistance with discussion of the prognosis and treatment options with patients or their surrogates ; and implementation of palliative care strategies when treatment goals changed to a focus on comfort measures . RESULTS Although our retrospective data demonstrated a high percentage of do-not-resuscitate decisions for the patients under investigation , a considerable time lag elapsed between identification of the poor prognosis and the establishment of end-of-life treatment goals ( 4.7 + /- 2.4 days and 3.5 + /- 0.5 days for patients with MOSF and GCI , respectively [ mean + /- SE ] ) . The proactive case finding approach decreased hospital length of stay ( mean , 20.6 + /- 4.1 days vs 15.1 + /- 2.5 days and 8.6 + /- 1.6 days vs 4.7 + /- 0.6 days for MOSF and GCI patients , respectively ; p = 0.063 and < 0.001 , respectively ) . More importantly , a proactive palliative care intervention decreased the time between identification of the poor prognosis and the establishment of comfort care goals ( 7.3 + /- 2.9 days vs 2.2 + /- 0.8 days and 6.3 + /- 1.2 days vs 3.5 + /- 0.4 days for MOSF and GCI patients , respectively ; p < 0.05 for both ) , decreased the time dying patients with MOSF remained in the ICU , and reduced the use of nonbeneficial re sources , thus reducing the cost of care . CONCLUSIONS Proactive interventions from a palliative care consultant within this subset of patients decreased the use of nonbeneficial re sources and avoided protracted dying PURPOSE We sought to determine the effects of a communication process that was design ed to encourage the use of advanced supportive technology when it is of benefit , but to limit its burdens when it is ineffective . We compared usual care with a proactive , multidisciplinary method of communicating that prospect ively identified for patients and families the criteria that would determine whether a care plan was effective at meeting the goals of the patient . This process allowed caregivers to be informed of patient preferences about continued advanced supportive technology when its continuation would result in a compromised functional outcome or death . MATERIAL S AND METHODS We performed a before- and -after study in 530 adult medical patients who were consecutively admitted to a university tertiary care hospital for intensive care . Multidisciplinary meetings were held within 72 hours of critical care admission . Patients , families , and the critical care team discussed the care plan and the patients ' goals and expectations for the outcome of critical care . Clinical " milestones " indicative of recovery were identified with time frames for their occurrence . Follow-up meetings were held to discuss palliative care options when continued advanced supportive technology was not achieving the patient 's goals . We measured length of stay , mortality , and provider team and family consensus in 134 patients before the intensive communication intervention and in 396 patients after the intervention . RESULTS Intensive communication significantly reduced the median length of stay from 4 days ( interquartile range , 2 to 11 days ) to 3 days ( 2 to 6 days , P = 0.01 by survival analysis ) . This reduction remained significant after adjustment for acute physiology and chronic health evaluation ( APACHE ) 3 score [ risk ratio ( RR ) = 0.81 ; 95 % confidence interval ( CI ) , 0.66 to 0.99 ; P = 0.04 ) . Subgroup analysis revealed that this reduction occurred in our target group , patients with acuity scores in the highest quartile who died ( RR = 0.60 ; 95 % CI , 0.38 to 0.92 ; P = 0.02 ) . The intervention , which allowed dying patients earlier access to palliative care , was not associated with increased mortality . CONCLUSIONS Intensive communication was associated with a reduction in critical care use by patients who died . Our multidisciplinary process targeted advanced supportive technology to patients who survived and allowed the earlier withdrawal of advanced supportive technology when it was ineffective CONTEXT Patients , families , and surgeons often have high expectations of life-saving surgery following liver transplantation ( LT ) , despite the presence of a severe life-limiting underlying illness . Hence , transition from curative to palliative care is difficult and may create conflicts around goals of care . OBJECTIVES We hypothesized that early communication with physicians/families would improve end-of-life care practice in the LT service patients . METHODS Prospect i ve , observational , pre/post study of consecutive LT service , surgical intensive care unit ( SICU ) patients , before and after a palliative care intervention was integrated . This included Part I ( at admission ) , family support , prognosis , and patient preferences delineation ; and Part II ( within 72 hours ) , interdisciplinary family meeting . Data on goals -of-care discussion s , do-not-resuscitate ( DNR ) orders , withdrawal of life support , and family perceptions were collected . RESULTS Seventy-nine LT patients with 21 deaths comprised the baseline group and 104 patients with 31 deaths the intervention group . Eighty-five percent of patients received Part I and 58 % Part II of the intervention . Goals -of-care discussion s on physician rounds increased from 2 % to 38 % of patient-days . During the intervention , although mortality rates were unchanged , DNR status increased ( 52 - 81 % ) ; withdrawal of life support increased ( 35 - 68 % ) ; DNR was instituted earlier ; admission to DNR decreased ( mean of 38 - 19 days ) ; DNR to death time increased ( two to four days ) ; and SICU mean length of stay decreased ( by three days ) . Family responses suggested more " time with family"/"time to say goodbye . " CONCLUSION Interdisciplinary communication interventions with physicians and families result ed in earlier consensus around goals of care for dying LT patients . Early integration of palliative care alongside disease-directed curative care can be accomplished in the SICU without change in mortality and has the ability to improve end-of-life care practice in LT patients RATIONALE Because of high mortality , end-of-life care is an important component of intensive care . OBJECTIVES We evaluated the effectiveness of a quality -improvement intervention to improve intensive care unit ( ICU ) end-of-life care . METHODS We conducted a cluster-r and omized trial r and omizing 12 hospitals . The intervention targeted clinicians with five components : clinician education , local champions , academic detailing , clinician feedback of quality data , and system supports . Outcomes were assessed for patients dying in the ICU or within 30 hours of ICU discharge using surveys and medical record review . Families completed Quality of Dying and Death ( QODD ) and satisfaction surveys . Nurses completed the QODD . Data were collected during baseline and follow-up at each hospital ( May 2004 to February 2008 ) . We used robust regression models to test for intervention effects , controlling for site , patient , family , and nurse characteristics . MEASUREMENTS AND MAIN RESULTS All hospitals completed the trial with 2,318 eligible patients and target sample sizes obtained for family and nurse surveys . The primary outcome , family-QODD , showed no change with the intervention ( P = 0.33 ) . There was no change in family satisfaction ( P = 0.66 ) or nurse-QODD ( P = 0.81 ) . There was a nonsignificant increase in ICU days before death after the intervention ( hazard ratio = 0.9 ; P = 0.07 ) . Among patients undergoing withdrawal of mechanical ventilation , there was no change in time from admission to withdrawal ( hazard ratio = 1.0 ; P = 0.81 ) . CONCLUSIONS We found this intervention was associated with no improvement in quality of dying and no change in ICU length of stay before death or time from ICU admission to withdrawal of life-sustaining measures . Improving ICU end-of-life care will require interventions with more direct contact with patients and families . Clinical trial registered with www . clinical trials.gov ( NCT00685893 ) CONTEXT Ethics consultations increasingly are being used to resolve conflicts about life-sustaining interventions , but few studies have reported their outcomes . OBJECTIVE To investigate whether ethics consultations in the intensive care setting reduce the use of life-sustaining treatments delivered to patients who ultimately did not survive to hospital discharge , as well as the reactions to the consultations of physicians , nurses , and patients /surrogates . DESIGN Prospect i ve , multicenter , r and omized controlled trial from November 2000 to December 2002 . SETTING Adult intensive care units ( ICUs ) of 7 US hospitals representing a spectrum of institutional characteristics . PATIENTS Five hundred fifty-one patients in whom value-related treatment conflicts arose during the course of treatment . INTERVENTIONS Patients were r and omly assigned either to an intervention ( ethics consultation offered ) ( n = 278 ) or to usual care ( n = 273 ) . MAIN OUTCOME MEASURES The primary outcomes were ICU days and life-sustaining treatments in those patients who did not survive to hospital discharge . We examined the same measures in those who did survive to discharge and also compared the overall mortality rates of the intervention and usual care groups . We also interviewed physicians and nurses and patients /surrogates about their views of the ethics consultation . RESULTS The intervention and usual-care groups showed no difference in mortality . However , ethics consultations were associated with reductions in hospital ( -2.95 days , P = .01 ) and ICU ( -1.44 days , P = .03 ) days and life-sustaining treatments ( -1.7 days with ventilation , P = .03 ) in those patients who ultimately did not survive to discharge . The majority ( 87 % ) of physicians , nurses , and patients /surrogates agreed that ethics consultations in the ICU were helpful in addressing treatment conflicts . CONCLUSION Ethics consultations were useful in resolving conflicts that may have inappropriately prolonged nonbeneficial or unwanted treatments in the ICU We search ed to see whether psychological support for relatives of intensive care unit patients helps them to donate organs of their brain-dead relatives . After receiving ethics committee permission , first-degree relatives of 200 general intensive care unit patients were enrolled in the study . The participants were divided into 2 groups r and omly : an interview group ( n = 100 ) and a control group ( n = 100 ) . Participants were asked to complete a question naire . Interviews with the psychologist and patients ' relatives in the interview group were therapeutic in nature and were conducted according to the relatives ' psychosocial needs in an unstructured format . In the control group , the psychologist and patients ' relatives were not interviewed . The study utilized demographic data , the question naire for relatives of patients to mention their attitude on organ donation and the reasons for this choice , and the Participant Information Form to record demographic data and relatives ' degree of relationship with the patient . There was no statistically significant difference between the 2 groups when compared according to sex ratio , patient age , and duration of patients ' hospital stay . Whereas in the interview group , 75 % agreed to allow their relatives to be organ donors , only 32 % in the control group agreed ( P < .0001 ) . Of the 200 patients enrolled in the study , 93 lost their lives : 50 from the interview group and 43 from the control group . Among the relatives whose patients had lost their lives , 78 % belonging to the interview group accepted to donate the organs of their patients , whereas in the control group 13.9 % accepted ( P < .0001 ) . We hope that psychological support for the relatives of the potential brain-dead donor to cope with the psychological problems to be faced can improve the rate of organ donation Objective : In the ICU , discussion s between clinicians and surrogate decision makers are often accompanied by conflict about a patient ’s prognosis or care plan . Trust plays a role in limiting conflict , but little is known about the determinants of trust in the ICU . We sought to identify the dimensions of trust and clinician behaviors conducive to trust formation in the ICU . Design : Prospect i ve qualitative study . Setting : Medical ICU of a major urban university hospital . Subjects : Surrogate decision makers of intubated , mechanically ventilated patients in the medical ICU . Measurements and Main Results : Semistructured interviews focused on surrogates ’ general experiences in the ICU and on their trust in the clinicians caring for the patient . Interviews were audio-recorded , transcribed verbatim , and coded by two review ers . Constant comparison was used to identify themes pertaining to trust . Thirty surrogate interviews revealed five dimensions of trust in ICU clinicians : technical competence , communication , honesty , benevolence , and interpersonal skills . Most surrogates emphasized the role of nurses in trust formation , frequently citing their technical competence . Trust in physicians was most commonly related to honesty and the quality of their communication with surrogates . Conclusions : Interventions to improve trust in the ICU should be role-specific , since surrogate expectations are different for physicians and nurses with regard to behaviors relevant to trust . Further research is needed to confirm our findings and explore the impact of trust modification on clinician-family conflict RATIONALE Communication with family of critically ill patients is often poor and associated with family distress . OBJECTIVES To determine if an intensive care unit ( ICU ) communication facilitator reduces family distress and intensity of end-of-life care . METHODS We conducted a r and omized trial at two hospitals . Eligible patients had a predicted mortality greater than or equal to 30 % and a surrogate decision maker . Facilitators supported communication between clinicians and families , adapted communication to family needs , and mediated conflict . MEASUREMENTS AND MAIN RESULTS Outcomes included depression , anxiety , and post-traumatic stress disorder ( PTSD ) among family 3 and 6 months after ICU and re source use . We identified 488 eligible patients and r and omized 168 . Of 352 eligible family members , 268 participated ( 76 % ) . Family follow-up at 3 and 6 months ranged from 42 to 47 % . The intervention was associated with decreased depressive symptoms at 6 months ( P = 0.017 ) , but there were no significant differences in psychological symptoms at 3 months or anxiety or PTSD at 6 months . The intervention was not associated with ICU mortality ( 25 % control vs. 21 % intervention ; P = 0.615 ) but decreased ICU costs among all patients ( per patient : $ 75,850 control , $ 51,060 intervention ; P = 0.042 ) and particularly among decedents ( $ 98,220 control , $ 22,690 intervention ; P = 0.028 ) . Among decedents , the intervention reduced ICU and hospital length of stay ( 28.5 vs. 7.7 d and 31.8 vs. 8.0 d , respectively ; P < 0.001 ) . CONCLUSIONS Communication facilitators may be associated with decreased family depressive symptoms at 6 months , but we found no significant difference at 3 months or in anxiety or PTSD . The intervention reduced costs and length of stay , especially among decedents . This is the first study to find a reduction in intensity of end-of-life care with similar or improved family distress . Clinical trial registered with www . clinical trials.gov ( NCT 00720200 ) BACKGROUND There is a need for close communication with relatives of patients dying in the intensive care unit ( ICU ) . We evaluated a format that included a proactive end-of-life conference and a brochure to see whether it could lessen the effects of bereavement . METHODS Family members of 126 patients dying in 22 ICUs in France were r and omly assigned to the intervention format or to the customary end-of-life conference . Participants were interviewed by telephone 90 days after the death with the use of the Impact of Event Scale ( IES ; scores range from 0 , indicating no symptoms , to 75 , indicating severe symptoms related to post-traumatic stress disorder [ PTSD ] ) and the Hospital Anxiety and Depression Scale ( HADS ; subscale scores range from 0 , indicating no distress , to 21 , indicating maximum distress ) . RESULTS Participants in the intervention group had longer conferences than those in the control group ( median , 30 minutes [ interquartile range , 19 to 45 ] vs. 20 minutes [ interquartile range , 15 to 30 ] ; P<0.001 ) and spent more of the time talking ( median , 14 minutes [ interquartile range , 8 to 20 ] vs. 5 minutes [ interquartile range , 5 to 10 ] ) . On day 90 , the 56 participants in the intervention group who responded to the telephone interview had a significantly lower median IES score than the 52 participants in the control group ( 27 vs. 39 , P=0.02 ) and a lower prevalence of PTSD-related symptoms ( 45 % vs. 69 % , P=0.01 ) . The median HADS score was also lower in the intervention group ( 11 , vs. 17 in the control group ; P=0.004 ) , and symptoms of both anxiety and depression were less prevalent ( anxiety , 45 % vs. 67 % ; P=0.02 ; depression , 29 % vs. 56 % ; P=0.003 ) . CONCLUSIONS Providing relatives of patients who are dying in the ICU with a brochure on bereavement and using a proactive communication strategy that includes longer conferences and more time for family members to talk may lessen the burden of bereavement . ( Clinical Trials.gov number , NCT00331877 . Background Surrogate decision makers for incapacitated , critically ill patients often struggle with decisions related to goals of care . Such decisions cause psychological distress in surrogates and may lead to treatment that does not align with patients ' preferences . Methods We conducted a stepped‐wedge , cluster‐r and omized trial involving patients with a high risk of death and their surrogates in five intensive care units ( ICUs ) to compare a multicomponent family‐support intervention delivered by the interprofessional ICU team with usual care . The primary outcome was the surrogates ' mean score on the Hospital Anxiety and Depression Scale ( HADS ) at 6 months ( scores range from 0 to 42 , with higher scores indicating worse symptoms ) . Prespecified secondary outcomes were the surrogates ' mean scores on the Impact of Event Scale ( IES ; scores range from 0 to 88 , with higher scores indicating worse symptoms ) , the Quality of Communication ( QOC ) scale ( scores range from 0 to 100 , with higher scores indicating better clinician – family communication ) , and a modified Patient Perception of Patient Centeredness ( PPPC ) scale ( scores range from 1 to 4 , with lower scores indicating more patient‐ and family‐centered care ) , as well as the mean length of ICU stay . Results A total of 1420 patients were enrolled in the trial . There was no significant difference between the intervention group and the control group in the surrogates ' mean HADS score at 6 months ( 11.7 and 12.0 , respectively ; beta coefficient , ‐0.34 ; 95 % confidence interval [ CI ] , ‐1.67 to 0.99 ; P=0.61 ) or mean IES score ( 21.2 and 20.3 ; beta coefficient , 0.90 ; 95 % CI , ‐1.66 to 3.47 ; P=0.49 ) . The surrogates ' mean QOC score was better in the intervention group than in the control group ( 69.1 vs. 62.7 ; beta coefficient , 6.39 ; 95 % CI , 2.57 to 10.20 ; P=0.001 ) , as was the mean modified PPPC score ( 1.7 vs. 1.8 ; beta coefficient , ‐0.15 ; 95 % CI , ‐0.26 to ‐0.04 ; P=0.006 ) . The mean length of stay in the ICU was shorter in the intervention group than in the control group ( 6.7 days vs. 7.4 days ; incidence rate ratio , 0.90 ; 95 % CI , 0.81 to 1.00 ; P=0.045 ) , a finding mediated by the shortened mean length of stay in the ICU among patients who died ( 4.4 days vs. 6.8 days ; incidence rate ratio , 0.64 ; 95 % CI , 0.52 to 0.78 ; P<0.001 ) . Conclusions Among critically ill patients and their surrogates , a family‐support intervention delivered by the interprofessional ICU team did not significantly affect the surrogates ' burden of psychological symptoms , but the surrogates ' ratings of the quality of communication and the patient‐ and family‐centeredness of care were better and the length of stay in the ICU was shorter with the intervention than with usual care . ( Funded by the UPMC Health System and the Greenwall Foundation ; PARTNER Clinical Trials.gov number , NCT01844492 . IMPORTANCE Family caregivers of patients with chronic critical illness experience significant psychological distress . OBJECTIVE To determine whether family informational and emotional support meetings led by palliative care clinicians improve family anxiety and depression . DESIGN , SETTING , AND PARTICIPANTS A multicenter r and omized clinical trial conducted from October 2010 through November 2014 in 4 medical intensive care units ( ICUs ) . Adult patients ( aged ≥21 years ) requiring 7 days of mechanical ventilation were r and omized and their family surrogate decision makers were enrolled in the study . Observers were blinded to group allocation for the measurement of the primary outcomes . INTERVENTIONS At least 2 structured family meetings led by palliative care specialists and provision of an informational brochure ( intervention ) compared with provision of an informational brochure and routine family meetings conducted by ICU teams ( control ) . There were 130 patients with 184 family surrogate decision makers in the intervention group and 126 patients with 181 family surrogate decision makers in the control group . MAIN OUTCOMES AND MEASURES The primary outcome was Hospital Anxiety and Depression Scale symptom score ( HADS ; score range , 0 [ best ] to 42 [ worst ] ; minimal clinical ly important difference , 1.5 ) obtained during 3-month follow-up interviews with the surrogate decision makers . Secondary outcomes included posttraumatic stress disorder experienced by the family and measured by the Impact of Events Scale-Revised ( IES-R ; total score range , 0 [ best ] to 88 [ worst ] ) , discussion of patient preferences , hospital length of stay , and 90-day survival . RESULTS Among 365 family surrogate decision makers ( mean age , 51 years ; 71 % female ) , 312 completed the study . At 3 months , there was no significant difference in anxiety and depression symptoms between surrogate decision makers in the intervention group and the control group ( adjusted mean HADS score , 12.2 vs 11.4 , respectively ; between-group difference , 0.8 [ 95 % CI , -0.9 to 2.6 ] ; P = .34 ) . Posttraumatic stress disorder symptoms were higher in the intervention group ( adjusted mean IES-R score , 25.9 ) compared with the control group ( adjusted mean IES-R score , 21.3 ) ( between-group difference , 4.60 [ 95 % CI , 0.01 to 9.10 ] ; P = .0495 ) . There was no difference between groups regarding the discussion of patient preferences ( intervention , 75 % ; control , 83 % ; odds ratio , 0.63 [ 95 % CI , 0.34 to 1.16 ; P = .14 ] ) . The median number of hospital days for patients in the intervention vs the control group ( 19 days vs 23 days , respectively ; between-group difference , -4 days [ 95 % CI , -6 to 3 days ] ; P = .51 ) and 90-day survival ( hazard ratio , 0.95 [ 95 % CI , 0.65 to 1.38 ] , P = .96 ) were not significantly different . CONCLUSIONS AND RELEVANCE Among families of patients with chronic critical illness , the use of palliative care-led informational and emotional support meetings compared with usual care did not reduce anxiety or depression symptoms and may have increased posttraumatic stress disorder symptoms . These findings do not support routine or m and atory palliative care-led discussion of goals of care for all families of patients with chronic critical illness . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01230099 |
1,115 | 31,549,741 | We are uncertain if there are any benefits of interactive training of healthcare providers on the management of life-threatening emergencies in hospital as the certainty of the evidence is very low .
We were unable to identify any factors that may have allowed us to identify an essential element of these interactive training courses . | BACKGROUND Preparing healthcare providers to manage relatively rare life-threatening emergency situations effectively is a challenge .
Training sessions enable staff to rehearse for these events and are recommended by several reports and guidelines .
In this review we have focused on interactive training , this includes any element where the training is not solely didactic but provides opportunity for discussion s , rehearsals , or interaction with faculty or technology .
It is important to underst and the effective methods and essential elements for successful emergency training so that re sources can be appropriately targeted to improve outcomes .
OBJECTIVES To assess the effects of interactive training of healthcare providers on the management of life-threatening emergencies in hospital on patient outcomes , clinical care practice s , or organisational practice s , and to identify essential components of effective interactive emergency training programmes . | INTRODUCTION Majority of studies on evaluation of emergency management courses have focused on outcomes such as knowledge and skills demonstrated in non- clinical or traditional testing manner . Such surrogate outcomes may not necessarily reflect vital changes in practice . The aim of this study was to determine if and to what extent , specific training in the management of life threatening emergencies result ed in an increased in compliance with established care guidelines of doctors working in the emergency departments of public sector hospitals in Pakistan . METHODS A cluster r and omised controlled trial was conducted in three districts hospitals in three cities ( Khairpur , Vehari and Peshawar ) of Pakistan . Thirty-six doctors , 18 in intervention ( trained in ESS-EMNCH training ) and 18 in control ( untrained ) , were enrolled and 248 life threatening emergency events , 124 in each group , were observed for the correct use of the Airway , Breathing , Circulation ( ABC ) structured approach . The outcome measure was structured approach defined a priori . Data was analysed by using STATA software . RESULTS At individual level , 79 ( 63.7 % ) life threatening episodes were managed according to the structured approach in the intervention group and 46 ( 37.1 % ) were managed according to the structured approach in controls ( OR 2.98 , 95%CI 1.78 - 4.99 , p-value=0.0001 ) . At cluster level , the mean percentage ( 95 % CI ) of the structured approach used by doctors in the intervention group [ 62.9 % ( 50.4 - 75.3 % ) ] , was significantly higher than those in the control group , [ 36.3 % ( 26.3 - 46.4 ) ] ( p-value=0.001 ) . CONCLUSIONS 5-day training of ESS-EMNCH significantly increased the compliance with established care guidelines of doctors during their management of life threatening emergency episodes in the public sector hospitals in Pakistan Objectives : To assess the effect of high-fidelity simulation ( SIM ) on cognitive performance after a training session involving several mock resuscitations design ed to teach and reinforce Pediatric Advanced Life Support ( PALS ) algorithms . Methods : Pediatric residents were r and omized to high-fidelity simulation ( SIM ) or st and ard mannequin ( MAN ) groups . Each subject completed 3 study phases : ( 1 ) mock code exercises ( asystole , tachydysrhythmia , respiratory arrest , and shock ) to assess baseline performance ( PRE phase ) , ( 2 ) a didactic session review ing PALS algorithms , and ( 3 ) repeated mock code exercises requiring identical cognitive skills in a different clinical context to assess change in performance ( POST phase ) . SIM subjects completed all 3 phases using a high-fidelity simulator ( SimBaby , Laerdal Medical , Stavanger , Norway ) , and MAN subjects used SimBaby without simulated physical findings ( ie , as a st and ard mannequin ) . Performance in PRE and POST was measured by a scoring instrument design ed to measure cognitive performance ; scores were scaled to a range of 0 to 100 points . Improvement in performance from PRE to POST phases was evaluated by mixed modeling using a r and om intercept to account for within-subject variability . Results : Fifty-one subjects ( SIM , 25 ; MAN , 26 ) completed all phases . The PRE performance was similar between groups . Both groups demonstrated improvement in POST performance . The improvement in scores between PRE and POST phases was significantly better in the SIM group ( mean [ SD ] , 11.1 [ 4.8 ] vs. 4.8 [ 1.7 ] , P = 0.007 ) . Conclusions : The use of high-fidelity simulation in a PALS training session result ed in improved cognitive performance by pediatric house staff . Future studies should address skill and knowledge decays and team dynamics , and clearly defined and reproducible outcome measures should be sought AIM Advanced simulation tools are increasingly being incorporated into cardiopulmonary resuscitation ( CPR ) training . These educational methods have been shown to improve trainee performance in simulated setting s , but translation into clinical practice remains unknown for many aspects of CPR quality . This study attempts to measure the impact of simulation-based training for resuscitation team leaders on some measures of CPR quality during actual in-hospital resuscitation attempts . METHODS In this prospect i ve , r and omized interventional cluster trial , internal medicine resident physicians ( post-graduate year 2 ) were r and omized using a r and om number generator to participate in a 4-h , immersive simulation course in cardiopulmonary resuscitation leadership using a high-fidelity simulator with video debriefing prior to serving as resuscitation team leaders at an academic medical center . Objective metrics of actual resuscitation performance were obtained from a CPR-sensing monitor/defibrillator . RESULTS Thirty-two residents were r and omized to receive simulation training or no additional training between April and July 2007 and data were collected following 98 actual resuscitations between July 2007 and June 2008 . CPR quality from resuscitations led by 14 simulation-trained and 16 control group residents was similar in terms of mean compression depth ( 48 vs 49 mm ; p = 0.53 ) ; compression rate ( 107 vs 104 min⁻¹ ; p = 0.30 ) ; ventilation rate ( 12 vs 12 min⁻¹ ; p = 0.45 ) and no-flow fraction ( 0.08 vs 0.07 ; p = 0.34 ) . CONCLUSIONS Although we failed to detect any significant differences in objective measures of CPR quality , we have demonstrated that CPR-sensing technology has the potential for use in assessing the impact of a simulation curriculum on some aspects of actual resuscitation performance . A larger study , performed in a setting with lower baseline performance , would be required to assess the specific simulation curriculum Objective To investigate the effect of in situ simulation ( ISS ) versus off-site simulation ( OSS ) on knowledge , patient safety attitude , stress , motivation , perceptions of simulation , team performance and organisational impact . Design Investigator-initiated single-centre r and omised superiority educational trial . Setting Obstetrics and anaesthesiology departments , Rigshospitalet , University of Copenhagen , Denmark . Participants 100 participants in teams of 10 , comprising midwives , specialised midwives , auxiliary nurses , nurse anaesthetists , operating theatre nurses , and consultant doctors and trainees in obstetrics and anaesthesiology . Interventions Two multiprofessional simulations ( clinical management of an emergency caesarean section and a postpartum haemorrhage scenario ) were conducted in teams of 10 in the ISS versus the OSS setting . Primary outcome Knowledge assessed by a multiple choice question test . Exploratory outcomes Individual outcomes : scores on the Safety Attitudes Question naire , stress measurements ( State-Trait Anxiety Inventory , cognitive appraisal and salivary cortisol ) , Intrinsic Motivation Inventory and perceptions of simulations . Team outcome : video assessment of team performance . Organisational impact : suggestions for organisational changes . Results The trial was conducted from April to June 2013 . No differences between the two groups were found for the multiple choice question test , patient safety attitude , stress measurements , motivation or the evaluation of the simulations . The participants in the ISS group scored the authenticity of the simulation significantly higher than did the participants in the OSS group . Expert video assessment of team performance showed no differences between the ISS versus the OSS group . The ISS group provided more ideas and suggestions for changes at the organisational level . Conclusions In this r and omised trial , no significant differences were found regarding knowledge , patient safety attitude , motivation or stress measurements when comparing ISS versus OSS . Although participant perception of the authenticity of ISS versus OSS differed significantly , there were no differences in other outcomes between the groups except that the ISS group generated more suggestions for organisational changes . Trial registration number NCT01792674 Background Newborn deaths comprise nearly half of under-5 deaths in Ghana , despite the fact that skilled birth attendants ( SBAs ) are present at 68 % of births , which implies that evidence -based care during labor , birth and the immediate postnatal period may be deficient . We assessed the effect of a low-dose , high-frequency ( LDHF ) training approach on long-term evidence -based skill retention among SBAs and impact on adverse birth outcomes . Methods From 2014 to 2017 , we conducted a cluster-r and omized trial in 40 hospitals in Ghana . Eligible hospitals were stratified by region and r and omly assigned to one of four implementation waves . We assessed the relative risks ( RRs ) of institutional intrapartum stillbirths and 24-h newborn mortality in months 1–6 and 7–12 of implementation as compared to the historical control period , and in post-intervention facilities compared to pre-intervention facilities during the same period . All SBAs providing labor and delivery care were invited to enroll ; their knowledge and skills were assessed pre- and post-training , and 1 year later . Results Adjusting for region and health facility type , the RR of 24-h newborn mortality in the 40 enrolled hospitals was 0·41 ( 95 % CI 0·32–0·51 ; p < 0.001 ) in months 1–6 and 0·30 ( 95 % CI 0·21–0·43 ; p < 0·001 ) in months 7–12 compared to baseline . The adjusted RR of intrapartum stillbirth was 0·64 ( 95 % CI 0·53–0·77 ; p < 0·001 ) in months 1–6 and 0·48 ( 95 % CI 0·36–0·63 ; p < 0·001 ) in months 7–12 compared to baseline . Four hundred three SBAs consented and enrolled . After 1 year , 200 SBAs assessed had 28 % ( 95 % CI 25–32 ; p < 0·001 ) and 31 % ( 95 % CI 27–36 ; p < 0·001 ) higher scores than baseline on low-dose 1 and 2 content skills , respectively . Conclusions This training approach results in a sustained decrease in facility-based newborn mortality and intrapartum stillbirths , and retained knowledge and skills among SBAs after a year . We recommend use of this approach for future maternal and newborn health in-service training and programs . Trial registration Retrospectively registered on 25 September 2017 at Clinical Trials , identifier NCT03290924 Background Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries . These differences have been related to poor access to and poor quality of obstetric and neonatal care . Methods This trial tested the hypothesis that teams of health care providers , administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations . In seven geographic areas in five low-income and one middle-income country , most with high perinatal mortality rates and substantial numbers of home deliveries , we performed a cluster r and omized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport , community birth attendant training in problem recognition , and facility staff training in the management of obstetric and neonatal emergencies . The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g. Results Despite extensive effort in all sites in each of the three intervention areas , no differences emerged in the primary or any secondary outcome between the intervention and control clusters . In both groups , the mean perinatal mortality was 40.1/1,000 births ( P = 0.9996 ) . Neither were there differences between the two groups in outcomes in the last six months of the project , in the year following intervention cessation , nor in the clusters that best implemented the intervention . Conclusions This cluster r and omized comprehensive , large-scale , multi-sector intervention did not result in detectable impact on the proposed outcomes . While this does not negate the importance of these interventions , we expect that achieving improvement in pregnancy outcomes in these setting s will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial , and without them provider training and community mobilization will not be sufficient . Our results highlight the critical importance of evaluating outcomes in r and omized trials , as interventions that should be effective may not be . Trial registration Clinical Trials.gov Objective : To determine if high fidelity simulation based team training can improve clinical team performance when added to an existing didactic teamwork curriculum . Setting : Level 1 trauma center and academic emergency medicine training program . Participants : Emergency department ( ED ) staff including nurses , technicians , emergency medicine residents , and attending physicians . Intervention : : ED staff who had recently received didactic training in the Emergency Team Coordination Course ( ETCC ® ) also received an 8 hour intensive experience in an ED simulator in which three scenarios of graduated difficulty were encountered . A comparison group , also ETCC trained , was assigned to work together in the ED for one 8 hour shift . Experimental and comparison teams were observed in the ED before and after the intervention . Design : Single , crossover , prospect i ve , blinded and controlled observational study . Teamwork ratings using previously vali date d behaviorally anchored rating scales ( BARS ) were completed by outside trained observers in the ED . Observers were blinded to the identification of the teams . Results : There were no significant differences between experimental and comparison groups at baseline . The experimental team showed a trend towards improvement in the quality of team behavior ( p = 0.07 ) ; the comparison group showed no change in team behavior during the two observation periods ( p = 0.55 ) . Members of the experimental team rated simulation based training as a useful educational method . Conclusion : High fidelity medical simulation appears to be a promising method for enhancing didactic teamwork training . This approach , using a number of patients , is more representative of clinical care and is therefore the proper paradigm in which to perform teamwork training . It is , however , unclear how much simulator based training must augment didactic teamwork training for clinical ly meaningful differences to become apparent Background There are many avoidable deaths in hospitals because the care team is not well attuned . Training in emergency situations is generally followed on an individual basis . In practice , however , hospital patients are treated by a team composed of various disciplines . To prevent communication errors , it is important to focus the training on the team as a whole , rather than on the individual . Team training appears to be important in contributing toward preventing these errors . Obstetrics lends itself to multidisciplinary team training . It is a field in which nurses , midwives , obstetricians and paediatricians work together and where decisions must be made and actions must be carried out under extreme time pressure . It is attractive to belief that multidisciplinary team training will reduce the number of errors in obstetrics . The other side of the medal is that many hospitals are buying expensive patient simulators without proper evaluation of the training method . In the Netherl and s many hospitals have 1,000 or less annual deliveries . In our small country it might therefore be more cost-effective to train obstetric teams in medical simulation centres with well trained personnel , high fidelity patient simulators , and well defined training programmes . Methods / design The aim of the present study is to evaluate the cost-effectiveness of multidisciplinary team training in a medical simulation centre in the Netherl and s to reduce the number of medical errors in obstetric emergency situations . We plan a multicentre r and omised study with the centre as unit of analysis . Obstetric departments will be r and omly assigned to receive multidisciplinary team training in a medical simulation centre or to a control arm without any team training . The composite measure of poor perinatal and maternal outcome in the non training group was thought to be 15 % , on the basis of data obtained from the National Dutch Perinatal Registry and the guidelines of the Dutch Society of Obstetrics and Gynaecology ( NVOG ) . We anticipated that multidisciplinary team training would reduce this risk to 5 % . A sample size of 24 centres with a cluster size of each at least 200 deliveries , each 12 centres per group , was needed for 80 % power and a 5 % type 1 error probability ( two-sided ) . We assumed an Intraclass Correlation Coefficient ( ICC ) value of maximum 0.08.The analysis will be performed according to the intention-to-treat principle and stratified for teaching or non-teaching hospitals . Primary outcome is the number of obstetric complications throughout the first year period after the intervention . If multidisciplinary team training appears to be effective a cost-effective analysis will be performed . Discussion If multidisciplinary team training appears to be cost-effective , this training should be implemented in extra training for gynaecologists . Trial Registration The protocol is registered in the clinical trial register number Background Ineffective management of obstetric emergencies contributes significantly to maternal and neonatal morbidity and mortality in Mexico . PRONTO ( Programa de Rescate Obstétrico y Neonatal : Tratamiento Óptimo y Oportuno ) is a highly-realistic , low-tech simulation-based obstetric and neonatal emergency training program . A pair-matched hospital-based controlled implementation trial was undertaken in three states in Mexico , with pre/post measurement of process indicators at intervention hospitals . This report assesses the impact of PRONTO simulation training on process indicators from the pre/post study design for process indicators . Methods Data was collected in twelve intervention facilities on process indicators , including pre/post changes in knowledge and self-efficacy of obstetric emergencies and neonatal resuscitation , achievement of strategic planning goals established during training and changes in teamwork scores . Authors performed a longitudinal fixed-effects linear regression model to estimate changes in knowledge and self-efficacy and logistic regression to assess goal achievement . Results A total of 450 professionals in interprofessional teams were trained . Significant increases in knowledge and self-efficacy were noted for both physicians and nurses ( p < 0.001- 0.009 ) in all domains . Teamwork scores improved and were maintained over a three month period . A mean of 58.8 % strategic planning goals per team in each hospital were achieved . There was no association between high goal achievement and knowledge , self-efficacy , proportion of doctors or nurses in training , state , or teamwork score . Conclusions These results suggest that PRONTO ’s highly realistic , locally appropriate simulation and team training in maternal and neonatal emergency care may be a promising avenue for optimizing emergency response and improving quality of facility-based obstetric and neonatal care in re source -limited setting s . Trial registration OBJECTIVE : The goal was to determine the effect of training in newborn care and resuscitation on 7-day ( early ) neonatal mortality rates for very low birth weight ( VLBW ) infants . The study was design ed to test the hypothesis that these training programs would reduce neonatal mortality rates for VLBW infants . METHODS : Local instructors trained birth attendants from 96 rural communities in 6 developing countries in protocol and data collection , the World Health Organization Essential Newborn Care ( ENC ) course , and a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program ( NRP ) , by using a train-the-trainer model . To test the impact of ENC training , data on infants of 500 to 1499 g were collected by using a before/after , active baseline , controlled study design . A cluster-r and omized , controlled trial design was used to test the impact of the NRP . RESULTS : A total of 1096 VLBW ( 500–1499 g ) infants were enrolled , and 98.5 % of live-born infants were monitored to 7 days . All-cause , 7-day neonatal mortality , stillbirth , and perinatal mortality rates were not affected by ENC or NRP training . CONCLUSIONS : Neither ENC nor NRP training of birth attendants decreased 7-day neonatal , stillbirth , or perinatal mortality rates for VLBW infants born at home or at first-level facilities . Encouragement of delivery in a facility where a higher level of care is available may be preferable when delivery of a VLBW infant is expected BACKGROUND Maternal mortality is higher in west Africa than in most industrialised countries , so the development and validation of effective interventions is essential . We did a trial to assess the effect of a multifaceted intervention to promote maternity death review s and onsite training in emergency obstetric care in referral hospitals with high maternal mortality rates in Senegal and Mali . METHODS We did a pragmatic cluster-r and omised controlled trial , with hospitals as the units of r and omisation and patients as the unit of analysis . 46 public first-level and second-level referral hospitals with more than 800 deliveries a year were enrolled , stratified by country and hospital type , and r and omly assigned to either the intervention group ( n=23 ) or the control group with no external intervention ( n=23 ) . All women who delivered in each of the participating facilities during the baseline and post-intervention periods were included . The intervention , implemented over a period of 2 years at the hospital level , consisted of an initial interactive workshop and quarterly educational clinical ly-oriented and evidence -based outreach visits focused on maternal death review s and best practice s implementation . The primary outcome was reduction of risk of hospital-based mortality . Analysis was by intention-to-treat and relied on the generalised estimating equations extension of the logistic regression model to account for clustering of women within hospitals . This study is registered with Clinical Trials.gov , number IS RCT N46950658 . FINDINGS 191,167 patients who delivered in the participating hospitals were analysed ( 95,931 in the intervention groups and 95,236 in the control groups ) . Overall , mortality reduction in intervention hospitals was significantly higher than in control hospitals ( odds ratio [ OR ] 0·85 , 95 % CI 0·73 - 0·98 , p=0·0299 ) , but this effect was limited to capital and district hospitals , which mainly acted as first-level referral hospitals in this trial . There was no effect in second-level referral ( regional ) hospitals outside the capitals ( OR 1·02 , 95 % CI 0·79 - 1·31 , p=0·89 ) . No hospitals were lost to follow-up . Concrete actions were implemented comprehensively to improve quality of care in intervention hospitals . INTERPRETATION Regular visits by a trained external facilitator and onsite training can provide health-care professionals with the knowledge and confidence to make quality improvement suggestions during audit sessions . Maternal death review s , combined with best practice s implementation , are effective in reducing hospital-based mortality in first-level referral hospitals . Further studies are needed to determine whether the benefits of the intervention are generalisable to second-level referral hospitals . FUNDING Canadian Institutes of Health Research Background Unexpected obstetric emergencies threaten the safety of pregnant women . As emergencies are rare , they are difficult to learn . Therefore , simulation-based medical education ( SBME ) seems relevant . In non- systematic review s on SBME , medical simulation has been suggested to be associated with improved learner outcomes . However , many questions on how SBME can be optimized remain unanswered . One unresolved issue is how ' in situ simulation ' ( ISS ) versus ' off site simulation ' ( OSS ) impact learning . ISS means simulation-based training in the actual patient care unit ( in other words , the labor room and operating room ) . OSS means training in facilities away from the actual patient care unit , either at a simulation centre or in hospital rooms that have been set up for this purpose . Methods and design The objective of this r and omized trial is to study the effect of ISS versus OSS on individual learning outcome , safety attitude , motivation , stress , and team performance amongst multi-professional obstetric-anesthesia teams . The trial is a single-centre r and omized superiority trial including 100 participants . The inclusion criteria were health-care professionals employed at the department of obstetrics or anesthesia at Rigshospitalet , Copenhagen , who were working on shifts and gave written informed consent . Exclusion criteria were managers with staff responsibilities , and staff who were actively taking part in preparation of the trial . The same obstetric multi-professional training was conducted in the two simulation setting s. The experimental group was exposed to training in the ISS setting , and the control group in the OSS setting . The primary outcome is the individual score on a knowledge test . Exploratory outcomes are individual scores on a safety attitudes question naire , a stress inventory , salivary cortisol levels , an intrinsic motivation inventory , results from a question naire evaluating perceptions of the simulation and suggested changes needed in the organization , a team-based score on video-assessed team performance and on selected clinical performance . Discussion The perspective is to provide new knowledge on context ual effects of different simulation setting s . Trial registration ClincialTrials.gov NCT01792674 Background Birth asphyxia kills 0.7 to 1.6 million newborns a year globally with 99 % of deaths in developing countries . Effective newborn resuscitation could reduce this burden of disease but the training of health-care providers in low income setting s is often out date d. Our aim was to determine if a simple one day newborn resuscitation training ( NRT ) alters health worker resuscitation practice s in a public hospital setting in Kenya . Methods /Principal Findings We conducted a r and omised , controlled trial with health workers receiving early training with NRT ( n = 28 ) or late training ( the control group , n = 55 ) . The training was adapted locally from the approach of the UK Resuscitation Council . The primary outcome was the proportion of appropriate initial resuscitation steps with the frequency of inappropriate practice s as a secondary outcome . Data were collected on 97 and 115 resuscitation episodes over 7 weeks after early training in the intervention and control groups respectively . Trained providers demonstrated a higher proportion of adequate initial resuscitation steps compared to the control group ( trained 66 % vs control 27 % ; risk ratio 2.45 , [ 95 % CI 1.75–3.42 ] , p<0.001 , adjusted for clustering ) . In addition , there was a statistically significant reduction in the frequency of inappropriate and potentially harmful practice s per resuscitation in the trained group ( trained 0.53 vs control 0.92 ; mean difference 0.40 , [ 95 % CI 0.13–0.66 ] , p = 0.004 ) . Conclusions / Significance Implementation of a simple , one day newborn resuscitation training can be followed immediately by significant improvement in health workers ' practice s. However , evidence of the effects on long term performance or clinical outcomes can only be established by larger cluster r and omised trials . Trial Registration Controlled-Trials.com IS RCT Background Despite exp and ing access to institutional birth in Guatemala , maternal mortality remains largely unchanged over the last ten years . Enhancing the quality of emergency obstetric and neonatal care is one important strategy to decrease mortality . An innovative , low-tech , simulation-based team training program ( PRONTO ) aims to optimize care provided during obstetric and neonatal emergencies in low-re source setting s. Methods We conducted PRONTO simulation training between July 2012 and December 2012 in 15 clinics in Alta Verapaz , Huehuetenango , San Marcos , and Quiche , Guatemala . These clinics received PRONTO as part of a larger pair-matched cluster r and omized trial of a comprehensive intervention package . Training participants were obstetric and neonatal care providers that completed pre- and post- training assessment s for the two PRONTO training modules , which evaluated knowledge of evidence -based practice and self-efficacy in obstetric and neonatal topics . Part of the training included a session for trained teams to establish strategic goals to improve clinical practice . We utilized a pre/post-test design to evaluate the impact of the course on both knowledge and self-efficacy with longitudinal fixed effects linear regression with robust st and ard errors . Pearson correlation coefficients were used to assess the correlation between knowledge and self-efficacy . Poisson regression was used to assess the association between the number of goals achieved and knowledge , self-efficacy , and identified facility-level factors . Results Knowledge and self-efficacy scores improved significantly in all areas of teaching . Scores were correlated for all topics overall at training completion . More than 60 % of goals set to improve clinic functioning and emergency care were achieved . No predictors of goal achievement were identified . Conclusions PRONTO training is effective at improving provider knowledge and self-efficacy in training areas . Further research is needed to evaluate the impact of the training on provider use of evidence -based practice s and on maternal and neonatal health outcomes .Trial registration BACKGROUND Birth trauma is a low-frequency , high-severity event , making obstetrics a major challenge for patient safety . Yet , few strategies have been shown to eliminate preventable perinatal harm . Interdisciplinary team training was prospect ively evaluated to assess the relative impact of two different learning modalities to improve nontechnical skills (NTS)--the cognitive and interpersonal skills , such as communication and teamwork , that supplement clinical and technical skills and are necessary to ensure safe patient care . METHODS Between 2005 and 2008 , perinatal morbidity and mortality data were prospect ively collected using the Weighted Adverse Outcomes Score ( WAOS ) and a culture of safety survey ( Safety Attitudes Question naire ) at three small-sized community hospitals . In a small cluster r and omized clinical trial conducted in the third quarter of 2007 , one of the hospitals served as a control group and two served as the treatment intervention sites -- one hospital received the TeamSTEPPS didactic training program and one hospital received both the TeamSTEPPS program along with a series of in-situ simulation training exercises . RESULTS A statistically significant and persistent improvement of 37 % in perinatal morbidity was observed between the pre- and postintervention for the hospital exposed to the simulation program . There were no statistically significant differences in the didactic-only or the control hospitals . Baseline perceptions of culture of safety were high at all three hospitals , and there were no significant changes . CONCLUSIONS A comprehensive interdisciplinary team training program using in-situ simulation can improve perinatal safety in the hospital setting . This is the first evidence providing a clear association between simulation training and improved patient outcomes . Didactics alone were not effective in improving perinatal outcomes OBJECTIVE : To evaluate the effect of teamwork training on the occurrence of adverse outcomes and process of care in labor and delivery . METHODS : A cluster-r and omized controlled trial was conducted at seven intervention and eight control hospitals . The intervention was a st and ardized teamwork training curriculum based on crew re source management that emphasized communication and team structure . The primary outcome was the proportion of deliveries at 20 weeks or more of gestation in which one or more adverse maternal or neonatal outcomes or both occurred ( Adverse Outcome Index ) . Additional outcomes included 11 clinical process measures . RESULTS : A total of 1,307 personnel were trained and 28,536 deliveries analyzed . At baseline , there were no differences in demographic or delivery characteristics between the groups . The mean Adverse Outcome Index prevalence was similar in the control and intervention groups , both at baseline and after implementation of teamwork training ( 9.4 % versus 9.0 % and 7.2 % versus 8.3 % , respectively ) . The intracluster correlation coefficient was 0.015 , with a result ant wide confidence interval for the difference in mean Adverse Outcome Index between groups ( –5.6 % to 3.2 % ) . One process measure , the time from the decision to perform an immediate cesarean delivery to the incision , differed significantly after team training ( 33.3 minutes versus 21.2 minutes , P=.03 ) . CONCLUSION : Training , as was conducted and implemented , did not transfer to a detectable impact in this study . The Adverse Outcome Index could be an important tool for comparing obstetric outcomes within and between institutions to help guide quality improvement . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00381056 LEVEL OF EVIDENCE : OBJECTIVE To evaluate an intervention package promoting effective neonatal resuscitation training at county level hospitals across China . METHODS The intervention package was implemented across 4 counties and included expert seminars , training workshops , establishment of hospital-based resuscitation teams , and supervision of training by national and provincial instructors . Upon completing the activities , a survey was conducted in all county hospitals in the 4 intervention counties and 4 r and omly selected control counties . Data on healthcare providers ' knowledge and self-confidence , and incidence of deaths from birth asphyxia from 2009 to 2011 in all hospitals were collected and compared between the two groups . RESULTS Eleven intervention and eleven control hospitals participated in the evaluation , with 97 and 87 health providers , respectively , completing the question naire survey . Over 90 % of intervention hospitals had implemented neonatal resuscitation related practice protocol s , while in control hospitals the proportion was less than 55 % . The average knowledge scores of health providers in the intervention and control counties taking a written exam were 9.2±1.2 and 8.4±1.5 , respectively ( P<0.001 ) out of maximum possible score of 10 , and the average self-confidence scores were 57.3±2.5 and 54.1±8.2 , respectively ( P<0.001 ) . Incidence of birth asphyxia ( defined as 1-min Apgar score≤7 ) decreased from 8.8 % to 6.0 % ( P<0.001 ) in the intervention counties , and asphyxia-related deaths in the delivery room decreased from 27.6 to 5.0 per 100,000 ( P=0.076 ) . There was no difference over time in asphyxia rates for the control counties . CONCLUSIONS The intervention has not only improved skills of health providers , decreased the mortality and morbidity of birth asphyxia , but also result ed in effective implementation of guidelines and protocol s within hospitals Does the effect of one-day simulation team training in obstetric emergencies decline within one year ? A post-hoc analysis of a multicentre cluster r and omised controlled trial . J van de Ven , AF Fransen , E Schuit , PJ van Runnard Heimel , BW Mol , SG Oei OBJECTIVE : To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time . STUDY DESIGN Post-hoc analysis of a multicentre , open , r and omised controlled trial that evaluated team training in obstetrics ( TOSTI study ) .We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units . Included obstetric units were r and omised to either a one-day , multi-professional simulation-based team training focusing on crew re source management in a medical simulation centre ( 12 units ) or to no team training ( 12 units ) . We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters . Primary outcome was a composite outcome of low Apgar score , severe postpartum haemorrhage , trauma due to shoulder dystocia , eclampsia and hypoxic-ischemic encephalopathy . RESULTS During a one year period after the team training the rate of obstetric complications , both on the composite level and the individual component level , did not differ between any of the quarters . For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter ( 0.06 % versus 0.26 % , OR 0.19 , 95 % CI 0.03 to 0.98 ) but in the subsequent quarters no significant reductions were observed . Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter ( 0.4 % versus 0.03 % , OR 19 , 95 % CI 2.5 - 147 ) , and not thereafter . CONCLUSION The beneficial effect of a one-day , simulation-based , multiprofessional , obstetric team training seems to decline after three months . If team training is further evaluated or implemented , repetitive training sessions every three months seem therefore recommended BACKGROUND : Training surgical residents to manage critically injured patients in a timely fashion presents a significant challenge . Simulation may have a role in this educational process , but only if it can be demonstrated that skills learned in a simulated environment translate into enhanced performance in real-life trauma situations . METHODS : A five-part , scenario-based trauma curriculum was developed specifically for this study . Midlevel surgical residents were r and omized to receiving this curriculum in didactic lecture ( LEC ) fashion or with the use of a human performance simulator ( HPS ) . A written learning objectives test was administered at the completion of the training . The first four major trauma resuscitations performed by each participating resident were captured on videotape in the emergency department and grade d by two experienced judges blinded to the method of training . The assessment tool used by the judges included an evaluation of both initial trauma evaluation or treatment skills ( part I ) and crisis management skills ( part II ) as well as an overall score ( poor/fail , adequate , or excellent ) . RESULTS : The two groups of residents received almost identical scores on the posttraining written test . Average SIM and LEC scores for part I were also similar between the two groups . However , SIM-trained residents received higher overall scores and higher scores for part II crisis management skills compared with the LEC group , which was most evident in the scores received for the teamwork category ( p = 0.04 ) . CONCLUSIONS : A trauma curriculum incorporating simulation shows promise in developing crisis management skills that are essential for evaluation of critically injured patients Background Many adverse pregnancy outcomes in the UK could be prevented with better intrapartum care . Training for intrapartum emergencies has been widely recommended but there are conflicting data about their effectiveness . Observational studies have shown sustained local improvements in perinatal outcomes associated with the use of the PRactical Obstetric Multi-Professional Training – ( PROMPT ) training package . However this effect needs to be investigated in the context of r and omised study design in setting s other than enthusiastic early adopter single-centres . The main aim of this study is to determine the effectiveness of PROMPT to reduce the rate of term infants born with low APGAR scores . Methods THISTLE ( Trial of H and s-on Interprofessional Simulation Training for Local Emergencies ) is a multi-centre stepped-wedge clustered r and omised controlled superiority trial conducted across 12 large Maternity Units in Scotl and . On the basis of prior observational findings all Units have been offered the intervention and have been r and omly allocated in groups of four Units , to one of three intervention time periods , each six months apart . Teams of four multi-professional clinicians from each participating Unit attended a two-day PROMPT Train the Trainers ( T3 ) programme prior to the start of their allocated intervention step . Following the T3 training , the teams commenced the implementation of local intrapartum emergency training in their own Units by the start of their allocated intervention period . Blinding has not been possible due to the nature of the intervention . The aim of the study is to follow up each Unit for at least 12-months after they have commenced their local courses . The primary outcome for the study is the proportion of Apgar scores < 7 at 5 min for term vaginal or emergency caesarean section births ( ≥37 weeks ) occurring in each of the study Units . These data will be extracted from the Information Services Division Scottish Morbidity Record 02 , a national routine data collection on pregnancy and births . Mixed or marginal logistic regression will be employed for the main analysis . Discussion THISTLE is the first stepped wedge cluster r and omised trial to evaluate the effectiveness of an intrapartum emergencies training programme . The results will inform training , trainers and policy going forward . Trial registration IS RCT N11640515 ( registered on 09/09/2013 ) BACKGROUND Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year , 98 % occur in developing countries . An evaluation of community-based interventions design ed to reduce the number of these deaths is needed . METHODS With the use of a train-the-trainer model , local instructors trained birth attendants from rural communities in six countries ( Argentina , Democratic Republic of Congo , Guatemala , India , Pakistan , and Zambia ) in the World Health Organization Essential Newborn Care course ( which focuses on routine neonatal care , resuscitation , thermoregulation , breast-feeding , " kangaroo " [ skin-to-skin ] care , care of the small baby , and common illnesses ) and ( except in Argentina ) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program ( which teaches basic resuscitation in depth ) . The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before- and -after design . The Neonatal Resuscitation Program intervention was assessed as a cluster-r and omized , controlled trial involving 62,366 infants . The primary outcome was neonatal death in the first 7 days after birth . RESULTS The 7-day follow-up rate was 99.2 % . After birth attendants were trained in the Essential Newborn Care course , there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth ( relative risk with training , 0.99 ; 95 % confidence interval [ CI ] , 0.81 to 1.22 ) or in the rate of perinatal death ; there was a significant reduction in the rate of stillbirth ( relative risk with training , 0.69 ; 95 % CI , 0.54 to 0.88 ; P=0.003 ) . In clusters of births in which attendants had been r and omly assigned to receive training in the Neonatal Resuscitation Program , as compared with control clusters , there was no reduction in the rates of neonatal death in the 7 days after birth , stillbirth , or perinatal death . CONCLUSIONS The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants , although the rate of stillbirths was reduced . Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates . ( Clinical Trials.gov number , NCT00136708 . An urgent need exists to improve and maintain intrapartum skills of providers in sub-Saharan Africa . Peer-assisted learning may address this need , but few rigorous evaluations have been conducted in real-world setting s. A pragmatic , cluster-r and omized trial in 12 Ug and an districts provided facility-based , team training for prevention and management of postpartum hemorrhage and birth asphyxia at 125 facilities . Three approaches to facilitating simulation-based , peer assisted learning were compared . The primary outcome was the proportion of births with uterotonic given within one minute of birth . Outcomes were evaluated using observation of birth and supplemented by skills assessment s and service delivery data . Individual and composite variables were compared across groups , using generalized linear models . Overall , 107 , 195 , and 199 providers were observed at three time points during 1,716 births across 44 facilities . Uterotonic coverage within one minute increased from : full group : 8 % ( CI 4%‒12 % ) to 50 % ( CI 42%‒59 % ) ; partial group : 19 % ( CI 9%‒30 % ) to 42 % ( CI 31%‒53 % ) ; and control group : 11 % ( 5%‒7 % ) to 51 % ( 40%‒61 % ) . Observed care of mother and newborn improved in all groups . Simulated skills maintenance for postpartum hemorrhage prophylaxis remained high across groups 7 to 8 months after the intervention . Simulated skills for newborn bag- and -mask ventilation remained high only in the full group . For all groups combined , incidence of postpartum hemorrhage and retained placenta declined 17 % and 47 % , respectively , from during the intervention period compared to the 6‒9 month period after the intervention . Fresh stillbirths and newborn deaths before discharge decreased by 34 % and 62 % , respectively , from baseline to after completion , and remained reduced 6‒9 months post-implementation . Significant improvements in uterotonic coverage remained across groups 6 months after the intervention . Findings suggest that while short , simulation-based training at the facility improves care and is feasible , more complex clinical skills used infrequently such as newborn resuscitation may require more practice to maintain skills . Trial Registration : Clinical Trials.gov NCT03254628 |
1,116 | 25,404,581 | The directly-observed , shorter regimen had higher treatment completion ( 82 % vs 69 % , RR 1.19 , 95 % CI 1.16 to 1.22 , moderate quality evidence ) , and less hepatotoxicity ( 0.4 % versus 2.4 % ; RR 0.16 , 95 % CI 0.10 to 0.27 ; high quality evidence ) , though treatment-limiting adverse events were more frequent ( 4.9 % versus 3.7 % ; RR 1.32 , 95 % CI 1.07 to 1.64 moderate quality evidence ) AUTHORS ' CONCLUSIONS Trials to date of shortened prophylactic regimens using rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH .
Treatment completion is probably higher and adverse events may be fewer with shorter rifampicin regimens .
Shortened regimens of rifampicin with INH may offer no advantage over longer INH regimens .
Rifampicin combined with pyrazinamide is associated with more adverse events .
A weekly regimen of rifapentine plus INH has higher completion rates , and less liver toxicity , though treatment discontinuation due to adverse events is probably more likely than with INH | BACKGROUND Preventing active tuberculosis ( TB ) from developing in people with latent tuberculosis infection ( LTBI ) is important for global TB control .
Isoniazid ( INH ) for six to nine months has 60 % to 90 % protective efficacy , but the treatment period is long , liver toxicity is a problem , and completion rates outside trials are only around 50 % .
Rifampicin or rifamycin-combination treatments are shorter and may result in higher completion rates .
OBJECTIVES To compare the effects of rifampicin monotherapy or rifamycin-combination therapy versus INH monotherapy for preventing active TB in HIV-negative people at risk of developing active TB . | Background Tuberculosis ( TB ) is a major cause of morbidity and mortality among children infected with HIV . Strategies to prevent TB in children include isoniazid preventive therapy ( IPT ) and antiretroviral therapy ( ART ) . IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children . Objective To investigate the combined effect of IPT and ART on TB risk in children infected with HIV . Methods A cohort analysis was done within a prospect i ve , double-blinded , placebo-controlled trial of isoniazid ( INH ) compared with placebo in children infected with HIV in Cape Town , South Africa , a high TB incidence setting . In May 2004 the placebo arm was terminated and all children were switched to INH . ART was not widely available at the start of the study , but children were started on ART following the establishment of the national ART program in 2004 . Data were analysed using Cox proportional hazard regression . Results After adjusting for age , nutritional status and immunodeficiency at enrolment , INH alone , ART alone and INH combined with ART reduced the risk of TB disease by 0.22 ( 95 % CI 0.09 to 0.53 ) , 0.32 ( 95 % CI 0.07 to 1.55 ) and 0.11 ( 95 % CI 0.04 to 0.32 ) respectively . INH reduced the risk of TB disease in children on ART by 0.23 ( 95 % CI 0.05 to 1.00 ) . Conclusions The finding that IPT may offer additional protection in children on ART has significant public health implication s because this offers a possible strategy for reducing TB in children infected with HIV . Widespread use of this strategy will however require screening of children for active TB disease . Trial registration Trial registration — Clinical Trials NCT00330304 The data from 2 U. S. Public Health Service trials of isoniazid preventive therapy were review ed in an effort to evaluate the risk of death from cancer among persons who received such therapy . Each of these prospect i ve trials used r and om assignment to either isoniazid or placebo . More than 25,000 persons participated in each of the trials . The length of follow-up ranged from 10 to 14 years in one trial and from 9 to 11 years in the other . No significant difference in the incidence of death from cancer was noted between groups treated with placebo or with isoniazid in either of the studies . This was true even when deaths due to specific types of cancer and age-specific cancer death rates were compared . These data do not support a carcinogenic effect of isoniazid in humans BACKGROUND The dual epidemic of human immunodeficiency virus ( HIV ) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa . We conducted a double-blind , r and omized , placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period . METHODS We r and omly assigned 548 HIV-infected and 804 HIV-uninfected infants ( 91 to 120 days of age ) to isoniazid ( 10 to 20 mg per kilogram of body weight per day ) or matching placebo for 96 weeks . All patients received bacille Calmette-Guérin ( BCG ) vaccination against tuberculosis within 30 days after birth . HIV-infected children had access to antiretroviral therapy . The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection , tuberculosis disease , and death in HIV-uninfected children within 96 to 108 weeks after r and omization . RESULTS Antiretroviral therapy was initiated in 98.9 % of HIV-infected children during the study . Among HIV-infected children , protocol -defined tuberculosis or death occurred in 52 children ( 19.0 % ) in the isoniazid group and 53 ( 19.3 % ) in the placebo group ( P=0.93 ) . Among HIV-uninfected children , there was no significant difference in the combined incidence of tuberculosis infection , tuberculosis disease , or death between the isoniazid group ( 39 children , 10 % ) and the placebo group ( 45 children , 11 % ; P=0.44 ) . The rate of tuberculosis was 121 cases per 1000 child-years ( 95 % confidence interval [ CI ] , 95 to 153 ) among HIV-infected children as compared with 41 per 1000 child-years ( 95 % CI , 31 to 52 ) among HIV-uninfected children . There were no significant differences in clinical or severe laboratory toxic effects between treatment groups . CONCLUSIONS Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine . Despite access to antiretroviral therapy , the burden of tuberculosis remained high among HIV-infected children . ( Funded by the National Institutes of Health and Secure the Future ; Clinical Trials.gov number , NCT00080119 . ) OBJECTIVE To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide ( 2RZ ) and 6 months of isoniazid ( 6H ) . BACKGROUND Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis . A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half . METHOD Patients with silicosis and a Mantoux skin test reaction > or = 10 mm were r and omized to receive either 2RZ or 6H daily . Liver function testing was done monthly during the initial 2 months . The adverse effects and treatment adherence were compared between the two regimens . RESULTS Forty patients ( mean age , 61.6 + /- 9.1 years ) and 36 patients ( mean age , 57.6 + /- 9.7 years ) were r and omized to the 2RZ and 6H arms , respectively ( p > 0.05 ) [ + /- SD ] . Baseline characteristics were comparable . Nineteen patients in the 2RZ arm had peak alanine transaminase ( ALT ) levels > 1.5 times the upper limit of normal ( ULN ) in comparison with only five study subjects of the 6H arm ( 47.5 % vs 13.9 % , p < 0.01 ) . Fourteen patients ( 35 % ) in the 2RZ arm and 1 patient ( 2.8 % ) in the 6H arm had peak ALT levels more than five times the ULN ( p < 0.001 ) . Only seven patients had symptoms suggestive of hepatitis ; none of the patients had jaundice . All recovered after withholding treatment . In the 2RZ study arm , none of the baseline characteristics predicted hepatotoxicity . Other adverse effects were generally mild and comparable between both study arms . Treatment was stopped prematurely in 45 % and 36.1 % of patients in the 2RZ and 6H arms , respectively ( p = 0.43 ) . The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm . CONCLUSION A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong This article reports the findings from a clinical study that examined the impact of health education and counseling on the decision of a patient infected with tuberculosis ( TB ) to complete a regimen of isoniazid ( INH ) chemoprophylaxis for 6 months to prevent TB . Forty patients were divided into two groups ; both groups were administered a question naire to collect demographic data and medical history . One group received additional health education and counseling independent of clinic staff , and the other group only received health education and counseling from clinic staff . The proportion of patients in the first group who completed INH for 6 months ( 63.6 % ) was significantly greater than the proportion of patients in the second group ( 11.1 % ) . These findings suggest that health education and counseling did make an impact on the decision of a patient infected with TB to conform with a rational choice when provided with information and a supportive relationship about the consequences of TB infection SETTING An 8-month isoniazid ( INH , H ) and ethambutol ( EMB , E ) based regimen recommended by the World Health Organization ( WHO ) had never been evaluated in a r and omised controlled multicentre trial . OBJECTIVE To compare , in a non-inferiority study design , two 8-month INH+EMB-based regimens with a st and ard INH and rifampicin ( RMP , R ) based regimen . DESIGN A total of 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were r and omly allocated to receive 1 ) daily EMB , INH , RMP and pyrazinamide ( PZA , Z ) for 2 months , followed by EMB+INH for 6 months ( 2EHRZ/6HE ) ; 2 ) the same drugs in the intensive phase but given three times weekly , followed by the same continuation phase of daily EMB+INH ( 2(EHRZ)(3)/6HE ) ; or 3 ) a control regimen with the same intensive phase as in regimen 1 , followed by 4 months of daily RMP+INH ( 2EHRZ/4HR ) . All patients were to be seen and sputum examinations for microscopy and culture carried out at regular intervals up to 30 months after r and omisation . RESULTS At 30 months , failure/relapse rates were 11.7 % of 281 2EHRZ/6HE , 15.3 % of 301 2(EHRZ)(3)/6HE and 6.0 % of 282 2EHRZ/4HR patients ( χ(2 ) , 2 degrees of freedom = 12.8 , P = 0.002 ) . CONCLUSION These results confirm earlier findings demonstrating the inferiority of the INH+EMB-based regimens to the st and ard 6-month regimen . The WHO has withdrawn its recommendation of these regimens Rationale Treatment for latent tuberculosis infection with isoniazid for 9 months ( 9INH ) has poor completion and serious adverse events , while treatment for 4 months with daily rifampin ( 4RIF ) has significantly higher completion and fewer adverse events . Objectives To compare the health system costs of 4RIF and 9INH . Methods In a r and omised trial conducted in five Canadian centres , one Brazilian and one Saudi Arabian centre , consenting subjects were r and omised to receive 4RIF or 9INH . Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits , investigations and drugs . All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute . Costs were expressed in Canadian dollars . Results Total health system cost per patient allocated to 4RIF was $ 854 compared with $ 970 for 9INH ( p<0.0001 ) . The average cost per patient for the 328 of 420 ( 78 % ) who completed 4RIF therapy was $ 1094 compared with $ 1625 for the 254 of 427 ( 60 % ) completing 9INH ( p<0.0001 ) . Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events . Total costs related to management of adverse events with 9INH were $ 48 142 compared with $ 25 684 for 4RIF ( p=0.008 ) . Using these data , incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74 % , and cost saving if efficacy exceeded 65 % . Conclusions The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events . RCT registration number NCT00170209 BACKGROUND Cases of severe and fatal liver injury were reported after a 2-month course of rifampin-pyrazinamide therapy was recommended in 2000 as an alternative to isoniazid for treatment of latent tuberculosis infection . We estimated rates of rifampin-pyrazinamide-associated liver injury and compared these with historical rates for isoniazid . METHODS We conducted a survey of state and city tuberculosis programs and other health care setting s in the United States where rifampin-pyrazinamide was prescribed . The number of rifampin-pyrazinamide therapy initiations was collected , as well as the number of occurrences of ( 1 ) asymptomatic aspartate aminotransferase serum concentration > 5 times the upper limit of normal , ( 2 ) symptomatic hepatitis ( in which the patient was not hospitalized ) , ( 3 ) hospitalization for liver injury , ( 4 ) death with liver injury , and ( 5 ) treatment completion . We also search ed a national pharmacy cl aims data base ( Verispan ) . Rates of these events were calculated . RESULTS Among 139 programs , 110 ( 79 % ) responded ; 87 ( 79 % ) had initiated rifampin-pyrazinamide therapy for a total of 8087 patients between January 2000 and June 2002 . Rates per 1000 rifampin-pyrazinamide therapy initiations during this period were 25.6 ( 95 % confidence interval [ CI ] , 22.3 - 29.3 ) for asymptomatic aspartate aminotransferase level > 5 times the upper limit of normal and 18.7 ( 95 % CI , 15.9 - 21.9 ) for hepatitis . Seven fatalities and 23 hospitalizations occurred , with rates of 0.9 ( 95 % CI , 0.4 - 1.9 ) and 2.8 ( 95 % CI , 1.8 - 4.3 ) per 1000 rifampin-pyrazinamide therapy initiations , respectively . Of 8087 patients , 64 % completed rifampin-pyrazinamide therapy . The Verispan search revealed 1 rifampin-pyrazinamide-associated hospitalization ( 2.9 hospitalizations per 1000 rifampin-pyrazinamide therapy initiations ; 95 % CI , 0.1 - 18.4 ) and no deaths . Articles on the use of isoniazid therapy for latent tuberculosis infection that were published after 1990 reported fatality rates of 0.0 - 0.3 deaths per 1000 persons . CONCLUSIONS Rates of liver injury , hospitalization , and death associated with rifampin-pyrazinamide therapy exceed rates reported for isoniazid therapy . Because earlier r and omized trials of rifampin-pyrazinamide lacked adequate statistical power to detect fatal events , the Centers for Disease Control and Prevention recommends that rifampin-pyrazinamide generally should not be used for treatment of latent tuberculosis infection Schoolchildren were Mantoux-tested with 2 TU freeze-dried PPD RT23 , and the strong reactors with in duration s of 14.0 mm or more were selected for treatment with one of three different fixed drug combinations containing isoniazid or with placebo for 2 to 6 months . The initial tuberculin test was repeated after 8 , 14 , and 27 months . Of the 8,934 black schoolchildren initially tested , 5,165 did not react to the skin test , 2,898 had in duration s up to 14.0 mm , and 871 reacted strongly . Of these strong reactors , 808 were allocated to four preventive treatment groups . On completion of treatment , the mean tuberculin reaction for all groups was significantly decreased . Because the placebo group showed changes similar to those seen in the other treatment groups , the tuberculin skin test is probably not suitable for monitoring the success of preventive therapy . Differences between skin test results before and after treatment when retesting only strong reactors are caused by a combination of effects that are difficult to distinguish . Assuming r and om variation in tuberculin sensitivity , the decrease can be explained as a combined effect of regression to the mean and some boosting . The increased reaction sizes in the subsequent Mantoux tests are explained by the booster phenomenon and possibly by reinfection . When using a cutting point for deriving a positive reactor , the chance of being selected for preventive treatment may depend primarily on the moment in time when the test is done . Thus , all reactors with no recent BCG vaccination should equally be considered for treatment BACKGROUND South Africa has the third highest annual number of new tuberculosis ( TB ) cases globally . The resurgence of TB which has particularly affected gold miners in South Africa , is attributed to occupational risk factors for TB including silica dust exposure and high HIV prevalence . Isoniazid preventive therapy ( IPT ) is recommended for individuals at high risk to prevent both HIV-related TB and silicotuberculosis , but global uptake has been poor . We describe the design of a cluster r and omised study , " Thibela TB " , which compares routine IPT targeted to those identified as at higher risk of TB ( due to HIV infection or silicosis ) against a " community-wide " approach in which IPT is offered to all employees . The trial is registered with the Current Controlled Trials : Registration number IS RCT N63327174 . METHODS We describe the rationale for the intervention of community-wide IPT , drawing on studies conducted in 1950 - 1960s in the pre-HIV era . The design of the study , including the definition of the cluster , is presented and advantages and limitations of such a design are discussed . CONCLUSION If successful in reducing TB incidence and prevalence , this trial has potential to make a major contribution to TB control policy in high HIV setting s , providing evidence concerning efficacy , and additionally safety and population -level effects on drug susceptibility patterns . Such rigorous evaluation is essential to provide policy makers with an evidence base to guide community-level TB prevention strategies BACKGROUND A 9-month course of isoniazid monotherapy is currently recommended for the treatment of latent tuberculosis infection ( LTBI ) and has been shown to be effective in both children and adults . Reduced compliance with this regimen has forced physicians to explore shorter regimens . The aim of this study was to compare 3- and 4-month combination regimens of isoniazid plus rifampin with a 9-month regimen of isoniazid monotherapy for the treatment of LTBI in children . METHODS This prospect i ve , r and omized , controlled study was conducted over an 11-year period ( 1995 - 2005 ) . In period 1 ( 1995 - 1998 ) , 232 patients received isoniazid therapy for 9 months ( group A ) , and 238 patients received isoniazid and rifampin for 4 months ( group B ) . In period 2 ( 1999 - 2002 ) , 236 patients were treated with isoniazid and rifampin for 4 months ( group C ) , and 220 patients received the same regimen for 3 months ( group D ) . All patients were observed for > or = 3 years . RESULTS Overall compliance with treatment was good , but patients who received isoniazid monotherapy were less compliant than were those who received short-course combination therapy ( P=.011 , for group A vs. group B ; P=.510 , for group C vs. group D ) . No patient in any group developed clinical disease during the follow-up period . New radiographic findings suggestive of possible active disease were more common in patients who received isoniazid monotherapy ( 24 % ) than in those treated with shorter regimens ( 11.8 % , 13.6 % , and 11 % for groups B , C , and D , respectively ; P=.001 for group A vs. group B ; P=.418 for group C vs. group D ) . Serious drug-related adverse effects were not detected . CONCLUSIONS Short-course treatment with isoniazid and rifampin for 3 - 4 months is safe and seems to be superior to a 9-month course of isoniazid monotherapy Context Guidelines from the American Thoracic Society and Centers for Disease Control and Prevention for treating latent tuberculosis infection advocate 2 months of rifampin plus pyrazinamide as an effective alternative to 6 to 9 months of isoniazid or 4 months of rifampin . However , case reports have described severe liver injury in patients who were receiving the 2-month regimen . Contribution This nonr and omized , open-label trial found that the risk for grade 3 or 4 liver injury was higher in patients taking 2 months of rifampin plus pyrazinamide ( 7.7 % ) than in patients taking 6 months of isoniazid ( 1 % ) . Clinical Implication s If clinicians use the short-course regimen , they should vigilantly follow patients ' liver enzyme levels . The Editors As rates of tuberculosis cases in the United States have decreased ( 1 , 2 ) , the focus of prevention and control efforts has shifted toward identification and treatment of persons with latent tuberculosis infection who are at increased risk for developing tuberculosis . This approach was endorsed in a recent report from the Institute of Medicine ( 3 ) . Isoniazid given for at least 6 months has been the st and ard therapy for latent tuberculosis infection for decades , but its use has been limited by toxicity , especially hepatitis ( 4 - 6 ) , and by poor adherence to treatment ( 7 ) . A 2-month course of rifampin and pyrazinamide has been shown to be effective and well tolerated as treatment of latent tuberculosis infection in HIV-infected persons ( 8 - 10 ) . Guidelines from the American Thoracic Society and Centers for Disease Control and Prevention ( 11 ) offer three main regimens for treatment of latent tuberculosis infection : isoniazid for 6 to 9 months , rifampin for 4 months , or rifampin and pyrazinamide for 2 months . However , there is relatively little experience with use of rifampin plus pyrazinamide to treat latent tuberculosis infection in persons without HIV infection , and case reports of severe hepatitis causing five deaths have raised concerns about the safety of the regimen ( 12 , 13 ) . We therefore conducted a multicenter , prospect i ve , open-label trial comparing daily treatment with rifampin and pyrazinamide for 2 months with daily treatment with isoniazid for 6 months in nonHIV-infected adults with latent tuberculosis infection ( the Short-Course Rifampin and Pyrazinamide for Tuberculosis Infection [ SCRIPT ] study ) . Our primary goals were to compare risk for toxicity , particularly hepatotoxicity , and completion of therapy . We also investigated whether persons with latent tuberculosis infection who were older than 35 years of age , a group known to have increased rates of hepatitis while taking isoniazid ( 5 ) , would have fewer adverse events while taking rifampin plus pyrazinamide than while taking isoniazid . Methods Patients All adults older than 17 years of age who had a positive tuberculin skin test ( as defined by American Thoracic Society/Centers for Disease Control and Prevention criteria [ 11 ] ) and in whom active tuberculosis was excluded and treatment of latent tuberculosis infection would ordinarily be recommended ( for example , persons with close contact to an infectious case or those with a medical risk factor , such as diabetes ) were eligible for the study . In addition , we enrolled foreign-born persons older than 35 years of age who had been in the United States for fewer than 6 years . These latter patients were not included in the American Thoracic Society/Centers for Disease Control and Prevention guidelines when the study was begun . Before being invited to participate , all patients who met initial criteria for enrollment were asked about previous liver disease , current medications and illnesses , previous gout , and risk factors for HIV infection . Liver enzymes ( alanine aminotransferase [ ALT ] , aspartate aminotransferase , and alkaline phosphatase ) , bilirubin , and creatinine were measured . Testing for and counseling about HIV infection were recommended for patients whose HIV status was not known , and a urine pregnancy test was performed for all women of childbearing age . During their baseline visit , patients underwent a review of symptoms that included history of nausea , vomiting , jaundice , abdominal pain , weight loss , arthralgia , headache , and neuropathy . Exclusion criteria were pregnancy , HIV infection , serum creatinine concentration more than twice the upper limit of normal , serum aspartate aminotransferase or ALT level more than three times the upper limit of normal , and a history of gout . Institutional review boards at each site approved the study , and written informed consent was obtained from all patients . Design Persons who met study criteria and agreed to participate were allocated in alternate weeks to receive rifampin ( 600 mg/d ) plus pyrazinamide ( 20 mg/kg of body weight daily ) for 2 months or isoniazid ( 300 mg/d ) for 6 months ( the recommended minimum duration when the study started [ 14 ] ) . Tables were used to st and ardize weight-based dosing of pyrazinamide to the closest 250 mg . At each site , the allocation during the first week of patient enrollment was determined by a coin toss . For the remainder of the trial , allocation to treatment regimen was alternated weekly . This systematic allocation design was chosen for ease of implementation in busy public health tuberculosis clinics in San Francisco , Boston , and Atlanta . Serum levels of liver enzymes and bilirubin were measured in all patients after 1 month of treatment . Patients receiving isoniazid had repeated liver enzyme testing at 3 months . Patients receiving rifampin and pyrazinamide also had a complete blood count and measurement of uric acid and creatinine after 1 month of treatment . All treatment was self-administered , and specific incentives , financial or otherwise , were not provided . All patients received monthly supplies of medication and were instructed to take medication daily and return in 1 month ( or sooner if any of the symptoms mentioned previously occurred ) . At each visit , patients were evaluated for signs and symptoms of adverse events by tuberculosis control nurses and evaluated for adherence to treatment . Hepatotoxicity was based on the World Health Organization classification and was defined as grade 1 for any serum ALT level of 51 to 125 U/L , or 1.25 to 2.5 times normal ; grade 2 for any serum ALT level of 126 to 250 U/L , or 2.6 to 5.0 times normal ; grade 3 for any serum ALT level of 251 to 500 U/L , or 5.1 to 10.0 times normal ; and grade 4 for any serum ALT level greater than 500 U/L , or > 10 times normal , or greater than 250 U/L if accompanied by compatible symptoms ( 15 ) . At the 1-month evaluation in recipients of rifampin plus pyrazinamide or the 3-month evaluation in isoniazid recipients , patients who had grade 1 or 2 liver injury continued to take study medication and had repeated liver enzyme testing in 2 weeks . In patients with grade 3 hepatotoxicity , treatment with study drugs was stopped and not resumed unless another cause of hepatitis could be found ( such as alcohol abuse ) . Treatment with study drugs was permanently discontinued in patients with grade 4 hepatotoxicity . Outcomes Primary end points were development of any adverse event , especially grade 3 or 4 hepatotoxicity , and completion of the prescribed amount of treatment . Adverse events were determined on the basis of interviews and by laboratory examination when indicated . Completion of the regimen was defined as taking at least 80 % of prescribed medication . Statistical Analysis A sample of 540 patients was calculated to provide 80 % power in two-sided tests , with an value of 0.05 , to detect an increase in the expected incidence of hepatotoxicity of any grade ( the primary end point ) from 15 % in the isoniazid group to 25 % in the rifampin plus pyrazinamide group . The first patient was enrolled on 15 February 1999 . A scheduled interim analysis of the first 313 patients that was performed in July 2000 indicated no statistically significant differences between the two groups in terms of adverse events or completion of therapy . Enrollment continued until October 2000 . Between-regimen comparisons of hepatotoxicity , other adverse events , and completion were based on the treatment initially assigned , without regard to the duration of treatment actually received . In an initial analysis of treatment effects on hepatotoxicity , the Fisher exact test was used to compare the proportion of patients with ALT values greater than 250 U/L among 411 participants who had liver enzyme testing at 1 or 3 months . Confirmatory analyses were then used to vali date the initial result . Because the study was not r and omized , treatment assignment was potentially confounded by imbalances in baseline covariates between the two treatment groups . In addition , grade 3 or 4 hepatotoxicity was uncommon . Therefore , to adjust for potential confounding , the initial exact analysis of hepatotoxicity was repeated with stratification by quintile of a propensity score that was estimated by using a multivariable logistic model for treatment assignment ( 16 , 17 ) . Furthermore , liver enzyme values were missing for 78 of 282 ( 27.7 % ) patients in the isoniazid group and 100 of 307 ( 32.6 % ) patients in the rifampin plus pyrazinamide group . To correct for this possible source of bias , we used multiple imputation . Specifically , the odds ratio for treatment was estimated in each of 10 data sets with imputed values for the missing liver enzyme tests by using logistic models to adjust for the propensity score as a continuous covariate . In the final step , a summary odds ratio estimate was calculated by using st and ard methods ( 18 , 19 ) . In a further analysis , treatment-by-site interaction was examined in an exact analysis that was stratified by site . We also used logistic models to assess possible violations of independence due to clustering by site by comparing model-based st and ard errors with robust st and ard errors that accounted for within-site correlation . Finally , more common outcomes , including Background Attrition , which leads to missing data , is a common problem in cluster r and omized trials ( CRTs ) , where groups of patients rather than individuals are r and omized . St and ard multiple imputation ( MI ) strategies may not be appropriate to impute missing data from CRTs since they assume independent data . In this paper , under the assumption of missing completely at r and om and covariate dependent missing , we compared six MI strategies which account for the intra-cluster correlation for missing binary outcomes in CRTs with the st and ard imputation strategies and complete case analysis approach using a simulation study . Method We considered three within-cluster and three across-cluster MI strategies for missing binary outcomes in CRTs . The three within-cluster MI strategies are logistic regression method , propensity score method , and Markov chain Monte Carlo ( MCMC ) method , which apply st and ard MI strategies within each cluster . The three across-cluster MI strategies are propensity score method , r and om-effects ( RE ) logistic regression approach , and logistic regression with cluster as a fixed effect . Based on the community hypertension assessment trial ( CHAT ) which has complete data , we design ed a simulation study to investigate the performance of above MI strategies . Results The estimated treatment effect and its 95 % confidence interval ( CI ) from generalized estimating equations ( GEE ) model based on the CHAT complete data set are 1.14 ( 0.76 1.70 ) . When 30 % of binary outcome are missing completely at r and om , a simulation study shows that the estimated treatment effects and the corresponding 95 % CIs from GEE model are 1.15 ( 0.76 1.75 ) if complete case analysis is used , 1.12 ( 0.72 1.73 ) if within-cluster MCMC method is used , 1.21 ( 0.80 1.81 ) if across-cluster RE logistic regression is used , and 1.16 ( 0.82 1.64 ) if st and ard logistic regression which does not account for clustering is used . Conclusion When the percentage of missing data is low or intra-cluster correlation coefficient is small , different approaches for h and ling missing binary outcome data generate quite similar results . When the percentage of missing data is large , st and ard MI strategies , which do not take into account the intra-cluster correlation , underestimate the variance of the treatment effect . Within-cluster and across-cluster MI strategies ( except for r and om-effects logistic regression MI strategy ) , which take the intra-cluster correlation into account , seem to be more appropriate to h and le the missing outcome from CRTs . Under the same imputation strategy and percentage of missingness , the estimates of the treatment effect from GEE and RE logistic regression models are similar Background Interferon-gamma ( IFN-γ ) Release Assays ( IGRA ) are more specific than the tuberculosis skin test ( TST ) in the diagnosis of latent tuberculosis ( TB ) infection ( LTBI ) . We present the performance of the QuantiFERON ® -TB Gold In-tube ( QFT-TB ) assay as diagnostic test and during follow-up of preventive TB therapy in out patients from a TB low-endemic country . Methods 481 persons with suspected TB infection were tested with QFT-TB . Thoracic X-ray and sputum sample s were performed and a question naire concerning risk factors for TB was filled . Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months . Results The QFT-TB test was positive in 30.8 % ( 148/481 ) of the total , in 66.9 % ( 111/166 ) of persons with origin from a TB endemic country , in 71.4 % ( 20/28 ) previously treated for TB and in 100 % ( 15/15 ) of those diagnosed with active TB with no inconclusive results . The QFT-TB test was more frequently positive in those with TST ≥ 15 mm ( 47.5 % ) compared to TST 11 - 14 mm ( 21.3 % ) and TST 6 - 10 mm ( 10.5 % ) , ( p < 0.001 ) . Origin from a TB endemic country ( OR 6.82 , 95 % CI 1.73 - 26.82 ) , recent stay in a TB endemic country ( OR 1.32 , 95 % CI 1.09 - 1.59 ) , duration of TB exposure ( OR 1.59 , 95 % CI 1.14 - 2.22 ) and previous TB disease ( OR 11.60 , 95 % CI 2.02 - 66.73 ) were all independently associated with a positive QFT-TB test . After preventive therapy , 35/40 ( 87.5 % ) and 22/26 ( 84.6 % ) were still QFT-TB positive after three and 15 months , respectively . IFN-γ responses were comparable at start ( mean 6.13 IU/ml ± SD 3.99 ) and after three months ( mean 5.65 IU/ml ± SD 3.66 ) and 15 months ( mean 5.65 IU/ml ± SD 4.14 ) , ( p > 0.05 ) . Conclusion Only one third of those with suspected TB infection had a positive QFT-TB test . Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening . Since most patients remained QFT-TB positive after therapy , the test should not be used to monitor the effect of preventive therapy . Prospect i ve studies are needed in order to determine the usefulness of IGRA tests during therapy BACKGROUND Treatment of latent TB infection ( LTBI ) is essential for preventing TB in North America , but acceptance and completion of this treatment have not been systematic ally assessed . METHODS We performed a retrospective , r and omized two-stage cross-sectional survey of treatment and completion of LTBI at public and private clinics in 19 regions of the United States and Canada in 2002 . RESULTS At 32 clinics that both performed tuberculin skin testing and offered treatment , 123 ( 17.1 % ; 95 % CI , 14.5%-20.0 % ) of 720 subjects tested and offered treatment declined . Employees at health-care facilities were more likely to decline ( odds ratio [ OR ] , 4.74 ; 95 % CI , 1.75 - 12.9 ; P = .003 ) , whereas those in contact with a patient with TB were less likely to decline ( OR , 0.19 ; 95 % CI , 0.07 - 0.50 ; P = .001 ) . At 68 clinics starting treatment regardless of where skin testing was performed , 1,045 ( 52.7 % ; 95 % CI , 48.5%-56.8 % ) of 1,994 people starting treatment failed to complete the recommended course . Risk factors for failure to complete included starting the 9-month isoniazid regimen ( OR , 2.08 ; 95 % CI , 1.23 - 3.57 ) , residence in a congregate setting ( nursing home , shelter , or jail ; OR , 2.94 ; 95 % CI , 1.58 - 5.56 ) , injection drug use ( OR , 2.13 ; 95 % CI , 1.04 - 4.35 ) , age > or= 15 years ( OR , 1.49 ; 95 % CI , 1.14 - 1.94 ) , and employment at a health-care facility ( 1.37 ; 95 % CI , 1.00 - 1.85 ) . CONCLUSIONS Fewer than half of the people starting treatment of LTBI completed therapy . Shorter regimens and interventions targeting residents of congregate setting s , injection drug users , and employees of health-care facilities are needed to increase completion There is little published information regarding treatment completion , safety , and efficacy of rifampin administered daily for 4 months-a recommended alternative to 9 months of isoniazid for therapy of latent tuberculosis infection . In an open-label r and omized trial at a university-affiliated respiratory hospital , consenting patients whose treating physician had recommended therapy for latent tuberculosis infection were r and omized to daily self-administered rifampin for 4 months or daily self-administered isoniazid for 9 months . Of 58 patients r and omized to rifampin , 53 ( 91 % ) took 80 % of doses , and 50 ( 86 % ) took more than 90 % of doses within 20 weeks compared with 44 ( 76 % ) and 36 ( 62 % ) who took 80 and 90 % , respectively , of doses of isoniazid within 43 weeks ( relative risks : 80 % of doses , 1.2 [ 95 % confidence interval : 1.02 , 1.4 ] ; 90 % of doses , 1.4 [ 1.1 , 1.7 ] ) . Adverse events result ed in permanent discontinuation of therapy for two ( 3 % ) patients taking rifampin , and for eight ( 14 % ) patients taking isoniazid . Three patients developed drug-induced hepatitis -- all were taking isoniazid . Total costs of therapy were significantly higher for isoniazid . In conclusion , completion of therapy was significantly better with 4 months of rifampin and major side effects were somewhat lower . Further studies are needed to assess the safety and efficacy of the 4-month rifampin regimen A controlled and double-blind study to determine the efficacy of isoniazid in preventing the development of pulmonary tuberculosis among the household contacts of open cases of the disease has been carried out in a rural area of Kenya-a financially h and icapped country-under realistic field conditions . A one-year course of isoniazid ( 5 - 10 mg per kg of body-weight in one daily dose ) administered to the contacts of active cases gave a reduction in respect of the excretion of tubercle bacilli of the order of 90 % at the end of the year . In the subsequent observation period ( 2 - 4 years ) both the control and the isoniazid-treated group showed a low and similar rate of adverse findings .Previous studies by the Tuberculosis Chemotherapy and BCG Centre , Nairobi , had revealed that the risk of tuberculosis among household contacts , especially children , was high and , further , that the acceptability of the drug and the regularity of drug-taking were poor among these contacts . Even so , a very considerable prophylactic effect of isoniazid was demonstrated in the present study . It therefore seems justifiable to conclude that the treatment of household contacts with isoniazid could contribute to tuberculosis control in financially h and icapped countries , particularly where a tuberculosis case-finding programme is reasonably well established Background : Current international guidelines recommend 6–9 months of isoniazid ( INH ) preventive chemotherapy to prevent the development of active tuberculosis in children exposed to a susceptible strain of M tuberculosis . However , this is dependent on good adherence and retrospective studies have indicated that adherence to unsupervised INH preventive chemotherapy is poor . Aim : To prospect ively document adherence to six months of unsupervised INH monotherapy and outcome in children with household exposure to an adult pulmonary tuberculosis index case . Methods : From February 2003 to January 2005 in two suburbs of Cape Town , South Africa , all children < 5 years old in household contact with an adult pulmonary tuberculosis index case were screened for tuberculosis and given unsupervised INH preventive chemotherapy once active tuberculosis was excluded . Adherence and outcome were monitored . Results : In total , 217 index cases from 185 households were identified ; 274 children < 5 years old experienced household exposure , of whom 229 ( 84 % ) were fully evaluated . Thirty eight children were treated for tuberculosis and 180 received preventive chemotherapy . Of the children who received preventive chemotherapy , 36/180 ( 20 % ) completed ⩾5 months of unsupervised INH monotherapy . During the subsequent surveillance period six children developed tuberculosis : two received no preventive chemotherapy , and four had very poor adherence . Conclusion : Adherence to six months of unsupervised INH preventive chemotherapy was poor . Strategies to improve adherence , such as using shorter duration multidrug regimens and /or supervision of preventive treatment require further evaluation , particularly in children who are at high risk to progress to disease following exposure The risk of " Gesunde Befundträger " ( healthy carriers of pulmonary lesions ) to develop pulmonary tuberculosis is compared with that of persons with X-ray shadows in the lung . In the group of " Gesunde Befundträger " this risk can be further differentiated , being highest among males with positive tuberculin skin test and more extended X-ray shadows in the lung . Judging from a follow-up of 4 years in the double-blind trial on isoniazid preventive treatment in persons with fibrotic lesions , the risk of developing pulmonary tuberculosis is reduced by 2/3 by giving 300 mg isoniazid daily during 24 weeks . In the present epidemiological stage of tuberculosis in GDR , preventive treatment of persons with highest risk of developing tuberculosis disease is the most promising prophylactic measure . The recommedations to reduce side-effects must be observed BACKGROUND Nine months of isoniazid therapy is the recommended regimen for treatment of latent tuberculosis infection , but low completion rates are a serious problem . The search for shorter regimens , compared with the st and ard isoniazid regimen , is of vital importance . We describe our experience using short-course regimens for the treatment of latent tuberculosis infection . METHODS We conducted a nonr and omized , observational study of 459 patients in a county health department from June 2000 to January 2006 . Short-course therapy was defined as pyrazinamide and rifampin taken daily or twice weekly for 2 months or rifampin taken daily for 4 - 6 months . Conventional therapy consisted of a 9-month regimen of isoniazid . Liver function testing was performed for both groups in accordance with clinical guidelines . Treatment completion and hepatotoxicity ( according to the World Health Organization classification ) were determined for the short-course and conventional therapy groups . RESULTS Treatment was completed by 241 ( 77.7 % ) of 310 patients in the short-course group and by 98 ( 65.8 % ) of 149 patients in the isoniazid group ( P = .009 ) . Moderate to severe hepatotoxicity ( grade s 3 and 4 ) occurred in 6.1 % of patients receiving short-course therapy and in 2.0 % of patients receiving isoniazid ( P=.09 ) . The hepatotoxicity observed in the short-course group was confined to patients receiving pyrazinamide and rifampin daily and was self limited in all cases after the medications were discontinued . CONCLUSIONS The rate of treatment completion was significantly higher with short-course regimens , compared with the isoniazid regimen . Although the overall risk of hepatotoxicity in patients receiving pyrazinamide and rifampin daily for the treatment of latent tuberculosis infection was higher , liver functions returned to normal after the medications were discontinued Background Tuberculosis ( TB ) is a major public health problem in Rio de Janeiro , where a high proportion of HIV-infected adults are co-infected with latent TB . Health officials in Brazil have recommended that HIV patients be tested for TB infection and given TB prophylaxis ( isoniazid ) if positive . In practice , although Brazil is a model for provision of antiretroviral therapy to patients with advanced HIV disease , relatively few such patients receive TB testing and prevention services . Purpose We initiated a r and omized study of a health services intervention to train health personnel in implementation of the recommended routine of TB testing and isoniazid prophylaxis . The primary goal is to reduce incident TB disease in the HIV clinic population . Methods The clinic-level intervention will be phased in gradually over the study period until all clinics have received the intervention . The clinics ' order of initiation of intervention was r and omized and subjected to constraints based on clinic-level covariates . This phased intervention cluster-r and omized trial required special attention to power/ sample size calculation and r and omization procedures , of which we provide the relevant details . Results Special design considerations accounted for within-clinic correlation , variation in the clinic size , time-varying ratio of intervention to control clinics and guaranteed post-r and omization covariate balance . These were successfully implemented for the estimation of power and execution of the r and omization strategy . Limitations Although the design features of r and omization by clinic and phased implementation of the intervention meet logistic and local needs , they substantially lower the statistical power of the study . Conclusions Studies with cluster-r and omized order of intervention introduction can provide useful information on intervention effects . Their design and analysis are more complicated than for individually r and omized parallel design trials . The methods we describe represent practical approaches to the challenges raised in the course of design ing this study . Clinical Trials 2007 ; 4 : 190—199 . RATIONALE Treatment of latent tuberculosis ( TB ) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies . OBJECTIVES To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil . METHODS Contacts of patients with TB were r and omized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 wk or rifampin 450 - 600 mg/pyrazinamide 750 - 1,500 mg daily for 8 wk and followed for at least 2 yr . MEASUREMENTS TB rates , adverse events , and adherence to therapy . MAIN RESULTS A total of 399 household contacts were enrolled , 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm . The median age was 34 yr , median weight was 63 kg , 60 % of participants were female , and only one patient was HIV infected . Rifapentine/isoniazid was well tolerated , but the trial was halted by the investigators before completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm . Twenty of 193 participants ( 10 % ) receiving rifampin/pyrazinamide experienced grade 3 or 4 hepatotoxicity , compared with 2 of 206 participants ( 1 % ) on rifapentine/isoniazid ( p<0.001 ) . There were no hospitalizations or deaths due to hepatotoxicity , and all participants ' liver enzyme levels returned to normal during follow-up . During follow-up , four cases of active TB developed , three in the rifapentine/isoniazid group and one in the rifampin/pyrazinamide group ( 1.46 vs. 0.52 % ; difference , 0.94 % ; 95 % confidence interval , -1.6 to 3.7 % ) . CONCLUSIONS Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB . Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection SETTING Two health clinics in Los Angeles County , California . OBJECTIVE To identify factors associated with completion of care among foreign-born adolescents treated for latent tuberculosis infection ( LTBI ) . DESIGN A total of 766 low-income adolescents ( 79 % participation rate ) , including 610 foreign-born , were recruited . In prospect i ve face-to-face interviews , data were obtained on socio-demographic and lifestyle characteristics , psychosocial factors and clinic-related variables . Medical chart data were abstract ed regarding clinic appointment keeping and completion of treatment . Univariate and multivariate logistic regression analyses were performed to identify factors associated with completion of care . RESULTS Foreign-born adolescents were more likely to complete care than US-born adolescents , with 82 % completion of care rate . In logistic regression analyses after controlling for age , medication taking behavior ( OR 1.26 , 95%CI 1.15 - 1.39 ) , living with both parents ( OR 1.74 , 95%CI 1.02 - 2.97 ) , sexual intercourse ( OR 0.66 , 95%CI 0.36 - 1.19 ) and speaking mostly or only English with parents ( OR 0.39 , 95%CI 0.15 - 1.03 ) were independently associated with completion of care . CONCLUSION These findings contribute to our underst and ing of the factors that may explain why some adolescents complete care whereas others do not . They provide supportive evidence that tailored intervention programs should be developed to support the screening and completion of treatment of foreign-born adolescents An earlier report showed that , in patients with bacteriologically quiescent pulmonary tuberculosis at the end of 1 year of chemotherapy , isoniazid alone in a single daily dose of 150 - 200 mg , given as maintenance therapy in the second year , did not markedly prevent relapse over a 4-year period of follow-up in patients who had had residual cavitation ( the " open-negative " syndrome ) at 1 year , but was highly effective in patients who had not . As a result of these findings , two controlled studies , reported here , were undertaken . The first study was undertaken in patients with bacteriologically quiescent disease and residual cavitation at 1 year , and investigated the value of isoniazid in a higher daily dose ( 400 mg ) throughout the second year ; this is known to be the optimum therapeutic dose when isoniazid is prescribed alone for 1 year in the initial treatment of the disease . The second study was carried out in patients with bacteriologically quiescent disease and no residual cavitation at 1 year , and sought to determine the value of a shorter duration ( 6 months ) of chemotherapy in the second year with a daily dose of 300 mg of isoniazid . Neither of the two isoniazid regimens was highly satisfactory , although both appeared to have had some effect in preventing relapse during the 4-year period of follow-up PURPOSE To determine the effect of several interventions on adherence to tuberculosis preventive therapy . METHODS We conducted a r and omized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis . Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly ( Supervised group , n = 99 ) , daily self-administered isoniazid with peer counseling and education ( Peer group , n = 101 ) , or routine care ( Routine group , n = 100 ) . Patients within each arm were also r and omly assigned to receive an immediate or deferred monthly $ 10 stipend for maintaining adherence . The endpoints of the trial were completing 6 months of treatment , pill-taking as measured by self-report or observation , isoniazid metabolites present in urine , and bottle opening as determined by electronic monitors in a subset of patients . RESULTS Completion of therapy was 80 % for patients in the Supervised group , 78 % in the Peer group , and 79 % in the Routine group ( P = 0.70 ) . Completion was 83 % ( 125 of 150 ) among patients receiving immediate incentives versus 75 % ( 112 of 150 ) among patients with deferred incentives ( P = 0.09 ) . The proportion of patients who were observed or reported taking at least 80 % of their doses was 82 % for the Supervised arm of the study , compared with 71 % for the Peer arm and 90 % for the Routine arm . The proportion of patients who took 100 % of doses was 77 % for the Supervised arm ( by observation ) , 6 % for the Peer arm ( by report ) , and 10 % for the Routine arm ( by report ; P < 0.001 ) . Direct observation showed the median proportion of doses taken by the Supervised group was 100 % , while electronic monitoring in a subset of patients showed the Peer group ( n = 27 ) took 57 % of prescribed doses and the Routine group ( n = 32 ) took 49 % ( P < 0.001 ) . Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold st and ard . There were no significant differences in electronically monitored adherence by type of incentive . CONCLUSION Adherence to isoniazid preventive therapy by injection drug users is best with supervised care . Peer counseling improves adherence over routine care , as measured by electronic monitoring of pill caps , and patients receiving peer counseling more accurately reported their adherence . More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups Once-weekly rifapentine 600 mg plus isoniazid ( INH ) during the continuation phase treatment of tuberculosis is associated with a relapse rate higher than that of twice-weekly rifampin plus INH . The safety and tolerability of higher rifapentine doses need to be determined . We conducted a prospect i ve , r and omized , double-blind trial of rifapentine at three doses ( 600 , 900 , and 1,200 mg ) plus INH 15 mg/kg once weekly in the continuation phase treatment of culture-positive tuberculosis in 150 human immunodeficiency virus-seronegative adults . Outcome measures were discontinuation of therapy for any reason and adverse events on therapy . Treatment was discontinued in 3 of 52 ( 6 % ) , 2 of 51 ( 4 % ) , and 3 of 47 ( 6 % ) in the rifapentine 600- , 900- , and 1,200-mg treatment arms , respectively . Only one discontinuation , in the rifapentine 1,200-mg arm , was due to an adverse event possibly associated with study therapy . There was a trend toward more adverse events , possibly associated with study therapy , in the highest-dose arms ( p = 0.051 ) . Rifapentine 900-mg , once-weekly dosing appears to be safe and well tolerated and is being evaluated in Phase III efficacy trials of treatment of latent tuberculosis . Further evaluation of the safety and tolerability of rifapentine 1,200 mg is warranted OBJECTIVES The aims of this study were to ( 1 ) identify trends and risk factors for mycobacterial disease and ( 2 ) determine the effect of exp and ed access to isoniazid chemoprophylaxis on tuberculosis incidence . METHODS A prospect i ve observational cohort study was conducted among community-based injecting drug users ( IDUs ) ; 2960 IDUs ( 942 human immunodeficiency virus [ HIV ] seropositive ) were followed up from January 1988 to June 1994 . Directly observed chemoprophylaxis with twice-weekly isoniazid ( 10 to 15 mg/kg ) was offered to purified protein derivative ( PPD ) tuberculin-positive ( > or = 5-mm in duration diameter in HIV-seropositive subjects and > or = 10-mm diameter in HIV-seronegative subjects ) individuals but not to those with cutaneous anergy . Overall and annual incidence rates of disease due Mycobacterium tuberculosis , Mycobacterium avium complex , and other atypical mycobacteria were estimated using Poisson regression . RESULTS HIV seropositivity was the strongest risk factor for tuberculosis , M avium complex , and other mycobacterial disease ( relative risk [ RR ] , 3.8 , 17.2 , and 6.9 , respectively ) . Median CD4 lymphocyte cell counts for the three groups of mycobacterial disease were 0.17 , 0.03 , and 0.02 x 10(9)/L ( 167/microL , 30/microL , 18/microL ) within 6 months of diagnosis ( before or after ) . Overall incidence rates of tuberculosis , M avium complex disease , and other mycobacterial disease were 1.9 , 8.8 , and 2.7 per 1000 person-years , respectively . Tuberculosis incidence peaked in 1991 at six per 1000 person-years . However , after access to directly observed preventive therapy was exp and ed for tuberculin-positive subjects , incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994 . During this period the number of PPD-positive patients who completed at least 26 weeks of therapy ( or were still receiving isoniazid ) more than tripled ( from 21 to 70 ) . None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy . In addition , no tuberculosis developed among participants with cutaneous anergy . Calendar trends in risk for M avium complex and tuberculosis diverged after exp and ed access to isoniazid prophylaxis . Compared with 1988 - 1989 , risk of M avium complex increased sevenfold . Tuberculosis risk fell 83 % from the peak risk in 1990 - 1991 . CONCLUSIONS Exp and ed access to directly observed isonazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83 % drop in tuberculosis incidence , while in the same period M avium complex incidence significantly increased . These population -based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous energy BACKGROUND Rifapentine has a long half-life in serum , which suggests a possible treatment once a week for tuberculosis . We aim ed to compare rifapentine and isoniazid once a week with rifampicin and isoniazid twice a week . METHODS We did a r and omised , multicentre , open-label trial in the USA and Canada of HIV-negative people with drug-susceptible pulmonary tuberculosis who had completed 2 months of a 6-month treatment regimen . We r and omly allocated patients directly observed treatment with either 600 mg rifapentine plus 900 mg isoniazid once a week or 600 mg rifampicin plus 900 mg isoniazid twice a week . Primary outcome was failure/relapse . Analysis was by intention to treat . FINDINGS 1004 patients were enrolled ( 502 per treatment group ) . 928 successfully completed treatment , and 803 completed the 2-year 4-month study . Crude rates of failure/relapse were 46/502 ( 9.2 % ) in those on rifapentine once a week , and 28/502 ( 5.6 % ) in those given rifampicin twice a week ( relative risk 1.64 , 95 % CI 1.04 - 2.58 , p=0.04 ) . By proportional hazards regression , five characteristics were independently associated with increased risk of failure/relapse : sputum culture positive at 2 months ( hazard ratio 2.8 , 95 % CI 1.7 - 4.6 ) ; cavitation on chest radiography ( 3.0 , 1.6 - 5.9 ) ; being underweight ( 3.0 , 1.8 - 4.9 ) ; bilateral pulmonary involvement ( 1.8 , 1.0 - 3.1 ) ; and being a non-Hispanic white person ( 1.8 , 1.1 - 3.0 ) . Adjustment for imbalances in 2-month culture and cavitation diminished the association of treatment group with outcome ( 1.34 ; 0.83 - 2.18 ; p=0.23 ) . Of participants without cavitation , rates of failure/relapse were 6/210 ( 2.9 % ) in the once a week group and 6/241 ( 2.5 % ) in the twice a week group ( relative risk 1.15 ; 95 % CI 0.38 - 3.50 ; p=0.81 ) . Rates of adverse events and death were similar in the two treatment groups . INTERPRETATION Rifapentine once a week is safe and effective for treatment of pulmonary tuberculosis in HIV-negative people without cavitation on chest radiography . Clinical , radiographic , and microbiological data help to identify patients with tuberculosis who are at increased risk of failure or relapse when treated with either regimen SETTING A prison in northern Taiwan . OBJECTIVE To compare safety and the completion rate of the 4-month daily rifampicin regimen ( 4R ) vs. the st and ard 6-month daily isoniazid regimen ( 6H ) for latent tuberculosis infection ( LTBI ) in prison inmates . DESIGN This was an open-label r and omised trial among human immunodeficiency virus negative male inmates . Inmates without active tuberculosis ( TB ) who tested positive for both the tuberculin skin test and QuantiFERON ® -TB Gold In-Tube were eligible , but those with baseline glutamic pyruvic transaminase ( GPT ) levels ≥ 120 U/l , bilirubin levels ≥ 2.4 U/l or a platelet count < 150 k/mm(3 ) were excluded . The primary endpoint was any adverse event that result ed in discontinuation of LTBI treatment . RESULTS Participants ( n = 373 ; 14 % hepatitis B surface antigen positive , 21 % anti-hepatitis C virus [ HCV ] positive ) were r and omised ( stratified by hepatitis B virus , HCV status and 2-year prison term ) to receive either 4R or 6H under directly observed treatment . The 4R group ( n = 190 ) was less likely to experience an adverse event leading to discontinuation of treatment ( 2 % vs. 12 % , P < 0.001 for all adverse events ; 0 % vs. 8 % , P < 0.001 for hepatotoxicity ) , and more likely to complete LTBI treatment ( 86 % vs. 78 % , P = 0.041 ) , compared with the 6H group ( n = 183 ) . CONCLUSIONS 4R is safer and has a higher completion rate than 6H as treatment for LTBI among male prison inmates Substance abuse is associated with high risk for tuberculosis ( TB ) and poor adherence to medication regimens . This study compared completion rates for isoniazid ( INH ) preventive therapy for injection drug users ( IDUs ) r and omly assigned to methadone treatment combined with directly observed preventive treatment ( DOPT ) versus those assigned to routine TB clinic referral without methadone treatment . One hundred and eleven opioid-dependent patients with latent TB were assigned to one of three 6-month treatment conditions : st and ard methadone treatment including substance abuse counseling combined with daily INH DOPT ( n=37 ) ; minimal methadone treatment without counseling , also combined with daily INH DOPT ( n=35 ) ; or routine care referral to TB clinic for monthly INH supplies without DOPT and without methadone treatment ( n=39 ) . INH completion rates were 77.1 % for minimal methadone and 59.5 % for st and ard methadone , as compared with only 13.5 % for routine care ( P<0.0001 ) . Mean duration of INH treatment retention was 5.7 , 5.0 and 1.6 months , respectively ( P<0.0001 ) . TB incidence at 4-year follow-up was 0 of 54 subjects who completed preventive therapy versus 2 of 57 who failed to complete . One of these two had been assigned to routine care , and the other to minimal methadone . In conclusion , INH retention time and completion rates were significantly improved by methadone treatment combined with observed INH , whether or not substance abuse counseling was provided . The results of this study indicate that methadone treatment offers clear public health benefits when it is used to deliver preventive medical services Two isoniazid prophylaxis programs were conducted in the Bethel area of Alaska : a placebo-controlled trial started in 1957 , and a community-wide administration of isoniazid in 1964 . In both programs , the recommended dose of isoniazid was 4 to 8 mg per kg of body weight taken in a single daily dose for one year . Tuberculosis case rates in the period from 1964 through 1973 indicate that the effectiveness of isoniazid prophylaxis persisted through the fifteenth year after its administration . The results of this and other studies raise the possibility that six months of the st and ard daily dose of isoniazid may be sufficient for prophylaxis SETTING A medical facility for approximately 90,000 gold miners employed on 24 South African gold mines . OBJECTIVE To evaluate the effectiveness of rifampicin , isoniazid and pyrazinamide given for 3 months for the prevention of tuberculosis in men with silicosis . DESIGN A r and omised double-blind placebo controlled trial with active 4-year follow up of subjects by routine radiographic screening . RESULTS A total of 382 gold miners with silicosis were r and omised to receive rifampicin 600 mg , isoniazid 400 mg and pyrazinamide 1.25 g daily as Rifater or a placebo . These men have been followed for 4 years since the end of the treatment period . Eleven men who received the combination tablet and 15 men who received the placebo tablet have developed tuberculosis ( chi 2 df1 = 0.66 , P = 0.4 ) . CONCLUSION This multi-drug short course chemoprophylaxis regimen has failed to prevent tuberculosis in miners with silicosis . Even if a larger study had demonstrated a statistically significant effect of the regimen as compared with placebo , the rate of tuberculosis in the men who received the three-drug regimen was unacceptably high BACKGROUND Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination . The current st and ard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion . METHODS We conducted an open-label , r and omized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine ( 900 mg ) plus isoniazid ( 900 mg ) ( combination-therapy group ) with 9 months of self-administered daily isoniazid ( 300 mg ) ( isoniazid-only group ) in subjects at high risk for tuberculosis . Subjects were enrolled from the United States , Canada , Brazil , and Spain and followed for 33 months . The primary end point was confirmed tuberculosis , and the noninferiority margin was 0.75 % . RESULTS In the modified intention-to-treat analysis , tuberculosis developed in 7 of 3986 subjects in the combination-therapy group ( cumulative rate , 0.19 % ) and in 15 of 3745 subjects in the isoniazid-only group ( cumulative rate , 0.43 % ) , for a difference of 0.24 percentage points . Rates of treatment completion were 82.1 % in the combination-therapy group and 69.0 % in the isoniazid-only group ( P<0.001 ) . Rates of permanent drug discontinuation owing to an adverse event were 4.9 % in the combination-therapy group and 3.7 % in the isoniazid-only group ( P=0.009 ) . Rates of investigator-assessed drug-related hepatotoxicity were 0.4 % and 2.7 % , respectively ( P<0.001 ) . CONCLUSIONS The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate . Long-term safety monitoring will be important . ( Funded by the Centers for Disease Control and Prevention ; PREVENT TB Clinical Trials.gov number , NCT00023452 . ) Twelve years ago , a controlled trial of isonlazid prophylaxis was started in the Bethel area of Alaska . Six years ago , because of its demonstrated effectiveness , isoniazid prophylaxis was offered to the entire population . There were 1,349 persons in the controlled trial who were classified as having untreated , nonactive tuberculosis , and 1,567 such persons in the subsequent demonstration project . Over the six-year period after the controlled trial , persons with untreated , nonactive tuberculosis who took isoniazid well had 71 % less tuberculosis than those who took it poorly . Following the subsequent demonstration program , the reduction among those who took isoniazid well was 89 % . Preventive treatment of previously untreated , nonactive tuberculosis can make a major contribution to tuberculosis control among population s with a tuberculosis problem similar to that among Alaskan Eskimos Efficacy of preventive chemotherapy in tuberculosis-infected children depends to a great extend on medical compliance and drug tolerability . Two new short-course chemoprevention-regimes of tuberculosis -- four months Rifampin ( A ) and two months Rifampin plus Pyrazinamide (B)--were compared with the well established regimen of six months Isoniacid ( C ) . 150 children ( mean age 3.6 years with Tb conversion ) were r and omly allocated to these three regimens . 13 patients were non-compliant , in terms of interview , urinary INH-test strips , urine colour and prescription frequency : 7 in group C and 3 in group A and B , respectively . Adverse effects were observed in 5 patients : 3 in group C and 1 in group A and B. 1 child ( group B ) developed tuberculosis two years after stopping short course chemoprevention . Good compliance ( 94 % ) as well as neglectable risks of adverse effects ( 2 % ) justify further controlled studies to evaluate the efficacy of short course chemoprevention in childhood Context Isoniazid is hepatotoxic and must be taken for 9 months by patients with latent tuberculosis infection . Contribution In this trial comparing 4 months of rifampin therapy with 9 months of isoniazid therapy , patients who took rifampin had fewer adverse events and were more likely to complete treatment . Caution The investigators did not compare efficacy of the 2 treatments . Implication These safety and adherence data justify a larger trial to compare the efficacy of rifampin and isoniazid for latent tuberculosis infection . The Editors After detection and treatment of active tuberculosis cases , the next priority in tuberculosis control is the diagnosis and treatment of persons with latent tuberculosis infection ( LTBI ) who are at increased risk for active tuberculosis . Treatment of such individuals can provide individual and public health benefits ( 14 ) . The current recommended st and ard therapy in most countries is 9 months of isoniazid therapy ( 4 , 5 ) . The drug has more than 90 % efficacy if taken the entire 9 months ( 6 ) , but completion rates under routine practice conditions are about 50 % or less ( 79 ) . Another important disadvantage of isoniazid therapy is the occurrence of serious adverse events , particularly drug-induced hepatitis ( 10 ) . Drug-induced hepatitis was not recognized as a complication of isoniazid therapy in early trials involving more than 50000 participants ( 11 ) , but it was a frequent and potentially severe problem after isoniazid was recommended for tuberculosis prevention in 1970 ( 12 ) and was subsequently used more widely ( 13 , 14 ) . This complication makes close monitoring necessary , increasing costs . These problems have stimulated considerable interest in finding shorter and safer regimens for the treatment of LTBI ( 15 ) . One alternative , 2 months of daily rifampinpyrazinamide , was recommended in 2000 ( 4 ) on the basis of evidence from several trials ( 1618 ) . However , subsequent reports of severe and fatal hepatotoxicity ( 19 , 20 ) have rendered this regimen unacceptable for most patients . The remaining recommended alternative is 4 months of daily rifampin , but published outcome information is limited and systematic review s on this regimen have not been done . In the only published trial that compared 3 months of daily rifampin therapy with 6 months of daily isoniazid therapy in 332 patients , efficacy and safety were similar ( 21 ) . In 2 uncontrolled case series , 6 months of daily rifampin was well tolerated in 49 homeless persons in Boston ( 22 ) and in 157 high school students in California ( 23 ) . Two nonr and omized studies have described better treatment completion and less hepatotoxicity with 4 months of rifampin than with 9 months of isoniazid under program conditions ( 8 , 9 ) . However , rifampin has been reported to cause other problemsnotably drug interactions ( 24 ) , a flu-like syndrome ( 24 ) , and rare hematologic problems ( immune-mediated thrombocytopenia and anemia ) ( 25 ) . Also , development of drug resistance is a theoretical concern . Given the experience with isoniazid and 2 months of rifampinpyrazinamide , both of which were thought to be safe on the basis of early studies but caused deaths when used more widely , we design ed a multicenter , r and omized trial to compare the frequency of serious adverse events and treatment completion rates in patients given 4 months of daily rifampin or 9 months of daily isoniazid for LTBI . Methods Setting , Study Sample , and R and omization This open-label trial was conducted at 9 university-affiliated hospitals : 7 in Canada and 1 each in Saudi Arabia and Brazil . We considered patients to be eligible if they were age 18 years or older and had a documented tuberculin skin test that met the criteria for a positive result ( 5 ) and if their primary treating physician initially recommended isoniazid for LTBI following national or international guidelines ( 4 , 26 , 27 ) . Patients were ineligible if they were contacts of isoniazid- or rifampin-resistant cases ( 28 ) , were allergic to isoniazid or rifamycins , or were taking concomitant medications that had clinical ly significant potential drug interactions that could not be easily managed . To ensure a realistic assessment of adverse events , we considered all other adults eligible , regardless of age or additional risk factors for adverse events , as long as their treating physician felt that therapy for LTBI was indicated . A Web-based program verified eligibility and r and omly assigned participants ( by using a r and om-number generator ) , after they signed informed consent , to 4 months of daily rifampin ( 10 mg per kg of body weight , up to 600 mg/d ) or 9 months of daily isoniazid ( 5 mg/kg , up to 300 mg/d ) in blocks of varying size , stratified by center . A team at the University of Sherbrooke , Sherbrooke , Quebec , Canada , prepared the Web-based program and allocation sequence . Study personnel in the different centers enrolled and registered participants , obtained consent , verified assignment , and administered treatment . All study participants signed informed consent before r and omization . Institutional review boards in each participating institution approved the study . Processes and Outcomes Patients were followed in routine fashion by their usual treating physician , who made all management decisions , including discontinuation of therapy . By study protocol , all patients had blood tests ( complete blood count , liver aminotransferase levels [ aspartate aminotransferase and alanine aminotransferase ] , and bilirubin level ) before and after 1 and 2 months of therapy and were seen every month for the first 4 months of therapy and ( for those receiving 9 months of isoniazid ) at physician discretion every 6 weeks thereafter . Adverse events could be detected at any time throughout the course of therapy . When the treating physician suspected an adverse event and therapy was suspended , investigations , including blood tests , were performed according to study protocol . The treating physician decided whether to discontinue , rechallenge with , or restart the study therapy , although the protocol specified that participants with grade 3 or 4 adverse events ( Appendix Table 1 ) were not to be rechallenged . When all investigations were complete , and if therapy was permanently discontinued in response to the event , the patient 's clinical course and results of investigations and rechallenge ( if any ) were made available to a 3-member independent review panel who were blinded to study drug . If therapy was resumed ( for example , after resolution of a grade 1 or 2 adverse event ) and the event did not recur , the patient 's information was not review ed by the panel . Appendix Table 1 . Grading System for Adverse Events Used by Independent Panel Each review panel member had substantial experience and expertise in clinical and epidemiologic aspects of tuberculosis , and each independently judged the type and severity of the adverse events and its likely relationship to the study drug . We grade d adverse events as recommended by the National Cancer Institute Common Terminology Criteria for Adverse Events , version 2.0 ( 29 ) ( Appendix Table 1 ) . Liver aminotransferase levels that increased to 5 to 10 or 3 to 10 times the upper limit of normal in the presence of compatible symptoms met criteria for grade 3 hepatotoxicity , whereas those that exceeded 10 times the upper limit of normal met criteria for grade 4 toxicity ( 30 ) . In the event of disagreement , panel members re- review ed the information ; if disagreement remained , the majority opinion was used . The study 's primary outcome was the frequency of grade 3 or 4 adverse events that result ed in study drug discontinuation and were judged by the review panel to be probably related to the drug ( Appendix Table 1 ) . The study 's secondary outcome was on-time treatment completion , defined as taking more than 80 % of doses within a maximum of 150 days for 4 months of rifampin or 301 days ( 43 weeks ) for 9 months of isoniazid . Doses taken were measured with the Medical Event Monitoring System , an electronic device in the pill container cap that recorded the date and time of bottle opening ( APREX Corporation , Fremont , California ) . Other secondary outcomes included grade 1 or 2 adverse events that were judged by the independent panel to be probably study drugrelated and result ed in permanent discontinuation of therapy and changes in liver aminotransferase levels and leukocyte and platelet counts before and 1 and 2 months after beginning treatment . Statistical Analysis We initially calculated a trial sample size by assuming that the frequency of serious adverse events would be significantly higher with rifampin . We calculated that 630 patients per group would provide 90 % power ( 2-sided = 0.05 ) to detect a difference between frequency of adverse events of 9 % and 4 % in the rifampin and isoniazid groups , respectively . This estimate also accounted for an anticipated 15 % dropout rate during therapy . Because we were unsure about the actual frequency of adverse events with rifampin , we also noted that 630 patients per group provided 80 % power to detect a statistically significant difference between rates of adverse events in the 2 groups if the event rates were 2 % and 5 % in the rifampin and isoniazid groups , respectively , and the dropout rate was 15 % . To ensure safety of study participants , we planned 3 interim analyses for when 25 % , 50 % , and 75 % of the planned total sample size had been r and omly assigned . The data safety and monitoring board , blinded to the identity of the 2 groups , review ed the overall rate of serious adverse events in each group . If the rate was significantly higher in 1 group , then the results were unblinded and the data safety and monitoring board made a decision , based on clinical judgment and statistical input , about stopping or continuing the trial . We used an value of 0.01 to account for multiple testing ( 31 ) . We reported summary baseline liver function test results for each group as the ratio of each patient 's test result to the upper As knowledge of the epidemiology of tuberculosis in Greenl and has increased , it has become evident that the majority of cases develop long after the primary infection and that it would therefore be valuable from the public health point of view if the disease rate among naturally infected persons could be reduced . To examine the possibility of achieving this , a double-blind drug trial with isoniazid and a placebo was conducted among some 70 % of the adult population of western Greenl and . The results show that throughout the six years of the study the incidence of tuberculosis was lower in the group treated with isoniazid and that this reduction occurred whether the initial X-rays pictures were normal or showed suspicious or healed lesions . It is concluded that chemoprophylaxis programmes should probably be administered only to selected groups of the population . The delimitation of such groups is discussed on the basis of their tuberculosis risk and of the expected yield in terms of reduction in tuberculosis prevalence CONTEXT Fixed-dose combinations ( FDCs ) of drugs for treatment of tuberculosis have been advocated to prevent the emergence of drug resistance . OBJECTIVE To assess the efficacy and safety of a 4-drug FDC for the treatment of tuberculosis . DESIGN , SETTING , AND PATIENTS The Study C trial , a parallel-group , open-label , noninferiority , r and omized controlled trial conducted in 11 sites in Africa , Asia , and Latin America between 2003 and 2008 . Patients were 1585 adults with newly diagnosed smear-positive pulmonary tuberculosis . INTERVENTIONS Patients were r and omized to receive daily treatment with 4 drugs ( rifampicin , isoniazid , pyrazinamide , ethambutol ) given as an FDC ( n = 798 patients ) or separately ( n = 787 ) in the 8-week intensive phase of treatment . MAIN OUTCOME MEASURE Favorable treatment outcome , defined as negative culture result at 18 months post r and omization and not having already been classified as unfavorable . Noninferiority was dependent on consistent results from a per- protocol and modified intention-to-treat analysis , using 2 different models for the latter , classifying all changes of treatment or refusal to continue treatment ( eg , bacteriological failure/relapse , adverse event , default , drug resistance ) as unfavorable ( model 1 ) and classifying changes of treatment for reasons other than therapeutic outcomes according to their 18-month bacteriological outcome if available ( post hoc model 2 ) . The prespecified noninferiority margin was 4 % . RESULTS In the per- protocol analysis , 555 of 591 patients ( 93.9 % ) had a favorable outcome in the FDC group vs 548 of 579 ( 94.6 % ) in the separate-drugs group ( risk difference , -0.7 % [ 90 % confidence interval { CI } , -3.0 % to 1.5 % ] ) . In the model 1 analysis , 570 of 684 patients ( 83.3 % ) had a favorable outcome in the FDC group vs 563 of 664 ( 84.8 % ) in the separate-drugs group ( risk difference , -1.5 % [ 90 % CI , -4.7 % to 1.8 % ] ) . In the post hoc model 2 analysis , 591 of 658 patients ( 89.8 % ) in the FDC group and 589 of 647 ( 91.0 % ) in the separate-drugs group had a favorable outcome ( risk difference , -1.2 % [ 90 % CI , -3.9 % to 1.5 % ] ) . Adverse events related to trial drugs were similarly distributed among treatment groups . CONCLUSIONS Compared with a regimen of separately administered drugs , a 4-drug FDC regimen for treatment of tuberculosis satisfied prespecified noninferiority criteria in 2 of 3 analyses . Although the results do not demonstrate full noninferiority of the FDCs compared with single drugs given separately using the strict definition applied in this trial , use of FDCs is preferred because of potential advantages associated with the administration of FDCs compared with separate-drug formulations . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00216333 BACKGROUND Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus ( HIV ) is efficacious , but few patients around the world receive such treatment . We evaluated three new regimens for latent tuberculosis that may be more potent and durable than st and ard isoniazid treatment . METHODS We r and omly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine ( 900 mg ) plus isoniazid ( 900 mg ) weekly for 12 weeks , rifampin ( 600 mg ) plus isoniazid ( 900 mg ) twice weekly for 12 weeks , isoniazid ( 300 mg ) daily for up to 6 years ( continuous isoniazid ) , or isoniazid ( 300 mg ) daily for 6 months ( control group ) . The primary end point was tuberculosis-free survival . RESULTS The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter . Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine-isoniazid group , 2.9 per 100 person-years in the rifampin-isoniazid group , and 2.7 per 100 person-years in the continuous-isoniazid group , as compared with 3.6 per 100 person-years in the control group ( P>0.05 for all comparisons ) . Serious adverse reactions were more common in the continuous-isoniazid group ( 18.4 per 100 person-years ) than in the other treatment groups ( 8.7 to 15.4 per 100 person-years ) . Two of 58 isolates of Mycobacterium tuberculosis ( 3.4 % ) were found to have multidrug resistance . CONCLUSIONS On the basis of the expected rates of tuberculosis in this population of HIV-infected adults , all secondary prophylactic regimens were effective . Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; Clinical Trials.gov number , NCT00057122 . ) BACKGROUND In accordance with WHO guidelines , people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test , but duration of prophylaxis is restricted to 6 months . We aim ed to assess effectiveness of extended isoniazid therapy . METHODS In our r and omised , double-blind , placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana . Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia . Eligible individuals were r and omly allocated ( 1:1 ) to receive 6 months ' open-label isoniazid followed by 30 months ' masked placebo ( control group ) or 6 months ' open-label isoniazid followed by 30 months ' masked isoniazid ( continued isoniazid group ) on the basis of a computer-generated r and omisation list with permuted blocks of ten at each clinic . Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups . Cox regression models were used to estimate the effect of antiretroviral therapy . The trial is registered at Clinical Trials.gov , number NCT00164281 . FINDINGS Between Nov 26 , 2004 , and July 3 , 2009 , we recorded 34 ( 3·4 % ) cases of incident tuberculosis in 989 participants allocated to the control group and 20 ( 2·0 % ) in 1006 allocated to the continued isoniazid group ( incidence 1·26 % per year vs 0·72 % ; hazard ratio 0·57 , 95 % CI 0·33 - 0·99 , p=0·047 ) . Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid . Participants who were tuberculin skin test positive ( ie , ≥5 mm in duration ) at enrolment received a substantial benefit from continued isoniazid treatment ( 0·26 , 0·09 - 0·80 , p=0·02 ) , whereas participants who were tuberculin skin test-negative received no significant benefit ( 0·75 , 0·38 - 1·46 , p=0·40 ) . By study completion , 946 ( 47 % ) of 1995 participants had initiated antiretroviral therapy . Tuberculosis incidence was reduced by 50 % in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy ( adjusted hazard ratio 0·50 , 95 % CI 0·26 - 0·97 ) . Severe adverse events and death were much the same in the control and continued isoniazid groups . INTERPRETATION In a tuberculosis-endemic setting , 36 months ' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection , and chiefly benefited those who were tuberculin skin test positive . FUNDING US Centers for Disease Control and Prevention and US Agency for International Development |
1,117 | 31,776,827 | This review highlights the lack of st and ardization of the TTD approach for the analysis of PRO data in RCTs . | The time to deterioration ( TTD ) approach has been proposed as a modality of longitudinal analysis of patient-reported outcomes ( PROs ) in cancer r and omized clinical trials ( RCTs ) .
The objective of this study was to perform a systematic review of how the TTD approach has been used in phase III RCTs to analyze longitudinal PRO data . | BACKGROUND In the phase 3 KEYNOTE-024 trial , treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive , advanced non-small-cell lung cancer ( NSCLC ) with a programmed cell death-lig and 1 ( PD-L1 ) tumour proportion score of 50 % or greater ( PD-L1-positive ) . Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes ( PROs ) . METHODS In this multicentre , international , r and omised , open-label , phase 3 trial , we recruited patients with treatment-naive , stage IV NSCLC in 102 sites in 16 countries . Eligible patients had measurable disease ( per RECIST version 1.1 ) and an Eastern Cooperative Oncology Group ( ECOG ) performance status 0 or 1 . Patients were r and omly assigned ( 1:1 ) via an interactive voice response system and integrated web response system to receive either pembrolizumab 200 mg every 3 weeks ( 35 cycles ) or investigator-choice platinum-doublet chemotherapy ( 4 - 6 cycles or until documented disease progression or unacceptable toxicity ) . R and omisation was stratified according to geography , ECOG performance status , and histology . PROs were assessed at day 1 of cycles 1 - 3 , every 9 weeks thereafter , at the treatment discontinuation visit , and at the 30-day safety assessment visit using the European Organisation for the Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire Core 30 items ( QLQ-C30 ) , the EORTC Quality of Life Question naire Lung Cancer 13 items ( QLQ-LC13 ) , and the European Quality of Life 5 Dimensions-3 Level ( EQ-5D-3L ) question naire . The key exploratory PRO endpoints ( analysed for all patients who received at least one dose of study treatment and completed at least one PRO instrument at at least one timepoint ) were baseline-to-week-15 change in the QLQ-C30 global health status (GHS)/ quality -of-life ( QOL ) score and time to deterioration of the composite of cough , chest pain , and dyspnoea in the QLQ-LC13 . This study is registered with Clinical Trials.gov , number NCT02142738 , and is ongoing but no longer enrolling patients . FINDINGS Between Sept 19 , 2014 , and Oct 29 , 2015 , 305 patients were r and omly assigned to pembrolizumab ( n=154 ) or chemotherapy ( n=151 ) . Three patients in each group did not complete any PRO instruments at any timepoints , and so 299 patients were included in the full analysis set . Of these patients , one in each group did not complete any PRO instruments before week 15 , and so were not included in analyses of change from baseline to week 15 . PRO compliance was greater than 90 % at baseline and approximately 80 % at week 15 for both groups . Least-squares mean baseline-to-week-15 change in QLQ-C30 GHS/QOL score was 6·9 ( 95 % CI 3·3 to 10·6 ) for pembrolizumab and -0·9 ( -4·8 to 3·0 ) for chemotherapy , for a difference of 7·8 ( 2·9 to 12·8 ; two-sided nominal p=0·0020 ) . Fewer pembrolizumab-treated patients had deterioration in the QLQ-LC13 composite endpoint than did chemotherapy-treated patients ( 46 [ 31 % ] of 151 patients vs 58 [ 39 % ] of 148 patients ) . Time to deterioration was longer with pembrolizumab than with chemotherapy ( median not reached [ 95 % CI 8·5 to not reached ] vs 5·0 months [ 3·6 to not reached ] ; hazard ratio 0·66 , 95 % CI 0·44 - 0·97 ; two-sided nominal p=0·029 ) . INTERPRETATION Pembrolizumab improves or maintains health-related QOL compared with that for chemotherapy , and might represent a new first-line st and ard of care for PD-L1-expressing , advanced NSCLC . FUNDING Merck & Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality . Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials BACKGROUND In the phase 3 RADIANT-4 trial , everolimus increased progression-free survival compared with placebo in patients with advanced , progressive , non-functional , well-differentiated gastrointestinal or lung neuroendocrine tumours ( NETs ) . We now report the health-related quality of life ( HRQOL ) secondary endpoint . METHODS RADIANT-4 is a multicentre , r and omised , double-blind , placebo-controlled , phase 3 trial done in 97 centres in 25 countries worldwide . Adults ( aged ≥18 years ) were eligible for the study if they had pathologically confirmed , advanced ( unresectable or metastatic ) , non-functional , well-differentiated ( grade 1 or 2 ) NETs of lung or gastrointestinal origin . Patients were r and omly allocated ( 2:1 ) using block r and omisation ( block size of three ) by an interactive voice response system to receive oral everolimus ( 10 mg per day ) or placebo , both with best supportive care , with stratification by tumour origin , WHO performance status , and previous somatostatin analogue treatment . HRQOL was assessed with the Functional Assessment of Cancer Therapy-General ( FACT-G ) question naire at baseline ( visit 2 , day 1 ) , every 8 weeks ( ± 1 week ) during the study for the first 12 months after r and omisation , and every 12 weeks thereafter until study drug discontinuation . The primary endpoint , reported previously , was progression-free survival assessed by central review ; HRQOL was a prespecified secondary endpoint . The prespecified secondary outcome measure was time to definitive deterioration ( ≥7 points ) in FACT-G total score . Analyses were done on the full analysis set , consisting of all r and omised patients , by intention to treat . Only data obtained while receiving the r and omly allocated treatment were included in this analysis . Enrolment for RADIANT-4 was completed on Aug 23 , 2013 , but the trial is ongoing pending final analysis of the key secondary endpoint of overall survival . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , 302 patients were enrolled ; 205 were r and omly allocated everolimus and 97 were assigned placebo . At baseline , 193 ( 94 % ) of 205 patients assigned everolimus and 95 ( 98 % ) of 97 allocated placebo had completed either fully or partly the FACT-G question naire ; at week 48 , 70 ( 83 % ) of 84 patients assigned everolimus and 22 ( 85 % ) of 26 allocated placebo completed FACT-G. Median time to definitive deterioration in FACT-G total score was 11·27 months ( 95 % CI 9·27 - 19·35 ) with everolimus and 9·23 months ( 5·52-not estimable ) with placebo ( adjusted hazard ratio 0·81 , 95 % CI 0·55 - 1·21 ; log-rank p=0·31 ) . INTERPRETATION HRQOL was maintained for patients with advanced , non-functional , gastrointestinal or lung NETs , with no relevant differences noted between the everolimus and placebo groups . In view of the previous RADIANT-4 findings of longer progression-free survival with everolimus , our findings suggest that everolimus delays disease progression while preserving overall HRQOL , even with the usual toxic effects related to active targeted drug treatment for cancer . FUNDING Novartis Pharmaceuticals Purpose In the phase III KEYNOTE-045 study ( Clinical Trials.gov identifier : NCT02256436 ) , pembrolizumab significantly prolonged overall survival compared with investigator 's choice of chemotherapy in patients with previously treated advanced urothelial cancer . Here , we report the results of health-related quality -of-life ( HRQoL ) analyses from the KEYNOTE-045 trial . Patients and Methods Patients were r and omly assigned 1:1 to pembrolizumab 200 mg or investigator 's choice of docetaxel 75 mg/m2 , paclitaxel 175 mg/m2 , or vinflunine 320 mg/m2 administered intravenously every 3 weeks . Key prespecified HRQoL analyses were time to deterioration ( TTD ) and mean change from baseline to week 15 in European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 global health status/ quality -of-life score . Results Of 542 patients who were r and omly assigned , 519 were included in HRQoL analyses ( pembrolizumab , n = 266 ; chemotherapy , n = 253 ) . HRQoL compliance was > 95 % at baseline and approximately 88 % at week 15 for both groups . Pembrolizumab prolonged TTD in global health status/ quality -of-life score compared with chemotherapy ( median , 3.5 months v 2.3 months ; hazard ratio , 0.72 ; nominal one-sided P = .004 ) . Mean ( 95 % CI ) change from baseline to week 15 in global health status/ quality -of-life score was 0.69 ( -2.40 to 3.77 ) with pembrolizumab and -8.36 ( -11.84 to -4.89 ) with chemotherapy ( mean difference , 9.05 points ; 95 % CI , 4.61 to 13.50 ; nominal two-sided P < .001 ) . Conclusion Pembrolizumab prolonged TTD in HRQoL compared with chemotherapy . Patients who were treated with pembrolizumab had stable or improved global health status/ quality of life , whereas those who were treated with investigator 's choice of chemotherapy experienced declines in global health status/ quality of life . Combined with efficacy and safety outcomes , these data support pembrolizumab as st and ard of care for patients with platinum-refractory advanced urothelial cancer In the Intergroupe Francophone de Cancérologie Thoracique 0501 trial the carboplatin-paclitaxel chemotherapy increased toxicity ( most frequent , decreased neutrophil count , asthenia ) . We longitudinally compared health-related quality of life ( HRQoL ) of the two treatment arms . In total , 451 patients aged 70–89 years with advanced non-small cell lung cancer ( NSCLC ) were r and omly assigned to receive carboplatin plus paclitaxel or vinorelbine or gemcitabine . HRQoL was assessed by means of the European Organisation for Research and Treatment of Cancer QLQ-C30 question naire at baseline , week 6 and week 18 . Using a five-point decrease as the minimal clinical ly important difference , patients treated with the chemotherapy doublet exhibited a significant longer time until definitive deterioration ( TUDD ) for two HRQoL dimensions : physical functioning ( median TUDD : 2.04 for the doublet versus 1.71 months for monotherapy ; log-rank p=0.01 ) and nausea and vomiting ( median : not reached versus 4.83 , respectively ; log-rank p=0.046 ) . Cox multivariate analysis revealed the carboplatin and paclitaxel arm to be independently associated with longer TUDD for these two HRQoL dimensions . In addition , TUDD did n't significantly differ between the two arms for all the other HRQoL dimensions . The chemotherapy doublet did not reduce TUDD in elderly patients with advanced NSCLC . Moreover , TUDD was prolonged for two HRQoL dimensions , namely physical functioning and nausea and vomiting . Carboplatin plus paclitaxel chemotherapy does not reduce quality of life in elderly patients with advanced NSCLC Abstract Purpose Evaluate patient-reported outcomes ( PROs ) for postmenopausal women with hormone receptor-positive ( HR+ ) , human epidermal growth factor receptor 2-negative ( HER2− ) advanced breast cancer treated with first-line ribociclib plus letrozole . Methods In the phase III MONALEESA-2 study ( NCT01958021 ) , 668 patients were r and omized 1:1 to ribociclib ( 600 mg/day ; 3-weeks-on/1-week-off ) plus letrozole ( 2.5 mg/day ) or placebo plus letrozole . PROs were assessed using the European Organisation for Research and Treatment of Cancer core quality -of-life ( EORTC QLQ-C30 ) and breast cancer-specific ( EORTC QLQ-BR23 ) question naires . Changes from baseline and time to deterioration in health-related quality of life ( HRQoL ) were analyzed using linear mixed-effect and stratified Cox regression models , respectively . Exploratory analysis of area-under-the-curve for change from baseline in pain score ( AUC-pain ) was performed . Results On-treatment HRQoL scores were consistently maintained from baseline and were similar between arms . A clinical ly meaningful ( > 5 points ) reduction in pain score was observed as early as Week 8 and was maintained up to Cycle 15 in the ribociclib arm . A statistically significant increase in mean AUC-pain was also observed in the ribociclib arm . Scores for all other EORTC QLQ-C30 and EORTC QLQ-BR23 domains were maintained from baseline and were similar between arms . Conclusions HRQoL was consistently maintained from baseline in postmenopausal women with HR+ , HER2− advanced breast cancer receiving ribociclib plus letrozole and was similar to that observed in the placebo plus letrozole arm . Together with the improved clinical efficacy and manageable safety profile , these PRO results provide additional support for the benefit of ribociclib plus letrozole in this patient population Introduction In the phase III LUX‐Lung 8 trial , afatinib significantly improved progression‐free survival ( PFS ) and overall survival ( OS ) versus erlotinib in patients with squamous cell carcinoma ( SCC ) of the lung progressing during or after platinum‐based chemotherapy . Patient‐reported outcomes ( PROs ) and health‐related quality of life ( QoL ) in these patients are presented . Patients and Methods Patients ( n = 795 ) were r and omized 1:1 to oral afatinib ( 40 mg/d ) or erlotinib ( 150 mg/d ) . PROs were collected ( baseline , every 28 days until progression , 28 days after discontinuation ) using the European Organization for Research and Treatment of Cancer QoL question naire and lung cancer‐specific module . The percentage of patients improved during therapy , time to deterioration ( TTD ) , and changes over time were analyzed for prespecified lung cancer‐related symptoms and global health status (GHS)/QoL. Results Question naire compliance was 77.3 % to 99.0 % and 68.7 % to 99.0 % with afatinib and erlotinib , respectively . Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL ( 36 % vs. 28 % ; P = .041 ) and cough ( 43 % vs. 35 % ; P = .029 ) . Afatinib significantly delayed TTD in dyspnea ( P = .008 ) versus erlotinib , but not cough ( P = .256 ) or pain ( P = .869 ) . Changes in mean scores favored afatinib for cough ( P = .0022 ) , dyspnea ( P = .0007 ) , pain ( P = .0224 ) , GHS/QoL ( P = .0320 ) , and all functional scales . Differences in adverse events between afatinib and erlotinib , specifically diarrhea , did not affect GHS/QoL. Conclusion In patients with SCC of the lung , second‐line afatinib was associated with improved prespecified disease‐related symptoms and GHS/QoL versus erlotinib , complementing PFS and OS benefits with afatinib . Micro‐ Abstract The effect of treatment on health‐related quality of life ( HRQoL ) is an important consideration for patients . In the LUX‐Lung 8 trial , second‐line afatinib improved survival outcomes versus erlotinib in patients with squamous cell carcinoma of the lung . In this report , afatinib was also associated with improvements in disease‐related symptoms and HRQoL versus erlotinib , contributing to the overall clinical benefit of afatinib BACKGROUND A recent prospect i ve r and omised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy ( CRT ) regimens for inoperable non-metastatic oesophageal cancer patients . This secondary analysis aim ed to describe the impact of CRT on health-related quality of life ( HRQOL ) , physical functioning , dysphagia , fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival . PATIENTS AND METHODS A total of 267 patients were r and omly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1 . HRQOL was prospect ively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Question naire version 3.0 with the oesophageal cancer module ( QLQ-OES18 ) . RESULTS Both groups showed high baseline compliance . Subsequently , compliance reduced to 41 % at the 6-month follow-up . Baseline HRQOL scores showed no statistical differences between treatment arms . During treatment , both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea , although dysphagia moderately improved in the fluorouracil-cisplatin arm only ( p = 0.047 ) . During follow-up , HRQOL scores revealed no significant differences between chemotherapy regimens . Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia ( p = 0.017 ) with a greater decrease in dysphagia in the fluorouracil-cisplatin group . Time until definitive deterioration analysis showed no significant differences in global HRQOL , functional or main symptom domains . However , time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss ( p = 0.002 ) , QLQ-OES-18 pain ( p = 0.008 ) , trouble swallowing saliva ( p = 0.011 ) and trouble talking ( p = 0.020 ) . CONCLUSION Analyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil-cisplatin regimen as part of definitive CRT In patients with advanced melanoma in the CheckMate 066 study , baseline health-related quality of life ( HRQoL ) with nivolumab was maintained over time , with statistically significant and clinical ly meaningful improvements in some exploratory analyses , and no HRQoL improvements with dacarbazine . Added to the survival benefit of nivolumab , the benefit-to-risk ratio favors nivolumab over dacarbazine INTRODUCTION The LUME-Lung 1 trial ( NCT00805194 ; Study 1199.13 ) demonstrated a significant overall survival ( OS ) advantage for nintedanib plus docetaxel compared with placebo plus docetaxel as second-line therapy for patients with advanced non-small cell lung cancer ( NSCLC ) and adenocarcinoma histology . Patient-reported outcomes ( PROs ) for symptoms and health-related quality of life ( QoL ) are reported here . METHODS PROs were assessed at screening , on Day 1 of each 21-day treatment cycle , at the end of active treatment , and at the first follow-up visit . PRO instruments were the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and Lung Cancer-13 supplement , and the EuroQol disease-generic question naire ( EQ-5D and EQ-VAS ) . Analyses of PRO items for lung cancer-specific symptoms of cough , dyspnoea and pain were prespecified . RESULTS Rates of question naire completion were high . There was no significant difference in time to deterioration of global health status/QoL , or symptoms of cough , dyspnoea or pain , between the treatment groups for both the overall study population and the adenocarcinoma population . Time to deterioration of some gastrointestinal events was shorter with nintedanib versus placebo . Longitudinal analysis for the adenocarcinoma population showed comparable changes between the groups in symptom scores over time , with numerical differences in favour of nintedanib for cough and pain scales , and significant reductions in some pain items with nintedanib versus placebo . There was no statistically significant difference in EQ-5D or EQ-VAS between the groups . CONCLUSION The significant OS benefit observed with the addition of nintedanib to docetaxel therapy was achieved with no detrimental effect on patient self-reported This report aim ed to provide the full results of QoL assessment in INFORM study . QoL was assessed by FACT-L question naire . QoL improvement ratio in gefitinib arm was higher than placebo arm ( FACT-L : 46 % vs. 22 % , p < 0.001 ; TOI : 41 % vs. 18 % , p < 0.001 ; LCS : 46 % vs. 22 % , p < 0.001 ) . Gefitinib prolonged time-to-worsening of QoL ( FACT-L : 2.8 m vs 1.4 m , p = 0.019 ; TOI : 3.5 m vs 1.4 m , p = 0.006 ; LCS : 2.8 vs 1.4 m , p = 0.028 ) . Patients with an improvement in QoL had longer PFS ( FACT-L : 9.4 m vs. 2.8 m vs. 2.7 m , P < 0.001 ; TOI : 9.9 m vs. 2.8 m vs. 2.1 m , P < 0.001 ; LCS : 9.4 m vs. 2.9 m vs. 2.1 m , P < 0.001 ) and OS ( FACT-L : 25.4 m vs. 19.9 m vs. 14.4 m , P = 0.003 ; TOI : 25.7 m vs. 19.0 m vs. 12.7 m , P = 0.002 ; LCS : 25.4 m vs. 19.3 m vs. 14.7 m , P = 0.004 ) compared with patients with stable or worsened QoL. Furthermore , in patients with good QoL at baseline , the treatment of gefitinib could n’t improve OS compared to placebo , whereas patients with low QoL experienced marginal significant improvement in OS ( 20.6 m vs 14.4 , p = 0.051 ) . Our study indicated that gefitinib could improve patients ’ QoL , confirmed the prognostic value of QoL changes during treatment , and implied patients with low QoL at baseline may be the potential population which will gain OS benefit from maintenance EGFR-TKI therapy Introduction : In the phase III , LUX-Lung 6 trial , afatinib prolonged progression-free survival ( PFS ) versus cisplatin/gemcitabine in Asian patients with epidermal growth factor receptor ( EGFR ) mutation-positive non – small-cell lung cancer ( NSCLC ) . This article provides detailed assessment s of patient-reported outcomes ( PROs ) , a LUX-Lung 6 secondary end point , and explores the relationship between PFS and health-related quality of life ( QoL ) in these patients . Methods : Patients ( n = 364 ) were r and omized ( 2:1 ) to oral afatinib ( 40 mg/day ) or up to six cycles of cisplatin/gemcitabine ( 21-day cycle ; cisplatin 75 mg/m2 [ d1 ] ; gemcitabine 1000 mg/m2 [ d1,8 ] ) . QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Question naire and its lung cancer-specific module . The relationship between PFS ( investigator assessment and independent review ) and QoL was evaluated using analysis of covariance and a longitudinal model . Results : More patients treated with afatinib versus cisplatin/gemcitabine showed improvements in global health status/QoL ( p < 0.0001 ) and physical ( p < 0.0001 ) , role ( p = 0.013 ) , and social ( p < 0.001 ) functioning scales . Delayed symptom deterioration and better QoL over time was also observed with afatinib . QoL measured before tumor assessment was considerably poorer for patients with progression than those without progression , with significant differences in mean scores at multiple assessment time points . Results from the longitudinal analysis consistently demonstrated a significant negative impact of progression on QoL ( p < 0.0001 ) . Conclusion : Afatinib improved PFS and PROs versus chemotherapy in EGFR mutation-positive NSCLC patients . Progression was associated with statistically significant worsening in QoL measured before tumor assessment , underscoring the value of PFS as a clinical ly relevant end point Purpose The st and ard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined . The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil ( FU ) and oxaliplatin using the oxaliplatin , folinic acid , and FU ( OFF ) regimen . 1 PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 ( mFOLFOX6 ; infusional fluorouracil , leucovorin , and oxaliplatin ) versus infusional FU/leucovorin ( LV ) in this setting . Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0 - 2 were eligible . A total of 108 patients were r and omly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression . Progression-free survival ( PFS ) was the primary end point . Results Baseline patient characteristics were similar in both arms . No difference was observed in PFS ( median , 3.1 months v 2.9 months ; P = .99 ) . Overall survival ( OS ) was inferior in patients assigned to mFOLFOX6 ( median , 6.1 months v 9.9 months ; P = .02 ) . Increased toxicity was observed with the addition of oxaliplatin , with grade 3/4 adverse events occurring in 63 % of patients who received mFOLFOX6 and 11 % of those who received FU/LV . More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm ( 20 % v 2 % ) , whereas the use of postprogression therapy was significantly higher in the FU/LV arm ( 25 % v 7 % ; P = .015 ) . No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Question naire Core 30 global health scale . Conclusion No benefit was observed with the addition of oxaliplatin , administered as mFOLFOX6 , versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine Overall survival ( OS ) has been considered as the most relevant primary endpoint but trials using OS often require large numbers of patients and long-term follow-up . Therefore composite endpoints , which are assessed earlier , are frequently used as primary endpoint but suffer from important limitations specially a lack of validation as surrogate of OS . Therefore , Health-related quality of life ( HRQoL ) could be considered as an outcome to judge efficacy of a treatment . An alternative approach would be to combine HRQoL with composite endpoints as co- primary endpoint to ensure a clinical benefit for patients of a new therapy . The decision rules of such design , the procedure to control the Type I error and the determination of sample size remain questions to debate . Here , we discusses HRQoL as co- primary endpoints in r and omized clinical trials in oncology and provide some solutions to promote such design The main objectives of this study were to identify the number of r and omized controlled trials ( RCTs ) including a patient‐reported outcome ( PRO ) endpoint across a wide range of cancer specialties and to evaluate the completeness of PRO reporting according to the Consoli date d St and ards of Reporting Trials ( CONSORT ) PRO extension Objective The objective of this analysis was to compare patient-reported outcomes and health-related quality of life ( HRQoL ) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive , well-differentiated pancreatic neuroendocrine tumors ( NCT00428597 ) . Patients and Methods Patients received sunitinib 37.5 mg ( n = 86 ) or placebo ( n = 85 ) on a continuous daily-dosing schedule until disease progression , unacceptable adverse events ( AEs ) , or death . Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Question naire – Core 30 at baseline , Day 1 of every 4-week cycle , and end of treatment or withdrawal . Changes ≥10 points on each scale or item were deemed clinical ly meaningful . Results Sunitinib had anti-tumor effects and improved progression-free survival ( PFS ) compared with placebo . The study was terminated early for this reason and because of more serious AEs and deaths with placebo . Baseline HRQoL scores were well balanced between study arms , and were generally maintained over time in both groups . In the first 10 cycles , there were no significant differences between groups in global HRQoL , cognitive , emotional , physical , role , and social functioning domains , or symptom scales , except for worsening diarrhea with sunitinib ( p < 0.0001 vs. placebo ) . Insomnia also worsened with sunitinib ( p = 0.0372 vs. placebo ) , but the difference was not clinical ly meaningful . Conclusion With the exception of diarrhea ( a recognized side effect ) , sunitinib had no impact on global HRQoL , functional domains , or symptom scales during the progression-free period . Hence , in patients with pancreatic neuroendocrine tumors , sunitinib provided a benefit in PFS without adversely affecting PURPOSE This prospect i ve multicenter study explored different definitions of time to deterioration ( TTD ) in quality of life ( QoL ) scores , according to different cutoffs of the minimal clinical ly important difference ( MCID ) as a modality for longitudinal QoL assessment in breast cancer patients . METHODS QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 and BR-23 before surgery , after surgery , and 6 and 12 months later . The global health score , arm symptoms score ( BRAS ) , and breast symptoms score were analyzed . For a given baseline score , QoL was considered to have deteriorated if this score decreased by ≥5 points at any time point after baseline . Analyses were repeated using an MCID of 10 points and taking the score after surgery as the reference score ( to explore the occurrence of response shift ) . TTD was calculated using the Kaplan-Meier method and Cox regression was used to identify independent factors associated with TTD . RESULTS Two hundred thirty-five patients underwent axillary lymph node dissection ( ALND ) , 222 underwent sentinel lymph node biopsy ( SLNB ) , and 61 underwent SLNB plus ALND . Patients who underwent SLNB had a significantly longer TTD for the BRAS dimension than those who underwent ALND . Cox multivariate analyses showed that treatment using SLNB and age > 59 years were independently associated with longer TTD for the BRAS , whereas surgery elsewhere than at the Centre Georges François Leclerc was associated with a shorter TTD . CONCLUSION Exploration of different definitions of TTD in QoL provides meaningful longitudinal QoL results for clinicians BACKGROUND The Trastuzumab for Gastric Cancer phase III trial demonstrated that combining trastuzumab with chemotherapy significantly improved overall survival compared with chemotherapy alone in HER2-positive advanced gastric or gastroesophageal junction cancer . We report health-related quality of life ( HRQoL ) and quality -adjusted time without symptoms of disease or toxicity ( Q-TWiST ) results from this trial . PATIENTS AND METHODS Patients were r and omized to receive six cycles of chemotherapy given every 3 weeks ( capecitabine or fluorouracil , plus cisplatin ) either alone or combined with administration of trastuzumab every 3 weeks until disease progression . At each clinical visit , HRQoL was assessed using two European Organization for Research and Treatment of Cancer quality of life question naires , QLQ-C30 and QLQ-STO22 . Q-TWiST methodology was applied retrospectively using the clinical data and utility coefficients . RESULTS Trastuzumab plus chemotherapy prolonged time to 10 % definitive deterioration in all QLQ-C30 and QLQ-STO22 scores , including QLQ-C30 global health status versus chemotherapy alone , from 6.4 months to 10.2 months . In addition , trastuzumab plus chemotherapy extended Q-TWiST by 2.42 months compared with chemotherapy alone . CONCLUSION Compared with chemotherapy alone , trastuzumab plus chemotherapy prolongs time to deterioration of HRQoL and increases quality -adjusted survival in patients with HER2-positive gastric or gastroesophageal junction cancer The phase III RAINBOW trial showed the addition of ramucirumab to paclitaxel yielded survival benefits for previously treated patients with advanced gastric or gastroesophageal junction adenocarcinoma . Now analyses reveal that ramucirumab also maintains patient-reported quality of life , lengthening the time to deterioration of patient symptoms and functions , and slowing performance status decline PURPOSE To compare epirubicin , cisplatin , and capecitabine ( ECX ) with fluorouracil , leucovorin , and irinotecan ( FOLFIRI ) as first-line treatments in patients with advanced gastric or esophagogastric junction ( EGJ ) adenocarcinoma . PATIENTS AND METHODS This open , r and omized , phase III study was carried out in 71 centers . Patients with locally advanced or metastatic gastric or EGJ cancer were r and omly assigned to receive either ECX as first-line treatment ( ECX arm ) or FOLFIRI ( FOLFIRI arm ) . Second-line treatment was predefined ( FOLFIRI for the ECX arm and ECX for the FOLFIRI arm ) . The primary criterion was time-to-treatment failure ( TTF ) of the first-line therapy . Secondary criteria were progression-free survival ( PFS ) , overall survival ( OS ) , toxicity , and quality of life . RESULTS In all , 416 patients were included ( median age , 61.4 years ; 74 % male ) . After a median follow-up of 31 months , median TTF was significantly longer with FOLFIRI than with ECX ( 5.1 v 4.2 months ; P = .008 ) . There was no significant difference between the two groups in median PFS ( 5.3 v 5.8 months ; P = .96 ) , median OS ( 9.5 v 9.7 months ; P = .95 ) , or response rate ( 39.2 % v 37.8 % ) . First-line FOLFIRI was better tolerated ( overall rate of grade 3 to 4 toxicity , 69 % v 84 % ; P < .001 ; hematologic adverse events [ AEs ] , 38 % v 64.5 % ; P < .001 ; nonhematologic AEs : 53 % v 53.5 % ; P = .81 ) . CONCLUSION FOLFIRI as first-line treatment for advanced gastric and EGJ cancer demonstrated significantly better TTF than did ECX . Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents PURPOSE Therapy of patients with advanced gastric or gastroesophageal junction cancer should provide symptom relief and improve quality of life ( QOL ) because most patients are symptomatic at baseline . Using vali date d instruments , we prospect ively assessed QOL ( even after completion of protocol treatment ) as one of the secondary end points of the V325 phase III trial . PATIENTS AND METHODS Four hundred forty-five patients r and omly received either docetaxel 75 mg/m(2 ) and cisplatin 75 mg/m(2 ) each on day 1 plus fluorouracil 750 mg/m(2)/d continuous infusion on days 1 to 5 every 3 weeks ( DCF ) or cisplatin 100 mg/m(2 ) on day 1 plus fluorouracil 1,000 mg/m(2)/d continuous infusion on days 1 to 5 every 4 weeks ( CF ) . The European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) and , where available , the EuroQOL EQ-5D question naire were administered every 8 weeks from baseline until progression and then every 3 months . Time to definitive deterioration of QOL parameters was analyzed . RESULTS The proportions of patients having assessable EORTC QLQ-C30 and EQ-5D question naires at baseline were 86.0 % and 78.7 % with DCF , respectively , and 89.7 % and 92.8 % with CF , respectively . Time to 5 % deterioration of global health status ( primary end point ) significantly favored DCF over CF ( log-rank test , P = .01 ) . QOL was preserved longer for patients on DCF than those on CF for all time to deterioration analyses , demonstrating the statistical superiority of DCF compared with CF . CONCLUSION V325 represents the largest trial with the longest prospect ively controlled evaluations of QOL during protocol chemotherapy and follow-up in patients with advanced gastric or gastroesophageal junction cancer . In V325 , advanced gastric or gastroesophageal junction cancer patients receiving DCF not only had statistically improved overall survival and time to tumor-progression , but they also had better preservation of QOL compared with patients receiving CF PURPOSE As glioblastoma progresses , patients experience a decline in health-related quality of life ( HRQoL ) . Delaying this decline is an important treatment goal . In newly diagnosed glioblastoma , progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide ( RT/TMZ ) versus placebo plus RT/TMZ ( phase III AVAglio study ; hazard ratio , 0.64 ; 95 % CI , 0.55 to 0.74 ; P < .001 ) . To ensure that addition of bevacizumab to st and ard-of-care therapy was not associated with HRQoL detriment , HRQoL assessment was a secondary objective . PATIENTS AND METHODS Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Question naires C30 and BN20 at each tumor assessment ( Appendix Table A1 , online only ) . Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated ( stable : < 10-point change ; clinical ly relevant deterioration/improvement : ≥ 10-point change ) . Deterioration-free survival was the time to deterioration/progression/death ; time to deterioration was the time to deterioration/death . RESULTS Most evaluable patients who had not progressed ( > 74 % ) completed all HRQoL assessment s for at least 1 year of treatment , and almost all completed at least one HRQoL assessment at baseline ( 98.3 % and 97.6 % , bevacizumab and placebo arms , respectively ) . Mean changes from baseline did not reach a clinical ly relevant difference between arms for most items . HRQoL declined at progression in both arms . The addition of bevacizumab to RT/TMZ result ed in statistically longer ( P < .001 ) deterioration-free survival across all items . Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm ( v bevacizumab ) for any HRQoL item . CONCLUSION The addition of bevacizumab to st and ard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period Purpose Patient-reported outcomes ( PRO ) of health-related quality of life ( HRQoL ) and time to worsening of clinical benefit parameters were evaluated as secondary end points in the phase 3 first-line advanced gastric cancer study ( FLAGS ) trial of cisplatin/S-1 versus cisplatin/5-fluorouracil ( 5-FU ) in patients with previously untreated advanced gastric cancer . Methods The primary PRO end point was the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Gastric ( FACT-Ga ) . FACT-Ga was completed at the beginning of the first 4 cycles , cycle 6 , and then every 3 cycles thereafter . The Chemotherapy Convenience and Satisfaction Question naire ( CCSQ ) was administered before the first 4 cycles ; clinical benefit parameters ( performance status , weight loss , and anorexia ) were assessed at baseline , prior to study drug administration on day 1 of each cycle after cycle 1 , and at the end of study treatment . Results Compliance to question naire fulfillment was more than 80 % through cycle 9 . Significantly , fewer patients treated with cisplatin/S-1 reported worsened physical well-being ( PWB ) scores ( 45.1 versus 51.7 % , p = 0.044 ) and experienced significantly longer time to worsening in PWB scores , with a median of 4.5 months ( 95 % confidence interval ( CI ) , 3.1–5.1 ) compared to 3.0 months ( 2.8–4.6 ) with cisplatin/5-FU ( CF ) ( p = 0.01 ) . Patients receiving cisplatin/S-1 also reported significantly higher best and worst score of PWB as well as CCSQ scores and a longer median time to worsening in clinical benefit parameters . Conclusions Differences in secondary end points of PWB , CCSQ scores , and clinical benefit parameters favoring the cisplatin/S-1 arm provide further evidence for considering this combination a st and ard therapeutic option for first-line treatment of advanced gastric cancer Introduction : In the phase III CheckMate 017 study , nivolumab prolonged overall survival versus docetaxel in previously treated patients with advanced squamous NSCLC . Study objectives included health‐related quality of life ( HRQoL ) and symptom assessment s. Methods : Patients serially completed the Lung Cancer Symptom Scale ( LCSS ) and European Quality of Life Five Dimensions ( EQ‐5D ) question naires . The LCSS average symptom burden index ( ASBI ) ( mean score for six lung cancer – specific symptoms ; range 0–100 ) , LCSS three‐item global index , EQ‐5D utility index , and EQ‐5D visual analog scale scores were analyzed . The proportion of patients exhibiting clinical ly meaningful improvement ( a ≥10‐point decrease ) in ASBI scores by week 12 was a secondary end point . Mixed‐effect model repeated measures analysis of HRQoL changes from baseline and analyses of time to HRQoL deterioration were conducted . Results : Baseline mean plus or minus SD LCSS ASBI scores were similar in the nivolumab ( 29.6 ± 16.4 ) and docetaxel ( 29.6 ± 14.7 ) groups . By week 12 , the proportions of patients ( 95 % confidence interval ) with clinical ly meaningful improvement in ASBI scores were 20.0 % ( 13.6–27.7 ) with nivolumab and 21.9 % ( 15.3–29.8 ) with docetaxel . At weeks 16 to 54 , significant improvements in ASBI scores from baseline were seen with nivolumab ; clinical ly meaningful improvements were observed at weeks 42 to 84 . No significant changes in ASBI scores from baseline were observed with docetaxel ; at week 36 , a clinical ly meaningful deterioration was seen . Improvements in HRQoL with nivolumab versus with docetaxel were supported by other measures , and time to first HRQoL deterioration was longer . Conclusion : Nivolumab alleviates symptom burden and improves health status versus docetaxel as second‐line squamous NSCLC treatment Importance Tumor-treating fields ( TTFields ) therapy improves both progression-free and overall survival in patients with glioblastoma . There is a need to assess the influence of TTFields on patients ’ health-related quality of life ( HRQoL ) . Objective To examine the association of TTFields therapy with progression-free survival and HRQoL among patients with glioblastoma . Design , Setting , and Participants This secondary analysis of EF-14 , a phase 3 r and omized clinical trial , compares TTFields and temozolomide or temozolomide alone in 695 patients with glioblastoma after completion of radiochemotherapy . Patients with glioblastoma were r and omized 2:1 to combined treatment with TTFields and temozolomide or temozolomide alone . The study was conducted from July 2009 until November 2014 , and patients were followed up through December 2016 . Interventions Temozolomide , 150 to 200 mg/m2/d , was given for 5 days during each 28-day cycle . TTFields were delivered continuously via 4 transducer arrays placed on the shaved scalp of patients and were connected to a portable medical device . Main Outcomes and Measures Primary study end point was progression-free survival ; HRQoL was a predefined secondary end point , measured with question naires at baseline and every 3 months thereafter . Mean changes from baseline scores were evaluated , as well as scores over time . Deterioration-free survival and time to deterioration were assessed for each of 9 preselected scales and items . Results Of the 695 patients in the study , 639 ( 91.9 % ) completed the baseline HRQoL question naire . Of these patients , 437 ( 68.4 % ) were men ; mean ( SD ) age , 54.8 ( 11.5 ) years . Health-related quality of life did not differ significantly between treatment arms except for itchy skin . Deterioration-free survival was significantly longer with TTFields for global health ( 4.8 vs 3.3 months ; P < .01 ) ; physical ( 5.1 vs 3.7 months ; P < .01 ) and emotional functioning ( 5.3 vs 3.9 months ; P < .01 ) ; pain ( 5.6 vs 3.6 months ; P < .01 ) ; and leg weakness ( 5.6 vs 3.9 months ; P < .01 ) , likely related to improved progression-free survival . Time to deterioration , reflecting the influence of treatment , did not differ significantly except for itchy skin ( TTFields worse ; 8.2 vs 14.4 months ; P < .001 ) and pain ( TTFields improved ; 13.4 vs 12.1 months ; P < .01 ) . Role , social , and physical functioning were not affected by TTFields . Conclusions and Relevance The addition of TTFields to st and ard treatment with temozolomide for patients with glioblastoma results in improved survival without a negative influence on HRQoL except for more itchy skin , an expected consequence from the transducer arrays . Trial Registration clinical trials.gov Identifier : BACKGROUND Olaparib combined with paclitaxel has previously shown a significant improvement in overall survival versus placebo plus paclitaxel as second-line therapy in a phase 2 study in Asian patients with advanced gastric cancer , especially in those with ataxia-telangiectasia mutated protein (ATM)-negative tumours . Here , we report the primary efficacy and safety analyses from a subsequent phase 3 trial . METHODS This double-blind , r and omised , placebo-controlled , phase 3 study ( GOLD ) recruited Asian patients aged 18 years or older ( ≥20 years if Japanese ) with advanced gastric cancer that had progressed following , or during , first-line chemotherapy . Patients were r and omly assigned ( 1:1 ) to receive oral olaparib ( 100 mg twice daily ) plus paclitaxel ( 80 mg/m2 intravenously ) or matching placebo plus paclitaxel . R and omisation was done through an interactive voice response system and no stratification factors were used . Patients and investigators were masked to treatment allocation . Two co- primary population s were assessed : the overall population of all patients and patients whose tumours were ATM-negative ( identified after r and omisation , before the data cutoff date , March 28 , 2016 ) . The primary endpoint in both population s was overall survival ( defined as the time from the date of r and omisation until death from any cause before data cutoff ) ; a significant difference was defined as p<0·025 . Efficacy was assessed in the intention-to-treat population s and safety in patients who received at least one dose of treatment . This trial is registered with Clinical Trials.gov , number NCT01924533 ( study ID , D081BC00004 ) , and is ongoing but no longer recruiting participants . FINDINGS Between Sept 3 , 2013 , and March 28 , 2016 , 643 patients were enrolled from 58 study sites in hospitals and medical centres in China , Japan , South Korea , and Taiwan . 525 eligible patients were r and omly assigned : 263 to receive olaparib plus paclitaxel and 262 to receive placebo plus paclitaxel . 94 patients were determined to have ATM-negative tumours before unmasking for the primary analysis ( 48 in the olaparib plus paclitaxel group and 46 in the placebo plus paclitaxel group ) . Overall survival did not differ between treatment groups in the overall patient population ( median overall survival 8·8 months [ 95 % CI 7·4 - 9·6 ] in the olaparib group vs 6·9 months [ 6·3 - 7·9 ] in the placebo group ; HR 0·79 [ 97·5 % CI 0·63 - 1·00 ] ; p=0·026 ) or in the ATM-negative population ( 12·0 months [ 7·8 - 18·1 ] vs 10·0 months [ 6·4 - 13·3 ] ; 0·73 [ 0·40 - 1·34 ] ; p=0·25 ) . In the overall patient population , the most common grade 3 or worse adverse events in the olaparib plus paclitaxel group were neutropenia ( 78 [ 30 % ] of 262 patients ) , leucopenia ( 42 [ 16 % ] ) , and decreased neutrophil count ( 40 [ 15 % ] ) ; in the placebo plus paclitaxel group , they were neutropenia ( 59 [ 23 % ] of 259 patients ) , leucopenia ( 27 [ 10 % ] ) , and decreased white blood cell count ( 21 [ 8 % ] ) . Adverse events with an outcome of death causally related to study treatment ( according to investigator assessment ) were reported in two patients : liver injury in one patient ( < 1 % ) in the olaparib plus paclitaxel group and cardiac failure in one patient ( < 1 % ) in the placebo plus paclitaxel group . INTERPRETATION The GOLD study did not meet its primary objective of showing a significant improvement in overall survival with olaparib in the overall or ATM-negative population of Asian patients with advanced gastric cancer . The study generated informative efficacy and safety data regarding the use of olaparib in combination with a chemotherapeutic agent and provides a foundation for future studies in this difficult-to-treat patient population . FUNDING AstraZeneca OBJECTIVE Report results of patient-reported health-related quality of life ( HRQoL ) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma . PATIENTS AND METHODS Patients received pembrolizumab 10 mg/kg every 2 ( Q2W ) or every 3 weeks ( Q3W ) for up to 2 years , or four cycles of ipilimumab 3 mg/kg Q3W . The European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) was administered at baseline and throughout the study . Patient-reported outcome ( PRO ) analyses were pre-specified exploratory endpoints ; the primary PRO assessment was the score change from baseline to week 12 in EORTC QLQ-C30 global health status (GHS)/HRQoL score between the arms using constrained longitudinal data analysis . RESULTS The PRO analysis population included 776 patients : pembrolizumab Q2W ( n = 270 ) ; pembrolizumab Q3W ( n = 266 ) ; ipilimumab ( n = 240 ) . Baseline GHS was similar across arms . QLQ-C30 compliance rates at week 12 were 87 % ( n = 214 ) , 97 % ( n = 226 ) , and 96 % ( n = 178 ) , for the pembrolizumab Q2W , pembrolizumab Q3W , and ipilimumab arms , respectively . From baseline to week 12 , GHS/HRQoL scores were better maintained with pembrolizumab than with ipilimumab ( decrease of -1.9 and -2.5 for pembrolizumab versus -10.0 for ipilimumab ; p < 0.001 for each pembrolizumab arm versus ipilimumab ) . Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 ( 31 % for pembrolizumab Q2W ; 29 % for Q3W and 44 % for ipilimumab ) , with similar trends observed for individual functioning and symptoms scales . CONCLUSIONS HRQoL was better maintained with pembrolizumab than with ipilimumab in patients with ipilimumab-naive advanced melanoma . CLINICAL TRIALS . GOV IDENTIFIER NCT01866319 BACKGROUND In the AFFIRM trial of patients with metastatic castration-resistant prostate cancer after progression with docetaxel treatment , enzalutamide significantly increased overall survival compared with placebo . Here we present the prospect ively defined analyses of some secondary endpoints , including occurrence of skeletal-related events , measures of pain control , and patient-reported health-related quality of life ( HRQoL ) . METHODS In this phase 3 , double-blind trial , patients were r and omly assigned ( 2:1 ) to receive enzalutamide 160 mg/day or placebo orally , stratified by ECOG baseline performance status ( 0 or 1 vs 2 ) and mean pain score ( Brief Pain Inventory-Short Form [ BPI-SF ] question 3 worst pain , score ≤3 vs ≥4 ) . Secondary endpoints were time to first skeletal-related event ( defined as radiation therapy or surgery to bone ) ; change from baseline to week 13 in pain severity and interference ; pain palliation and progression at week 13 ; time to pain progression ; overall improvement in HRQoL ; improvements in HRQoL domains ; and time to HRQoL deterioration . Analysis was done on the intention-to-treat population for each endpoint . AFFIRM is registered with Clinical Trials.gov , number NCT00974311 . FINDINGS Median time to first skeletal-related event in the enzalutamide ( n=800 ) and placebo ( n=399 ) groups was 16·7 months ( 95 % CI 14·6 to 19·1 ) and 13·3 months ( 95 % CI 9·9 to not yet reached ) , respectively ( hazard ratio [ HR ] 0·69 [ 95 % CI 0·57 - 0·84 ] ; p=0·0001 ) . Pain progression at week 13 occurred in 174 ( 28 % ) of 625 evaluable patients in the enzalutamide group versus 101 ( 39 % ) of 259 patients in the placebo group ( difference -11·2 % , 95 % CI -18·1 to -4·3 ; p=0·0018 ) . Median time to pain progression was not yet reached in the enzalutamide group ( 95 % CI not yet reached to not yet reached ) versus 13·8 ( 13·8 to not yet reached ) months in the placebo group ( HR 0·56 [ 95 % CI 0·41 to 0·78 ] ; p=0·0004 ) . Mean treatment effects for pain severity ( mean change from baseline in the enzalutamide group -0·15 , 95 % CI -0·28 to -0·02 , vs placebo 0·50 , 0·29 to 0·70 ; difference -0·65 , 95 % CI -0·89 to -0·41 ; p<0·0001 ) and interference ( -0·01 , -0·18 to 0·16 , vs 0·74 , 0·47 to 1·00 ; respectively , difference -0·74 , 95 % -1·06 to -0·43 ; p<0·0001 ) were significantly better with enzalutamide than with placebo . 22 ( 45 % ) of 49 evaluable patients in the enzalutamide group reported pain palliation at week 13 versus one ( 7 % ) of 15 in the placebo group ( difference 38·2 % , 95 % CI 19·4 - 57·0 ; p=0·0079 ) . Overall improvement in HRQoL was reported in more patients receiving enzalutamide ( 275 [ 42 % ] of 652 ) than in those receiving placebo ( 36 [ 15 % ] of 248 ; p<0·0001 ) . Patients in the enzalutamide group had longer median time to HRQoL deterioration than did those in the placebo group ( 9·0 months , 95 % CI 8·3 - 11·1 , vs 3·7 months , 95 % CI 3·0 - 4·2 ; HR 0·45 , 95 % CI 0·37 - 0·55 ; p<0·0001 ) in risk of deterioration . INTERPRETATION Our results show that , in addition to improving overall survival , enzalutamide improves wellbeing and everyday functioning of patients with metastatic castration-resistant prostate cancer . FUNDING Astellas Pharma and Medivation |
1,118 | 25,240,141 | Evidence suggested that stepped care interventions for depression are at least as effective as usual care .
However , the clinical and organisational superiority of stepped care is yet to be scientifically verified .
Differential benefits of stepped care may ultimately depend on service quality . | BACKGROUND Stepped care service delivery models involve treatments that become increasingly intense through successive steps , with patients re-assigned via pre-defined decision criteria .
This article review s the clinical effectiveness of stepped care systems for depression in working age adults . | BACKGROUND Data on the duration of major depressive episodes ( MDE ) in the general population are sparse . AIMS To assess the duration of MDE and its clinical and socio-demographic determinants in a study group drawn from the general population with newly originated episodes of major depression . METHOD The Netherl and s Mental Health Survey and Incidence Study is a prospect i ve epidemiological survey in the adult population ( n=7076 ) , using the Composite International Diagnostic Interview . Duration of MDE over 2 years was assessed with a Life Chart Interview . RESULTS The median duration of MDE was 3.0 months ; 50 % of participants recovered within 3 months , 63 % within 6 months , 76 % within 12 months and nearly 20 % had not recovered at 24 months . Determinants of persistence were severity of depression and comorbid dysthymia . A recurrent episode predicted shorter duration . CONCLUSIONS Although half of those affected with MDE recovered rapidly , the risk of chronicity ( duration 24 months or more ) was considerable . This underlines the necessity of diagnosing and treating those at risk CONTEXT Given the public health significance of late-life depression and anxiety , and the limited capacity of treatment , there is an urgent need to develop effective strategies to prevent these disorders . OBJECTIVE To determine the effectiveness of an indicated stepped-care prevention program for depression and anxiety disorders in the elderly . DESIGN R and omized controlled trial with recruitment between October 1 , 2004 , and October 1 , 2005 . SETTING Thirty-three primary care practice s in the northwestern part of the Netherl and s. PARTICIPANTS A total of 170 consenting individuals , 75 years and older , with subthreshold symptom levels of depression or anxiety who did not meet the full diagnostic criteria for the disorders . INTERVENTION Participants were r and omly assigned to a preventive stepped-care program ( n = 86 ) or to usual care ( n = 84 ) . Stepped-care participants sequentially received a watchful waiting approach , cognitive behavior therapy-based bibliotherapy , cognitive behavior therapy-based problem-solving treatment , and referral to primary care for medication , if required . MAIN OUTCOME MEASURES The cumulative incidence of DSM-IV major depressive disorder or anxiety disorder after 12 months as measured using the Mini International Neuropsychiatric Interview . RESULTS The intervention halved the 12-month incidence of depressive and anxiety disorders , from 0.24 ( 20 of 84 ) in the usual care group to 0.12 ( 10 of 86 ) in the stepped-care group ( relative risk , 0.49 ; 95 % confidence interval , 0.24 to 0.98 ) . CONCLUSIONS Indicated stepped-care prevention of depression and anxiety in elderly individuals is effective in reducing the risk of onset of these disorders and is valuable as seen from the public health perspective Abstract Objectives : To determine whether problem solving treatment combined with antidepressant medication is more effective than either treatment alone in the management of major depression in primary care . To assess the effectiveness of problem solving treatment when given by practice nurses compared with general practitioners when both have been trained in the technique . Design : R and omised controlled trial with four treatment groups . Setting : Primary care in Oxfordshire . Participants : Patients aged 18 - 65 years with major depression on the research diagnostic criteria —a score of 13 or more on the 17 item Hamilton rating scale for depression and a minimum duration of illness of four weeks . Interventions : Problem solving treatment by research general practitioner or research practice nurse or antidepressant medication or a combination of problem solving treatment and antidepressant medication . Main outcome measures : Hamilton rating scale for depression , Beck depression inventory , clinical interview schedule ( revised ) , and the modified social adjustment schedule assessed at 6 , 12 , and 52 weeks . Results : Patients in all groups showed a clear improvement over 12 weeks . The combination of problem solving treatment and antidepressant medication was no more effective than either treatment alone . There was no difference in outcome irrespective of who delivered the problem solving treatment . Conclusions : Problem solving treatment is an effective treatment for depressive disorders in primary care . The treatment can be delivered by suitably trained practice nurses or general practitioners . The combination of this treatment with antidepressant medication is no more effective than either treatment alone . Key messages Problem solving treatment is an effective treatment for depressive disorders in primary care Problem solving treatment can be delivered by suitably trained practice nurses as effectively as by general practitioners The combination of problem solving treatment and antidepressant medication is no more effective than either treatment alone Problem solving treatment is most likely to benefit patients who have a depressive disorder of moderate severity and who wish to participate in an active psychological We evaluated , among depressed medical patients who are high utilizers of health care , whether improved vs unimproved depression is associated with differences in the course of functional disability . At baseline , 6 months , and 12 months , depression and disability were assessed among a sample of enrollees in health maintenance organizations ( N = 145 ) in the top decile of users of ambulatory health care who exceeded the 70th percentile of health maintenance organization population norms for depression . Improved depression was defined as a reduction of at least one third in depressive symptoms averaged across the two follow-up times . At the 12-month follow-up , persons with severe-improved depression experienced a 36 % reduction in disability days ( 79 days per year to 51 days per year ) and a 45 % reduction in disability score . Persons with moderate-improved depression experienced a 72 % reduction in disability days ( 62 days per year to 18 days per year ) and a 40 % reduction in disability score . In contrast , persons with severe-unimproved depression reported 134 disability days per year at baseline , while persons with moderate-unimproved depression reported 77 disability days per year at baseline . Neither group with unimproved depression showed improvement in either disability days or disability score during the 1-year follow-up period . High utilizers of health care with severe-unimproved depression were more likely to have current major depression and to be unemployed . Improved ( relative to unimproved ) depression was associated with borderline differences in the severity of physical disease and in the percent married . We conclude that depression and disability showed synchrony in change over time . However , depression and disability may show synchrony in change with disability because both depression and disability are controlled by some other factor that influences the chronicity of depression ( eg , chronic disease or personality disorder ) . The finding of synchronous change of depression and disability provides a rationale for r and omized controlled trials of depression treatments among depressed and disabled medical patients to determine whether psychiatric intervention might improve functional status in such patients . Such research is needed to determine whether there is a causal relationship between depression offset and reductions in functional disability BACKGROUND The current nonr and omized clinical trial explored changes over time in children with an anxiety disorder during stepped care , manual-based cognitive behaviour therapy ( CBT ) . METHODS Clinical ly anxious children ( 8 - 12 years , n = 133 ) and their parents participated in child focused CBT ( 10 sessions ) . If assessment s indicated additional treatment was necessary , participants could step up to a second and possibly third treatment phase ( each 5 sessions ) including more parental involvement . RESULTS After the first treatment phase 45 % of the Intention-To-Treat sample was free of any anxiety disorder ; after the second and third phase an additional 17 % and 11 % respectively . In total , 74 % of the children no longer met criteria for any anxiety disorder following treatment . Child and parent reported anxiety and depression symptoms of children improved significantly during all treatment phases , as well as child reported anxiety sensitivity and negative affect . Children participating in more treatment showed significant improvements during additional treatment phases , indicating that late change occurred for the subgroup that had not changed during the first phase . CONCLUSIONS Stepped care offers a st and ardized , assessment based , yet tailored treatment approach for children with anxiety disorders . A more intensive treatment is offered when initial CBT is insufficient , providing children additional opportunities to reach the desired outcome INTRODUCTION Worldwide , health systems are improving access to empirically supported psychological therapies for anxiety and depression . Evaluations of this effort are limited by the cross sectional nature of studies , short implementation periods , poor data completeness rates and lack of clinical ly significant and reliable change metrics . OBJECTIVE Assess the impact of implementing stepped care empirically supported psychological therapies by measuring the prospect i ve outcomes of patients referred over a two year period to one Improving Access to Psychological Therapies service in the UK . METHOD We collected demographic , therapeutic and outcome data on depression ( PHQ-9 ) and anxiety ( GAD-7 ) from 7859 consecutive patients for 24 months between 1st July 2006 and 31st August 2008 , following up these patients for a further one year . RESULTS 4183 patients ( 53 % ) received two or more treatment sessions . Uncontrolled effect size for depression was 1.07 ( 95 % CI : 0.88 to 1.29 ) and for anxiety was 1.04 ( 0.88 to 1.23 ) . 55.4 % of treated patients met reliable improvement or reliable and clinical ly significant change criteria for depression , 54.7 % for anxiety . Patients received a mean of 5.5 sessions over 3.5h , mainly low-intensity CBT and phone based case management . Attrition was high with 47 % of referrals either not attending for an assessment or receiving an assessment only . CONCLUSIONS Recovery rates for patients receiving stepped care empirically supported treatments for anxiety and depression in routine practice are 40 to 46 % . Only half of all patients referred go on to receive treatment . Further work is needed to improve routine engagement of patients with anxiety and depression OBJECTIVES To determine the effects of implementing stepped care evidence -based psychological treatments for anxiety and depression in routine practice using a collaborative care implementation model . DESIGN Observational prospect i ve cohort study /Phase IV field trial . METHODS We collected data on depression and anxiety from a prospect i ve cohort of 3,994 consecutive patients referred to the UK Improving Access to Psychological Therapies demonstration site in Doncaster for 12 months from August 2006 using PHQ-9 and GAD-7 . We collected demographic and process information including the type and methods of treatments received . We calculated effect sizes , remission , and recovery rates for patients competing treatment and those who dropped out or were considered to be unsuitable . RESULTS Two thous and seven hundred and ninety-five patients received an assessment , out of which 2,017 received two or more appointments . Out of these , 869 had completed treatment by the census date , 743 remained in treatment , 319 had dropped out , and 85 had been found to be unsuitable . Pre-post treatment effect sizes for anxiety and depression in those patients completing treatment were 1.39 and 1.41 , respectively , with post-treatment relative risks of depression and anxiety 0.29 and 0.34 . The combined remission and recovery rates were 76 % for depression and 74 % for anxiety . The mean number of treatment sessions was 5.15 in a mean time of 2 h and 45 min . On an average , patients received at least three of these contacts by telephone . Outcomes are comparable with benchmarked trials , review s , and routine data sets . CONCLUSIONS Combining low-intensity stepped care psychological treatment with a telephony-based collaborative care organizational system can deliver good clinical outcomes in routine practice OBJECTIVE To determine the clinical predictors and rate of relapse for major depression in primary care . DESIGN A cohort study of subjects in 2 r and omized trials of depressed patients diagnosed and prescribed antidepressant medicine by primary care physicians . Baseline , 7-month , and 19-month assessment s were conducted . SETTING A large primary care clinic of a staff-model health maintenance organization . PATIENTS Two hundred fifty-one primary care patients who did not satisfy Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition ( DSM-III-R ) criteria for major depression at 7 months . MAIN OUTCOME MEASURES Relapse was defined as ( 1 ) satisfying DSM-III-R criteria for major depression at 19 months , or ( 2 ) reporting an interval episode of 2 weeks or more of depressed mood and symptoms between 7 and 19 months . Predictors examined included demographic characteristics , medical comorbidity , disability , and psychological symptoms . Depressive symptoms were measured by Inventory of Depressive Symptoms and Hopkins Symptoms Checklist . RESULTS Of the patients , 37.1 % reported relapse of depression in the 12-month relapse-risk period . The 2 major risk factors associated with relapse were ( 1 ) persistence of subthreshold depressive symptoms 7 months after the initiation of antidepressant therapy ( odds ratio , 3.3 ; 95 % confidence interval , 2.74 - 3.93 ) and ( 2 ) history of 2 or more episodes of major depression , or chronic mood symptoms for 2 years ( odds ratio , 2.1 ; 95 % confidence interval , 1.41 - 2.76 ) . Patients with both risk factors were approximately 3 times more likely to relapse than patients with neither . CONCLUSIONS The relapse rate among primary care patients treated for depression approached that of specialty sample s , with more than one third reporting relapse in 1 year . Clinical characteristics can help target high-risk patients for relapse prevention efforts |
1,119 | 29,080,978 | The significant association for BMI and CRC risk was stronger in men than in women .
Conclusion The positive association between height and risk of CRC suggests that life factors during childhood and early adulthood might play a role in CRC aetiology .
Higher general and abdominal body fatness during adulthood are risk factors of CRC and these associations are stronger in men than in women | Purpose There is no published dose – response meta- analysis on the association between height and colorectal cancer risk ( CRC ) by sex and anatomical sub-site .
We conducted a meta- analysis of prospect i ve studies on the association between height and CRC risk with subgroup analysis and up date d evidence on the association between body fatness and CRC risk . | Adult height has been found in some but not all studies to be associated positively with overall cancer incidence as well as several site-specific cancers . The Physicians ' Health Study ( PHS ) , a r and omized trial of beta-carotene and aspirin in the primary prevention of cancer and cardiovascular disease in men , provided an opportunity to examine the association between height and total malignant neoplasms ( excluding non-melanoma skin cancer ) , as well as site-specific cancers including prostate , colorectal , and lung cancer . The PHS is comprised of 22,071 US male physicians in the United States , a population homogeneous for adult socioeconomic status , aged 40 to 84 years in 1982 . Participants were classified into five height categories at study entry . After an average follow-up of over 12 years , there were 2,566 cases of incident total malignant neoplasms , including 1,047 prostate , 341 colorectal , and 170 lung cancer cases . Height was associated positively with both total malignant neoplasms and prostate cancer . Compared with men in the shortest category(≤ 67 inches ) , relative risks and 95 percent confidence intervals (CI)for total malignant neoplasms for men whose height ( in inches ) was 68 - 69,70 - 71 , 72 , and 73 + were , respectively : 1.13 ( CI = 0.99 - 1.28 ) , 1.15 ( CI = 1.02 - 1.30 ) , 1.29 ( CI = 1.12 - 1.49 ) , and 1.21 ( CI = 1.05 - 1.39 ) , P trend 0.001,adjusted for age , r and omized treatment assignments , body mass index ( wt/ht2 ) , cigarette smoking , alcohol use , and exercise frequency . For prostatecancer , the corresponding RR values were 1.23 ( CI = 1.00 - 1.51 ) , 1.26 ( CI = 1.04 - 1.54 ) , 1.59 ( CI = 1.27 - 1.98 ) , and 1.26 ( CI = 1.00 - 1.59 ) , P trend 0.005.For colorectal cancer , in some but not all height categories compared with the shortest , there were elevated RRs without a significant linear trend : RR= 1.51 ( CI = 1.06 - 2.14 ) , 1.14 ( CI = 0.80 - 1.62 ) , 1.19 ( CI = 0.79 - 1.80 ) , and 1.53 ( CI = 1.04 - 2.25 ) , P trend 0.23 . In contrast , there was no evidence of an association of height with lung cancer . These data indicate a positive association between height and risk of total malignant neoplasms , as well as of prostate cancer and , possibly , colorectal cancer Background : Because of its nutrients and anabolic hormones , cow 's milk may promote height growth , which in turn has been related to breast cancer risk . We prospect ively investigated associations between dairy intakes and height growth . Methods : A cohort of 5,101 girls from throughout the United States completed annual surveys ( 1996 - 2001 , 2003 ) , providing height , weight , and past-year diet . At baseline , all were premenarchal , ages 9 years and above , with no serious medical conditions . We studied three outcomes : annual height growth , peak growth velocity , and adult height . Multivariate models estimated the effects of milk , cheese , yogurt , and energy on subsequent growth , adjusted for race/ethnicity , age , prior height , and body mass index . Other models studied fats and proteins . Results : Premenarchal girls who drank > 3 servings per day of milk grew 0.11 in . ( P = 0.02 ) more the following year than girls consuming < 1 serving per day . Yogurt ( + 0.13 in./cup ; P = 0.02 ) , but not cheese or total calories , predicted height growth . In a separate model , dairy protein ( + 0.034 in./10 g ; P < 0.001 ) predicted height growth . Larger peak velocities were seen among girls reporting , at baseline , more milk ( > 3 glasses per day versus < 1 ; + 0.14 in . , P = 0.01 ) , more yogurt ( + 0.17 in./cup , P = 0.02 ) , and , in a separate model , more dairy protein ( + 0.039 in./10 g ; P = 0.003 ) . Baseline milk and dairy protein predicted taller adults . Dairy protein was more important than dairy fat , for all outcomes . Nondairy animal protein and vegetable protein were never significant , nor were nondairy animal fat and vegetable fat . Conclusion : Of the foods/nutrients studied , dairy protein had the strongest association with height growth . These findings suggest that a factor in the nonlipid phase of milk , but not protein itself , has growth-promoting action in girls . ( Cancer Epidemiol Biomarkers Prev 2009;18(6):1881–7 AIM To examine whether peanut consumption is associated with a reduced risk of colorectal cancer in a prospect i ve cohort with a 10-year follow-up . METHODS In 1990 - 1992 , residents ( 12026 men and 11917 women aged 30 to 65 years ) in 7 townships , Taiwan , were interviewed and recruited into a cancer-screening cohort and annually followed up . Colorectal cancer cases in this cohort were identified from cancer registry and death certificates . Incidence rates of this disease by the end of 2001 were calculated by gender for the primary study variable and covariates . The dietary intake was assessed by means of weekly food frequency measures , including frequently consumed food groups and folk dishes including sweet potato , bean products , peanut products , pickled foodstuffs , nitrated or smoked foodstuffs . RESULTS During the study period , 107 new colorectal cancer cases ( 68 men and 39 women ) were confirmed . The multivariate Cox 's proportional hazard model showed that the relative risk ( RR ) of peanut consumption was 0.73 [ 95 % confidence interval ( CI ) = 0.44 - 1.21 ] for men and 0.42 ( 95 % CI = 0.21 - 0.84 ) for women . However , frequent intake of pickled foodstuffs was harmful for women ( RR = 2.15 , 95 % CI = 0.99 - 4.65 ) . The risk of colorectal cancer was also elevated among cigarette smokers but not significant ( P<0.05 ) . CONCLUSION This study suggests that frequent intake of peanut and its products may reduce colorectal cancer risk in women , demonstrating the anti-proliferating effect of peanut intake To investigate the relation of dietary intakes of sucrose , meat , and fat , and anthropometric , lifestyle , hormonal , and reproductive factors to colon cancer incidence , data were analyzed from a prospect i ve cohort study of 35,215 Iowa ( United States ) women , aged 55–69 years and without a history of cancer , who completed mailed dietary and other question naires in 1986 . Through 1990 , 212 incident cases of colon cancer were documented . Proportional hazards regression was used to adjust for age and other risk factors . Risk factors found to be associated significantly with colon cancer included : ( i ) sucrose-containing foods and beverages other than ice cream/milk ; relative risks ( RR ) across the quintiles=1.00 , 1.73 , 1.56 , 1.54 , and 2.00 ( 95 % confidence intervals [ CI ] for quintiles two and five exclude 1.0 ) ; ( ii ) sucrose ; RR across the quintiles=1.00 , 1.70 , 1.81 , 1.82 , and 1.45 ( CI for quintiles two through four exclude 1.0 ) ; ( iii ) height ; RR=1.23 for highest to lowest quintile ( P for trend-0.02 ) ; ( iv ) body mass index ; RR=1.41 for highest to lowest quintile ( P for trend=0.03 ) ; and ( v ) number of livebirths , RR=1.59 for having had one to two livebirths and 1.80 for having had three or more livebirths compared with having had none ( P for trend=0.04 ) . These data support hypotheses that sucrose intake or being tall or obese increases colon cancer risk ; run contrary to the hypothesis that increased parity decreases risk ; support previous findings of no association with demographic factors other than age , cigarette smoking , or use of oral contraceptives or estrogen replacement therapy ; and raise questions regarding previous associations with meat , fat , protein , and physical activity . Cancer Causes and Control 1994 , 5 , 38–52 The relation between diet and female colorectal cancer was analyzed in a prospect i ve study of 14,727 women aged 34 - 65 years , who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991 . They were followed through the end of 1994 ( average 7.1 yrs ) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries , result ing in 100 incident cases of colorectal cancer . There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories , total or subclasses of fat , carbohydrate , or dietary fiber , whereas there was an inverse association with total protein . Among major food groups , there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish ( relative risk for 4th vs. 1st quartile = 0.49 , 95 % confidence interval = 0.27 - 0.89 ) . A similar inverse association was also observed for consumption of dairy products , and this association was explained mainly by calcium , not by other nutrients , such as fat or protein . The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer , whereas the relations with red meat or total fat remained unclear Cancer is a leading cause of death , and the dietary pattern in Korea is changing rapidly from a traditional Korean diet to a Westernised diet . In the present study , we investigated the effects of dietary factors on cancer risk with a prospect i ve cohort study . Among 26,815 individuals who participated in cancer screening examinations from September 2004 to December 2008 , 8024 subjects who completed a self-administered question naire concerning demographic and lifestyle factors , and a 3 d food record were selected . As of September 2013 , 387 cancer cases were identified from the National Cancer Registry System , and the remaining individuals were included in the control group . The hazard ratio ( HR ) of cancer for the subjects older than or equal to 50 years of age was higher ( HR 1.80 , 95 % CI 1.41 , 2.31 ; P < 0.0001 ) than that for the other subjects . Red meat consumption , Na intake and obesity ( BMI ≥ 25 kg/m² ) were positively associated with overall cancer incidence in men ( HR 1.41 , 95 % CI 1.02 , 1.94 ; P= 0.0382 ) , gastric cancer ( HR 2.34 , 95 % CI 1.06 , 5.19 ; P= 0.0365 ) and thyroid cancer ( HR 1.56 , 95 % CI 1.05 , 2.31 ; P= 0.0270 ) , respectively . Participants who had at least three dietary risk factors among the high intakes of red meat and Na , low intakes of vegetables and fruits , and obesity suggested by the World Cancer Research Fund/American Institute for Cancer Research at baseline tended to have a higher risk of cancer than the others ( HR 1.26 , 95 % CI 0.99 , 1.60 ; P= 0.0653 ) . In summary , high intakes of red meat and Na were significant risk factors of cancer among Koreans BACKGROUND Although obesity has been linked to an increased risk of colorectal cancer ( CRC ) , the risk associated with long-term status or change of body fat distribution has not been fully eluci date d. METHODS Using repeated anthropometric assessment s in the Nurses ' Health Study and Health Professionals Follow-up Study , we prospect ively investigated cumulative average waist circumference , hip circumference and waist-to-hip ratio , as well as their 10-year changes over adulthood , in relation to CRC risk over 23 - 24 years of follow-up . Cox proportional hazards models were used to calculate the hazard ratio ( HR ) and 95 % confidence interval ( CI ) . RESULTS High waist circumference , hip circumference and waist-to-hip ratio were all associated with a higher CRC risk in men , even after adjusting for body mass index . The association was attenuated to null in women after adjusting for body mass index . Ten-year gain of waist circumference was positively associated with CRC risk in men ( P for trend = 0.03 ) , but not in women ( P for trend = 0.34).Compared with men maintaining their waist circumference , those gaining waist circumference by ≥ 10 cm were at a higher risk of CRC , with a multivariable-adjusted HR of 1.59 ( 95 % CI , 1.01 - 2.49 ) . This association appeared to be independent of weight change . CONCLUSIONS Abdominal adiposity , independent of overall obesity , is associated with an increased CRC risk in men but not in women . Our findings also provide the first prospect i ve evidence that waist circumference gain during adulthood may be associated with higher CRC risk in men , thus highlighting the importance of maintaining a healthy waist for CRC prevention Studies of colon cancer risk in males have reported strong positive associations with obesity , particularly with central adiposity . The association has been weaker and less consistent for women . In a prospect i ve cohort study of women , body measurements were taken directly ; fat mass and fat‐free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist‐to‐hip ratio ( WHR ) . Among 24,072 women followed on average for 10.4 years , 212 colon cancers were ascertained via the population cancer registry . We review ed medical records of all cases and classified them according to anatomic site and stage . The central adiposity measures of WHR ( hazard ratio per 0.1 unit increase = 1.31 , 95 % confidence interval ( CI ) 1.08–1.58 ) and waist circumference ( hazard ratio per 10 cm increase = 1.14 , 95 % CI 1.02–1.28 ) were positively associated with colon cancer risk . There was little or no association between other anthropometric measures and risk of colon cancer . There was some evidence that the associations were stronger for proximal tumors , but no evidence that risk differed by stage for any of the anthropometric measures . Central adiposity appears to be associated with colon cancer risk in women . © 2005 Wiley‐Liss , OBJECTIVE Although abdominal obesity and related metabolic abnormalities are hypothesized to promote colorectal carcinogenesis , direct confirmation of this effect is required . Here , we examined the relation of early-stage colorectal neoplasia to visceral fat area and markers of insulin resistance . RESEARCH DESIGN AND METHODS Subjects were participants in a comprehensive health screening conducted at the Hitachi Health Care Center , Ibaraki , Japan . During a 3-year period ( 2004–2007 ) , a total of 108 patients with early-stage colorectal neoplasia , including 22 with early cancer , were identified among individuals who received both colorectal cancer screening and abdominal computed tomography scanning . Three control subjects matched to each case subject were r and omly selected from those whose screening results were negative . Conditional logistic regression analysis was used to examine the association of measures of obesity and markers of insulin resistance with colorectal neoplasia , with adjustment for smoking and alcohol drinking . RESULTS Visceral fat area , but not subcutaneous fat area , was significantly positively associated with colorectal cancer , with odds ratios ( 95 % CI ) for the lowest to highest tertile of visceral fat area of 1 ( reference ) , 2.17 ( 0.45–10.46 ) , and 5.92 ( 1.22–28.65 ) , respectively ( Ptrend = 0.02 ) . Markers of insulin resistance , particularly fasting glucose , were also positively associated with colorectal cancer risk . In contrast , no associations were observed for colorectal adenomas . CONCLUSIONS These results suggest that visceral adipose tissue accumulation and insulin resistance may promote the development of early-stage cancer but not adenoma in the colorectum The authors chose to examine the association between body mass index ( BMI ) and incident colorectal cancer across the spectrum of BMI , including underweight persons , because detailed prospect i ve cohort data on this topic in Asians is scarce , as is data on underweight persons ( BMI , < 18.5 kg/m2 ) in any population Abstract Objective : Epidemiologic data relating obesity to risk of colorectal cancer in women have been inconclusive . Two recent studies have suggested that the association may be modified by estrogen status ; BMI was positively associated with colorectal cancer risk among women with high estrogen exposures [ premenopausal women , and postmenopausal women who currently received postmenopausal hormone therapy ( PMH ) ] . We prospect ively investigated the role of BMI in colorectal cancer risk along with the modifying effects of estrogen in a large cohort from the Women 's Health Study . Methods : Among 39,876 apparently healthy women aged ≥45 years at baseline ( 54 % of them were postmenopausal ) , 37,671 were eligible for the present study . During an average of 8.7 years of follow-up , 202 women had a confirmed diagnosis of colorectal cancer . Baseline BMI was calculated by dividing self-reported weight in kilograms by height in meters squared . Results : The multivariate relative risks ( RRs ) and 95 % confidence interval ( CI ) of colorectal cancer were 1.72 ( 1.12–2.66 ) for 27–29.9 kg/m2 , and 1.67 ( 1.08–2.59 ) for ≥30 kg/m2 , as compared with BMI < 23 kg/m2(p for trend = 0.02 ) . This positive association was seen primarily in the proximal colon ( p for trend = 0.004 ) . When the association was further examined according to PMH use among postmenopausal women , we found that both current and never users with higher BMI were at a greater risk of colorectal cancer ( p for interaction between BMI and PMH use = 0.33 ) . As compared with BMI < 23 kg/m2 , the multivariate RRs and 95 % CI for 27–29.9 and ≥30 kg/m2 were 1.98 ( 0.98–3.99 ) and 1.41 ( 0.65–3.06 ) among current users , and 1.05 ( 0.42–2.65 ) and 2.91 ( 1.40–6.06 ) among never users . Conclusions : These data suggest that higher BMI was associated with an elevated risk of colorectal cancer , and the positive relationship was not altered by estrogen exposure among postmenopausal women Objective To examine the relation between body mass index ( kg/m2 ) and cancer incidence and mortality . Design Prospect i ve cohort study . Participants 1.2 million UK women recruited into the Million Women Study , aged 50 - 64 during 1996 - 2001 , and followed up , on average , for 5.4 years for cancer incidence and 7.0 years for cancer mortality . Main outcome measures Relative risks of incidence and mortality for all cancers , and for 17 specific types of cancer , according to body mass index , adjusted for age , geographical region , socioeconomic status , age at first birth , parity , smoking status , alcohol intake , physical activity , years since menopause , and use of hormone replacement therapy . Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period . Increasing body mass index was associated with an increased incidence of endometrial cancer ( trend in relative risk per 10 units=2.89 , 95 % confidence interval 2.62 to 3.18 ) , adenocarcinoma of the oesophagus ( 2.38 , 1.59 to 3.56 ) , kidney cancer ( 1.53 , 1.27 to 1.84 ) , leukaemia ( 1.50 , 1.23 to 1.83 ) , multiple myeloma ( 1.31 , 1.04 to 1.65 ) , pancreatic cancer ( 1.24 , 1.03 to 1.48 ) , non-Hodgkin 's lymphoma ( 1.17 , 1.03 to 1.34 ) , ovarian cancer ( 1.14 , 1.03 to 1.27 ) , all cancers combined ( 1.12 , 1.09 to 1.14 ) , breast cancer in postmenopausal women ( 1.40 , 1.31 to 1.49 ) and colorectal cancer in premenopausal women ( 1.61 , 1.05 to 2.48 ) . In general , the relation between body mass index and mortality was similar to that for incidence . For colorectal cancer , malignant melanoma , breast cancer , and endometrial cancer , the effect of body mass index on risk differed significantly according to menopausal status . Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined . Among postmenopausal women in the UK , 5 % of all cancers ( about 6000 annually ) are attributable to being overweight or obese . For endometrial cancer and adenocarcinoma of the oesophagus , body mass index represents a major modifiable risk factor ; about half of all cases in postmenopausal women are attributable to overweight or obesity The authors investigated the relations of body mass index at different ages and adult weight change to incident colorectal cancer risk in the prospect i ve National Institutes of Health-AARP Diet and Health Study ( 1995 - 1996 ) , using a subcohort with repeated recall weights ( 273,679 participants ; mean baseline age = 62.8 years ) . During 2,509,662 person-years follow-up , 4076 incident colorectal cancers were ascertained . For men , an increased risk of colon cancer but not rectal cancer was associated with body mass index at baseline age ( per 5-kg/m(2 ) increase , hazard ratio ( HR ) = 1.18 , 95 % confidence interval ( CI ) : 1.11 , 1.25 ) , at age 50 years ( HR = 1.18 , 95 % CI : 1.10 , 1.26 ) , and at age 35 years ( HR = 1.16 , 95 % CI : 1.07 , 1.25 ) but less so at age 18 years . Weight gained between the ages of 18 and 35 years and between 18 years of age and the baseline age was associated with an increased risk of colon cancer in men ( per 0.5-kg/year increase , HR = 1.18 , 95 % CI : 1.11 , 1.25 and HR = 1.29 , 95 % CI : 1.16 , 1.56 , respectively ) . For women , relations throughout were weaker than those observed for men . These findings suggest that weight gains during early to middle adulthood have important influences on colon cancer risk , especially in men BACKGROUND Most cancers occur more frequently in men . Numerous explanations for this excess risk have been proposed , yet no study has quantified the degree to which height explains the sex difference even though greater height has been associated with increased risk for many cancers . METHODS During the period from 2000 to 2002 , 65308 volunteers aged 50 to 76 years were recruited to the Vitamins And Lifestyle ( VITAL ) study . Cancers of shared anatomic sites ( n = 3466 ) were prospect ively identified through 2009 through the Surveillance , Epidemiology , and End Results cancer registry . Age- and race-adjusted hazard ratios ( HRs ) for the associations between sex and incident cancers were estimated using Cox proportional hazards models , with and without adjustment for height and height squared as measures of body size . RESULTS Men had a 55 % increased risk of cancer at shared sites ( HR = 1.55 ; 95 % confidence interval [ CI ] = 1.45 to 1.66 ) . When height was accounted for , 33.8 % ( 95 % CI = 10.2 % to 57.3 % ) of the excess risk for men was explained by the height differences between sexes . The proportion mediated by height was 90.9 % , 57.3 % , and 49.6 % for kidney , melanoma , and hematologic malignancies , respectively , with little evidence that height mediates the sex difference for gastrointestinal tract , lung , and bladder cancers . For comparison , more than 35 lifestyle and medical risk factors only explained 23.1 % of the sex difference in cancer risk at shared sites . CONCLUSIONS Height is an important explanatory factor for the excess risk for men for many shared-site cancers . This suggests that some of the excess risk is due to factors associated with height ( eg , number of susceptible cells in a specific organ or growth-influencing exposures in childhood ) Obesity is a risk factor for colorectal cancer , and hyperinsulinemia , a common condition in obese patients , may underlie this relationship . Insulin , in addition to its metabolic effects , has promitotic and antiapoptotic activity that may be tumorigenic . Insulin-like growth factor (IGF)-I , a related hormone , shares sequence homology with insulin , and has even stronger mitogenic effects . However , few prospect i ve colorectal cancer studies directly measured fasting insulin , and none evaluated free IGF-I , or endogenous estradiol , a potential cofactor in postmenopausal women . Therefore , we conducted a case-cohort investigation of colorectal cancer among nondiabetic subjects enrolled in the Women 's Health Initiative Observational Study , a prospect i ve cohort of 93,676 postmenopausal women . Fasting baseline serum specimens from all incident colorectal cancer cases ( n = 438 ) and a r and om subcohort ( n = 816 ) of Women 's Health Initiative Observational Study subjects were tested for insulin , glucose , total IGF-I , free IGF-I , IGF binding protein-3 , and estradiol . Comparing extreme quartiles , insulin [ hazard ratio (HR)(q4-q1 ) , 1.73 ; 95 % confidence interval ( CI ) , 1.16 - 2.57 ; P(trend ) = 0.005 ] , waist circumference ( HR(q4-q1 ) , 1.82 ; 95 % CI , 1.22 - 2.70 ; P(trend ) = 0.001 ) , and free IGF-I ( HR(q4-q1 ) , 1.35 ; 95 % CI , 0.92 - 1.98 ; P(trend ) = 0.05 ) were each associated with colorectal cancer incidence in multivariate models . However , these associations each became nonsignificant when adjusted for one another . Endogenous estradiol levels , in contrast , were positively associated with risk of colorectal cancer ( HR comparing high versus low levels , 1.53 ; 95 % CI , 1.05 - 2.22 ) , even after control for insulin , free IGF-I , and waist circumference . These data suggest the existence of at least two independent biological pathways that are related to colorectal cancer : one that involves endogenous estradiol , and a second pathway broadly associated with obesity , hyperinsulinemia , and free BACKGROUND Recent clinical guidelines on the health risks of obesity use body mass index ( BMI ; calculated as weight in kilograms divided by the square of height in meters ) and waist circumference , but the waist-hip ratio may provide independent information . METHODS To assess the joint and relative associations of BMI , waist circumference , and waist-hip ratio with multiple disease end points , we conducted a prospect i ve cohort study of 31,702 Iowa women , aged 55 to 69 years and free of cancer , heart disease , and diabetes , assembled by r and om sampling and mail survey in 1986 . Study end points were total and cause-specific mortality and incidence of site-specific cancers and self-reported diabetes , hypertension , and hip fracture over 11 to 12 years . RESULTS The waist-hip ratio was the best anthropometric predictor of total mortality , with the multivariable-adjusted relative risk for quintile 5 vs 1 of 1.2 ( 95 % confidence interval , 1.1 - 1.4 ) , compared with 0.91 ( 95 % confidence interval , 0.8 - 1.0 ) for BMI and 1.1 ( 95 % confidence interval , 1.0 - 1 . 3 ) for waist circumference . The waist-hip ratio was also associated positively with mortality from coronary heart disease , other cardiovascular diseases , cancer , and other causes . The waist-hip ratio was associated less consistently than BMI or waist circumference with cancer incidence . All anthropometric indexes were associated with incidence of diabetes and hypertension . For example , women simultaneously in the highest quintiles of BMI and waist-hip ratio had a relative risk of diabetes of 29 ( 95 % confidence interval , 18 - 46 ) vs. women in the lowest combined quintiles . CONCLUSION The waist-hip ratio offers additional prognostic information beyond BMI and waist circumference Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics , but evidence is inconsistent . In a large UK‐based prospect i ve study we examined associations of 14 postulated risk factors with colorectal cancer risk overall , and across three anatomical sites and four morphological subtypes . Among 1.3 million women , 18,518 incident colorectal cancers were identified during 13.8 ( SD 3.4 ) years follow‐up via record linkage to national cancer registry data . Cox regression yielded adjusted relative risks . Statistical significance was assessed using correction for multiple testing . Overall , colorectal cancer risk was significantly associated with height , body mass index ( BMI ) , smoking , alcohol intake , physical activity , parity and menopausal hormone therapy use . For smoking there was substantial heterogeneity across morphological types ; relative risks around two or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours . Obese women were also at higher risk for signet ring cell tumours . For adenocarcinomas , the large majority of colorectal cancers in the cohort , all risk factor associations were weak . There was little or no heterogeneity in risk between tumours of the right colon , left colon and rectum for any of the 14 factors examined . These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types The relation between relative body weight and colorectal cancer among women is unclear . In a large prospect i ve cohort study , we found a positive association only for distal cancers among younger women that became attenuated at older ages . These results support previous reports in which results were stratified by age or colorectal cancer site . © 2001 Cancer Research The authors previously reported equations , derived from the Nutrient Biomarker Study within the Women 's Health Initiative , that produce calibrated estimates of energy , protein , and percentage of energy from protein consumption from corresponding food frequency question naire estimates and data on other factors , such as body mass index , age , and ethnicity . Here , these equations were applied to yield calibrated consumption estimates for 21,711 women enrolled in the Women 's Health Initiative dietary modification trial comparison group and 59,105 women enrolled in the observational study . These estimates were related prospect ively to total and site-specific invasive cancer incidence ( 1993 - 2005 ) . In combined cohort analyses that do not control for body mass , uncalibrated energy was not associated with total cancer incidence or site-specific cancer incidence for most sites , whereas biomarker-calibrated energy was positively associated with total cancer ( hazard ratio = 1.18 , 95 % confidence interval : 1.10 , 1.27 , for 20 % consumption increase ) , as well as with breast , colon , endometrial , and kidney cancer ( respective hazard ratios of 1.24 , 1.35 , 1.83 , and 1.47 ) . Calibrated protein was weakly associated , and calibrated percentage of energy from protein was inversely associated , with total cancer . Calibrated energy and body mass index associations were highly interdependent . Implication s for the interpretation of nutritional epidemiology studies are described OBJECTIVE : The objective was to evaluate the association of body size and fat distribution with the risk of colorectal cancer ( CRC ) in Chinese men and women . DESIGN : This was a population -based , prospect i ve cohort study .SUBJECTS : The analysis included 134 255 Chinese adults enrolled in the Shanghai Women ’s Health Study and the Shanghai Men ’s Health Study , with an average follow-up of 11.0 and 5.5 years , respectively . MEASUREMENTS : Waist circumference ( WC ) , body mass index ( BMI ) and waist-to-hip ratio ( WHR ) were measured by trained interviewers at baseline . Multivariable Cox models were used to calculate adjusted hazard ratios ( HRs ) for incident CRC . RESULTS : A total of 935 incident CRC cases were identified . Both measures of general adiposity ( measured by BMI ) and central adiposity ( measured by WHR and WC ) were significantly associated with an increased risk of colon cancer in men but not in women . Multivariable-adjusted HRs for colon cancer in men in the highest compared with the lowest quintiles were 2.15 ( 95 % confidence interval ( CI ) : 1.35–3.43 ; P for trend=0.0006 ) for BMI , 1.97 ( 95 % CI : 1.19–3.24 ; P for trend=0.0004 ) for WHR and 2.00 ( 95 % CI : 1.21–3.29 ; P for trend=0.0002 ) for WC . The BMI -associated risk was attenuated in analyses stratified by WHR , whereas the WHR-associated risk remained significant in the high BMI stratum ( HR for comparison of extreme tertiles of WHR : 3.38 , 95 % CI : 1.47–7.75 ; P for trend = 0.0002 ) . None of these anthropometric measures were significantly associated with rectal cancer . CONCLUSION : Obesity , particularly central obesity , was associated with an increased risk of colon cancer in men Background : With an increasing elderly population , the United States will experience an increased cancer burden in the coming years . We evaluated associations between anthropometric , lifestyle , and reproductive factors and risk of breast , ovarian , and colorectal cancer in a prospect i ve study of postmenopausal women with a focus on diagnoses occurring among very elderly women ( ≥75 years ) . Methods : For each cancer type , we estimated associations with relevant exposures in 2 age b and s ( < 75 vs. ≥75 years of age ) . During 22 years of follow-up , 322 ovarian , 1,311 colon , 315 rectal , and 2,664 breast cancers occurred among 37,459 postmenopausal women ( mean age at baseline 62 years , range 55–71 years ) . Results : For ovarian cancer , we identified few significant associations in either age b and . Colon cancer cases had a higher body mass index and were less likely to report estrogen or aspirin use than non-cases , yet these associations were consistent in both age b and s. Few risk factors were identified for rectal cancer in women of 75 years of age or more . For breast cancer , notably different patterns were revealed , with alcohol consumption associated with risk in the younger group and previous hysterectomy associated with risk only in the older group . Conclusion : These analyses suggest some important differences in risk factors for cancer depending on the age at diagnosis . Impact : This study suggests that etiologic differences may exist in cancers occurring in the very elderly women . The ongoing demographic shift in the United States provides a strong rationale for studies evaluating cancer etiology in the elderly . Cancer Epidemiol Biomarkers Prev ; 22(4 ) ; 681–7 . © 2013 AACR Higher body mass index ( BMI ) , higher body adiposity and obesity have been associated with increased risk of colorectal cancer . Evidence suggests that excess energy balance may influence systemic immune and inflammatory status . Thus , we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor . We collected biennial question naire data on weight and baseline height information in two prospect i ve cohort studies , the Nurses ' Health Study ( 1980 - 2010 ) and the Health Professionals Follow-up Study ( 1986 - 2010 ) . Utilizing duplication- method Cox proportional hazards regression models , we prospect ively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction , peritumoral lymphocytic reaction , intratumoral perigl and ular reaction , tumor-infiltrating lymphocytes , the overall lymphocytic reaction score , or T-cell [ CD3(+ ) , CD8(+ ) , CD45RO (PTPRC)(+ ) or FOXP3(+ ) ] density in tumor tissue . Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction . During follow up of 1,708,029 men and women ( over 3,346,752 person-years ) , we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue material s and pathological immunity data . BMI was significantly associated with higher risk of overall colorectal cancer ( Ptrend < 0.001 ) ; however , the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status ( Pheterogeneity > 0.10 ) . BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor BACKGROUND Physical inactivity and high body mass index ( weight in kilograms divided by height in square meters ) have been linked to increased risk of colon cancer . However , none of the few prospect i ve studies in women has shown a statistically significant reduction in colon cancer incidence or mortality associated with increased leisure-time physical activity . PURPOSE In this prospect i ve study , we asked whether leisure-time physical activity , body mass index , or body fat distribution could significantly influence the risk of colon cancer in women . METHODS The participants in this study were enrolled in the Nurses ' Health Study , which began in 1976 . Every 2 years , the women provided additional personal information and information on medical risk factors and major medical events . The time spent per week at a variety of leisure-time physical activities was determined , and the time spent at each activity was multiplied by its typical energy expenditure , expressed in terms of metabolic equivalents or METs . The result ing values for each woman were added to yield an MET-hours-per-week score . Reported diagnoses of colon cancer were confirmed by review of hospital records and pathology reports . Relative risks and associated 95 % confidence intervals were calculated . RESULTS In multivariate analyses that included body mass index , women who expended more than 21 MET-hours per week on leisure-time physical activity had a relative risk of colon cancer of 0.54 ( 95 % confidence interval [ CI ] = 0.33 - 0.90 ) in comparison with women who expended less than 2 MET-hours per week . Women who had a body mass index greater than 29 kg/m2 had a relative risk of colon cancer of 1.45 ( 95 % CI = 1.02 - 2.07 ) in comparison with women who had a body mass index less than 21 kg/m2 . A tendency toward higher colon cancer risk was observed for increasing waist-to-hip ratio ( relative risk = 1.48 [ 95 % CI = 0.88 - 2.49 ] for comparison of the highest quintile ratio [ > 0.833 ] to the lowest [ < 0.728 ] ) . CONCLUSIONS AND IMPLICATION S The significant inverse association between leisure-time physical activity and incidence of colon cancer in women in this study is consistent with what has been found in men . Recommendations to increase physical activity and maintain lean body weight should receive greater emphasis as part of a feasible approach to the prevention of colon cancer Westernization or industrialization leads to an increase in rates of colon cancer , which is the second leading cause of malignant death in the United States [ 1 ] . Although the precise causes of colon cancer remain unclear , a diet high in red meat or animal fat and low in fruits and vegetables appears to increase the risk for this malignancy [ 2 , 3 ] . It is perhaps less well recognized that an inverse association between physical activity and risk for colon cancer has been seen in studies of occupational activity only [ 4 - 12 ] and of both job-related and recreational activity [ 13 - 23 ] . In addition , many studies have found an association between body mass and elevated risk for colon cancer in men ; this association is weaker in women [ 24 - 33 ] . The fact that the association is stronger in men suggests that the abdominal distribution of adiposity typical in men may be an important component of enhanced risk . More limited evidence suggests that height , which may be a proxy for a person 's net energy intake during childhood and adolescence , is related to a higher risk for colon cancer [ 33 - 35 ] . We examine the association between physical activity , obesity , and attained height in relation to risk for colon cancers and their precursory adenomas in a large cohort of male health professionals in the United States . Waist and hip circumferences were available for a subcohort of the study population . We address the hypotheses that physical inactivity , obesity , and height increase the risk for colon cancer and adenoma independently of each other and of diet , and that the abdominal pattern of obesity is an additional independent risk factor . Methods Study Population The Health Professionals Follow-up Study [ 36 ] was started in 1986 ; in that year , 51 529 male dentists , optometrists , osteopaths , podiatrists , pharmacists , and veterinarians in the United States between 40 and 75 years of age responded to a mailed question naire . They reported on their leisure-time physical activity ( described below ) ; current body weight ; weight at age 21 years ; height ; history of cancer and other medical conditions ; parental history of various diseases , including colorectal cancer ; and use of aspirin and other nonsteroidal anti-inflammatory medications . They also reported dietary and alcohol intake using a vali date d [ 37 , 38 ] , semi-quantitative food-frequency question naire . We mailed an optional question naire in 1987 to assess waist and hip circumferences . In 1988 , 1990 , and 1992 , we up date d exposure information and ascertained newly diagnosed medical conditions and history of colonoscopy or sigmoidoscopy , including the indications for endoscopy : bleeding in stool , positive results from tests for occult fecal blood , abdominal pain , diarrhea or constipation , family history of colorectal cancer , routine screening without symptoms , or follow-up [ 39 ] . Most of the deaths in the cohort were reported by family members or by the postal system in response to the follow-up question naires . We also used the National Death Index to identify deaths among nonrespondents [ 40 ] . Assessment of Physical Activity The 1986 question naire included a section about mainly recreational or leisure-time physical activity . The reliability and validity of question naires design ed to assess physical activity have been investigated [ 41 - 43 ] . A question naire such as the one used in our cohort was evaluated in a cohort of U.S. nurses and was found to provide useful information [ 44 ] , and similar results were found during a similar validation study done within the Health Professionals cohort ( Chasan-Taber S. Personal communication ) . Participants reported the average time per week spent doing each of eight moderate and vigorous activities , choosing from among 10 possible responses that ranged from 0 minutes to 11 or more hours per week . The specific activities listed were walking or hiking outdoors ( including walking during golf ) ; jogging ( slower than 10 minutes/mile ) ; running ( 10 minutes/mile or faster ) ; bicycling ( including that done on a stationary machine ) ; lap swimming ; tennis , squash , or racquetball ; and calisthenics or rowing . In addition , each respondent reported the number of flights of stairs he climbed daily and his usual walking pace . The reported time spent at each activity per week was multiplied by its typical energy expenditure requirements expressed in metabolic equivalents ( METs ) [ 45 ] to yield a MET-hour score . One MET , which is the energy expended by sitting quietly , is equivalent to 3.5 mL of oxygen uptake per kilogram of body weight per minute for a 70-kg adult . For example , 1 hour per week of running contributed 10.2 MET-hours , 1 hour of tennis contributed 6 MET-hours , and 1 hour of walking at a moderate pace contributed 3.2 MET-hours . Body weight was excluded from the derivation of energy expenditure from physical activity to avoid confounding the expenditure variable by body weight . If more than one published intensity level was available for a given activity , the moderate or general MET value was chosen . An average MET value was assigned to the categories that listed more than one activity , such as rowing or calisthenics , and squash or racquetball . Assessment of Anthropometric Variables Each man reported his current weight and height and his weight at age 21 years on the 1986 question naire . In 1987 , we mailed an optional question naire once to obtain additional exposure information , including body circumference measurements . We instructed each participant to measure ( to the nearest quarter inch ) his waist at the umbilicus and his hips at the largest circumference between the waist and thighs while st and ing and without measuring over bulky clothing [ 46 ] . We provided a tape measure and an illustration to help st and ardize the measurements . Sixty-five percent of the cohort responded . We used the Quetelet index ( kilograms/height in meters2 ) as a measure of total adiposity , waist-to-hip ratio to measure relative distribution of fat , and waist circumference to estimate total abdominal fat . Although the waist-to-hip ratio has been used more widely , waist circumference provides an estimate of absolute abdominal adiposity , the component most closely related to important metabolic abnormalities , including hyperinsulinemia , hypertension , and high triglyceride levels . To remove extraneous variation in the waist circumference because of height ( taller men tend to have larger waist circumferences due to their larger body size rather than to obesity ) , we adjusted waist for height using residual analysis [ 47 ] . We first regressed waist on height using multiple linear regression and then added the residual to the average waist size ( 37.4 inches ) for a man of average height ( 70 inches ) to convert this measure back to the initial scale . This conversion created for each man a st and ardized waist circumference unconfounded by height . We evaluated the precision of self-reported anthropometric measures among 123 cohort members who were part of a dietary validation study [ 46 ] . Trained technicians paid the sub study participants two visits , approximately 6 months apart , to measure current weight and waist and hip circumferences . The Pearson correlation between self-report and the average of the technicians ' two measurements was 0.97 for weight , 0.95 for waist circumference , 0.88 for hip circumference , and 0.69 for waist-to-hip ratio . The men 's self- measurements of their waist circumferences were 0.36 inches greater , their self- measurements of hip circumferences were 0.78 inches smaller , and their self- measurements of weight were 2.3 pounds less than the technician 's measurements . Identification of Patients with Colorectal Cancers In 1988 , 1990 , and 1992 , we asked each participant whether cancer had been diagnosed during the previous 2 years . The response rate to the follow-up question naires was 94 % through 31 January 1992 . When a participant ( or a decedent 's next-of-kin ) reported a diagnosis of cancer of the colon or rectum , we sought permission to obtain hospital records and pathology reports . A study physician , blinded to exposure information , review ed all medical records received and extracted data about histologic type , anatomic location , and stage of the cancer . Proximal colon cancers were defined as those from the cecum to and including the splenic flexure , and distal colon cancers were defined as those in the descending and sigmoid colon . We confirmed 249 new cases of colorectal adenocarcinoma ( excluding carcinoma in situ ) , 90 % by medical records and the remainder with corroborating information about diagnosis and treatment from the cohort member . Two hundred three cancers were in the colon and 46 were in the rectum . Identification of Patients with Colorectal Adenomas and Controls Because more than 90 % of the adenomas were diagnosed during endoscopic procedures for screening or for unrelated gastrointestinal conditions , we restricted the adenoma analysis to men who had had a colonoscopy or sigmoidoscopy . This was done to reduce the potential for detection bias . Most procedures were sigmoidoscopies ; thus , we analyzed only adenomas of the distal colorectum . Although we did not examine proximal colon adenomas , this should not have biased inferences for the distal colorectum . However , different causes for proximal adenomas may exist . A total of 12 879 men who did not meet any of the exclusion criteria ( see Data Analysis ) reported having had an endoscopy between 1986 and 1992 . In 1993 , we sent a mailing to a r and om sample of 200 controls ( men who reported negative results from an endoscopy ) to confirm that they did not have adenomas . After one mailing , 140 ( 70 % ) controls granted us permission to review the medical records of their endoscopic procedure ; none had an unreported , histologically confirmed adenoma . We were able to recontact 96 % of the men who reported a diagnosis of polyp , and we received medical records in response to more than 96 % of the requests sent to medical record departments , The relation between body mass index ( BMI ) and risk of cancer incidence is controversial . Cancer incidence during 1972–2008 in relation to BMI was investigated in a prospect i ve cohort of 54,725 Finns aged 24–74 years and free of cancer at enrollment . Over a mean follow-up of 20.6 years , 8,429 ( 15.4 % ) incident cancers were recorded , 4,208 ( 49.9 % ) from men . Both parametric and nonparametric approaches were used to evaluate the shape of the relationship between BMI and incidence of cancer . BMI had a linear positive association with incidence of cancers of the colon , liver , kidney , bladder and all sites combined in men , and of cancers of the stomach , colon , gallbladder and ovary in women , an inverse association with incidence of cancers of the lung in men and the lung and breast in women , a J-shaped association with incidence of all cancers combined in women . High BMI in women was associated with an increased overall cancer risk in never smokers but a reduced risk in smokers . Elevated BMI was associated with an increased risk of incidence of cancers of certain sites Obesity is a controversial risk factor for colorectal cancer ( CRC ) in older women . We evaluated associations between multiple body size parameters and incident CRC in the prospect i ve , population -based Iowa Women 's Health Study ( IWHS ) . IWHS participants , ages 55 to 69 years , provided data regarding height ; weight ; weight at ages 50 , 40 , 30 , 18 years ; hip circumference ; and waist circumference at baseline ( 1986 ) . Derived variables included body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , and “ overweight years ” ( OWY ; conceptually similar to cigarette pack-years ) . Incident CRC cases ( n = 1,464 ) were ascertained from the State Health Registry of Iowa , through 2005 . Multivariable Cox regression models were fit to estimate body size – associated CRC risks . Among 36,941 women ( 619,961 person-years ) , baseline height , weight , BMI , hip circumference , waist circumference , and WHR were all positively associated with incident CRC ( P trend ≤ 0.003 for each ) . Baseline BMI yielded the highest CRC risk estimates ( obese III versus normal , RR = 1.56 ; 95 % CI = 1.10–2.22 ; P trend < 0.001 ) and was more closely associated with distal than proximal tumors ( P trend < 0.001 versus 0.06 ) . Conversely , height was more closely associated with proximal than distal tumors ( P trend < 0.001 versus 0.04 ) . Other body size parameters were less predictive of incident CRC . These data strongly support a positive association between increased body size and CRC risk among older women . Further investigation of when increased body size has the greatest effect on CRC risk ( i.e. , early adulthood versus later adulthood ) might also be informative , particularly with respect to defining subsite-specific pathways of colorectal carcinogenesis . Cancer Prev Res ; 3(12 ) ; 1608–20 . © 2010 AACR General obesity , typically measured using body mass index ( BMI ) , has been associated with an increased risk of several cancers . However , few prospect i ve studies have been conducted in Asian population s. Although central obesity , often measured using waist-hip ratio ( WHR ) , is more predictive for type 2 diabetes and cardiovascular diseases ( CVD ) risk than BMI , knowledge of its association with cancer incidence is limited . In a cohort of 68,253 eligible Chinese women , we prospect ively investigated the association of BMI , WHR and weight change during adulthood with risk of overall cancer and major site-specific cancers using multivariate Cox proportional hazard models . Compared to the BMI group of 18.5 - 22.9 kg/m(2 ) , obese ( BMI ≥ 30 kg/m(2 ) ) women were at an increased risk of developing overall cancer ( hazard ratio = 1.36 , 95 % confidence interval = 1.21 - 1.52 ) , postmenopausal breast cancer ( HR : 2.43 , 95 % CI : 1.73 - 3.40 ) , endometrial cancer ( HR : 5.34 , 95 % CI : 3.48 - 8.18 ) , liver cancer ( HR : 1.93 , 95 % CI : 1.14 - 3.27 ) and epithelial ovarian cancer ( HR : 2.44 , 95 % CI : 1.37 - 4.35 ) . Weight gain during adulthood ( per 5 kg gain ) was associated with increased risk of all cancers combined ( HR : 1.05 , 95 % CI : 1.03 - 1.08 ) , postmenopausal breast cancer ( HR : 1.17 , 95 % CI : 1.10 - 1.24 ) and endometrial cancer ( HR : 1.37 , 95 % CI : 1.27 - 1.48 ) . On the other h and , WHR was not associated with cancer risk after adjustment for baseline BMI . These findings suggest that obesity may be associated with cancer risk through different mechanisms from those for type 2 diabetes and CVD and support measures of maintaining health body weight to reduce cancer risk in Chinese women In a 6-year prospect i ve study , the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study ( California , 1976 - 1982 ) who , at baseline , had no documented or reported history of cancer . The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates . The authors found a positive association with total meat intake ( risk ratio ( RR ) for > or = 1 time/week vs. no meat intake = 1.85 , 95 % confidence interval ( CI ) 1.19 - 2.87 ; p for trend = 0.01 ) and , among subjects who favored specific types of meat , positive associations with red meat intake ( RR for > or = 1 time/week vs. no red meat intake = 1.90 , 95 % CI 1.16 - 3.11 ; p for trend = 0.02 ) and white meat intake ( RR for > or = 1 time/week vs. no white meat intake = 3.29 , 95 % CI 1.60 - 6.75 ; p for trend = 0.006 ) . An inverse association with legume intake ( RR for > 2 times/week vs. < 1 time/week = 0.53 , 95 % CI 0.33 - 0.86 ; p for trend = 0.03 ) was observed . Among men , a positive association with body mass index was observed ( relative to the RR for tertile III ( > 25.6 kg/m2 ) vs. tertile I ( < 22.5 kg/m2 ) = 2.63 , 95 % CI 1.12 - 6.13 ; p for trend = 0.05 ) . A complex relation was identified whereby subjects exhibiting a high red meat intake , a low legume intake , and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables . This pattern of putative risk factors would likely contribute to increases in both insulin resistance ( high body mass , high red meat intake ) and glycemic load ( low legume intake ) , a synergism that , if causal , implicates hyperinsulinemic exposure in colon carcinogenesis . The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology Background Although body mass index has been shown to be associated with colon cancer , studies of rectal cancer risk have generally reported no association . The relationship between rectal cancer risk and central adiposity , overall fat mass , and fat-free mass is unknown . Methods In a prospect i ve cohort study of people aged 27–75 years , body measurements were taken directly ; fat mass and fat-free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist-to-hip ratio . Among 16,867 men and 24,247 women followed on average for 10.3 years , 229 rectal cancers were ascertained via the population cancer registry . Results When comparing the highest tertile with the lowest tertile , weight ( hazard ratio = 1.4 , 95 % confidence interval ( CI ) 1.1–2.0 ) , waist circumference ( hazard ratio = 1.4 , 95 % CI 1.0–1.9 ) , fat mass ( hazard ratio = 1.4 , 95 % CI 1.0–2.0 ) and percent fat ( hazard ratio = 1.4 , 95 % CI 1.0–2.0 ) were positively associated with rectal cancer risk . There was no evidence that risk differed by sex for any of the anthropometric measures . Conclusions Waist circumference and fat mass may be weakly related to risk of rectal cancer BACKGROUND While previous studies suggest that overweight , middle-aged men may face increased risk of colon cancer , it is unclear whether their weights as young adults influence this risk . It is also unknown whether their level of physical activity affects their risk of developing colon cancer . PURPOSE To determine the relationship between being overweight in middle-age or young adulthood and colon cancer risk , we prospect ively studied alumni of Harvard University . We also investigated whether being overweight influences risk differently for men with different levels of physical activity . METHODS In 1962 or 1966 ( 1962/1966 ) , alumni completed question naires on weight , height , other sociodemographic characteristics , and medical history . We obtained information on weight and height at college entry from university archives . Alumni ( n = 17,595 ) were followed from 1962/1966 to 1988 for colon cancer occurrence , ascertained from follow-up question naires in 1977 and 1988 and death certificates . RESULTS Between 1962/1966 and 1988 , 302 cases of colon cancer were diagnosed . Colon cancer risk increased with higher levels of Quetelet 's index ( weight [kg]/height [m]2 ) in 1962/1966 . Relative risk per unit increase , adjusted for age , physical activity , and parental history of cancer , was 1.08 ( 95 % confidence interval [ CI ] , 1.04 - 1.13 ) . Quetelet 's index at college entry did not predict risk as well ( adjusted relative risk per unit increase , 1.05 ; 95 % CI , 1.00 - 1.10 ) . The heaviest fifth of alumni during both college time and in 1962/1966 had almost two and one-half times the risk of the lightest fifth of alumni ( adjusted relative risk , 2.40 ; 95 % CI , 1.40 - 4.13 ) . When alumni were classified according to activity level in 1962/1966 , higher levels of Quetelet 's index were significantly associated with colon cancer risk only among those who were less active . CONCLUSIONS Overweight during middle-age or young adulthood is associated with higher colon cancer risk ; in overweight , physically active men , however , the risk of colon cancer may not be increased Background : Prospect i ve studies in Western and Asian population s suggest that height is a risk factor for various cancers . However , few studies have explored potential confounding or effect modification of the association by other factors . Methods : We examined the association between height measured at enrollment in 144,701 women participating in the Women 's Health Initiative and risk of all cancers combined and cancer at 19 specific sites . Over a median follow-up of 12.0 years , 20,928 incident cancers were identified . We used Cox proportional hazards models to estimate HR and 95 % confidence intervals ( CI ) per 10 cm increase in height , with adjustment for established risk factors . We also examined potential effect modification of the association with all cancer and specific cancers . Results : Height was significantly positively associated with risk of all cancers ( HR = 1.13 ; 95 % CI , 1.11–1.16 ) , as well as with cancers of the thyroid , rectum , kidney , endometrium , colorectum , colon , ovary , and breast , and with multiple myeloma and melanoma ( range of HRs : 1.13 for breast cancer to 1.29 for multiple myeloma and thyroid cancer ) . These associations were generally insensitive to adjustment for confounders , and there was little evidence of effect modification . Conclusions : This study confirms the positive association of height with risk of all cancers and a substantial number of cancer sites . Impact : Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help eluci date the association . Cancer Epidemiol Biomarkers Prev ; 22(8 ) ; 1353–63 . © 2013 AACR The incidence of several cancers increases with height . Some studies report that leg length , a marker of prepubertal growth , is the component of height underlying these associations , but few prospect i ve studies have investigated this issue . We examined height-cancer associations in a 21-yr follow-up of a cohort based on 2,512 men aged 45 - 59 living in the town of Caerphilly , South Wales , U.K. , between 1979 and 1983 . The men underwent a detailed examination , and 2,393 ( 95.3 % ) had measures of height and sitting height ( from which leg length and trunk length were derived ) recorded and were cancer-free at baseline . Cox proportional hazards models were used to investigate associations of height , leg length , and trunk length with overall and site-specific cancer incidence ; 328 men developed cancer over the follow-up period . Associations with height were weak and did not reach conventional levels of statistical significance . In models controlling for age , socioeconomic position , smoking , and body mass index , cancer incidence was weakly positively associated with increases in height ; hazard ratio ( HR , 95 % confidence interval ) per st and ard deviation ( 6 cm ) increase in height was 1.09 ( 0.97 , 1.21 ; P = 0.14 ) . Associations were somewhat stronger in relation to leg length ( HR 1.09 ; ( 0.97 - 1.22 ) than trunk length ( HR 1.05 ; 0.94 - 1.18 ) . Height-cancer associations were strongest for lung cancer ( HR 1.21 ; 0.96 - 1.51 ) . This analysis provides limited support for the suggestion that leg length is the component of height underlying height-cancer associations Predictors of colorectal cancer have been extensively studied with some evidence suggesting that risk factors vary by subsite . Using data from 2 prospect i ve cohort studies , we examined established risk factors to determine whether they were differentially associated with colon and rectal cancer . Our study population included 87,733 women from the Nurses ' Health Study ( NHS ) and 46,632 men from the Health Professionals Follow Up Study ( HPFS ) . Exposure information was collected via biennial question naires ( dietary variables were collected every 4 years ) . During the follow-up period ( NHS : 1980 to May 31 , 2000 ; HPFS : 1986 to January 31 , 2000 ) , we identified 1,139 cases of colon cancer and 339 cases of rectal cancer . We used pooled logistic regression to estimate multivariate relative risks for the 2 outcomes separately and then used polytomous logistic regression to compare these estimates . In the combined cohort , age , gender , family history of colon or rectal cancer , height , body mass index , physical activity , folate , intake of beef , pork or lamb as a main dish , intake of processed meat and alcohol were significantly associated with colon cancer risk . However , only age and sex were associated with rectal cancer . In a stepwise polytomous logistic regression procedure , family history and physical activity were associated with statistically significant different relative risks of colon and rectal cancer . Our findings support previous suggestions that family history and physical activity are not strong contributors to the etiology of rectal cancer . Future investigations of colon or rectal cancer should take into consideration risk factor differences by subsite Although the influence of body mass index on cancer risk has been intensively investigated , few epidemiologic studies have examined the association of adult height with risk of cancer . We assessed the association of height with risk of all cancer and of 19 site‐specific cancers in the Canadian National Breast Screening Study , a prospect i ve cohort of nearly 90,000 women . Weight and height were measured at enrollment , and information on reproductive and medical history as well as lifestyle exposures was obtained by means of question naire . After exclusions , 5,679 incident invasive cancers were identified among 88,256 women . We used Cox proportional hazards model to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CI ) per 10 cm increase in height . All tests of statistical significance were two sided . All cancers combined and ten specific sites ( colorectum , colon , premenopausal breast , postmenopausal breast , endometrium , ovary , kidney , thyroid , melanoma and leukemia ) showed statistically significant positive associations with height . The HR for all cancers combined was 1.13 ( 95 % CI : 1.08–1.18 ) , and the magnitude of the associations for specific sites ranged from HR 1.11 ( 95 % CI : 1.03–1.20 ) for postmenopausal breast cancer to HR 1.51 ( 95 % CI : 1.27–1.80 ) for melanoma . Our study provides strong support for a positive association of adult height with risk of certain cancers . The underlying biological mechanisms are not clear but may differ by anatomic site Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer . Anthropometric measures ( height , weight , and body mass index ( weight (kg)/height (m)(2 ) ) and metabolic abnormalities associated with insulin resistance syndrome ( IRS ) ( abnormalities in measured blood pressure , high density lipoprotein ( HDL ) cholesterol , and total cholesterol ) were prospect ively evaluated for associations with incident colon ( n = 227 ) , rectal ( n = 183 ) , and colorectal ( n = 410 ) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study . Cox proportional hazards models were used to calculate hazard ratios and 95 % confidence intervals . In comparison with the lowest quintile , the highest quintile of body mass index was significantly associated with colorectal cancer ( hazard ratio ( HR ) = 1.70 , 95 % confidence interval ( CI ) : 1.01 , 2.85 ; p-trend = 0.01 ) , particularly colon cancer . Subjects with a cluster of three IRS-related conditions ( hypertension , body mass index > /=25 kg/m(2 ) , and HDL cholesterol level < 40 mg/dl ( < 1.55 mmol/liter ) ) , compared with those with fewer conditions , had a significantly increased risk of colorectal cancer ( HR = 1.40 , 95 % CI : 1.12 , 1.74 ) , particularly colon cancer ( HR = 1.58 , 95 % CI : 1.18 , 2.10 ) , but not rectal cancer . These results support the hypothesis that the significant association observed between IRS-defining metabolic abnormalities and colorectal cancer is determined primarily by adiposity BACKGROUND For men and women , taller height is associated with increased risk of all cancers combined . For colorectal cancer ( CRC ) , it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies . We performed a Mendelian r and omization study to examine the association between height and CRC risk . METHODS To minimize confounding and bias , we derived a weighted genetic risk score predicting height ( using 696 genetic variants associated with height ) in 10,226 CRC cases and 10,286 controls . Logistic regression was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) for associations between height , genetically predicted height and CRC . RESULTS Using conventional methods , increased height ( per 10-cm increment ) was associated with increased CRC risk ( OR = 1.08 , 95 % CI = 1.02 - 1.15 ) . In sex-specific analyses , height was associated with CRC risk for women ( OR = 1.15 , 95 % CI = 1.05 - 1.26 ) , but not men ( OR = 0.98 , 95 % CI = 0.92 - 1.05 ) . Consistent with these results , carrying greater numbers of ( weighted ) height-increasing alleles ( per 1-unit increase ) was associated with higher CRC risk for women and men combined ( OR = 1.07 , 95 % CI = 1.01 - 1.14 ) and for women ( OR = 1.09 , 95 % CI = .01 - 1.19 ) . There was weaker evidence of an association for men ( OR = 1.05 , 95 % CI = 0.96 - 1.15 ) . CONCLUSION We provide evidence for a causal association between height and CRC for women . The CRC-height association for men remains unclear and warrants further investigation in other large studies PURPOSE To evaluate an association between obesity , measured by body mass index ( BMI ; kg/m(2 ) ) , and risk of cancer at individual and all sites in postmenopausal women . METHODS A cohort of 170,481 postmenopausal Korean women who were age 40 to 64 years at baseline measurement of BMI was observed prospect ively from 1994 to 2003 for cancer incidence . Multivariable adjusted proportional hazard models were used for evaluating the association . RESULTS Women with a BMI of 30 kg/m(2 ) or higher had a 23 % higher risk of cancer than women with a BMI between 21.0 and 22.9 kg/m(2 ) ( hazard ratio = 1.23 ; 95 % CI , 1.08 to 1.41 ) . According to the increase in BMI level , significant positive trends existed in cancers of colon , breast , corpus uteri , and kidney with hazard ratios of 1.05 ( 95 % CI , 1.02 to 1.08 ) , 1.07 ( 95 % CI , 1.05 to 1.10 ) , 1.13 ( 95 % CI , 1.07 to 1.20 ) , and 1.08 ( 95 % CI , 1.02 to 1.15 ) , respectively , for the increase of BMI by 1 kg/m(2 ) . When the analysis was limited to never-smokers , women with a BMI of 25 kg/m(2 ) or higher showed a significantly increased risk of cancers of the colon , breast , corpus uteri , and kidney and leukemia compared with the normal BMI ( 18.5 to 22.9 kg/m(2 ) ) group . CONCLUSION Although variations exist between the individual cancer sites , obesity was associated with an overall increased risk of cancer in postmenopausal Korean women . To reduce the risk of cancer , active strategies to prevent obesity should be implemented in postmenopausal women PURPOSE Obesity has consistently been linked to an increased risk of colorectal cancer , particularly among men . Whether body mass index ( BMI ) differentially influences the risk across the stages of colorectal cancer development remains unclear . We evaluated the associations of BMI with colorectal adenoma incidence , adenoma recurrence , and cancer in the context of a large screening trial , in which cases and controls had an equal chance for disease detection . METHODS We prospect ively evaluated the association between baseline BMI and the risk of incident distal adenoma ( 1,213 cases ) , recurrent adenoma ( 752 cases ) , and incident colorectal cancer ( 966 cases ) among men and women , ages 55 to 74 years , r and omly assigned to receive flexible sigmoidoscopy screening as part of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . We calculated odds ratios ( ORs ) and 95 % CIs for adenoma incidence and recurrence , and hazard ratios ( HRs ) and 95 % CIs for colorectal cancer incidence , using multivariable-adjusted models . RESULTS Compared with normal-weight men ( 18.5 to 24.9 kg/m(2 ) ) , obese men ( ≥ 30 kg/m(2 ) ) had significantly higher risk of incident adenoma ( OR , 1.32 ; 95 % CI , 1.06 to 1.65 ) and colorectal cancer ( HR , 1.48 ; 95 % CI , 1.16 to 1.89 ) and a borderline increased risk of recurrent adenoma ( OR , 1.50 ; 95 % CI , 0.98 to 2.30 ) . No associations were observed for either adenoma or cancer in women . CONCLUSION Data from this large prospect i ve study suggest that obesity is important throughout the natural history of colorectal cancer , at least in men , and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings Epidemiological studies are remarkably consistent , especially among men , in showing that overweight and obesity [ body mass index ( BMI ) > 25 ] are associated with increased risk of colon cancer . However , no prospect i ve studies address the influence of weight change in adulthood on subsequent colon cancer risk . In this study , we investigated whether weight change influences colon cancer risk utilizing prospect ively collected weight data . We included 46,349 men aged 40 - 75 participating in the Health Professionals Follow-Up Study . Question naires including items on weight were completed every second year during follow-up from 1986 to 2004 . Up date d weight change between consecutive question naires during follow-up and recalled weight gain since age 21 was evaluated . All eligible men were cancer-free at baseline . Proportional hazard and restricted spline regression models were implemented . Over an 18-year period , we documented 765 cases of colon cancer . Cumulative mean BMI > 22.5 was associated with significantly increased risk of colon cancer . The short-term weight change in the prior 2 to 4 years was positively and significantly associated with risk [ HR = 1.14 ( 95 % confidence interval , 1.00 - 1.29 ) for 4.54 kg ( 10 pounds ) increment , p = 0.04 for overall trend ] . Weight gain per 10 years since age 21 was associated with significantly increased risk [ HR = 1.33 ( 1.12 - 1.58 ) for 4.54 kg increase per 10 years , p = 0.001 ] . We estimated that 29.5 % of all colon cancer cases was attributable to BMI above 22.5 . Our results add support that overweight and obesity are modifiable risk factors for colon cancer among men and suggest that weight has an important influence on colon cancer risk even in later life Background : Several large studies of obesity and colorectal cancer risk have found no association among women but a reasonably consistent positive association among men . In women , a positive association that is stronger among , or limited to , those who are premenopausal has been suggested by studies that stratified analyses by age , although no previous study has examined the association by menopausal status . Methods : We used proportional hazards analyses to estimate hazard ratios relating obesity to colorectal cancer risk among 89 835 women aged 40–59 years at recruitment into the Canadian National Breast Screening Study , a multicentre r and omised controlled trial of mammography screening for breast cancer . During an average 10.6 years of follow up ( 936 433 person years ) , a total of 527 women were diagnosed with incident colorectal cancer ( 363 colon and 164 rectal ) . Results : We found that obesity ( body mass index ≥30 kg/m2 ) was associated with an approximately twofold increased risk of colorectal cancer among women who were premenopausal at baseline ( hazard ratio 1.88 , 95 % confidence interval 1.24–2.86 ) . There was no association among postmenopausal women ( p for interaction=0.01 ) , and there was only a weak positive association in the entire cohort . Conclusions : Our data suggest that obesity is associated with a twofold increased risk of colorectal cancer in premenopausal women but is not associated with altered risk in postmenopausal women . Effect modification by menopausal status may better explain the inconsistent or weak findings in previous studies than the presumed lack of an association among women BACKGROUND Body weight and body mass index ( BMI ) are positively related to risk of colon cancer in men , whereas weak or no associations exist in women . This discrepancy may be related to differences in fat distribution between sexes or to the use of hormone replacement therapy ( HRT ) in women . METHODS We used multivariable adjusted Cox proportional hazards models to examine the association between anthropometric measures and risks of colon and rectal cancer among 368 277 men and women who were free of cancer at baseline from nine countries of the European Prospect i ve Investigation Into Cancer and Nutrition . All statistical tests were two-sided . RESULTS During 6.1 years of follow-up , we identified 984 and 586 patients with colon and rectal cancer , respectively . Body weight and BMI were statistically significantly associated with colon cancer risk in men ( highest versus lowest quintile of BMI , relative risk [ RR ] = 1.55 , 95 % confidence interval [ CI ] = 1.12 to 2.15 ; P(trend ) = .006 ) but not in women . In contrast , comparisons of the highest to the lowest quintile showed that several anthropometric measures , including waist circumference ( men , RR = 1.39 , 95 % CI = 1.01 to 1.93 ; P(trend ) = .001 ; women , RR = 1.48 , 95 % CI = 1.08 to 2.03 ; P(trend ) = .008 ) , waist-to-hip ratio ( WHR ; men , RR = 1.51 , 95 % CI = 1.06 to 2.15 ; P(trend ) = .006 ; women , RR = 1.52 , 95 % CI = 1.12 to 2.05 ; P(trend ) = .002 ) , and height ( men , RR = 1.40 , 95 % CI = 0.99 to 1.98 ; P(trend ) = .04 ; women , RR = 1.79 , 95 % CI = 1.30 to 2.46 ; P(trend)<.001 ) were related to colon cancer risk in both sexes . The estimated absolute risk of developing colon cancer within 5 years was 203 and 131 cases per 100,000 men and 129 and 86 cases per 100,000 women in the highest and lowest quintiles of WHR , respectively . Upon further stratification , no association of waist circumference and WHR with risk of colon cancer was observed among postmenopausal women who used HRT . None of the anthropometric measures was statistically significantly related to rectal cancer . CONCLUSIONS Waist circumference and WHR , indicators of abdominal obesity , were strongly associated with colon cancer risk in men and women in this population . The association of abdominal obesity with colon cancer risk may vary depending on HRT use in postmenopausal women ; however , these findings require confirmation in future studies Obesity is associated with diverse health risks , but the role of body weight ( BMI ) as a risk factor for all and site-specific cancers remains controversial and risks for cancer associated with obesity have not been well-characterized in Asians . Body weight and risk for cancer were examined in a 14-year prospect i ve cohort study of 1,213,829 Koreans aged 30 - 95 years insured by the National Health Insurance Corporation who had a biennial medical evaluation in 1992 - 1995 . Incidence rates for all cancers and site-specific cancers were examined in relation to BMI . Age- and smoking-status adjusted hazard ratios ( HR ) with 95 % confidence intervals ( CI ) were examined using the Cox proportional hazards model . For both sexes , the average baseline BMI was 23.2 kg/m(2 ) , and the association of risk for all-cancers with BMI was positive . Obese men ( BMI > or= 30 kg/m(2 ) ) were at increased risk for developing the following cancers : stomach ( 1.31 , 1.05 - 1.64 ) , colon ( 1.42 , 1.02 - 1.98 ) , liver ( 1.63 , 1.27 - 2.10 ) and gallbladder ( 1.65 , 1.11 - 2.44 ) . Obese women ( BMI > or= 30 kg/m(2 ) ) were at increased risk for developing liver cancer ( 1.39 , 1.00 - 1.94 ) , pancreatic cancer ( 1.80 , 1.14 - 2.86 ) and breast cancer among women aged > or=50 years old ( 1.38 , 1.00 - 1.90 ) . The HRs were comparable in never and ever smokers for all cancers and all specific sites except for lung cancer . For all cancers common to both sexes , the association was significantly weaker ( p < 0.01 ) in females . Our study provides further confirmation of the excess cancer risk associated with obesity . Rising obesity in Asian population s raises concern that increasing numbers of avoidable cancer cases will occur among Asians |
1,120 | 21,524,852 | The results indicate that there is evidence of central hyperexcitability in people with chronic musculoskeletal pain .
Our review also suggests that shorter inter-pulse duration tends to yield smaller variability in NFR threshold . | Chronic musculoskeletal conditions are increasingly conceived as involving altered central nervous system processing , and impaired nociceptive flexor reflex ( NFR ) appears to reflect altered central nervous system processing .
The primary objective was to synthesize the evidence for impaired NFR in these conditions .
The secondary objective was to evaluate the NFR stimuli parameters employed by review ed studies . | Background The evidence that exercise intervention is effective for treatment of chronic low back pain comes from trials that are not placebo-controlled . Objective The purpose of this study was to investigate the efficacy of motor control exercise for people with chronic low back pain . Design This was a r and omized , placebo-controlled trial . Setting The study was conducted in an outpatient physical therapy department in Australia . Patients The participants were 154 patients with chronic low back pain of more than 12 weeks ’ duration . Intervention Twelve sessions of motor control exercise ( ie , exercises design ed to improve function of specific muscles of the low back region and the control of posture and movement ) or placebo ( ie , detuned ultrasound therapy and detuned short-wave therapy ) were conducted over 8 weeks . Measurements Primary outcomes were pain intensity , activity ( measured by the Patient-Specific Functional Scale ) , and patient 's global impression of recovery measured at 2 months . Secondary outcomes were pain ; activity ( measured by the Patient-Specific Functional Scale ) ; patient 's global impression of recovery measured at 6 and 12 months ; activity limitation ( measured by the Rol and -Morris Disability Question naire ) at 2 , 6 , and 12 months ; and risk of persistent or recurrent pain at 12 months . Results The exercise intervention improved activity and patient 's global impression of recovery but did not clearly reduce pain at 2 months . The mean effect of exercise on activity ( measured by the Patient-Specific Functional Scale ) was 1.1 points ( 95 % confidence interval [CI]=0.3 to 1.8 ) , the mean effect on global impression of recovery was 1.5 points ( 95 % CI=0.4 to 2.5 ) , and the mean effect on pain was 0.9 points ( 95 % CI=−0.01 to 1.8 ) , all measured on 11-point scales . Secondary outcomes also favored motor control exercise . Limitation Clinicians could not be blinded to the intervention they provided . Conclusions Motor control exercise produced short-term improvements in global impression of recovery and activity , but not pain , for people with chronic low back pain . Most of the effects observed in the short term were maintained at the 6- and 12-month follow-ups Objective .—The aim of this study was to determine whether clinical indicators of cutaneous allodynia predict the success of migraine therapy with sumatriptan using a brief question naire Objective To investigate the efficacy of a programme of manual therapy and exercise treatment compared with placebo treatment delivered by physiotherapists for people with chronic rotator cuff disease . Design R and omised , participant and single assessor blinded , placebo controlled trial . Setting Metropolitan region of Melbourne , Victoria , Australia . Participants 120 participants with chronic ( > 3 months ) rotator cuff disease recruited through medical practitioners and from the community . Interventions The active treatment comprised a manual therapy and home exercise programme ; the placebo treatment comprised inactive ultrasound therapy and application of an inert gel . Participants in both groups received 10 sessions of individual st and ardised treatment over 10 weeks . For the following 12 weeks , the active group continued the home exercise programme and the placebo group received no treatment . Main outcome measures The primary outcomes were pain and function measured by the shoulder pain and disability index , average pain on movement measured on an 11 point numerical rating scale , and participants ’ perceived global rating of overall change . Results 112 ( 93 % ) participants completed the 22 week trial . At 11 weeks no difference was found between groups for change in shoulder pain and disability index ( 3.6 , 95 % confidence interval −2.1 to 9.4 ) or change in pain ( 0.7 , −0.1 to 1.5 ) ; both groups showed significant improvements . More participants in the active group reported a successful outcome ( defined as “ much better ” ) , although the difference was not statistically significant : 42 % ( 24/57 ) of active participants and 30 % ( 18/61 ) of placebo participants ( relative risk 1.43 , 0.87 to 2.34 ) . The active group showed a significantly greater improvement in shoulder pain and disability index than did the placebo group at 22 weeks ( between group difference 7.1 , 0.3 to 13.9 ) , although no significant difference existed between groups for change in pain ( 0.9 , −0.03 to 1.7 ) or for the percentage of participants reporting a successful treatment outcome ( relative risk 1.39 , 0.94 to 2.03 ) . Several secondary outcomes favoured the active group , including shoulder pain and disability index function score , muscle strength , interference with activity , and quality of life . Conclusion A st and ardised programme of manual therapy and home exercise did not confer additional immediate benefits for pain and function compared with a realistic placebo treatment that controlled for therapists ’ contact in middle aged to older adults with chronic rotator cuff disease . However , greater improvements were apparent at follow-up , particularly in shoulder function and strength , suggesting that benefits with active treatment take longer to manifest . Trial registration Clinical trials NCT00415441 & NA ; Widespread sensory hypersensitivity is present in acute whiplash and is associated with poor recovery . Decreased nociceptive flexion reflex ( NFR ) thresholds ( spinal cord hyperexcitability ) are a feature of chronic whiplash but have not been investigated in the acute to chronic injury stage . This study compared the temporal development of sensory hypersensitivity and NFR responses from soon after injury to either recovery or to transition to chronicity . It also aim ed to identify predictors of persistent spinal cord hyperexcitability . Pressure and cold pain thresholds , NFR responses ( threshold and pain VAS ) were prospect ively measured in 62 participants at <3 weeks , 3 and 6 months post whiplash injury and in 22 healthy controls on two occasions a month apart . Pain levels and psychological distress ( GHQ‐28 ; IES ) were measured at baseline . Whiplash participants were classified at 6 months post‐injury using the Neck Disability Index : recovered ( ≤8 % ) , mild pain and disability ( 10–28 % ) or moderate/severe pain and disability ( ≥30 % ) . All whiplash groups demonstrated spinal cord hyperexcitability ( lowered NFR thresholds ) at 3 weeks post‐injury . This hyperexcitability persisted in those with moderate/severe symptoms at 6 months but resolved in those who recovered or reported lesser symptoms at 6 months . In contrast generalized sensory hypersensitivity ( pressure and cold ) was only ever present in those with persistent moderate/severe symptoms and remained unchanged throughout the study period . This suggests different mechanisms underlie sensory hypersensitivity and NFR responses . In multivariate analyses only initial NDI scores ( p = 0.003 ) were a unique predictor of persistent spinal cord hyperexcitability indicating possible ongoing peripheral nociception following whiplash injury The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls ( DNICs ) in primary headaches . DNICs were examined in 24 migraineurs , 17 patients with chronic tension-type headache ( CTTH ) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test ( CPT ) as heterotopic noxious conditioning stimulation ( HNCS ) . The subjective pain thresholds ( Tp ) and the RIII reflex threshold ( Tr ) were significantly lower in CTTH vs. controls . In controls a significant inhibition of the RIII reflex was observed during the CPT ( -30± , P < 0.05 ) . Conversely , migraine and CTTH patients showed facilitation ( + 31± , P < 0.05 and + 40± , P < 0.01 , respectively ) of the RIII reflex during the HNCS . This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH . Impairment of endogenous supraspinal pain modulation systems may contribute to the development and /or maintenance of central sensitization in primary headaches UNLABELLED Pain catastrophizing is among the most robust predictors of pain outcomes , and a disruption in endogenous pain-inhibitory systems is 1 potential mechanism that may account for increased pain among individuals who report higher pain catastrophizing . Pain catastrophizing may negatively influence diffuse noxious inhibitory controls ( DNIC ) , a measure of endogenous pain inhibition , through complex anatomical circuitry linking cortical responses to pain with processes that modulate pain . The current study examined whether DNIC mediated the relationship between catastrophizing and pain among 35 healthy young adults and examined the moderating effects of sex to determine whether the magnitude or direction of associations differed among men and women . DNIC was assessed using pressure pain thresholds on the forearm before and during a cold pressor task . Using bias-corrected bootstrapped confidence intervals , results showed that diminished DNIC was a significant partial mediator of the relation between greater pain-related catastrophizing and more severe pain ratings . Participant sex moderated these associations ; higher catastrophizing predicted lower DNIC for men and women , however , the effect of catastrophizing on pain ratings was partially mediated by DNIC for women only . These findings further support the primary role of pain catastrophizing in modulation of pain outcomes . PERSPECTIVE These findings support the hypothesis that the heightened pain reported by individuals higher in pain catastrophizing may be related to a disruption in the endogenous modulation of pain , operationalized by assessing DNIC . Whether interventions that reduce pain catastrophizing affect pain outcomes via effects on DNIC is in need of investigation OBJECTIVE To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation ( TENS ) would modify chronic clinical pain , acute experimental pain , and the flexion reflex evoked in chronic low back pain patients . STUDY DESIGN Thirty young subjects with chronic low back pain were r and omly allocated to two groups , receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes . The flexion reflex was elicited by an electrical stimulation applied to the subject 's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles . MAIN OUTCOME MEASURES Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales , termed VAS(LBP ) and VAS(FR ) , respectively . Data obtained before , during , and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA . RESULTS The VAS(LBP ) score was significantly reduced to 63.1 % of the prestimulation value after TENS ( p<.001 ) , but the reduction was negligible after placebo stimulation ( to 96.7 % , p = .786 ) . In contrast , no significant change was found in the VASFR score ( p = .666 ) and the flexion reflex area ( p = .062 ) during and after stimulation within each group and between the two groups ( p = .133 for VASFR and p = .215 for flexion reflex area ) . CONCLUSIONS The same TENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients 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 OBJECTIVE To determine whether abnormalities of peripheral and central nociceptive sensory input processing exist outside areas of spontaneous pain in patients with fibromyalgia ( FM ) as compared with controls , by using quantitative sensory testing ( QST ) and a neurophysiologic paradigm independent from subjective reports . METHODS A total of 164 out patients with FM who were attending a self-management program were invited to participate in the study . Data for 85 patients were available and were compared with those for 40 non-FM controls matched for age and sex . QST was performed using thermal , mechanical , and electrical stimuli at locations of nonspontaneous pain . Pain assessment was 2-fold and included use of subjective scales and the spinal nociceptive flexion reflex ( NFR ) , a specific physiologic correlate for the objective evaluation of central nociceptive pathways . Question naires regarding quality of life and the impact of FM were available . RESULTS Participants were mainly middle-aged women , with a mean disease duration of 8 years . Between-group differences were significant for neurophysiologic , clinical , and quality of life measures . In patients with FM , peripheral QST showed significantly altered cold and heat pain thresholds , and tolerance to cold pain was radically reduced . The median NFR threshold in patients with FM ( 22.7 mA [ range 17.5 - 31.7 ] ) was significantly decreased compared with that in controls ( 33 mA [ range 28.1 - 41 ] ) . A cutoff value of < 27.6 mA for NFR provided sensitivity of 73 % and specificity of 80 % for detecting central allodynia in the setting of FM . CONCLUSION Our results strongly , although indirectly , point to a state of central hyperexcitability of the nociceptive system in patients with FM . The NFR can be used to assess central allodynia in FM . It may also help discriminate patients who may benefit from use of central ly acting analgesics OBJECTIVE To determine whether delayed infusion of COX1/COX2 inhibitors ( ketorolac , indomethacin ) will stop migraine in allodynic patients , and suppress ongoing sensitization in central trigeminovascular neurons in the rat . BACKGROUND The majority of migraineurs seeking secondary or tertiary medical care develop cutaneous allodynia during the course of migraine , a sensory abnormality mediated by sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus . Triptan therapy can render allodynic migraineurs pain free within a narrow window of time ( 20 to 120 minutes ) that opens with the onset of pain and closes with the establishment of central sensitization . Can drugs that tackle ongoing central sensitization render allodynic migraineurs pain free after the window for triptan therapy has expired ? METHODS Patients exhibiting migraine with allodynia were divided in two groups ( n=14 , each ) : group 1 received delayed sumatriptan injection ( 6 mg ) 4 hours after onset of attack -- which failed to render them pain free- and ketorolac infusion ( two 15-mg boluses ) 2 hours later ; group 2 received delayed ketorolac monotherapy 4 hours after onset of attack . Pain intensity ( visual analog scale ) and skin sensitivity ( quantitative sensory testing ) were measured when the patients were migraine free ( baseline ) ; 4 hours after onset of migraine ( just before treatment ) ; 2 hours after sumatriptan ; 1 hour after ketorolac . In the rat , we tested whether infusion of ketorolac ( 0.4 mg/kg ) or indomethacin ( 1 mg/kg ) will block ongoing sensitization in peripheral and central trigeminovascular neurons . The induction of sensitization ( using topical application of inflammatory soup on the dura ) and its suppression by COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity and responses to mechanical and thermal stimuli . RESULTS Patients had normal skin sensitivity in the absence of migraine , and presented cutaneous allodynia 4 hours after onset of migraine . In group 1 , all patients continued to exhibit allodynia 2 hours after sumatriptan treatment , and none of them became pain free . However , 71 % and 64 % of the patients in groups 1 and 2 , respectively , were rendered free of pain and allodynia within 60 minutes of ketorolac infusion . Nonresponders from both groups , in contrast to the responders , had had a history of opioid treatment . In the rat , infusion of COX1/COX2 inhibitors blocked sensitization in meningeal nociceptors and suppressed ongoing sensitization in spinal trigeminovascular neurons . This inhibitory action was reflected by normalization of neuronal firing rate and attenuation of neuronal responsiveness to mechanical stimulation of the dura , as well as mechanical and thermal stimulation of the skin . CONCLUSIONS The termination of migraine with ongoing allodynia using COX1/COX2 inhibitors is achieved through the suppression of central sensitization . Although parenteral administration of COX1/COX2 inhibitors is impractical as routine migraine therapy , it should be the rescue therapy of choice for patients seeking emergency care for migraine . These patients should never be treated with opioids , particularly if they had no prior opioid exposure OBJECTIVE To examine possible deficiencies in endogenous pain modulating mechanisms in fibromyalgia patients compared with matched pain-free control subjects . DESIGN /SUBJECTS/ METHODOLOGY : Pain reduction was investigated in 25 female patients with fibromyalgia and 26 age-matched healthy women using the diffuse noxious inhibitory controls ( DNIC ) paradigm . Tonic thermal stimuli at painful and nonpainful intensities , tailored to individual heat pain thresholds , were employed to induce pain inhibition . The anticipated effect was assessed by measuring the electrical pain threshold and detection threshold , using a double staircase method . Only nontender control points were stimulated ( thermode on the foot , electrodes on the inner forearm ) . RESULTS The patients with fibromyalgia had significantly lower heat pain thresholds than the healthy subjects , but similar electrical detection and pain thresholds . The repeatedly applied electrical stimuli result ed in a degree of perceptual adaptation that was similar between the two groups . However , concurrent tonic thermal stimuli , at both painful and nonpainful levels , significantly increased the electrical pain threshold in the healthy subjects but not in the fibromyalgia patients . The electrical detection threshold was not affected in either group . CONCLUSIONS Pain modulation , produced by a concurrent tonic stimulus in healthy persons , was not seen in the fibromyalgia group . The patients either had deficient pain modulation or were unable to tolerate a tonic stimulus intense enough to engage a modulatory process . It remains to be established whether the pain reduction found in the healthy subjects was the conventional DNIC effect , another effect ( e.g. , distraction ) , or a combination of both & NA ; Little is known about sex differences in the temporal pattern of descending inhibitory mechanisms , such as descending noxious inhibitory control ( DNIC ) . Sex differences in temporal characteristics of DNIC were investigated by measuring pressure pain thresholds ( PPTs ) over time in the trapezius muscles ( local pain areas ) and the posterolateral neck muscles ( referred pain areas ) following repeated bilateral injection of hypertonic versus isotonic saline into both trapezius muscles . Ten females and 11 males received two consecutive bilateral injections , with 15 min interval , of either 5.8 % hypertonic saline ( 0.5 ml in each side for each bilateral injection ) or isotonic saline as a control in a r and omized manner . Following hypertonic saline injection , the maximal pain intensities of the first and second bilateral injections were significantly higher in females than in males . The PPTs in the trapezius muscles were significantly lower in females than in males . Significantly higher PPTs ( hypoalgesia ) in men than in women were shown 15 min after the first bilateral injection , and 7.5 and 15 min after the second bilateral injection in the referred pain areas . Importantly , the second bilateral injection failed to further increase the PPTs for both sexes . These results showed that there were sex differences in temporal characteristics of descending inhibition with long‐lasting hypoalgesia in men than in women . Repeated noxious muscular stimuli may inhibit further build‐up of DNIC , which may reflect a mechanism of plasticity of the descending inhibitory systems following recurrent nociceptive barrage for both sexes The aim of this investigation was to study the effect of suggestions of hypnotic analgesia on spinal pain transmission and processing . Pain intensity and amplitude of nociceptive withdrawal reflexes to electrical stimuli were measured in 10 high- and 10 low-hypnotizable subjects during two sessions taking place at least 24 h apart under five conditions of : ( 1 ) pre-hypnosis ; ( 2 ) neutral hypnotic relaxation ; ( 3 ) suggestions of hypnotic analgesia ; ( 4 ) suggestions of hypnotic analgesia after injections of either naloxone ( 1 ml , 1 mg/ml ) or saline ( 1 ml ) under double-blinded conditions ; and ( 5 ) post-hypnosis . The conditions of naloxone or saline were allocated at r and om to either Day 1 or Day 2 in a double-blinded fashion . Results showed significant reductions of pain intensity during hypnotic analgesia , and a significant reduction in nociceptive reflexes during hypnotic analgesia on Day 1 in the highly hypnotizable group . No differences were found for low-hypnotizable subjects . The results support previous findings that pain intensity as well as the nociceptive reflex can be modulated by suggestions of hypnotic analgesia . While no effect of naloxone on pain intensity was found during hypnotic analgesia , naloxone significantly reversed the suppressive effect of suggestions of hypnotic analgesia on reflexes in high-hypnotizable subjects . Subsequent analysis showed that the effect of naloxone was associated with the intensity of the stimulus needed to elicit a reflex , and was unrelated to hypnotic susceptibility when controlling for stimulus intensity . These results suggest that the effect of naloxone was related to the greater stimulus intensities needed to elicit a reflex in the high-hypnotizable group , rather than to hypnosis or hypnotic susceptibility in itself . It is unclear why greater stimulus intensities were needed in high-hypnotizable subjects and further studies are needed . Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain |
1,121 | 26,840,339 | Whether inhaled bronchodilators and inhaled corticosteroids improve long-term outcomes in BPD remains unclear .
There appears to be heterogeneity in treatment responses , and may be related to varying modes of administration . | BACKGROUND There is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia ( BPD ) .
OBJECTIVE The objective of this systematic review was to identify strengths and knowledge gaps in the literature regarding inhaled therapies in BPD and guide future research to improve long-term outcomes .
Literature regarding these therapies mostly addresses evolving BPD . | Objective To compare the effects of intravenously injected with inhaled salbutamol in ventilator dependent infants with chronic lung disease ( CLD ) . Design Prospect i ve r and omized study in which each patient served as his/her own control . Setting Multidisciplinary neonatal and pediatric ICU . Patients 8 ventilator dependent premature infants with CLD . Interventions Salbutamol , 10 μg/kg was given intravenously , and 10–19 h later , twice 100 μg as pressurized aerosol , or vice versa , sequence r and omized . The pressurized aerosol was delivered by a metered dose inhaler into a newly developed aerosol holding chamber , integrated into the inspiratory limb of the patient circuit . Respiratory system mechanics were assessed by the single breath occlusion method before and 10 and 60 min after drug administration . Measurements and results Compliance improved significantly after intravenous injection ( 0.48±0.18 to 0.67±0.16 , p<0.01 and 0.59±0.23 ml/cmH2O/kg , NS , ( mean±1 SD ) and after inhalation ( 0.46±0.19 to 0.64±0.32,p<0.01 and 0.56±0.31 ml/cmH2O/kg , NS ) . Resistance decreased after i.v . use ( 0.38±0.17 to 0.25±0.11,p<0.001 and 0.25±0.10 cmH2O/ml/s , NS ) and after inhalation ( 0.35±0.12 to 0.27±0.09,p<0.01 and 0.28±0.12 cmH2O/ml/s , NS ) . Heart rate increased significantly after both routes of application , whereas mean arterial pressure , respirator setting s , FIO2 , transcutaneous SO2 and capillary PCO2 did not change . Conclusions Inhaled and intravenous salbutamol improves pulmonary mechanics to the same extent with comparable side effects , and may therefore be used to facilitate weaning from respirators UNLABELLED Several studies have demonstrated that normal infants exhibit bronchoconstriction after inhalation of nonspecific agonists and that the induced airway narrowing can be reversed by the inhalation of a beta-agonist . However , there are very limited data on baseline airway tone and the airway response to a beta-agonist in this subject population . The purpose of our study was to evaluate in normal infants baseline airway responsiveness to the inhaled beta-agonist , albuterol , using changes in maximal expiratory flows . Forty-one healthy infant volunteers with no history of respiratory disease or recurrent wheezing ( ages 5.4 to 141.4 wk ) were studied . Maximal expiratory flow- volume curves were obtained at baseline and 10 min after inhalation of albuterol ( n = 28 ) or placebo ( n = 13 ) using a metered-dose inhaler with a spacer . The mean percent change was significantly greater ( p < 0.05 ) in the albuterol versus placebo group for FEV(0.5 ) ( 2.2 % versus -1.5 % ) , FEF(75 % ) ( 10.6 % versus -3.1 % ) , and FEF(85 % ) ( 12.9 % versus 0.5 % ) . Six of 28 albuterol-treated infants demonstrated increases in FEF(75 % ) greater than two st and ard deviations from the mean change in FEF(75 % ) seen in the placebo group . These infants were younger and more frequently exposed to maternal smoking during pregnancy . We conclude that normal healthy infants have overall levels of baseline airway tone that are similar to that reported in adults and older children ; however , among the infants we evaluated the response to an inhaled bronchodilator was greatest in the youngest infants and in those exposed to tobacco smoking . KEYWORDS airway responsiveness ; asthma ; tobacco smoke ; infant pulmonary function ; Abstract Early inflammatory lesions and bronchial hyperresponsiveness are characteristics of the respiratory distress in premature neonates and are susceptible to aggravation by assisted ventilation . We hypothesized that treatment with inhaled salbutamol and beclomethasone might be of clinical value in the prevention of bronchopulmonary dysplasia ( BPD ) in ventilator-dependent premature neonates . The study was double-blinded and placebo controlled . We studied 173 infants of less than 31 weeks of gestational age , who needed ventilatory support at the 10th postnatal day . They were r and omised to four groups and received either placebo + placebo , placebo + salbutamol , placebo + beclomethasone or beclomethasone + salbutomol , respectively for 28 days . The major criteria for efficacy were : diagnosis of BPD ( with score of severity ) , mortality , duration of ventilatory support and oxygen therapy . The trial groups were similar with respect to age at entry ( 9.8–10.1 days ) , gestational age ( 27.6–27.8 weeks ) , birth weight and oxygen dependence . We did not observe any significant effect of treatment on survival , diagnosis and severity of BPD , duration of ventilatory support or oxygen therapy . For instance , the odds-ratio ( 95 % confidence interval ) for severe or moderate BPD were 1.04 ( 0.52–2.06 ) for inhaled beclomethasone and 1.54 ( 0.78–3.05 ) for inhaled salbutamol . Conclusion This r and omised prospect i ve trial does not support the use of treatment with inhaled beclomethasone , salbutamol or their combination in the prevention of BPD in premature ventilated neonates Objective .This r and omized , controlled trial was design ed to determine the efficacy of inhaled fluticasone propionate on oxygen therapy weaning in a population of preterm infants who were born at < 32 weeks of gestation and experienced moderate bronchopulmonary dysplasia ( BPD ) . Methods .Thirty-two infants who were ≤32 weeks of gestation , had moderate BPD that required supplemental oxygen ( fraction of inspired oxygen ≥0.25 ) , and were aged between 28 and 60 days were r and omized . Fluticasone propionate 125 μg twice daily for 3 weeks and once daily for a fourth week was delivered to infants who weighed between 500 and 1200 g. The dosage was doubled for infants who weighed ≥1200 g. Results .Compared with placebo , treatment had no effect on either duration of supplemental O2 therapy or ventilatory support as assessed by survival analysis . At 28 days , a trend toward a lower cortisol/creatinine ratio in the treatment group was noted compared with placebo ( 25.1 ± 18.9 vs 43 ± 14.4 ) . In the fluticasone group at 28 days , the systolic arterial pressure ( 78 ± 3 vs 68 ± 3 mm Hg ) and diastolic arterial pressure ( 43 ± 3.4 mm Hg vs 38 ± 2.0 mm Hg ) were higher compared with baseline fluticasone values . The chest radiograph score was lower than baseline ( 2.8 ± 1.4 vs 3.7 ± 2.2 ) in the fluticasone group at 28 days . This study has a statistical power of 1.0 to detect a significant difference in the duration of oxygen supplementation of > 21 days between the study groups . Conclusion .We conclude that fluticasone propionate reduces neither supplemental O2 use nor the need for ventilatory support in this patient population . However , fluticasone does have a positive radiologic effect in lowering chest radiograph scores . In addition , our data point to a possible association among inhaled fluticasone treatment and higher arterial blood pressure . Thus , the results of this investigation do not support the use of inhaled corticosteroids in the treatment of oxygen-dependent infants who have established moderate BPD AIMS To compare the efficacy of salbutamol delivered by metered dose inhaler ( MDI ) , jet nebuliser , and ultrasonic nebuliser in ventilated infants with chronic lung disease . METHODS Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies . In study 1 ( n=10 ) , each infant was given 200 μg of salbutamol at 4 hour intervals and in r and om sequence from a metered dose inhaler – spacer device , a jet nebuliser , and an ultrasonic nebuliser with a small medication cup . The infants were monitored for heart rate , transcutaneous pO2 , pCO2 , and oxygen saturation , respiratory system resistance and compliance before and after each treatment . Infants in study 2 ( n=10 ) were similarly studied except for the use of a different jet nebuliser . RESULTS The mean ( SEM ) maximum percentage decreases in respiratory system resistance , observed at 30 minutes after aerosol delivery were study 1 : MDI : 44.3 (4.3)% ; jet : 32.3 (3.4)% ; ultrasonic : 56.1 (3.2)% ; study 2 : MDI : 28.6 (1.0)% ; jet : 16.9 (1.4)% ; ultrasonic : 42.1 (1.6)% . During the first hour after treatment , a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies . The use of the ultrasonic nebuliser but not the other devices also result ed in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2 . CONCLUSIONS These findings suggest that among the devices tested , the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser , and least with the jet nebulisers Abstract Bronchodilators are often used in the treatment of patients with bronchopulmonary dysplasia ( BPD ) . However , few studies evaluate their efficacy in patients with stable disease beyond the newborn period . Therefore , pulmonary function was measured before and after aerosol treatment with salbutamol ( 0.25 ml Ventolin 0.5 % ) and subsequently after aerosol with ipratropium bromide ( 0.25 ml Atrovent 0.025 % ) . Studies were performed at the corrected postnatal age of 52±2 weeks in 52 patients who had been ventilated after birth because of newborn lung disease . Twenty-two of these 52 patients had developed BPD . Pulmonary function was measured after sedation and using the PEDS system . Expiratory resistance ( median 52.1 versus 39.1 cmH2O/l/s ; P<.008 ) and inspiratory resistance ( median 42.5 vs 27.8 cmH2O/l/s ; P<.04 ) were significantly worse in BPD patients at the age of 1 year . Half of the BPD patients had a decrease in pulmonary resistance after salbutamol . However , there was no statistically significant decrease in pulmonary resistance after salbutamol or ipratropium in the BPD patients as a group . After salbutamol pulmonary resistance significantly worsened in the patients who did not develop BPD . Conclusion Although individual patients may benefit , routine administration of bron chodilators seems not warranted in stable BPD patients at the age of 1 year Objective : To identify factors associated with bronchodilator administration to infants with bronchopulmonary dysplasia ( BPD ) and evaluate inter-institutional prescribing patterns . Study Design : A retrospective cohort study of < 29-week-gestation infants with evolving BPD defined at age 28 days within the Pediatric Health Information System data base . Controlling for observed confounding with r and om-effects logistic regression , we determined demographic and clinical variables associated with bronchodilator use and evaluated between-hospital variation . Result : During the study period , 33 % ( N=469 ) of 1429 infants with BPD received bronchodilators . Lengthening mechanical ventilation duration increased the odds of receiving a bronchodilator ( odds ratio 19.6 ( 11 to 34.8 ) at ⩾54 days ) . There was profound between-hospital variation in use , ranging from 0 to 81 % . Conclusion : Bronchodilators are frequently administered to infants with BPD at US children ’s hospitals with increasing use during the first hospital month . Increasing positive pressure exposure best predicts bronchodilator use . Frequency and treatment duration vary markedly by institution even after adjustment for confounding variables Parenteral glucocorticoids have been shown to be effective in the treatment of oxygen- and ventilator-dependent bronchopulmonary dysplasia . We conducted a r and omized , prospect i ve study using a nebulized , water-soluble form of beclomethasone dipropionate for the treatment of infants with oxygen- and ventilator-dependent lung disease . Newborn infants with chest x-ray changes consistent with bronchopulmonary dysplasia at 14 days of age were r and omly assigned , in a paired sequential fashion by birth weight , to treatment ( beclomethasone ) or placebo ( saline solution ) groups . Treatment included three nebulized doses of beclomethasone ( 50 micrograms ) or saline solution per day for 28 days . Measured variables included tidal volume , total dynamic compliance , and airway resistance . Weight gain , gender , and incidence of infection during therapy were also recorded . Pulmonary functions were measured before initiation of therapy and weekly thereafter . Thirteen infants , seven in the saline solution group and six in the beclomethasone group , met study criteria and completed treatment . Infants treated with beclomethasone had reductions in airway resistance that were significant in weeks 2 , 3 , and 4 ( p < 0.05 , p < 0.02 , and p < 0.001 , respectively ) . Dynamic lung compliance increased at weeks 3 and 4 ( p < 0.01 and p < 0.05 , respectively ) . As expected , tidal volume increased with weight and time , but there were no significant differences between groups . There were no differences between the groups in weight gain , gender , or infection . This study demonstrates that beclomethasone by nebulization ( 1 ) reduced airway resistance in oxygen-dependent neonates with bronchopulmonary dysplasia , ( 2 ) improved dynamic lung compliance , as reported with parenterally administered glucocorticoids , and ( 3 ) produced no apparent increase in the incidence of infection Abstract The speed of action and side-effects of systemic versus inhaled steroids was compared in infants with mild-moderate oxygen dependency . Forty infants ( median gestational age 27 weeks ) were r and omized to receive either 10 days of dexamethasone ( systemic group ) or budesonide ( 100 μg qds ) ( inhaled group ) . At r and omization , there was no significant difference in the gestational or postnatal age , inspired oxygen requirements or compliance of the respiratory system of the two groups . After 36 h of treatment , there were significant changes ( P < 0.01 ) in both the inspired oxygen concentration and compliance of the respiratory system in the systemic but not the inhaled group . Only after 1 week of inhaled therapy were improvements in respiratory status noted but , even at that time , the inspired oxygen requirement was significantly lower in the systemic versus the inhaled group . In the systemic group only , however , were there significant increases in blood pressure . Conclusion Systemically administered rather than inhaled steroids appear to have a faster onset of action AIM To compare early ( <3 days ) with late ( > 15 days ) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease . METHODS Five hundred seventy infants from 47 neonatal intensive care units were enrolled . Criteria for enrollment included gestational age < 30 weeks , postnatal age < 72 hours , and need for mechanical ventilation and inspired oxygen concentration > 30 % . Infants were r and omly allocated to 1 of 4 treatment groups in a factorial design : early ( < 72 hours ) dexamethasone , early budesonide , delayed selective ( > 15 days ) dexamethasone , and delayed selective budesonide . Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed . Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days . Delayed selective treatment was started if infants needed mechanical ventilation and > 30 % oxygen for > 15 days . The factorial design allowed 2 major comparisons : early versus late treatment and systemic dexamethasone versus inhaled budesonide . The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis . Secondary outcome measures included death or major cerebral abnormality , duration of oxygen treatment , and complications of prematurity . Adverse effects were also monitored daily . RESULTS There were no significant differences among the groups for the primary outcome . Early steroid treatment was associated with a lower primary outcome rate ( odds ratio [ OR ] : 0.85 ; 95 % confidence interval [ CI ] : 0.61,1.18 ) but even after adjustment for confounding variables the difference remained nonsignificant . Dexamethasone-treated infants also had a lower primary outcome rate ( OR : 0.86 ; 95 % CI : 0.62,1.20 ) but again this difference remained not significant after adjustment . For death before discharge , dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment ( OR : 1.42 ; 95 % CI : 0.93,2.16 ; OR : 1.51 ; 95 % CI : 0.99,2.30 after adjustment , respectively ) with the results not quite reaching significance . Duration of supplementary oxygen was shorter in the early dexamethasone group ( median : 31 days vs 40 - 44 days ) . Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment ( 52 g vs 3 g ) compared with early budesonide , but over 30 days there was no difference . In the early dexamethasone group , there was a reduced incidence of persistent ductus arteriosus ( 34 % vs 52%-59 % ) and an increased risk of hyperglycemia ( 55 % vs 29%-34 % ) compared with the other 3 groups . Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance . CONCLUSIONS Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide , respectively , but results for survival to discharge were in the opposite direction ; however , none of these findings attained statistical significance . Early dexamethasone treatment reduced the risk of persistent ductus arteriosus . Inhaled budesonide may be safer than dexamethasone , but there is no clear evidence that it is more or less effective OBJECTIVE : We aim ed to prospect ively and longitudinally measure lung function in a cohort of children with bronchopulmonary dysplasia ( BPD ) during their first 3 years of life . METHODS : Forty-four children with BPD with a mean ( ±SD ) gestational age of 25.6 ( ±1.7 ) weeks and birth weight of 0.767 ( ±0.2 ) kg underwent serial measurements of lung function ( maximum flow at functional residual capacity [ VmaxFRC ] and functional residual capacity [ FRC ] ) at 6 , 12 , and 24 months after initial discharge from the neonatal care unit . RESULTS : Compared with normative data , children with BPD had low partial expiratory airflow , measured by VmaxFRC , with mean z score ( ±SD ) of −1.92 ( ±1.04 ) , −1.79 ( ±1.5 ) , and −1.67 ( ±1.5 ) at 6 , 12 , and 24 months , respectively . Over time there was no significant improvement in z scores ( P = .66 ) , and 45 % of the patients had a z score value of less than −2 ( 2 SDs below the mean ) at the end of the study . FRC measurements steadily and significantly increased over time . Partial expiratory flow showed no correlation with gestational age , birth weight , or length of mechanical ventilation . Mean FRC was significantly higher in children who were using bronchodilators and inhaled steroids but showed no correlation with clinical symptoms . Bronchodilator response was initially present in 30 % of the patients and declined to 20 % at the end of the study . CONCLUSIONS : During the first 3 years of life , children with mostly moderate-to-severe BPD continue to show significant abnormalities with airflow limitation according to lung-function testing Objective . To evaluate the effectiveness of nebulized pentoxifylline ( PTXF ) compared to intravenous dexamethasone ( DX ) or placebo ( nebulized distilled water ) for the prevention of bronchopulmonary dysplasia ( BPD ) . Methods . One hundred and fifty very low birth weight infants were r and omly assigned to three groups . Entry criteria were the need for oxygen administration on the fourth day of life , irrespective of whether ventilatory support was required . PTXF was administered with a nebulizer every 6 hours on three consecutive days ( a single course ) in a dose of 20 mg/kg when infants were breathing spontaneously or 10 mg/kg when they needed ventilatory support . DX was given every 12 hours on three consecutive days in a dose of 0.25 mg/kg . Nebulized distilled water was administered with the schedule of inhalation as in the PTXF group . When the need for ventilatory support or oxygen dependency persisted , the course of both drugs and placebo administration was repeated every seven days until the diagnosis of BPD was established . Results . Both PTXF and DX reduced the incidence of disease when compared with placebo . The respective data obtained for the PTXF-group versus the placebo group were as follows : difference in risk , 27 % ; OR : 0.32 ; CI : 0.11–0.94 ; p = 0.039 ; whereas the results for the DX-group versus the placebo group were : difference in risk , − 23 % ; OR : 0.39 ; CI : 0.14–1.14 ; p = 0.07 . Conclusion . Our data show that nebulized PTXF reduces the risk of BPD and may be a potential alternative to steroids in the prevention of this disease In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease ( CLD ) in very low birthweight ( VLBW ) infants , 60 ventilator‐dependent infants ≤ 1500 g were r and omly assigned to receive either steroids or placebo as of 7d . The steroid group ( n= 30 , GA = 25:8 ± 1:6 weeks , BW = 731 ± 147 g ) received systemic dexamethasone for 3 d , followed by nebulized budesonide for 18 d. Control infants ( n= 30 , GA = 25:9 ± 1.8 weeks , BW = 796 ± 199 g ) received systemic and inhaled saline . Steroid‐treated infants required less ventilatory support between 9 and 17 d ( p < 0:01 ) , and had greater lung compliance at 10 d ( p= 0:01 ) , but not subsequently . CLD incidence at 36 weeks was 45.5 % vs 56.0 % in controls , and fewer steroid‐treated infants required dexamethasone rescue ( 23.3 % vs 56.7 % , p= 0:017 ) . Survival to discharge was similar ( 73.3 % vs 83.3 % ) , as were the duration s of mechanical ventilation , supplemental oxygen use , and hospitalization . Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups , and no adverse effects were noted . We conclude that early dexamethasone administration was associated with improved pulmonary function , which was not sustained with nebulized budesonide . However , the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD BACKGROUND The safety and efficacy of inhaled glucocorticoid therapy for asthma stimulated its use in infants to prevent bronchopulmonary dysplasia . We tested the hypothesis that early therapy with inhaled glucocorticoids would decrease the frequency of bronchopulmonary dysplasia in premature infants . METHODS We conducted a r and omized , multicenter trial of inhaled beclomethasone or placebo in 253 infants , 3 to 14 days old , born before 33 weeks of gestation and weighing 1250 g or less at birth , who required ventilation therapy . Beclomethasone was delivered in a decreasing dosage , from 40 to 5 microg per kilogram of body weight per day , for four weeks . The primary outcome measure was bronchopulmonary dysplasia at 28 days of age . Secondary outcomes included bronchopulmonary dysplasia at 36 weeks of postmenstrual age , the need for systemic glucocorticoid therapy , the need for bronchodilator therapy , the duration of respiratory support , and death . RESULTS One hundred twenty-three infants received beclomethasone , and 130 received placebo . The frequency of bronchopulmonary dysplasia was similar in the two groups : 43 percent in the beclomethasone group and 45 percent in the placebo group at 28 days of age , and 18 percent in the beclomethasone group and 20 percent in the placebo group at 36 weeks of postmenstrual age . At 28 days of age , fewer infants in the beclomethasone group than in the placebo group were receiving systemic glucocorticoid therapy ( relative risk , 0.6 ; 95 percent confidence interval , 0.4 to 1.0 ) and mechanical ventilation ( relative risk , 0.8 ; 95 percent confidence interval , 0.6 to 1.0 ) . CONCLUSIONS Early beclomethasone therapy did not prevent bronchopulmonary dysplasia but was associated with lower rates of use of systemic glucocorticoid therapy and mechanical ventilation OBJECTIVE We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia does not cause adrenal suppression . STUDY DESIGN Infants receiving ventilatory support with birth weights < /=1250 g and born at <33 weeks ' gestation , age 3 to 14 days , were enrolled in a multicenter r and omized trial to study the efficacy and safety of beclomethasone therapy versus placebo for prevention of bronchopulmonary dysplasia . Adrenal function was assessed on study day 21 ( + /- 2 days ) by determination of basal and stimulated plasma cortisol levels . Initially , cortisol response was assessed with insulin-induced hypoglycemia test ( IIHT ) ( n = 63 ) until an interim analysis revealed insignificant cortisol response in both study groups . Thereafter , cosyntropin stimulation was used ( n = 85 ) . RESULTS Beclomethasone therapy was associated with lower median basal cortisol levels ( 5 microg/dL beclomethasone , 6 microg/dL placebo , P = .04 ) . IIHT revealed insignificant change in cortisol response within each group . Cortisol response to cosyntropin stimulation was similar for each group ( 17 microg/dL beclomethasone , 18 microg/dL placebo , P = .86 ) . CONCLUSION Beclomethasone therapy was associated with a small decrease in basal cortisol levels . There was no evidence of adrenal suppression in response to cosyntropin stimulation during beclomethasone therapy . Lack of cortisol response to hypoglycemia may reflect missed timing and /or decreased response of the premature infants ' hypothalamic-pituitary-adrenal axis to hypoglycemia OBJECTIVE : Intravenous steroids improve the respiratory course in ventilator-dependent preterm infants but have adverse effects . We hypothesized that inhaled steroids would be as effective , but with less systemic effects . STUDY DESIGN : We conducted a r and omized , prospect i ve trial comparing inhaled beclomethasone , either 400 or 800 μg/d , to intravenous dexamethasone in preterm infants dependent on conventional mechanical ventilation and supplemental oxygen at 2 weeks of age . RESULTS : Seventy-eight infants were r and omized . By day three of therapy , the intravenous steroid group had significantly decreased ventilator and oxygen requirements compared to either inhaled group . The inhaled 800-μg/d group trended toward more rapid decreases in ventilator and oxygen requirements than the 400-μg/d group . By day 14 , all groups had similar reductions in ventilator and oxygen requirements . The incidence of adverse effects did not differ between groups . CONCLUSIONS : In this small , r and omized study , inhaled steroids conferred no advantages to intravenous steroids in the management of ventilator-dependent preterm infants Treatment of chronic lung disease of prematurity requires effective aerosol delivery of different therapeutic agents . Aerosols can be generated by a metered dose inhaler ( MDI ) or a jet nebulizer . An MDI combined with a spacer device is easier to use and avoids undesirable effects noted in conjunction with jet nebulization . We compared the clinical effectiveness of 200 micrograms ( 2 puffs ) salbutamol delivered from an MDI in conjunction with a valved spacer device ( Aerochamber ) , and 600 micrograms given via jet nebulizer ( PariBaby ) on 2 consecutive days , the order being r and omized . Thirteen spontaneously breathing very preterm infants [ mean ( SD ) gestational age 27.2 ( 1.8 ) weeks ; birth weight 0.90 ( 0.34 ) kg ] were studied at a corrected age of 37 ( 2.3 ) weeks . Mean ( SD ) study weight was 1.83 ( 0.38 ) kg . Dynamic lung compliance and resistance were determined from measurements of flows , volumes , and transpulmonary pressures , using a pneumotachometer and a small esophageal microtransducer catheter before and 20 min after salbutamol application . Baseline values before salbutamol administration were similar on both occasions : the mean ( SD ) compliance was 7.7 ( 3.0 ) mL.kPa-1.kg-1 pre-MDI plus-spacer and 8.4 ( 3.1 ) pre-jet nebulizer ; the resistance was 10.4 ( 4.0 ) kPa . L-1.s pre-MDI plus-spacer and 9.7 ( 3.4 ) pre-jet nebulizer . Following salbutamol , compliance did not change significantly with either MDI plus spacer or jet nebulizer . Resistance fall significantly with MDI plus spacer ( mean -2.2 ; 99.9 % CI -0.35 , -4.35 ) and jet nebulizer ( -2.4 ; 99 % CI -0.39 , -4.42 ) . We conclude that even in small preterm infants 200 micrograms salbutamol via MDI plus spacer improves dynamic resistance as effectively as 600 micrograms via jet nebulizer and may therefore be a preferable mode of aarosol administration AIM To investigate the therapeutic efficacy of inhaled fluticasone propionate , started on day 1 of age , on ventilated preterm infants with respiratory distress syndrome . METHODS Starting within 24 hours of age , ventilated preterm infants ( gestation < 32 weeks , birthweight < 1.5 kg ) with respiratory distress syndrome were given a 14 day course ( two puffs , 12 hourly ) of either fluticasone propionate ( 250 μg/puff ) ( group 1 , n=27 ) or placebo ( group 2 , n=26 ) with a metered dose inhaler – spacer device . Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age , changes in respiratory system mechanics , death , occurrence of chronic lung disease , and other neonatal complications . RESULTS More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group ( 17/27 vs8/26 ; p = 0.038 ) . The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life . The two groups , however , did not differ significantly in their need for systemic steroids after day 14 of age , death , or the occurrence of chronic lung disease . The treatment was not associated with any increase in neonatal complications , including those attributable to steroid induced side effects . CONCLUSION These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress . Further study of its use in a large scale r and omised trial is warranted Our objective was to determine the safety and efficacy of aerosol beclomethasone vs. systemic dexamethasone for extubation in premature infants at high risk for chronic lung disease ( CLD ) . Intubated preterm infants who were identified as being at high risk for moderate-severe CLD on day 14 of life were r and omized to one of four groups . The control group received systemic dexamethasone and aerosol placebo , while the other three groups received either high ( 2.40 - 3.69 microg/kg/day delivered to lungs ) , medium ( 1.0 - 1.85 microg/kg/day ) , or low ( 0.48 - 0.74 microg/kg/day ) dose aerosol beclomethasone and systemic placebo . Those receiving aerosol steroids who remained ventilator-dependent after 7 days were switched to st and ard 42-day tapering doses of systemic dexamethasone . The primary outcome was extubation within 1 week of starting steroids , using predefined criteria . Secondary variables included changes in lung function , rates of side effects , and tracheal aspirate white blood cell counts . Sixty-one infants with birth weights of 761 + /- 18 g ( mean + /- SEM ) and gestational ages of 25.7 + /- 0.2 weeks were r and omized to one of the four groups . Seven of 15 infants in the control systemic dexamethasone group were successfully extubated compared with 3/16 in the high-dose beclomethasone group , 1/15 in the medium-dose group , and 2/15 in the low-dose group ( P < 0.01 ) . Only dexamethasone subjects demonstrated improvements in lung function over the study period . These infants also had significant increases in blood pressure and blood glucose levels , as well as a decline in their tracheal aspirate white blood cell count . In conclusion , aerosol beclomethasone at the very low doses used in this study did not facilitate extubation in intubated premature infants at high risk for moderate-severe CLD Objective : To compare infants ’ discomfort , nursing-time and caregiver preference , and assess the clinical efficiency ( as a secondary outcome ) of hood versus facemask nebulization in infants with evolving bronchopulmonary dysplasia ( BPD ) in the neonatal intensive care unit . Study Design : A prospect i ve , open , r and omized , controlled crossover clinical trial . In total , 10 infants with BPD who were on inhaled beta-agonist bronchodilators and corticosteroids were r and omly assigned to receive their nebulized treatments either by a facemask , or by a hood for 2–3 days , and then crossover to receive the same treatments with the other technique for another 2–3 days . Infants ’ discomfort , nursing-time , caregiver preference and clinical efficiency were compared . Results : At baseline there was no significant clinical difference between the groups . Nurse-time required for administering the hood nebulization ( mean±s.e.m . : 1.9±0.1 min ) was significantly shorter than the time for mask nebulization ( 12.0±0.6 min , P<0.0001 ) . Infants ’ discomfort score was significantly lower ( 0.1±0.04 ) for hood versus mask nebulization ( 2.5±0.2 , P<0.0001 ) . Nurses and parents unequivocally preferred the hood treatment . During both mask and hood nebulization therapies ( 2–3 days ) clinical efficiency was comparable . While both methods caused an immediate ( 20 min post ) clinical improvement , the immediate respiratory assessment change score was significantly greater for the hood versus the mask nebulization ( 0.62±0.27 versus 0.13±0.14 , P<0.05 ) . Conclusions : Nebulization of aerosolized medications in infants with evolving BPD by hood was less time-consuming for caregivers and was much better tolerated by the infants while being at least as effective as the conventional facemask nebulization Objective : Bronchopulmonary dysplasia ( BPD ) in preterm infants is associated with impaired alveolar growth , inflammation and airway hyperreactivity . In animal models of BPD , inhaled nitric oxide ( NO ) improves alveolar growth and inhibits airway smooth muscle proliferation . This study was design ed to assess the effect of inhaled NO on resistance and compliance in ventilated preterm infants with evolving BPD . Study Design : Expiratory resistance and compliance of the respiratory system were measured in 71 ventilated preterm infants , ⩽32 weeks gestation , r and omized to NO ( n=34 ) versus placebo ( n=37 ) for ⩾24 days at 7 to 21 days of life . Result : At baseline expiratory resistance ( 231±71 versus 215±76 cm H2O l−1 s−1 ) and compliance ( 0.49±0.14 versus 0.53±0.13 ml cm H2O−1 kg−1 ) were comparable between placebo and NO groups , respectively . There was no effect of NO on expiratory resistance or compliance at 1 h , 1 week or 2 weeks of study gas administration . Conclusion : NO had no short- or medium-term effect on expiratory resistance or compliance in ventilated preterm infants The effects of isoproterenol inhalation on pulmonary mechanics in ten infants with bronchopulmonary dysplasia ( BPD ) , aged 41 + /- 1 ( SE ) weeks postconception , with gestational age at birth 30 + /- 1 weeks , and birth weight 1,590 + /- 200 g were studied . The infants had : ( 1 ) hyaline membrane disease requiring mechanical ventilation in the first five days of life , ( 2 ) mechanical ventilation and /or FIo2 greater than 30 % for at least 30 days , and ( 3 ) stage III or IV radiographic changes . Thoracic gas volume , airway resistance , and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing . Dynamic pulmonary compliance was measured using an esophageal balloon . These infants with BPD had greater airway resistance , lower specific airway conductance , and lower dynamic pulmonary compliance than 16 normal control infants ( age 40 + /- 1 weeks postconception ) . In the infants with BPD , measurements were obtained before and 1/2 , 1 , 2 , and 6 hours after the administration of isoproterenol aerosol 0.1 % inhalation or saline aerosol placebo , five breaths by slow inflation of the lungs with an anesthesia bag . Within 30 minutes after isoproterenol inhalation , airway resistance decreased 28 % + /- 5 % and specific airway conductance increased 53 % + /- 15 % . Thoracic gas volume and dynamic pulmonary compliance did not change . There were no changes following administration of the placebo . Isoproterenol inhalation is associated with rapid short-term improvement in airway resistance and specific airway conductance in infants with BPD Beclomethasone dipropionate administered by metered-dose inhaler to ventilated infants with early chronic lung disease was evaluated in a double-blind , placebo-controlled study to determine the feasibility and safety of administration . Patients selected for study were less than 1500 g birthweight , had previous radiographic evidence of respiratory distress syndrome with early changes of bronchopulmonary dysplasia ( BPD ) , were greater than 2 weeks of age , and had failed attempts at extubation . The metered-dose inhaler was connected to the respirator circuit by an in-line spacer device and either saline placebo or beclomethasone was delivered for 7 days or until extubated . Beclomethasone was delivered in a dose calculated to be approximately 1 mg/kg/day in three divided doses . Nineteen infants were enrolled . Nine received placebo and 10 received beclomethasone . No adverse effects on blood pressure , heart rate , respiratory rate , ventilator setting s , concentration or duration of oxygen therapy , incidence of retinopathy of prematurity ( ROP ) or infections , blood glucose , daily weight , or serum cortisol levels before and after adrenal stimulation tests were observed in the beclomethasone group compared with the placebo group . One infant in the placebo and six infants in the steroid group were extubated during the study period ( p = 0.03 ) . These data indicate that beclomethasone dipropionate may be administered safely to intubated neonates without adverse effects of hypertension , hyperglycemia , diminished weight gain , or adrenal suppression frequently seen with systemic steroid administration . Beclomethasone may enhance extubation in infants with early BPD , however , further data are required to substantiate this preliminary observation We compared the change in passive respiratory system compliance ( Crs ) and resistance ( Rrs ) after albuterol aerosol treatment administered by either low-flow nebulizer ( NEB ) or a metered dose inhaler ( MDI ) and spacer into a ventilator circuit . We hypothesized that albuterol delivered to ventilated infants older than 7 days of life by an MDI and a spacer would improve Crs more than albuterol delivered by a low-flow nebulizer . The treatments were administered 6 hr apart to premature infants with Crs < or = 0.8 mL/cm H2O per kg , requiring ventilation after 7 days of age . Patients served as their own controls and treatment order was r and omized . Eighteen studies were performed in eight infants before and 1 and 3 hr after treatment . Differences between methods were compared by analyses of variance . Mean ( range ) birth weight and study age were 888 ( 619 - 1,283 ) g and 12 ( 7 - 29 ) days , respectively . Mean respiratory system compliance increased by 34 % with MDI and by 11 % with NEB at 1 hr after treatment ( P < 0.02 ) . By 3 hr after treatment , Crs returned to baseline with both methods of aerosol delivery . There was no significant difference in Rrs between the two methods at 1 and 3 hr after treatment . We conclude that albuterol delivered by MDI improves Crs more than low-flow NEB in ventilated premature infants The purpose of this study was to examine lung function and bronchodilator responsiveness in infants with a history of prematurity and bronchopulmonary dysplasia ( BPD ) , using the raised volume rapid thoracoabdominal compression technique as well as with whole-body plethysmography . Spirometric measurements were obtained in 28 infants with a history of BPD , defined as preterm birth with O2 requirement at 36 weeks postmenstrual age ( gestational age at birth , 26.4 + /- 2.1 weeks , mean + /- SD ; birthweight , 898 + /- 353 g ; age at study , 68.0 + /- 35.6 weeks ) . Fractional lung volumes were measured in 27 subjects . Values were expressed as percentage of predicted normal values . Compared to normal infants , those with a history of BPD exhibited decreases in forced expiratory flows including forced expiratory volume in 0.5 sec ( 76.3 + /- 19.6 % ) , forced expiratory flow at 75 % of expired forced vital capacity ( FEF75 ; 59.5 + /- 30.7 % ) , and FEF(25 - 75 ) ( 74.0 + /- 26.8 % ; P<0.01 for all ) . Functional residual capacity ( 107.9 + /- 25.3 % ) , residual volume ( RV , 124.5 + /- 42.7 % ) , and RV/total lung capacity ( RV/TLC , 128.2 + /- 35.3 % ) were increased in infants with a history of BPD ( P<0.05 for each ) . There was no difference in TLC between groups . Seventeen infants were studied both pre- and postalbuterol , and 6 ( 35 % ) demonstrated significant bronchodilator responsiveness . Infants with recurrent wheezing showed greater expiratory flow limitation , hyperinflation , and airways responsiveness , whereas those without wheezing showed only modest airway dysfunction . We conclude that infants with a history of BPD have pulmonary function abnormalities characterized by mild to moderate airflow obstruction and air trapping The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia ( BPD ) is uncertain . We aim ed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers ( MDI ) in ventilated and non-ventilated BPD infants . In a r and omized , crossover sequence , salbutamol lung deposition was measured using an MDI ( 2 puffs or 200 micrograms ) or sidestream jet nebulizer ( 5 minutes of nebulization with 100 micrograms/kg ) in 10 ventilated ( mean birthweight , 1,101 g ) and 13 non-ventilated ( mean birthweight , 1,093 g ) prematurely born infants . Non-ventilated infants inhaled aerosol through a face mask , connected to a nebulizer or an MDI and spacer ( Aerochamber ) . Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit . Lung deposition by both methods was low : mean ( SEM ) from the MDI was 0.67 (0.17)% of the actuated dose , and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses , respectively . Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer . In both groups , and for both methods of delivery , there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions A new method that permits the measurement of adult-type maximal expiratory flow-volume curves and fractional lung volumes in se date d infants was recently described . The purpose of this study was to define the normal range for these new measures of pulmonary function in infants and young children . Measurements of forced expiratory flows and fractional lung volume were made on 35 occasions in 22 children ( ages 3 - 120 weeks ) without respiratory disease . Maximal expiratory flow-volume curves were measured by the raised lung volume , thoracoabdominal compression technique . Functional residual capacity ( FRC ) was measured plethysmographically . Measurements of total lung capacity ( TLC ) , residual volume ( RV ) , FRC , forced vital capacity ( FVC ) , and forced expiratory flows at 25 , 50 , 75 , 85 , and between 25 % and 75 % of expired FVC ( FEF(25 ) , FEF(50 ) , FEF(75 ) , FEF(85 ) , and FEF(25 - 75 ) , respectively ) all increased in relation to infant length ( P<0.001 ) . RV/TLC , FRC/TLC , and FEF(25 - 75)/FVC declined in relation to increasing length ( P<0.001 ) . The forced expiratory flow and fractional lung volume measurements using this method were similar to previously reported estimates using other methods . These estimates represent a reasonable reference st and ard for infants and young children with respiratory problems AIMS A hydrofluoroalkane formulation of budesonide pressurized metered-dose inhaler has been developed to replace the existing chlorofluorocarbon one . The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic characteristics of both formulations . METHODS Systemic bioavailability and bioactivity of both hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler formulations at 800 µg twice daily was determined during a r and omized crossover systemic pharmacokinetic/pharmacodynamic study at steady state in healthy volunteers . Measurements included the following : plasma cortisol AUC(24h ) [ area under the concentration-time curve ( 0 - 24 h ) ] , budesonide AUC(0 - 12h ) and C(max ) . Clinical efficacy was determined during a r and omized crossover pharmacodynamic study in asthmatic patients receiving 200 µg followed by 800 µg budesonide via chlorofluorocarbon or hydrofluoroalkane pressurized metered-dose inhaler each for 4 weeks . Methacholine PC(20 ) ( primary outcome ) , exhaled nitric oxide , spirometry , peak expiratory flow and symptoms were evaluated . RESULTS In the pharmacokinetic study , there were no differences in cortisol , AUC(0 - 12h ) [ area under the concentration-time curve ( 0 - 12 h ) ] , T(max ) ( time to maximum concentration ) or C(max ) ( peak serum concentration ) between the hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler . The ratio of budesonide hydrofluoroalkane vs. chlorofluorocarbon pressurized metered-dose inhaler for cortisol AUC(24h ) was 1.02 ( 95 % confidence interval 0.93 - 1.11 ) and budesonide AUC(0 - 12h ) was 1.03 ( 90 % confidence interval 0.9 - 1.18 ) . In the asthma pharmacodynamic study , there was a significant dose response ( P < 0.0001 ) for methacholine PC(20 ) ( provocative concentration of methacholine needed to produce a 20 % fall in FEV(1 ) ) with a relative potency ratio of 1.10 ( 95 % confidence interval 0.49 - 2.66 ) , and no difference at either dose . No significant differences between formulations were seen with the secondary outcome variables . CONCLUSIONS Hydrofluoroalkane and chlorofluorocarbon formulations of budesonide were therapeutically equivalent in terms of relative lung bioavailability , airway efficacy and systemic effects We compared the effect of salbutamol and placebo in a double-blind study of preterm infants with bronchopulmonary dysplasia , using a r and omized , crossover design with several replicates per subject . Sixty-two tests were performed on 20 ventilator-dependent infants weighing less than 1500 gm . Patients were entered as early as the first week of life and studied for at least 4 weeks or until extubation . Each subject was his own control subject and was r and omly assigned to a placebo-salbutamol or salbutamol-placebo sequence administered on 2 consecutive days of each week . Static compliance , expiratory resistance of the respiratory system , and changes in transcutaneous oxygen and carbon dioxide tension were measured . Static compliance improved by 0.240 ml/cm H2O/kg ( 35.3 % ) after salbutamol and by 0.010 ml/cm H2O/kg ( 2.8 % ) after placebo ( p less than 0.0001 ) . The presence of a predetermined decrease in carbon dioxide tension correlated with large changes in static compliance per kilogram and with the need for a high level of fractional inspired oxygen . The magnitude of the clinical and physiologic improvement observed , and the early response suggest that long-term bronchodilator therapy starting as early as the second week of life may be beneficial for very low birth weight infants with early bronchopulmonary dysplasia We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia ( BPD ) reduces pulmonary inflammation . As part of a r and omized , placebo-controlled trial , interleukin-8 ( IL-8 ) and interleukin-1 receptor antagonist ( IL-1ra ) concentrations in tracheal aspirates were measured as markers of pulmonary inflammation . On study days 1 ( baseline ) , 8 , 15 , and day 28 of age , sample s were obtained from enrolled infants ( birth weights < 1,251 g , gestational age <33 week , 3 to 14 days of age ) who remained ventilated and had not received systemic glucocorticoid therapy . Cytokine levels ( pg/microg of free secretory component of immunoglobulin A ) were compared between groups . We determined whether baseline cytokine levels modified treatment effect regarding subsequent need for systemic glucocorticoid therapy or occurrence of BPD ( age 28 days ) . Tracheal aspirates were obtained from 161 infants ( 77 receiving beclomethasone , 84 receiving placebo ) . Median IL-8 levels were lower in beclomethasone versus placebo infants on study days 8 ( 82.9 vs. 209.2 , P < 0.01 ) and 15 ( 37.4 vs. 77.4 , P < 0.03 ) after controlling for antenatal glucocorticoid therapy and maternal race . Median IL-1ra levels were lower in beclomethasone versus placebo infants only on study day 8 ( 86.5 vs. 153.3 , P < 0.01 ) . Fewer beclomethasone infants with baseline IL-8 levels in the interquartile range required systemic glucocorticoid therapy ( beclomethasone 30.6 % vs. placebo 65.8 % , P < 0.01 ) or developed BPD ( beclomethasone 42.4 % vs. placebo 69.4 % , P < 0.03 ) . We conclude that early-inhaled beclomethasone therapy was associated with a reduction in pulmonary inflammation after 1 week of therapy . Beclomethasone-treated infants with moderately elevated baseline IL-8 levels received less subsequent systemic glucocorticoid therapy and had a lower incidence of BPD than nontreated infants The aim of this r and omized , double-blind pilot study was to evaluate the short-term efficacy of early inhalation therapy with budesonide in ventilator-dependent preterm infants . The primary outcome variable was the duration of artificial ventilation ; secondary outcome variables were the need for supplemental oxygen and the release of several inflammatory mediators in the tracheobronchial aspirate fluid . The infants of the budesonide group could not be weaned earlier from the ventilator . The ventilatory parameters on day 14 of life and the need for supplemental oxygen were similar in both groups . The release of inflammatory mediators was not reduced in the budesonide group . No adverse side effects were observed in either group . In conclusion , aerosolized budesonide failed to demonstrate significant short-term pulmonary improvement in ventilator- dependent preterm infants |
1,122 | 25,557,222 | With the data available , only the presence of structural integrity showed good intra- and inter-observer agreement . | Purpose The purpose of this systematic review was to detect the reliability of the currently available magnetic resonance imaging measurements used in the evaluation of repaired rotator cuff . | HYPOTHESIS Local application of autologous platelet rich plasma ( PRP ) improves tendon healing in patients undergoing arthroscopic rotator cuff repair . STUDY DESIGN Prospect i ve , r and omized , controlled , double blind study ; considering an alpha level of 5 % , a power of 80 % , 22 patients for group are needed . MATERIAL S AND METHODS Fifty-three patients who underwent shoulder arthroscopy for the repair of a complete rotator cuff tear were r and omly divided into 2 groups , using a block r and omization procedure . A treatment group ( N = 26 ) consisted of those who received an intraoperative application of PRP in combination with an autologous thrombin component . A control group ( N = 27 ) consisted of those who did not receive that treatment . Patients were evaluated with vali date d outcome scores . A magnetic resonance image ( MRI ) was performed in all cases at more than 1 year post-op . All patients had the same accelerated rehabilitation protocol . RESULTS The 2 groups were homogeneous . The pain score in the treatment group was lower than the control group at 3 , 7 , 14 , and 30 days after surgery ( P < .05 ) . On the Simple Shoulder Test ( SST ) , University of California ( UCLA ) , and Constant scores , strength in external rotation , as measured by a dynamometer , were significantly higher in the treatment group than the control group at 3 months after surgery ( strength in external rotation [ SER ] : 3 ± 1.6 vs 2.1 ± 1.3 kg ; SST : 8.9 ± 2.2 vs 7.1 ± 2.7 ; UCLA : 26.9 ± 3 vs 24.2 ± 4.9 ; Constant : 65 ± 9 vs 57.8 ± 11 ; P < .05 ) . There was no difference between the 2 groups after 6 , 12 , and 24 months . The follow-up MRI showed no significant difference in the healing rate of the rotator cuff tear . In the subgroup of grade 1 and 2 tears , with less retraction , SER in the PRP group was significant higher at 3 , 6 , 12 , and 24 months postoperative ( P < .05 ) . CONCLUSION The results of our study showed autologous PRP reduced pain in the first postoperative months . The long-term results of subgroups of grade 1 and 2 tears suggest that PRP positively affected cuff rotator healing AIM The value of MRI for pre-operative evaluation of the rotator cuff is proven . In spite of its clinical relevance , there have been only few studies on MR imaging of patients who have already been operated . Thus , the question rises to what extent the post-operative MRI can contribute to the evaluation of the integrity of the rotator cuff . METHOD At least 10 months after successful open repair of the supraspinatus tendon , mostly combined with Neer 's anterior acromioplasty , an MR scan was performed on 33 shoulders . Only patients satisfied with the outcome of surgery and showing a Constant score of 65 to 100 points were included . RESULTS More than half the patients had positive direct diagnostic criteria for a full- or partial-thickness tear of the supraspinatus tendon , in the form of signal intensity or morphological alterations . In addition , the indirect diagnostic criteria described by Zlatkin , such as the absence of the subacromial-subdeltoid fat or the appearance of subacromial-subdeltoid fluid , were often positive . Atrophy of the supraspinatus muscle , as a further indirect diagnostic criterion of a rupture , was also frequently noted . CONCLUSION Taking the excellent clinical outcome of our patients into consideration , this study shows that caution should be taken in evaluating postoperative MR images . There is a high risk of over-interpreting MR findings Periosteal augmentation of tendons in the course of refixation to bone has been shown to be a suitable method for early primarily stable osteofibroblastic integration . The aim of this study was to evaluate the clinical and radiological results of open rotator cuff reconstruction using an autologous periosteal flap augmentation technique . The research was performed as a prospect i ve cohort study . Twenty-three prospect i ve patients ( average age 59.7 years ) with degenerative rotator cuff tears were operated on with an open technique and a subtendinous periosteal flap augmentation using bioabsorbable suture anchors and a modified Mason – Allen technique . Clinical evaluation consisted of the Constant-Score and the Simple Shoulder test . Radiological evaluation included st and ard radiographs and magnetic resonance imaging ( MRI ) . Twenty patients were evaluated at a mean follow-up of 14.4 months . The average Constant Score increased significantly from 51.7 to 80.9 points ( p<0.05 ) with 12 excellent , seven good and one satisfactory result . The Simple Shoulder test showed a significant increase of an average of 4.8–10.7 questions answered with yes ( p<0.05 ) . Four patients ( 20 % ) demonstrated a retear of the tendon on postoperative MRI . Ectopic ossifications in the supraspinatus tendon were found in four patients ( 20 % ) but these had no impact on the final clinical results . Open rotator cuff repair augmented with an autologous periosteal flap shows high patient satisfaction level with low rerupture rates . Mid- and long-term results remain to be seen . The potential benefits compared with conventional open or arthroscopic rotator cuff surgery must be examined in prospect i ve r and omized studies BACKGROUND Controversy exists regarding the optimal technique for arthroscopic rotator cuff repair . The purpose of this multicenter , r and omized , double-blind controlled study was to compare the functional outcomes and healing rates after use of single-row and double-row suture techniques for repair of the rotator cuff . METHODS Ninety patients undergoing arthroscopic rotator cuff repair were r and omized to receive either a single-row or a double-row repair . The primary objective was to compare the Western Ontario rotator cuff index ( WORC ) score at twenty-four months . Secondary objectives included comparison of the constant and american shoulder and elbow surgeons ( ASES ) scores and strength between groups . Anatomical outcomes were assessed with magnetic resonance imaging ( MRI ) or ultrasonography to determine the postoperative healing rates . RESULTS Baseline demographic data including age ( p = 0.29 ) , sex ( p = 0.68 ) , affected side ( p = 0.39 ) , and rotator cuff tear size ( p = 0.28 ) did not differ between groups . The WORC score did not differ significantly between groups at any time point ( p = 0.48 at baseline , p = 0.089 at three months , p = 0.52 at six months , p = 0.83 at twelve months , and p = 0.60 at twenty-four months ) . The WORC score at each postoperative time point was significantly better than the baseline value . The Constant score , ASES score , and strength did not differ significantly between groups at any time point . Logistic regression analysis demonstrated that a smaller initial tear size and double-row fixation were associated with higher healing rates . CONCLUSIONS No significant differences in functional or quality -of-life outcomes were identified between single-row and double-row fixation techniques . A smaller initial tear size and a double-row fixation technique were associated with higher healing rates as assessed with ultrasonography or MRI . LEVEL OF EVIDENCE Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence Objectives To retrospectively evaluate fatty degeneration ( FD ) of rotator cuff muscles on CTA using Goutallier ’s grading system and quantitative measurements with comparison between pre- and postoperative states . Material s and methods IRB approval was obtained for this study . Two radiologists independently review ed pre- and postoperative CTAs of 43 patients ( 24 males and 19 females , mean age , 58.1 years ) with 46 shoulders confirmed as full-thickness tears with r and om distribution . FD of supraspinatus , infraspinatus/teres minor , and subscapularis was assessed using Goutallier ’s system and by quantitative measurements of Hounsfield units ( HUs ) on sagittal images . Changes in FD grade s and HUs were compared between pre- and postoperative CTAs and analyzed with respect to preoperative tear size and postoperative cuff integrity . The correlations between qualitative grade s and quantitative measurements and their inter-observer reliabilities were also assessed . Results There was statistically significant correlation between FD grade s and HU measurements of all muscles on pre- and postoperative CTA ( p < 0.05 ) . Inter-observer reliability of fatty degeneration grade s were excellent to substantial on both pre- and postoperative CTA in supraspinatus ( 0.8685 and 0.8535 ) and subscapularis muscles ( 0.7777 and 0.7972 ) , but fair in infraspinatus/teres minor muscles ( 0.5791 and 0.5740 ) ; however , quantitative Hounsfield units measurements showed excellent reliability for all muscles ( ICC : 0.7950 and 0.9346 for SST , 0.7922 and 0.8492 for SSC , and 0.9254 and 0.9052 for IST/TM ) . No muscle showed improvement of fatty degeneration after surgical repair on qualitative and quantitative assessment s ; there was no difference in changes of fatty degeneration after surgical repair according to preoperative tear size and post-operative cuff integrity ( p > 0.05 ) . The average dose-length product ( DLP , mGy · cm ) was 365.2 mGy · cm ( range , 323.8 - 417.2 mGy · cm ) and estimated average effective dose was 5.1 mSv . Conclusions Goutallier grade s correlated well with HUs of rotator cuff muscles . Reliability was excellent for both systems , except for FD grade of IST/TM muscles , which may be more reliably assessed using quantitative measurements In 13 patients , the development of supraspinatus muscle atrophy and fatty infiltration after rotator cuff tendon repair was quantified prospect ively via magnetic resonance imaging . Intraoperative electrical nerve stimulation at repair showed that the maximal supraspinatus tension ( up to 200 N ) strongly correlated with the anatomic cross-sectional muscle area and with muscle fatty infiltration ( ranging from 12 N/cm(2 ) in Goutallier stage 3 to 42 N/cm(2 ) in Goutallier stage 0 ) . Within 1 year after successful tendon repair ( n = 8) , fatty infiltration did not recover , and atrophy improved partially at best ; however , if the repair failed ( n = 5 ) , atrophy and fatty infiltration progressed significantly . The ability of the rotator cuff muscles to develop tension not only correlates with their atrophy but also closely correlates with their degree of fatty infiltration . With current repair techniques , atrophy and fatty infiltration appear to be irreversible , despite successful tendon repair . Unexpectedly , not only weak but also very strong muscles are at risk for repair failure Background Subacromial impingement syndrome is a frequently observed disorder in orthopedic practice . Lasting symptoms and impairment may occur when a subsequent atraumatic rotator cuff rupture is also present . However , degenerative ruptures of the rotator cuff can also be observed in asymptomatic elderly individuals . Treatment of these symptomatic degenerative ruptures may be conservative or surgical . Acceptable results are reported for both treatment modalities . No evidence -based level-1 studies have been conducted so far to compare these treatment modalities . The objective of this study is to determine whether there is a difference in outcome between surgical reconstruction and conservative treatment of a degenerative atraumatic rotator cuff tendon rupture . Methods / Design A r and omized controlled trial will be conducted . Patients aged between 45 and 75 with a symptomatic atraumatic rotator cuff rupture as diagnosed by MRI will be included . Exclusion criteria are traumatic rotator cuff rupture , frozen shoulder and diabetes mellitus . Patients will be r and omized into two groups . Conservative treatment includes physical therapy according to a st and ardized protocol , NSAIDs and , if indicated , subacromial infiltration with a local anesthetic and corticosteroids . Surgical reconstruction is performed under general anesthesia in combination with an interscalenus plexus block . An acromioplasty with reconstruction of the rotator cuff tendon is performed , as described by Rockwood et al. Measurements take place preoperatively and 6 weeks , 3 months , 6 months and 1 year postoperatively . The primary outcome measure is the Constant score . Secondary measures include both disease-specific and generic outcome measures , and an economic evaluation . Additionally , one year after inclusion a second MRI will be taken of all patients in order to determine whether extent and localization of the rupture as well as the amount of fatty degeneration are prognostic factors . Discussion Both surgical as conservative treatment of a symptomatic atraumatic rotator cuff tendon rupture is used in current practice . There is a lack of level-1 studies comparing surgical vs. conservative treatment . This r and omized controlled trial has been design ed to determine whether the surgical treatment of a degenerative atraumatic rotator cuff tendon rupture may lead to a better functional and radiological outcome than conservative treatment after one year of follow-up . Trial registration numberNetherl and s Trial Register ( NTR ) : Purpose The purpose of this study was to compare arthroscopic rotator cuff repair with single-row and double-row techniques because research has demonstrated the superiority of double-row repair from a biological and mechanical point of view but there is no evidence of clinical superiority . Methods A total of 160 patients with a full-thickness rotator cuff tear underwent arthroscopic repair with suture anchors . They were r and omised into two groups of 80 patients according to the repair technique : single-row ( group 1 ) and double-row ( group 2 ) . Results were evaluated by use of the University of California , Los Angeles ( UCLA ) , American Shoulder and Elbow Surgeons ( ASES ) and Constant question naires , the Shoulder Strength Index ( SSI ) and range of motion . Follow-up time was two years . Magnetic resonance imaging ( MRI ) studies were performed on each shoulder preoperatively and two years after repair . Results One hundred per cent of the patients were followed up . All measurements showed significant improvement compared with the preoperative status . The UCLA score showed significant improvement in group 2 . In over 30-mm tears UCLA and ASES showed significant differences . SSI showed significant improvement in group 2 . Range of motion showed significant improvements in flexion and abduction in group 2 . In under 30-mm tears group 2 showed also significant improvement in internal and external rotation . In MRI studies there were no significant differences . Conclusions At two years follow-up the double-row repair technique showed a significant difference in clinical outcome compared with single-row repair and this was even more significative in over 30-mm tears . No MRI differences were observed Background The main objective of this study was to evaluate the association between the acromial index ( AI ) and the incidence of recurrent tears of the rotator cuff ( RC ) in a cohort of patients with full thickness tears who underwent arthroscopic primary repair . Methods A prognostic study of a prospect i ve case series of 103 patients with full thickness RC tears was undertaken . The average age was 59.5 years ( 39–74 ) and follow-up was 30.81 months ( 12–72 ) . True anterior – posterior X-rays were obtained during the pre-operative evaluation . Pre and post-operative magnetic resonance imaging ( MRI ) were recorded . Results Eighteen cases with recurrent tears ( 17.4 % ) were seen on post-operative MRI . The average AI for patients with recurrent tears was 0.711 ± 0.065 and for patients without recurrent tears 0.710 ± 0.064 ( p < 0.05 ) . A positive association between age and recurrent tears of the RC was noted ( average ages : recurrent tears group 63 ± 5.9 years ; group without recurrent tears 58.8 ± 7.5 years ) ( r = −0.216 ; p = 0.029 ) . We did not find an association between size of the primary tear and recurrent tears ( r = −0.075 ; p < 0.05 ) or between degrees of retraction of the primary and recurrent tears of the cuff ( r = −0.073 ; p < 0.05 ) . We observed that 38.9 % of the recurrent tears cases presented with more than one tendon affected before the arthroscopy . At follow-up , none of these recurrent tears showed more than one tendon affected on MRI evaluation . Conclusion In this study , we found that the AI radiological measurement is not a predictor for recurrent tears of the RC after primary arthroscopic repair PURPOSE To evaluate the efficacy of a marrow-stimulating technique with microfractures of the greater tuberosity during arthroscopic rotator cuff repair . METHODS Eighty patients with a full-thickness rotator cuff tear underwent an arthroscopic single-row repair . Patients were divided into 2 groups of 40 cases each . In group 1 , st and ard repair was performed ; in group 2 , microfractures of the greater tuberosity were performed to enhance tendon repair . Clinical outcome was assessed with the Disabilities of the Arm , Shoulder and H and ( DASH ) score and normalized Constant score . Tendon integrity was assessed with magnetic resonance imaging . Multivariate analysis was performed to determine which predictors were independently associated with the outcome . Significance was set at P < .05 . RESULTS The mean follow-up was 28.1 ± 3 months . Seven patients were lost to follow-up ( 2 in group 1 and 5 in group 2 ) . Comparison between groups did not show significant differences for baseline characteristics . The mean DASH score was 28.6 ± 21.3 points in group 1 and 23.3 ± 20.1 points in group 2 . Although the difference was not statistically significant , the confidence interval included a 10-point value ( minimal clinical ly important difference ) in favor of the microfracture group . The difference in the Constant score between groups was not significant . The tendon healing rate was 52.6 % in group 1 and 65.7 % in group 2 , without a significant difference between groups . Subgroup analysis for tear size showed that group 2 had a significantly greater healing rate than group 1 for large tears ( P = .040 ) . Multivariate analysis showed that age , timing of symptoms , tear location , tendon retraction , and fatty infiltration significantly affected the outcomes . CONCLUSIONS Postoperative magnetic resonance imaging did not show any significant difference between groups in structural integrity . However , subgroup analysis showed a significantly greater healing rate in the microfracture group for large tears involving the supraspinatus and infraspinatus . LEVEL OF EVIDENCE Level I , high- quality r and omized controlled trial with no statistically significant difference but narrow confidence intervals PURPOSE To compare range of motion and healing rates between 2 different rehabilitation protocol s after arthroscopic single-row repair for full-thickness rotator cuff tear . METHODS Sixty-four shoulders available for postoperative magnetic resonance imaging ( MRI ) evaluation after arthroscopic rotator cuff repair were enrolled in this study . Aggressive early passive rehabilitation ( manual therapy [ 2 times per day ] and unlimited self-passive stretching exercise ) was performed in 30 shoulders ( group A ) and limited early passive rehabilitation ( limited continuous passive motion exercise and limited self-passive exercise ) in 34 shoulders ( group B ) . A postoperative MRI scan was performed at a mean of 7.6 months ( range , 6 to 12 months ) after surgery . RESULTS Regarding range of motion , group A improved more rapidly in forward flexion , external rotation at the side , internal and external rotation at 90 ° of abduction , and abduction than group B until 3 months postoperatively with significant differences . However , there were no statistically significant differences between the 2 groups at 1-year follow-up ( P = .827 for forward flexion , P = .132 for external rotation at the side , P = .661 for external rotation at 90 ° of abduction , and P = .252 for abduction ) , except in internal rotation at 90 ° of abduction ( P = .021 ) . In assessing the repair integrity with postoperative MRI scans , 7 of 30 cases ( 23.3 % ) in group A and 3 of 34 cases ( 8.8 % ) in group B had retears , but the difference was not statistically significant ( P = .106 ) . CONCLUSIONS Pain , range of motion , muscle strength , and function all significantly improved after arthroscopic rotator cuff repair , regardless of early postoperative rehabilitation protocol s. However , aggressive early motion may increase the possibility of anatomic failure at the repaired cuff . A gentle rehabilitation protocol with limits in range of motion and exercise times after arthroscopic rotator cuff repair would be better for tendon healing without taking any substantial risks . LEVEL OF EVIDENCE Level II , r and omized controlled trial Background : Platelet-rich plasma ( PRP ) is expected to have a biological augmentation potential in the healing of various diseases and injuries , including rotator cuff tears . However , few evaluations have been performed specifically for large to massive tears . Purpose : To assess the efficacy of PRP augmentation in patients undergoing arthroscopic repair for large to massive rotator cuff tears . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 48 patients scheduled for arthroscopic repair of large to massive rotator cuff tears were r and omly assigned to receive either PRP-augmented ( PRP group ) or conventional treatment ( conventional group ) . In the PRP group , 3 PRP gels ( 3 × 3 mL ) were applied to each patient between the torn end and the greater tuberosity . The primary outcome measure was the retear rate assessed by magnetic resonance imaging ( MRI ) or computed tomographic arthrography ( CTA ) at a minimum of 9 months after surgery . Secondary outcome measures included pain , range of motion , muscle strength , overall satisfaction , functional scores , and the change in cross-sectional area ( CSA ) of the supraspinatus . Results : The retear rate of the PRP group ( 20.0 % ) was significantly lower than that of the conventional group ( 55.6 % ) ( P = .023 ) . Clinical outcomes showed no statistical difference between the 2 groups ( all P > .05 ) except for the overall function ( P = .043 ) . The change in 1-year postoperative and immediately postoperative CSA was significantly different between the 2 groups : –15.54 ± 94.34 mm2 in the PRP group versus −85.62 ± 103.57 mm2 in the conventional group ( P = .047 ) . Conclusion : The application of PRP for large to massive rotator cuff repairs significantly improved structural outcomes , as evidence d by a decreased retear rate and increased CSA of the supraspinatus compared with repairs without PRP augmentation . While there was no significant difference in clinical outcomes except the overall shoulder function after 1-year follow-up , better structural outcomes in the PRP group might suggest improved clinical outcomes at longer term follow-up Purpose We evaluated the functional and radiological outcomes of arthroscopic trans-tendon suture-bridge repair for partial-thickness articular-side rotator cuff tears . Methods From December 2008 to May 2010 , 32 consecutive patients with partial-thickness articular-side rotator cuff tears prospect ively underwent arthroscopic trans-tendon suture-bridge repair . We included patients with articular-side partial-thickness supraspinatus tears involving more than half the normal thickness . Patients underwent ultrasonography or magnetic resonance imaging postoperatively . The functional outcomes of patients were evaluated at a minimum 1 year postoperatively . The mean age and follow-up period for the patients were 51.8 ± 13.7 years and 17.4 ± 4.2 months , respectively . Five outcome measures were used before surgery and at the final follow-up : a visual analog scale ( VAS ) pain score , the American Shoulder and Elbow Surgeons ( ASES ) score , the Shoulder Rating Scale of the University of California at Los Angeles ( UCLA ) , the Constant – Murley score and range of motion ( ROM ) . Results The radiological follow-up rate was 87.5 % , and the follow-up rate for clinical evaluation was 96.9 % . Mean UCLA , ASES and Constant – Murley scores improved from 19.1 ± 5.4 , 45.2 ± 16.0 and 58.0 ± 19.6 preoperatively to 35.7 ± 8.5 , 79.0 ± 15.8 and 78.1 ± 12.9 at final follow-up , respectively ( all p ≤ 0.001 ) . Mean VAS score and ROM ( forward flexion ) improved from 6.1 ± 1.9 and 140 ± 36.6 preoperatively to 2.6 ± 1.9 and 163 ± 25.2 at the final follow-up , respectively ( p ≤ 0.001 ) . Additionally , the postoperative radiological examination showed cuff integrity without retear in all patients . Conclusions Arthroscopic trans-tendon suture-bridge repair for partial-thickness articular-side rotator cuff tears result ed in significant improvement in function compared with that before the operation Background : Increased age , larger tear size , and more advanced fatty degeneration of the rotator cuff musculature have been correlated with poorer healing rates after rotator cuff repair . Platelets are an endogenous source of growth factors present during rotator cuff healing . Hypothesis : Augmentation of rotator cuff repairs with platelet-rich fibrin matrix ( PRFM ) may improve the biology of rotator cuff healing and thus improve functional outcome scores and retear rates after repair . Study Design : Cohort study ; Level of evidence , 3 . Methods : Rotator cuff tears at risk for retear were prospect ively identified using an algorithm ; points were assigned for age ( 50 - 59 years = 1 ; 60 - 69 years = 2 ; > 70 years = 3 ) , anterior-to-posterior tear size ( 2 - 2.9 cm = 0 ; 3 - 3.9 cm = 1 ; > 4 cm = 2 ) , and fatty atrophy ( Goutallier score 0 - 2 = 0 ; Goutallier score 3 - 4 = 1 ) . Three points were required for enrollment . Arthroscopic rotator cuff repair was performed with the addition of PRFM . Preoperative and 1-year postoperative magnetic resonance imaging ( MRI ) and functional outcome scores were obtained . Imaging and functional outcomes were compared with historical controls meeting the same enrollment criteria . Results : Sixteen and 21 patients were enrolled in the PRFM and control groups , respectively . Mean age ( 65 ± 7 and 65 ± 9 years ; P = .89 ) , tear size ( 3.8 ± 1.1 and 3.9 ± 1.1 cm ; P = .79 ) , and median Goutallier scores ( 2 and 3 ; P = .18 ) were similar between the PRFM and control groups , respectively . Retear rates ( 56.2 % vs 38.1 % ) were statistically significantly higher ( P = .024 ) in the PRFM group compared with controls . Functional outcome scores postoperatively were not significantly improved compared with controls . Complications included 2 infections in the PRFM group . Conclusion : The augmentation of at-risk rotator cuff tears with PRFM did not result in improved retear rates or functional outcome scores compared with controls Background : The clinical outcome for patients with documented rerupture after open repair of one or more rotator cuff tendons is not well known . The purpose of this study was to evaluate the clinical outcomes of a consecutive series of rotator cuff reruptures after repair and to provide information concerning the advisability of rotator cuff repair in situations in which there may be a high probability of rerupture . Methods : During prospect i ve follow-up after rotator cuff repairs , we detected , with magnetic resonance imaging , structural failure of the repair in twenty patients , who had a mean age of fifty-nine years at the time of the rotator cuff repair . All patients were clinical ly examined for the purpose of this report at a mean of thirty-eight months . Results : The reruptures invariably involved the originally torn tendon but were smaller than the original tear in sixteen of the twenty patients . Fatty degeneration of the supraspinatus and infraspinatus muscles , atrophy of the supraspinatus muscle , and glenohumeral osteoarthritis progressed significantly from the preoperative state ( p < 0.05 ) . At the time of the most recent follow-up , the subjective shoulder value averaged 75 percent of the value for a normal shoulder . Eleven patients were very satisfied with the result , six were satisfied , two were disappointed , and one was dissatisfied . The mean relative score according to the system of Constant and Murley had increased from 49 percent of the score for a normal shoulder preoperatively to 83 percent postoperatively ( p = 0.0001 ) . Pain had decreased significantly , and the ranges of active , pain-free forward elevation and abduction as well as the abduction strength had improved significantly ( p < 0.05 ) . The clinical outcome was significantly correlated with the size of the postoperative tear , the stage of postoperative fatty muscle degeneration of the infraspinatus and subscapularis , the postoperative acromiohumeral distance , and the degree of postoperative glenohumeral osteoarthritis ( p < 0.05 ) . Conclusions : This study documents that an attempt at rotator cuff repair significantly decreases pain ( p = 0.0026 ) and significantly improves function ( p = 0.0005 ) and strength ( p = 0.0137 ) even if magnetic resonance imaging documents that the repair has failed . This finding suggests that the potential for rerupture should not be considered a formal contraindication to an attempt at repair if optimal functional recovery is the goal of treatment BACKGROUND Failure of tendon healing after a rotator cuff repair is demonstrated by magnetic resonance imaging ( MRI ) as a fluid-filled defect within the tendon . The frequency of , and factors associated with , failure of the tendon repair to heal have been the focus of many clinical studies . The timing of when these defects occur has not been previously studied in a large prospect ively defined patient population , to our knowledge . It was our hypothesis that the majority of failures occur within twelve weeks after surgery . METHODS One hundred and thirteen patients were enrolled in a multi-institutional prospect i ve study . All patients had a st and ardized arthroscopic repair of a full-thickness tear of 1 to 4 cm as well as sequential MRI studies at six intervals from two weeks to fifty-two weeks . MRIs were review ed at the time of imaging by the treating surgeon . St and ardized patient-oriented clinical data were collected , physical examination was performed , and strength measurements were made preoperatively and postoperatively . RESULTS The treating surgeons diagnosed a recurrent tear with MRI in nineteen ( 17 % ) of the 113 patients within one year after surgery . The mean time to the retear was 19.2 weeks . There was a linear increase in retears over the first twenty-six weeks after surgery , and one additional tear was diagnosed between twenty-six and fifty-two weeks after repair . CONCLUSIONS Retears primarily occur between six and twenty-six weeks after arthroscopic rotator cuff repair , and few additional tears occur thereafter . A substantial number of retears occur between twelve and twenty-six weeks after repair . LEVEL OF EVIDENCE Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence The reported functional results of rotator cuff repair performed arthroscopically have been good . Only little is known about the cuff integrity after arthroscopic repair and how it influences the outcome . The aim of the study is to set a baseline of what rate of healing response respectively re-tears to expect and how cuff integrity alters the outcome . Fifty-three consecutive patients with an isolated supraspinatus tendon tear were arthroscopically operated and their tendons repaired . All pre- and postoperative data were prospect ively collected . At a minimum follow-up after 24 months ( average 26.4 months ) , the integrity of the cuff was evaluated by an open magnetic resonance imaging and the patients ’ function and satisfaction were documented and grade d to the sex- and age-related Constant-score also using a dynamometer for strength testing . The re-tear rate was 24.5 % with 13 non-healed tendons . The Constant-score of all patients improved significantly . The scores of the patients with a re-tear were significantly lower than those of the patient with an intact cuff . That was due to a less good performance in strength testing . The other categories of the Constant-score did not show any differences . The age of the patients with a re-tear was significantly higher . With the exception of age , we did not find any negative prognostic factor for a re-tear , and with the exception of re-tear no other factor influenced the Constant-score . Arthroscopic supraspinatus tendon repair yields a re-tear rate of 25 % which is comparable with the results of open or mini/open repair . Cuff integrity influences postoperative strength and Constant-score . Patients older than 65 years show a higher re-tear rate . Therapeutic Level IV is the level of evidence Purpose To compare the accuracy of ultrasonography and MR arthrography ( MRA ) imaging in detecting of rotator cuff tears with arthroscopic finding used as the reference st and ard . Methods The ultrasonography and MRA findings of 51 shoulders that underwent the arthroscopic surgery were prospect ively analysed . Two orthopaedic doctors independently performed ultrasonography and interpreted the findings at the office . The tear size measured at ultrasonography and MRA was compared with the size measured at surgery using Pearson correlation coefficients ( r ) . The sensitivity , specificity , accuracy , positive predictive value , negative predictive value and false-positive rate were calculated for a diagnosis of partial- and full-thickness rotator cuff tears . The kappa coefficient was calculated to verify the inter-observer agreement . Results The sensitivity of ultrasonography and MRA for detecting partial-thickness tears was 45.5 and 72.7 % , and that for full-thickness tears was 80.0 and 100 % , respectively . The accuracy of ultrasonograpy and MRA for detecting partial-thickness tears was 45.1 and 88.2 % , and that for full-thickness tears was 82.4 and 98 % , respectively . Tear size measured based on ultrasonography examination showed a poor correlation with the size measured at arthroscopic surgery ( r = 0.21 ; p < 0.05 ) . However , tear size estimated by MRA showed a strong correlation ( r = 0.75 ; p < 0.05 ) . The kappa coefficient was 0.47 between the two independent examiners . Conclusions The accuracy of office-based ultrasonography for beginner orthopaedic surgeons to detect full-thickness rotator cuff tears was comparable to that of MRA but was less accurate for detecting partial-thickness tears and torn size measurement . Inter-observer agreement on the interpretation was fair . These results highlight the importance of the correct technique and experience in operation of ultrasonography in shoulder joint . Level of evidence Diagnostic study , Level II Background Anterosuperior rotator cuff tears involving the subscapularis and supraspinatus tendons are less common than other tears of the rotator cuff . The purpose of this study was to report the clinical outcome , rotator cuff strength and structural integrity of open repair of combined anterosuperior rotator cuff tears . Patients and methods Forty-eight patients at an average age of 58 years underwent open repair of a combined supraspinatus and subscapularis tendon tear . The follow-up evaluation included clinical scores , rotator cuff strength testing with a custom-made force measurement plate ( FMP ) and postoperative MRI to evaluate repair integrity and muscle cross-sectional area . Results After a mean follow-up of 49 months the average Constant score improved from 43 points preoperatively to 79 points postoperatively . The SST and the pain VAS were significantly improved by the procedure ( each < 0.05 ) . The combined tear group with partial subscapularis tears ( G1 ) did not achieve significantly better score results than the combined tear group with a full-thickness subscapularis tear ( G2 ) ( p > 0.05 ) . Strength for all rotator cuff components was reduced significantly ( p < 0.05 ) compared with the contralateral shoulder in both groups . MRI revealed a retear-rate of 4 % for the subscapularis and a retear-rate of 19 % for the supraspinatus . Postoperative muscle cross-sectional area of all rotator cuff muscles did not differ significantly between G1 and G2 ( p > 0.05 ) . Conclusion Open repair of combined anterosuperior rotator cuff tears achieved good postoperative results despite a residual rotator cuff strength deficit . Combined supraspinatus-/full-thickness subscapularis tears achieved equal clinical and radiographic results compared with supraspinatus-/partial-thickness subscapularis tears This prospect i ve study determined whether single-row anchor fixation would reliably improve clinical outcome and maintain structural integrity after arthroscopic repair of single-tendon and 2-tendon rotator cuff tears . In 39 patients , 21 shoulders had single-tendon tears and 18 had 2-tendon tears . Mean follow-up was 38 months ( minimum , 24 months ) . A st and ardized assessment was done preoperatively and postoperatively at yearly intervals . Postoperative magnetic resonance imaging ( MRI ) was performed at a minimum 1-year follow-up . Mean forward elevation , pain , satisfaction , and American Shoulder and Elbow Surgeons scores significantly improved for both groups ( P < .01 ) . Postoperative MRI examinations showed 19 cuffs ( 90 % ) were intact for single-tendon tears and 15 ( 83 % ) were intact for 2-tendon tears . A recurrent tear on postoperative MRI was significantly correlated with the intraoperative finding of asymmetric retraction . Arthroscopic rotator cuff repair using single-row anchor fixation result ed in significant improvements in clinical outcome and reliable repair integrity for both single-tendon and 2-tendon tears Background Double-row arthroscopic rotator cuff repair has become more popular , and some studies have shown better footprint coverage and improved biomechanics of the repair . Hypothesis Double-row rotator cuff repair leads to superior cuff integrity and early clinical results compared with single-row repair . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Forty patients were r and omized to either single-row or double-row rotator cuff repair at the time of surgical intervention . Patients were followed with clinical measures ( UCLA , Constant , WORC , SANE , ASES , as well as range of motion , internal rotation strength , and external rotation strength ) . Magnetic resonance imaging ( MRI ) studies were performed on each shoulder preoperatively , 6 weeks , 3 months , and 1 year after repair . Results Mean anteroposterior tear size by MRI was 1.8 cm . A mean of 2.25 anchors for single row ( SR ) and 3.2 for double row ( DR ) were used . There were 2 retears at 1 year in each group . There were 2 additional cases that had severe thinning in the DR repair group at 1 year . The MRI measurements of footprint coverage , tendon thickness , and tendon signal showed no significant differences between the 2 repair groups . At 1 year , there were no differences in any of the postoperative measures of motion or strength . At 1 year , mean WORC ( SR , 84.8 ; DR , 87.9 ) , Constant ( SR , 77.8 ; DR , 74.4 ) , ASES ( SR , 85.9 ; DR , 85.5 ) , UCLA ( SR , 28.6 ; DR , 29.5 ) , and SANE ( SR , 90.9 ; DR , 89.9 ) scores showed no significant differences between groups . Conclusions No clinical or MRI differences were seen between patients repaired with a SR or DR technique Background The role of degenerative changes in rotator cuff musculature with respect to the functional outcomes of rotator cuff repair have only recently been recognized and are still not well understood . In addition , the reversibility of these changes with repair of the tendons is question able . Hypothesis Poorer preoperative muscle quality negatively affects outcome , and a successful outcome ( in terms of a healed repair ) might demonstrate improvements in fatty infiltration and muscle atrophy . Study Design Cohort study ; Level of evidence , 2 . Methods Thirty-eight patients ( mean age , 62 years ) were prospect ively evaluated with preoperative and 1-year postoperative clinical examination and appropriate magnetic resonance image sequencing to determine grade s of muscle atrophy and fatty infiltration of the supraspinatus and infraspinatus muscles . American Shoulder and Elbow Society ( ASES ) , Constant , and pain scores were determined as well as strength measurements . The retear rate and progression of muscle degeneration were also evaluated . Independent predictors of outcome measurements and cuff integrity were determined . Results The overall clinical outcome , including ASES , Constant , and pain scores , improved significantly ( P < .0001 ) . Strength in forward elevation improved significantly ( P < .006 ) , while external rotation strength did not . There was a strongly negative correlation between muscle quality and outcome results in most cases . When the results were adjusted for multivariate effect , muscle atrophy and fatty infiltration of the infraspinatus muscle were the only independent predictors of ASES and Constant scores ( P < .03 ) . Tear size and rotator cuff healing did not play an independent role . Tear size , however , was the only independent predictor of ultimate cuff integrity ( P = .002 ) . Both atrophy and fatty infiltration progressed significantly over the course of the study . In cases in which the tendon had re-torn , the progression was found to be more significant than when the repair proved successful ( P < .003 ) . Conclusion Muscle atrophy and fatty infiltration of the rotator cuff muscles , particularly of the infraspinatus , play a significant role in determining functional outcome after cuff repair . Tear size appears to have the most influential effect on repair integrity . A successful repair did not lead to improvement or reversal of muscle degeneration and a failed repair result ed in significantly more progression . In general , healed repairs demonstrated minimal progression . These findings suggest that repairs should be performed , if possible , before more significant deterioration in the cuff musculature in order to optimize outcomes , and that underst and ing the degree of muscle atrophy and fatty infiltration before surgery can help guide patient expectations Thirty chronic rotator cuff tears were repaired consecutively and evaluated prospect ively using a precise anatomic description of the tear that included the rotator interval , the Constant functional score , and an assessment of the tendon state and the atrophy of the supraspinatus muscle by preoperative and postoperative magnetic resonance imaging . Early correlations ( mean followup , 21.1 months ) attempted to define predictive factors of the final outcome of the repair , physical factors indicative of final tendon state , and postoperative evolution of supraspinatus atrophy . Magnetic resonance imaging oblique sagittal views showed that supraspinatus atrophy correlated with the sagittal and coronal extent of the tear and represented a strong predictive factor of postoperative retearing . At followup , 15 ( 50 % ) cuffs were continuous and thick , seven ( 23 % ) were continuous but thin , and six ( 20 % ) were retorn . Two ( 7 % ) cuffs had been repaired only partly . In the group with a persistent tear , flexion strength and differential Constant score were correlated with the final tendon state with no excellent or good results , and with less than 4 kg of strength . Supraspinatus atrophy improved in 18 of the 22 postoperative continuous cuffs , but never decreased in persistent tears , although there was pain relief and functional gain Background Open rotator cuff repairs have led to excellent clinical results ; however , several studies have linked postoperative structural integrity to patient outcomes . The purpose of this study is to prospect ively assess postoperative cuff integrity after open rotator cuff repair and assess its relationship to clinical outcome . Hypothesis Preoperative rotator cuff tear size and postoperative rotator cuff integrity are important factors in overall clinical outcomes . Study Design Prospect i ve nonr and omized clinical outcomes study . Methods Forty-seven consecutive patients undergoing repair of full-thickness rotator cuff tears by a single surgeon were enrolled in this prospect i ve study . A st and ardized evaluation was performed preoperatively and postoperatively at annual intervals . All patients underwent postoperative magnetic resonance imaging at least 1 year after surgery . Statistical evaluation was performed using paired and unpaired 2-tailed t tests for comparison . Results Thirty-two patients were available for evaluation . Overall , the patients experienced a significant ( P < .05 ) improvement in their American Shoulder and Elbow Surgeons survey ( 40 - 85 ) and Constant ( 53 - 80 ) scores . The overall retear rate was 31 % . Although patients with large tears preoperatively and retears postoperatively had lower overall outcomes scores , this was not significant . Conclusion These data support open rotator cuff repair as an effective technique that restores excellent shoulder function . The authors did not find postoperative cuff integrity to have a significant effect on outcomes when compared with those with an intact cuff . In fact , those with a retear still had a significant improvement in all clinical areas assessed , including strength PURPOSE This prospect i ve r and omized study compared the clinical outcomes of patients who underwent partial-thickness articular-sided rotator cuff repairs by 2 surgical techniques . METHODS Forty-eight patients with a symptomatic partial-thickness articular-sided rotator cuff tear exceeding 50 % of the tendon thickness were r and omly assigned to 2 groups at the time of operation . Of the patients , 24 received arthroscopic rotator cuff repair with a transtendon technique ( group I ) and 24 received arthroscopic rotator cuff repairs after tear completion ( group II ) . Pain intensity and patient satisfaction were assessed by visual analog scales , and functional outcomes were evaluated by use of American Shoulder and Elbow Surgeons and Constant shoulder scores . Tendon integrity was evaluated by magnetic resonance imaging at 6 months after surgery . RESULTS Clinical outcomes were significantly improved after repair in both groups at a mean of 31 months ' follow-up . In each group 22 patients ( 92 % ) were satisfied with surgery . However , shoulder function and range of shoulder motion recovered faster in group II during the recovery period ( American Shoulder and Elbow Surgeons score , 54.9 ± 3.7 in group I v 64.6 ± 3.2 in group II ; P = .037 ) ( Constant score , 57.9 ± 2.9 in group I v 70.8 ± 3.3 in group II ; P = .019 ) . Furthermore , patients in group I had significantly more pain ( 5.9 ± 0.4 ) than patients in group II ( 2.8 ± 0.5 ) ( P = .001 ) until 3 months after surgery . Postoperative adhesive capsulitis developed in 3 patients in group I and in 2 patients in group II . According to postoperative 6-month magnetic resonance imaging assessment s , all patients in group I achieved complete integrity whereas a retear developed in 2 patients in group II . CONCLUSIONS Arthroscopic repair of partial-thickness articular-sided rotator cuff tears exceeding 50 % of the tendon thickness provided satisfactory functional improvements and pain relief regardless of the repair technique . Although repair after conversion to a full-thickness tear showed less postoperative morbidity , tendon integrity is of primary concern after repair . On the other h and , the transtendon repair technique result ed in complete tendon integrity but slower functional recovery . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Background : Massive tears of the tendons of the rotator cuff cause atrophy and fatty degeneration of the rotator cuff muscles and painful loss of function of the shoulder . Repair of massive rotator cuff tears is often followed by retears of the tendons , additional muscular degeneration , and a poor clinical outcome . The purpose s of this study were to determine whether a new method of repair of rotator cuff tendons can yield a lower retear rate and a better clinical outcome than previously reported methods , to assess the muscular changes following repair of massive tears of the musculotendinous units , and to correlate findings on magnetic resonance imaging with the clinical results . Methods : Twenty-nine massive rotator cuff tears involving complete detachment of at least two tendons were repaired operatively with use of a new laboratory-tested technique in a prospect i ve study . At least two years ( average , thirty-seven months ; range , twenty-four to sixty-one months ) postoperatively , twenty-seven patients were evaluated clinical ly and with magnetic resonance imaging to determine the clinical outcome , the integrity of the repair , and the condition of the rotator cuff muscles . Results : The age and gender-adjusted Constant score improved from an average of 49 percent preoperatively to an average of 85 percent postoperatively , corresponding to a subjective shoulder value of 78 percent of that of a normal shoulder . Pain-free flexion improved from an average of 92 degrees to an average of 142 degrees , and abduction improved from an average of 82 degrees to an average of 137 degrees . Pain decreased and performance of activities of daily living improved significantly ( p < 0.05 ) . The seventeen patients who had a structurally successful repair all had an excellent clinical outcome . Muscle atrophy could not be reversed except in successfully repaired supraspinatus musculotendinous units . Fatty degeneration increased in all muscles . Conclusions : The method of repair of massive rotator cuff tears that was used in this study yielded a comparatively low retear rate and good-to-excellent clinical results ; however , the repair did not result in substantial reversal of muscular atrophy and fatty degeneration . Retears occurred more often in patients who had had a shorter interval between the onset of the symptoms and the operation ( p < 0.05 ) . Patients who had a retear had improvement of the shoulder compared with the preoperative state , but they had less improvement than did those who had a successful repair PURPOSE Our goal in this analysis was to compare clinical outcomes and radiographic healing rates of double-row ( DR ) transosseous-equivalent versus single-row ( SR ) Mason-Allen configuration ( MAC ) arthroscopic repair techniques . METHODS A prospect i ve , nonr and omized assessment of 132 arthroscopic rotator cuff repair patients included 78 SR repair patients and 54 with DR repair . Tears measured between 1.5 and 4.5 cm . Patients were evaluated with a visual analog scale ; University of California , Los Angeles score ; American Shoulder and Elbow Surgeons score ; active range of motion ; and dynamometric strength . Scores and measurements were obtained preoperatively and at 3 , 6 , 12 , and 24 months postoperatively . The SR repairs were performed with the arthroscopic MAC . For DR repairs , two 5.5-mm fully threaded Bio-Corkscrew anchors ( Arthrex , Naples , FL ) , single loaded with FiberWire ( Arthrex ) , were used for the medial row . The lateral row was secured with PushLock bioabsorbable anchors ( Arthrex ) . Forty-four patients in the SR group and 37 patients in the DR group returned for magnetic resonance imaging ( MRI ) evaluation of repair integrity between 12 and 28 months postoperatively . RESULTS DR repairs result ed in higher outcome scores , though not significantly . Patient satisfaction rates were 95 % in the SR group and 92 % in the DR group . MRI showed a statistically significantly improved healing rate with SR repair compared with DR repair in our entire patient population ( P ≤ .017 ) . A more homogeneous subset of patients with tears between 2.5 and 3.5 cm showed a significantly improved healing rate for the DR repair ( P ≤ .03 ) . CONCLUSIONS Our short-term results suggest that SR MAC repair provides comparable clinical results to DR repair . Although our MRI data suggest improved healing rates in our SR repairs in the entire patient population , when similar-sized tears were compared , the DR repair group showed improved radiographic healing . LEVEL OF EVIDENCE Level III , retrospective comparative study BACKGROUND Arthroscopic rotator cuff repair generally provides satisfactory results including decreased shoulder pain and improved shoulder motion . Unfortunately , imaging studies demonstrate that the retear rate associated with the available arthroscopic techniques may be high . The purpose of this study was to evaluate the clinical and magnetic resonance imaging ( MRI ) results of arthroscopic rotator cuff repair with and without the use of platelet-leukocyte membrane in patients with a large posterosuperior rotator cuff tear . METHODS Eighty consecutive patients with a large full-thickness posterosuperior rotator cuff tear were enrolled . All tears were repaired using an arthroscopic single-row technique . Patients were r and omized to treatment either with or without a platelet-leukocyte membrane inserted between the rotator cuff tendon and its footprint . In patients treated with this membrane , one membrane was utilized for each suture anchor . The primary outcomes were the difference between the preoperative and postoperative Constant scores and the repair integrity assessed by MRI according to the Sugaya classification . The secondary outcome was the difference between the preoperative and postoperative Simple Shoulder Test ( SST ) scores . RESULTS The only significant differences between the two groups involved the patient age and the preoperative and postoperative Constant scores ; the differences in the Constant score were due to differences in the shoulder pain subscore . At a mean of thirteen months of follow-up , rotator cuff retears were observed only in the group of patients in whom the membrane had not been used , and a thin but intact tendon was observed more frequently in this group as well . The use of the membrane was associated with significantly better repair integrity ( p = 0.04 ) . CONCLUSIONS The use of the platelet-leukocyte membrane in the treatment of rotator cuff tears improved repair integrity compared with repair without membrane . However , the improvement in repair integrity was not associated with greater improvement in the functional outcome . In fact , the Constant scores of the two groups would have been similar if the shoulder pain component ( which had differed preoperatively ) had been excluded PURPOSE The purpose of this study was to compare the clinical outcomes and the retear rates of arthroscopic single-row ( SR ) and double-row ( DR ) suture anchor repair in 2- to 4-cm rotator cuff tears . METHODS From 2005 to 2007 , 71 patients with a 2- to 4-cm rotator cuff tear ( proven by arthroscopy ) were prospect ively r and omized to SR and DR repair groups . Of these patients , 62 ( 31 in each group ) were available for evaluation at final follow-up . Demographic data , clinical scores , mean surgical times , and patient satisfaction were compared . Retear rates and clinical scores were also analyzed for 47 patients who underwent follow-up magnetic resonance imaging . RESULTS Comparisons of demographic data , tear size on preoperative magnetic resonance imaging , global fatty degeneration index , and concomitant procedures showed no differences between the SR and DR groups . Preoperative clinical scores were significantly improved postoperatively in both groups . No intergroup differences in pain visual analog scale , American Shoulder and Elbow Surgeons , Constant , or University of California , Los Angeles scores were found at final follow-up . Only mean surgical time was significantly different between the 2 groups . In the SR group , there were 4 full-thickness retears and 11 partial-thickness retears , whereas in the DR group , there were 6 full-thickness retears and 1 partial-thickness retear . However , despite numerical differences , these differences were not statistically different . Statistically , there were no significant differences both in full-thickness retear ( P = .999 ) and retear including partial-thickness tear between the 2 groups ( P = .124 ) . CONCLUSIONS This study indicates that the clinical results and retear rates of DR repair with 1 additional medial suture anchor were not significantly different from those of SR repairs with 2 lateral suture anchors in patients with medium to large rotator cuff tear . LEVEL OF EVIDENCE Level I , r and omized controlled trial PURPOSE To assess the role of acromioplasty in the arthroscopic repair of small- to medium-sized rotator cuff tears . METHODS A prospect i ve r and omized trial of 120 patients who had small- to medium-sized rotator cuff tears and various types of acromions without spurs were included . Sixty patients received arthroscopic rotator cuff repair with acromioplasty ( group I ) , and another sixty received the same procedure without acromioplasty ( group II ) . The mean age at surgery was 57.8 ± 9.3 years in group I and 55.8 ± 8.0 years in group II . The shape of the acromion was flat in 18 patients , curved in 32 , and hooked in 10 in group I , and it was flat in 15 patients , curved in 36 , and hooked in 9 in group II . The mean tear size was similar in the two groups ( 14.6 ± 5.2 mm in group I and 15.3 ± 7.0 mm in group II ) . Pain and satisfaction were estimated and range of motion was measured at a mean of 35 months after surgery . Functional outcomes were assessed with American Shoulder and Elbow Surgeons : Constant ; and University of California , Los Angeles scores . Tendon healing was evaluated by magnetic resonance imaging postoperatively . RESULTS Clinical outcome was significantly improved in both groups after arthroscopic rotator cuff repair ( P < .05 ) . There were no significant differences with respect to pain and range of motion between the groups at the final follow-up ( 1.1 ± 0.9 v 1.3 ± 1.4 on visual analog scale ) . Functional outcomes also showed no significant differences between the 2 groups ( American Shoulder and Elbow Surgeons score , 90.7 ± 13.1 v 87.5 ± 12.0 ; Constant score , 85.0 ± 11.3 v 83.3 ± 13.0 ; and University of California , Los Angeles score , 33.4 ± 3.3 v 32.3 ± 3.5 ) . Postoperative imaging showed that the retear rate was 17 % in group I and 20 % in group II ( P = .475 ) . CONCLUSIONS Arthroscopic repair of small- to medium-sized rotator cuff tears provided pain relief and improved functional outcome with or without acromioplasty . Clinical outcomes were not significantly different , and acromioplasty may not be necessary in the operative treatment of patients with small- to medium-sized rotator cuff tears in the absence of acromial spurs . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Background : Important differences in clinical outcomes likely exist between patients with healed and nonhealed rotator cuff repairs . The survival probability of rotator cuff repairs has not been published in a time-dependent manner up to now . Hypotheses : Recurrent tears occur more frequently in the early postoperative period . Early failures of the repair are a prognostic factor for the long-term outcome . Study Design : Cohort study ; Level of evidence , 3 . Methods : A series of 107 consecutive patients undergoing arthroscopically assisted mini-open repair of the rotator cuff between 1998 and 2002 were evaluated in a prospect i ve study . Of these , 95 patients finished the study after a maximum follow-up of 11 years . The evaluation included 1 postoperative magnetic resonance imaging scan as well as multiple ultrasonographies and determinations of the American Shoulder and Elbow Surgeons ( ASES ) and Constant scores at 3 months , 6 months , 1 year , and then yearly with a median follow-up of 96 months . Results : The overall failure rate was 33 % ( 35 of 107 ) . The survivorship analysis revealed that 74 % of all failures occurred atraumatically in the first 3 months and 11 % occurred between the third and the sixth month after the repair . The remaining reruptures ( 14 % ) happened 2 to 5 years postoperatively and were related to sports activities or direct trauma . The overall clinical results did not deteriorate over time . The parameters healed tendon , rerupture of less than 2 cm2 , and rerupture of more than 2 cm2 at 6 months were predictors of the gender- and age-adjusted ( normalized ) Constant score at 84 months ( P < .0001 ) . Conclusion : The majority of recurrent tears occurred in the first 3 months after surgical repair . The parameters “ recurrent tear ” as well as “ healed tendon ” evaluated at 6 months postoperatively appear to be predictors for the clinical outcomes at 7 years . Efforts to improve healing during the initial 3 months have long-term implication s for maintenance of cuff integrity and clinical outcomes Background The suture-bridging technique is a new arthroscopic technique to repair rotator cuff tears . Biomechanical advantages compared with double-row fixations have been described . Hypothesis The authors hypothesized that arthroscopic suture-bridging repair of the supraspinatus tendon would result in a superior clinical outcome and lower retear rates compared with previously published results after double-row fixation . Study Design Case series ; Level of evidence , 4 . Methods Fifty-one consecutive patients , with a median age of 62 years ( range , 37 - 76 years ) , who had undergone an arthroscopic suture-bridging repair of an isolated supraspinatus tendon tear were evaluated in this prospect i ve study 4 , 12 , and a median of 24 months postoperatively . Subjective and functional outcome was assessed using the simple shoulder test and Constant score . With magnetic resonance imaging 12 months postoperatively , the tendon integrity and potential predictors of failures were evaluated . Results The simple shoulder test scores improved significantly from 9 points ( range , 1 - 12 points ) at 4 months , to 12 points ( range , 1 - 12 points ) at 12 months , and 12 points ( range , 5 - 12 points ) at 24 months postoperatively . The Constant score increased significantly from preoperative 64 % ( range , 37%-92 % ) to 82 % ( range , 36%-100 % ) at 4 months , 96 % ( range , 49%-100 % ) at 12 months , and 96 % ( range , 64%-100 % ) at 24 months postoperatively . Magnetic resonance imaging 12 months after surgery showed retears in 28.9 % . Two different types of retears could be observed : insufficiently healed and medially retorn supraspinatus tendons . The Constant score did not differ significantly between the groups with retears and intact repairs . A patient age of more than 60 years was found to influence tendon healing significantly . Conclusion The hypothesis , that arthroscopic suture-bridging repair of the supraspinatus tendon would result in a superior clinical outcome and lower retear rates compared with previously published results after double-row fixation , could not be confirmed . The functional outcome after the new suture-bridging technique was good and comparable with the reported results after double-row repair from the literature . A structural failure of tendon repair was not identical to clinical failure Purpose The aim of this study was to compare the functional and structural outcomes of 2 techniques for double-row , suture-bridging cuff repair . Methods A consecutive series of 73 patients who underwent arthroscopic , double-row , suture-bridge primary rotator cuff repair of full-thickness supraspinatus tear were evaluated . Thirty-eight shoulders were repaired by the arthroscopic , tied , suture-bridging technique ( group A ) , and 35 shoulders by knot-less bridging with suture tape material ( group B ) . Constant scores , pain , range of motion , strength , and complications were measured after a minimum follow-up period of 12 months post-operatively . Structural integrity of the repairs was evaluated systematic ally by either magnetic resonance imaging or computed tomography arthrography . Results Median follow-up after surgery was 29 ( 23–32 ) months in group A , and 21 ( 12–23 ) months in group B. Mean pain relief , range of motion , strength , and constant score improved significantly in both groups . No statistical differences were found between groups in the post-operative period . According to control imaging , the re-tear rate trended to be higher in group A ( 23.4 % ) than in group B ( 17.1 % ) , although not significantly . Conclusion Both bridging repair techniques achieved successful functional outcomes . In terms of structural outcome , the knot-less tape-bridging construct showed a lower but not significant re-tear rate . Longer follow-up is needed to confirm these results and to evaluate potential differences between the two techniques . Level of evidence A prospect i ve , non-r and omized , comparative study , Level III PURPOSE Arthroscopic rotator cuff repair produces equally good clinical results compared with open or mini-open repair . However , there are concerns about whether the same repair integrity can be achieved . The purpose of our study was to compare clinical and structural results of arthroscopic and mini-open rotator cuff repair . METHODS Nineteen patients who had arthroscopic rotator cuff repair ( mean follow-up , 25.0 months ) were matched for age , gender , and duration of symptoms with nineteen patients who had mini-open repair ( mean follow-up , 17.6 months ) . We compared preoperative and follow-up Constant scores , as well as early range of motion after 6 weeks and 3 months . All patients were examined with the same magnetic resonance imaging system at follow-up to evaluate cuff integrity . RESULTS There was no difference in clinical and structural outcome . The overall Constant score improved from 53.8 to 83.9 in the arthroscopic group and from 53.5 to 83.7 in the mini-open group . Early range of motion did not differ significantly at 6 weeks or 3 months postoperatively . The number of retears was 6 ( 31.6 % ) in the arthroscopic group and 7 ( 36.8 % ) in the mini-open group . This difference was not statistically significant ( P = .7358 ) . Although smaller retears had no influence on the clinical result , more retracted retears correlated with lower abduction strength regardless of the repair method . CONCLUSIONS In isolated supraspinatus tears arthroscopic rotator cuff repair produces excellent clinical results and equivalent tendon integrity compared with mini-open repair . LEVEL OF EVIDENCE Level III , retrospective therapeutic comparative study A study of 5 fresh cadaveric shoulders demonstrated that an oblique-sagittal plane which crosses the scapula through the medial border of the coracoid process offers a view of the supraspinatus fossa mostly limited by bone . This view could easily be reproduced by MRI and we called it the Y-shaped view . It allowed a reliable measurement of supraspinatus muscle atrophy by the calculation of the occupation ratio ( R ) which is the ratio between the surface of the cross-section of the muscle belly and that of the fossa . This ratio was calculated in a prospect i ve study based on 55 shoulders divided into 3 groups with different rotator cuff status : group I , 15 controls ; group II , 10 degenerative cuffs , without tears ; group III , 30 operated tears . There was no difference between groups I ( mean ratio 0.7 ) and II ( mean ratio 0.62 ) , but the ratio was decreased in group III ( mean ratio 0.44 ) , in which the extent of the tear in both the sagittal and coronal planes aggravated the muscle atrophy . We propose a three-stage classification to improve indications for rotator cuff tear treatment OBJECTIVE This study assessed the utility of MRI in patients with new or persistent pain after surgery with bioabsorbable rotator cuff anchors . SUBJECTS AND METHODS . Three musculoskeletal radiologists prospect ively review ed MRIs of 30 patients with pain after rotator cuff repair with fixation by rotator cuff anchors . Each radiologist described the location of the rotator cuff anchors and whether the supraspinatus tendon was intact or not . MRI findings were correlated with second-look arthroscopy . Consensus MRI interpretations by the three radiologists were obtained retrospectively . RESULTS Of the 30 patients , nine had dislodgement of the rotator cuff anchors from the humeral head along with a full-thickness supraspinatus tendon retear . The dislodged rotator cuff anchor position could be determined on coronal and sagittal MRIs , providing the orthopedic surgeon a preoperative map for tendon reattachment and retrieval of the dislodged rotator cuff anchor . Four patients had loose rotator cuff anchors but intact supraspinatus tendons . Three patients had supraspinatus tendon retears , but the rotator cuff anchors were intact . In all 16 patients , arthroscopic findings confirmed MRI findings . Fourteen patients had intact rotator cuff anchors and intact supraspinatus tendons on MRI . Of these 14 patients , five had second-look arthroscopy confirming MRI findings . CONCLUSION MRI is useful in the assessment of patients with persistent or new-onset pain after supraspinatus tendon repair with rotator cuff anchors . MRI provides a presurgical map for second-look arthroscopy to assess retear of the supraspinatus tendon and also aids in retrieval of dislodged rotator cuff anchors The aim of this study was to compare the accuracy of ultrasonography ( US ) and magnetic resonance artrography ( MRA ) for the detection and measurement of rotator cuff tears , using surgical findings as a st and ard . A total of 77 consecutive patients with suspected rotator cuff tears were prospect ively studied with US and MRA . Rotator cuff tears were identified by US with sensitivity , specificity , positive predictive and negative predictive values of 92 % , 45 % , 91 % and 50 % , respectively , and by MRA with values of 97 % , 82 % , 97 % and 82 % , respectively . US was not reliable for differentiating between partial and full thickness tears . US and MRA underestimated the tear sizes by an average of 15 mm and 4 mm , respectively . Our results suggest that US could be used as a screening test to confirm a suspected rotator cuff tear . In patients with negative findings , an MRA should be considered for substantiation Arthroscopic rotator cuff repair ( RCR ) has been reported to have good clinical results but high retear rates by ultrasound . We prospect ively assessed postoperative cuff integrity and outcome after arthroscopic RCR ( 40 patients ) and compared these results with open RCR ( 32 patients ) . Evaluation preoperatively and at 1 year included a physical examination and magnetic resonance imaging . American Shoulder and Elbow Surgeons and Constant scores improved significantly in both groups ( P < .0001 ) . Overall , 69 % of repairs in the open group and 53 % in the arthroscopic group were intact by magnetic resonance imaging . Of tears less than 3 cm in size , 74 % in the open group and 84 % in the arthroscopic group were intact . Of tears greater than 3 cm in size , 62 % in the open group and 24 % in the arthroscopic group were intact ( P < .036 ) . In the arthroscopic group , patients with an intact cuff had significantly greater strength of elevation ( P = .01 ) and external rotation ( P = .02 ) . We conclude that open and arthroscopic RCRs have similar clinical outcomes . Cuff integrity is comparable for small tears , but large tears have twice the retear rate after arthroscopic repair BACKGROUND The retear rate following rotator cuff repair is variable . Recent biomechanical studies have demonstrated that double-row tendon-to-bone fixation excels in initial fixation strength and footprint coverage compared with the single-row or transosseous fixation methods . This study was design ed to report the repair integrity and clinical outcome following arthroscopic double-row rotator cuff repair . METHODS A consecutive series of 106 patients with full-thickness rotator cuff tears underwent arthroscopic double-row rotator cuff repair with use of suture anchors and were followed prospect ively . Twenty patients lacked complete follow-up data or were lost to follow-up . The eighty-six study subjects included fifty-two men and thirty-four women , with an average age of 60.5 years . There were twenty-six small , thirty medium , twenty-two large , and eight massive tears . Clinical outcomes were evaluated at an average of thirty-one months . Repair integrity was estimated with use of magnetic resonance imaging , which was performed , on the average , fourteen months postoperatively , and was classified into five categories , with type I indicating sufficient thickness with homogeneously low intensity ; type II , sufficient thickness with partial high intensity ; type III , insufficient thickness without discontinuity ; type IV , the presence of a minor discontinuity ; and type V , the presence of a major discontinuity . RESULTS The average clinical outcome scores all improved significantly at the time of the final follow-up ( p < 0.01 ) . At a mean of fourteen months postoperatively , magnetic resonance imaging revealed that thirty-seven shoulders had a type-I repair ; twenty-one , a type-II repair ; thirteen , a type-III repair ; eight , a type-IV repair ; and seven , a type-V repair . The overall rate of retears ( types IV and V ) was 17 % . The retear rate was 5 % for small-to-medium tears , while it was 40 % for large and massive tears . The shoulders with a type-V repair demonstrated significantly inferior functional outcome in terms of overall scores and strength compared with the other types of repairs ( p < 0.01 ) . CONCLUSIONS Arthroscopic double-row repair can result in improved repair integrity compared with open or miniopen repair methods . However , the retear rate for shoulders with large and massive tears remains higher than that for smaller tears , and shoulders with large repair defects ( type V ) demonstrate significantly inferior functional outcomes PURPOSE To assess the effect of platelet-rich plasma fibrin matrix ( PRPFM ) construct augmentation on postoperative tendon healing as determined by magnetic resonance imaging ( MRI ) and clinical outcome of arthroscopic rotator cuff repair . METHODS A comparative series of patients undergoing arthroscopic rotator cuff repair was studied . Two matched groups of patients ( 20 each ) were included : rotator cuff repairs without PRPFM augmentation ( group 1 ) and rotator cuff repairs augmented with 2 sutured platelet-rich plasma ( PRP ) constructs ( group 2 ) . A single-row cuff repair to the normal footprint without tension or marrow vents was performed by a single surgeon . Postoperative rehabilitation was held constant . Postoperative MRI scans were used to evaluate rotator cuff healing . Outcome measures included American Shoulder and Elbow Surgeons , Rowe , Single Assessment Numeric Evaluation , Simple Shoulder Test , and Constant scores . RESULTS We followed up 40 patients ( 2 matched groups with 20 patients each ) with a mean age of 57 years ( range , 44 to 69 years ) for a mean of 31 months ( range , 24 to 44 months ) . Postoperative MRI studies showed persistent full-thickness tendon defects in 60 % of controls ( 12 of 20 ) and 30 % of PRPFM-augmented repairs ( 6 of 20 ) ( P = .03 ) . Of the control group tears measuring less than 3 cm in anteroposterior length , 50 % ( 7 of 14 ) healed fully , whereas 86 % of the PRPFM group tears measuring less than 3 cm in anteroposterior length ( 12 of 14 ) healed fully ( P < .05 ) . There was no significant difference between groups 1 and 2 in terms of American Shoulder and Elbow Surgeons ( 94.7 and 95.7 , respectively ; P = .35 ) , Single Assessment Numeric Evaluation ( 93.7 and 94.5 , respectively ; P = .37 ) , Simple Shoulder Test ( 11.4 and 11.3 , respectively ; P = .41 ) , and Constant ( 84.7 and 88.1 , respectively ; P = .19 ) scores . The Rowe scores ( 84.8 and 94.9 , respectively ; P = .03 ) were statistically different . CONCLUSIONS The addition of 2 PRPFM constructs sutured into a primary rotator cuff tendon repair result ed in lower retear rates identified on MRI than repairs without the constructs . Other than the Rowe scores , there was no postoperative clinical difference by use of st and ard outcome measures . LEVEL OF EVIDENCE Level III , case-control study BACKGROUND The clinical outcomes of open rotator cuff repair are well established , but the structural results and their effect on clinical outcome are poorly known . We assessed the structural changes in the musculotendinous units after open rotator cuff repair and correlated these findings with the clinical outcome to establish a benchmark for future series . METHODS Thirty-two consecutive st and ardized open repairs of a single tendon tear of the rotator cuff were analyzed in twenty-one men and eleven women with an average age of 59.0 years . The supraspinatus tendon was involved in twenty-two patients and the subscapularis tendon , in ten . The clinical outcome , including the Constant score , was assessed prospect ively for all patients at an average of thirty-eight months postoperatively . The structural outcome was assessed on st and ardized magnetic resonance imaging scans . RESULTS The mean overall subjective shoulder value was 82.8 % of the value for a normal shoulder . On the average , the age and gender-adjusted Constant score increased from 63.9 % preoperatively to 94.5 % postoperatively ( p < 0.0001 ) ; the score for pain , from 6.8 points to 13.2 points ( p < 0.0001 ) ; and the score for activities of daily living , from 11.2 points to 17.9 points ( p < 0.0001 ) . The overall rerupture rate was 13 % ( four of the thirty-two shoulders ) . All reruptures were distinctly smaller than the original tear . Muscular atrophy or fatty infiltration did not significantly decrease after the tendon repair . In fact , fatty infiltration in the supraspinatus ( p < 0.0053 ) and infraspinatus ( p < 0.003 ) muscles increased significantly . CONCLUSIONS Direct open repair of a complete , isolated tear of one tendon of the rotator cuff result ed in significant subjective and objective improvement and very high patient satisfaction . Successful direct repair was not associated with a decrease in preoperative muscular atrophy and was associated with increased fatty infiltration of the muscle The aim of this study was to investigate tendon integrity after surgical repair of single-tendon rotator cuff lesions . In 31 patients , 31 single-tendon repairs were evaluated . Thirty-one patients were available for clinical assessment and magnetic resonance imaging ( MRI ) at follow-up . A st and ard series of MR images was obtained for each . The results of functional assessment were scored according to the system of Constant . According to MRI evaluation , 21 ( 68 % ) patients had an intact or thinned rotator cuff and 10 ( 32 % ) had recurrence of a full-thickness cuff defect at follow-up . Patients with an intact or thinned rotator cuff had a median Constant score of 75.5 points ; patients with a full-thickness cuff defect had a median score of 62 points . There was no correlation between tendon integrity on postoperative MR images and functional outcome . Patients with intact or thinned cuffs did not have significantly better functional results than patients with retorn cuffs . Because of the presence of metal artifacts and the difficulty in distinguishing postoperative scar tissue from partial tears or thinning , MRI is of minor diagnostic value in assessing the shoulder after cuff repair . However , full-thickness tears are readily diagnosed after operation with MRI PURPOSE The purpose of our study was to evaluate the outcome of massive rotator cuff tears repaired by use of an arthroscopic biceps augmentation technique , interpositioning the tenotomized biceps tendon to bridge the gap between the torn edges of the cuff tendon . METHODS Sixty-eight shoulders with massive rotator cuff tears were included in this study . Arthroscopic rotator cuff repairs with the biceps augmentation technique were performed in 37 patients ( group A ) , whereas 31 patients underwent repair without biceps augmentation ( group B ) . The mean follow-up period was 21 months ( range , 14 to 78 months ) in group A and 20 months ( range , 13 to 63 months ) in group B. RESULTS The mean University of California , Los Angeles score improved from 14.1 points ( range , 6 to 21 points ) in group A and 13.9 points ( range , 7 to 22 points ) in group B preoperatively to 32.6 points ( range , 22 to 35 points ) and 30.3 points ( range , 20 to 35 points ) postoperatively , respectively ( P < .001 and P < .001 , respectively ) . However , the difference between the postoperative scores was not statistically significant ( P = .198 ) . At the last follow-up , group A showed better results than group B in forward flexion , external rotation , and internal rotation strength , with statistically significant differences ( P = .017 , P = .001 , and P < .001 , respectively ) . According to the postoperative repair integrity analyzed by use of magnetic resonance imaging , 58.3 % of group A cases ( 14/24 ) and 26.3 % of group B cases ( 5/19 ) had complete healing ( P = .036 ) . CONCLUSIONS An arthroscopic augmentation technique using the tenotomized biceps tendon was effective in achieving fewer structural failures , equivalent clinical outcomes , and significant improvement in muscle strength in comparison traditional arthroscopic repairs by avoiding undue tension in cases with massive rotator cuff tear PURPOSE The purpose of this study was to evaluate the clinical results and healing status of rotator cuff repairs with less than 50 % footprint coverage . METHODS During the 18-month period from October 2005 to March 2007 , 89 large to massive rotator cuff tears were arthroscopically repaired . Among them , 23 consecutive large to massive rotator cuff tears were repaired completely but with less than 50 % of the original footprint . All tears were arthroscopically repaired with suture anchors . Preoperative and postoperative clinical assessment s were performed with the Constant score , American Shoulder and Elbow Surgeons score , and pain visual analog scale . The healing status of repaired tendon was evaluated by postoperative magnetic resonance imaging with a focus on tendon integrity , muscle fatty degeneration , and muscle atrophy . RESULTS The mean follow-up period was 30.2 months ( range , 24 to 41 months ) . At final follow-up visits , American Shoulder and Elbow Surgeons score , Constant score , and score on pain visual analog scale were found to have improved significantly from 40.1 , 35.9 , and 57.7 to 82.4 , 86.6 , and 12.3 , respectively ( P < .01 ) . The overall retear rate was 45.5 % ( 10 cases ) . However , clinical results showed no difference between the retear group and no retear group . Furthermore , rerupture size was smaller than original tear size in all 10 patients , and no significant progression of fatty degeneration or muscle atrophy of rotator cuff muscles was observed . CONCLUSIONS Less-than-optimal coverage of the original greater tuberosity footprint during arthroscopic repair of large to massive rotator cuff tears was found to be associated with a relatively high retear rate ( 45.5 % ) . However , clinical results improved significantly , and no significant difference was observed in the clinical results between the retear and no retear groups . LEVEL OF EVIDENCE Level IV , therapeutic case series |
1,123 | 23,995,037 | Having a history of PTSD is associated with higher rates of morbidity and mortality and increased the risk for suicidal behavior .
The association between PTSD and suicidal behavior was confirmed by the presence of other risk factors and high rates of comorbidity . | Posttraumatic stress disorder ( PTSD ) is frequently associated with suicidal ideation and suicide attempts .
Suicide is an important cause of death in veterans , and the risk for intentional death continues to be high many years after service .
The aim of the present study was to investigate whether there is a relationship between PTSD and suicidal behavior among veterans .
We also discussed the risk factors of suicide among war veterans with PTSD . | Background .There have been major reductions in the availability of inpatient psychiatric care in the United States in recent years . Objective .The objective of this study was to evaluate the clinical impact of cost-cutting changes in the delivery of inpatient psychiatric care . Design .This was a nonequivalent control group pre/post design . Subjects . Outcome data on 6,397 veterans treated between 1993 and 2000 at 35 specialized VA inpatient and residential programs for posttraumatic stress disorder ( PTSD ) were used to compare changes in effectiveness ( measured as patient improvement from admission to 4 months after discharge ) at programs that either shortened their average length of stay or converted from a hospital-based program to a low-cost residential rehabilitation program . For comparison , outcome data are also presented over the same years from both inpatient PTSD programs and residential PTSD programs that did not experience program change . Measures . Measures addressed baseline characteristics and 4-month postdischarge outcome measures of PTSD symptoms , substance abuse , violent behavior , and employment . Results .Analyses of covariance showed no significant change in outcomes at inpatient programs that either reduced their length of stay or did not change at all . However , effectiveness declined on some measures at inpatient programs that converted to residential treatment during this period but improved at residential treatment programs that had been established before this period of change . Conclusions .Although there was no deterioration in effectiveness related to reduced length of inpatient stay , programs that converted to a residential model showed decreased effectiveness OBJECTIVE To study the relation between posttraumatic stress disorder ( PTSD ) psychiatric comorbidity and suicidal ideation in a representative sample of Ohio Army National Guard soldiers . METHOD Using retrospective data collected on the telephone from a r and om sample of 2,616 National Guard soldiers who enrolled in a 10-year longitudinal study ( baseline data collected November 2008-November 2009 ) , we examined ( 1 ) the prevalence of other psychopathologies among those with DSM-IV-diagnosed PTSD compared to those without PTSD and ( 2 ) the association between PTSD comorbidity and suicidal ideation ( reporting thoughts of being better off dead or hurting themselves ) . All analyses were carried out using logistic regression . RESULTS Of guard members with PTSD in the last year , 61.7 % had at least 1 other psychopathology ; 20.2 % had at least 2 other co-occurring conditions . The most common co-occurring psychopathology was depression . While those with PTSD overall were 5.4 ( 95 % CI , 3.8 - 7.5 ) times more likely to report suicidality than those without PTSD , those who had at least 2 additional conditions along with PTSD were 7.5 ( 95 % CI , 3.0 - 18.3 ) times more likely to report suicidal ideation at some point in their lifetime than those with PTSD alone . CONCLUSIONS Soldiers with PTSD were at increased risk for suicidality , and , among those with PTSD , those with at least 2 additional conditions were at the highest risk of suicidal ideation . Future research should address the mechanisms that contribute to multimorbidity in this population and the appropriate treatment methods for this high-risk group Trauma risk management ( TRiM ) is an intensive posttraumatic stress disorder ( PTSD ) psychoeducational management strategy based on peer-group risk assessment developed by the UK Royal Navy ( RN ) . TRiM seeks to modify attitudes about PTSD , stress , and help-seeking and trains military personnel to identify at-risk individuals and refer them for early intervention . This quasiexperimental study found that TRiM training significantly improved attitudes about PTSD , stress , and help-seeking from TRiM-trained personnel . There was a nonsignificant effect on attitudes to seeking help from normal military support networks and on general health . Within both the military and civilian population s , stigma is a serious issue preventing help-seeking and reducing quality of life . The results suggest that TRiM is a promising antistigma program within organizational setting |
1,124 | 29,163,868 | The effect sizes lagged behind the effects observed in traumatized minors in general , and often were small or non-significant . | ABSTRACT Background : The United Nations reported that in 2016 over 65 million people worldwide have forcibly left home .
Over 50 % are children and adolescents ; a substantial number has been traumatized and displaced by war .
Objective : To provide an overview of the effectiveness of psychosocial interventions in this group we conducted a narrative review and a meta- analysis of intervention studies providing data on posttraumatic stress symptoms ( PTSS ) , depression , anxiety , grief , and general distress . | Background The North-Eastern part of Sri Lanka had already been affected by civil war when the 2004 Tsunami wave hit the region , leading to high rates of posttraumatic stress disorder ( PTSD ) in children . In the acute aftermath of the Tsunami we tested the efficacy of two pragmatic short-term interventions when applied by trained local counselors . Methods A r and omized treatment comparison was implemented in a refugee camp in a severely affected community . 31 children who presented with a preliminary diagnosis of PTSD were r and omly assigned either to six sessions Narrative Exposure Therapy for children ( KIDNET ) or six sessions of meditation-relaxation ( MED-RELAX ) . Outcome measures included severity of PTSD symptoms , level of functioning and physical health . Results In both treatment conditions , PTSD symptoms and impairment in functioning were significantly reduced at one month post-test and remained stable over time . At 6 months follow-up , recovery rates were 81 % for the children in the KIDNET group and 71 % for those in the MED-RELAX group . There was no significant difference between the two therapy groups in any outcome measure . Conclusion As recovery rates in the treatment groups exceeded the expected rates of natural recovery , the study provides preliminary evidence for the effectiveness of NET as well as meditation-relaxation techniques when carried out by trained local counselors for the treatment of PTSD in children in the direct aftermath of mass disasters . Trial registration Clinical Trials.gov Identifier : BACKGROUND There are no psychosocial interventions to address both educational needs and psychological distress among displaced children in post-conflict setting s. AIMS To assess the psychosocial status of displaced children enrolled in the Rapid-Ed intervention ; and to determine whether the Rapid-Ed intervention alleviated traumatic stress symptoms that interfere with learning among war-affected children in Sierra Leone . METHOD A r and omly selected sample of 315 children aged 8 - 18 years who were displaced by war were interviewed about their war experiences and reactions to the violence before and after participating in the 4-week Rapid-Ed intervention combining basic education with trauma healing activities . RESULTS High levels of intrusion , arousal and avoidance symptoms were reported at the pre-test interviews conducted 9 - 12 months after the war . Post-test findings showed statistically significant decreases in intrusion and arousal symptoms ( P<0.0001 ) , a slight increase in avoidance reactions ( P<0.0001 ) and greater optimism about the future . CONCLUSIONS The findings suggest potential for combining basic education with trauma healing activities for children in post-conflict setting s , but confirmatory studies using a control group are needed . Conducting research in post-conflict setting s presents unique challenges Cognitive theories point to reduction in dysfunctional posttraumatic cognitions ( PTCs ) as one mechanism involved in recovery from posttraumatic stress symptoms ( PTSS ) , yet research findings have shown individual differences in the recovery process . We tested the cognitive mediation hypothesis above in a previously published psychosocial group intervention among war-affected children . We also examined heterogeneity in children 's PTCs during the intervention . We used a cluster r and omized trial of Smith et al. 's ( 2002 ) teaching recovery techniques ( TRT ) intervention among 482 Palestinians 10 - 13 years of age ( n = 242 for intervention group , n = 240 for control group ) . Children reported PTSS , PTCs , and depressive symptoms at baseline , midpoint , postintervention , and at 6-month follow-up . Path analysis results showed that TRT was not effective in reducing dysfunctional PTCs , and the reductions did not mediate intervention effects on PTSS . Using latent class growth analysis , we chose the model with 3 differing trajectories in the intervention group : high , decreasing , moderate , downward trending , and severe , stable levels of PTCs . Higher PTSS and depressive symptoms at baseline were associated with membership in the severe , stable trajectory . The intervention did not produce the kind of beneficial cognitive change needed in the cognitive mediation conceptualization . Nevertheless , cognitive changes differed substantially across children during the intervention , and were associated with their preintervention mental health status . These findings call for more detailed examination of the process of cognitive mediation Effective evidence -based intervention for traumatic bereavement is one of the current major research issues in the field of Post Traumatic Stress Disorder ( PTSD ) in children and adolescents . The “ Writing for Recovery ” group intervention is a new treatment approach developed by the Children and War Foundation for traumatized and bereaved children and adolescents after disasters . The purpose of this project was an empirical examination of this intervention with 12- to 18-year-old war bereaved Afghani refugees . Eighty-eight war bereaved Afghani refugees were screened using the Traumatic Grief Inventory for Children ( TGIC ) . From those with the highest total score , 61 were r and omly assigned to either an experimental ( n = 29 ) or control group ( n = 32 ) . The experimental group received six sessions of group training on 3 consecutive days in their school . The difference of TGIC scores between the experimental group in pretest and posttest was significant ( p = 0.001 ) . Results of analysis of covariance also showed a significant effect of Writing for Recovery on the experimental group ( p < 0.001 ) . It is concluded that “ Writing for Recovery ” is an effective group intervention for bereaved children and adolescents after disasters Background : Preventative and treatment programs for people at risk of developing psychological problems after exposure to war trauma have mushroomed in the last decade . However , there is still much contention about evidence -based and culturally sensitive interventions for children . The aim of this study was to examine the efficacy of the Teaching Recovery Techniques in improving the emotional and behavioral outcomes of war-affected children resettled in Australia . Methods and Findings : A cluster r and omized controlled trial with pre-test , post-test , and 3-month follow-up design was employed . A total of 82 participants ( aged 10–17 years ) were r and omized by school into the 8-week intervention ( n = 45 ) or the waiting list ( WL ) control condition ( n = 37 ) . Study outcomes included symptoms of post-traumatic stress disorder , depression , internalizing and externalizing problems , as well as psychosocial functioning . A medium intervention effect was found for depression symptoms . Participants in the intervention condition experienced a greater symptom reduction than participants in the WL control condition , F(1 , 155 ) = 5.20 , p = 0.024 , partial η2 = 0.07 . This improvement was maintained at the 3-month follow-up , F(2 , 122 ) = 7.24 , p = 0.001 , partial η2 = 0.20 . Conclusions : These findings suggest the potential benefit of the school and group-based intervention on depression symptoms but not on other outcomes , when compared to a waiting list control group . Trial Registration : Australian New Zeal and Clinical Trials Registry ACTRN12611000 948998 CONTEXT Prior qualitative work with internally displaced persons in war-affected northern Ug and a showed significant mental health and psychosocial problems . OBJECTIVE To assess effect of locally feasible interventions on depression , anxiety , and conduct problem symptoms among adolescent survivors of war and displacement in northern Ug and a. DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial from May 2005 through December 2005 of 314 adolescents ( aged 14 - 17 years ) in 2 camps for internally displaced persons in northern Ug and a. INTERVENTIONS Locally developed screening tools assessed the effectiveness of interventions in reducing symptoms of depression and anxiety , ameliorating conduct problems , and improving function among those who met study criteria and were r and omly allocated ( 105 , psychotherapy-based intervention [ group interpersonal psychotherapy ] ; 105 , activity-based intervention [ creative play ] ; 104 , wait-control group [ individuals wait listed to receive treatment at study end ] ) . Intervention groups met weekly for 16 weeks . Participants and controls were reassessed at end of study . MAIN OUTCOME MEASURES Primary measure was a decrease in score ( denoting improvement ) on a depression symptom scale . Secondary measures were improvements in scores on anxiety , conduct problem symptoms , and function scales . Depression , anxiety , and conduct problems were assessed using the Acholi Psychosocial Assessment Instrument with a minimum score of 32 as the lower limit for clinical ly significant symptoms ( maximum scale score , 105 ) . RESULTS Difference in change in adjusted mean score for depression symptoms between group interpersonal psychotherapy and control groups was 9.79 points ( 95 % confidence interval [ CI ] , 1.66 - 17.93 ) . Girls receiving group interpersonal psychotherapy showed substantial and significant improvement in depression symptoms compared with controls ( 12.61 points ; 95 % CI , 2.09 - 23.14 ) . Improvement among boys was not statistically significant ( 5.72 points ; 95 % CI , -1.86 to 13.30 ) . Creative play showed no effect on depression severity ( -2.51 points ; 95 % CI , -11.42 to 6.39 ) . There were no statistically different improvements in anxiety in either intervention group . Neither intervention improved conduct problem or function scores . CONCLUSIONS Both interventions were locally feasible . Group interpersonal psychotherapy was effective for depression symptoms among adolescent girls affected by war and displacement . Other interventions should be investigated to assist adolescent boys in this population who have symptoms of depression . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00280319 PURPOSE As we build the evidence base of interventions for depression among war-affected youth , it is critical to underst and factors moderating treatment outcomes . The current study investigated how gender and history of abduction by Lord 's Resistance Army rebels moderated treatment outcomes for war-affected youth . METHODS The study -a three-armed , r and omized , controlled trial-was conducted with internally displaced war-affected adolescents in northern Ug and a. Participants with significant depression symptoms ( N = 304 ; 57 % female ; 14 - 17 years of age ) were r and omly assigned to an interpersonal psychotherapy group ( IPT-G ) , a creative play/recreation group , or a wait-list control condition . Secondary analyses were conducted on data from this r and omized controlled trial . RESULTS A history of abduction by Lord 's Resistance Army rebels was reported by 42 % of the sample . Gender and abduction history interacted to moderate the effectiveness of IPT-G for the treatment of depression . In the IPT-G intervention arm , treatment effectiveness was greatest among female subjects without an abduction history , with effect size = 1.06 . IPT-G was effective for the treatment of depression for both male and female subjects with a history of abduction ( effect size = .92 and .50 , respectively ) . Male subjects with no abduction history in IPT-G showed no significant improvement compared with those in the control conditions . CONCLUSIONS Abduction history and gender are potentially important moderators of treatment effects , suggesting that these factors need to be considered when providing interventions for war-affected youth . IPT-G may be an effective intervention for female subjects without an abduction history , as well as for both male and female former child soldiers , but less so for male subjects without an abduction history CONTEXT Little is known about the efficacy of mental health interventions for children exposed to armed conflicts in low- and middle-income setting s. Childhood mental health problems are difficult to address in situations of ongoing poverty and political instability . OBJECTIVE To assess the efficacy of a school-based intervention design ed for conflict-exposed children , implemented in a low-income setting . DESIGN , SETTING , AND PARTICIPANTS A cluster r and omized trial involving 495 children ( 81.4 % inclusion rate ) who were a mean ( SD ) age of 9.9 ( 1.3 ) years , were attending r and omly selected schools in political violence-affected communities in Poso , Indonesia , and were screened for exposure ( > or = 1 events ) , posttraumatic stress disorder , and anxiety symptoms compared with a wait-listed control group . Nonblinded assessment took place before , 1 week after , and 6 months after treatment between March and December 2006 . INTERVENTION Fifteen sessions , over 5 weeks , of a manualized , school-based group intervention , including trauma-processing activities , cooperative play , and creative-expressive elements , implemented by locally trained paraprofessionals . MAIN OUTCOME MEASURES We assessed psychiatric symptoms using the Child Posttraumatic Stress Scale , Depression Self-Rating Scale , the Self-Report for Anxiety Related Disorders 5-item version , and the Children 's Hope Scale , and assessed function impairment as treatment outcomes using st and ardized symptom checklists and locally developed rating scales . RESULTS Correcting for clustering of participants within schools , we found significantly more improvement in posttraumatic stress disorder symptoms ( mean change difference , 2.78 ; 95 % confidence interval [ CI ] , 1.02 to 4.53 ) and maintained hope ( mean change difference , -2.21 ; 95 % CI , -3.52 to -0.91 ) in the treatment group than in the wait-listed group . Changes in traumatic idioms ( stress-related physical symptoms ) ( mean change difference , 0.50 ; 95 % CI , -0.12 to 1.11 ) , depressive symptoms ( mean change difference , 0.70 ; 95 % CI , -0.08 to 1.49 ) , anxiety ( mean change difference , 0.12 ; 95 % CI , -0.31 to 0.56 ) , and functioning ( mean change difference , 0.52 ; 95 % CI , -0.43 to 1.46 ) were not different between the treatment and wait-listed groups . CONCLUSIONS In this study of children in violence-affected communities , a school-based intervention reduced posttraumatic stress symptoms and helped maintain hope , but did not reduce traumatic-stress related symptoms , depressive symptoms , anxiety symptoms , or functional impairment . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N25172408 The present study was design ed to evaluate the effects on children ( age : M = 5.5 years ) in war-torn Bosnia and Herzegovina of a psychosocial intervention program consisting of weekly group meetings for mothers for 5 months . An additional aim was to investigate the children 's psychosocial functioning and the mental health of their mothers . Internally displaced mother-child dyads were r and omly assigned to an intervention group receiving psychosocial support and basic medical care ( n = 42 ) or to a control group receiving medical care only ( n = 45 ) . Participants took part in interviews and tests to provide information about war exposure , mental health , psychosocial functioning , intellectual abilities , and physical health . Results showed that although all participants were exposed to severe trauma , their manifestations of distress varied considerably . The intervention program had a positive effect on mothers ' mental health , children 's weight gain , and several measures of children 's psychosocial functioning and mental health , whereas there was no difference between the two groups on other measures . The findings have implication s for policy The study examines , first , the effectiveness of a psychosocial intervention based on Teaching Recovery Techniques ( TRT ) to increase resiliency among Palestinian children , exposed to a major trauma of war . Second , it analyses the role of family factors ( maternal attachment and family atmosphere ) as moderating the intervention impacts on resilience . School classes in Gaza were r and omized into intervention ( N=242 ) and control ( N=240 ) groups . The percentage of girls ( 49.4 % ) and boys ( 50.6 % ) were equal , and the child age was 10 - 13 years in both groups . Children reported positive indicators of their mental health ( prosocial behaviour and psychosocial well-being ) at baseline ( T1 ) , post-intervention ( T2 ) and at a six-month follow-up ( T3 ) . At T1 they accounted their exposure to war trauma . Mothers reported about their willingness to serve as an attachment figure , and the child reported about the family atmosphere . Resilience was conceptualized as a presence of positive indications of mental health despite trauma exposure . Against our hypothesis , the intervention did not increase the level of resilience statistically significantly , nor was the effect of the intervention moderated by maternal attachment responses or family atmosphere The aim of this study was to evaluate the short-term impact of a group crisis intervention for children aged 9–15 years from five refugee camps in the Gaza Strip during ongoing war conflict . Children were selected if they reported moderate to severe posttraumatic stress reactions , and were allocated to group intervention ( N=47 ) encouraging expression of experiences and emotions through storytelling , drawing , free play and role-play ; education about symptoms ( N=22 ) ; or no intervention ( N=42 ) . Children completed the CPTSD-RI and the CDI pre- and post-intervention . No significant impact of the group intervention was established on children ’s posttraumatic or depressive symptoms . Possible explanations of the findings are discussed , including the continuing exposure to trauma and the non-active nature of the intervention We aim ed to examine outcomes , moderators and mediators of a preventive school-based mental health intervention implemented by paraprofessionals in a war-affected setting in northern Sri Lanka . A cluster r and omized trial was employed . Subsequent to screening 1,370 children in r and omly selected schools , 399 children were assigned to an intervention ( n=199 ) or waitlist control condition ( n=200 ) . The intervention consisted of 15 manualized sessions over 5 weeks of cognitive behavioral techniques and creative expressive elements . Assessment s took place before , 1 week after , and 3 months after the intervention . Primary outcomes included post-traumatic stress disorder ( PTSD ) , depressive , and anxiety symptoms . No main effects on primary outcomes were identified . A main effect in favor of intervention for conduct problems was observed . This effect was stronger for younger children . Furthermore , we found intervention benefits for specific subgroups . Stronger effects were found for boys with regard to PTSD and anxiety symptoms , and for younger children on pro-social behavior . Moreover , we found stronger intervention effects on PTSD , anxiety , and function impairment for children experiencing lower levels of current war-related stressors . Girls in the intervention condition showed smaller reductions on PTSD symptoms than waitlisted girls . We conclude that preventive school-based psychosocial interventions in volatile areas characterized by ongoing war-related stressors may effectively improve indicators of psychological wellbeing and posttraumatic stress-related symptoms in some children . However , they may undermine natural recovery for others . Further research is necessary to examine how gender , age and current war-related experiences contribute to differential intervention effects PURPOSE Mental disorders are among the largest contributors to the global burden of disease . Since the cessation of the Sierra Leonean civil war in 2002 , there have been few mental health re sources available for war-affected youth . Co-occurring psychological problems are commonly reported by youth in the post-conflict setting , suggesting a need for evidence -based interventions that cater to comorbid psychological difficulties . This feasibility study outlines the implementation and evaluation of a mixed- methods approach for developing and piloting a culturally grounded group mental health treatment-the Youth Readiness Intervention (YRI)-for war-affected Sierra Leonean youth . METHODS Participating youth ( N = 32 ; 50 % female ; ages , 15 - 24 years ) were allocated to one of four gender- and age-stratified groups , facilitated by gender-matched Sierra Leonean interventionists . The intervention comprised adapted cognitive behavioral therapy techniques to address issues pertinent to war-affected youth . Analyses comprised assessment s of reliable symptom change , mental health , functional adaptation , and interventionist fidelity outcomes . RESULTS The YRI was found to be acceptable , feasible and associated with reliable changes in internalizing and externalizing symptoms and improvements in functional impairments and emotion regulation ( mean effect size , d = .64 ) . CONCLUSIONS Youth struggling with the mental health consequences of past trauma due to war merit special attention . The YRI presents a feasible and acceptable intervention for use in this low re source setting . A r and omized controlled trial is planned to further test intervention effectiveness and scalability The authors examined the effectiveness of narrative exposure therapy for children ( KIDNET ) in treating posttraumatic stress disorder ( PTSD ) in refugee children living in exile . Twenty-six children traumatized by organized violence were r and omly assigned to KIDNET or to a waiting list . Significant treatment by time interactions on all PTSD-relevant variables indicated that the KIDNET group , but not the controls , showed a clinical ly significant improvement in symptoms and functioning . Success of the KIDNET group remained stable at 12-month follow-up . This study confirms previous findings that , if left untreated , PTSD in children may persist for an extended period . However , it also shows that it is possible to effectively treat chronic PTSD and restore functioning in traumatized refugee children in only 8 treatment sessions Background Armed conflicts are associated with a wide range of impacts on the mental health of children and adolescents . We evaluated the effectiveness of a school-based intervention aim ed at reducing symptoms of posttraumatic stress disorder , depression , and anxiety ( treatment aim ) ; and improving a sense of hope and functioning ( preventive aim ) . Methods We conducted a cluster r and omized trial with 329 children in war-affected Burundi ( aged 8 to 17 ( mean 12.29 years , st and ard deviation 1.61 ) ; 48 % girls ) . One group of children ( n = 153 ) participated in a 15-session school-based intervention implemented by para-professionals , and the remaining 176 children formed a waitlist control condition . Outcomes were measured before , one week after , and three months after the intervention . Results No main effects of the intervention were identified . However , longitudinal growth curve analyses showed six favorable and two unfavorable differences in trajectories between study conditions in interaction with several moderators . Children in the intervention condition living in larger households showed decreases on depressive symptoms and function impairment , and those living with both parents showed decreases on posttraumatic stress disorder and depressive symptoms . The groups of children in the waitlist condition showed increases in depressive symptoms . In addition , younger children and those with low levels of exposure to traumatic events in the intervention condition showed improvements on hope . Children in the waitlist condition who lived on their original or newly bought l and showed improvements in hope and function impairment , whereas children in the intervention condition showed deterioration on these outcomes . Conclusions Given inconsistent effects across studies , findings do not support this school-based intervention as a treatment for posttraumatic stress disorder and depressive symptoms in conflict-affected children . The intervention appears to have more consistent preventive benefits , but these effects are contingent upon individual ( for example , age , gender ) and context ual ( for example , family functioning , state of conflict , displacement ) variables . Results suggest the potential benefit of school-based preventive interventions particularly in post-conflict setting s . Trial registration The study was registered as IS RCT |
1,125 | 21,415,247 | CT colonography is highly sensitive for colorectal cancer , especially when both cathartic and tagging agents are combined in the bowel preparation .
Given the relatively low prevalence of colorectal cancer , primary CT colonography may be more suitable than OC for initial investigation of suspected colorectal cancer , assuming reasonable specificity . | PURPOSE To perform a systematic review and meta- analysis of published studies assessing the sensitivity of both computed tomographic ( CT ) colonography and optical colonoscopy ( OC ) for colorectal cancer detection . | Context How often does colonoscopy miss adenomas ? Contribution During a multicenter screening trial , experienced colonoscopists performed same-day optical ( OC ) and virtual colonoscopy ( VC ) on 1233 asymptomatic adults . Optical colonoscopy performed without knowledge of the VC findings missed 55 of 511 polyps ; 21 of these polyps were adenomas measuring 6 mm or greater . Adenomas missed by OC were usually on the proximal side of a fold or near the anal verge . Virtual colonoscopy missed 14 % of the adenomas that measured 6 mm or greater that were de-tected by OC . Implication s Neither OC nor VC is a perfect test : Each misses 10 % to 14 % of adenomas that measure 6 mm or greater . The Editors Optical colonoscopy ( OC ) is widely accepted as the gold st and ard for detecting colorectal neoplasia ( 1 , 2 ) . However , even in the most experienced h and s , this skilled examination is underst and ably not infallible . Retrospective analysis has suggested that the OC miss rate for adenomas 10 mm or greater is approximately 10 % ( 3 ) . More recently , prospect i ve back-to-back or t and em colonoscopy studies have reported miss rates for 10-mm adenomas ranging from 0 % to 6 % ( 4 , 5 ) . However , in addition to evaluating relatively small population s of patients with a high prevalence of polyps , a notable weakness common to these studies was that they used OC as its own reference st and ard . In a large , prospect i ve , multicenter trial that was primarily intended to evaluate the performance of virtual colonoscopy ( VC ) in asymptomatic adults ( 6 ) , we also had a unique opportunity to evaluate the adenoma miss rate on OC by segmentally unblinding the results from same-day VC . By using a reference st and ard other than OC itself for comparison , we could uncover lesions that may be systematic ally missed on repeated colonoscopies . These data not only provide novel insight into OC miss rates but also indicate the relative blind spots where more attention could be focused . Methods Study Design The institutional review boards at all 3 participating medical centers approved the study protocol for same-day VC and OC , and all patients provided written informed consent . We recruited asymptomatic adults who were referred for colorectal cancer screening . Exclusion criteria were a positive stool guiaic test result or iron deficiency anemia within the past 6 months ; rectal bleeding , hematochezia , or unintentional weight loss of more than 10 pounds within the past 12 months ; OC within the past 10 years or barium enema within the past 5 years ; personal history of adenomatous polyps , colorectal cancer , or inflammatory bowel disease ; and family history of familial adenomatous polyposis or nonpolyposis cancer syndromes . Between May 2002 and June 2003 , 1253 asymptomatic adults enrolled in the study . Eight patients were excluded because of failure to reach the cecum at OC , 6 patients were excluded because of inadequate colonic preparation , and another 6 patients were excluded because of computed tomography ( CT ) system failure . The final study group comprised 1233 asymptomatic adults ( 728 men and 505 women ; mean age , 57.8 years ) who successfully completed same-day VC and OC . Study participants underwent colonic preparation with oral intake of 90 mL of phospho-soda and 10 mg of bisacodyl . To opacify residual colonic fluid and stool for VC examination , patients also consumed dilute oral contrast as previously described ( 7 ) . Our CT protocol and VC technique have also been detailed previously ( 6 ) . To briefly summarize , we obtained supine and prone CT acquisitions on multidetector scanners after patient-controlled rectal insufflation of room air . One of 6 trained radiologists interpreted VC studies by using a commercially available CT colonography system ( Viatronix V3D-Colon , version 1.2 , Viatronix , Inc. , Stony Brook , New York ) . We used the 3-dimensional endoluminal fly-through view primarily for detecting polyps and 2-dimensional images for confirmation and problem solving . We measured polyps on the 3-dimensional view and recorded them by segment ( cecum , ascending colon , hepatic flexure , transverse colon , splenic flexure , descending colon , sigmoid colon , or rectum ) . We defined the proximal colon as including the cecum to the splenic flexure . We prospect ively rated diagnostic confidence for each detected lesion on a 3-point scale ( most certain , intermediate , and least certain ) . One of 17 experienced colonoscopists performed OC immediately after VC interpretation by using st and ard commercial video colonoscopes ( Olympus , Inc. , Melville , New York ) . The colonoscope was advanced to the cecum and then sequentially withdrawn into more distal segments for polyp detection . The colonoscopist measured polyps by using a calibrated linear probe , which is more accurate than either visual or biopsy forceps estimation ( 8) . Our polyp-matching algorithm requires VC and OC agreement according to size ( within a 50 % margin of error ) and location ( within the same or adjacent segment ) . After the colonoscopist evaluated a given segment , a study nurse unblinded the VC results for the previous segment . For any suspected polyp seen on VC that measured 5 mm or greater but was not seen on the initial blinded OC , the colonoscopist closely reexamined that segment and could review the VC images for guidance . We sent all retrieved polyps for histologic examination . For all cases in which a colorectal neoplasm measuring 6 mm or greater was found on second-look OC , we retrospectively review ed both the VC and OC images . We recorded polyp characteristics , such as size , morphologic characteristic ( sessile , pedunculated , or flat ) , and location on VC . If the polyp was situated on a colonic fold on VC , we further subcategorized it as being located on the back ( proximal ) side , front ( distal ) side , or edge of the fold . We analyzed both supine and prone VC sets for all cases . The primary reason that diminutive polyps measuring 5 mm at VC were included for potential unblinding at OC was that , given the relative error in polyp measurement , such polyps found on second-look OC might , in fact , measure 6 mm or greater . This allows for more accurate assessment of the OC miss rate at the 6-mm threshold . We did not include unblinded polyps that measured 5 mm or less on both VC and OC examinations in the final analysis . All study participants completed a detailed question naire on their personal and family medical history . For the purpose s of this study , particular attention was given to the question about previous abdominal or pelvic surgery , since adhesions could conceivably result in a more difficult colonoscopic examination . Statistical Analysis Prospect i ve OC performance was compared against the enhanced reference st and ard of second-look OC after segmental unblinding of VC results . We estimated exact binomial 95 % CIs for OC miss rates . We used the chi-square test to compare the frequency of previous abdominal surgery among patients with and without polyps missed at OC and also to compare the OC miss rates among the 3 medical centers . We calculated the 95 % CIs by using Stata software , version 7.0 for Windows ( Stata Corp. , College Station , Texas ) , and performed the chi-square tests by using SAS software , version 8.0 for Windows ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The funding source had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results The performance characteristics of VC from this prospect i ve , multicenter screening trial , using OC as the reference st and ard , have been previously reported ( 6 ) . Our technique of segmental unblinding also allows for a separate assessment of OC by using the blinded VC results for comparison , which is the focus of this study . We identified 1310 polyps at OC in the 1233 asymptomatic adults ; 511 ( 39.0 % ) of these polyps measured 5 mm or greater ( Figure 1).Of these 511 polyps , 55 ( 10.8 % ) were found only on second-look OC after segmental unblinding of VC results . Twenty-four ( 43.6 % ) of the 55 unblinded lesions were nonadenomatous , including 16 hyperplastic polyps . Of the 31 missed neoplasms , 10 adenomas that measured only 5 mm were excluded from further analysis because of their diminutive size ( 9 ) . Including unblinded lesions , 554 adenomas were detected on OC in this screening sample ; 210 of these measured 6 mm or greater and 51 measured 10 mm or greater . Figure 1 . Polyp flowchart . In 20 patients ( 17 men and 3 women ; mean age , 58.2 years ) , 21 adenomas measuring 6 mm or greater ( range , 6 mm to 17 mm ; mean , 8.1 mm ) were found on OC only after the VC results were unblinded , which represent the lesions of primary interest for this study ( Table ) . The corresponding adenoma miss rate on prospect i ve OC examination was 10.0 % ( 95 % CI , 6.3 % to 14.9 % ) ( 21 of 210 adenomas ) at a 6-mm cutoff . The 20 patients with missed adenomas that measured 6 mm or greater represented only 1.6 % of the study sample ( 20 of 1233 patients ) but 11.9 % of patients with adenomas 6 mm or greater ( 20 of 168 patients ) . At 8-mm and 10-mm thresholds , the OC adenoma miss rates by polyp were 10.5 % ( CI , 5.2 % to 18.5 % ) ( 10 of 95 adenomas ) and 11.8 % ( CI , 4.4 % to 23.9 % ) ( 6 of 51 adenomas ) , respectively . The 10 patients with missed adenomas 8 mm or greater represented 12.2 % ( 10 of 82 patients ) of all patients with neoplasms of this size or greater ; the 6 patients with missed adenomas 8 mm or greater represented 12.5 % of all patients with neoplasms 10 mm or greater . Table . Characteristics of Neoplasms Missed at Prospect i ve Colonoscopic Evaluation Seventeen ( 81.0 % ) of the 21 unblinded neoplasms 6 mm or greater were tubular adenomas , 3 ( 14.3 % ) were tubulovillous adenomas , and 1 ( 4.8 % ) was an adenocarcinoma . Seven ( 33.3 % ) of the 21 unblinded polyps were classified as advanced lesions ( that is , size 10 mm or high- grade dysplasia , prominent villous component , or focus of malignancy ) . There were 15 sessile lesions , 4 pedunculated lesions , and 2 flat BACKGROUND : Colorectal cancer is the second leading cause of death from cancer in Western countries . Early detection by colorectal cancer screening can effectively cut its mortality rate . CT colonography represents a promising , minimally invasive alternative to conventional methods of colorectal carcinoma screening . AIMS : The purpose of this prospect i ve single institutional study was to compare the abilities of routine clinical CT colonography and conventional colonoscopy to detect colorectal neoplasms using second-look colonoscopy to clarify discrepant results . PATIENTS AND METHODS : CT colonography was performed in 100 symptomatic patients using contrast enhanced multidetector CT followed by conventional colonoscopy on the same day . If results were discrepant , a second-look colonoscopy was performed after unblinding . CT colonographic findings were compared with those of conventional colonoscopy . RESULTS : Conventional colonoscopy found 122 colorectal neoplasms in 49 patients . The overall sensitivity of CT colonography at detecting patients with at least one polyp 6 mm or larger was 76 % and its specificity was 88 % . Its by-patient sensitivity for polyps 10 mm or larger was 95 % and its specificity was 98 % . By-polyp sensitivities were 71 % for polyps 10 mm or larger , and 61 % for polyps 6 mm or larger . A second-look colonoscopy was performed in 19 patients and two initial false-positive findings of CT colonography were reclassified as true-positive . For conventional colonoscopy , this produced a by-polyp sensitivity of 94 % for detection of lesions 6 mm and larger . CONCLUSIONS : CT colonography had both a high by-patient sensitivity and specificity for detection of clinical ly important colorectal neoplasms 10 mm or larger . This suggests that CT colonography has the potential to become a valuable clinical screening method for colorectal neoplasms CONTEXT Conventional colonoscopy is the best available method for detection of colorectal cancer ; however , it is invasive and not without risk . Computed tomographic colonography ( CTC ) , also known as virtual colonoscopy , has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers . OBJECTIVE To assess the accuracy of CTC in a large number of participants across multiple centers . DESIGN , SETTING , AND PARTICIPANTS A nonr and omized , evaluator-blinded , noninferiority study design of 615 participants aged 50 years or older who were referred for routine , clinical ly indicated colonoscopy in 9 major hospital centers between April 17 , 2000 , and October 3 , 2001 . The CTC was performed by using multislice scanners immediately before st and ard colonoscopy ; findings at colonoscopy were reported before and after segmental unblinding to the CTC results . MAIN OUTCOME MEASURES The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm . Secondary outcomes included detection of all lesions , detection of advanced lesions , possible technical confounders , participant preferences , and evidence for increasing accuracy with experience . RESULTS A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures ; 104 participants had lesions sized at least 6 mm . The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0 % ( 95 % confidence interval [ CI ] , 29.6%-48.4 % ) and for lesions sized at least 10 mm , it was 55.0 % ( 95 % CI , 39.9%-70.0 % ) . These results were significantly lower than those for conventional colonoscopy , with sensitivities of 99.0 % ( 95 % CI , 97.1%->99.9 % ) and 100 % , respectively . A total of 496 participants were without any lesion sized at least 6 mm . The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5 % ( 95 % CI , 87.9%-93.1 % ) and 100 % , respectively , and without lesions sized at least 10 mm , 96.0 % ( 95 % CI , 94.3%-97.6 % ) and 100 % , respectively . Computed tomographic colonography missed 2 of 8 cancers . The accuracy of CTC varied considerably between centers and did not improve as the study progressed . Participants expressed no clear preference for either technique . CONCLUSIONS Computed tomographic colonography by these methods is not yet ready for widespread clinical application . Techniques and training need to be improved BACKGROUND AND AIMS We prospect ively compared the performance of low-dose multidetector computed tomographic colonography ( CTC ) without cathartic preparation with that of colonoscopy for the detection of colorectal polyps . METHODS A total of 203 patients underwent low-dose CTC without cathartic preparation followed by colonoscopy . Before CTC , fecal tagging was achieved by adding diatrizoate meglumine and diatrizoate sodium to regular meals . No subtraction of tagged feces was performed . Colonoscopy was performed 3 - 7 days after CTC . Three readers interpreted the CTC examinations separately and independently using a primary 2-dimensional approach using multiplanar reconstructions and 3-dimensional images for further characterization . Colonoscopy with segmental unblinding was used as reference st and ard . The sensitivity of CTC was calculated both on a per-polyp and a per-patient basis . For the latter , specificity , positive predictive values , and negative predictive values were also calculated . RESULTS CTC had an average sensitivity of 95.5 % ( 95 % confidence interval [ CI ] , 92.1%-99 % ) for the identification of colorectal polyps > or = 8 mm . With regard to per-patient analysis , CTC yielded an average sensitivity of 89.9 % ( 95 % CI , 86%-93.7 % ) , an average specificity of 92.2 % ( 95 % CI , 89.5%-94.9 % ) , an average positive predictive value of 88 % ( 95 % CI , 83.3%-91.5 % ) , and an average negative predictive value of 93.5 % ( 95 % CI , 90.9%-96 % ) . Interobserver agreement was high on a per-polyp basis ( kappa statistic range , .61-.74 ) and high to excellent on a per-patient basis ( kappa statistic range , .79-.91 ) . CONCLUSIONS Low-dose multidetector CTC without cathartic preparation compares favorably with colonoscopy for the detection of colorectal polyps The purpose was to evaluate low-dose CT colonography without cathartic cleansing in terms of image quality , polyp visualization and patient acceptance . Sixty-one patients scheduled for colonoscopy started a low-fiber diet , lactulose and amidotrizoic-acid for fecal tagging 2 days prior to the CT scan ( st and ard dose , 5.8–8.2 mSv ) . The original raw data of 51 patients were modified and reconstructed at simulated 2.3 and 0.7 mSv levels . Two observers evaluated the st and ard dose scan regarding image quality and polyps . A third evaluated the presence of polyps at all three mSv levels in a blinded prospect i ve way . All observers were blinded to the reference st and ard : colonoscopy . At three times patients were given question naires relating to their experiences and preference . Image quality was sufficient in all patients , but significantly lower in the cecum , sigmoid and rectum . The two observers correctly identified respectively 10/15 ( 67 % ) and 9/15 ( 60 % ) polyps ≥10 mm , with 5 and 8 false-positive lesions ( st and ard dose scan ) . Dose reduction down to 0.7 mSv was not associated with significant changes in diagnostic value ( polyps ≥10 mm ) . Eighty percent of patients preferred CT colonography and 13 % preferred colonoscopy ( P<0.001 ) . CT colonography without cleansing is preferred to colonoscopy and shows sufficient image quality and moderate sensitivity , without impaired diagnostic value at dose-levels as low as 0.7 mSv AIM Patients referred under the Department of Health 2-week wait initiative with symptoms of colorectal cancer frequently undergo whole-colon examination . We investigated the use of computed tomography ( CT ) colonography as an alternative to colonoscopy in this scenario . MATERIAL S AND METHODS Fifty-four consecutive patients , referred via the 2-week wait initiative and scheduled for colonoscopy , consented to undergo multidetector CT colonography immediately before endoscopy . The site and morphology of any polyp or cancer detected by CT was noted and comparison made with subsequent colonoscopy . RESULTS Colonoscopy detected polyps or cancer in 29 patients ( 53.7 % ) . CT colonography prospect ively detected 18 of 41 ( 44 % ) polyps of 1 - 5 mm , three of four ( 75 % ) polyps of 6 - 9 mm , four of four ( 100 % ) polyps 10 mm or larger , and five of six ( 83 % ) cancers . The missed cancer occurred early in the series and was a perceptive error . The overall sensitivity , specificity , positive predictive value and negative predictive value of CT colonography for cancer and polyps 10 mm or greater on a per patient basis were 90 , 100 , 100 and 98 % , respectively . CT detected one renal cancer and one colonic cancer , initially missed due to incomplete colonoscopy . CONCLUSION CT colonography is a robust technique for investigation of symptomatic patients . The learning curve must be overcome for optimal performance BACKGROUND The identification and removal of adenomatous polyps and post-polypectomy surveillance are considered to be important for the control of colorectal cancer . In current practice , the intervals between colonoscopies after polypectomy are variable , often a year long , and not based on data from r and omized clinical trials . We sought to determine whether follow-up colonoscopy at three years would detect important colonic lesions as well as follow-up colonoscopy at both one and three years . METHODS Patients were eligible if they had one or more adenomas , no previous polypectomy , and a complete colonoscopy and all their polyps had been removed . They were r and omly assigned to have follow-up colonoscopy at one and three years or at three years only . The two study end points were the detection of any adenoma , and the detection of adenomas with advanced pathological features ( defined as those > 1 cm in diameter and those with high- grade dysplasia or invasive cancer ) . RESULTS Of 2632 eligible patients , 1418 were r and omly assigned to the two follow-up groups , 699 to the two-examination group and 719 to the one-examination group . The percentage of patients with adenomas in the group examined at one and three years was 41.7 percent , as compared with 32.0 percent in the group examined at three years ( P = 0.006 ) . The percentage of patients with adenomas with advanced pathological features was the same in both groups ( 3.3 percent ) . CONCLUSIONS Colonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years . An interval of at least three years is recommended before follow-up colonoscopy after both one and three years . An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps . Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening Objective . Early detection of precancerous or malignant lesions may be decisive for prognosis of patients with colorectal cancer . In this prospect i ve feasibility study , multi-detector spiral computed tomography ( CT ) colonography was compared with conventional colonoscopy for the detection of colorectal polyps . Material and methods . Seventy-eight patients underwent CT colonography ( st and ard colonoscopy preparation , distension with room air , prone and supine position ) immediately before colonoscopy . Sixty-five ( 83 % ) were asymptomatic screening subjects , while the rest had symptoms suggestive of colorectal disease . Presence , location , and size of lesions were prospect ively assessed . Sensitivity , specificity , and positive and negative predictive values of CT colonography were calculated using conventional colonoscopy as the reference st and ard . Results . Conventional colonoscopy was normal in 52 patients . In 26 patients a total of 49 polyps and 3 carcinomas were identified . All three carcinomas and 39 polyps ( 80 % ) were identified by CT colonography . Seven of 7 polyps ≥10 mm ( 100 % ) , 13 of 16 polyps of 6 to 9 mm ( 81 % ) , and 19 of 26 polyps ≤5 mm ( 73 % ) in diameter were identified . Fourteen false-positive findings ( 10 of which were ≤5 mm in diameter ) were related to 8 patients ( specificity at the patient level was 86 % ) . In 10 patients , a total of 10 polyps were missed by CT colonography , 7 of which were ≤5 mm in diameter . Conclusions . In this feasibility study , multi-detector spiral CT colonography allows accurate detection of polyps>5 mm in diameter , but at the expense of low specificity in the small size range To establish the optimum barium-based reduced-laxative tagging regimen prior to CT colonography ( CTC ) . Ninety-five subjects underwent reduced-laxative ( 13 g senna/18 g magnesium citrate ) CTC prior to same-day colonoscopy and were r and omised to one of four tagging regimens using 20 ml 40%w/v barium sulphate : regimen A : four doses , B : three doses , C : three doses plus 220 ml 2.1 % barium sulphate , or D : three doses plus 15 ml diatriazoate megluamine . Patient experience was assessed immediately after CTC and 1 week later . Two radiologists grade d residual stool ( 1 : none/scattered to 4 : > 50 % circumference ) and tagging efficacy for stool ( 1 : untagged to 5 : 100 % tagged ) and fluid ( 1 : untagged , 2 : layered , 3 : tagged ) , noting the HU of tagged fluid . Preparation was good ( 76–94 % segments grade d 1 ) , although best for regimen D ( P = 0.02 ) . Across all regimens , stool tagging quality was high ( mean 3.7–4.5 ) and not significantly different among regimens . The HU of layered tagged fluid was higher for regimens C/D than A/B ( P = 0.002 ) . Detection of cancer ( n = 2 ) , polyps ≥6 mm ( n = 21 ) , and ≤5 mm ( n = 72 ) was 100 , 81 and 32 % respectively , with only four false positives ≥6 mm . Reduced preparation was tolerated better than full endoscopic preparation by 61 % . Reduced-laxative CTC with three doses of 20 ml 40 % barium sulphate is as effective as more complex regimens , retaining adequate diagnostic accuracy BACKGROUND Colorectal cancer is the third most common cancer worldwide and has a high mortality rate . We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality . METHODS This r and omised controlled trial was undertaken in 14 UK centres . 170 432 eligible men and women , who had indicated on a previous question naire that they would accept an invitation for screening , were r and omly allocated to the intervention group ( offered flexible sigmoidoscopy screening ) or the control group ( not contacted ) . R and omisation by sequential number generation was done central ly in blocks of 12 , with stratification by trial centre , general practice , and household type . The primary outcomes were the incidence of colorectal cancer , including prevalent cases detected at screening , and mortality from colorectal cancer . Analyses were intention to treat and per protocol . The trial is registered , number IS RCT N28352761 . FINDINGS 113 195 people were assigned to the control group and 57 237 to the intervention group , of whom 112 939 and 57 099 , respectively , were included in the final analyses . 40 674 ( 71 % ) people underwent flexible sigmoidoscopy . During screening and median follow-up of 11.2 years ( IQR 10.7 - 11.9 ) , 2524 participants were diagnosed with colorectal cancer ( 1818 in control group vs 706 in intervention group ) and 20 543 died ( 13 768 vs 6775 ; 727 certified from colorectal cancer [ 538 vs 189 ] ) . In intention-to-treat analyses , colorectal cancer incidence in the intervention group was reduced by 23 % ( hazard ratio 0.77 , 95 % CI 0.70 - 0.84 ) and mortality by 31 % ( 0.69 , 0.59 - 0.82 ) . In per- protocol analyses , adjusting for self- selection bias in the intervention group , incidence of colorectal cancer in people attending screening was reduced by 33 % ( 0.67 , 0.60 - 0.76 ) and mortality by 43 % ( 0.57 , 0.45 - 0.72 ) . Incidence of distal colorectal cancer ( rectum and sigmoid colon ) was reduced by 50 % ( 0.50 , 0.42 - 0.59 ; secondary outcome ) . The numbers needed to be screened to prevent one colorectal cancer diagnosis or death , by the end of the study period , were 191 ( 95 % CI 145 - 277 ) and 489 ( 343 - 852 ) , respectively . INTERPRETATION Flexible sigmoidoscopy is a safe and practical test and , when offered only once between ages 55 and 64 years , confers a substantial and longlasting benefit . FUNDING Medical Research Council , National Health Service R&D , Cancer Research UK , KeyMed BACKGROUND & AIMS The miss rate of colonoscopy for neoplasms is poorly understood . The aim of this study was to determine the miss rate of colonoscopy by same day back-to-back colonoscopy . METHODS Two consecutive same day colonoscopies were performed in 183 patients . The patients were r and omized to undergo the second colonoscopy by the same or a different endoscopist and in the same or different position . RESULTS The overall miss rate for adenomas was 24 % , 27 % for adenomas < or = 5 mm , 13 % for adenomas 6 - 9 mm , and 6 % for adenomas > or = 1 cm . Patients with two or more adenomas at the first examination were more likely than patients with no or one adenoma detected at the first examination to have one or more adenomas at the second examination ( odds ratio , 3.3 ; 95 % confidence interval , 1.69 - 6.46 ) . Right colon adenomas were missed more often ( 27 % ) than left colon adenomas ( 21 % ) , but the difference was not significant . There was evidence of variation in sensitivity between endoscopists , but significant miss rates for small adenomas were found among essentially all endoscopists . CONCLUSIONS Using current colonoscopic technology , there are significant miss rates for adenomas < 1 cm even with meticulous colonoscopy . Miss rates are low for adenomas > or = 1 cm . The results suggest the need for improvements in colonoscopic technology PURPOSE To prospect ively compare thin-section low-dose multi-detector row computed tomographic ( CT ) colonography with conventional colonoscopy for the detection of colorectal neoplasms . MATERIAL S AND METHODS One hundred five patients underwent CT colonography immediately before colonoscopy . Supine and prone CT colonographic acquisitions to image the region during a 30-second breath hold were performed . CT colonographic images were prospect ively interpreted for the presence , location , size , and morphologic features of polyps . The time of image interpretation was noted . Sensitivity , specificity , and positive and negative predictive values of CT colonography were calculated , with 95 % CIs , by using colonoscopic findings as the reference st and ard . The weighted CT dose index was calculated on the basis of measurements in a st and ard body phantom . Effective dose was calculated by using commercially available software . RESULTS Median CT data interpretation time was 12 minutes . One hundred thirty-two polyps in 59 patients were identified at colonoscopy ; no polyps were detected in 46 patients . Sensitivities for detection of polyps smaller than 5 mm , 6 - 9 mm , and larger than 10 mm in diameter were 12 % ( 11 of 91 polyps ) , 70 % ( 19 of 27 polyps ) , and 93 % ( 13 of 14 polyps ) , respectively . Estimated overall specificity was 97.7 % ( 515 of 527 imaging results ) . The total weighted CT dose index for combined supine and prone CT colonography was 11.4 mGy . The effective doses for combined CT colonography were 5.0 mSv and 7.8 mSv for men and women , respectively . CONCLUSION Low-dose multi-detector row CT colonography has excellent sensitivity and specificity for detection of colorectal neoplasms 10 mm and larger BACKGROUND / AIMS Diagnosis of colorectal diseases might be a challenge . This prospect i ve study aim ed to evaluate virtual CT colonoscopy ( CT colonography ) as a new diagnostic modality in colorectal diseases . METHODOLOGY Thirty-two patients ( 22 males and 10 females , mean age 47 years ) with different colorectal complaints were investigated by CT colonography . Scanning parameters were collimation of 5 mm , table speed of 6.25mm/s and pitch of 1.25 . All images were evaluated in axial slices , reformatted images with endoluminal and extraluminal views . All patients were re-examined by the conventional colonoscope . The CT colonography and the colonoscopy findings were correlated . RESULTS CT colonography suspected colorectal malignancy in 14 patients , diagnosed colorectal polyps in 4 ( out of 6 ) , suspected inflammatory bowel diseases in 5 ( out of 6 ) , showed colonic diverticulae in 3 ( out of 4 ) , and found no abnormality in 2 patients . CT colonography displayed the proximal colon above the obstructing lesion in extraluminal views , fungating mass in endoluminal view and accurately localized the lesion . In inflammatory bowel diseases , segmental ( in 4 patients ) or skipped ( one patient ) wall thickening , loss of colonic haustration ( 3 patients ) and pseudopolyps ( one patient ) were detected . Superficial ulcers were missed . Endoluminal images displayed the orifices of the diverticulae in 3 patients . The CT colonography sensitivity was 86.7 % and its specificity was 100 % . CONCLUSIONS The high resolution and multiple image display of CT colonography allow detection of many colorectal lesions . CT colonography is also a noninvasive imaging modality that is particularly valuable in poor risk patients and for colorectal examination proximal to an obstructing lesion PURPOSE To prospect ively evaluate the diagnostic accuracy of low-radiation-dose computed tomographic ( CT ) colonography for detection of colorectal polyps by using two sequential colonoscopies , with the second colonoscopy as the reference st and ard . MATERIAL S AND METHODS The study was local ethics committee approved , and all patients gave written informed consent . Colonographic images were acquired by using a low-dose multi-detector row CT protocol ( effective milliampere-second setting , 10 mAs ) . Three observers interpreted the CT colonographic data separately and independently by using a two-dimensional technique . Initial conventional colonoscopy was performed by an endoscopist unaware of the CT colonographic findings . Second colonoscopy performed within 2 weeks by a colonoscopist aware of both the CT colonographic and the initial colonoscopic findings served as the reference st and ard . The sensitivities of CT colonography and initial colonoscopy were calculated on a per-polyp and a per-patient basis . Specificities and positive and negative predictive values also were calculated on a per-patient basis . RESULTS Eighty-eight patients underwent CT colonography and initial conventional colonoscopy on the same day . Per-polyp sensitivities were 62 % and 83 % for CT colonography and initial colonoscopy , respectively . Sensitivities for detection of polyps 6 mm in diameter or larger were 86 % and 84 % for CT colonography and initial colonoscopy , respectively . Initial colonoscopy failed to depict 16 polyps , six of which were correctly detected with CT colonography . For identification of patients with polyps 6 mm in diameter or larger , CT colonography and initial colonoscopy , respectively , had sensitivities of 84 % and 90 % , specificities of 82 % and 100 % , positive predictive values of 70 % and 100 % , and negative predictive values of 91 % and 95 % . CONCLUSION Low-dose CT colonography compares favorably with colonoscopy for detection of colorectal polyps 6 mm in diameter or larger , with markedly decreased performance for detection of polyps 5 mm in diameter or smaller Abstract PURPOSE : Multislice CT colonography is an alternative to colonoscopy . The purpose of this study was to compare multislice CT colonography with colonoscopy in the detection of colorectal polyps and cancers . METHODS : Between June 2000 and December 2001 , 45 males and 35 females ( median age , 68 ( 29–83 ) years ) with symptoms of colorectal disease were studied prospect ively . All patients underwent multislice CT colonography and colonoscopy , and the findings were compared . RESULTS : Colonoscopy was incomplete in 18 ( 22 percent ) patients because of obstructing lesions or technical difficulty , and multislice CT colonography was unsuccessful in 4 ( 5 percent ) because of fecal residue . Colonoscopy was normal in 26 patients and detected 29 colorectal cancers and 33 polyps in 35 patients , diverticulosis in 16 patients , and colitis in 3 patients . Multislice CT colonography identified 28 of 29 colorectal cancers with one false negative and one false positive ( sensitivity , 97 percent ; specificity , 98 percent ; positive predictive value , 96 percent ; negative predictive value , 98 percent ) . Multislice CT colonography identified all 12 polyps measuring ≥10 mm in diameter ( sensitivity , 100 percent ) , 5 of 6 measuring 6 to 9 mm in diameter ( sensitivity , 83 percent ) , 8 of 15 polyps ≤5 mm ( sensitivity , 53 percent ) , and false-positive for 8 polyps . The overall sensitivity was 74 percent and specificity 96 percent . The positive predictive value for polyps was 88 percent , and the negative predictive value was 90 percent . Multislice CT colonography also detected 5 of 16 patients with diverticulosis ( sensitivity , 31 percent ; specificity , 98 percent ) and colitis in 2 of 3 patients ( sensitivity , 67 percent ; specificity , 100 percent ) . In ten ( 13 percent ) patients , extracolonic findings on multislice CT colonography altered management and included five patients with colorectal liver metastases . In 15 ( 19 percent ) patients , there were incidental findings that did not dem and further investigation . CONCLUSIONS : The results from this study indicate that the efficacy of multislice CT colonography in the detection of colorectal cancers and polyps ≥6 mm is similar to colonoscopy . Multislice CT colonography allows clinical staging of colorectal cancers , outlines the whole length of the colon in obstructing carcinoma when colonoscopy fails , and can identify extracolonic causes of abdominal symptoms BACKGROUND / AIMS To determine the sensitivity and specificity of multidetector computed tomography-based virtual colonoscopy for colorectal polyp detection by using conventional colonoscopy as the reference st and ard . METHODS 48 patients with high risk for colorectal cancer underwent virtual colonoscopy followed by conventional colonoscopy . Examination results were compared with conventional colonoscopy , which served as the gold st and ard . RESULTS Virtual colonoscopy correctly depicted 19 of 22 polyps ( sensitivity , 86 % ) that were detected in conventional colonoscopy . All 4 polyps that were greater than 10 mm in size ( 100 % ) , 6 of 7 polyps 6 - 9 mm in size ( 85 % ) , and 9 of 11 polyps 5 mm in size or smaller ( 81 % ) were correctly depicted with virtual colonoscopy . Virtual colonoscopy had an overall sensitivity of 86 % and specificity of 98 % . CONCLUSION Multidetector computed tomography-based virtual colonoscopy has excellent sensitivity for the detection of clinical ly important colorectal polyps Context The effect of colonoscopy on colorectal cancer ( CRC ) mortality is unknown . Contribution By using a Canadian province-wide data set , the authors identified 10292 case patients who died of CRC and , for each case patient , 5 matched controls who did not . A total of 7.0 % of the case patients and 9.8 % of the controls had colonoscopy . Colonoscopy was associated with fewer CRC deaths ( odds ratio , 0.69 [ 95 % CI , 0.63 to 0.74 ] ) . The odds ratios for death from CRC that developed in the left and right colon were 0.33 ( CI , 0.28 to 0.39 ) and 0.99 ( CI , 0.86 to 1.14 ) , respectively . Caution This was an observational casecontrol study . The data set did not identify a reason for colonoscopy . Implication Colonoscopy may be much less effective in preventing death from CRC of the right colon compared with the left colon . The Editors Colorectal cancer ( CRC ) is the second most common cause of cancer death in North America ( 1 ) . Although colonoscopy is untested in r and omized trials , many lay organizations ( 2 , 3 ) and specialty societies ( 46 ) advocate it as the preferred screening method ( 7 , 8) . In the United States , screening colonoscopy rates have rapidly increased ( 911 ) . The evidence for effectiveness of screening colonoscopy is indirect , inferred from reductions in CRC deaths in r and omized trials of screening with fecal occult blood testing ( 12 ) , a test that is much less sensitive than colonoscopy ( 13 ) . In casecontrol studies , large-bowel endoscopy was associated with a 50 % reduction in CRC development and 60 % reduction in CRC deaths ( 14 , 15 ) . However , most of these studies included few women and evaluated sigmoidoscopy . Casecontrol studies of the association of colonoscopy with the incidence of CRC ( 16 , 17 ) have been conducted but are more prone to bias than those defining case status by cancer death ( 18 ) . Colonoscopy has real-world limitations . In a population -based study , 6 % of patients with newly discovered right-sided CRC had undergone colonoscopy 6 months to 3 years before diagnosis , indicating a substantial miss rate in the community setting ( 19 ) . Detection rates vary by endoscopist and by endoscope withdrawal time ( 20 ) . The accuracy of colonoscopy done in the real world is unknown but may be substantially less than that in published reports ( 2123 ) . We studied colonoscopy throughout Ontario , Canada , hypothesizing that it would be associated with fewer CRC deaths , but to a lesser degree than estimated in the literature . Methods The research ethics board of St. Michael 's Hospital , Toronto , Ontario , Canada , approved the study . Study Design We did a casecontrol study of the association of colonoscopy and CRC deaths . We measured the odds of exposure to colonoscopy in case patients ( persons who died of CRC ) and controls ( persons who did not die of CRC ) and calculated an odds ratio ( OR ) for exposure . Because this OR is mathematically equal to the ratio of the odds of being a case patient given colonoscopy exposure to the odds of being a control given colonoscopy exposure , it estimates the association between colonoscopy and CRC death . Data Sources We used 4 data sources . The Ontario Cancer Registry tracks all incident cancer cases diagnosed in Ontario since 1964 ; it is more than 95 % complete ( 24 ) . It is linked to the Mortality File , an electronic data base maintained by the Registrar General of Ontario to tally deaths of Ontario residents . Data on vital status and cause of death were available through 31 December 2003 . The Ontario Health Insurance Plan data base contains information on cl aims billed by physicians for services and has been linkable since 1991 , permitting identification of almost all medical procedures occurring in Ontario . The Registered Persons Data base , a roster of all Ontario Health Insurance Plan beneficiaries , contains almost all Ontario residents . The Canadian Institute for Health Information hospital discharge abstract data base , linkable since 1988 , contains information on every patient discharged from a hospital or same-day surgery unit in Ontario and includes patient demographic information , major diagnoses , procedures , and discharge status . Identification of Case Patients We identified case patients from the Ontario Cancer Registry . They received a diagnosis of CRC ( International Classification of Diseases , Ninth Revision , codes 153.0 to 153.4 or 153.6 to 154.1 ) from 1 January 1996 to 31 December 2001 and died of CRC or related causes between 1 January 1996 and 31 December 2003 ( International Classification of Diseases , Ninth Revision , codes 159 [ malignant neoplasm of other or ill-defined sites within the digestive organs and peritoneum ] , 197 [ secondary malignant neoplasm of respiratory and digestive systems ] , or 199 [ malignant neoplasm without specification of site ] ) . Complete identification of CRC deaths by using the cause of death on Ontario death certificates requires including deaths from these closely related causes . We included only persons age 52 to 90 years so that all controls would be in the screening-eligible age range during the exposure period . We excluded persons who had received a previous diagnosis of CRC , lived where physicians do not bill directly ( < 5 % of the sample ) , or were not continuously eligible for an Ontario Health Insurance Plan from 1 January 1992 . For secondary analyses , we stratified case patients by age ; sex ; and site of primary CRC , as assessed by registrars of the Ontario Cancer Registry from pathology reports and hospital discharge summaries ( right-sided cancer [ proximal to the splenic flexure ] , left-sided cancer [ splenic flexure to rectum ] , or unknown site of cancer ) . Identification of Controls From the Registered Persons Data base , we selected persons continuously eligible for Ontario Health Insurance Plan coverage from 1 January 1992 to 31 December 2003 or death . Case patients were matched to controls for factors known to influence colonoscopy rates and risk for CRC death : sex ( 1 , 25 ) , socioeconomic status ( 25 , 26 ) , and age ( 25 ) . To minimize bias from differing access to colonoscopy , we matched for geographic location . Consequently , each case patient had 5 controls matched for sex , income quintile ( based on the mean household income of the enumeration area of residence ) , residence location by health care region during year of diagnosis , and calendar year of birth . For each potential match , we defined the referent date , the date on which case patients received a diagnosis of cancer , determined from the Ontario Cancer Registry , a source that uses a st and ardized hierarchy for date of diagnosis . The date of pathologic confirmation of cancer , if available , was considered the date of diagnosis . We then linked the cohort of potential matches to the Ontario Cancer Registry to detect and exclude potential matches with a diagnosis of CRC on or before the referent date or death from CRC before 31 December 2003 . Controls were alive at the date of the case patients ' death . We included controls who developed CRC after the referent date . By matching for calendar year of birth , case patients and controls had an equal period to be exposed to colonoscopy before the date of CRC diagnosis ( referent date ) . By using r and om numbers , we r and omly selected 5 controls from all matches and assigned them to a case patient to form the control group . Determining Exposure By using the Ontario Health Insurance Plan billing codes ( Appendix Table ) , we detected exposure to colonoscopy from 1 January 1992 to an index date 6 months before case patients received a diagnosis of CRC . Every case patient and control had more than 42 months of potential exposure to colonoscopy and at least 18 months of potential exposure while of screening-eligible age . We defined 2 exposures : any colonoscopy regardless of completeness ( Appendix Table ) and complete colonoscopy ( colonoscopy coded as reaching the cecum ) . We did not consider flexible sigmoidoscopy to be an exposure . We treated exposure to colonoscopy as a binary variable : Persons who had at least 1 colonoscopy were considered exposed , and if any colonoscopy was complete to the cecum , those persons were considered exposed to complete colonoscopy . For persons who had more than 1 colonoscopy , we included only the first complete colonoscopy . In persons with no complete colonoscopy , we included the first incomplete colonoscopy . From billing codes , we detected polypectomies done during colonoscopy . We ascertained the self- design ated specialty of the physician who billed for the included colonoscopy from the Ontario Physicians Human Re sources Data Centre . Appendix Table . Diagnostic and Procedure Codes Diagnostic colonoscopies ( those done to evaluate CRC symptoms , confirm the diagnosis , or search for metachronous tumors ) would be associated with greater odds of CRC death than screening colonoscopies , which could mask any effect of screening colonoscopy on preventing death from CRC . Because Ontario Health Insurance Plan billing codes do not distinguish between screening and diagnostic colonoscopies ( 27 ) , we tried to increase the proportion of screening colonoscopies by excluding all colonoscopies done within 6 months before the date of CRC diagnosis ( referent date ) . This strategy assumes that most diagnoses of CRC in the Ontario Cancer Registry would be made within 6 months of a colonoscopy to investigate symptoms , confirm diagnosis , or search for metachronous tumors . Previous investigators have used a 6-month window of exclusion ( 19 ) , although some chose a shorter period ( 14 ) . To vali date our choice , we recalculated the OR for the association of colonoscopy and CRC death for windows varying from 0 to 12 months . Determining Comorbid Conditions We identified comorbid conditions at a hospital discharge occurring within 60 months before the index date . We calculated the Charlson Comorbidity Index score ( 28 ) as 0 , 1 , 2 , or 3 or more . We assigned a score of 0 to those who were not hospitalized . Statistical Analysis We calculated descriptive statistics for study variables Purpose : To compare and find the optimal combination of bowel preparation regimens and different concentrations of barium-based fecal-tagging agents on computed tomographic colonography in terms of tagging efficacy , patients ' compliance , and diagnostic performance . Material s and Methods : Sixty-nine consecutive patients were prospect ively enrolled and r and omly divided into 4 groups according to a combination of bowel preparation regimens ( sodium phosphate [ Colclean ] vs magnesium citrate [ LoSoPrep ] ) and different concentrations of barium-based fecal-tagging agents ( Tagitol V [ thick , 40 % wt/vol ] 60 mL vs EasyCT [ thin , 4.6 % wt/vol ] 600 mL ) . Patients who received Colclean and EasyCT were design ated as group 1 ; Colclean and Tagitol V as group 2 ; LoSoPrep and EasyCT , group 3 ; and LoSoPrep and Tagitol V , group 4 . For objective analysis , the volume of tagged feces and fluid was semiautomatically calculated using a threshold of 150 Hounsfield units . The volume of untagged feces and fluid was also calculated using the seeded region-growing method . The tagging efficacy was then calculated and compared using the analysis of variance test . For subjective analysis , 2 radiologists visually determined the overall tagging efficacy on a segmental basis . The numbers of homogeneously tagged , heterogeneously tagged , heterogeneously untagged , and homogeneously untagged feces greater than or equal to 6 mm and fluid were counted in each segment . The rates of homogeneously tagged stool and fluid were compared between the groups using the & khgr;2 test . Patients ' compliance for taking the regimens was recorded and compared using the Kruskal-Wallis test . Per-polyp and per-patient sensitivity for polyps greater than or equal to 6 mm were analyzed and compared using the & khgr;2 or Fisher exact test . Results : Objective analysis showed that tagging efficacy was significantly lower in group 1 than in the other 3 groups . In a subjective analysis , overall tagging efficacy was significantly higher in group 4 than in the other groups . The rate of homogeneously tagged fluid was significantly higher in group 4 than in the other groups . The rate of homogeneously tagged feces was significantly higher in the thick barium group than in the thin barium group . Patients ' compliance was significantly worse in group 1 than in the other 3 groups . Per-polyp and per-patient sensitivities for polyps greater than or equal to 6 mm were not significantly different among all groups . However , per-patient specificity for lesions greater than or equal to 10 mm was significantly lower in group 2 than in the other groups . Conclusions : With better tagging efficacy and compliance while maintaining comparable diagnostic performance , it is our belief that the best combination of bowel preparation and fecal-tagging regimen is a combination of magnesium citrate and a high concentration of a barium tagging agent Objective Virtual colonoscopy (VC)/CT colonography has advantages over the well‐documented limitations of colonoscopy/barium enema . This prospect i ve blinded investigative comparison trial aim ed to evaluate the ability of VC to assess the large bowel , compared to conventional colonoscopy ( CC ) , in patients at high risk of colorectal cancer ( CRC ) RATIONALE AND OBJECTIVES To compare prospect ively 64-detector-row computed tomographic colonography ( CTC ) after a full-laxative tagging-based preparation ( full preparation ) with a minimum-laxative tagging-based preparation ( minimum preparation ) with respect to diagnostic performance in the detection of polyps , tagging quality , and patient acceptance . MATERIAL S AND METHODS Consecutive 101 patients at high risk for developing colorectal cancer were alternately assigned to either a full preparation group ( n = 51 ) or a minimum preparation group ( n = 50 ) for fecal-tagging CTC . The full preparation consisted of administration of 2-L polyethylene glycol solution with 20 mL of sodium diatrizoate for fecal tagging . The minimum preparation consisted of ingestion of a total of 45 mL of sodium diatrizoate during the 3 days before and 10 mL of sodium picosulfate solution the night before CT . Colonoscopy was used as the reference st and ard . We assessed the accuracy of polyp detection and the tagging quality for each preparation . All patients were given question naires related to their acceptance . RESULTS Per-patient sensitivity , specificity , and positive and negative predictive values for polyps > or = 6 mm were as follows : full preparation group , 97 % , 92 % , 88 % , and 98 % , respectively ; minimum preparation group , 88 % , 68 % , 56 % , and 92 % , respectively . Average visual subjective tagging scores for the full and minimum preparation groups were 94.6 % and 76.1 % , respectively ( P < .0001 ) . Minimum preparation was better tolerated than full preparation . CONCLUSION Although full-laxative and minimum-laxative fecal-tagging CTC yielded an equally high sensitivity in the detection of polyps > or = 6 mm , the full-laxative fecal-tagging CTC yielded a better specificity than did the minimum-laxative fecal-tagging CTC . Thus , it is desirable to offer patients an option of either full-laxative fecal-tagging CTC for highest diagnostic accuracy and ability to perform a same-day therapeutic colonoscopy without additional bowel preparation , or minimum-laxative fecal-tagging CTC for those unwilling to undergo full preparation but willing to accept moderate decrease in specificity PURPOSE To compare the performance of virtual and conventional colonoscopy for the detection of colorectal polyps using a multislice spiral CT scanner ( MSCT ) . MATERIAL S AND METHODS 48 patients ( 20 women , 28 men , mean age 61.5 years ) with clinical indication for conventional colonoscopy were prospect ively studied using a MSCT ( Somatom Volume Zoom , Siemens , Forchheim ) . Examination was performed after st and ard oral preparation for colonoscopy and colonic distension with room air and i. v. butylscopolamin . Images were obtained in prone and supine position using a detector configuration of 4 x 1 mm , a table feed of 5 mm/rotation at 140 mAs and 120 kV. Slice thickness and reconstruction increment were 3 and 1.5 mm , respectively . CT data were assessed by two blinded radiologists on a Vitrea workstation ( Vital Images , USA ) using a software with multiplanar and volume-rendering capabilities . RESULTS 33 patients had normal findings on conventional colonoscopy . In 15 patients a total of 30 polyps and one carcinoma with stenosis were identified . MSCT-colonography identified the carcinoma and 23 polyps ( 77 % ) . 3 of 3 polyps were 10 mm or more ( 100 % ) , 6 of 7 were 5.1 to 9.9 mm ( 86 % ) and 14 of 20 were 5 mm or smaller ( 70 % ) . There were 13 false positive findings for polyps ( 10 lesions < 6 mm in 5 patients ) and no false positive finding of carcinoma . CONCLUSIONS MSCT colonography allows accurate detection of polyps larger than 10 mm . Compared to published results of single-slice CT , multislice CT colonography increases the rate of detection of small colorectal polyps in particular . However , false positive results still remain a problem OBJECTIVES : Computed tomographic ( CT ) colonography or virtual colonoscopy is a new diagnostic method for the colon and rectum , developed on the basis of spiral computed axial tomography and employing virtual reality technology . The aim of this study was to determine the sensitivity , specificity , and diagnostic accuracy of CT colonography compared with colonoscopy in a prospect i ve , blinded study in one single institution in Italy . METHODS : Ninety-nine patients r and omly selected among those attending the open-access endoscopy unit for diagnostic colonoscopy underwent colonoscopy and spiral CT . The images obtained were transmitted to generate the virtual colonoscopy pictures . A supervisor compared the results with the findings of conventional colonoscopy . RESULTS : CT colonography diagnosed seven of eight tumors , one being missed because the patient had been inadequately prepared . In 28 patients , CT colonography identified 26 polyps of 45 ( 57.8 % sensitivity , 92.6 % specificity , 86.7 % positive predictive value ) , regardless of their size . The sensitivity in detecting colonic polyps was 31.8 % ( 7/22 ) in the first 25 cases and 91.6 % ( 11/12 ) in the last 20 patients . CT colonography missed one flat adenoma , some angioectasias and colonic lesions because of portal hypertension in one patient , Crohn 's disease ulcers in two patients , and ulcerative colitis lesions in three . CONCLUSIONS : CT colonography shows poor sensitivity for identifying colonic polyps and does not always detect neoplastic lesions . Flat lesions are impossible to see by this method PURPOSE To assess the added benefits of prone positioning in addition to supine positioning and oral iodinated contrast medium for help in the detection of colonic polyps at computed tomographic ( CT ) colonography . MATERIAL S AND METHODS CT colonography was performed in prone and supine positions in 180 patients with polyps or risk factors for colonic neoplasia . Patients were r and omly assigned to receive a st and ard bowel preparation or a st and ard preparation plus oral iodinated contrast medium . One radiologist interpreted supine images alone , and another analyzed supine and prone images . All patients subsequently underwent colonoscopy . RESULTS At colonoscopy , 121 large ( > or = 1-cm-diameter ) polyps and 142 smaller ( 0.5 - 0.9-cm ) polyps were identified . Prone positioning result ed in increased sensitivity for identification of patients with large ( > or = 1-cm ) polyps ( increase from 70 % to 85 % , P : = .004 ) and of patients with polyps 0.5 cm or larger ( increase from 75 % to 88 % , P : < .005 ) , with no change in specificity . Use of oral contrast medium did not significantly improve polyp detection even in the subset of patients in whom colonic fluid attenuation was markedly increased . CONCLUSION Acquisition and review of supine and prone CT colonographic images significantly improves the ability to identify patients with polyps 0.5 cm in diameter or larger . Administration of oral iodinated contrast medium does not significantly improve polyp detection BACKGROUND This prospect i ve study compared multislice CT colonography with ultra-low-dose technique to high-resolution videocolonoscopy as the st and ard for detection of colorectal cancer and polyps . METHODS After st and ard bowel preparation , 115 patients underwent multislice CT colonography with an ultra-low-dose multislice CT colonography protocol immediately before videocolonoscopy . After noise reduction by using a mathematical algorithm , ultra-low-dose multislice CT colonographic images were analyzed in blinded fashion , and the results were compared with the results of high-resolution videocolonoscopy . RESULTS A total of 150 lesions were detected by high-resolution videocolonoscopy in 115 patients . For ultra-low-dose multislice CT colonography , sensitivities for detection of polyps less than 5 mm in size , 5 to 10 mm , and greater than 10 mm in diameter were 76 % , 91 % , and 100 % , respectively . Although the sensitivity for detection of flat lesions was only 50 % , the sensitivity and the specificity for detection of polyps 5 mm or greater in size were 94 % and 84 % , respectively . For adenomatous lesions greater than 5 mm in size , sensitivity was 94 % and specificity was 92 % . The overall specificity was 79 % . The calculated effective radiation dose ranged between 0.75 and 1.25 mSv . CONCLUSIONS Compared with high-resolution videocolonoscopy , ultra-low-dose multislice CT colonography has excellent sensitivity and specificity for detection of colorectal lesions 5 mm or greater in size , and the radiation exposure is relatively low . However , before this technique can be generally recommended for colorectal screening , further improvement in the detection of flat and extremely small lesions must be achieved INTRODUCTION Aim of this study was to evaluate the sensitivity of virtual colonoscopy ( CT colonography ) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality , as well as indications to the examination . MATERIAL AND METHODS We examined prospect ively 62 symptomatic patients aged 36 to 82 years ( 28 women and 34 men ) . All patients underwent both conventional and virtual colonoscopy on the same day ; the conventional examination allowed exploration of the entire colon . RESULTS Conventional colonoscopy identified 89 lesions 3 - 50 mm in diameter , namely 84 benign and 5 malignant lesions . No lesions were identified in 12 patients . CT colonography identified 52 of the 89 lesions , with 57.1 % diagnostic accuracy . There were 11 false positives ( 82.5 % positive predictive value and 52.2 % specificity ) and 37 false negatives ( 24.5 % negative predictive value and 58.4 % sensitivity ) . Sensitivity was significantly higher ( 85.7 % ) for polyps > or = 1 cm . CONCLUSIONS Virtual colonoscopy is an imaging modality with good diagnostic yield , well tolerated by patients and with great potentials for further development . We suggest that the examination be performed in symptomatic patients who can not undergo total colonoscopy or refuse the other imaging modalities . Further studies are warranted in larger series of patients , possibly introducing it in screening programs BACKGROUND & AIMS Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk . METHODS We pooled individual data from 8 prospect i ve studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance . RESULTS During a median follow-up period of 47.2 months , advanced colorectal neoplasia was diagnosed in 1082 ( 11.8 % ) of the patients , 58 of whom ( 0.6 % ) had invasive cancer . Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas ( 24.1 % ; st and ard error , 2.2 ) and those with an adenoma 20 mm in size or greater ( 19.3 % ; st and ard error , 1.5 ) . Risk factor patterns were similar for advanced adenomas and invasive cancer . In multivariate analyses , older age ( P < .0001 for trend ) and male sex ( odds ratio [ OR ] , 1.40 ; 95 % confidence interval [ CI ] , 1.19 - 1.65 ) were associated significantly with an increased risk for metachronous advanced neoplasia , as were the number and size of prior adenomas ( P < .0001 for trend ) , the presence of villous features ( OR , 1.28 ; 95 % CI , 1.07 - 1.52 ) , and proximal location ( OR , 1.68 ; 95 % CI , 1.43 - 1.98 ) . High- grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics . CONCLUSIONS Occurrence of advanced colorectal neoplasia is common after polypectomy . Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas Purpose : To evaluate the diagnostic performance ( colorectal lesions ) of computed tomography ( CT ) colonography in 111 patients , a majority of whom were at high risk for colorectal neoplasia . Material and Methods : After bowel preparation , CT colonography was performed , immediately followed by conventional colonoscopy . The diagnostic performance of CT colonography was analyzed relative to lesion size , histological diagnosis , and diagnostic certainty . Results : The sensitivity of CT colonography increased with lesion size ( P<0.001 ) , and was 91 % ( 21/23 ) for lesions ⩾10 mm . All 10 carcinomas and 86 % ( 19/22 ) of adenomas ⩾5 mm were detected . Unconfirmed or false-positive CT findings were generally small and /or reported with low diagnostic certainty . The specificity of CT colonography would be 45 % ( 30/66 ; 95 % CI 34 % to 57 % ) if patients with findings of any size and any diagnostic certainty were selected for follow-up , and 92 % ( 85/92 ; 95 % CI 85 % to 96 % ) if only patients with CT findings ⩾10 mm classified as certain were selected . Conclusion : CT colonography had a high sensitivity for lesions ⩾5 mm . The diagnostic performance increased with lesion size and degree of diagnostic certainty , and was higher for adenomas OBJECTIVE We compared the accuracy and tolerability of intravenous contrast enhanced spiral computed tomography colonography ( CTC ) and optical colonoscopy ( OC ) for the detection of colorectal neoplasia in symptomatic patients for colorectal neoplasia . METHODS A prospect i ve study was performed in 48 patients with symptomatic patients with increased risk for colorectal cancer . Spiral CTC was performed in supine and prone positions after colonic cleansing . The axial , 2D MPR and virtual endoluminal views were analyzed . Results of spiral CTC were compared with OC which was done within 15 days . The psychometric tolerance test was asked to be performed for both CTC and colonoscopy after the procedure . RESULTS Ten lesions in 9 of 48 patients were found in CTC and confirmed with OC . Two masses and eight polyps , consisted of 1 tubulovillous , 1 tubular , 2 villous adenoma , 4 adenomatous polyp , 4 adenocarcinoma , were identified . Lesion prevalence was 21 % . Sensitivity , specificity , accuracy , positive and negative predictive values were found 100 % , 87 % , 89 % , 67 % and 100 % , respectively . Psychometric tolerance test showed that CTC significantly more comfortable comparing with OC ( p=0.00 ) . CTC was the preferred method in 37 % while OC was preferred in 6 % of patients . In both techniques , the most unpleasant part was bowel cleansing . CONCLUSION Contrast enhanced CTC is a highly accurate method in detecting colorectal lesions . Since the technique was found to be more comfortable and less time consuming compare to OE , it may be preferable in management of symptomatic patients with increased risk for colorectal cancer The aim of this study was to examine the efficacy of IV Buscopan as a muscle relaxant in CT colonography in terms of colonic distension and polyp detection , and to determine its particular efficacy in patients with diverticular disease . Seventy-three consecutive patients were r and omised to receive IV Buscopan or no muscle relaxant prior to CT colonography . CT colonography was performed using a Siemens Somatom 4-detector multislice CT scanner . The following parameters were recorded : degree of colonic distension using a 4-point scale ; diagnostic adequacy of colonic distension ; presence or absence of diverticular disease ; and presence of colonic polyps . Accuracy of polyp detection was assessed using subsequent conventional colonoscopy as a gold st and ard . There was no significant difference between the two groups in the number of segments that were deemed to be optimally or adequately distended ( p=0.37 ) . Although IV Buscopan did improve distension of certain segments , this effect was not sufficient to improve the number of diagnostically adequate studies in the Buscopan group ( p=0.14 ) . In patients with diverticular disease , IV Buscopan did not have any significant effect on segments affected by diverticulosis but was associated with an improvement in distension of more proximal segments . There was no significant difference between the two groups in terms of polyp detection ( p=0.34 ) . The addition of prone scanning to supine scanning was found to be the most useful technique for maximising colonic distension . Intravenous Buscopan at CT colonography does not improve the overall adequacy of colonic distension nor the accuracy of polyp detection . In patients with sigmoid diverticular disease IV Buscopan improves distension of more proximal colonic segments and may be useful in selected cases , but our results do not support its routine use for CT colonography PURPOSE To retrospectively determine the detection rates , clinical stages , and short-term patient survival for all unsuspected cancers identified at screening computed tomographic ( CT ) colonography , including both colorectal carcinoma ( CRC ) and extracolonic malignancies . MATERIAL S AND METHODS From April 2004 through March 2008 , prospect i ve colorectal and extracolonic interpretation was performed in 10,286 outpatient adults ( 5388 men , 4898 women ; mean age , 59.8 years ) undergoing screening CT colonography at two centers in this institutional review board-approved , HIPAA-compliant study . For all histologically proved , clinical ly unsuspected cancers detected at CT colonography that were identified at retrospective review of the medical records , the stage of disease , treatment , and clinical outcome were analyzed . Benign neoplasms ( including advanced colorectal adenomas ) , symptomatic lesions , and tumors without pathologic proof were excluded . Statistical analysis was performed with Fisher exact test and two- sample z test . RESULTS Unsuspected cancer was confirmed in 58 ( 0.56 % ) patients ( 33 women , 25 men ; mean age , 60.8 years ) , which included invasive CRC in 22 patients ( 0.21 % ) and extracolonic cancer in 36 patients ( 0.35 % ) . Extracolonic malignancies included renal cell carcinoma ( n = 11 ) , lung cancer ( n = 8) , non-Hodgkin lymphoma ( n = 6 ) , and a variety of other tumors ( n = 11 ) . Cancers in 31 patients ( 53.4 % ) were stage I or localized . At the most recent clinical follow-up ( mean , 30.0 months + /- 11.8 [ st and ard deviation ] ; range , 12 - 56 months ) , three patients ( 5.2 % ) had died of their cancer . CONCLUSION The overall detection rate of unsuspected cancer is approximately one per 200 asymptomatic adults undergoing routine screening CT colonography , including about one invasive CRC per 500 cases and one extracolonic cancer per 300 cases . Detection and treatment at an early presymptomatic stage may have contributed to the favorable outcome Background : “ Perspective-filet view ” is a novel three-dimensional ( 3D ) viewing technique for computed tomography colonography ( CTC ) . Studies with experienced readers have shown a sensitivity for perspective-filet view similar to that of 2D or 3D endoluminal fly-through in detection of colorectal lesions . It is not known whether perspective-filet view , compared to axial images , improves lesion detection by inexperienced readers . Purpose : To compare primary 3D analysis using perspective-filet view ( 3D Filet ) with primary 2D analysis , as used by inexperienced CTC readers . Secondary aims were to compare lesion detection by 3D Filet when used by experienced and inexperienced readers , and to evaluate the effect of combined 3D Filet + 2D analysis . Material and Methods : Fifty symptomatic patients were prospect ively enrolled . An experienced reader performed 3D Filet analysis followed by complete 2D analysis ( 3D Filet + 2D ) , before colonoscopy with segmental unblinding . Two inexperienced readers ( readers 2 and 3 ) , blinded to CTC and colonoscopy findings , retrospectively performed 3D Filet analysis and , after 5 weeks , 2D analysis . True positives ≥6 mm detected by the inexperienced readers with 3D Filet and /or 2D were combined to obtain 3D Filet + 2D . Results : Colonoscopy revealed 116 lesions : 16 lesions ≥10 mm , 19 lesions 6–9 mm , and 81 lesions ≤5 mm . For the experienced reader , sensitivities for lesions ≥6 mm with 3D Filet and 3D Filet + 2D were 77 % and 83 % , respectively . For the inexperienced readers , sensitivities for lesions ≥6 mm with 3D Filet and 2D were 51 % and 57 % ( reader 2 ) and 40 % and 43 % ( reader 3 ) , respectively . There was no significant difference between 3D Filet and 2D regarding sensitivity and reading time . For lesions ≥6 mm , 3D Filet + 2D improved the sensitivity of reader 2 to 63 % and of reader 3 to 51 % . Conclusion : Lesion detection by inexperienced readers using perspective-filet view is comparable to that obtained by 2D . Lesion detection improves by combining 3D Filet + 2D , but not to the level of an experienced reader BACKGROUND AND STUDY AIMS The aim of the present study was to analyze the reasons for false findings on computed-tomographic ( CT ) colonography . PATIENTS AND METHODS A total of 100 consecutive CT colonography examinations were carried out before conventional colonoscopies scheduled on the same day . Before the study , an experienced radiologist received training in analyzing CT colonographies . The radiologists and endoscopists were blinded to each others ' findings . The patients received st and ard polyethylene glycol bowel preparation and were scanned in the prone and supine positions using a helical CT scanner and commercially available software for image analysis . Each pair of examinations was later followed by an unblinded analysis , comparing the CT colonographies with video recordings of the conventional colonographies in order to determine the reasons for tumors being missed or false-positive diagnoses arising on CT colonography . RESULTS Ninety polyps were detected in 41 patients . For patients with tumors > or = 5 mm and > or = 10 mm , the sensitivity was 67 % and 75 % , respectively , and the specificity was 84 % and 95 % , respectively . The most important reasons for the 38 false findings of tumors > or = 5 mm were perception errors ( 21 of 38 ) and misinterpretation of flat lesions in particular , including a high- grade dysplasia and a flat elevated Dukes A carcinoma . Residual stool was frequently the reason for misinterpreting lesions > or = 10 mm ( four of 10 ) . CONCLUSIONS Perception errors were the main reason for false findings of lesions > or = 5 mm , including one flat malignant lesion . Residual stool caused four of 10 false findings for lesions > or = 10 mm . Reading CT colonographies requires a high level of expertise , and conventional colonography is still regarded as the gold st and ard for detecting colorectal lesions OBJECTIVE The objective of our study was to compare the performance of primary 3D search using 360 degree virtual dissection with primary 2D search using a 2.5- versus a 1.25-mm slice thickness . SUBJECTS AND METHODS Four hundred fifty-two asymptomatic patients underwent CT colonography ( CTC ) and colonoscopy . Examinations were reconstructed to 1.25- and 2.5-mm slice thicknesses and interpreted using primary 3D search ( 360 degree virtual dissection ) and primary 2D search . Two of three experienced review ers were r and omly assigned to each case ; 1,808 interpretations were performed . RESULTS There were 64 adenomas > or = 6 mm , 26 of which were large adenomas > or = 1 cm . For adenomas 6 - 9 mm in diameter , the area under the receiver operating characteristic curve ( AUC ) using 2.5-mm data sets was 0.66 , 0.62 , 0.90 and 0.78 , 0.69 , 0.67 for review ers 1 , 2 , and 3 , respectively , using primary 3D versus 2D search ( p = not significant [ NS ] ) . For neoplasms > or = 10 mm , the AUC using 2.5-mm data sets was 0.74 , 0.85 , 0.89 and 0.66 , 0.86 , 0.92 for review ers 1 , 2 , and 3 using primary 3D versus 2D search ( p = NS ) . There was no significant difference using 1.25-mm collimation . Double review using both primary 3D and 2D search yielded sensitivities of 84 % ( 16/19 ) and 95 % ( 18/19 ) for large neoplasms ( > or = 1 cm ) using 2.5- and 1.25-mm data sets , respectively . Five of five ( 100 % ) adenocarcinomas were identified . The sensitivity of colonoscopy for large neoplasms was 77 % ( 20/26 ) ( 20 % [ 1/5 ] for adenocarcinoma ) . CONCLUSION No advantage exists for 1.25- or 2.5-mm slice thickness or for primary 3D versus 2D search at CTC . Double review using primary 3D ( virtual dissection ) and 2D search reduces interobserver variability and competes with colonoscopy for the detection of large lesions |
1,126 | 27,486,835 | There is moderate quality evidence showing that the prophylactic administration of xylitol among healthy children attending daycare centres can reduce the occurrence of AOM .
There is inconclusive evidence with regard to the efficacy of xylitol in preventing AOM among children with respiratory infection , or among otitis-prone children . | BACKGROUND Acute otitis media ( AOM ) is the most common bacterial infection among young children in the United States .
There are limitations and concerns over its treatment with antibiotics and surgery and so effective preventative measures are attractive .
A potential preventative measure is xylitol , a natural sugar substitute that reduces the risk of dental decay .
Xylitol can reduce the adherence of Streptococcus pneumoniae ( S pneumoniae ) and Haemophilus influenzae ( H influenzae ) to nasopharyngeal cells in vitro .
This is an up date of a review first published in 2011 .
OBJECTIVES To assess the efficacy and safety of xylitol to prevent AOM in children aged up to 12 years . | BACKGROUND : Acute otitis media ( AOM ) is a common childhood illness and the leading indication for antibiotic prescriptions for US children . Xylitol , a naturally occurring sugar alcohol , can reduce AOM when given 5 times per day as a gum or syrup , but a more convenient dosing regimen is needed for widespread adoption . METHODS : We design ed a pragmatic practice -based r and omized controlled trial to determine if viscous xylitol solution at a dose of 5 g 3 times per day could reduce the occurrence of clinical ly diagnosed AOM among otitis-prone children 6 months through 5 years of age . RESULTS : A total of 326 subjects were enrolled , with 160 allocated to xylitol and 166 to placebo . In the primary analysis of time to first clinical ly diagnosed AOM episode , the hazard ratio for xylitol versus placebo recipients was 0.88 ( 95 % confidence interval [ CI ] 0.61 to 1.3 ) . In secondary analyses , the incidence of AOM was 0.53 episodes per 90 days in the xylitol group versus 0.59 in the placebo group ( difference 0.06 ; 95 % CI –0.25 to 0.13 ) ; total antibiotic use was 6.8 days per 90 days in the xylitol group versus 6.4 in the placebo group ( difference 0.4 ; 95 % CI –1.8 to 2.7 ) . The lack of effectiveness was not explained by nonadherence to treatment , as the hazard ratio for those taking nearly all assigned xylitol compared with those taking none was 0.93 ( 95 % CI 0.56 to 1.57 ) . CONCLUSIONS : Viscous xylitol solution in a dose of 5 g 3 times per day was ineffective in reducing clinical ly diagnosed AOM among otitis-prone children PURPOSE The aim of this study was to evaluate the lactic acid concentration in supragingival plaque from caries-active pre-school children after a short-term use of either xylitol- or sorbitol-containing chewing gums . MATERIAL AND METHODS The investigation consisted of a prospect i ve crossover design with 10 healthy children aged 2 - 4 years each with at least two caries lesions within the dentine ( ds > or = 2 ) . The children were instructed to chew 6 pieces of a test or a control gum every day for a 14-day period . The test gum contained 65 % xylitol and the control gum was sweetened with sorbitol . At baseline and after 14 days , salivary mutans streptococci were enumerated with a chair-side test ( Strip mutans ) and dental plaque was collected from the upper maxillary incisors . After a washout period of 6 weeks , the same procedure was repeated with the corresponding test or control gum . Lactic acid was determined enzymatically in glucose-challenged plaque suspensions . RESULTS The lactic acid concentration was significantly reduced ( p<0.05 ) by 22 % compared with baseline following the xylitol gum regimen but was unaltered after the control gum . The levels of salivary mutans streptococci were mainly unaffected by both chewing gums . CONCLUSION A 14-day use of xylitol-containing chewing gums , corresponding to a daily amount of 5 grams of xylitol , could diminish glucose-initiated lactic acid formation in supragingival plaque in caries-active pre-school children CONTEXT Adenoidectomy and adenotonsillectomy are commonly performed in US children to reduce the occurrence of persistent or recurrent otitis media , but evidence supporting the efficacy of the operations is limited . OBJECTIVES To test the efficacy of adenoidectomy and adenotonsillectomy in children with persistent or recurrent otitis media who had not previously undergone tube placement and to compare the relative efficacy of adenoidectomy alone vs adenotonsillectomy in such children . DESIGN Two parallel r and omized clinical trials . SETTING AND PARTICIPANTS A total of 461 children aged 3 to 15 years were enrolled at Children 's Hospital of Pittsburgh , Pa , between April 1980 and April 1994 . Four hundred ten children were observed for up to 3 years . INTERVENTIONS Children without recurrent throat infection or tonsillar hypertrophy ( 304 enrolled ; 266 followed up ) were r and omized to either an adenoidectomy , adenotonsillectomy , or control group ; children who had such conditions ( 157 enrolled ; 144 followed up ) were r and omized to an adenotonsillectomy or control group . MAIN OUTCOME MEASURES Occurrence rate of episodes of acute otitis media by treatment group and estimated proportion of time with otitis media . RESULTS In both trials , most subjects were eligible because of recurrent acute otitis media , with or without persistent otitis media with effusion . A total of 47 children assigned to surgical treatment groups had no surgery . The efficacy of surgery in both trials was modest and limited mainly to the first follow-up year . The largest differences in that year were found in the 3-way trial between the adenotonsillectomy group and the control group : mean annual rate of episodes of acute otitis media , 1.4 vs 2.1 ( P<.001 ) ; and mean estimated percentage of time with otitis media , 18.6 % vs 29.9 % ( difference , 11.3 % ; 95 % confidence interval , 4.4%-18.2 % ; P=.002 ) . Perioperative and postoperative complications or other adverse events occurred not infrequently , especially among subjects undergoing adenotonsillectomy ( 14.6 % ) . CONCLUSIONS Our study showed limited and short-term efficacy of both adenoidectomy and adenotonsillectomy ; given the risks , morbidity , and costs of these procedures , these data suggest that neither operation should ordinarily be considered as a first surgical intervention in children whose only indication is recurrent acute otitis media Abstract Objective : To examine whether xylitol , which reduces the growth of Streptococcus pneumoniae , might have clinical importance in the prevention of acute otitis media . Design : A double blind r and omised trial with xylitol administered in chewing gum . Setting : Eleven day care nurseries in the city of Oulu . Most of the children had had problems with recurrent acute otitis media . Subjects : 306 day care children : 149 children in the sucrose group ( 76 boys ; mean ( SD ) age 4.9 ( 1.5 ) years ) and 157 in the xylitol group ( 80 boys ; 5.0 ( 1.4 ) years ) . Intervention : Either xylitol ( 8.4 g a day ) or sucrose ( control ) chewing gum for two months . Main outcome measures : The occurrence of acute otitis media and antimicrobial treatment received during the intervention and nasopharyngeal carriage of S pneumoniae . Results : During the two month monitoring period at least one event of acute otitis media was experienced by 31/149 ( 20.8 % ) children who received sucrose compared with 19/157 ( 12.1 % ) of those receiving chewing gum containing xylitol ( difference 8.7 % ; 95 % confidence interval 0.4 % to 17.0 % ; P = 0.04 ) . Significantly fewer antimicrobials were prescribed among those receiving xylitol : 29/157 ( 18.5 % ) children had at least one period of treatment versus 43/149 ( 28.9 % ) ( difference 10.4 % ; 0.9 % to 19.9 % ; P = 0.032 ) . The carriage rate of S pneumoniae varied from 17.4 % to 28.2 % with no difference between the groups . Two children in the xylitol group experienced diarrhoea , but no other adverse effects were noted among the xylitol users . Conclusion : Xylitol seems to have a preventive effect against acute otitis media . Key messages It also inhibits the growth of S pneumoniae When given to children with recurrent otitis mediain chewing gum xylitol reduced the occurrence of otitis media by about 40 % The daily dose required is not known , but 8.4 g given daily in a chewing gum seems to be effective Xylitol had no effect on the nasopharyngeal car- riage of OBJECTIVES To evaluate the effectiveness of a xylitol pediatric topical oral syrup to reduce the incidence of dental caries among very young children and to evaluate the effect of xylitol in reducing acute otitis media in a subsequent study . DESIGN Double-blind r and omized controlled trial . SETTING Communities in the Republic of the Marshall Isl and s. PARTICIPANTS One hundred eight children aged 9 to 15 months were screened , and 100 were enrolled . Intervention Children were r and omized to receive xylitol topical oral syrup ( administered by their parents ) twice a day ( 2 xylitol [ 4.00-g ] doses and 1 sorbitol dose ) ( Xyl-2 x group ) or thrice per day ( 3 xylitol [ 2.67-g ] doses ) ( Xyl-3x group ) vs a control syrup ( 1 xylitol [ 2.67-g ] dose and 2 sorbitol doses ) ( control group ) . MAIN OUTCOME MEASURES The primary outcome end point of the study was the number of decayed primary teeth . A secondary outcome end point was the incidence of acute otitis media for reporting in a subsequent report . RESULTS Ninety-four children ( mean [ SD ] age , 15.0 [ 2.7 ] months at r and omization ) with at least 1 follow-up examination were included in the intent-to-treat analysis . The mean ( SD ) follow-up period was 10.5 ( 2.2 ) months . Fifteen of 29 of the children in the control group ( 51.7 % ) had tooth decay compared with 13 of 32 children in the Xyl-3x group ( 40.6 % ) and eight of 33 children in the Xyl-2x group ( 24.2 % ) . The mean ( SD ) numbers of decayed teeth were 1.9 ( 2.4 ) in the control group , 1.0 ( 1.4 ) in the Xyl-3x group , and 0.6 ( 1.1 ) in the Xyl-2x group . Compared with the control group , there were significantly fewer decayed teeth in the Xyl-2x group ( relative risk , 0.30 ; 95 % confidence interval , 0.13 - 0.66 ; P = .003 ) and in the Xyl-3x group ( 0.50 ; 0.26 - 0.96 ; P = .04 ) . No statistical difference was noted between the 2 xylitol treatment groups ( P = .22 ) . CONCLUSION Xylitol oral syrup administered topically 2 or 3 times daily at a total daily dose of 8 g was effective in preventing early childhood caries BACKGROUND The decision to seek medical advise for children during upper respiratory infections is largely based on the parental assumption that the child 's symptoms are related to acute otitis media . The symptoms related to acute otitis media , however , are considered nonspecific . METHODS Altogether 857 healthy day-care children ( mean age , 3.7 years ) were followed up for 3 months , and the symptoms of each child were compared during upper respiratory infections with and without acute otitis media . RESULTS A total of 138 children had upper respiratory infections with and without acute otitis media . The symptom with the strongest association with acute otitis media was earache [ relative risk ( RR ) , 21.3 ; 95 % confidence intervals ( CI ) , 7.0 to 106 , P < 0.0001 ] but sore throat ( RR = 3.2 ; CI = 1.1 to 11 ; P = 0.027 ) , night restlessness ( RR = 2.6 ; CI = 1.1 to 6.9 ; P = 0.024 ) and fever ( RR = 1.8 ; CI = 1.1 to 3.2 ; P = 0.025 ) also had significant associations . Logistic regression analysis showed 71 % of the cases to be correctly diagnosed on the basis of the symptoms of earache and night restlessness . The parents were able to predict the presence of acute otitis media with a sensitivity and specificity of 71 and 80 % , respectively ( positive predictive value , 51 % ; negative predictive value , 90 % ) . CONCLUSIONS Despite the limited value of symptoms in differentiating acute otitis media from upper respiratory infection , the parents are able to predict acute otitis media somewhat reliably . More symptoms than have been reported earlier appeared to be associated with acute otitis media OBJECTIVE Xylitol , given as 2 g orally five times-a-day , significantly reduces the incidence of acute otitis media ( AOM ) in children . A less frequent dosing schedule , if tolerable and efficacious , would promote the more widespread use of this treatment . We sought to determine the tolerability and acceptability in young children of oral xylitol solution at doses of 5 g three times-a-day ( TID ) and 7.5 g once daily ( QD ) . METHODS The study was a 3-month r and omized placebo-controlled trial of the tolerability and acceptability of oral xylitol solution in 120 children 6 - 36 months of age performed in the SCOR Network . RESULTS Study withdrawals and unscheduled medical visits for gastrointestinal complaints did not differ significantly among the study groups . The proportions of subjects in the xylitol TID group who experienced excessive gas or diarrhea at months 1 , 2 , and 3 were 22.7 % , 10.0 % , and 14.3 % , respectively , and in the xylitol QD group were 27.3 % , 17.4 % , and 14.3 % , respectively , and these did not differ from the placebo groups . The proportions who accepted the study solution easily or with only minor difficulty at 1 , 2 , and 3 months in the xylitol TID group were 77.3 % , 90.0 % , and 90.5 % and in the xylitol QD group , 77.3 % , 82.6 % , and 90.5 % , respectively . CONCLUSIONS Oral xylitol solution at dosages of 5 g TID and 7.5 g QD is well-tolerated by young children . Given the potential for xylitol as a safe , inexpensive option for AOM prophylaxis , clinical trials using these dosages of xylitol can be conducted OBJECTIVE As regular administration of xylitol had been effective in preventing acute otitis media ( AOM ) in children , we tested whether xylitol administered only at times of acute respiratory infection ( ARI ) reduces the occurrence of AOM . METHODS Healthy children ( N = 1277 ) were recruited from child care centers and r and omized after screening with tympanometry to receive either control mixture ( n = 212 ) , xylitol mixture ( n = 212 ) , control chewing gum ( n = 280 ) , xylitol chewing gum ( n = 286 ) , or xylitol lozenges ( n = 287 ) during an ARI . The trial was r and omized and double blinded within the mixture and chewing gum groups . The parents began administering the products to their children at the onset of symptoms of ARI . The follow-up lasted until resolution of the symptoms or up to 3 weeks . RESULTS A total of 1253 of the 1277 r and omized children were eligible for the analysis . Altogether , 980 ( 78 % ) of 1253 children had at least 1 episode of ARI during the 4 months that the trial lasted . The occurrence of AOM during this episode was 34 ( 20.5 % ) of 166 in the xylitol mixture group , as compared with 32 ( 20.4 % ) of 157 among the children who received the control mixture . Among the older children who received control chewing gum , xylitol chewing gum , or xylitol lozenges , AOM was experienced by 24 ( 11.0 % ) of 218 , 31 ( 14.1 % ) of 220 , and 34 ( 15.5 % ) of 219 , respectively . None of the differences between the groups was statistically significant . CONCLUSIONS Xylitol administered only during an ARI was ineffective in preventing AOM Background : Xylitol administered regularly 5 times a day after each meal is successful in preventing acute otitis media ( AOM ) in children , but if given only during respiratory infections it is ineffective against AOM . To find a more convenient dosing regimen , we tested whether xylitol administered 3 times a day reduces the occurrence of AOM . Methods : In this 3-month r and omized , double-blind trial , 663 healthy day care children were r and omized to receive either a control product ( n = 331 ) or xylitol ( n = 332 ) . Xylitol was given in chewing gum or in a mixture 3 times a day , the daily dose being 0.5 g in the control group and 9.6 g in the xylitol group . The occurrence of the first AOM diagnosed during any period of respiratory symptoms during the follow-up was the main outcome measure . Results : At least one AOM episode was diagnosed in 98 of the 331 children who received control products ( 30 % ) and in 94 of the 332 who received xylitol products ( 28 % ) . A total of 142 episodes of AOM were diagnosed in the control group compared with 156 in the xylitol group . The differences were not statistically significant . Conclusions : Xylitol given regularly 3 times a day for 3 months during the respiratory infection season failed to prevent AOM Many studies have shown the effects of chewing xylitol gum on mutans streptococci ( MS ) over short- and long-term periods in children ; however , few studies have addressed long-term periods in adults . The objective of this investigation was to examine for 6 months the effects of chewing xylitol gum on MS in saliva and plaque in 127 adults ( mean age 28.0 years ) . The participants were assigned to three groups according to gum type , in part taking preference for flavor into account and in part at r and om : xylitol ( XYL ) , maltitol ( MAL ) and control ( CR ) ; 33 , 34 and 27 subjects in each group , respectively , completed the trial . Daily gum use of the XYL and MAL groups was 7.9 and 7.1 g , respectively . MS levels , which declined significantly in saliva ( p < 0.05 ) and plaque ( p < 0.001 ) in the XYL group after 6 months , exhibited a significant increase in plaque in the MAL group ( p < 0.001 ) . Differences in relative changes of MS levels in plaque during the experimental period were significant between the XYL group and the CR ( p < 0.05 ) and MAL groups ( p < 0.001 ) . Differences in relative change of amount of plaque during the experimental period were not statistically significant between the groups . The present study demonstrated that chewing xylitol gum for 6 months continued to inhibit the growth of mutans streptococci in adults BACKGROUND Acute otitis media ( AOM ) is the main reason for physician visits and antibiotic prescriptions in children . Pediatricians ( Peds ) are gatekeepers for services and sources of information for families . The 2004 American Academy of Pediatrics/American Academy of Family Physicians ( AAP/AAFP ) Clinical Practice Guideline : Diagnosis and Management of Acute Otitis Media recommended preventative and management measures for Peds ' practice . Treatments for AOM ( antimicrobial therapy and surgery ) sometimes have question able effectiveness , risks , and high costs . Thus , Peds should consider using prophylactics for AOM that are easy to administer , cost-effective , and have minimal side effects . Xylitol , a naturally occurring sugar alcohol , is widely used to prevent AOM and for other health conditions in Europe , and as a dental caries prophylaxis in the United States . It would be helpful to know Peds ' attitudes and practice s to identify barriers to xylitol 's use as a prophylaxis for AOM in the United States . PURPOSE To conduct a national survey of Peds in the United States to evaluate how closely they adhered to the AAP/AAFP guideline , and their knowledge and opinions about xylitol use . RESEARCH DESIGN A r and omized , national postal survey . METHOD A 48-item question naire developed for this study was mailed to a r and om sample of 506 Peds within the United States during spring 2009 . It assessed Peds ' demographics , adherence to the guideline , and knowledge and opinions about and use of xylitol as a prophylaxis for AOM in children . RESULTS The question naire response rate was 22 % ( 98 useable/506 mailed - 63 returned undeliverable ) . Participants were about equal for gender , and almost all were in private practice for over 10 yr . Most had pediatric patients with at least one bout of AOM annually . The majority adhered to the guideline ( e.g. , almost all routinely assessed and managed patients ' pain for AOM and encouraged prevention by recommending that families reduce risk factors ) . Most used and were comfortable with otoscopy for diagnosing AOM , but not tympanometry . Almost all believed that conductive hearing loss could hinder speech- language and academic development , and AOM could reduce quality of life of children . They also believed that those under 6 mo of age with AOM should receive antibacterial therapy beginning with amoxicillin but did not use complementary and alternative medicine ( CAM ) . Only about half knew about medical uses for xylitol , but of those , most were aware of its use in chewing gum to prevent AOM but had not used it with patients . They were not sure of xylitol 's effectiveness or appropriate dosages but cited stomach cramping and diarrhea as possible side effects . Most would use xylitol if evidence supported it and wanted information about it via reprints or electronically . Few agreed that audiologists are important in diagnosing/managing AOM . CONCLUSIONS Most of these Peds adhered to the AAP/AAFP guideline . They were not using CAMs like xylitol for preventing AOM in children . Future research should focus on prevention and the use of xylitol as a possible prophylaxis regimen for AOM in patients Background . Xylitol , a commonly used sweetener , is effective in preventing dental caries . As it inhibits the growth of pneumococci , we evaluated whether xylitol could be effective in preventing acute otitis media ( AOM ) . Design . Altogether , 857 healthy children recruited from day care centers were r and omized to one of five treatment groups to receive control syrup ( n = 165 ) , xylitol syrup ( n = 159 ) , control chewing gum ( n = 178 ) , xylitol gum ( n = 179 ) , or xylitol lozenge ( n = 176 ) . The daily dose of xylitol varied from 8.4 g ( chewing gum ) to 10 g ( syrup ) . The design was a 3-month r and omized , controlled trial , blinded within the chewing gum and syrup groups . The occurrence of AOM each time the child showed any symptoms of respiratory infection was the main outcome . Results . Although at least one event of AOM was experienced by 68 ( 41 % ) of the 165 children who received control syrup , only 46 ( 29 % ) of the 159 children receiving xylitol syrup were affected , for a 30 % decrease ( 95 % confidence interval [ CI ] : 4.6%–55.4 % ) . Likewise , the occurrence of otitis decreased by 40 % compared with control subjects in the children who received xylitol chewing gum ( CI : 10.0%–71.1 % ) and by 20 % in the lozenge group ( CI : −12.9%–51.4 % ) . Thus , the occurrence of AOM during the follow-up period was significantly lower in those who received xylitol syrup or gum , and these children required antimicrobials less often than did controls . Xylitol was well tolerated . Conclusions . Xylitol sugar , when given in a syrup or chewing gum , was effective in preventing AOM and decreasing the need for antimicrobials BACKGROUND Treatment of acute otitis media ( AOM ) differs worldwide . The Dutch avoid antimicrobials unless fever and pain persist ; the British use them for 5 to 7 days , and Americans use them for 10 days . If effects of therapies are to be compared , it is necessary to evaluate rates of risk factors , severity of attacks , and their influence on treatment decisions . We wanted to compare the prevalence of risk factors for AOM and evaluate their association with severity of attacks and of severity with antimicrobial treatment . METHODS We undertook a prospect i ve cohort study of 2,165 patients with AOM enrolled by primary care physicians ; 895 were enrolled from North America , 571 were enrolled from the United Kingdom , and 699 were enrolled from The Netherl and s. The literature was search ed using the key words " acute otitis media , " " severity , " and " international comparisons . " RESULTS The prevalence of several AOM risk factors differs significantly among patients from the three country networks ; these factors include race , parent smoking habits , previous episodes , previous episodes without a physician visit , tonsillectomy or adenoidectomy , frequency of upper respiratory tract infections , day care , and recumbent bottle-feeding . Dutch children have the most severe attacks as defined by fever , ear discharge , decreased hearing during the previous week , and moderate or severe ear pain . In country-adjusted univariate analyses , increasing age , exposure to tobacco smoke , day care , previous attacks of AOM , previous attacks without physician care , past prophylactic antimicrobials , ear tubes , adenoidectomy , and tonsillectomy all contribute to severity . Only country network , age , history of AOM , previous episode without physician care , and history of adenoidectomy and tympanostomy tubes are independently related to increased severity , while current breast-feeding is protective . Severity of attacks influences treatment decisions . Dutch children are least likely to receive antimicrobials , and even for severe attacks the British and Dutch physicians usually use amoxicillin or trimethoprim-sulfa ; North American children with severe attacks are more likely to receive a broad-spectrum second-line antimicrobial . CONCLUSION Dutch children have the highest ratings in all severity measures , possibly reflecting parental decisions about care seeking for earaches . When comparing groups of patients with AOM , it is necessary to adjust for baseline characteristics . Severity of episode affects physician treatment decisions . Adoption of Dutch guidelines restricting use of antimicrobials for AOM in the United States could result in annual savings of about $ 185 million Background : Watchful waiting management of nonsevere acute otitis media ( AOM ) can reduce the use of antibiotics , but it requires a reliable means of assessing clinical severity . Objective : We present the development of a pocket AOM card with which the clinician can rapidly assess total AOM severity . Design / Methods : The components of the pocket card consisted of a faces scale , to assess parent perception of severity , and a st and ard set of tympanic membrane photographs , with which the pediatrician can grade the severity of tympanic membrane inflammation . The components of the pocket card were tested for validity , reliability and responsiveness with the use of data from parents , pediatricians and pediatric otolaryngologists . Statistics : Instruments were assessed for concurrent correlation , sequence validity and reliability against previously published question naires with the use of Spearman correlation . Responsiveness was calculated with the use of enrollment , day 12 and day 30 data from a r and omized clinical trial . Results : The components of the pocket AOM card demonstrated excellent sequence validity , concurrent correlation and reliability ( r = 0.58–0.99 ) . Total AOM card severity , consisting of the sum of the 2 scales , demonstrated better responsiveness to change than any of the scales taken individually . Conclusions : The AOM card combines a parent assessment of symptoms and the clinician assessment of the tympanic membrane to provide an assessment of total AOM severity that can be used to facilitate shared decision making between parent and clinician . The combined score of the AOM card was more responsive to change than any of the instruments used alone . The AOM card provides a useful tool for teaching and research BACKGROUND Acute otitis media ( AOM ) is one of the most common acute bacterial infection in childhood and also the most frequent reason for outpatient antibiotic therapy . Little recent information about susceptibility patterns of AOM bacterial pathogens in Turkish children has been reported . OBJECTIVE To determine the bacterial etiology of acute otitis media in children and to compare the efficiency of 3 days course of azithromycin with a 10 days course of amoxicillin-clavulanate . METHODS This prospect i ve , single blind , r and omised comparative study was carried out in 180 children with AOM . Paracentesis was performed for middle ear fluid culture before the first dose antibiotic therapy . Children with acute otitis media were r and omised to receive either low dose amoxicillin-clavulanate ( 45/6.4 mg/kg/day in two divided doses for 10 days ) or low dose azithromycin ( 10mg/kg/day for 3 days ) . Clinical response was assessed on days 2 - 4 , 11 - 13 , 26 - 28 . RESULTS Bacterial pathogens were isolated from 108 ( 60 % ) of 180 children . Streptococcus pneumoniae was the most common isolated pathogen ( 39.7 % ) , followed by Haemophilus influenzae ( 20.7 % ) , Moraxella catarrhalis ( 15.5 % ) , Staphylococcus aureus ( 13.8 % ) , Group A beta-hemolytic streptococcus ( 5.1 % ) , Escherichia coli ( 3.4 % ) and Enterococcus faecalis ( 1.7 % ) . This study demonstrated low resistance rates compared to studies of different countries . Although clinical response rates were better in patients treated with amoxicillin-clavulanate , this was not statistically significant [ 86.6 % ( 78 of 90 ) ] versus [ 95.2 % ( 80 of 84 ) ] . Success rates of amoxicillin-clavulanate were high for both S. pneumoniae and H. influenzae . Difference between success rates was not statistically significant ( P=0.144 and 0.352 ) . CONCLUSIONS Bacteria were isolated in 60 % of AOM cases . The clinical efficiency of amoxicillin-clavulanate was found to be equal compared to azithromycin in children with acute otitis media |
1,127 | 29,947,755 | There is moderate-to-high quality of evidence that reminders have a positive effect on OH and adherence to appointments in orthodontic patients .
These effects were demonstrated in the short- and long-term . | BACKGROUND Reminders are implemented in healthcare services to increase compliance with treatment and to decrease the rate of failed appointments .
Their effects in the provision of orthodontic care are not yet fully understood .
OBJECTIVES The main objectives of this review were to assess the effectiveness of reminder systems in improving oral hygiene ( OH ) and adherence to appointments in orthodontic patients . | Objective : To test the effectiveness of different systems of reminding patients about their appointments in order to reduce the rate of failed attendance . The expense in implementing a reminder system for patients was also estimated . Design : A clinical study in a single-h and ed dental practice .Subjects : Patients were reminded about their appointment using either postal , manual telephone or automated telephone reminders ( or all three combined ) . A control group received no reminders . 500 patient attendances were recorded in each group . Results : Patients failed to attend for 130 of the 2500 appointments considered in the study . There was a significant reduction in the failed attendance rate from 9.4 % ( with no reminder ) to a minimum of 3 % when a reminder was given to the patient before the appointment . However , there was no significant difference among the four reminder test groups , indicating that the form of the reminder made no difference to the failure rate . Conclusions : Reminding patients using postal or manual telephone techniques is effective at improving attendance . All of the reminder methods , telephone and postal , provided net cost savings rather than additional Background Several studies have recently demonstrated that a post-treatment communication to explain the importance of an oral hygiene can improve the orthodontic patients ’ compliance over a period of 66 days . The main goal of this study is to evaluate the effects of a structured follow-up communication after orthodontic appliance application on oral hygiene compliance after 30–40 days . Methods Eighty-four orthodontic participants enrolled from patients who were beginning fixed orthodontic treatment at the Orthodontic Department , Gaslini Hospital , Genova , between July and October 2014 were r and omly assigned to one of three trial arms . Before the bonding , all patients underwent a session of oral hygiene aim ed at obtaining an plaque index of “ zero . ” At the following orthodontic appointment , the plaque index was calculated for each patient in order to assess oral hygiene compliance . The first group served as control and did not receive any post-procedure communication , the second group received a structured text message giving reassurance , and the third group received a structured telephone call . Participants were blinded to group assignment and were not made aware that the text message or the telephone call was part of the study . ( The research protocol was approved by the Italian Comitato Etico Regionale della Liguria-sezione 3^ c/o IRCCS-Istituto G. Gaslini 845/2014 , and it is not registered in the trial ’s register . ) Results Thirty patients were r and omly assigned to the control group , 28 participants to the text message group , and 26 to the telephone group . Participants who received a post-treatment communication reported higher level of oral hygiene compliance than participants in the control group . The plaque index was 0.3 ( interquartile range ( Iqr ) , 0.60 ) and 0.75 ( Iqr , 1.30 ) , respectively , with a significant difference ( P = 0.0205 ) . Conclusions A follow-up procedure after orthodontic treatment may be an effective tool to increase oral hygiene compliance also over a short period OBJECTIVE To evaluate the influence of an app-based approach in a protocol for domestic oral hygiene maintenance in a group of adolescent patients wearing fixed multibracket appliances . MATERIAL S AND METHODS Eighty adolescent patients scheduled to start an orthodontic multibracket treatment were r and omly divided into two groups of 40 . Plaque index ( PI ) , gingival index ( GI ) , white spots ( WS ) , and caries presence were recorded in all patients , and they were instructed regarding domestic oral hygiene maintenance on the day of braces application ( t0 ) and every 3 months ( t1 , t2 , t3 , t4 ) during the first year of treatment . Study group ( SG ) patients were enrolled in a WhatsApp chat room-based competition and instructed to share monthly with the other participants two self-photographs ( selfies ) showing their oral hygiene status . RESULTS SG patient participation in the chat room was regular and active throughout the observation period . At t2 , t3 , and t4 , SG patients had significantly lower values of both PI and GI and a lower incidence of new WS and caries , compared with the control group . CONCLUSION Integration of new " social " technologies in a st and ard oral hygiene motivation protocol is effective in improving compliance of adolescent patients and in improving their oral health status during orthodontic multibracket treatment OBJECTIVE To determine if text message reminders regarding oral hygiene compliance have an influence on the level of compliance within an orthodontic population . MATERIAL S AND METHODS In this prospect i ve , r and omized , controlled clinical trial , 42 orthodontic patients were assigned to a text message or control group . Parents of patients assigned to the text message group received a reminder text message one weekday each week . Oral hygiene compliance was measured using bleeding index ( BI ) , modified gingival index ( MGI ) , and plaque index ( PI ) , and visual examination of white spot lesion ( WSL ) development at baseline ( T0 ) , two appointments after baseline ( T1 ) , and four appointments after baseline ( T2 ) . RESULTS BI , MGI , and PI scores were significantly lower in the text message group than in the control group at T2 . CONCLUSION A text message reminder system is effective for improving oral hygiene compliance in orthodontic patients Background Telephone or text-message reminders have been shown to significantly reduce the rate of missed appointments in different medical setting s. Since text-messaging is less re source -dem and ing , we tested the hypothesis that text-message reminders would be as effective as telephone reminders in an academic primary care clinic . Methods A r and omized controlled non-inferiority trial was conducted in the academic primary care division of the Geneva University Hospitals between November 2010 and April 2011 . Patients registered for an appointment at the clinic , and for whom a cell phone number was available , were r and omly selected to receive a text-message or a telephone call reminder 24 hours before the planned appointment . Patients were included each time they had an appointment . The main outcome was the rate of unexplained missed appointments . Appointments were not missed if they were cancelled or re-scheduled before or independently from the intervention . We defined non-inferiority as a difference below 2 % in the rate of missed appointments and powered the study accordingly . A satisfaction survey was conducted among a r and om sample of 900 patients ( response rate 41 % ) . Results 6450 patients were included , 3285 in the text-message group and 3165 in the telephone group . The rate of missed appointments was similar in the text-message group ( 11.7 % , 95 % CI : 10.6 - 12.8 ) and in the telephone group ( 10.2 % , 95 % CI : 9.2 - 11.3 p = 0.07 ) . However , only text message reminders were cost-effective . No patient reported any disturbance by any type of reminder in the satisfaction survey . Three quarters of surveyed patients recommended its regular implementation in the clinic . Conclusions Text-message reminders are equivalent to telephone reminders in reducing the proportion of missed appointments in an academic primary care clinic and are more cost-effective . Both types of reminders are well accepted by patients PURPOSE This prospect i ve longitudinal study compared the patterns of oral health behaviors between low and high socioeconomic status ( SES ) families participating in the Iowa Fluoride Study for a period of 9 years . METHODS Information on oral health behaviors , including consumption of juices/juice drinks , soda pop , and powder-based drinks , dental visits , and tooth-brushing frequency , was collected longitudinally at periodic intervals from 6 to 108 months of age . Dental exams were conducted at 5 and 9 years of age . Classification of low socioeconomic status ( SES ; n=70 ) and high-SES ( n= 128 ) children was based on baseline family income and mothers ' education levels , with middle SES excluded . RESULTS Low SES children consistently had significantly greater consumption of soda pop and powder-based beverages . There were , however , virtually no differences at any time point between groups in : ( 1 ) tooth-brushing frequency ; ( 2 ) use of dentifrice ; or ( 3 ) fluoride concentration in drinking water . Furthermore , the mean number of decayed and filled surfaces was significantly higher in the low-SES group . CONCLUSIONS Results suggest that beverage consumption patterns are a key difference between high- and low-socioeconomic status families and could in part explain differences in caries experience between subjects of different SES . Modification of the pattern of soda pop and powder-based beverage consumption in the low-SES groups might reduce their caries experience OBJECTIVE To investigate the effects on plaque index ( PI ) scores of manual or electric toothbrush with or without repeated oral hygiene instructions ( OHI ) and motivation on patients wearing fixed orthodontic appliances . MATERIAL S AND METHODS One month after the orthodontic fixed appliance bonding on both arches , 60 patients were r and omly assigned to four groups ; groups E1 ( n = 15 ) and E2 ( n = 15 ) received a powered rotating-oscillating toothbrush , and groups M1 ( n = 15 ) and M2 ( n = 15 ) received a manual toothbrush . Groups E1 and M1 received OHI and motivation at baseline ( T0 ) and after 4 , 8 , 12 , 16 , and 20 weeks ( T4 , T8 , T12 , T16 , and T20 , respectively ) by a Registered Dental Hygienist ; groups E2 and M2 received OHI and motivation only at baseline . At each time point a blinded examiner scored plaque of all teeth using the modified Quigley-Hein PI . RESULTS In all groups the PI score decreased significantly over time , and there were differences among groups at T8 , T12 , T16 , and T20 . At T8 , PI scores of group E1 were lower than those of group E2 , and at T12 , T16 , and T20 , PI scores of groups M1 and E1 were lower compared to those of groups M2 and E2 . A linear mixed model showed that the effect of repeated OHI and motivation during time was statistically significant , independently from the use of manual or electric toothbrush . CONCLUSIONS The present results showed that repeated OHI and motivation are crucial in reducing PI score in orthodontic patients , independent of the type of toothbrush used 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 INTRODUCTION Fixed orthodontic treatment is frequently associated with increased plaque accumulation leading to gingivitis and white spot lesions ( WSLs ) . AIM This study evaluated the role of text message reminder on oral hygiene of orthodontic patients . MATERIAL S AND METHODS A total of 60 patients under fixed orthodontic treatment were r and omly divided into two equal groups as control group and study ( text message ) group . Text message group received reminders about oral hygiene , while the control group did not receive any messages . Oral hygiene of both the groups was evaluated at baseline , 2 , and 3 months using plaque indices ( PIs ) along with WSL status . Data were statistically analyzed using Statistical Package for the Social Sciences ( SPSS ) statistical software , version 19 , with chi-square test and t-test . RESULTS At the baseline , plaque score was higher in the study group over control group ( p > 0.038 ) , whereas it was decreased after 3 months in the test group ( p > 0.001 ) . For WSL , there was no significant difference at baseline , but it was significantly lower in study group ( p > 0.003 ) . CONCLUSION Oral hygiene status improved with text message reminder Objectives To evaluate the effect of issuing a patient reminder plus a confirmation slip on the attendance of orthodontic new patients . Setting Department of Orthodontics , University Dental Hospital of Manchester . Design A r and omised controlled trial . Method New patients were r and omly allocated to : receive a reminder letter and return a confirmation slip ornot receive a reminder . Outcome measures Patient attendance at the clinic . Results A total of 232 patients were entered into the study between June 18 , 2001 and August 29 , 2001 . These were r and omly allocated to 115 ( 49.8 % ) in the reminder group and 116 ( 50.2 % ) in the no reminder group . If the patient received a reminder and returned the confirmation they were less likely to fail the appointment than if they did not receive a reminder ( OR 0.4 , 95 % CI 0.2 to 0.96 ) There was an effect of social deprivation , if the patients lived in an area of high social deprivation they were 2.7 ( 95 % CI 1.1 to 6.5 ) times more likely to fail to attend an appointment than people who were more affluent . Conclusions The use of postal reminders for orthodontic consultation appointments appears to result in a useful increase of appointments that are kept or cancelled in advance BACKGROUND The aim of this study was to retest the hypotheses of Reekie and Devlin ( 1998 ) by conducting a similar r and omized controlled trial in an orthodontic clinic in the Netherl and s. It was hypothesized that a reminder would reduce the failed attendance rate and that the form of the reminder would be irrelevant . METHODS All patients with appointments in the orthodontic clinic at the Academic Centre of Dentistry Amsterdam during a 3-week period were divided into 4 groups . Three groups received a reminder 1 day before the appointment , either by telephone , mail , or short message service ( SMS , a service used to send and receive short text messages to and from cell phones ) . A control group did not receive a reminder . In a follow-up study , r and om sub sample s in each group were interviewed by telephone . Subjects were asked how they felt about receiving a reminder and which reminder they preferred . RESULTS The hypothesis that a reminder would reduce the failed attendance rate was not confirmed . Also , no differences were found between the 4 conditions , indicating that the form of the reminder is irrelevant . However , most of the interviewed participants felt positive or very positive about receiving a reminder . There was a significant preference for a reminder by mail ( 56.3 % ) , followed by a telephone reminder ( 26.0 % ) and a reminder by SMS ( 17.7 % ) . No less than 20 % of the interviewed participants felt negative or very negative about the reminders and considered them to be a waste of time and money . CONCLUSIONS The hypothesis that reminders are useful in the prevention of failed appointments was not confirmed . This study underlines the importance of replication studies . It demonstrates that every research result , whether it is generated by evidence -based or tradition-based research , should be interpreted with care and should be replicated in other studies before the results can be generalized Objective To investigate the effect of using mobile applications active reminders to improve oral hygiene in comparison to verbal oral hygiene instructions . Design Two-arm parallel r and omised controlled trial . Setting orthodontic clinics at two branches of a university hospitals of the college of dentistry of Riyadh Colleges of Dentistry and Pharmacy , Riyadh , Saudi Arabia . Participants Forty-four 12-year-old and older subjects . Method Subjects undergoing orthodontic treatment with fixed appliances were r and omly assigned to one of two groups using simple r and omisation . Group I : subjects received a mobile application that sends active reminders of oral hygiene three times a day ( n = 22 ) . Group II : subjects received verbal oral hygiene instructions verbally during their routine orthodontic visits ( n = 22 ) . Two primary outcomes were assessed using plaque index ( PI ) and gingival index ( GI ) for Ramfjord teeth to evaluate the level of oral hygiene at baseline and after 4 weeks . Results Mean differences for PI and GI for group I were reduced from T1 to T2 ( P < 0.05 , P < 0.05 ) but did not significantly change for group II ( P > 0.05 , P > 0.05 ) . Both PI and GI significantly reduced for group I compared to group II between T1 and T2 ( P < 0.05 , P < 0.05 ) . Conclusions PI and GI all significantly decreased after 4 weeks of using active reminders of oral hygiene instructions on mobile application compared to verbal oral hygiene instructions . The study was registered at clinical trials.gov with number : NCT03109769 OBJECTIVE To investigate whether text message reminders regarding oral hygiene have an effect on plaque removal in orthodontic patients . MATERIAL S AND METHODS In this r and omized , controlled clinical trial , 50 orthodontic patients were assigned to either a text message or control group . Patients in the text message group received 12 text messages over the course of 4 weeks and one text message for 8 weeks thereafter . Photos were taken at baseline ( T0 ) , at 4 weeks after baseline ( T1 ) , and at 12 weeks after baseline ( T2 ) . For each subject , photos of eight teeth were taken and then the area of the tooth and amount of plaque were measured using planimetry . RESULTS There was a statistically significant difference in plaque coverage between baseline and both T1 and T2 in the text message group as measured using planimetry . This was demonstrated by comparing the average measurements of the control group and the treatment group . CONCLUSION This study demonstrated that the use of automated text message reminders sent from an orthodontic office was effective in improving oral hygiene compliance in orthodontic patients Objectives This study aims to determine the effectiveness of a messaging app ( WeChat ) in improving patients ’ compliance and reducing the duration of orthodontic treatment ( DOT ) . Material s and methods A r and omized controlled trial was performed in a dental hospital and a clinic from August 2012 to May 2015 . Orthodontic patients were included at the beginning of treatment . Patients with multiphase treatment or braceless technique were excluded . Participants were r and omized to WeChat group ( received regular reminders and educational messages ) or control group ( received conventional management ) and were followed up until the treatment was completed . Primary outcome measure was DOT . Others were late and failed attendance , bracket bond failure , and oral hygiene condition . Results One hundred twelve patients in each group participated and completed the trial . DOT in WeChat group were 7.3 weeks shorter ( P = 0.007 ) . There were less failed attendance ( 3.1 vs. 10.9 % , P < 0.001 ) , late attendance ( 20.1 vs. 29.9 % , P < 0.001 ) , and bracket bond failure ( 11.8 vs. 16.1 % , P < 0.001 ) in WeChat group than control . There was no difference in orthodontic plaque index nor modified gingivitis index between the two groups before and after treatment . Number of failed attendances was identified as an independent factor affecting DOT ( P = 0.004 ; HR = 0.89 , 95 % CI 0.84 to 0.95 ) . Conclusions The intervention with WeChat is effective in reducing the treatment duration and bracket bond failure , and improving the attendance in orthodontic patients . Clinical relevance DOT can be reduced by improving patient ’s compliance . The messaging app is useful for outpatient education and management Failures in the bonding of dental bracket are a big concern for orthodontists . Clinical experience suggests that some patients are more prone than others to experience failures . Therefore , it can be expected that in statistical analysis of orthodontic bracket failures , the usual assumption of independence between the observations is violated . An approach to overcome this problem is to apply the frailty model , in which the association between failure times is modelled with a r and om-effect term ( i.e. frailty ) . We postulated that brackets of the same subject share the same frailty , that is , a latent common group effect , due to some unknown or unobserved covariates . The aim of this study was to investigate possible risk factors related to bracket failure using Cox proportional hazards model with a shared frailty term and to compare the results with those obtained using a basic Cox proportional hazards model . Survival data for 1677 brackets were obtained from a cohort of 54 females ( mean age + /- SD : 13.3+/-4.8 yrs ) and 46 males ( mean age + /-SD : 13.1+/-3.8 yrs ) over a eight-year period . Age , gender , vertical craniofacial morphology and anatomical location of brackets were entered into Cox models as covariates . The findings indicated that bracket failure was significantly affected by tooth position within the dental arch , with the highest failure risk in maxillary posterior region . Age , gender and vertical craniofacial morphology did not affect bracket failure . A Cox proportional hazards model with a shared frailty term represents a useful approach for modelling orthodontic bracket failures OBJECTIVE To evaluate the effectiveness of daily tooth brushing with high-fluoride toothpaste on white spot lesion ( WSL ) formation in adolescents during treatment with fixed orthodontic appliances ( FOA ) . MATERIAL S AND METHODS Four hundred and twenty-four healthy 11- to 16-year-old patients , referred to five Orthodontic Specialist Clinics , were r and omized to use either toothpaste containing 5000 ppm fluoride or regular toothpaste with 1450 ppm fluoride . To be eligible for inclusion , the patients had to be scheduled for bimaxillary treatment with FOA for an expected duration of at least 1 year . The primary and secondary outcome measures were prevalence and incidence of WSL , as registered from digital photos of the maxillary incisors , canines , and premolars taken before onset and immediately after debonding . The photos were evaluated separately by two blinded and calibrated clinicians using a 4-step score . A r and om sample of 50 cases was reassessed to check intra- and interexaminer reliability ( Kappa = 0.70 ; 0.74 ) . RESULTS The use of high-fluoride toothpaste result ed in fewer WSL ( P = 0.042 ) with a prevented fraction of 32 % . The lateral incisor was most commonly affected in both groups . CONCLUSION To prevent WSL during treatment of FOA , daily use of high-fluoride toothpaste may be recommended INTRODUCTION Enamel demineralization and gingival inflammation are the most prevalent consequences of biofilm formation in orthodontics . Our hypothesis was that educating patients about the severe consequences of biofilm accumulation could enhance their oral hygiene while wearing fixed appliances . METHODS This study was design ed as a r and omized controlled 4-arm parallel trial . A total of 148 participants in Chengdu , China , matching the eligibility criteria of 11 to 25 years of age , at least 20 natural teeth , and a treatment plan that included conventional stainless steel brackets , were r and omly assigned to 4 intervention groups based on computer-generated r and om sequencing using simple r and omization without blocking . In group A ( n = 37 ) , the subjects were shown images illustrating the severe consequences of biofilm formation , including enamel demineralization and gingival inflammation ; subjects in group B ( n = 40 ) were given biofilm disclosing tablets ; those in group C ( n = 38 ) received a combination of A and B ; the subjects in group D ( n = 33 ) served as the controls . The investigators were blinded to the allocations , and the research er managing the r and om sequence did not participate in allocation or measurement . All groups received routine oral hygiene instructions . Plaque index and gingival index scores were recorded at each appointment during a 6-month follow-up . RESULTS Eighteen participants were lost during follow-up , result ing in a total of 130 participants after the trial ( group A , 35 ; group B , 32 ; group C , 34 ; group D , 29 ) . No adverse events were recorded . Groups A and C exhibited a significantly lower plaque index scores ( parameter-estimate [ 95 % confidence interval ] = -1.20 [ -1.76 to -0.63 ] for group A , and -1.12 [ -1.69 to -0.56 ] for group C ) and gingival index scores ( -0.13 [ -0.21 to -0.04 ] , and -0.19 [ -0.28 to -0.10 ] ) , respectively , compared with group D ( P < 0.001 for all ) , whereas no significant difference was found between groups B and D , or between groups A and C ( P > 0.05 ) . The adults had significantly lower plaque index ( 0.48 [ 0.13 - 0.84 ] , P < 0.001 ) and gingival index ( 0.06 [ 0.01 - 0.11 ] , P = 0.018 ) scores than did the teenagers , and the female subjects had significantly higher gingival index ( -0.06 [ -0.11 to -0.01 ] , P = 0.040 ) scores than did the male subjects . CONCLUSIONS The use of images showing the severe consequences of biofilm accumulation enhanced the oral hygiene of patients treated with fixed appliances INTRODUCTION Good oral hygiene is a challenge for orthodontic patients because food readily becomes trapped around the brackets and under the archwires , and appliances are an obstruction to mechanical brushing . The purpose of this study was to compare plaque removal efficacy of 3 toothbrush treatments in orthodontic subjects . METHODS This was a replicate-use , single-brushing , 3-treatment , examiner-blind , r and omized , 6-period crossover study with washout periods of approximately 24 hours between visits . Forty-six adolescent and young adult patients with fixed orthodontics from a university clinic in Germany were r and omized , based on computer-generated r and omization , to 1 of 3 treatments : ( 1 ) oscillating-rotating electric toothbrush with a specially design ed orthodontic brush head ( Oral-B Triumph , OD17 ; Procter & Gamble , Cincinnati , Ohio ) ; ( 2 ) the same electric toothbrush h and le with a regular brush head ( EB25 ; Procter & Gamble ) ; and ( 3 ) a regular manual toothbrush ( American Dental Association , Chicago , Ill ) . The primary outcome was the plaque score change from baseline , which we determined using digital plaque image analysis . RESULTS Forty-five subjects completed the study . The differences in mean plaque removal ( 95 % confidence interval ) between the electric toothbrush with an orthodontic brush head ( 6 % [ 4.4%-7.6 % ] ) or a regular brush head ( 3.8 % [ 2.2%-5.3 % ] ) and the manual toothbrush were significant ( P < 0.001 ) . Plaque removal with the electric toothbrush with the orthodontic brush head was superior ( 2.2 % ; P = 0.007 ) to the regular brush head . No adverse events were seen . CONCLUSIONS The electric toothbrush , with either brush head , demonstrated significantly greater plaque removal over the manual brush . The orthodontic brush head was superior to the regular head INTRODUCTION Studies in the dental literature do not yet provide conclusive evidence for the functional and psychosocial benefits of orthodontic treatment . In this cross-sectional study , we aim ed to assess the oral health-related quality of life of young Brazilian adults , aged 18 to 30 years , who had completed orthodontic treatment compared with untreated subjects waiting for treatment . METHODS The subjects were recruited at a state-funded university clinic . The sample comprised 100 patients in the retention phase of orthodontic treatment for more than 6 months ( treated group ) and 100 persons who were seeking orthodontic treatment and were still on a waiting list ( nontreated group ) . Data were collected by using the oral health impact profile , the index of orthodontic treatment need ( malocclusion severity and esthetic impairment ) , the Brazilian economic classification criteria ( socioeconomic status ) , and the index of decayed , missing , and filled teeth ( oral health status ) . Statistical analyses were performed by using chi-square and Fisher exact tests and negative binomial regression . RESULTS The mean oral health impact profile scores were 3.1 ( SD ± 2.99 ) and 15.1 ( SD ± 8.02 ) in the treated and nontreated groups , respectively . The most frequent impacts in the treated and nontreated groups were " painful aching " and " been self-conscious , " respectively . Comparisons between the groups were controlled for malocclusion severity , clinician-assessed esthetic impairment , age , sex , socioeconomic status , and oral health status . Nontreated young adults had mean oral health impact profile scores 5.3 times higher than did the treated subjects . CONCLUSIONS Young Brazilian adults who received orthodontic treatment had significantly better oral health-related quality of life scores in the retention phase , after treatment completion , than did nontreated subjects OBJECTIVES To determine whether a text message reduces the severity of patient self-reported levels of pain and anxiety following initial placement of orthodontic appliances . MATERIAL S AND METHODS Thirty-nine orthodontic patients were r and omly assigned to one of two groups and matched for age , gender , and bracket type ( self-ligating vs conventional ) . The subjects completed baseline question naires to ascertain their levels of pain and anxiety before initiating orthodontic treatment . Following the initial appointment , subjects completed the pain question naire and anxiety inventory at the same time daily for 1 week . One group received a structured text message showing concern and reassurance , while the second group served as a control and received no postprocedural communication . RESULTS There was a statistically significant difference in pain in relation to time between the text message group and the control group as it was demonstrated that demonstrated that compared with the text message group , mean pain intensity increased and selfreported discomfort was longer in the control group . Anxiety was determined to be at its peak the day following initial orthodontic appliance placement and gradually tapered off from that time point . No intergroup difference was noted when analyzing anxiety . CONCLUSIONS This study demonstrated that a text message sent from an orthodontic office following initial appliance placement result ed in a lower level of patient 's self-reported pain . Additionally , patient anxiety is at its peak the day following the initial appointment and decreases from that point forward |
1,128 | 30,120,508 | The effects of oral NSAIDs , COX-2 inhibitors , and opioids in controlling pain were similar to what has been demonstrated in previous literature .
Topical NSAIDs were found to have a greater RC than oral NSAIDs | Objective Pain management is a cornerstone of osteoarthritis ( OA ) management .
The aim of this review is to obtain current , literature -based estimates of the effect of common pharmacologic treatments on pain reduction in OA . | BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) The aim of this study was to verify the clinical responses to Thai massage ( TM ) and Thai herbal compression ( THC ) for treating osteoarthritis ( OA ) of the knee in comparison to oral ibuprofen . This study was a r and omized , evaluator-blind , controlled trial . Sixty patients with OA of the knee were r and omly assigned to receive either a one-hour session of TM or THC ( three times weekly ) or oral ibuprofen ( three times daily ) . The duration of treatment was three weeks . The clinical assessment s included visual analog scale assessing pain and stiffness , Lequesne 's functional index , time for climbing up ten steps , and physician 's and patient 's overall opinions on improvement . In a within-group comparison , each treatment modality caused a significant improvement of all variables determined for outcome assessment s. In an among group comparison , all modalities provided nearly comparable clinical efficacy after a three-week symptomatic treatment of OA of the knee , in which a trend toward greatest improvement was likely to be found in THC group . In conclusion , TM and THC generally provided comparable clinical efficacy to oral ibuprofen after three weeks of treatment and could be considered as complementary and alternative treatments for OA of the knee Objective . Two studies evaluated efficacy and safety of tanezumab versus naproxen for treatment of knee or hip osteoarthritis ( OA ) . Methods . R and omized controlled studies [ NCT00830063 ( Study 1015 , n = 828 ) and NCT00863304 ( Study 1018 , n = 840 ) ] of subjects with hip or knee OA compared intravenous tanezumab ( 5 mg or 10 mg ) to placebo and naproxen ( 500 mg twice daily ) . Co primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) Pain , WOMAC Physical Function ( 0–10 numerical rating scale ) , and patient ’s global assessment of OA at Week 16 . Results . In both studies , tanezumab reduced pain versus placebo [ least squares mean differences , 95 % CI , tanezumab 5 mg : −1.21 ( −1.72 , −0.70 ) ; −1.13 ( −1.65 , −0.62 ) ; tanezumab 10 mg : −0.91 ( −1.42 , −0.40 ) ; −0.80 ( −1.32 , −0.29 ) ] , and improved function and global scores . Tanezumab 5 mg produced greater pain reduction [ −0.76 ( −1.28 , −0.25 ) ; −0.69 ( −1.21 , −0.17 ) ] , and favorable functional and global outcomes versus naproxen . Pain reductions with tanezumab 10 mg versus naproxen did not reach significance , unlike functional ( both studies ) and global ( 1 study ) outcomes ; thus , tanezumab 10 mg was not superior to naproxen , and predefined statistical testing procedures were not met , allowing for conclusion of superiority of tanezumab 5 mg over naproxen despite replicated favorable co primary outcomes . Tanezumab was associated with greater incidence of peripheral sensory adverse events ( paresthesia , hyperesthesia , hypoesthesia , burning sensation ) , pain in extremity , peripheral edema , and arthralgia . Overall frequency and discontinuations as a result of adverse events were similar to placebo and naproxen . Conclusion . Tanezumab provides efficacious treatment of knee or hip OA and may have therapeutic utility in patients with OA who experience inadequate analgesia with nonsteroidal antiinflammatory drugs Purpose Osteoarthritic pain is largely considered to be inflammatory pain . Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis ( OA ) in which the subchondral bone junction is destroyed , and this induces neuropathic pain ( NP ) . Pregabalin was developed as a pain killer for NP ; however , there are no reports on pregabalin use in OA patients . The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients . Material s and Methods Eighty-nine knee OA patients were evaluated in this r and omized prospect i ve study . Patients were divided into meloxicam , pregabalin , and meloxicam+pregabalin groups . Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale ( VAS ) , and Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Pain scales among groups were compared using a Kruskal-Wallis test . Results Before drug application , there was no significant difference in VAS and WOMAC scores among the three groups ( p>0.05 ) . Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1 , 2 , and 4 weeks , and WOMAC score at 4 weeks , compared with the other groups ( p<0.05 ) . No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group ( p>0.05 ) . Conclusion Meloxicam+pregabalin was effective for pain in OA patients . This finding suggests that OA pain is a combination of inflammatory and NP OBJECTIVE To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib . METHODS ; A multicentre , double-blind controlled study in which patients with knee OA and moderate pain were r and omized to one of the six arms : topical ketoprofen 50 or 100 mg in ultradeformable vesicles ( IDEA-033 ) , 2.2 or 4.4 g ketoprofen-free vehicle ( TDT 064 ) , oral celecoxib 100 mg or matching oral placebo , all bd . The primary outcome was change from baseline in the WOMAC pain subscale at week 12 . RESULTS A total of 1395 patients received treatment . Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups . The mean reduction in WOMAC pain score at week 12 was -1.9 ( -40.8 % ) for ketoprofen 50 mg , -1.9 ( -40.9 % ) for ketoprofen 100 mg , -1.9 ( -39.8 % ) for 2.2 g TDT 064 , -1.8 ( -37.8 % ) for 4.4 g TDT 064 , -1.9 ( -40.4 % ) for celecoxib and -1.4 ( -29.3 % ) for oral placebo . IDEA-033 was not statistically superior to TDT 064 . All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib . The most frequent types of treatment-related adverse events reported were gastrointestinal for oral ( 15.9 % for celecoxib ) and dermal for topical applications ( 12.2 % for ketoprofen 100 mg ) . CONCLUSION IDEA-033 was not superior to ketoprofen-free vehicle , but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain . TRIAL REGISTRATION Clinical Trials.gov , http:// clinical trials.gov/ , NCT00716547 OBJECTIVE To evaluate the efficacy and tolerability of aceclofenac , 200 mg/day , and paracetamol , 3000 mg/day , in the treatment of osteoarthritis ( OA ) of the knee . METHODS This was a double-blind , parallel-group , multicentre clinical trial involving patients with symptomatic OA of the knee , conducted in Spain . Patients were r and omly allocated to aceclofenac 100 mg twice daily ( n=82 ) or paracetamol 1000 mg three times daily ( n=86 ) . Patients were assessed at baseline and 6 weeks . Primary efficacy measures were severity of pain ( visual analogue scale , VAS ) , Lequesne OA knee index , and patient 's and physician 's global assessment of disease activity . Severity of knee pain at rest or walking , stiffness , knee swelling and tenderness , and assessment of health-related quality of life ( Health Assessment Question naire , Western Ontario and McMaster Universities Osteoarthritis Index , and Short Form 36 ) were included as secondary endpoints . RESULTS Both treatment groups showed significant improvement compared with their baseline values in the four primary endpoints . Mean between-treatment differences favoured aceclofenac over paracetamol on pain ( VAS , 7.64 mm [ 95 % confidence interval ( CI ) , 0.44 - 14.85 mm ] ) , Lequesne OA index ( 1.41 [ 95 % CI , 0.45 - 2.36 ] ) , and patient 's ( 0.33 [ 95 % CI , 0.06 - 0.61 ] ) and physician 's ( 0.23 [ 95 % CI , 0.01 - 0.47 ] ) global assessment s. Adverse events were similar for both drugs ( paracetamol , 29 % patients vs aceclofenac , 32 % ; P=0.71 ) . Four patients withdrew in each group due to adverse events . Patients tended to prefer aceclofenac to paracetamol ( P=0.001 ) , and more treated with paracetamol withdrew from the study due to lack of efficacy ( n=8 vs n=1 , P=0.035 , for paracetamol and aceclofenac , respectively ) . CONCLUSION At 6 weeks , patients with symptomatic OA of the knee showed a greater improvement in pain and functional capacity with aceclofenac than paracetamol with no difference in tolerability The aim of this 13-week , multicenter , r and omized , double-blind , double-dummy , placebo- and positive-internal (celecoxib)-controlled , parallel-group study was to demonstrate the efficacy , safety , and tolerability of lumiracoxib in primary hip osteoarthritis ( OA ) patients . Eligible patients ( n = 1,262 ; ACR criteria ) were r and omized ( 1:1:1 ) to receive lumiracoxib 100 mg once daily ( o.d . ) ( n = 427 ) , celecoxib 200 mg o.d . ( n = 419 ) , or matching placebo o.d . ( n = 416 ) administered orally . The primary objective was to compare lumiracoxib 100 mg o.d . and placebo with respect to three co- primary efficacy variables : the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 ( WOMAC ™ LK 3.1 ) question naire , the function subscale of the WOMAC ™ LK 3.1 question naire , and patient ’s global assessment of disease activity ( 100-mm visual analog scale ( VAS ) ) after 13 weeks of treatment . Of the 1,262 r and omized patients , 951 completed the study . All r and omized patients were included in the intention-to-treat and safety population s. Lumiracoxib was superior to the placebo ( p < 0.001 ) after 13 weeks for all three co- primary endpoints . By week 13 , the patient ’s global assessment of disease activity ( 100-mm VAS ) improved by 23.3 mm ( ±SD , 27.83 mm ) with lumiracoxib and 13.3 mm ( ±26.71 mm ) with placebo . The WOMAC ™ function score decreased by 10.4 ( ±13.56 ) with lumiracoxib and 6.8 ( ±12.55 ) with placebo . The WOMAC ™ pain scores decreased by 3.4 ( ±4.16 ) with lumiracoxib and 2.2 ( ±3.94 ) with placebo at week 13 . Similar results were observed for secondary endpoints : OA pain intensity and WOMAC ™ total score . Lumiracoxib was similar to celecoxib for all three co- primary endpoints . All treatments were well tolerated . In conclusion , lumiracoxib is effective in reducing pain and improving function in hip OA patients . Clinical trial registration information : www . clinical trials.gov ; OBJECTIVE To assess the effects of the prescription formulation of glucosamine sulfate ( 1,500 mg administered once daily ) on the symptoms of knee osteoarthritis ( OA ) during a 6-month treatment course . METHODS Three hundred eighteen patients were enrolled in this r and omized , placebo-controlled , double-blind trial in which acetaminophen , the currently preferred medication for symptomatic treatment of OA , was used as a side comparator . Patients were r and omly assigned to receive oral glucosamine sulfate 1,500 mg once daily ( n = 106 ) , acetaminophen 3 gm/day ( n = 108 ) , or placebo ( n = 104 ) . The primary efficacy outcome measure was the change in the Lequesne index after 6 months . Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and response according to the Osteoarthritis Research Society International criteria . These outcome measures were assessed using an intent-to-treat analysis . RESULTS At baseline , the study patients had moderately severe OA symptoms ( mean Lequesne index approximately 11 points ) . Glucosamine sulfate was more effective than placebo in improving the Lequesne score , with a final decrease of 3.1 points , versus 1.9 with placebo ( difference between glucosamine sulfate and placebo -1.2 [ 95 % confidence interval -2.3 , -0.8 ] ) ( P = 0.032 ) . The 2.7-point decrease with acetaminophen was not significantly different from that with placebo ( difference -0.8 [ 95 % confidence interval -1.9 , 0.3 ] ) ( P = 0.18 ) . Similar results were observed for the WOMAC . There were more responders to glucosamine sulfate ( 39.6 % ) and acetaminophen ( 33.3 % ) than to placebo ( 21.2 % ) ( P = 0.004 and P = 0.047 , respectively , versus placebo ) . Safety was good , and was comparable among groups . CONCLUSION The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms . Although acetaminophen also had a higher responder rate compared with placebo , it failed to show significant effects on the algofunctional indexes ABSTRACT Objective : This study evaluated the efficacy and safety of tramadol extended-release ( tramadol ER ) tablets once daily in subjects with osteoarthritis pain . Methods : This 12‐week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity ≥ 40 on a 100‐mm pain visual analog scale ( 0 = no pain , 100 = extreme pain ) . Subjects took placebo or were titrated to a target dose of tramadol ER 100 , 200 , 300 , or 400 mg once daily . Main outcome measures : The co- primary efficacy variables were pain and physical function subscales of the WOMAC Osteoarthritis Index and subject global assessment of disease activity . Results : Mean changes in WOMAC Osteoarthritis Index pain and physical function subscales were significantly different between tramadol ER and placebo , overall ( p ≤ 0.021 ) and for each dose ( p ≤ 0.050 ) . However , the protocol -specified decision rule for the 3 co- primary endpoints was not satisfied because the overall comparison of subject global assessment of disease activity was not statistically significant ( p = 0.079 ) . All doses of tramadol ER once daily were more effective than placebo ( p ≤ 0.050 ) for WOMAC Osteoarthritis Index joint stiffness subscale , WOMAC Osteoarthritis Index composite score , pain intensity of the index joint , and daily pain intensity scores . Tramadol ER 200 and 300 mg were significantly more effective than placebo ( p ≤ 0.050 ) for subject global assessment of disease activity and pain intensity of non-index joints . Adverse events ( e.g. , constipation , dizziness , nausea , somnolence , headache ) occurred most often with tramadol ER 400 mg . Conclusions : Tramadol ER 100–300 mg once daily was associated with significant improvement in pain intensity and physical function , and was well tolerated , despite the use of a fixed-dose study design not reflective of usual clinical practice . Tramadol ER is a useful treatment option for patients with osteoarthritis pain This 12-week , multicenter , r and omized , double-blind , placebo-controlled , dose-ranging trial evaluated tramadol ER ( extended-release tramadol ) in the management of osteoarthritis pain . Adults with knee and /or hip osteoarthritis and baseline pain intensity of ≥40 on a 100-mm visual analog scale ( 0 = no pain , 100 = extreme pain ) received once-daily tramadol ER 100 mg ( n = 201 ) , 200 mg ( n = 199 ) , or 300 mg ( n = 199 ) , celecoxib 200 mg ( n = 202 ; to test model sensitivity ) , or placebo ( n = 200 ) . Co primary efficacy variables were Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale , WOMAC physical function subscale , and patient global assessment of disease activity . Tramadol ER 300 mg significantly improved patient global assessment scores compared with placebo ( P ≤ 0.05 ) , but not the other 2 co primary efficacy variables . Tramadol ER 200 and 100 mg were not significantly different from placebo for the co primary efficacy variables . Daily diary arthritis pain intensity scores improved significantly for tramadol ER 300 and 200 mg compared with placebo . WOMAC joint stiffness subscale , physician 's global assessment , arthritis pain intensity in index and nonindex joints , and overall sleep quality scores improved significantly for tramadol ER 300 mg compared with placebo . Significant differences in efficacy between celecoxib and placebo vali date d the model sensitivity . Adverse events occurred more frequently with tramadol ER than placebo in the gastrointestinal ( nausea , constipation , diarrhea ) and central nervous ( dizziness , headache ) systems . In this study , tramadol ER 300 mg was effective in the management of moderate to severe painful osteoarthritis of the hip or knee . A large , increasing placebo response during the study may have contributed to the lack of statistical separation between tramadol ER 200 or 100 mg and placebo OBJECTIVES Nonsteroidal anti-inflammatory drugs have dose-related adverse effects . Topical nonsteroidal anti-inflammatory drugs may offer local efficacy with low systemic drug levels . This study assessed the efficacy and safety of topical diclofenac sodium 1 % gel ( DSG ) in mild to moderate symptomatic knee osteoarthritis . METHODS In a r and omized , double-blind , vehicle-controlled trial , 492 adults aged > or=35 years with symptomatic knee osteoarthritis of > or=6 months ' duration were r and omized to DSG 4 g ( n = 254 ) or vehicle ( n = 238 ) 4 times daily for 12 weeks . Primary efficacy outcomes at week 12 were the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale , WOMAC physical function subscale , and global rating of disease . Secondary outcomes included these outcomes assessed after 1 , 4 , and 8 weeks , and pain on movement assessed using a 100-mm visual analog scale . All adverse events were recorded . RESULTS At week 12 , the DSG group had significant decreases versus the vehicle group in mean WOMAC pain ( P = 0.01 ) , mean WOMAC physical function ( P = 0.001 ) , and mean global rating of disease ( P < 0.001 ) . Efficacy outcomes significantly favored DSG versus vehicle beginning at week 1 . Application site reactions occurred in 5.1 % and 2.5 % of patients in the DSG and vehicle groups , respectively . The incidence of gastrointestinal disorders was 5.9 % with DSG and 5.0 % with vehicle . CONCLUSIONS Over a 3-month treatment period , topical treatment with DSG achieved statistically and clinical ly significant improvements of pain and measures of physical function in patients with knee osteoarthritis Objective . This r and omized , double-blind , phase III study evaluated the efficacy and safety of ketoprofen in an ultradeformable vesicle gel compared with ketoprofen-free gel in osteoarthritis ( OA ) knee pain . Methods . Patients with American College of Rheumatology-defined OA of the knee and moderate pain were r and omized to receive 100 mg ketoprofen in 4.4 g transfersome gel ( IDEA-033 ) or 4.4 g ketoprofen-free vehicle ( TDT 064 ) topically , twice daily , for 12 weeks . The primary endpoint was mean change in Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale score from baseline to Week 12 . Results . Patients ( n = 555 ) were r and omized and treated . Mean baseline WOMAC pain scores were 5.2 ( SD 1.0 ) for IDEA-033 and 5.3 ( SD 1.0 ) for TDT 064 . Mean change in WOMAC pain scores from baseline to Week 12 was 38.6 % for IDEA-033 and 44.6 % for TDT 064 ( Mann-Whitney estimator 0.4505 ; p = 0.022 ) . Both groups reported progressive decreases in pain and improvements in function and stiffness . Mean baseline WOMAC function scores decreased from 5.4 to 3.4 with IDEA-033 and 3.1 with TDT 064 at Week 12 . The proportion of patients achieving ≥ 50 % decrease in WOMAC pain score from baseline at Week 12 was 41.2 % ( 95 % CI 0.35–0.47 ) with IDEA-033 and 50.5 % ( 95 % CI 0.45–0.57 ) with TDT 064 . Mild skin and subcutaneous tissue disorders were the most frequently reported treatment-related adverse events ( AE ) . Conclusions . IDEA-033 was inferior to drug-free gel ( TDT 064 ) in relieving moderate OA knee pain and improving joint function ( Clinical Trials NCT00722852 ) Introduction Flavocoxid is a novel flavonoid-based “ dual inhibitor ” of the 5-lipoxygenase ( 5-LOX ) enzyme and the cyclooxygenase ( COX ) enzymes . This study was design ed to compare the effectiveness and safety of flavocoxid to naproxen in subjects with moderate to severe osteoarthritis ( OA ) of the knee . Methods In this r and omized , multicenter , double-blind study , 220 subjects were assigned to receive either flavocoxid ( 500 mg twice daily ) or naproxen ( 500 mg twice daily ) for 12 weeks . The trial was structured to show noninferiority of flavocoxid to naproxen . Primary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and subscales and a timed walk . Results More than 90 % of the subjects in both groups noted significant reduction in the signs and symptoms of knee OA . There were no statistically significant differences in efficacy between the flavocoxid and naproxen groups when the entire intent-to-treat population was analyzed . The flavocoxid group had significantly fewer upper gastrointestinal ( UGI ) and renal ( edema ) adverse events ( AEs ) as well as a strong trend toward fewer respiratory AEs . Conclusion Flavocoxid , a first-in-class flavonoid-based therapeutic that inhibits COX-1 and COX-2 as well as 5-LOX , was as effective as naproxen in managing the signs and symptoms of OA of the knee . Flavocoxid demonstrated better UGI , renal ( edema ) , and respiratory safety profiles than naproxen This placebo-controlled study examined the analgesic efficacy , safety , and clinical benefit of Tramadol Contramid OAD , a once-daily formulation with both immediate- and extended-release components . Five hundred and fifty-two patients with moderate to severe pain due to osteoarthritis ( OA ) of the knee were r and omized into this multicenter , double-blind , parallel arm study . After r and omization to Tramadol Contramid OAD 100 , 200 , or 300 mg , or to placebo , patients ' dose was titrated to the fixed r and omized dose and maintained for 12 weeks . Efficacy was evaluated with the Patients ' Global Rating of Pain Relief ( median ratings at maintenance visits ) , and the Western Ontario and McMaster University ( WOMAC ) Pain and Physical Function subscales ( percent difference , baseline to end of study ) as co primary endpoints . A responder analysis was conducted ( percentage of patients who achieved a 30 percent improvement on their baseline WOMAC pain score ) . The difference from placebo on the median Patient Global Rating of Pain Relief at the four maintenance visits was statistically significant ( 200 and 300 mg : p < or = 0.001 ) . Treatment was rated effective or very effective by 75 percent and 80 percent of patients r and omized to Tramadol Contramid OAD 200 mg and 300 mg , respectively . There was a 46 percent ( 300-mg dose ; p = 0.016 ) and 43 percent ( 200-mg dose ; p = 0.05 ) improvement on the WOMAC pain score ( baseline to the end of the study ) with Tramadol Contramid OAD compared with 32percent for placebo . The responder analysis demonstrated a statistically significant difference in the percentage of patients who achieved a 30 percent improvement in their baseline WOMAC pain score for both Tramadol Contramid OAD 200 mg ( 65 percent ; p = 0.0095 ) and 300 mg ( 65 percent ; p = 0.0104 ) compared with placebo ( 50 percent ) . The type and incidence of adverse events were typical of tramadol ( nausea , dizziness/vertigo , vomiting , somnolence , and constipation ) and the intensity was mild to moderate in 87percent of patients who experienced them regardless of dose . This study shows the efficacy and safety of Tramadol Contramid OAD 200 mg and 300 mg in patients with moderate or severe pain of the knee due to OA Abstract Objective : Determine efficacy and safety of acetaminophen extended release ( ER ) 1300 mg given three times daily compared to placebo for relieving signs and symptoms of hip or knee osteoarthritis . Research design and methods : Sixty investigators at 58 private , ambulatory , primary care sites in the US enrolled 542 outpatient adults ≥40 years old with moderate to severe idiopathic osteoarthritis pain into a r and omized , placebo-controlled , double-blind 12 week clinical trial . Patients were r and omly assigned to treatment given three times daily of acetaminophen 1300 mg ( n = 267 ) or placebo ( n = 275 ) . Results : The three primary endpoints measured through week 12 favored acetaminophen ER as follows : least squares ( LS ) mean change from baseline for WOMAC physical function subscale score was significantly greater for acetaminophen ER than for placebo ( P = 0.011 ) ; LS mean patient ’s global assessment of response to therapy was significantly greater for acetaminophen ER than for placebo ( P = 0.010 ) ; and LS mean change from baseline for WOMAC pain subscale score was marginally greater for acetaminophen ER than for placebo ( P = 0.054 ) . LS mean change from baseline for secondary endpoints through week 12 also favored acetaminophen ER compared with placebo : significantly for WOMAC stiffness subscale score ( P = 0.004 ) , significantly for WOMAC total index score ( P = 0.013 ) , and marginally for Nottingham Health Profile energy subscale score ( P = 0.057 ) . The percentage of patients with any adverse event was similar for both treatment groups . Hepatic transaminases exceeded 3 × ULN in seven acetaminophen ER patients and one placebo patient . Elevations were attributed to health conditions in three of seven acetaminophen ER patients ; elevations in the remaining four patients returned to or toward normal . Conclusions : Acetaminophen ER 1300 mg , a nonprescription drug , given three times daily , can provide effective relief of signs and symptoms of osteoarthritis of the hip or knee and was well tolerated . Clinical Trials.gov registration number : Clinical Trials.gov identifier : NCT00240799 The objectives of the study are to demonstrate the non-inferiority of PG201 ( Layla ® ) 600 mg in comparison with celecoxib 200 mg for the treatment of symptomatic knee osteoarthritis ( OA ) . In total , 309 patients were r and omly assigned to receive either the test drug , PG201 600 mg ( n = 154 ) or celecoxib 200 mg ( n = 155 ) . The primary efficacy variable was improvement in mean 100-mm pain VAS score from baseline to the final visit ( week 8) , and this value was compared between the 2 treatment groups . Secondary outcome variables included changes from baseline in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain VAS score and subscale score , patient ’s global assessment of disease status quality of life ( short form-36 ) and responder index at weeks 4 and 8 . For safety assessment , adverse events were recorded at each clinical visit . At weeks 8 , the 100-mm pain VAS scores were significantly decreased in patients receiving both PG201 600 mg ( p < 0.0001 ) and celecoxib 200 mg ( p < 0.0001 ) as compared to the baseline scores ; however , no statistically significant differences in these values were noted between the groups ( p = 0.312 ) . These results met pre-specified criteria for non-inferiority for both the intent-to-treat and per- protocol population s. PG201 600 mg and celecoxib 200 mg were both well tolerated and no statistically significant differences in the tolerability profile between the groups . PG201 600 mg was as effective and safe as celecoxib 200 mg in the treatment of symptomatic knee OA and might be a useful new medication for the treatment of symptomatic knee OA OBJECTIVE To examine the efficacy and safety of two doses of long-acting acetaminophen in patients with osteoarthritis ( OA ) of the hip or knee . METHODS This multicenter , r and omized , double-blind , parallel-group , placebo-controlled study evaluated the efficacy and safety of acetaminophen extended-release ( ER ) 650 mg and 1300 mg given three times daily for the treatment of moderate to moderately severe OA of the hip or knee . Primary efficacy end points were mean change from baseline through 12 weeks in the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscale scores and mean patient global assessment of response to therapy at week 12 . Safety assessment s included monitoring vital signs , adverse events , study joint assessment s , and clinical laboratory results at each study visit . RESULTS Four hundred eighty-three patients were r and omized to treatment and included in the intent-to-treat analysis . All groups were similar with respect to baseline demographics except for gender , weight , and body mass index . Acetaminophen ER 3900 mg was significantly superior to placebo for all three primary end points ; acetaminophen ER 1950 mg was significantly superior to placebo only with respect to patient assessment of response to therapy . Study treatments were generally well tolerated , and there was no significant difference among the groups in the overall number of adverse events . CONCLUSIONS Acetaminophen ER 3900 mg/d administered for up to 12 weeks was effective in treating moderate to moderately severe chronic OA pain of the hip or knee and was generally well tolerated Abstract Objective : Nonsteroidal anti-inflammatory drugs ( NSAIDs ) are st and ard therapy for osteoarthritis ( OA ) . Topically applied NSAIDs reduce systemic exposure compared with oral NSAIDS , and European guidelines recommend their use . The NSAID diclofenac is available in a range of topical formulations . Diclofenac 1 % gel and 1.5 % four times daily and 2 % twice daily ( BID ) solutions are approved to reduce pain from OA of the knee(s ) . The objective of this study was to investigate the efficacy and safety of diclofenac sodium 2 % topical solution BID versus vehicle control solution for treating pain associated with OA of the knee . Research design and methods : A phase II , 4 week , r and omized , double-blind , parallel-group , two-arm , vehicle-controlled study compared pain relief with diclofenac sodium 2 % topical solution versus control ( vehicle only ) in patients aged 40 to 85 years with radiographically confirmed primary OA of the knee . Clinical trial registration : Clinical Trials.gov identifier NCT01119898 . Main outcome measures : The primary efficacy outcome was change from baseline to the final visit in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale . Secondary outcomes included additional WOMAC subscales and patient global assessment of OA . Treatment-emergent adverse events ( TEAEs ) , skin irritation , and vital signs were assessed and collected throughout the study . Results : Of 260 patients r and omized , 259 received ≥1 dose of study drug . Significantly greater reductions in least-squares mean ( st and ard error ) WOMAC pain scores were observed for diclofenac-treated ( −4.4 [ 0.4 ] ) versus vehicle-treated patients ( −3.4 [ 0.4 ] ) at the final visit ( p = 0.040 ) . The most commonly reported TEAEs were administration site conditions . The vehicle-treated group experienced slightly more TEAEs than the active treatment group ( 38.8 % vs. 31.5 % ) . No serious adverse events were reported . Conclusions : Administration of diclofenac sodium 2 % topical solution BID result ed in significantly greater improvement in pain reduction in patients with OA of the knee versus vehicle control and was generally well tolerated Objective : To compare epicutaneous ketoprofen in Transfersome ( ultra-deformable vesicles , IDEA-033 ) versus oral celecoxib and placebo for relief of signs and symptoms in knee osteoarthritis . Methods : This was a multicentre , r and omised , double-blind , controlled trial ; 397 patients with knee osteoarthritis participated and 324 completed the trial . They were r and omly assigned 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo ( n = 138 ) , 100 mg oral celecoxib plus placebo gel ( n = 132 ) , or both placebo formulations ( n = 127 ) twice daily for 6 weeks . Primary efficacy outcome measures were the changes from baseline to end of the study on the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index pain subscale , physical function subscale and patient global assessment ( PGA ) of response . Results : The mean WOMAC pain subscale scores in the intent to treat population were reduced by 18.2 ( 95 % confidence interval −22.1 to −14.3 ) , 20.3 ( −24.3 to −16.2 ) and 9.9 ( −13.9 to −5.8 ) in the IDEA-033 , celecoxib and placebo groups , respectively , and the physical function subscale score by 14.6 ( −18.1 to −11.0 ) , 16.6 ( −20.2 to −13.0 ) and 10.2 ( −13.8 to −6.6 ) , respectively . The mean PGA of response scores were 1.8 ( 1.6 to 2.1 ) , 1.7 ( 1.5 to 1.9 ) and 1.3 ( 1.1 to 1.5 ) , respectively . The differences in change between IDEA-033 and placebo were statistically significant for pain subscale ( p<0.01 ) and PGA of response ( p<0.01 ) . Gastrointestinal adverse events for IDEA-033 were similar to placebo . Conclusion : IDEA-033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis Summary Tanezumab is efficacious in a phase III clinical trial of patients with moderate to severe osteoarthritis pain of the hip or knee . ABSTRACT Tanezumab is a humanized monoclonal antinerve growth factor antibody in development for treatment of chronic pain . In a phase III , placebo‐ and active‐controlled study , we investigated the efficacy and safety of tanezumab for osteoarthritis ( OA ) hip or knee pain . Patients ( N = 610 ) received up to 2 doses of intravenous tanezumab ( 5 or 10 mg in 8‐week intervals ) , controlled‐release oral oxycodone ( 10 to 40 mg every 12 hours ) , or placebo . The primary endpoint was mean change from baseline to week 8 in Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) Pain score for tanezumab versus placebo and oxycodone . Secondary endpoints included change from baseline in WOMAC Physical Function and Stiffness scores , Patient 's Global Assessment ( PGA ) of OA , and patient response , defined as ≥30 % , ≥50 % , ≥70 % , and ≥90 % improvement from baseline in WOMAC Pain score . Tolerability and safety also were assessed . Both tanezumab groups demonstrated significant improvements in WOMAC Pain score versus placebo ( P < .001 ) and oxycodone ( P ≤ .018 ) . Tanezumab also provided significant improvements versus placebo and oxycodone for WOMAC Physical Function and Stiffness scores and PGA of OA ( P ≤ .002 for all ) at week 8 . For all analyses , oxycodone did not differ from placebo . Adverse event frequency was higher with oxycodone ( 63.3 % ) than tanezumab ( 40.7 % to 44.7 % ) or placebo ( 35.5 % ) ; serious adverse event frequency was similar among treatments . The adverse event profile for tanezumab was similar to previous tanezumab studies . Results indicate that tanezumab is efficacious in the treatment of OA pain ; no new safety signals were identified Objective . To measure the efficacy and safety of diclofenac sodium gel in patients with primary h and osteoarthritis ( OA ) . Methods . In a r and omized , double-blind , placebo-controlled trial , men and women aged ≥ 40 years diagnosed with primary OA in the dominant h and were r and omly assigned to self-apply topical 1 % diclofenac sodium gel ( Voltaren ® Gel ) ( n = 198 ) or vehicle ( n = 187 ) to both h and s 4 times daily for 8 weeks . Primary outcome measures included OA pain intensity ( 100-mm visual analog scale ) , total Australian/Canadian Osteoarthritis H and Index ( AUSCAN ) score , and global rating of disease activity at 4 and 6 weeks . Secondary outcomes included onset of efficacy in Weeks 1 and 2 , durability of efficacy at 8 weeks , measures of disease activity in the dominant h and , pain intensity in the non-dominant h and , AUSCAN subindices , end of study rating of efficacy , and Osteoarthritis Research Society International response criteria . Results . Diclofenac sodium gel decreased pain intensity scores by 42%–45 % , total AUSCAN scores by 35%–40 % , and global rating of disease by 36%–40 % . Significant differences favoring diclofenac sodium gel over vehicle were observed at Week 4 for pain intensity and AUSCAN , with a trend for global rating of disease activity . At Week 6 , diclofenac sodium gel treatment significantly improved each primary outcome measure compared with vehicle . Secondary outcomes generally supported the primary outcomes . The most common treatment-related adverse event ( AE ) was application-site paresthesia . Most AE were mild . No cardiac events , gastrointestinal bleeding , or ulcers were reported . Conclusion . Topical diclofenac sodium gel was generally well tolerated and effective in primary h and OA . ( NCT ID : NCT00171665 ABSTRACT Objective : Osteoarthritis is one of the most common forms of arthritis seen in primary care . Non-steroidal anti-inflammatory drugs ( NSAIDs ) play an important role in the management of osteoarthritis . However , gastrointestinal ( GI ) side effects limit their use . Cyclooxygenase-2 ( COX‐2 ) selective inhibitors exhibit better GI tolerability than conventional NSAIDs , but their cardiovascular safety is controversial . An NSAID with high efficacy , high GI tolerability and devoid of adverse cardiovascular effects is therefore a profile preferred by physicians . Aceclofenac is an anti-inflammatory and analgesic drug with preferential COX-2 inhibition . The objective of this study was to assess the efficacy and safety of aceclofenac in the treatment of osteoarthritis in an Indian population . Research design and methods : The trial was controlled , comparative , r and omized , and double-blind . The study included 247 patients ( 82 males and 165 females , 40–82 years ) , suffering from osteoarthritis . Patients were r and omized to receive either aceclofenac ( 100 mg twice daily ) or diclofenac ( 75 mg twice daily ) . Main outcome measures : Clinical assessment was done at screening , r and omization , and at 2 weeks , 4 weeks and 8 weeks of treatment by calculating Western Ontario MacMaster ( WOMAC ) scores , time taken to walk 100 feet , visual analogue scores for pain , investigator 's assessment on a Likert scale and joint tenderness . Tolerability assessment was based on adverse events . Patient compliance was also assessed . Results : Aceclofenac was found to be statistically superior to diclofenac in efficacy parameters of WOMAC scores , investigator 's assessment and joint tenderness . Aceclofenac was found to be statistically superior to diclofenac in terms of epigastric discomfort , dyspepsia and abdominal pain . Compliance was also better with aceclofenac . The overall response of patients ’ osteoarthritis to aceclofenac was found to be statistically superior to diclofenac by both physician and patient . Conclusions : Aceclofenac is an effective and well-tolerated drug in osteoarthritis in the Indian setting ABSTRACT While topical non‐steroidal anti‐inflammatory drugs are considered safe , their long‐term efficacy for osteoarthritis has been suspect . We conducted a 12‐week , double‐blind , double‐dummy , r and omized controlled trial of topical diclofenac ( TDiclo ) in a vehicle solution containing dimethyl sulfoxide ( DMSO ) in 775 subjects with radiologically confirmed , symptomatic primary osteoarthritis of the knee . This 5‐arm study compared TDiclo with a placebo solution , the DMSO vehicle , oral diclofenac ( ODiclo ) and the combination of TDiclo + ODiclo for relieving the signs and symptoms of knee osteoarthritis . Subjects applied study solution , 40 drops four times daily , and took one study tablet daily for 12 weeks . Co‐ primary efficacy variables were WOMAC pain and physical function and a patient overall health assessment . Secondary variables were WOMAC stiffness and patient global assessment ( PGA ) of the knee osteoarthritis . TDiclo was superior to placebo for pain ( −6.0 vs. −4.7 , P = 0.015 ) , physical function ( −15.8 vs. −12.3 , P = 0.034 ) , overall health ( −0.95 vs. −0.37 , P < 0.0001 ) , and PGA ( −1.36 vs. −1.01 , P = 0.016 ) , and was superior to DMSO vehicle for all efficacy variables . No significant difference was observed between DMSO vehicle and placebo or between TDiclo and ODiclo . The commonest adverse event associated with TDiclo was dry skin ( 18.2 % ) . Fewer digestive system and laboratory abnormalities were observed with TDiclo than with ODiclo . Addition of TDiclo to ODiclo did not increase the incidence of systemic adverse events . TDiclo in DMSO vehicle is an effective treatment option for knee osteoarthritis with efficacy similar to , but tolerability better than ODiclo . DMSO vehicle was no more efficacious than placebo OBJECTIVE This study was design ed to investigate the analgesic effects of nimesulide and celecoxib in patients with knee osteoarthritis ( OA ) . In patients with joint effusion , the effects of these non-steroidal anti-inflammatory drugs ( NSAIDs ) on synovial fluid concentrations of substance P ( SP ) , interleukin (IL)-6 and IL-8 also were evaluated . METHODS Patients were r and omly assigned either nimesulide ( 100 mg twice a day ) or celecoxib ( 200 mg once a day ) for 2 weeks . The intensity of joint pain was assessed with a 100-mm visual analogue scale ( VAS ) . Furthermore , patients completed questions about analgesic efficacy and overall tolerability of the treatments on a five-point categorical scale . Synovial fluid sample s were drawn at baseline , 30 min after the first drug intake ( day 1 ) , and 30 min after the last drug intake ( day 14 ) . RESULTS We enrolled 44 patients , 20 of whom had a joint effusion . In this group , the effects of nimesulide were more marked than for celecoxib , with evidence of a faster onset of the analgesic action . Both after a single or repeated administration , nimesulide significantly reduced the synovial fluid concentrations of SP and IL-6 . Celecoxib , on the other h and , did not change the concentrations of SP and significantly reduced the levels of IL-6 only on day 14 . None of the drugs affected IL-8 . Both drugs were generally well tolerated . CONCLUSIONS These results provide evidence that nimesulide is an effective agent for the symptomatic treatment of OA . The effect on inflammatory pain mediators is consistent with the fast analgesic action of this NSAID OBJECTIVE To test the superiority of naproxcinod compared with placebo in relieving the signs and symptoms of hip osteoarthritis and to assess the safety of naproxcinod and its effects on blood pressure . METHODS In a 13-week , r and omized , double-blind , parallel-group , multicenter study , 810 patients were r and omized to receive either naproxcinod 750 mg twice daily , placebo , or naproxen 500 mg twice daily ( 2:2:1 ) . Primary efficacy analyses compared naproxcinod and placebo using an analysis of covariance for 3 co- primary end points ( the Western Ontario and McMaster Universities Osteoarthritis Index [ WOMAC ] pain and function subscales and patient 's overall rating of disease status ) . Safety assessment s included adverse events and in-office blood pressure measurements . RESULTS The least squares mean changes from baseline were significantly greater with naproxcinod than with placebo ( P < 0.0001 ) and were similar to those with naproxen at week 13 for the WOMAC pain score ( -25.81 , -17.97 , and -24.31 mm , respectively ) , the WOMAC function score ( -22.24 , -13.45 , and -21.67 mm , respectively ) , and patient 's rating of disease status ( 0.86 , 0.51 , and 0.82 , respectively ) . Changes from baseline in systolic blood pressure were similar in the naproxcinod and placebo groups at weeks 2 , 6 , and 13 ( differences between groups of 0.25 , -0.45 , and -0.11 mm Hg , respectively ) . Changes in the naproxen group were greater than those in the placebo group ( differences of 3.11 , 3.03 , and 2.00 mm Hg , respectively ) . Systolic blood pressure increases ≥10 mm Hg from baseline to week 13 occurred in 13.3 % , 15.0 % , and 20.3 % of patients receiving naproxcinod , placebo , and naproxen , respectively . Naproxcinod and naproxen had similar adverse event and general safety profiles . CONCLUSION The efficacy of naproxcinod for treating the signs and symptoms of hip osteoarthritis was statistically superior to that of placebo and similar to that of naproxen . Naproxcinod was well tolerated , with effects on systolic blood pressure similar to those of placebo Objectives Tanezumab , a monoclonal antibody , inhibits nerve growth factor and reduces chronic pain . This r and omised , double-blind , controlled multicentre study was conducted to evaluate the efficacy and safety of tanezumab added to oral diclofenac sustained release ( DSR ) in patients with hip or knee osteoarthritis ( OA ) pain . Methods Patients ( N=604 ) with moderate to severe knee or hip OA tolerating stable DSR were r and omised and treated with DSR 75 mg twice daily combined with intravenous tanezumab 10 , 5 or 2.5 mg or placebo at weeks 0 , 8 and 16 . Co- primary efficacy endpoints ( Western Ontario and McMaster Universities OA Index ( WOMAC ) Pain and Physical Function subscales and patient 's global assessment of OA ) were assessed at week 16 . Results All co- primary endpoints were significantly improved for all tanezumab+DSR groups versus placebo+DSR ( p≤0.039 ) . The incidence of adverse events of abnormal peripheral sensation was lower than in previous tanezumab trials . No new safety signals emerged . Overall incidence of adverse events was higher with tanezumab+DSR ( 45.2%–49.7 % ) than with placebo+DSR ( 34.9 % ) ; serious adverse event rates were similar across treatments ( 5.3%–7.6 % ) . Osteonecrosis was reported in six of 452 patients with tanezumab+DSR ( 1.3 % ) , but an external adjudication committee did not confirm osteonecrosis in any patient . Conclusions Addition of tanezumab to DSR result ed in significant improvements in pain , function and global assessment s in patients with OA . Although no new safety signals were observed , the higher incidence of adverse events in the tanezumab+diclofenac group suggests that combination therapy is unfavourable . Further investigations of tanezumab monotherapy for OA pain treatment are required . Clinical trial registration number |
1,129 | 31,014,262 | Conclusions There was evidence that engaging in moderate intensity aerobic exercises ( 55–85 % Maximum heart rate-MHR ) , for 30–60 min , two to five times/week for 6–24 weeks significantly improves role activity limitation due to physical health problems , otherwise physical(aerobic or/ and resistance ) exercises have no significant effects on CD4 + count and other domains of QoL. Also , there is lack of evidence on the impact of exercises on BMD in PLWHA due to the paucity of RCTs .
The moderate grade evidence for this review suggests that further research may likely have an important impact on our confidence in the estimate of effects and may change the estimate | Background Compromised immune function , associated with human immune deficiency virus(HIV ) infection , is improved by antiretroviral therapy(ART ) which also decreases bone mineral density(BMD ) , and possibly the quality of life(QoL ) .
However , physical(aerobic/resistance ) exercises , were reported to induce reverse effects in uninfected individuals and were appraised in the literature for evidence of similar benefits in people living with HIV/AIDS(PLWHA ) .
The main study objective was to evaluate the impact of physical ( aerobic and resistance ) exercises on CD4 + count , BMD and QoL in PLWHA . | Objective Our objective was to examine the effects of exercise training ( EXS ) on quality of life ( QoL ) in highly active antiretroviral therapy (HAART)-treated HIV-positive ( HIV+ ) subjects with body fat redistribution ( BFR ) in Rw and a. Methods The effects of a r and omised controlled trial of EXS on QoL were measured using World Health Organisation Quality of Life (WHOQOL)-BREF in HIV+ subjects with BFR r and omised to EXS ( n = 50 ; BFR + EXS ) or no exercise training ( n = 50 ; BFR + noEXS ) . Results At 6 months , scores on the psychological [ 1.3 ( 0.3 ) vs. 0.5 ( 0.1 ) ; P < 0.0001 ] , independence [ 0.6 ( 0.1 ) vs. 0.0 ( 0.0 ) ; P < 0.0001 ] , social relationships [ 0.6 ( 0.2 ) vs. 0.0 ( 0.0 ) ; P < 0.0001 ] and HIV HAART-specific QoL domains [ 1.4 ( 0.2 ) vs. −0.1 ( 0.2 ) ; P < 0.0001 ] improved more in BFR + EXS than BFR + noEXS group , respectively . Self-esteem [ 1.3 ( 0.8 ) vs. 0.1 ( 0.6 ) ; P < 0.001 ] , body image [ 1.5 ( 0.6 ) vs. 0.0 ( 0.5 ) ; P < 0.001 ] and emotional stress [ 1.6 ( 0.7 ) vs. 0.2 ( 0.5 ) ; P < 0.001 ] improved more in the BFR + EXS group than BFR + noEXS group , respectively . Psychological [ 1.5 ( 0.2 ) vs. 1.1 ( 0.3 ) ; P < 0.0001 ] , social relationship [ 0.8 ( 0.2 ) vs. 0.4 ( 0.2 ) ; P < 0.0001 ] , and HIV HAART-specific well-being [ 1.8 ( 0.2 ) vs. 1.0 ( 0.0 ) ; P < 0.0001 ] improved more in BFR + EXS female than male subjects . Conclusions Exercise training improved several components of QoL in HAART-treated HIV+ African subjects with BFR . Exercise training is an inexpensive and efficacious strategy for improving QoL in HIV+ African subjects , which may improve HAART adherence and treatment initiatives in re source -limited areas of sub-Saharan Africa QUESTION What is the effect of a six-month , supervised , aerobic and resistance exercise program on self-efficacy in men living with human immunodeficiency virus ( HIV ) ? DESIGN R and omised , controlled trial . PARTICIPANTS 40 ( 5 dropouts ) men living with HIV , aged 18 years or older . INTERVENTION The experimental group participated in a twice-weekly supervised aerobic and resistance exercise program for six months and the control group participated in a twice-weekly unsupervised walking program and attended a monthly group forum . OUTCOME MEASURES The primary outcome measure was self-efficacy using the General Self-Efficacy Scale . Secondary outcome measures were cardiovascular fitness using the Kasch Pulse Recovery test , and health-related quality of life using the Medical Outcomes Study HIV Health Survey . Measures were taken by an assessor blinded to group allocation . RESULTS By six months , the experimental group had improved their self-efficacy by 6.8 points ( 95 % CI 3.9 to 9.7 , p < 0.001 ) and improved their cardiovascular fitness by reducing their heart rate by 20.2 bpm ( 95 % CI -25.8 to -14.6 , p < 0.001 ) more than the control group . Health-related quality of life improved in only two out of the eleven dimensions : the experimental group improved their overall health by 20.8 points ( 95 % CI 2.0 to 39.7 , p = 0.03 ) and their cognitive function by 14 points ( 95 % CI 0.7 to 27.3 , p = 0.04 ) more than the control group . CONCLUSION The findings of this study add to the known benefits of exercise for the HIV-infected population Currently infection with the human immunodeficiency virus-1 ( HIV-1 ) is in most instances a chronic disease that can be controlled by effective antiretroviral therapy ( ART ) . However , chronic use of ART has been associated with a number of toxicities ; including significant reductions in bone mineral density ( BMD ) and disorders of the fat metabolism . The peroxisome proliferator-activated receptor gamma ( PPARγ ) transcription factor is vital for the development and maintenance of mature and developing adipocytes . Alterations in PPARγ expression have been implicated as a factor in the mechanism of HIV-1-associated lipodystrophy . Both reduced BMD and lipodystrophy have been well described as complications of HIV-1 infection and treatment , and a question remains as to their interdependence . Interestingly , both adipocytes and osteoblasts are derived from a common precursor cell type ; the mesenchymal stem cell . The possibility that dysregulation of PPARγ ( and the subsequent effect on both osteoblastogenesis and adipogenesis ) is a contributory factor in the lipid- and bone-abnormalities observed in HIV-1 infection and treatment has also been investigated . This review deals with the hypothesis that dysregulation of PPARγ may underpin the bone abnormalities associated with HIV-1 infection , and treats the current knowledge and prospect i ve developments , in our underst and ing of PPARγ involvement in HIV-1-associated bone disease OBJECTIVES : Human Immunodeficiency Virus ( HIV ) infection worsens the frailty of elderly people , compromising their quality of life . In this study we prospect ively evaluated eleven patients living with HIV and 21 controls older than 60 years and without prior regular physical activity , who engaged in a one-year progressive resistance exercise program to compare its effects on muscular strength , physical fitness and body composition . METHODS : Exercises for major muscular groups were performed 2 times/week , under professional supervision . Strength increase was evaluated bimonthly , while body composition , lipid and glycaemic profiles ( only of those living with HIV ) and physical fitness were evaluated before and after the one-year training . RESULTS : The participants living with HIV were lighter , had smaller Body Mass Index and were initially much weaker than controls . However , their strength increased more ( 1.52 - 2.33 times the baseline values for those living with HIV x 1.21 - 1.48 times for controls , p<0.01 ) , nullifying the differences initially seen . These effects were seen independently of gender , age or baseline physical activity . In addition , those living with HIV improved their fasting glucose levels and showed a tendency to improve their lipids after the one year training program . These effects were slightly more pronounced among those not using protease inhibitors , although not significantly . CONCLUSIONS : Resistance exercise safely increased the strength of older patients living with HIV adults , allowing them to achieve performance levels observed among otherwise healthy controls . These findings favor the recommendation of resistance exercise for elderly adults living with HIV adults PURPOSE The purpose s of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function , CD4 cell count , and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals ( N = 28 ) and to assess the degree to which ill health was associated with exercise relapse . METHODS Responses to grade d exercise test , physician-assessed health status , and CD4 cell counts were determined at baseline and 12-wk follow-up for participants r and omly assigned to exercise or control conditions , and reasons for exercise noncompliance were recorded . RESULTS Approximately 61 % of exercise-assigned participants complied ( > 50 % attendance ) with the exercise program , and analyses of exercise relapse data indicated that obesity and smoking status , but not exercise-associated illness , differentiated compliant from noncompliant exercisers . Compliant exercisers significantly improved peak oxygen consumption ( VO2peak ; 12 % ) , oxygen pulse ( O2pulse ; 13 % ) , tidal volume ( TV ; 8 % ) , ventilation ( VE ; 17 % ) , and leg power ( 25 % ) to a greater degree than control participants and noncompliant exercisers ( all P < 0.05 ) . Although no group differences in health status were found , a significant interaction effect indicated that noncompliant exercisers ' CD4 cells declined ( 18 % ) significantly , whereas compliant exercisers ' cell counts significantly increased ( 13 % ; P < 0.05 ) . CONCLUSION We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks , attention to factors associated with exercise adherence is warranted PURPOSE Highly active antiretroviral therapy has improved the prognosis of human immuno deficiency virus type 1 (HIV-1)-infected individuals , but it has been associated with the development of metabolic and fat distribution abnormalities known as the lipodystrophy syndrome . This study tested the hypothesis that aerobic exercise training added to a low-lipid diet may have favorable effects in HIV-1-infected individuals with dyslipidemia and lipodystrophy . METHODS Thirty healthy subjects , carriers of HIV-1 , with dyslipidemia and lipodystrophy , all of whom were using protease inhibitors and /or non-nucleoside reverse transcriptase inhibitors , were r and omly assigned to participate in either a 12-wk program of aerobic exercise or a 12-wk stretching and relaxation program . All subjects received recommendations for a low-lipid diet . Before and after intervention , peak oxygen uptake , body composition , CD4 , viral load , lipid profile , and plasma endothelin-1 levels were measured . RESULTS Peak oxygen uptake increased significantly in the diet and exercise group ( mean + /- SD : 32 + /- 5 mL x kg(-1 ) x min(-1 ) before ; 40 + /- 8 mL x kg(-1 ) x min(-1 ) after ) but not in the diet only group ( 34 + /- 7 mL x kg(-1 ) x min(-1 ) before ; 35 + /- 8 mL x kg(-1 ) x min(-1 ) after ) . Body weight , body fat , and waist-to-hip ratio decreased significantly and similarly in the two groups . There were no significant changes in immunologic variables in either group . Likewise , plasma triglycerides , total cholesterol , and HDL cholesterol levels did not change significantly in either group . Plasma endothelin-1 levels were elevated in both groups and presented no significant changes during the study . CONCLUSION HIV-seropositive individuals with lipodystrophy and dyslipidemia su bmi tted to a short-term intervention of low-lipid diet and aerobic exercise training are able to increase their functional capacity without any consistent changes in plasma lipid levels Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome ( AIDS ) wasting syndrome ( AWS ) . Testosterone and exercise increase muscle mass in men with AWS , with unclear effects on muscle composition . We examined muscle composition in 54 eugonadal men with AWS who were r and omized to 1 ) testosterone ( 200 mg i m weekly ) or placebo and simultaneously to 2 ) resistance training or no training in a 2 x 2 factorial design . At baseline and after 12 wk , we performed assessment s of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition . Leaner muscle has greater attenuation . Baseline muscle attenuation correlated inversely with whole body fat mass ( r = -0.52 , P = 0.0001 ) . This relationship persisted in a model including age , body mass index , testosterone level , viral load , lean body mass , and thigh muscle cross-sectional area ( P = 0.02 ) . Testosterone ( P = 0.03 ) and training ( P = 0.03 ) increased muscle attenuation . These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training . Anabolic therapy in these patients increases muscle leanness Patients on highly active antiretroviral therapy ( HAART ) spend less time on vigorous activities due to lower aerobic capacity with functional limitations that can be attributed to a detraining effect , result ing in a poor quality of life ( QoL ) . The overall aims of rehabilitation are to restore , to maintain , and to enhance the QoL and this detraining effect could possibly be reversed by a rehabilitation program . This r and omized controlled prospect i ve longitudinal descriptive study evaluated the impact of a rehabilitation program of moderate-intensity cycling and treadmill walking exercises with a home program on the QoL for individuals on HAART . Fifty-two participants with baseline QoL values formed the experimental and control groups with a 3-month pretest and posttest using the short-form health survey ( SF-36 ) question naire . No adverse effects from exercises were experienced , and 20 ( 77 % ) of the experimental and 16 ( 62 % ) of the controls completed the program . A significantly higher number of women dropped out ( P<0.04 ) , with four ( 15 % ) from the experimental group and six ( 23 % ) from the control group . There were significant improvements in all QoL domains ( P<0.05 ) for the experimental group compared with the control group , with the physical component summary ( P<0.018 ) and mental component summary ( P<0.021 ) scores being significantly higher after rehabilitation . Sick leave decreased from a mean of 7 days to 3 for the experimental group and 5 for the control group . These results indicate that a rehabilitation program of moderate-intensity exercises with a home program significantly improved the QoL for individuals on HAART . Further research with a comprehensive rehabilitation program and a larger sample is recommended Objectives The purpose of the study was to examine the effects of aerobic exercise on physiological fatigue ( time on treadmill ) , dyspnea [ rate of perceived exertion ( RPE ) and forced expiratory volume at 1 s ( FEV1 ) ] , weight , and body composition in HIV-1-infected adults ( 200–499 × 106 CD4 + cells/l ) . Design The study was a r and omized , wait-listed , controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment . Methods Sixty subjects were recruited and r and omized to two groups . Experimental subjects completed a 12-week supervised exercise program . Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program . Results At baseline , the groups were similar in age , weight , body mass index [ mean body mass index ( BMI ) > 27 ] , time since diagnosis , number of symptoms , CD4 + cell count , and number on protease inhibitor therapy ( n = 7 ) . Despite disproportionate attrition from the exercise group ( 38 % ) , exercise subjects were able to remain on the treadmill longer , lost weight , decreased BMI , subcutaneous fat , and abdominal girth when compared to controls . The improvement in weight and body composition occurred without a decrease in kilocalories consumed . Exercise did not seem to have an effect on RPE , a surrogate for dyspnea , and FEV1 . There was no significant difference in either the change in CD4 + cell count , percentage or copies of plasma HIV-1 RNA between groups . Conclusions We conclude that supervised aerobic exercise training safely decreases fatigue , weight , BMI , subcutaneous fat and abdominal girth ( central fat ) in HIV-1-infected individuals . It did not appear to have an effect on dyspnea Abstract The purpose of this study is to analyse the effect of 12 weeks of non-linear resistance training ( NLRT ) on anthropometry , muscle strength and inflammatory biomarkers in persons infected with human immunodeficiency virus ( PIHIV ) . Thirty previously sedentary PIHIVs were r and omized into the NLRT ( n = 15 ) and control ( CON , n = 15 ) groups . NLRT group were su bmi tted to 12 weeks of training , whereas the CON group maintained their daily habits . At baseline and after 12 weeks , both groups underwent anthropometric evaluations and blood sampling for the analysis of inflammatory biomarkers . Analysis of covariance using preintervention values as covariate was performed to determine the effects of exercise on anthropometry , muscle strength , cytokines levels and T cells . Significance was set at p < 0.05 . After 12 weeks of intervention , there was a decrease in subcutaneous body fat ( p < .0001 ) , neck , abdomen and waist circumferences ( p < .05 ) , waist-to-hip ratio ( p = .009 ) , blood levels of interleukin (IL)-1β ( p = .029 ) , IL-6 ( p = .005 ) , IL-8 ( p = .010 ) , and tumour necrosis factor (TNF)-α ( p = .001 ) and an increase in muscle strength ( p < .0001 ) , IL-10 levels ( p = .030 ) and CD4 + ( p = .004 ) and CD8 + ( p < .0001 ) counts in the NLRT compared to CON group . Twelve weeks of NLRT promoted positive changes in the body fat , body circumferences , muscular strength and inflammatory profile in PIHIV HIV-infected individuals are frequently active , but guidelines for exercise in this population lack scientific support , since studies on the effects of exercise training on immunologic variables of HIV-1 positive individuals have shown conflicting results . Exercise capacity , immunologic markers ( CD4 , CD8 and CD4:CD8 ratio ) , anthropometric measurements , and depression scores were evaluated to compare the effects of two intensities of aerobic exercise on HIV-1 seropositive individuals . Twenty-one healthy subjects ( 14 men , 7 women ) , carriers of the HIV-1 virus ( CD4>200 cells x mm(-3 ) ) , and inactive for at least 6 months , completed a 12 week exercise training program ( 36 sessions of 1 h , 3 times per week ) , in a moderate intensity group ( 60+/-4 % of maximal heart rate ) or a high intensity group ( 84+/-4 % of maximal heart rate ) . Exercise capacity estimated by treadmill time was increased significantly in both moderate intensity ( 680+/-81 s before ; 750+/-151 s after ) and high intensity ( 651+/-122 s before ; 841+/-158 s after ) groups , but the high intensity group presented a significantly larger increment ( p<0.01 ) . There were no significant changes in the immunologic variables , anthropometric measurements or depression scores . Thus , HIV-seropositive individuals that participate in moderate and high intensity exercise programs are able to increase their functional capacity without any detectable changes in immunologic variables , anthropometric measurements or depression scores ABSTRACT Distal symmetrical poly-neuropathy ( DSP ) is a neurological complication associated with HIV/AIDS and stavudine ( d4 T ) containing antiretroviral therapy . People with DSP experience pain , numbness and muscle weakness , which affect their quality of life ( QOL ) . The purpose of this study was to establish the effect of a progressive-resisted exercise ( PRE ) intervention on health-related quality of life ( HR-QOL ) in people living with HIV/AIDS-related DSP . An assessor-blinded r and omised controlled trial was conducted , with participants source d from 10 clinics with HIV services , the family care clinic at Wilkins Hospital and 2 large hospitals in Harare , Zimbabwe . A 12-week PRE intervention was conducted twice weekly for 80 participants , while the control group with 80 participants continued with usual daily activities . The main outcome variable was HR-QOL for which we controlled for demographic and clinical measures in generalised estimating equation population -averaged models . Data were summarised and analysed using an intention to treat analysis approach using the Stata v10 program . Mean age of participants was 42.2 years ( SD = 8.5 ) . While d4 T was used by 59 % ( n = 94 ) , an equal proportion of the participants also had moderate to severe neuropathy . PRE was found to significantly improve HR-QOL in the intervention group based on the mean difference between the intervention group mean change and the mean change in the control group ( F ratio 4.24 ; p = .04 ) . This study established that PREs have positive effects on HR-QOL for people living with HIV/AIDS-related DSP OBJECTIVE This study aim ed to assess the usefulness of two interventions in a group rehabilitation medicine setting to determine strategies and exercise guidelines for long-term care of the HIV/AIDS population with human immunodeficiency virus ( HIV ) and /or acquired immunodeficiency syndrome ( AIDS ) . DESIGN This was a r and omized clinical trial investigating the effects of tai chi ( TC ) and aerobic exercise ( EX ) on functional outcomes and quality of life ( QOL ) in patients with AIDS . SETTING Two outpatient infectious disease clinics in a mid-atlantic state were the setting . SUBJECTS AND INTERVENTION Thirty-eight ( 38 ) subjects with advanced HIV ( AIDS ) were r and omized to one of three groups : TC , EX , or control . Experimental groups exercised twice weekly for 8 weeks . OUTCOME MEASURES The primary outcomes included QOL as measured by the Medical Outcomes Short Form ( MOS-HIV ) and Spirituality Well-Being Scale ( SWB ) . Functional measures included the functional reach ( FR ) for balance , sit and reach ( SR ) for flexibility , and sit-up ( SU ) test for endurance . The physical performance test ( PPT ) was used to determine overall function , and the Profile of Mood States ( POMS ) was used to evaluate psychologic changes . To consider the patients ' explanations for these measurements , qualitative data were collected from subjects ' journals , focus groups , and nonparticipant observation . RESULTS Thirty-eight ( 38 ) subjects were included in data analysis : 13 in the TC group , 13 in the EX group , and 12 in the control group . Results of analysis of covariance showed significant changes in the exercise groups in overall functional measures ( p < 0.001 ) . The MOS-HIV showed a significant difference on the subscale of overall health ( p = 0.04 ) . The POMS showed significant main effect for time in confusion-bewilderment ( p = 0.000 ) and tension-anxiety ( p = 0.005 ) . Three dominant themes emerged from the qualitative data , including : positive physical changes , enhanced psychologic coping , and improved social interactions . CONCLUSIONS This study shows that TC and EX improve physiologic parameters , functional outcomes , and QOL . Group intervention provides a socialization context for management of chronic HIV disease . This study supports the need for more research investigating the effect of other types of group exercise for this population . This study sets the stage for a larger r and omized controlled trial to examine the potential short- and long-term effects of group exercise that may prove beneficial in the management of advanced HIV disease . Further research is warranted to evaluate additional exercise interventions that are accessible , safe , and cost-effective for the HIV population The authors conducted a r and omized controlled trial to assess the impact of a 15-week ( 20 minutes three times per week ) home-based aerobic exercise intervention versus usual care on the physical endurance , immune status , and self-reported health status of 99 HIV-infected adults . In the exercise group , there was no improvement in physical endurance or health-related quality of life ( HRQOL ) , except in the Medical Outcomes Study -HIV Health Survey Overall Health subscale ( difference = 12.1 , 95 % confidence interval = 2.0 - 22.2 , p = .02 ) . Although physical endurance levels were maintained at baseline levels in the intervention group and declined in the control group , differences between the groups were small and not significant . There were also no significant changes in CD4 + T-lymphocyte counts . Exercise appears to be safe in HIV-infected patients . Improvements in physical endurance and HRQOL might result if the exercise protocol is longer or progressive . Further research is needed to establish guidelines for exercise in patients on highly active antiretroviral therapy Objective To determine the effects of whey protein , resistance exercise , and combined protein and exercise treatment on body cell mass ( BCM ) , muscle strength , and quality of life ( QOL ) in HIV-infected women with reduced BCM . Design and setting Prospect i ve , r and omized , controlled trial at a university hospital in New York City . Methods A volunteer sample of 30 HIV-infected women were r and omized to whey protein ( PRO ) , progressive resistance exercise ( PRE ) , or combined treatment ( PRO – PRE ) for 14 weeks after a 6-week control period . The main outcome measures were body weight , BCM , skeletal muscle , fat mass , muscle strength , and QOL . Results There were no significant changes in BCM , strength , or QOL during the control period . PRO patients gained 3.6 kg ( P = 0.001 ) , and 2.5 kg fat ( P = 0.002 ) with no change in BCM ( 0.5 kg;P = 0.07 ) or skeletal muscle ( 0.6 kg;P = 0.12 ) . The PRE group increased BCM ( 0.74 kg;P = 0.03 ) and skeletal muscle ( 1.2 kg;P < 0.001 ) and decreased fat ( 1.7 kg;P = 0.02 ) . PRO – PRE increased BCM ( 0.61 kg;P = 0.01 ) without change in skeletal muscle ( 0.6 kg;P = 0.30 ) . Strength increased for both exercise groups ( range , 40.6–95.3%;P < 0.001 ) . The QOL physical activity score improved for PRE ( P = 0.02 ) and worsened for PRO ( P = 0.01 ) . Conclusions Resistance exercise significantly increased BCM , muscle mass , muscle strength , and QOL in HIV-infected women with reduced BCM . Whey protein had little effect on BCM accrual . Combined protein and exercise did not increase BCM in excess of gains achieved by exercise alone OBJECTIVE Despite the significant positive effect of Highly Active Antiretroviral Therapy on physical and psychosocial well-being of people living with human immunodeficiency virus/acquired immune deficiency syndrome ( HIV/AIDS ) ( PLWHA ) ; decreased physical activity and its associated cardiovascular risk still pose some consequences for health and general well-being . This study investigated the effect of an 8 week aerobic exercise training on cardiovascular parameters and CD4 cell ( T-cells ) count of PLWHA . MATERIAL S AND METHODS This r and omized controlled trial recruited 30 age matched PLWHA who were r and omly assigned into exercise group ( EG ) ( n = 15 ) and control group ( CG ) ( n = 15 ) respectively . The PLWHA were patients receiving treatment in President 's Emergency Plan for AIDS relief at the HIV clinic of the University of Nigeria Teaching Hospital , Nigeria . The EG in addition to conventional therapy received moderate intensity continuous exercise training ( 60 - 79 % of the maximum heart rate [ max ] ) of between 45 and 60 min , 3 times/week for 8 weeks , while the CG received conventional therapy involving antiretroviral therapy and counseling only . Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , maximum oxygen uptake ( VO₂ max ) and CD4 cell count were assessed at baseline ( week 1 ) and week 8 respectively . Analysis of co-variance and Pearson correlation tests were used in data analysis . RESULTS Findings of the study revealed a significant effect ( ANCOVA test ) of moderate intensity continuous exercise training program on , SBP , DBP , VO₂ max and CD4 cell count at P < 0.05 . Changes in VO₂ max significantly correlated ( Pearson correlation test ) with changes in CD4 cell count ( r = 0.528 ) at P < 0.05 . CONCLUSION Moderate intensity aerobic exercise is an effective complementary therapy in lowering blood pressure and increasing CD4 cell count in PLWHA Aerobic exercise training may help prevent or reduce depressive symptoms experienced by persons living with HIV infection . However , the psychological effects of aerobic exercise have not been studied extensively . This study evaluated the effects of an aerobic exercise training program on self-reported symptoms of depression in HIV-infected adults and examined the convergent validity of two widely used depressive symptom scales . Sixty HIV-infected adults participated in a r and omized , controlled trial of a supervised 12-week aerobic exercise training program . As compared to study controls , exercise participants showed reductions in depressive symptoms on all indices , and total depressive symptoms scores were highly correlated . Additional study of the psychological effects of aerobic exercise programs in the target population is recommended |
1,130 | 29,074,989 | Diabetic corneas are more vulnerable to stress and trauma , result ing in greater morphological abnormalities and longer recovery time | Corneal endothelium morphological abnormalities result in fluid imbalance , stromal swelling , and loss of transparency , thus impairing visual function .
Recently , growing number of studies have focused on diabetic corneal abnormalities after cataract surgery and its comparison with non-diabetic patients , the results remain conflicting . | PURPOSE To evaluate postoperative corneal swelling as a predictor of corneal endothelial cell loss after phacoemulsification cataract surgery . DESIGN Prospect i ve observational case series . METHODS Thirty patients planned for routine phacoemulsification cataract surgery were included . Ultrasonic pachymetry and specular microscope endothelial photography of the central and nasal portions of the cornea and Orbscan II slit-scan tomography were performed preoperatively and the day after surgery . The 30 patients were selected from 41 patients based on their increase in central corneal thickness : the first 10 cases with a < 5 % increase , the first 10 with a 6 % to 20 % increase , and the first 10 with a > or = 20 % increase . The same measurements were repeated after 1 , 2 , and 3 months . The primary outcome measures were corneal endothelial cell loss and increase in pachymetry . Several other parameters were also registered , including age , degree of cataract , visual acuity , phacoemulsification time and energy , total operation time , and the amount of infusion fluid used . RESULTS The central corneal swelling at postoperative day 1 was strongly correlated with the central corneal endothelial cell loss at 3 months ( R(2 ) = 0.785 , P < .001 ) . CONCLUSIONS In this series , with large variations in the corneal swelling at the first postoperative day , the degree of permanent corneal endothelial damage was reflected in the degree of early postoperative corneal swelling . Measuring the difference in pachymetry at postoperative day 1 is a useful way to assess the effects on the corneal endothelium exerted by the phacoemulsification procedure This study investigated whether diabetic-like corneal sensory deficits occur in the galactose-fed rat model of diabetic ocular complications and if such deficits could be prevented using either of two structurally different aldose reductase ( AR ) inhibitors , CT-112 or AL-1576 . S-D rats were r and omly grouped to receive a diet of Purina chow with either 50 % starch ( n=25 ) or 50 % D-galactose ( n=65 ) . Some of the galactosemic rats received either 0.25 % CT-112 topically 3x daily ( n=15 ) or 28 mg/kg body wt/day AL-1576 systemically ( n=10 ) . The control and untreated galactosemic rats in the CT-112 portion of the study received equivalent topical doses of the vehicle . Sensitivity measurements were made with a Cochet-Bonnet Aesthesiometer mounted on a micromanipulator . The filament was applied to the central corneal surface ( mean pressure of 0.96 g/mm2 ) and viewed using a slit-lamp biomicroscope . Ten consecutive stimuli were conducted on each cornea and the average number of blink-responses was expressed as a percent of total stimuli effected . Mean initial corneal sensitivities were similar in all groups . Corneal sensitivity in the galactosemic rat was reduced ( p<0.01 ) at each monthly measurement compared to control . Animals treated with CT-112 or AL-1576 showed a significant increase in the mean blink-response compared to untreated galactose-fed rats and did not differ significantly from controls towards the completion of the 7 month study . Animals treated with AL-1576 did not develop cataracts , whereas those treated topically with CT-112 and untreated galactose-fed rats developed bilateral nuclear cataracts within 3 weeks . This is the first study to demonstrate decreased corneal sensitivity in the galactose-fed rat model and its amelioration with AR inhibitors . Thus , aldose reductase , the first enzyme of the polyol pathway , may have an important role in the pathogenesis of decreased corneal sensitivity . The model could be useful for investigating the pathogenic mechanism(s ) involved in reduced corneal sensitivity associated with diabetic keratopathy in humans Purpose : To compare endothelial damage induced by different cataract incision sites and sizes using specular microscopy . Setting : Department of Ophthalmology , Hospital of San Donà di Piave , Venice , Italy . Methods : Eighty‐one eyes having phacoemulsification were r and omly assigned to 1 of 3 groups of 27 eyes each : 3.5 mm clear corneal incision ( CCI ) with silicone foldable intraocular lens ( IOL ) implantation ; 5.5 mm sutured CCI with poly(methyl methacrylate ) ( PMMA ) IOL implantation ; 5.5 mm scleral tunnel with PMMA IOL implantation . All incisions were centered at the 120‐degree semimeridian ; that is , they were superotemporal in right eyes and superonasal in left eyes . Noncontact specular microscopy was performed in the center and at the 12 o'clock position preoperatively as well as 1 week and 1 , 3 , and 12 months postoperatively . The endothelial cell density , mean cell area , cell size variation coefficient , percentage of hexagonality , and corneal thickness were considered . Results : Progressive endothelial cell loss and an increase in mean cell area occurred in all groups during the follow‐up . The cell loss percentages relative to the endothelial center appeared similar among the groups and slightly although not significantly lower in the scleral tunnel group . The scleral tunnel group had a statistically significant lower cell loss percentage at the 12 o'clock position than the 2 CCI groups at all follow‐ups . Conclusions : The scleral tunnel group had less postoperative endothelial damage than the 2 CCI groups , with a statistically significant difference at the 12 o'clock position . This is probably because the scleral tunnel incision is placed more posteriorly and therefore induces less direct and indirect endothelial trauma Purpose : To investigate the corneal endothelial cell density and morphology in patients with and without diabetes after phacoemulsification with intraocular lens implantation . Methods : A clinical prospect i ve study including 30 patients with type 2 diabetes and 30 control patients without diabetes scheduled to undergo cataract surgery . No difference in preoperative age was observed between the 2 groups ( P = 0.90 ) . Sample size was based on a power calculation ( power 0.90 ; P = 0.05 ) . The patients without diabetes had a casual blood glucose test performed to disclose undetected diabetes . The patients with diabetes had a serum glycosylated hemoglobin ( HbA1c ) test performed to reveal the glycemic control . The endothelial cell density , variation in endothelial cell size ( CV ) , percentage of hexagonal cells , and central corneal thickness ( CCT ) were recorded at baseline and at 3 months postoperatively . Results : The mean decrease in endothelial cell density at 3 months in the diabetic group was 154 cells per square millimeter ( 6.2 % ) and 42 cells per square millimeter ( 1.4 % ) in the control group . The difference in cell loss between the 2 groups was significant ( P = 0.04 ) . A significant decrease in the percentage of hexagonal cells was also seen in the diabetic group ( P = 0.01 ) . There was no statistically significant change in CV or CCT . Visual acuity increased significantly and equally in the 2 groups . Conclusions : The present study reveals a significantly greater loss of corneal endothelial cells in a diabetic group under good glycemic control , compared with nondiabetic group 3 months after phacoemulsification . The morphological changes in the endothelial cells in patients with well-controlled diabetes were not reflected in impaired function as judged by CCT Purpose : To evaluate intraoperative endothelial damage after planned extracapsular cataract extraction ( ECCE ) with different capsulotomy techniques and phacoemulsification . Setting s : San Carlos University Hospital , Castroviejo Institute , Madrid , Spain . Methods : In this prospect i ve , r and omized study , 60 patients with senile cataract scheduled for cataract surgery were divided into three groups of 20 each : Group 1 had phacoemulsification ; Group 2 , planned ECCE with continuous curvilinear capsulorhexis ; and Group 3 , ECCE with letter‐box capsulotomy . Preoperatively and 3 months postoperatively , endothelial cell density , percentage of hexagonality , and the cell size variation coefficient were determined by contact specular microscopy ; endothelial permeability was examined by anterior segment fluorophotometry and central comeal thickness , by ultrasonic pachymetry . Results were analyzed using the two‐tailed Students t‐test and analysis of variance . Results : In all three groups , endothelial permeability and cell loss increased significantly from the preoperative values , but there were no significant differences among the postoperative values . Mean cell loss was 11.8 % in Group 1 , 12.8 % in Group 2 , and 10.1 % in Group 3 . There were no differences between the preoperative and postoperative morphometric indexes . Postoperative pachymetric measurements were not significant . Conclusions : Endothelial response was not statistically significantly different among the surgical techniques , although endothelial damage was lower in Group 3 , which could indicate a protective effect of the anterior capsule during cataract extraction . Endothelial barrier function remained disturbed despite the apparent morphological stabilization Purpose : Cataract surgery is known to change the corneal endothelial cell density and morphology . In patients with diabetes , this change is more pronounced . This prospect i ve cohort study was conducted to assess and compare the endothelial cell loss and change in central corneal thickness ( CCT ) after manual small incision cataract surgery ( SICS ) in patients with diabetes versus age-matched patients without diabetes . Methods : Consecutive patients with diabetes ( 153 ) in the age group 40 - 70 years and age-matched patients without diabetes ( 163 ) undergoing manual SICS were enrolled . Preoperative and 1 week , 6 weeks , and 3 months postsurgery assessment s of corneal endothelial loss and change in CCT were done using specular microscopy and ultrasound pachymetry . Results : There was a steady drop in the endothelial density in both the groups postoperatively , with the percentage of endothelial loss at 6 weeks and 3 months being 9.26 ± 9.55 and 19.24 ± 11.57 , respectively , in patients with diabetes and 7.67 ± 9.2 and 16.58 ± 12.9 , respectively , in controls . The percentage of loss between 6 weeks and 3 months was found to be of significant difference ( P < 0.023 ) . In both the groups , an initial increase in CCT till the second postoperative week was followed by a reduction of CCT in the subsequent follow-up ( sixth week ) and a further reduction in the last follow-up ( 3 months ) . The change in CCT between the second and sixth weeks was significantly higher in the diabetic group ( P = 0.045 ) . Conclusions : The diabetic endothelium was found to be under greater metabolic stress and had less functional reserve after manual SICS than the normal corneal endothelium Purpose : To evaluate central endothelial cell loss ( ECL ) following clear corneal cataract surgery using two different incision sizes and the effect of ultrasound time ( UST ) and power on postoperative ECL and various cell parameters . Methods : Fifty‐eight patients had phacoemulsification through temporal , two‐step clear corneal tunnel incisions . In Group A ( n = 28 ) , a one‐piece , plate‐haptic , foldable silicone intraocular lens ( IOL ) was implanted through a 3.5 mm sutureless incision . In Group B ( n = 30 ) , a poly(methyl methacrylate ) IOL was implanted through a 5.0 mm incision with one radial suture . The central endothelial cell counts were recorded preoperatively and postoperatively at 2 to 5 days , after 6 months , and after 1 year . Color‐coded , computer‐assisted specular microscopy was used for special cell analysis after 1 year . Results : Collective data showed an ECL of 7.9 ± 4.1 % ( mean ± st and ard deviation ) at 2 to 5 days postoperatively , 6.7 ± 2.9 % after 6 months , and 7.3 ± 3.3 % after 1 year . A direct linear relationship was found between ECL and UST and power : ECL increased as UST and power increased . After 1 year , ECL in Group A was 4.2 % with UST ≤1 1/2 minutes , 6.7 % with UST ≥ 1 1/2 to 2 1/2 min , and 9.6 % with UST > 2 1/2 to 3 1/2 min ; in Group B , it was 6.0 % , 7.5 % , and 11.4 % , respectively . Specular microscopy showed normal , age‐related cell parameters 1 year postoperatively . Conclusions : Phacoemulsification with 3.5 mm clear corneal incisions produced slightly less ECL ( 6.7 % ) than phacoemulsification with 5.0 mm incisions ( 7.9 % ) . Total ECL of 7.3 % at 1 year postoperatively compared favorably with ECL rates of other cataract extraction methods PURPOSE To investigate whether modern phacoemulsification surgery results in more damage to the corneal endothelium than extracapsular cataract extraction ( ECCE ) , and to examine which preoperative , operative , and postoperative factors influence the effect of cataract surgery on the endothelium . DESIGN R and omized controlled trial . PARTICIPANTS Five hundred patients 40 years or older were r and omized into 2 groups ( ECCE , 249 ; phacoemulsification , 251 ) . METHODS Central corneal endothelial cell counts , coefficient of variation of cell size , and hexagonality were assessed before surgery and up to 1 year postoperatively . MAIN OUTCOME MEASURE Endothelial cell count . RESULTS Four hundred thirty-three patients completed the trial . The initial preoperative mean cell count for the entire sample was 2481 ( st and ard error [ SE ] : 18.6 ) , reduced at 1 year postoperatively to 2239 ( SE : 23.5 ) . An average 10 % reduction in cell count was recorded by 1 year postoperatively . There was no such change in hexagonality or in the coefficient of variation . There was no significant difference in overall percentage cell loss between the 2 treatment groups . Factors associated with excessive cell loss ( > or = 15 % by 1 year ) were a hard cataract ( odds ratio [ OR ] : 2.1 , 95 % confidence limits : 1.1 - 4.1 ; P = 0.036 ) , age ( OR : 1.04 , P = 0.005 ) , and capsule or vitreous loss at surgery ( OR : 2.38 , P = 0.106 ) . Phacoemulsification carried a significantly higher risk ( OR : 3.7 , P = 0.045 ) of severe cell loss in the 45 patients with hard cataracts relative to ECCE ( 52.6 % vs. 23.1 % ; chi-square test , P = 0.041 ) , with both procedures achieving similar postoperative visual acuity outcomes . CONCLUSIONS No significant difference in overall corneal endothelial cell loss was found between these 2 operative techniques . The increased risk of severe cell loss with phacoemulsification in patients with hard cataracts suggests that phacoemulsification may not be the optimal procedure in these cases , and that ECCE should be preferred Purpose : The aim of this study was to analyze microstructural corneal changes following phacoemulsification of cataract with intraocular lens insertion in diabetes mellitus ( DM ) . Methods : Prospect i ve study of consecutive patients undergoing phacoemulsification with intraocular lens insertion , over a period of 6 months . Age , gender , serum glycosylated hemoglobin A1c levels , and effective phacoemulsification time were recorded . Anterior segment optical coherence tomography and corneal in vivo confocal microscopy were performed preoperatively and 1-month postoperatively . Subbasal nerve plexus ( SBN ) density , basal epithelial cell density , and endothelial cell density ( ECD ) were quantitatively analyzed . Results : Twenty-eight patients with type 2 DM ( 71.2 ± 7.6 years ) and 23 healthy controls ( mean age , 74.4 ± 7.4 years ) were recruited . Mean hemoglobin A1c level was 7.5 % in patients with DM and 5.7 % in the control group ( P < 0.0001 ) . A significant reduction in SBN density was noted postoperatively in both DM ( P < 0.0001 ) and non-DM groups ( P < 0.0001 ) . Patients with DM had a lower mean SBN density compared with non-DM group , before ( P < 0.0001 ) and after surgery ( P < 0.0001 ) . Longer effective phacoemulsification time correlated with a greater decrease in ECD postoperatively in the whole cohort ( P < 0.0001 ) , and in the control ( P = 0.002 ) and DM ( P = 0.039 ) groups independently . There was no significant difference in the percentage decrease in ECD postoperatively between these 2 groups ( P = 0.173 ) . Conclusions : Subbasal nerve density is reduced after cataract surgery in patients with and without DM . However , lower initial SBN density in patients with DM may predispose them to develop diabetic keratopathy . DM does not predispose to greater endothelial loss following phacoemulsification BACKGROUND --Marked variations in cell size ( polymegethism ) and shape ( pleomorphism ) are characteristic of the corneal endothelium in diabetic patients and animals . METHOD --Wide field specular microscopy was used to evaluate the clinical efficacy of treating the diabetic corneal endothelium with topical instillation of 0.5 % aldose reductase inhibitor , CT-112 . RESULTS --Morphological variations ( polymegethism and pleomorphism ) of the endothelium in eight eyes from eight patients receiving CT-112 resolved within 3 months after initiation of treatment . In contrast , no change in endothelial morphology was noted in five eyes from five patients who received placebo . CONCLUSION --These observations suggest that aldose reductase may be involved in the aetiology of corneal endothelial variations in diabetic patients PURPOSE To evaluate the effect of the location of the corneoscleral tunnel incision as well as preoperative and intraoperative parameters on total and localized endothelial cell loss . SETTING Department of Ophthalmology , Humboldt-University of Berlin , Berlin , Germany . METHODS Fifty consecutive patients scheduled for routine cataract surgery were selected prospect ively for this clinical trial . Preoperatively , the axial length , anterior chamber depth , lens thickness , and astigmatism were measured . Phacoemulsification time and relative energy as well as total surgical time were recorded . With a specular microscope , endothelial cell counts were determined central ly , superiorly , and temporally preoperatively and 6 weeks and 6 and 12 months postoperatively . RESULTS After 12 months , the mean overall central endothelial cell loss in all eyes was 8.5 % . The mean endothelial cell loss was 11.9 % in the lateral quadrant and 11.4 % in the superior quadrant . There were no significant differences between superior and temporal surgical approaches in intraoperative parameters of phacoemulsification time , relative intensity of phacoemulsification , and surgical time . There were no significant differences in central endothelial cell loss or in the area localized in the quadrant of the positions of the corneal surgical site . The only risk factors found significant for higher endothelial cell loss were shorter axial length and longer phacoemulsification time . CONCLUSIONS The location of corneoscleral incisions for phacoemulsification can be chosen according to the preoperative astigmatism without inducing additional adverse effects on the corneal endothelium . Shorter eyes have a significantly higher risk for greater endothelial cell loss |
1,131 | 31,727,031 | Housing first , a structural intervention , led to improvements in housing stability .
Many interventions showed inconsistent results compared to services as usual or other interventions , but often led to improvements over time in both the intervention and comparison group .
The equity analysis showed that equity variables were inconsistently measured , but there was data to suggest differential outcomes based upon gender and ethnicity .
This review identified a variety of interventions for youth experiencing homelessness .
Promising interventions include cognitive behavioural therapy for addressing depression , family-based therapy for substance use outcomes , and housing programs for housing stability . | Youth often experience unique pathways into homelessness , such as family conflict , child abuse and neglect .
Most research has focused on adult homeless population s , yet youth have specific needs that require adapted interventions .
This review aims to synthesize evidence on interventions for youth and assess their impacts on health , social , and equity outcomes . | The objective of this study was to determine the prevalence of , and factors associated with , sexual violence in childhood , adolescence and adulthood , among injection drug using men and women . The Vancouver Injection Drug User Study is a prospect i ve cohort of injection drug users ( IDU ) begun in 1996 . The analysis included all individuals who completed the baseline question naire who responded to a question about sexual assault . Multivariate modeling was used to determine and to what extent a history of sexual violence at different ages is predictive of HIV risk and other health risk behaviors . HIV prevalence was calculated as the total current number of HIV-positive individuals in the cohort . Of the 1437 eligible individuals , 36 % reported a lifetime history of sexual violence ; 68 % of women , and 19 % of men ( p<0.001 ) . After adjusting for fixed sociodemographics , these individuals were more likely to have ever been in the sex trade , to knowingly share needles/rigs with HIV-positive people , to have attempted suicide , to have ever accidentally overdosed , to binge on alcohol , and to have been diagnosed with a mental disorder/disability . The prevalence of child sexual abuse in this cohort is 21 % ; 33 % for women , and 13 % for men . The data show a dose-response relationship between age at first sexual violence and most risk behaviors examined . These relationships are further mediated by gender . The prevalence of HIV among individuals who ever experienced sexual violence was 25 % , compared to 19 % among those who never experienced sexual violence ( p=0.006 ) . Sexual violence , and especially child sexual abuse , is highly prevalent among this cohort , particularly among women . Child sexual abuse has worse consequences for both genders than sexual violence later in life . Nevertheless , women and men are affected differently by sexual violence at different ages , and this has significant implication s for health promotion programs , and specifically HIV prevention Homeless young adults ages 18 - 25 exhibit high rates of alcohol and other drug ( AOD ) use , and sexual risk behaviors such as unprotected sex . Yet few programs exist for this population that are both effective and can be easily incorporated into setting s serving this population . This pilot cluster cross-over r and omized controlled trial evaluates AWARE , a voluntary four session group-based motivational interviewing ( MI ) intervention to reduce AOD use and sexual risk behavior . We evaluated AWARE with 200 homeless young adults using drop-in center services in Los Angeles County ( mean age=21.8years ; 73 % male ; 79 % heterosexual ; 31 % non-Hispanic White , 25 % African American , 24 % Hispanic , 21 % multiracial/other ) . Surveys were completed at baseline and three months after program completion . Retention in the AWARE program was excellent ( 79 % attended multiple sessions ) and participants reported high levels of satisfaction with the program . AWARE participants self-reported positive change in their past 3month and past 30day alcohol use ( ps≤0.05 ) , motivation to change drug use ( ps<0.05 ) , and condom use self-efficacy ( p=0.05 ) compared to the control group . Among those with multiple sex partners , AWARE participants showed a decrease in unprotected sexual events ( p<0.05 ) , whereas the control group did not . Results from this pilot evaluation are promising , suggesting that a brief group-MI risk reduction intervention can be effective in helping homeless young adults make positive changes in their alcohol and condom use . Further work is needed to more fully evaluate the efficacy of AWARE on AOD behavior and sexual risk behavior outcomes Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions PURPOSE We evaluate the efficacy of a short family intervention in reducing sexual risk behavior , drug use , and delinquent behaviors among homeless youth . METHODS A r and omized controlled trial of 151 families with a homeless adolescent aged 12 to 17 years . Between March 2006 and June 2009 , adolescents were recruited from diverse sites in Southern California and were assessed at recruitment ( baseline ) , and at 3 , 6 , and 12 months later . Families were r and omly assigned to an intervention condition with five weekly home-based intervention sessions or a control condition ( st and ard care ) . Main outcome measures reflect self-reported sexual risk behavior , substance use , and delinquent behaviors over the past 90 days . RESULTS Sexual risk behavior ( e.g. , mean number of partners ; p < .001 ) , alcohol use ( p = .003 ) , hard drug use ( p < .001 ) , and delinquent behaviors ( p = .001 ) decreased significantly more during 12 months in the intervention condition compared with the control condition . Marijuana use , however , significantly increased in the intervention condition compared with the control condition ( p < .001 ) . CONCLUSIONS An intervention to reengage families of homeless youth has significant benefits in reducing risk over 12 months BACKGROUND Although numerous interventions have been demonstrated to reduce targeted adolescent risk behaviors for brief periods , sustained behavior changes covering multiple risk behaviors have been elusive . OBJECTIVE To determine whether a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) with and without boosters can further reduce adolescent truancy , substance abuse , and sexual risk behaviors and can alter related perceptions 24 months after intervention among youth who have all received an adolescent risk-reduction intervention , Focus on Kids ( FOK ) . DESIGN R and omized , controlled , 3-celled longitudinal trial . SETTING Thirty-five low-income , urban community sites . PARTICIPANTS Eight hundred seventeen African American youth aged 13 to 16 at baseline . Intervention All youth participated in FOK , an 8-session , theory-based , small group , face-to-face risk-reduction intervention , 496 youth and parents received the 1-session ImPACT intervention ( a videotape and discussion ) , 238 of the ImPACT youth also received four 90-minute FOK boosters delivered in small groups . MAIN OUTCOME MEASURES Responses at baseline and 24 months after intervention to a question naire assessing risk and protective behaviors and perceptions . Analyses used General Linear Modeling , intraclass correlation coefficient , analysis of covariance , and multiple comparisons with least significant difference test adjustment . RESULTS After adjusting for the intraclass correlation coefficient , 6 of 16 risk behaviors were significantly reduced ( P < or = .05 ) among youth receiving ImPACT compared with youth who only received FOK ( respectively , mean number of days suspended , 0.65 vs 1.17 ; carry a bat as a weapon , 4.1 % vs 9.6 % ; smoked cigarettes , 12.5 % vs 22.7 % ; used marijuana , 18.3 % vs 26.8 % ; used other illicit drugs , 1.4 % vs 5.6 % ; and , asked sexual partner if condom always used , 77.9 % vs 64.9 % ) . Four of the 7 theory-based subscales reflected significant protective changes among youth who received ImPACT . ImPACT did not produce any significant adverse effects on behaviors or perceptions . CONCLUSION A parent monitoring intervention can significantly broaden and sustain protection beyond that conferred through an adolescent risk-reduction intervention Outreach and service linkage are key for engaging marginalized population s , such as homeless youth , in services . Research to date has focused primarily on engaging individuals already receiving some services through emergency shelters , clinics , or other programs . Less is known about those who are not connected to services and , thus , likely the most vulnerable and in need of assistance . The current study sought to engage non-service-connected homeless youth ( N = 79 ) into a strengths-based outreach and advocacy intervention . Youth were r and omly assigned to receive 6 months of advocacy that focused on linking youth to a drop-in center ( n = 40 ) or to a crisis shelter ( n = 39 ) . All youth were assessed at baseline and 3 , 6 , and 9 months post-baseline . Findings indicated that youth prefer drop-in center services to the shelter . Also , the drop-in center linkage condition was associated with more service linkage overall ( B = 0.34 , SE = 0.04 , p < 0.01 ) and better alcohol-l [ B = −0.39 , SE = 0.09 , t(75 ) = −4.48 , p < 0.001 ] and HIV-related outcomes [ B = 0.62 , SE = 0.10 , t(78 ) = 6.34 , p < 0.001 ] compared to the shelter linkage condition . Findings highlight the importance of outreach and service linkage for reconnecting service-marginalized youth , and drop-in centers as a primary service option for homeless youth BACKGROUND AND OBJECTIVES : " Housing First " has been shown to improve housing stability in homeless individuals with mental illness , but had not been empirically tested in homeless youth . We aim ed to evaluate the effect of " Housing First " on housing stability in homeless youth aged 18 to 24 years participating in At Home/Chez Soi , a 24-month r and omized trial of " Housing First " in 5 Canadian cities . METHODS : Homeless individuals with mental illness were r and omized to receive " Housing First " ( combined with assertive community treatment or intensive case management depending on their level of need ) or treatment as usual . We defined our primary outcome , housing stability , as the percent of days stably housed as a proportion of days for which residence data were available . RESULTS : Of 2148 participants who completed baseline interviews and were r and omized , 7 % ( n = 156 ) were youth aged 18 to 24 years ; 87 received " Housing First " and 69 received treatment as usual . In an adjusted analysis , youth in " Housing First " were stably housed a mean of 437 of 645 ( 65 % ) days for which data were available compared with youth in treatment as usual , who were stably housed a mean of 189 of 582 ( 31 % ) days for which data were available , result ing in an adjusted mean difference of 34 % ( 95 % confidence interval , 24%–45 % ; P < .001 ) . CONCLUSIONS : " Housing First " was associated with improved housing stability in homeless youth with mental illness . Future research should explore whether adaptations of the model for youth yield additional improvements in housing stability and other outcomes While research on homeless adolescents and young adults evidencing substance use disorder is increasing , there is a dearth of information regarding effective interventions , and more research is needed to guide those who serve this population . The current study builds upon prior research showing promising findings of the community reinforcement approach ( CRA ) ( Slesnick , Prestopnik , Meyers , & Glassman , 2007 ) . Homeless adolescents and young adults between the ages of 14 to 20 years were r and omized to one of three theoretically distinct interventions : ( 1 ) CRA ( n = 93 ) , ( 2 ) motivational enhancement therapy ( MET , n = 86 ) , or ( 3 ) case management ( CM , n = 91 ) . The relative effectiveness of these interventions was evaluated at 3 , 6 , and 12 months post-baseline . Findings indicated that substance use and associated problems were significantly reduced in all three interventions across time . Several moderating effects were found , especially for sex and history of childhood abuse . Findings show little evidence of superiority or inferiority of the three interventions and suggest that drop-in centers have choices for addressing the range of problems that these adolescents and young adults face The short-term results of a r and omized trial testing a brief feedback and motivational intervention for substance use among homeless adolescents are presented . Homeless adolescents ages 14 - 19 ( N = 285 ) recruited from drop-in centers at agencies and from street intercept were r and omly assigned to either a brief motivational enhancement ( ME ) group or 1 of 2 control groups . The 1-session motivational intervention presented personal feedback about patterns of risks related to alcohol or substance use in a style consistent with motivational interviewing . Follow-up interviews were conducted at 1 and 3 months postintervention . Youths who received the motivational intervention reported reduced illicit drug use other than marijuana at 1-month follow-up compared with youths in the control groups . Treatment effects were not found with respect to alcohol or marijuana . Post hoc analyses within the ME group suggested that those who were rated as more engaged and more likely to benefit showed greater drug use reduction than did those rated as less engaged . Limitations of the study are discussed as are implication s for development of future substance use interventions for this high-risk group Abstract Background : Homeless young adults are more likely than their never-homeless counterparts to abuse alcohol and engage in risky sexual behaviors , yet no interventions to simultaneously reduce both these behaviors among this vulnerable population have been systematic ally design ed and evaluated . We therefore developed a brief intervention ( BI ) to reduce both alcohol use and sexual risk behaviors among homeless young adults . The results of a r and omized trial testing the BI against an education comparison ( EC ) are presented . Method : Young adults ( N = 61 ; age 17–22 years ) from an urban , Northeastern crisis shelter were r and omly assigned to either the two-session , individual-level BI or a time-matched , two-session , individual-level EC . Generalized linear mixed models for repeated measures determined effects of treatment condition on outcomes . Results : The BI significantly increased participant readiness to change alcohol use . However , it did not significantly decrease primary alcohol or HIV sexual risk outcomes , independently or relative to EC ( all ps > 0.05 ) . Participants in the EC reduced times engaged in unprotected sex between baseline and post-intervention to a significantly greater extent ( p < 0.01 ) than those in the BI condition . Participants in both conditions reported satisfaction with respective interventions . Conclusions : Findings suggest that the BI was acceptable and successful in getting participants to consider changing their drinking . However , lack of change in alcohol and sexual behavior outcomes indicates the need for further research to determine how to translate readiness to change into actual behavioral change among homeless young adults A brief motivational intervention with 117 homeless adolescents was evaluated using a r and omized design and 3-month follow-up . The intervention was design ed to raise youths ' concerns about their substance use , support harm reduction , and encourage greater service utilization at a collaborating agency . The study was design ed to strengthen initial promising results of an earlier study ( P. L. Peterson , J. S. Baer , E. A. Wells , J. A. Ginzler , & S. B. Garrett , 2006 ) . Several modifications in the clinical protocol were included to enhance engagement with the intervention . Analyses revealed no significant benefits for intervention participants when homeless youths ' substance use rates were compared with those of control participants . Service utilization during the intervention period increased for those receiving the intervention but returned to baseline levels at follow-up . Participants reported overall reductions in substance use over time . Differences between sampling methods for the current and previous study are discussed , as are the limitations of brief interventions with this population . Future research needs to eluci date mechanisms of change and service engagement for highly vulnerable youth PURPOSE Almost everything known about risk factors for homelessness is based on cross-sectional studies of non-r and om sample s. Furthermore , most studies have focused on a small number of risk factors and have not evaluated their relative importance . Our aim was to examine which factors , in a population -based sample of adolescents , independently predict homelessness in young adults . METHODS Participants ( n = 10,433 ) in the US National Longitudinal Study of Adolescent Health ( Add Health ) were initially selected through systematic r and om sampling of US high schools . Interviews were conducted at home in 1994 - 1995 when the participants were 11 - 18 years of age and again in 2001 when participants were 18 - 28 years of age . We examined the relationships between a range of risk factors reported in adolescence ( mood-related problems , substance involvement , delinquency , personality , quality of family relations , neighborhood quality , school adjustment , religious affiliation , perpetration of violence , and experiences of victimization ) and experiences of homelessness reported in young adulthood , using regression analysis . RESULTS Each risk factor predicted homelessness . However , only family relationship quality ( odds ratio [ OR ] = .79 , 95 % confidence interval [ CI ] = .69-.90 ) , school adjustment problems ( OR = 1.57 , 95 % CI = 1.35 - 1.82 ) , and experiences of victimization ( OR = 1.27 , 95 % CI = 1.11 - 1.45 ) were found to independently predict homelessness . CONCLUSIONS Among a range of well-established risk factors , a troubled family background , school adjustment problems and experiences of victimization were found to be the strongest predictors of homelessness in a general population of young people . Our findings suggest possibilities for the early identification of young persons at risk for homelessness through schools , agencies offering family-based support , and clinical services Eligible adolescents ( 12 - 17 years old ) were recruited from a short-term crisis shelter for runaway adolescents in a large Midwestern city . Adolescents ( N = 179 ) were r and omly assigned to Ecologically-Based Family Therapy ( EBFT , n = 61 ) , the Community Reinforcement Approach ( CRA , n = 57 ) , or brief Motivational Enhancement Therapy ( MET , n = 61 ) with the primary focus on substance abuse . A significant increase in perceived family cohesion and a significant reduction in perceived family conflict were found among all treatment conditions from baseline to the 24-month follow-up . Adolescents who received EBFT demonstrated more improvement in family cohesion after treatment than those who received CRA or MET , and more reduction in family conflict during treatment than those who received MET This study examined the effects of cognitive-behavioral group therapy ( CBT ) on the self-esteem , depression , and self-efficacy of runaway adolescents residing in a shelter in Seoul , South Korea . The study used a control group pretest-posttest design . The experimental group and the control group consisted of 14 and 13 male subjects , respectively , with subjects having been r and omly assigned to these groups . The experimental group participated in a CBT that consisted of eight sessions over an 8-week period ; the control group did not participate in the program . To examine the effects of the CBT on dependent variables , the Wilcoxon signed rank test was used . The scores on depression decreased significantly ( z = -2.325 , p = .02 ) and those on self-efficacy increased significantly ( z = -2.098 , p = .03 ) after the intervention in the experimental group . There was no significant change on self-esteem ( z = -1.19 , p = .23 ) . In the control group , the scores on depression , self-esteem , and self-efficacy did not change significantly after the intervention period . The CBT developed in this study consisted of structured and specific content that could be usefully applied to runaway adolescents residing in a shelter Comprehensive intervention for homeless , street living youth that addresses substance use , social stability , physical and mental health issues has received very little attention . In this study , street living youth aged 14 - 22 were recruited from a drop-in center and r and omly assigned to the Community Reinforcement Approach ( CRA ) or treatment as usual ( TAU ) through a drop-in center . Findings showed that youth assigned to CRA , compared to TAU , reported significantly reduced substance use ( 37 % vs. 17 % reduction ) , depression ( 40 % vs. 23 % ) and increased social stability ( 58 % vs. 13 % ) . Youth in both conditions improved in many other behavioral domains including substance use , internalizing and externalizing problems , and emotion and task oriented coping . This study indicates that homeless youth can be engaged into treatment and respond favorably to intervention efforts . However , more treatment development research is needed to address the barriers associated with serving these youth OBJECTIVES To examine the efficacy of 3 theoretically distinct interventions among substance-abusing runaway adolescents and to explore individual differences in trajectories of change . METHOD Adolescents ( N = 179 ) between the ages of 12 and 17 were recruited from a runaway shelter in a midwestern city . The sample included 94 females ( 52.5 % ) and 85 males ( 47.5 % ) ; the majority of the adolescents were African American ( n = 118 , 65.9 % ) . Adolescents were r and omly assigned to the Community Reinforcement Approach ( CRA , n = 57 ) , Motivational Interviewing ( MI , n = 61 ) , or Ecologically-Based Family Therapy ( EBFT , n = 61 ) . Substance use was assessed at baseline , 3 , 6 , 9 , 12 , 18 , and 24 months via Form 90 and urine screens . RESULTS Hierarchical linear modeling revealed statistically significant improvement in frequency of substance use among runaways in all 3 treatment groups , with a slight increase at posttreatment . Latent trajectory profile analysis explored individual differences in change trajectories and yielded a 3-class model . The majority of adolescents ( n = 136 , 76 % ) showed reductions in substance use over time , with a slight increase at follow-up ( Class 1 : Decreasing ) . Twenty-four ( 13.4 % ) adolescents had shown high levels of substance use over time with patterns of increase and decrease ( Class 2 : Fluctuating high users ) , and 19 ( 10.6 % ) decreased but returned to baseline levels by 2 years postbaseline ( Class 3 : U shaped ) . Few differences among treatment conditions were noted ; within the " decreasing " group , adolescents in MI treatment showed a quicker decline in their substance use but a faster relapse compared with those receiving EBFT . CONCLUSIONS These findings suggest that CRA , EBFT , and MI are viable treatments for runaway substance-abusing adolescents |
1,132 | 11,405,968 | MAIN RESULTS Pre- and post-operative haemoglobin ( Hb ) and haematocrit ( HCT ) were significantly improved by GnRH analogue therapy prior to surgery , and uterine volume , uterine gestational size and fibroid volume were all reduced .
Pelvic symptoms were also reduced but some adverse events were more likely during GnRH analogue therapy .
Hysterectomy appeared to be easier after pre-treatment with GnRH analogue therapy ; there was reduced operating time and a greater proportion of hysterectomy patients were able to have a vaginal rather than an abdominal procedure .
Duration of hospital stay was also reduced .
Blood loss and rate of vertical incisions were reduced for both myomectomy and hysterectomy .
Evidence of increased risk of fibroid recurrence after GnRH analogue pre-treatment in myomectomy patients was equivocal and few data were available to assess change in post-operative fertility .
Lynestrenol did not offer any advantage over GnRH analogue therapy before fibroid surgery .
REVIEW ER 'S CONCLUSIONS The use of GnRH analogues for 3 to 4 months prior to fibroid surgery reduce both uterine volume and fibroid size .
They are beneficial in the correction of pre-operative iron deficiency anaemia , if present , and reduce intra-operative blood loss .
If uterine size is such that a mid-line incision is planned , this can be avoided in many women with the use of GnRH analogues .
For patients undergoing hysterectomy , a vaginal procedure is more likely following the use of these agents | BACKGROUND Uterine fibroids , smooth muscle tumours of the uterus , are found in at least 25 to 35 % of women over the age of 35 years .
Although some of these tumours are asymptomatic , up to 50 % cause symptoms severe enough to warrant therapy and surgery is the st and ard treatment .
Fibroid growth is stimulated by oestrogen and gonadotropin releasing hormone agonists ( GnRHa ) which induce a state of hypoestrogenism have been investigated as a potential treatment .
GnRHa treatment causes fibroids to shrink but can not be used long term because of unacceptable symptoms and bone loss .
Therefore , GnRHa may be useful pre-operatively both to reduce fibroid and uterine volume and control bleeding .
OBJECTIVES The objective of this review is to evaluate the role of pre-treatment with gonadotropin releasing hormone ( GnRH ) analogues prior to a major surgical procedure , either hysterectomy or myomectomy , for uterine fibroids . | Fifty premenopausal patients requiring hysterectomy as treatment for symptomatic uterine leiomyomas , which were the size of 14 to 18 weeks ' gestation , were r and omized into two groups to determine whether preoperative gonadotropin-releasing hormone agonist would increase the feasibility of vaginal rather than abdominal hysterectomy . The control group ( group A ; n = 25 ) did not receive preoperative gonadotropin-releasing hormone agonist , but patients in Group B ( n = 25 ) received 2 months of gonadotropin-releasing hormone agonist before undergoing hysterectomy . Patients in the two groups were similar with respect to age , gravidity , parity , pretreatment uterine size , and hemoglobin and hematocrit levels . Patients in group B had an increase in hemoglobin levels ( 10.75 to 12.12 gm/dl , p less than 0.05 ) and a decrease in uterine volume ( 1086.7 to 723.4 ml , p less than 0.05 ) after 8 weeks of agonist therapy and were more likely to undergo vaginal hysterectomy ( 76.0 % vs 16 % ) . Patients in group B also had shorter hospitalizations ( 5.2 vs 3.8 days , p less than 0.05 ) . We conclude that the administration of gonadotropin-releasing hormone agonist for 2 months followed by vaginal hysterectomy is preferable to abdominal hysterectomy in selected patients with uterine leiomyomas A. J. M. AUDEBERT , P. MADENELAT * , D. Q U E R L E U ? , G. P O N T O N N I E R ~ , C . R A C I N E T ~ , R.R E N A U D ~ , J.-Y. GILLET * * , D. R A U D R A N T ? ~ , J. LANSAC:~ , J.-P. B R E T T E ~ Cnbitiet Medical . Bordeaus : * Hdpital Bichat , Paris ; ? Centre Hospitalier , Roubai.r ; 1 Hdpital de la Grave , Toulouse ; $ Centre Hospiialier Sud , Ecliirolles : Hfipital Central , Strasbourg ; * * Hi?pital Saint Roch , Nice ; ttH6pital de I'Hdtel Dieu , Lyon ; : $ Hdpital de Tours , Tours ; and # Hipito1 Monwti . Brest . OBJECTIVE Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume . STUDY DESIGN Patients were r and omly assigned to group A ( eight patients ) receiving 25 mg of RU 486 daily for 3 months or group B ( six patients ) receiving 3.75 mg of leuprolide acetate monthly for 3 months . Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography . Uterine volume was measured before and during the study with abdominal ultrasonography . RESULTS Both groups showed an increase in resistive index . Patients receiving RU 486 had uterine artery blood flow decreased by 40 % , and those receiving leuprolide acetate had a 21 % decrease . We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months . There was no significant decrease between groups . CONCLUSION Both RU 486 ( 25 mg daily ) and leuprolide acetate ( 3.75 mg monthly ) are effective in decreasing blood flow to the uterus ( increasing resistive index ) and decreasing uterine volume at 3 months . A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery Summary . Twenty‐four women with symptomatic multiple uterine myomas were allocated r and omly to treatment with buserelin , 1200μg/day intranasally , for 3 months followed by myomectomy ( n = 8) or to immediate myomectomy ( n = 16 ) . Pre‐operative treatment with buserelin reduced the mean uterine volume from 432 ( SD 165 ) to 242 ( SD 82 ) ml ( P < 0.01 ) but intra‐operative blood loss and postoperative morbidity were not significantly less in this group . Six months after operation , pelvic examination was normal in all the patients . However , ultrasonography with transvaginal probe demonstrated the presence of myomas of < 1.5 cm in five women ( 63 % ) treated pre‐operatively with the analogue and in two women ( 13 % ) who underwent immediate surgery ( P < 0.05 ) . Induction of a period of hypo‐oestrogenism before myomectomy seems to favour short‐term recurrence of uterine myomas , limiting the efficacy of surgery OBJECTIVE Aims of our study were as follows : ( 1 ) to evaluate the therapeutic efficacy of the preoperative administration of a gonadotropin-releasing hormone analog before laparoscopic myomectomy and ( 2 ) to assess whether any ultrasonographic parameter of the fibroids ( number , size , Doppler velocimetry , or echogenicity ) was of prognostic value . STUDY DESIGN A prospect i ve r and omized study was performed on 67 patients with symptomatic uterine fibroids that were mainly intramural ; these patients were undergoing laparoscopic myomectomy . Patients were r and omized either to preoperative administration of two injections of a depot formulation of leuprolide acetate 28 days apart ( group A , n = 35 ) or to direct surgery ( group B , n = 32 ) . In each group we studied the number , volume , and echogenicity of the larger fibroids ; the resistance index of uterine arteries and of fibroid vessels ; hematologic parameters ; operative time ; and blood loss . RESULTS The two groups did not differ significantly in basal ultrasonographic parameters and hematologic data . Postoperatively , the red blood cell count and the serum hemoglobin and iron levels were significantly ( p < 0.05 ) lower in group B. Both blood loss ( p < 0.01 ) and operative time ( p < 0.05 ) were significantly lower in group A. However , the operative time was significantly longer when the main fibroid was markedly hypoechoic , probably because the increased softness of the tumor after leuprolide acetate pretreatment makes its enucleation much more cumbersome . CONCLUSION Our data confirm the therapeutic efficacy of preoperative administration of a gonadotropin-releasing hormone analog before laparoscopic myomectomy in reducing the blood loss and in decreasing the operative time . This preoperative course of leuprolide acetate in hypoechoic fibroids , because of the further reduction of the density of the myomas , causes a significant ( p < 0.05 ) increase in operative time Objective To investigate the effect of the gonadotrophin releasing hormone (GnRH)‐agonist goserelin , given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata , on the pre‐operative symptoms , difficulty of operation and operative blood loss The present study was undertaken in order to evaluate the usefulness or otherwise of preoperative gonadotrophin-releasing hormone ( GnRH ) analogue treatment prior to laparoscopic myomectomy . From June 1993 through December 1996 , 60 premenopausal women aged between 25 and 42 years and with a sonographic diagnosis of intramural or subserous myomas were selected for laparoscopic myomectomy at the Department of Obstetrics and Gynaecology of the Catholic University of The Sacred Heart , Rome . According to a computer-generated sequence , 30 patients were su bmi tted to three cycles of GnRH analogue treatment prior to surgery , whereas no preoperative treatment was prescribed to the other 30 patients . Laparoscopic myomectomy was successfully performed in all patients for a total of 174 myomas excised laparoscopically . The patients ' mean age , the number of myomas per patient , the mean diameter of the myomas , parity and estimated blood loss were similar in both groups . The operative time was significantly longer in the group of patients su bmi tted to GnRH analogue treatment than that of the group of patients not su bmi tted to any preoperative medical therapy ( 157.5 + /- 74.71 versus 112.33 + /- 54.71 min ; P = 0.01 ) . No intra-operative complications occurred . In no case was blood transfusion necessary . Two patients developed post-operative fever ( temperature > 38 degrees C. ) . The mean length of hospital stay was 2.39 days and was similar in both groups . Thirteen spontaneous pregnancies occurred among 24 infertile patients ( 54.1 % ) . The pregnancy rate for these patients was similar in both groups . The viable term delivery rate was 45.8 % . The authors conclude that laparoscopic myomectomy is a feasible and safe procedure . The post-operative pregnancy rate for infertile patients is similar to that following laparotomic myomectomy . The present study suggests that preoperative GnRH analogue treatment does not offer any significant advantages for laparoscopic myomectomy Objective . To investigate the usefulness of a routine short term treatment with gonadotropin releasing hormone agonist ( D‐Trp‐6‐LHRH depot ) before abdominal hysterectomy for leiomyoma The recurrence of myomas and myoma-related symptoms was evaluated in women participating in a r and omized , double-blind , P-controlled study of the efficacy of LA depot before myomectomy . After 27 to 38 months of follow-up , the recurrence of myomas was found to be greater when at least four myomas were resected . Myoma recurrence was not associated with pretreatment or preoperative uterine volume , resected myoma mass , or preoperative medical therapy To determine whether pre-operative treatment with gonadotrophin-releasing hormone ( GnRH ) analogue may have a beneficial effect on surgery outcome , 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy ( TAH ) , were r and omly divided into a study group ( n = 29 ) and a control group ( n = 24 ) . The study group of patients were treated by an i.m . injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery . The control group had no pre-operative treatment . Haemoglobin concentration and oestradiol , follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery , and at surgery . The duration of surgery was shorter in the study group ( 49 versus 70 min in the hysterectomy group ) and intra-operative blood loss was less ( 208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies ) . Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery , and diminishing the intra-operative blood loss in surgery for fibroid uteri . Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri OBJECTIVE To compare the effects of goserelin acetate treatment with or without iron with iron alone . DESIGN Multinational , multicenter , prospect i ve , r and omized , double-blind study . PATIENTS Premenopausal women with menorrhagia or metrorrhagia and anemia associated with uterine leiomyomata awaiting hysterectomy . INTERVENTION Patients were r and omized to one of three 12-week treatment groups namely goserelin acetate 3.6 mg once monthly plus placebo iron ; 3.6 mg goserelin acetate once monthly plus 600 mg/d iron ; or sham injection once monthly plus 600 mg/d iron . MAIN OUTCOME MEASURE Preoperative hemoglobin concentration ; preoperative uterine and fibroid volumes and operative blood loss . RESULTS Considering the entry and preoperative hemoglobin concentrations , there was a difference in least square means of just over 1 g/dL between the goserelin acetate plus iron and iron only groups and 2.6 g/dL between the goserelin acetate plus iron and goserelin acetate only group . These differences were both statistically significant . Uterine and fibroid volumes were decreased in the goserelin acetate-treated patients by between 37 % and 40 % and 44 % and 47 % , respectively , compared with 7 % decreases for both in the iron only group . The differences in absolute changes were statistically significant for both the goserelin acetate-treated groups versus the iron-treated group . The least square geometric mean operative blood loss was greatest in the iron only group . CONCLUSION In the patient with uterine leiomyomata and anemia , goserelin acetate in combination with iron therapy has shown significant advantages over the iron alone in restoring hematologic normality , decreasing uterine and fibroid volumes , and reducing operative blood loss Objective To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas . Methods This was a phase III , stratified , r and omized , double-blind , placebo-controlled , parallel-group , 12-week multicenter study . Enrolled patients had hemoglobin levels of 10.2 g/dL or less and /or hematocrit values of 30 % or less . Patients were entered into one of two strata based on their pre- study hematocrit level : stratum A , hematocrit less than or equal to 28 % , and stratum B , hematocrit greater than 28 % . Patients within each stratum were r and omized to one of three treatment arms : leuprolide acetate depot 7.5 mg , leuprolide acetate depot 3.75 mg , or placebo . All patients received iron orally . Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36 % or greater . Results Three hundred nine patients were entered into the study , of whom 265 were evaluated . Using our response criteria , a significantly greater number of patients in both leuprolide acetate groups ( combined strata ) responded to therapy than did those in the placebo group : 74 % in each leuprolide acetate group versus 46 % in the placebo group ( P < .001 ) . Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group ( P < .01 ) . Hot flashes and vaginitis were reported significantly more often ( P < .001 ) in the leuprolide acetate-treated groups than in the placebo group . Conclusion Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas , in reducing uterinemyoma volume , and in alleviating bleeding and other leiomyoma-related symptoms To evaluate the efficacy and safety of nafarelin before hysterectomy in a prospect i ve placebo-controlled trial , we r and omized 188 pre-menopausal women with uterine fibroids ( n = 111 ) , menometrorrhagia ( n = 58 ) or pelvic pain ( n = 19 ) to receive either nafarelin ( 200 micrograms twice daily as a nasal spray ) or a placebo for 3 months before abdominal hysterectomy . The data analysis could be performed in 166 women , of whom 107 received nafarelin and 59 a placebo . Nafarelin led to a rise in blood haemoglobin ( 5.5 g/l ) and to a decrease in uterine volume ( 23.7 % ) . This , however , gave no objective benefit during surgery ( similar operative duration s and blood losses ) . The uteri from patients treated with nafarelin ( 255.5 + /- 12.6 g , mean + /- SD ) were significantly lighter ( P = 0.029 ) than those from patients treated with a placebo ( 346.2 + /- 35.7 g ) . Histological examination of the fibroids or uteri revealed changes typical for hypo-oestrogenism , but no specific histological pattern could be established . The endometrium was proliferative in 56 % and showed mild hyperplastic features in 10 % of patients given nafarelin , whereas the respective figures for the placebo group were 41 and 0 % . Hot flushes were the most common side-effects , being reported by 61 % in the nafarelin group and 35 % in the placebo group . Nafarelin can be useful as a pre-surgical adjunct in a patient scheduled for abdominal hysterectomy if there is a need to raise the haemoglobin concentration or to reduce the size of the uterus OBJECTIVES To compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol , given prior to surgical treatment of symptomatic uterine myomas , on the pre-operative symptoms , tolerance , and operative blood loss . STUDY DESIGN Fifty-six women were r and omly selected to receive , during 16 weeks , either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release ( n=33 ) or lynestrenol 5 mg two tabs per day ( 5th to the 25th menstrual cycle ) ( n=23 ) . RESULTS Intent-to-treat analysis of the main efficacy criterion , namely ultrasonographic reduction of myoma(s ) diameter , showed a significant difference in favour of leuprorelin ( P=0.02 ) with a mean decrease of 26.5+/-4.5 % ( n=29 ) as opposed to 7.3+/-5 % in the lynestrenol group ( n=17 ) . Clinical improvement was satisfactory in both groups . Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one ( P=0.02 ) ( for hemoglobin : P=0.07 ) . CONCLUSION Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity . The tolerance was good , reflecting each drug mechanism of action Two hundred and forty-seven patients with uterine fibroids were r and omized to surgery alone or 3 months ' Zoladex ( Zeneca , Macclesfield , Ches . , UK ) followed by surgery . Zoladex significantly reduced uterine and fibroid volumes ( p = 0.0001 ) . There was a significantly ( p = 0.002 ) greater mean rise in haemoglobin from entry to preoperation in the Zoladex group ( 1 g/dl ) compared with the surgery-alone group ( 0.3 g/dl ) as well as a tendency towards easier surgery , and reduced operative blood loss . Zoladex-treated patients had a significantly ( p = 0.016 ) shorter hospital stay and pelvic pain and abdominal pressure symptoms were significantly ( p < 0.0001 ) reduced in this group . Zoladex was well tolerated Gonadotropin-releasing hormone agonists induce a reversible hypogonadotropic hypogonadal environment . Leiomyomas are common , estrogen-sensitive , benign neoplasms that decrease in size by 40 % to 50 % during gonadotropin-releasing hormone agonist treatment . During gonadotropin-releasing hormone agonist therapy most women are amenorrheic . After discontinuation of gonadotropin-releasing hormone agonist treatment , uterine and myoma size increase and a return to pretreatment menstrual patterns often occurs . Concerns about the safety of long-term hypoestrogenism have made long-term gonadotropin-releasing hormone agonist administration an undesirable treatment strategy . This article focuses on the use of gonadotropin-releasing hormone agonists as preoperative therapy in selected women undergoing hysterectomy or myomectomy and the combination of a gonadotropin-releasing hormone agonist with estrogen-progestin " add-back " treatment as a potential long-term medical therapy for women with symptomatic leiomyomas . Finally , an estrogen threshold hypothesis to assess the effects of circulating estrogen concentrations on different tissues , is presented Eighteen premenopausal women with symptomatic leiomyomata uteri were enrolled in a stratified , r and omized , double-blind , placebo-controlled study evaluating the efficacy of leuprolide acetate ( LA ) depot treatment before myomectomy . Stratification was based on pretreatment uterine volume ( less than 600 cm3 versus greater than or equal to 600 cm3 ) . Nine women received intramuscular ( IM ) depot LA 3.75 mg every 4 weeks for 12 weeks ( group A ) ; nine women received IM placebo with the same injection schedule ( group B ) . All women underwent myomectomy within 4 weeks of their last injection . Mean total intraoperative blood loss was 213 + /- 44 mL ( mean + /- st and ard error of the mean [ SEM ] ) in group A and 302 + /- 43 mL in group B. When data from patients with large uteri ( pretreatment uterine volumes of 600 cm3 or greater ) were analyzed , mean total blood loss was 189 + /- 44 mL in group A and 390 + /- 20 mL in group B. These data suggest that leuprolide depot treatment before myomectomy may decrease intraoperative blood loss in women with large leiomyomata uteri |
1,133 | 29,492,963 | The results of the meta-analyses presented a modest additional benefit of 0.14 mm ( 95 % confidence interval : 0.08 - 0.20 ) in reducing PPD but no further benefit in CAL gain .
CONCLUSION When the data for all antibiotic protocol s were considered together for the treatment of periodontitis patients with DM , a significant , albeit small , reduction of PPD and no improvement in CAL gain was observed .
When the antibiotic protocol s were analysed separately , the combination of amoxicillin plus metronidazole yielded the best results for PPD | OBJECTIVES To evaluate the effects of systemic antibiotics as adjuncts to nonsurgical periodontal treatment ( NSPT ) , as opposed to using NSPT alone , on periodontal clinical parameters of diabetic patients with periodontitis . | AIM To evaluate associations between glycaemic control and periodontitis progression among Gullah African Americans with type-2 diabetes mellitus ( T2DM ) . MATERIAL S AND METHODS From an ongoing clinical trial among T2DM Gullah , we extracted a cohort previously in a cross-sectional study ( N=88 ) . Time from baseline ( previous study ) to follow-up ( trial enrollment , before treatment interventions ) ranged 1.93 - 4.08 years [ mean=2.99 , st and ard deviation (SD)=0.36 ] . We evaluated tooth site-level periodontitis progression [ clinical attachment loss ( CAL ) worsening of > or = 2 mm , periodontal probing depth ( PPD ) increases of > or = 2 mm and bleeding on probing ( BOP ) from none to present ] by glycaemic control status ( well-controlled = HbA(1c)<7 % , poorly-controlled = HbA(1c ) > or = 7 % ) using multivariable generalized estimating equations logistic regression , nesting tooth sites/person . RESULTS Poorly-controlled T2DM ( 68.18 % ) was more prevalent than well-controlled T2DM ( 31.82 % ) . Proportions of tooth sites/person with CAL progression between baseline and follow-up ranged 0.00 - 0.59 ( mean=0.12 , SD=0.12 ) , while PPD and BOP progression ranged 0.00 - 0.44 ( mean=0.09 , SD=0.11 ) and 0.00 - 0.96 ( mean=0.24 , SD=0.18 ) , respectively . Site-level PPD at baseline was a significant effect modifier of associations between poorly-controlled T2DM and site-level CAL and PPD progression [ adjusted odds ratios ( OR ) according to poorly-controlled T2DM among PPD at baseline=3 , 5 and 7 mm , respectively : CAL progression=1.93 , 2.64 , and 3.62 , PPD progression=1.98 , 2.76 , and 3.84 ; p<0.05 for all ] . Odds of site-level BOP progression were increased ( OR=1.24 ) for poorly-controlled T2DM , yet the results were not significant ( p=0.32 ) . CONCLUSIONS These findings from a distinct , homogenous population further support the clinical relevance of identifying patients with poor glycaemic control and periodontitis , particularly among those with disparities for both diseases AIM To evaluate the clinical , microbiological and immunological effects of systemic doxycycline as an adjunct to scaling and root planing ( SRP ) in chronic periodontitis patients with well-controlled type 2 diabetes . MATERIAL S AND METHODS Sixty-six patients compliant to oral hygiene ( Hygiene Index < 20 % ) allocated to either a test ( systemic doxycycline for 21 days ) or a control ( placebo ) group participated in the present r and omized controlled trial ( RCT ) . Clinical assessment s were recorded at baseline , 3 and 6 months after therapy and included clinical attachment level ( CAL ) , set as the primary outcome of the study , probing pocket depth ( PPD ) , recession ( RE ) and bleeding on probing ( BOP ) . At the same time points , counts of 15 subgingival species were evaluated by " checkerboard " DNA-DNA hybridization , gingival crevicular fluid sample s were analysed for matrix metalloproteinase-8 ( MMP-8 ) by ELISA and HbA1c levels were determined . Comparisons between and within groups were performed by non-parametric tests ( Mann-Whitney , Wilcoxon signed-ranks and z-test for proportions with Bonferroni corrections ) at the 0.05 level . RESULTS No major differences were noticed in clinical and microbiological parameters of periodontal disease or levels of MMP-8 between the two groups . CONCLUSIONS Adjunctive systemic doxycycline does not seem to significantly enhance the effects of SRP in well-controlled diabetes type 2 patients Purpose The purpose of study was to compare glycemic control using glycated hemoglobin levels ( HbA1c ) in diabetic patients with chronic generalized periodontitis ( CGP ) undergoing scaling and root planing ( SRP ) with and without systemic doxycycline . Methods Fifty subjects with type 2 diabetes mellitus ( T2DM ) and CGP receiving antidiabetic therapy were selected for study . The selected subjects were r and omly assigned to two groups ( test group [ TG ] and control group [ CG ] ) comprising 25 patients each . The TG received SRP followed by systemic doxycycline . The CG received treatment with SRP only . The periodontal parameters were recorded at baseline ( day zero ) , and every 1 month for 4 months and included probing depth , clinical attachment level , plaque index , gingival index , and HbA1c level were recorded at baseline ( day zero ) and at the end of 4 months . Results A statistically significant effect was demonstrated for the periodontal parameters for both the TG and CG . HbA1c values did not show a statistically significant difference in the treatment group as compared to the CG . Conclusions The authors concluded that nonsurgical periodontal therapy improved glycemic control in patients with T2DM in both groups , but no statistical difference was observed with adjunctive systemic doxycycline therapy . A further study with a larger sample size is required Current evidence suggests that periodontal infection may aggravate diabetes control . The aim of this study was to determine the changes in the frequency with which Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola and Aggregatibacter actinomycetemcomitans were detected in patients with diabetes with the use of non-surgical therapy plus azithromycin in a r and omized clinical trial . One hundred and five ( 105 ) patients with diabetes and chronic periodontitis were r and omly assigned to three treatment groups : subgingival mechanical therapy with azithromycin , subgingival mechanical therapy with placebo and supragingival prophylaxis with azithromycin . Complete periodontal clinical examinations and detection of periodontal pathogens using polymerase chain reaction were carried out at baseline , 3 , 6 and 9 months after periodontal therapy . The frequency with which Porphyromonas gingivalis , Treponemadenticola and Aggregatibacter actinomycetemcomitans were detected decreased at 3 months in all groups . Tannerella forsythia increased after3 months in all groups . All organisms had similar frequencies at 9 months in all groups . Subgingival mechanical therapy with adjunctive azithromycin had no additional effect on the frequency with which the periodontal pathogens investigated were detected in patients with diabetes AIM Diabetic patients have more severe periodontal destruction , but periodontal therapy can improve metabolic control . Recently , interest has focused on the use of subantimicrobial dose doxycycline ( SDD ) as a treatment paradigm . Therefore , this study was undertaken to evaluate clinical efficacy of SDD with scaling and root planning ( SRP ) in chronic periodontitis patients with diabetes . METHODS AND MATERIAL S Twenty chronic periodontitis patients with diabetes mellitus were r and omly allocated to either a test and a control group . Clinical measurements were recorded at baseline and at six months for probing pocket depth ( PPD ) , clinical attachment level ( CAL ) , and gingival recession ( GR ) . After SRP , patients in the test group were instructed to take SDD 20-mg capsules twice a day while patients in the control group took a placebo twice a day . Both groups were on this regimen for a six-month period . RESULTS A greater reduction in mean PPD was demonstrated in patients in the test group compared to the control group . The mean CAL increase observed in the test group was significantly greater ( 0.67 mm ) than that in the control group . CONCLUSION It can be concluded that SRP , in conjunction with the SDD therapy described , is more effective then SRP alone in terms of CAL gain and PPD reduction in diabetic patients with severe periodontal disease . CLINICAL SIGNIFICANCE Given the widespread prevalence of both chronic periodontitis and diabetes , the proposed treatment approach will prove to be of great value and contribute significantly to the overall health of the patients Objectives : To evaluate the effects of systemic doxycycline on clinical and microbiological parameters of diabetic subjects with chronic periodontitis . Methods : This 9-month multi-center , r and omized , parallel , single-blinded study was conducted from different hospitals in Riyadh , Saudi Arabia between April 2010 and December 2010 . A total of 76 diabetic subjects with chronic periodontitis were r and omized into 2 groups : control group ( CG ) received only scaling and root planing ( SRP ) , and the treatment group ( TG ) receiving systemic doxycycline during the reevaluation visit 45 days after the completion of SRP . Probing pocket depth , clinical attachment level , gingival index , plaque index , and bleeding on probing were collected at baseline , 45 days after SRP , and one , 3 , and 6 months after the use of systemic doxycycline . Microbiological analysis comprised the detection of Tannerella forsythia ( Tf ) , Aggregatibacter actinomycetemcomitans ( Aa ) , Porphyromonas gingivalis ( Pg ) , and Prevotella intermedia ( Pi ) by polymerase chain reaction method . Results : Sixty-eight ( 33 CG and 35 TG ) subjects completed the study . Greater reduction in the population of Tf , Pg , and Pi were observed in TG compared with CG in the first month after the administration of systemic doxycycline . The TG showed a significant improvement in gingival index scores compared with the CG ( p<0.05 ) by the end of the first and 6 months after the administration of doxycycline . Conclusion : Adjunct systemic doxycycline can be associated with a reduction of Tf , Pg , and Pi in the first month after the administration of doxycycline with an improvement in the GI OBJECTIVE To investigate the effectiveness of short-term adjunctive subantimicrobial dose doxycycline ( SDD ) treatment in patients with diabetes mellitus type 2 and chronic periodontitis ( CP ) . METHODS Thirty-four patients with CP and type 2 diabetes mellitus were included in the placebo-controlled , double-blind study . After scaling and root planing ( SRP ) , patients were r and omly assigned to two groups , receiving either SDD or placebo bid for 3 months . The probing depth ( PD ) , clinical attachment level ( CAL ) , bleeding on probing ( BOP ) , approximal plaque index , glycated hemoglobin ( HbA1c ) level were recorded and gingival crevicular fluid ( GCF ) sample s were collected at baseline and after 3-month therapy for the estimation of matrix metalloproteinase-8 levels . RESULTS Clinical attachment level , PD , and BOP improved significantly in both groups after therapy ( P < 0.05 ) . The statistically significant difference between the two groups after the therapy was observed only in PD in tooth sites with initial PD ≥ 4 mm ( SRP + placebo : 3.41 ± 0.6 mm vs SRP + SDD : 2.92 ± 0.5 mm , P < 0.05 ) . GCF matrix metalloproteinase-8 levels were significantly reduced only in SRP + SDD group ( P < 0.01 ) . There were no changes in HbA1c levels after therapy . CONCLUSION The short-term administration of SDD gives significant benefit at tooth sites with moderate disease ( PD ≥ 4 mm ) when compared to SRP alone in patients with diabetes and CP Periodontal disease is a common infection-induced inflammatory disease among individuals suffering from diabetes mellitus . The purpose of this study was to assess the effects of treatment of periodontal disease on the level of metabolic control of diabetes . A total of 113 Native Americans ( 81 females and 32 males ) suffering from periodontal disease and non-insulin dependent diabetes mellitus ( NIDDM ) were r and omized into 5 treatment groups . Periodontal treatment included ultrasonic scaling and curettage combined with one of the following antimicrobial regimens : 1 ) topical water and systemic doxycycline , 100 mg for 2 weeks ; 2 ) topical 0.12 % chlorhexidine ( CHX ) and systemic doxycycline , 100 mg for 2 weeks ; 3 ) topical povidone-iodine and systemic doxycycline , 100 mg for 2 weeks ; 4 ) topical 0.12 % CHX and placebo ; and 5 ) topical water and placebo ( control group ) . Assessment s were performed prior to and at 3 and 6 months after treatment and included probing depth ( PD ) , clinical attachment level ( CAL ) , detection of Porphyromonas gingivalis in subgingival plaque and determination of serum glucose and glycated hemoglobin ( HbA1c ) . After treatment all study groups showed clinical and microbial improvement . The doxycycline-treated groups showed the greatest reduction in probing depth and subgingival Porphyromonas gingivalis compared to the control group . In addition , all 3 groups receiving systemic doxycycline showed , at 3 months , significant reductions ( P < or = 0.04 ) in mean HbA1c reaching nearly 10 % from the pretreatment value . Effective treatment of periodontal infection and reduction of periodontal inflammation is associated with a reduction in level of glycated hemoglobin . Control of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients AIMS : The purpose of this study is to investigate the effect of improved periodontal health on glycemic control in type 2 diabetes mellitus ( type 2 DM ) patients who have generalized periodontitis . MATERIAL S AND METHODS : A total of 45 type 2 DM patients with generalized periodontitis were selected for the study . The selected patients were r and omly assigned to three groups ( groups A , B , and C ) comprising 15 patients each : • Group A received treatment with scaling and root planing only . • Group B received treatment with scaling and root planing followed by systemic doxycycline . • Group C received no treatment ( control group ) . The periodontal parameters recorded included plaque index , gingival index , probing pocket depth , and clinical attachment level . These parameters were recorded at baseline ( day zero ) , at 1 month , and at the end of 3 months . The following metabolic parameters were recorded : fasting blood glucose ( FBG ) , postpr and ial blood glucose ( PPBG ) , and glycated hemoglobin . These were recorded at baseline ( day zero ) and at the end of 3 months . STATISTICAL ANALYSIS : All the parameters were subjected to repeated- measures ANOVA and Scheffe 's post hoc test . RESULTS : A statistically significant effect could be demonstrated for periodontal parameters for both group A and group B ( treatment groups ) . Glycated hemoglobin values showed statistically significant decrease in treatment groups compared to the control group , with group B showing more significant decrease than group A. CONCLUSIONS : The results of this study showed that nonsurgical periodontal treatment is associated with improved glycemic control in type 2 DM patients BACKGROUND Periodontitis is a major cause of tooth loss among adults . Several studies have shown a possible systemic impact of periodontal infection , including poor glycemic control in patients with diabetes . Recently , photodynamic therapy ( PDT ) was used to successfully treat periodontal infection . PDT provides a broad spectrum antimicrobial efficacy with no local or systemic side effects . The objective of this study was to examine the effect of the adjunctive use of PDT on periodontal status and glycemic control of patients with diabetes and periodontitis . METHODS Forty-five patients with type 2 diabetes and moderate to severe chronic periodontitis were selected and r and omly assigned to one of the following three treatment modalities ( 15 subjects each ) : scaling and root planing ( SRP ) only , SRP plus systemic doxycycline , and SRP plus PDT . The plaque and bleeding scores , probing depth , clinical attachment level , and glycosylated hemoglobin ( HbA1c ) level were recorded at baseline and 3 months after periodontal treatment . Descriptive statistics , the paired t test , and analysis of variance ( ANOVA ) were used for data analysis . RESULTS Statistically significant differences in the mean probing depth , clinical attachment level , plaque deposit , and bleeding on probing were found between baseline and 12 weeks post-treatment for all groups . No significant differences in periodontal parameters and glucose levels were detected among the three groups . Reduction in the mean HbA1c level after treatment was observed in all groups but was only significant for the SRP plus doxycycline group . CONCLUSION The results of the present study indicate that PDT does not benefit conventional non-surgical periodontal therapy in patients with diabetes UNLABELLED The AIM of this study was to evaluate the effect of non-surgical therapy on clinical variables and glycemic control on type 2 diabetics with chronic periodontitis . PATIENTS AND METHODS Forty six type 2 diabetics with chronic periodontitis were r and omized into two groups ( group A and group B ) . Treatment included scaling and root planning for group A plus systematic use of doxycycline in both groups . Assessment was made prior to and 16 weeks following the therapy . RESULTS Analysis of data showed that both groups had clinical and glycated hemoglobin ( HbAlc ) improvement after the treatment . Group A had a statistically significant reduction of plaque index and bleeding on probing scores compared with controls ( P < 0.05 ) at 16 weeks . CONCLUSION These results suggest that non-surgical therapy is of value in maintaining periodontal health and may be beneficial in reducing blood glucose level in type 2 diabetics with chronic periodontitis OBJECTIVES The purpose of this study was to evaluate the effect of subgingival administration of doxycycline as an adjunct to periodontal therapy in type 1 diabetes mellitus ( DM ) patients . MATERIAL AND METHODS Twenty-two paired periodontal defects > or = 5.0 mm were treated in 11 patients ( 35 - 55 years old ) . After initial therapy the sites were r and omly assigned into test ( scaling and root planing+subgingival administration of 10 % doxycycline hyclate gel ) or control ( scaling and root planing+subgingival placebo gel ) groups . The clinical parameters of clinical attachment level ( CAL ) , probing depth ( PD ) and gingival margin level ( GML ) for recession determination were assessed at baseline , after 6 weeks , and 6 , 9 and 12 months , using a computerized probe . Data were statistically evaluated using Duncan and F tests . RESULTS Between study group comparisons indicated PD reduction and CAL gain were greater in the test group than in the control group at 6 weeks and 6 , 9 and 12 months but only statistically significant at 12 months ( p<0.05 ) . Within study group comparisons indicated statistically significant differences were found for CAL and PD values favouring the adjunctive doxycycline group from baseline to 6 weeks and 6 , 9 and 12 months ( p<0.05 ) . CONCLUSIONS These findings suggest that subgingivally delivered doxycycline hyclate produces additional favorable clinical results to periodontal therapy in type 1 DM patients BACKGROUND The literature suggests that an alteration in glucose metabolism occurs as a result of antibacterial periodontal therapy . The objective of this study was to monitor the effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus ( DM ) . METHODS Thirty type 2 DM subjects with periodontitis were r and omly divided into two groups . Group 1 ( G1 ) , 15 subjects , received one-stage full-mouth scaling and root planing ( FMSRP ) plus amoxicillin/clavulanic acid 875 mg ; group 2 ( G2 ) , 15 patients , received only FMSRP . At baseline and after 3 months , the glycated hemoglobin ( HbA1c ) values , fasting glucose , and clinical parameters ( with computerized probing and individualized acrylic stents ) were recorded . Following therapy , the subjects were enrolled in a 2-week interval maintenance program for 3 months . RESULTS After treatment , both groups showed clinical improvements . A probing depth ( PD ) reduction of 0.8 + /- 0.6 mm ( P < 0.05 ) occurred in G1 and 0.9 + /- 0.4 mm in G2 ( P < 0.05 ) , but there were no significant changes in attachment level . Treatment reduced the HbA1c values after the 3-month observation period in both groups ; however , the reduction in HbA1c values for the G2 group was statistically significant , but not for the G1 group . The changes in fasting glucose levels were not significant for either group . CONCLUSIONS Periodontal therapy improved glycemic control in patients with type 2 DM in both groups ; however , the reduction in HbA1c values reached statistical significance only in the group receiving scaling and root planing alone [ correction ] The aim of this study was to assess the changes occurring in subgingival biofilm composition and in the periodontal clinical parameters of subjects with periodontitis and type 2 diabetes mellitus ( DM ) treated by means of scaling and root planing ( SRP ) only or combined with systemic metronidazole ( MTZ ) and amoxicillin ( AMX ) . Fifty-eight subjects were r and omly assigned to receive SRP only ( n = 29 ) or with MTZ ( 400 mg/thrice a day [ TID ] ) and AMX ( 500 mg/TID ) ( n = 29 ) for 14 d. Six subgingival plaque sample s/subject were analyzed by checkerboard DNA – DNA hybridization for 40 bacterial species at baseline and 3 mo , 1 y , and 2 y posttherapy . At 2 y posttherapy , the antibiotic-treated group harbored lower mean proportions ( 5.5 % ) of red complex pathogens than the control group ( 12.1 % ) ( P < 0.05 ) . The proportions of the Actinomyces species remained stable in the antibiotic group but showed a statistically significant reduction in the control group from 1 to 2 y in subjects achieving a low risk clinical profile for future disease progression ( i.e. , ≤4 sites with probing depth [ PD ] ≥5 mm ) . The test group also had a lower mean number of sites with PD ≥5 mm ( 3.5 ± 3.4 ) and a higher percentage of subjects reaching the low risk clinical profile ( 76 % ) than the control group ( 14.7 ± 13.1 and 22 % , respectively ) ( P < 0.05 ) at 2 y posttreatment . MTZ + AMX intake was the only significant predictor of subjects achieving the low risk at 2 y ( odds ratio , 20.9 ; P = 0.0000 ) . In conclusion , the results of this study showed that the adjunctive use of MTZ + AMX improves the microbiological and clinical outcomes of SRP in the treatment of subjects with generalized chronic periodontitis and type 2 DM up to 2 y ( Clinical Trials.gov NCT02135952 ) Objective The aim of the present short-term longitudinal r and omized case – control study was to assess the effect of nonsurgical periodontal therapy ( NSPT ) ( with and without oral doxycycline delivery ) on glycemic status and clinical periodontal parameters in patients with prediabetes . Material and methods Sixty-six patients with prediabetes and periodontal disease were included . Characteristics of the study cohort ( age , gender , socioeconomic status [ SES ] education status , duration of prediabetes , and type of treatment adopted for prediabetes management ) were recorded . Patients were r and omly divided into two groups ( 33 patients /group ) . In group 1 , scaling and root planing ( SRP ) was performed , and in group-2 , patients underwent SRP and oral doxycycline ( 100 mg ) administration once daily for 15 days . In each group , the following parameters were investigated at baseline and after 3 months : ( a ) fasting blood glucose level ( FBGL ) , ( b ) hemoglobin A1c ( HbA1c ) , and ( c ) periodontal parameters ( plaque index [ PI ] , bleeding on probing [ BOP ] , probing depth [ PD ] , and clinical attachment loss [ AL ] ) . Statistical analysis was performed using Student ’s t test . Results There was no significant difference in age , gender , SES , education status , and duration and treatment of prediabetes among individuals in groups 1 and 2 . Three months post-NSPT , FBGL and HbA1c were significantly reduced among patients in group 1 ( P < 0.05 ) and group 2 ( P < 0.05 ) compared to baseline . Three months post-NSPT , PI ( P < 0.05 ) , BOP ( P < 0.05 ) , and PD ( P < 0.05 ) were significantly reduced among patients in group 1 ( P < 0.05 ) and group 2 ( P < 0.05 ) compared to baseline . There was no difference in clinical AL between the groups after 3 months of NSPT . Conclusion NSPT ( with and without oral doxycycline delivery ) reduces hyperglycemia and periodontal inflammation in patients with prediabetes AIM The present investigation was performed to study how type 1 diabetics responded to non-surgical periodontal treatment with and without adjunctive doxycycline . METHOD Sixty diabetic type 1 patients ( mean age 35.3+/-9 years ) with moderate-to-severe periodontal disease were selected and divided into two groups of 30 patients each . Both groups were sex and age matched and had similar amounts of periodontal destruction . Plaque index ( PI ) , bleeding on probing ( BOP ) , probing depth ( PD ) and clinical attachment levels ( CAL ) were recorded . Group 1 ( 30 patients ) was treated with oral hygiene instruction , scaling and root planing , chlorhexidine rinses twice a day and doxycycline ( 100 mg/day for 15 days ) . Group 2 ( 30 patients ) had the same treatment but without doxycycline . After 12 weeks their periodontal condition was reevaluated . RESULTS After treatment , both groups had a significant improvement in all periodontal parameters , since PI , BOP , probing pocket depth ( PPD ) and CAL were significantly reduced . However , the reduction in PD in pockets > or = 6 mm and in BOP were more evident when doxycycline was used ( group 1 ) . Differences between groups for these parameters were statistically significant ( p=0.03 ) . CONCLUSION Although both periodontal treatment regimens are effective in type 1 diabetics , the use of doxycycline as an adjunct , provided more significant results when good plaque control was achieved BACKGROUND AND OBJECTIVE Periodontitis may alter the systemic condition in patients with diabetes and hence interfere with glycemic control . The objective of this study was to determine the quantifiable changes in glycated hemoglobin ( HbA1C ) after periodontal non-surgical therapy plus azithromycin in a mixed population of patients with poorly controlled diabetes . MATERIAL S AND METHODS One hundred and five patients were r and omized to receive non-surgical therapy plus azythromycin ( AZ-Sca = 33 ) , non-surgical therapy plus placebo ( PB-Sca = 37 ) and supragingival prophylaxis plus azithromycin ( AZ-Pro = 35 ) . Glycated hemoglobin , glycemia and periodontal parameters were measured at baseline , 3 , 6 and 9 mo after treatment . RESULTS Periodontal parameters were improved in the AZ-Sca and PB-Sca groups as compared to the AZ-Pro group . A greater reduction in probing depth was observed in the AZ-Sca as compared to the PB-Sca group . Improvement in clinical attachment level was similar between AZ-Sca and PB-Sca groups . A reduction from 8.0 % to 7.2 % ( ∆0.8 % ; p < 0.05 ) in HbA1C was observed in the AZ-Sca at 9 mo as compared to the PB-Sca group in which the reduction was from 7.9 % to 7.6 % ( ∆0.3 % ) . There was no decrease in HbA1C in the AZ-Pro group over time . Mean glycemia values decreased from 195 mg/dL to 159.2 mg/dL ( ∆35.8 mg/dL ; p < 0.05 ) in the AZ-Sca group whereas a decrease from 194 mg/dL to 174.8 mg/dL ( ∆19.2 mg/dL ) in the PB-Sca group at 9 mo was observed . There were no differences between the AZ-Sca and PB-Sca groups for glycemic parameters . No improvement in glycemic values in the AZ-Pro group was observed . CONCLUSIONS A modest improvement in glycemic control was detected with a trend towards the use of non-surgical therapy plus AZ as compared to the placebo AIM This study evaluated the effects of surgical ( SD ) and non-surgical ( NSD ) debridements , associated with systemic antimicrobials , on clinical and immunological outcomes of residual pockets [ RP ; probing depth ( PD ) ≥5 mm with bleeding on probing ] in type 2 diabetics . MATERIAL AND METHODS A split-mouth , r and omized controlled trial was conducted in 21 subjects presenting at least two RP per contralateral quadrant . Subjects received metronidazole plus amoxicillin for 10 days and , contralateral quadrants were assigned to receive SD or NSD . Clinical parameters and local levels of interferon-γ , interleukin (IL)-17 , IL-23 and IL-4 were assessed at baseline , 3 and 6 months post-therapies . RESULTS Overall , the mean number , PD and clinical attachment level ( CAL ) of RP improved significantly after therapies ( p < 0.05 ) , without differences between groups at any time-point ( p > 0.05 ) . At quadrant level , only SD produced significant reductions in the mean CAL . Also , SD promoted higher reduction in PD from baseline to 6 months than NSD ( p < 0.05 ) . Levels of all cytokines were increased after SD compared with NSD ( p < 0.05 ) . CONCLUSION SD and NSD associated with systemic antimicrobials did not differ in terms of clinical benefits for RP in diabetics up to 6 months post-therapies . RP treated by SD presented increased levels of cytokines AIM To evaluate the clinical and microbiological effects of the use of metronidazole ( MTZ ) + amoxicillin ( AMX ) as adjuncts to scaling and root planing ( SRP ) for the treatment of chronic periodontitis ( ChP ) in type 2 diabetic subjects . MATERIAL AND METHODS Fifty-eight type 2 diabetic subjects ( n = 29/group ) with generalized ChP were r and omly assigned to receive SRP alone or with MTZ [ 400 mg/thrice a day (TID)]+AMX ( 500 mg/TID ) for 14 days . Subgingival biofilm sample s were analyzed by qPCR for the presence of seven periodontal pathogens . Subjects were monitored at baseline , 3 , 6 and 12 months post-therapies . RESULTS The group receiving SRP+MTZ+AMX presented greater mean probing depth ( PD ) reduction and clinical attachment gain , a lower number of sites with PD ≥5 mm ( primary outcome variable ) and a reduced number of subjects with ≥9 of these residual pockets than the control group at 1-year post-therapy ( p < 0.05 ) . The antibiotic-treated group also presented reduced levels and greater decreases of the three red complex species , Eubacterium nodatum and Prevotella intermedia , compared to the control group at 1 year ( p < 0.05 ) . CONCLUSIONS The adjunctive use of MTZ+AMX significantly improved the clinical and microbiological outcomes of SRP in the treatment of type 2 diabetic subjects with |
1,134 | 27,862,851 | Results suggest that parents provided the impetus for programme initiation , and this was driven largely by a concern for their child 's psychological health and wellbeing .
More often than not , children went along without any real reason or interest in attending .
Over the course of the programme , however , children 's positive social experiences such as having fun and making friends fostered the desire to continue . | The success of childhood weight management programmes relies on family engagement .
While attendance offers many benefits including the support to make positive lifestyle changes , the majority of families referred to treatment decline .
Moreover , for those who do attend , benefits are often compromised by high programme attrition .
This systematic review investigated factors influencing attendance at community-based lifestyle programmes among families of overweight or obese children . | Objective : This study examined the role of demographic characteristics , psychological factors , and family functioning on attendance in a r and omized controlled trial of a family-based pediatric obesity program . Method : Participants included 155 children between the ages of 4 and 7 years ( M age = 5.77 , 57.4 % female , 73.6 % black , M body mass index = 25.5 ) and their primary caregivers who were r and omized to the treatment group . Three groups of participants were created based on their patterns of attendance during the program : ( 1 ) noncompleters , ( 2 ) partial completers , and ( 3 ) completers . Results : Results indicated no differences among the attendance groups in child gender , child body mass index , or child psychological functioning . Significant group differences were found with respect to race/ethnicity , parent marital status , and family income , such that noncompleters were more likely to be racial/ethnic minorities , to living in single parent households , and to have lower incomes than partial completers and completers . After controlling for the effects of these sociodemographic risk factors , noncompleters , and partial completers reported more family dysfunction characterized by high levels of disengagement than completers . Conclusion : Adapting existing weight management programs to include a focus on family engagement in the early stages of treatment may help to improve participation in family-based obesity interventions targeting high risk , socioeconomically disadvantaged youth Background When implemented at scale , the impact on health and health inequalities of public health interventions depends on who receives them in addition to intervention effectiveness . Methods The MEND 7–13 ( Mind , Exercise , Nutrition … Do it ! ) programme is a family-based weight management intervention for childhood overweight and obesity implemented at scale in the community . We compare the characteristics of children referred to the MEND programme ( N=18 289 referred to 1940 programmes ) with those of the population eligible for the intervention , and assess what predicts completion of the intervention . Results Compared to the MEND-eligible population , proportionally more children who started MEND were : obese rather than overweight excluding obese ; girls ; Asian ; from families with a lone parent ; living in less favourable socioeconomic circumstances ; and living in urban rather than rural or suburban areas . Having started the programme , children were relatively less likely to complete it if they : reported ‘ abnormal ’ compared to ‘ normal ’ levels of psychological distress ; were boys ; were from lone parent families ; lived in less favourable socioeconomic circumstances ; and had participated in a relatively large MEND programme group ; or where managers had run more programmes . Conclusions The provision and /or uptake of MEND did not appear to compromise and , if anything , promoted participation of those from disadvantaged circumstances and ethnic minority groups . However , this tendency was diminished because programme completion was less likely for those living in less favourable socioeconomic circumstances . Further research should explore how completion rates of this intervention could be improved for particular groups General Practitioners ( GPs ) have an important role to play in recognition of and intervention against childhood obesity in Irel and . Data were collected prospect ively on a cohort of children aged 4 - 14 and their parents ( n = 101 pairs ) who attended consecutively to a semi-rural group general practice . Parents estimated their child 's weight status . Actual weight status was determined for both parent and child using the United States Centres ' for Disease Control 's BMI -for-age references . 15 ( 14.9 % ) of the children and 49 ( 51.6 % ) of the parents were overweight or obese . While 71 ( 95.5 % ) of normal weight status children were correctly identified , parents showed poor concordance in identifying their children as overweight 2 ( 18.2 % ) or obese 0 ( 0 % ) . BMI was only evidently recorded in the clinical records of 1 out of 15 cases of overweight children identified . With parents failing to recognise childhood obesity , GPs have a responsibility in tackling this problem at a family level BACKGROUND The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours , and improve weight status among children . OBJECTIVE Test the feasibility of Helping H AND ( Healthy Activity and Nutrition Directions ) , an obesity intervention for 5- to 8-year-old children in primary care clinics . METHODS A r and omized controlled pilot study of Helping H AND , a 6-month intervention , targeted children with body mass index 85 - 99%tile and their parents . Intervention group attended monthly sessions and self-selected child behaviours and parenting practice s to change . Control group received regular paediatric care and was wait-listed for Helping H AND . Session completion , participant satisfaction , child anthropometrics , dietary intake , physical activity , TV viewing and behaviour-specific parenting practice s were measured pre and post intervention . RESULTS Forty parent-child dyads enrolled : 82.5 % were Hispanic , 80 % had a girl and 65 % reported income ≤ $ 30 , 000/year . There was 20 % attrition from Helping H AND ( attended < 4/6 sessions ) . Families self-selected 4.35 ( SD 1.75 ) behaviours to target during the 6-month programme and each of the seven behaviours was selected by 45 - 80 % of the families . There were no between group differences in the child 's body mass index z-score , dietary intake or physical activity post intervention . Intervention group viewed 14.9 ( SE 2.3 ) h/week of TV post intervention versus control group 23.3 ( SE 2.4 ) h/week ( P < 0.05 ) . CONCLUSION Helping H AND is feasible , due to low attrition , good programme attendance , and clinical ly relevant improvements in some child and parenting behaviours OBJECTIVE To explore factors influencing participation and attrition in a family-led weight-management programme for obese Pacific children . DESIGN Qualitative study used bilingual in-depth interviews at exit and end of an 8-week weight-management programme . SETTING New Zeal and . SUBJECTS Forty-two parents/ primary caregivers of obese children who were r and omised in the intervention weight-management programme . RESULTS Programmatic factors that enhanced retention included : simultaneous delivery to both children and parents as participants ; delivery of the programme in small group setting s at local community venues ; enabling trustworthy and accountable relationships ; providing re sources for travel to venues and regular telephone/text messaging follow-up calls reinforcing programme goals ; and day and time scheduling . Suggested programme improvements included having ethnic-specific Isl and - language delivery and practical sessions like cooking classes and shopping expeditions at local food stores . The research found that unpredictable external life crises like extended family deaths , a change in job shift , family illnesses ( both acute and those requiring chronic management ) and long-term family visitations affected participation and momentum . A loss of momentum through managing life crises was often difficult to overcome for participants , leading them to drop out of the weight-management programme . Most drop-out participants preferred to defer their programme participation with hopes of re-committing to future programmes at another time . CONCLUSIONS In order for weight-management programmes to be effective , participants must be able to complete them . Identifying factors that predict participation and attrition may serve as a basis for programme improvement OBJECTIVE The purpose of the current study is to describe the development , implementation , and success of recruitment and adherence strategies of 303 African American preadolescent girls and their primary caregiver in the Girls health Enrichment Multi-site Studies ( GEMS ) program . METHODS A socio-ecologic model was used to guide selection and implementation of recruitment and retention strategies which were continuously monitored and revised in response . Strategy mode and frequency associated with program enrollment , engagement , and retention were analyzed . RESULTS Successful recruitment approaches included radio messages ( 23.1 % ) , school fliers ( 20.1 % ) , and friend referral ( 15 % ) . Initially 463 potential participants responded , 320 girls were screened , and 303 enrolled . Significant increases in participant accrual were observed between Wave 4 ( n=28 ) and Wave 5 ( n=91 ) after using a team recruitment approach . Implementing case management strategies and providing make-up sessions also served to keep participants current and engaged in the program . In year 2 , community field trips replaced the more structured sessions providing participants with experiential learning opportunities . Overall intervention attendance rates ranged from 79.7 % to 90.5 % among waves . Further , 75.9 % and 80.2 % , respectively , of participants attended 1-year and 2-year follow-ups . CONCLUSION Multiple recruitment strategies and flexible , responsive approaches to recruitment and retention guided by the socio-ecologic model facilitated optimal implementation of an intervention for preadolescent girls . Through the application of the socio-ecologic model research ers and program leaders will be able to identify strategies to enhance the probability of successful outcomes |
1,135 | 28,160,589 | We can conclude that there is a significant effect of periodontal treatment on improvement of HbA1c in diabetes patients , although the effect size is extremely small . | OBJECTIVES There have been several systematic review s(SRs ) on whether periodontal treatment for an individual with both periodontal disease and diabetes can improve diabetes outcomes .
The purpose of this investigation was to conduct a systematic review ( SR ) of previous meta-analyses , and to assess the method ological quality of the SRs examining the effects of periodontal treatment and diabetes . ( | IMPORTANCE Chronic periodontitis , a destructive inflammatory disorder of the supporting structures of the teeth , is prevalent in patients with diabetes . Limited evidence suggests that periodontal therapy may improve glycemic control . OBJECTIVE To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin ( HbA1c ) in persons with type 2 diabetes and moderate to advanced chronic periodontitis . DESIGN , SETTING , AND PARTICIPANTS The Diabetes and Periodontal Therapy Trial ( DPTT ) , a 6-month , single-masked , multicenter , r and omized clinical trial . Participants had type 2 diabetes , were taking stable doses of medications , had HbA1c levels between 7 % and less than 9 % , and untreated chronic periodontitis . Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers . INTERVENTIONS The treatment group ( n = 257 ) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months . The control group ( n = 257 ) received no treatment for 6 months . MAIN OUTCOMES AND MEASURES Difference in change in HbA1c level from baseline between groups at 6 months . Secondary outcomes included changes in probing pocket depths , clinical attachment loss , bleeding on probing , gingival index , fasting glucose level , and Homeostasis Model Assessment ( HOMA2 ) score . RESULTS Enrollment was stopped early because of futility . At 6 months , mean HbA1c levels in the periodontal therapy group increased 0.17 % ( SD , 1.0 ) , compared with 0.11 % ( SD , 1.0 ) in the control group , with no significant difference between groups based on a linear regression model adjusting for clinical site ( mean difference , -0.05 % [ 95 % CI , -0.23 % to 0.12 % ] ; P = .55 ) . Periodontal measures improved in the treatment group compared with the control group at 6 months , with adjusted between-group differences of 0.28 mm ( 95 % CI , 0.18 to 0.37 ) for probing depth , 0.25 mm ( 95 % CI , 0.14 to 0.36 ) for clinical attachment loss , 13.1 % ( 95 % CI , 8.1 % to 18.1 % ) for bleeding on probing , and 0.27 ( 95 % CI , 0.17 to 0.37 ) for gingival index ( P < .001 for all ) . CONCLUSIONS AND RELEVANCE Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis . These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00997178 Abstract s on this page have been chosen and edited by Dr Trevor Watts Abstract Periodontal treatment improved periodontal health but did not affect glycaemic control AIMS : The purpose of this study is to investigate the effect of improved periodontal health on glycemic control in type 2 diabetes mellitus ( type 2 DM ) patients who have generalized periodontitis . MATERIAL S AND METHODS : A total of 45 type 2 DM patients with generalized periodontitis were selected for the study . The selected patients were r and omly assigned to three groups ( groups A , B , and C ) comprising 15 patients each : • Group A received treatment with scaling and root planing only . • Group B received treatment with scaling and root planing followed by systemic doxycycline . • Group C received no treatment ( control group ) . The periodontal parameters recorded included plaque index , gingival index , probing pocket depth , and clinical attachment level . These parameters were recorded at baseline ( day zero ) , at 1 month , and at the end of 3 months . The following metabolic parameters were recorded : fasting blood glucose ( FBG ) , postpr and ial blood glucose ( PPBG ) , and glycated hemoglobin . These were recorded at baseline ( day zero ) and at the end of 3 months . STATISTICAL ANALYSIS : All the parameters were subjected to repeated- measures ANOVA and Scheffe 's post hoc test . RESULTS : A statistically significant effect could be demonstrated for periodontal parameters for both group A and group B ( treatment groups ) . Glycated hemoglobin values showed statistically significant decrease in treatment groups compared to the control group , with group B showing more significant decrease than group A. CONCLUSIONS : The results of this study showed that nonsurgical periodontal treatment is associated with improved glycemic control in type 2 DM patients BACKGROUND , AIMS This study was design ed to explore the effect of periodontal therapy on glycemic control in persons with type 2 diabetes mellitus ( DM ) . METHODS 36 patients with type 2 DM ( treatment group ) received therapy for adult periodontitis during an 18-month period . A 36-person control group was r and omly selected from the same population of persons with type 2 DM who did not receive periodontal treatment . RESULTS These groups were well matched for most of the parameters investigated . During the nine-month observation period , there was a 6.7 % improvement in glycemic control in the control group when compared to a 17.1 % improvement in the treatment group , a statistically significant difference . Several parameters that could confound or moderate this glycemic control were explored . These included the treatment of non-dental infections , weight and medication changes . No moderating effect was associated with any of these variables . However , there were too few subjects in the study to have the statistical power necessary to assess these possible moderators of glycemic control . CONCLUSIONS We interpret the data in the study to suggest that periodontal therapy was associated with improved glycemic control in persons with type 2 DM AIM the purpose of the present study was to assess the effect of non-surgical periodontal therapy on glycaemic control of type 2 diabetes patients with moderate-to-severe periodontitis . MATERIAL S AND METHODS this was a r and omized , controlled clinical trial of patients with type 2 diabetes . A total of 60 patients with moderate-to-severe periodontal disease were assigned to either a periodontal treatment arm , consisting of scaling and root planing ( intervention group [ IG ] ) , or a delayed treatment arm that received periodontal care after 6 months ( control group [ CG ] ) . Periodontal parameters and glycosylated haemoglobin ( A1C ) were evaluated at 1 , 3 and 6 months . RESULTS all periodontal parameters improved significantly in the IG . A1C levels decreased statistically significantly more in the IG versus the CG ( 0.72%versus 0.13 % ; p<0.01 ) independently of other confounders . CONCLUSIONS this study provides evidence that periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients . Larger controlled trials are needed to confirm if this finding is generalizable to other population s of patients with type 2 diabetes UNLABELLED The AIM of this study was to evaluate the effect of non-surgical therapy on clinical variables and glycemic control on type 2 diabetics with chronic periodontitis . PATIENTS AND METHODS Forty six type 2 diabetics with chronic periodontitis were r and omized into two groups ( group A and group B ) . Treatment included scaling and root planning for group A plus systematic use of doxycycline in both groups . Assessment was made prior to and 16 weeks following the therapy . RESULTS Analysis of data showed that both groups had clinical and glycated hemoglobin ( HbAlc ) improvement after the treatment . Group A had a statistically significant reduction of plaque index and bleeding on probing scores compared with controls ( P < 0.05 ) at 16 weeks . CONCLUSION These results suggest that non-surgical therapy is of value in maintaining periodontal health and may be beneficial in reducing blood glucose level in type 2 diabetics with chronic periodontitis OBJECTIVES Report results of a r and omized- clinical trial of the efficacy of periodontal care in the improvement of glycemic control in 165 veterans with poorly controlled diabetes over 4 months . METHODS Outcomes were change in Haemoglobin A1c ( HbA1c ) in the Early Treatment versus untreated ( Usual Care ) groups and percent of participants with decreases in HbA1c . Analyses included simple/multiple variable linear/logistic regressions , adjusted for baseline HbA1c , age , and duration of diabetes . RESULTS Unadjusted analyses showed no differences between groups . After adjustment for baseline HbA1c , age , and diabetes duration , the mean absolute HbA1c change in the Early Treatment group was -0.65 % versus -0.51 % in the Usual Care group ( p=0.47 ) . Adjusted odds for improvement by 0.5 % in the Early Treatment group was 1.67 ( 95 % confidence interval : 0.84 , 3.34 , p=0.14 ) . Usual Care subjects were twice as likely to increase insulin from baseline to 4 months ( 20 % versus 11 % , p=0.12 ) and less likely to decrease insulin ( 1 % versus 6 % , p=0.21 ) than Early Treatment subjects . Among insulin users at baseline , more increased insulin in the Usual Care group ( 40 % versus 21 % , p=0.06 ) . CONCLUSIONS No significant benefit was found for periodontal therapy after 4 months in this study ; trends in some results were in favour of periodontal treatment |
1,136 | 29,600,334 | Conclusions Available evidence suggests that the use of SPC can be a viable option for postoperative urine drainage after RARP , as it can translate into decreased postoperative pain without carrying a significant higher risk of catheter-related complications . | Purpose To provide latest evidence on the use of suprapubic catheter ( SPC ) versus urethral catheter ( UC ) after robot-assisted laparoscopic radical prostatectomy ( RARP ) . | Objective To evaluate urethral catheter ( UC ) versus suprapubic tube ( SPT ) without stenting the anastomosis at robot-assisted radical prostatectomy ( RALP ) regarding surgical outcome and catheter-associated discomfort . One year after surgery , continence and patient satisfaction were evaluated . Material s and methods Sixty-two patients undergoing RALP were prospect ively r and omized to urinary drainage with UC or with SPT . Functional results were assessed with st and ardized question naires ( IPSS , IPSS Bother Score , IIEF and Visual Analogue Scale ) preoperatively , after catheter removal and 1 year after surgery . Moreover , bother by the catheter as well as pain due to the catheter was assessed . Results At personal hygiene , SPT was significantly less bothersome on the day of surgery as well as POD 1–6 . Pain caused by the catheter did not differ significantly between the two groups except for POD 5 and 6 , when the SPT performed significantly better . Differences regarding voiding parameters after catheter removal did not reach statistical significance . One year after surgery , no significant difference between the two groups was found regarding urinary function and IPSS . Though not statistically significant either , the need for the incision of bladder neck contracture ( BNC ) in two patients in the UC group is of note , as in the SPT group , no BNC occurred . Conclusion Draining the bladder with SPT only is a feasible option in patients undergoing RALP . Patients with SPT are significantly less bothered by the catheter at personal and genital hygiene compared to UC . The risk of BNC seems to be reduced in the SPT group BACKGROUND Robot-assisted radical prostatectomy ( RARP ) is a widespread option for the treatment of patients with clinical ly localised prostate cancer . Modifications in the surgical technique may help to further improve functional outcomes . OBJECTIVE To assess the outcome of early catheter removal 48h after surgery , as opposed to st and ard catheter removal 6 d after surgery following RARP , using a newly developed surgical technique for posterior reconstruction and anastomosis ( Aalst technique ) . DESIGN , SETTING , AND PARTICIPANTS Patients scheduled for RARP were prospect ively scheduled for early catheter removal at postoperative d 2 ( group A , n=37 ) and st and ard catheter removal at postoperative d 6 ( group B , n=37 ) . SURGICAL PROCEDURE RARP was performed using the Da Vinci Si system . The Aalst technique for the urethro-vesical anastomosis including posterior reconstruction was used as previously described . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary endpoint was spontaneous voiding after catheter removal . Secondary endpoints were rate of anastomotic urinary leakage after catheter removal , presence and severity of urethral , perineal , and abdominal pain , as well as patient 's bother after catheter removal using visual analogue scale ( VAS ) scores . Rate and severity of urinary incontinence after catheter removal were assessed using the International Consultation on Incontinence Question naire-Male Lower Urinary Tract Symptoms Module ( ICIQ-MLUTS ) question naire . RESULTS AND LIMITATIONS There was no significant difference between the groups with regard to baseline and perioperative parameters , as well as pathological features ; however , significantly more patients underwent bilateral nerve-sparing procedures in group A ( 34 vs 23 , p=0.008 ) . After catheter removal , patients in both groups showed spontaneous voiding , whereas only 11 % and 8 % of the patients in group A and group B experienced urinary retention after catheter removal ( p=0.7 ) . Patients in group B had significantly higher maximum flow rates , but lower voided volumes after catheter removal in comparison with patients in group A ( 21ml/s vs 10ml/s , p≤0.001 and 170ml vs 200ml , p≤0.001 , respectively ) . ICIQ-MLUTS question naire and VAS scores showed no significant differences between the groups at any time point . CONCLUSIONS The Aalst technique allows the removal of catheters 2 d after RARP and results in spontaneous voiding . Early removal showed no increased rate of urinary leakage , no negative impact on short-term continence and on perineal , urethral or penile pain , and no increase in urinary retention rates . Future studies have to confirm these results with longer follow-up including detailed parameters on return to daily activity . PATIENT SUMMARY We provide evidence that it is possible to remove the bladder catheter as early as 2 d after robot-assisted radical prostatectomy without any negative effects on voiding and pain parameters . Thus , leaving the hospital early without a catheter in place could represent a significant and relevant benefit for the patient PURPOSE Retrospective single institution data suggest that postoperative pain after robot-assisted laparoscopic radical prostatectomy is decreased by early removal of the urethral catheter with suprapubic tube drainage . In a r and omized patient population we determined whether suprapubic tube drainage with early urethral catheter removal would improve postoperative pain compared with urethral catheter drainage alone . MATERIAL S AND METHODS Men with a body mass index of less than 40 kg/m(2 ) who had newly diagnosed prostate cancer and elected robot-assisted laparoscopic radical prostatectomy were included in analysis . Block r and omization by surgeon was used and r and omization assignment was done after completing the urethrovesical anastomosis . In patients assigned to suprapubic tube drainage the urethral catheter was removed on postoperative day 1 and all catheters were removed on postoperative day 7 . Visual analog pain scale and satisfaction question naires were administered on postoperative days 0 , 1 and 7 . RESULTS A total of 29 patients were r and omized to the urethral catheter vs 29 to the suprapubic tube plus early urethral catheter removal at the time of interim futility analysis . Mean visual analog pain scale scores did not differ between the groups at any time point and a similar percent of patients cited the catheter as the greatest bother with nonsignificant differences in treatment related satisfaction . Complications during postoperative week 1 did not vary between the groups . Based on interim results the trial was terminated due to lack of effect . CONCLUSIONS Patients r and omized to suprapubic tube vs urethral catheter drainage for the week after prostatectomy had similar pain , catheter related bother and treatment related satisfaction in the perioperative period . We no longer routinely offer suprapubic tube drainage with early urethral catheter removal at our institution BACKGROUND The literature is lacking r and omised controlled trials comparing robot-assisted ( RARP ) and laparoscopic ( LRP ) radical prostatectomy , especially for follow-up > 1 yr . OBJECTIVE To report 5-yr outcomes for our previously published prospect i ve r and omised study comparing RARP and LRP . DESIGN , SETTING , AND PARTICIPANTS From January 2010 to January 2011 , 120 patients with organ-confined prostate cancer were enrolled and r and omly assigned to RARP or LRP . INTERVENTION A single surgeon performed all interventions using the same transperitoneal antero grade technique . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Continence , potency , and serum prostate-specific antigen were assessed postoperatively at 1 , 3 , 6 , and 12 mo , and then every 6 mo until 60 mo . At the end of the follow-up period , patients were administered questions 1 and 46 of the Exp and ed Prostate Cancer Index Composite question naire to assess their satisfaction with the intervention and general health status . A generalised estimating equations model was used to compare time series data for functional results , and Kaplan-Meier and Cox models were used to analyse oncologic outcomes . RESULTS AND LIMITATIONS The probability of achieving continence ( odds ratio [ OR ] 2.47 , p<0.021 ) and potency ( OR 2.35 , p<0.028 ) over time was more than doubled for the RARP compared to the LRP group . There was no difference between the two approaches in terms of patient survival . Pathologic Gleason score , positive surgical margins , and pT stage were associated with significantly higher biochemical recurrence in Cox multivariate models . Patient satisfaction with the intervention and their general health status was significantly higher in the RARP group . CONCLUSIONS Throughout the 5-yr follow-up , RARP yielded better functional results compared to LRP , without compromising oncologic outcomes . PATIENT SUMMARY In this report we looked at 5-yr outcomes for a study comparing robot-assisted radical prostatectomy ( RARP ) and laparascopic radical prostatectomy for the treatment of prostate cancer . We found that continence and potency are better among patients treated with RARP , while oncologic results are comparable BACKGROUND More than a decade since its inception , the benefits and cost efficiency of robot-assisted radical prostatectomy ( RARP ) continue to elicit controversy . OBJECTIVE To compare outcomes and costs between RARP and open RP ( ORP ) . DESIGN , SETTING , AND PARTICIPANTS A cohort study of 629 593 men who underwent RP for localized prostate cancer at 449 hospitals in the USA from 2003 to 2013 , using the Premier Hospital Data base . INTERVENTION RARP was ascertained through a review of the hospital charge description master for robotic supplies . OUTCOME MEASURES AND STATISTICAL ANALYSIS Outcomes were 90-d postoperative complications ( Clavien ) , blood product transfusions , operating room time ( ORT ) , length of stay ( LOS ) , and direct hospital costs . Propensity-weighted regression analyses accounting for clustering by hospitals and survey weighting ensured nationally representative estimates . RESULTS AND LIMITATIONS RARP utilization rapidly increased from 1.8 % in 2003 to 85 % in 2013 ( p<0.001 ) . RARP patients ( n=311 135 ) were less likely to experience any complications ( odds ratio [ OR ] 0.68 , p<0.001 ) or prolonged LOS ( OR 0.28 , p<0.001 ) , or to receive blood products ( OR 0.33 , p=0.002 ) compared to ORP patients ( n=318 458 ) . The adjusted mean ORT was 131min longer for RARP ( p=0.002 ) . The 90-d direct hospital costs were higher for RARP ( + $ 4528 , p<0.001 ) , primarily attributed to operating room and supplies costs . Costs were no longer signficantly different between ORP and RARP among the highest-volume surgeons ( ≥104 cases/yr ; + $ 1990 , p=0.40 ) and highest-volume hospitals ( ≥318 cases/yr ; + $ 1225 , p=0.39 ) . Limitations include the lack of oncologic characteristics and the retrospective nature of the study . CONCLUSIONS Our contemporary analysis reveals that RARP confers a perioperative morbidity advantage at higher cost . In the absence of large r and omized trials because of the widespread adoption of RARP , this retrospective study represents the best available evidence for the morbidity and cost profile of RARP versus ORP . PATIENT SUMMARY In this large study of men with prostate cancer who underwent either open or robotic radical prostatectomy , we found that robotic surgery has a better morbidity profile but costs more The purpose of this work was to assess the feasibility of urethral catheter removal 3 days after radical retropubic prostatectomy ( RRP ) . Twenty-two patients who underwent RRP with a watertight eight-suture vesicourethral anastomosis had their urethral catheter removed usually on postoperative day ( POD ) 3 . The average day of urethral catheter removal was POD 3.2 . At 3 months , 56 % of patients required no or one protective pad to stay dry and 68.4 % of patients ‘ never leaked ’ or ‘ leaked occasionally ’ . Following RRP , the urethral catheter can be removed as early as POD 3 if the intraoperative anastomosis is watertight without compromising urinary continence Purpose To evaluate the impact of the type of urinary diversion ( suprapubic vs. transurethral catheterization ) on patients ’ postoperative pain after radical prostatectomy , development of bacteriuria and long-term functional results . Methods A r and omized , prospect i ve clinical trial was performed including 160 patients who underwent robot-assisted radical prostatectomy after r and omization into two groups : intraoperatively , a transurethral catheter ( control group ) or an additional suprapubic tube ( with removal of the transurethral catheter in the morning of postoperative day 1 ; intervention group ) was placed . Primary study endpoint was postoperative pain objectified by the numeric rating scale question naire . Secondary endpoints were bacteriuria after catheter removal and functional outcomes after up to 2 years of follow-up . Results There were no significant differences in demographic and perioperative data . Starting on postoperative day 2 , patients in the suprapubic diversion group had significantly less pain on every time point preceding the removal of the catheter compared to the control cohort with a median overall numeric rating score on postoperative day 1–4 of 2.4 points in the transurethral versus 1.3 in the intervention group ( p = 0.012 ) . No statistical difference was found in postoperative bacteriuria and complications as well as in functional results , quality of life and incontinence rates after a median follow-up of 22 months . Conclusions Suprapubic drainage in robot-assisted radical prostatectomy shows significantly decreased pain levels during the catheterization period compared to the transurethral diversion without compromising long-term functional results . Intraoperative placement of a suprapubic tube should be discussed as a st and ard procedure for further improvement of patients ’ postoperative comfort © 2 0 1 0 T H E A U T H O R S J O U R N A L C O M P I L A T I O N © 2 0 1 0 B J U I N T E R N A T I O N A L 1 2 0 1 8 Faiz O , Brown T , Colucci G , Kennedy RH . A cohort study of results following elective colonic resection within an enhanced recovery programme . Colorectal Dis 2009 ; 11 : 366–72 9 Lassen K , Soop M , Nygren J et al. Consensus review of optimal perioperative care in colorectal surgery . Enhanced Recovery After Surgery ( ERAS ) Group Recommendations . Arch Surg 2009 ; 144 : 961–9 10 Halaszynski TM , Juda R , Silverman DG . Optimizing postoperative outcomes with efficient preoperative assessment and management . Crit Care Med 2004 ; 32 ( Suppl . ) : S76–86 11 Guenaga KF , Matos D , Castro AA , Atallah A , Wille-Jorgensen P. Mechanical bowel preparation for elective colorectal surgery . Cochrane Data base Syst Rev 2005 ; ( 1 ) : CDOO1544 12 Shafii M , Murphy DM , Donovan MG , Hickey DP . Is mechanical bowel preparation necessary in patients undergoing cystectomy and urinary diversion . BJU Int 2002 ; 89 : 879–81 13 Smith AF , Pittaway AJ . Premedication for anxiety in adult day surgery : up date of Cochrane Data base Syst Rev 2000 : CD002192 . Cochrane Data base Syst Rev 2003 ; ( 1 ) : CD002192 14 Gerts WH , Pineo GF , Heit JA et al. Prevention of venous thromboembolism : the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy . Chest 2004 ; 126 : 338S–400S 15 Fearon KC , Luff R. The nutritional management of surgical patients : enhanced recovery after surgery . Proc Nutr Soc 2003 ; 62 : 807–11 16 Noblett SE , Watson DS , Huong H , Davison B , Hainsworth PJ , Horgan AF . Pre-operative oral carbohydrate loading in colorectal surgery : a r and omized controlled trial . Colorectal Dis 2006 ; 8 : 563–9 17 Wong PF , Kumar S , Bohra A et al. R and omized clinical trial of perioperative systemic warming in major elective abdominal surgery . Br J Surg 2007 ; 94 : 421–6 18 Ratnaraj J , Kabon B , Talcoff MR , Sessler DI , Kurz A. Supplemental oxygen and carbon dioxide each increase subcutaneous and intestinal intramural oxygenation . Anesth Analg 2004 ; 99 : 207–11 19 Grief R , Akça O , Horn EP , Kurz A , Sessler DI . Supplemental perioperative oxygen to reduce the incidence of surgical wound infection . Outcomes Research Group . N Engl J Med 2000 ; 342 : 161–7 20 Grief R , Laciny S , Rapf B , Hickle RS , Sessler DI . Supplemental oxygen reduces the incidence of post operative nausea and vomiting . Anesthesiology 1999 ; 91 : 1246–52 21 HTA . Full report : systematic review of the clinical effectiveness and cost effectiveness of oesophageal Doppler monitoring in critically ill and high risk surgical patients . Available at : http:// www.hta.ac.uk/project/.asp . Accessed 5 December 2009 22 Cepeda MS , Carr DB , Mir and a N , Diaz A , Silva C , Morales O. Comparison of morphine , ketorolac , and their combination for postoperative pain : results from a large , r and omised , double blind trial . Anaesthesiology 2005 ; 103 : 1225–32 23 Arumainayagam N , McGrath J , Jefferson KP , Gillatt DA . Introduction of an enhanced recovery protocol for radical cystectomy . BJU Int 2008 ; 101 : 698–701 24 Pruthi RS , Chun J , Richman M. Reducing time to oral diet and hospital discharge in patients undergoing radical cystectomy using a perioperative care plan . Urology 2003 ; 62 : 661–6 25 Chang SS , Baumgartner RG , Wells N et al. Causes of increased hospital stay after radical cystectomy in a clinical pathway setting . J Urol 2002 ; 167 : 208– OBJECTIVE Robot-assisted laparoscopic prostatectomy ( RALP ) with suprapubic tube ( SPT ) , compared to urethral catheter ( UC ) drainage , has been proposed to improve patient comfort and recovery . We sought to compare short-term outcomes for pain and morbidity after RALP with SPT vs UC drainage . METHODS Between August 2012 and 2014 , 159 men underwent a RALP and prospect ively completed a question naire addressing postoperative pain and satisfaction . Group 1 ( n = 94 ) underwent a RALP by one surgeon who placed a UC and removed it between postoperative day ( POD ) 7 and 10 . Group 2 ( n = 65 ) underwent a RALP by a different surgeon who placed an SPT and UC . On POD 1 , the UC was removed . On POD 9 , the SPT was capped and removed on POD 11 if the patient was voiding adequately . Preoperative and intraoperative data , complications , question naires , and patient-reported morbidity , including unplanned telephone calls and emergency department ( ED ) visits , were compared between groups . RESULTS Patient characteristics were similar between groups . One week after surgery , the penile pain score was statistically significantly lower in Group 2 compared to Group 1 ( 56.9 % and 79.8 % , respectively , reported minimal-to-moderate pain , p = 0.003 ) . Bladder spasms and overall pain were not significantly higher for Group 1 compared to Group 2 ( p > 0.05 ) . When asked " How big a problem has your urine storage device been ? , " 20.2 % of patients in Group 1 reported it as a " moderate-to-big " problem compared to 10.8 % in Group 2 ( p > 0.05 ) . The number of catheter-related unplanned telephone encounters did not differ between the two groups ( p = 0.7 ) , however , although not statistically significant , 4.6 % of patients in Group 2 presented to the ED with catheter-related issues ( p = 0.07 ) . CONCLUSION SPT after RALP was associated with less penile pain compared to UC drainage , and modestly better patient satisfaction . There were no significant differences in bladder spasms , overall pain , and patient-reported morbidity between groups BACKGROUND The introduction of robotics revolutionized prostate cancer surgery because the magnified three-dimensional vision system and wristed instruments allow microsurgery to be performed . The advantages of robotic surgery could lead to improved continence outcomes in terms of early recovery compared with the traditional surgical methods . OBJECTIVE To describe the total anatomical reconstruction ( TAR ) technique during robot-assisted radical prostatectomy ( RARP ) . PRIMARY ENDPOINT evaluation of the continence rate at different time points . Secondary endpoint : evaluation of urine leakage and anastomosis stenosis rates related to the technique . DESIGN , SETTING , AND PARTICIPANTS June , 2013 to November , 2014 ; prospect i ve consecutive series of patients with localized prostate cancer ( cT1 - 3 , cN0 , cM0 ) . SURGICAL PROCEDURE RARP with TAR was performed in all cases . Lymph node dissection was performed if the risk of lymph nodal metastasis was over 5 % , according to the Briganti up date d nomogram . MEASUREMENTS Preoperative , intraoperative , postoperative , and pathological variables were analyzed . Enrolled patients were arbitrarily divided into three groups according to a time criterion . The relationships between the learning curve and the trend of the above-mentioned variables were analyzed using LOESS analysis . Continence was rigorously analyzed preoperatively and at 24h , 1 wk , 4 wk , 12 wk , and 24 wk after catheter removal . RESULTS AND LIMITATIONS In total , 252 patients were analyzed . The continence rates immediately after catheter removal and at 1 wk , 4 wk , 12 wk , and 24 wk after RARP were 71.8 % , 77.8 % , 89.3 % , 94.4 % , and 98.0 % , respectively . Multivariate analysis revealed that the nerve sparing technique , D'Amico risk groups , lymph node dissection , and prostate volume were involved in the early recovery of urinary continence . One ileal perforation requiring reoperation was recorded . The transfusion rate was 0.8 % . Thirty-one ( 12.3 % ) postoperative complications were recorded up to 6 mo after surgery . Among these , eight acute urinary retentions ( 3.2 % ) and three urine leakages ( 1.2 % ) were recorded . There was a lack of r and omization and comparison with other techniques . Both anatomical dissection of the prostatic apex and TAR were used . The results may not be generalized to low-volume centers . CONCLUSIONS The TAR technique showed promising results in the early recovery of urinary continence , as well as watertight anastomosis and a low rate of urine leakage . The oncologic results were not affected . Comparative studies are needed to support the quality of reported results . PATIENT SUMMARY On the basis of our findings , it seems that the risk of urinary incontinence following radical prostatectomy can be lowered via meticulous anatomical reconstruction using a robotic system . Comparative studies are required to support the reported results |
1,137 | 27,900,142 | Results Overall , the review showed that the ergogenic effect of pseudoephedrine is dose-dependent .
It is evident that there is a correlation between the dose administered and its ergogenic effects , but it is also evident that the side effects of using above the therapeutic dose outweigh the possible benefits of using pseudoephedrine in sport . | Objective Pseudoephedrine is a stimulant that can be purchased over-the-counter to relieve symptoms of nasal and sinus congestion .
Owing to its similar composition to ephedrine and other amphetamines , pseudoephedrine mirrors some of its ergogenic effects .
This study investigates its possible ergogenic effect through a systematic review .
Our primary aim was to determine the effects of pseudoephedrine in sport and its potential for performance enhancement . | UNLABELLED Pseudoephedrine is an over-the-counter drug to relieve nasal and sinus congestion . Although it has been suggested that pseudoephedrine could be a stimulant and ergogenic aid , pseudoephedrine was recently removed from the banned substance list by the International Olympic Committee and placed on the monitoring program ( from January 2004 ) . It was felt that evidence was lacking for an ergogenic effect , although few studies have investigated the effects of pseudoephedrine on exercise performance . This study , therefore , aim ed to investigate the effects of pseudoephedrine on 1500-m running performance . METHODS In a double-blind , r and omized crossover design , seven male athletes completed two 1500-m running trials on an outdoor track after having completed a familiarization trial . All trials were 7 d apart . After a 12-h overnight fast , subjects reported to the laboratory and received a st and ardized breakfast ( energy asymptotically equal to 500 kcal 50 % CHO ) . Subjects were given either 2.5 mg.kg(-1 ) bw pseudoephedrine or 2.5 mg.kg(-1 ) bw maltodextrins ( placebo ) in gelatin capsules 70 min before the start of the warm-up , which started 20 min before they ran 1500 m all-out . Pre- and postexercise blood sample s were collected and analyzed for lactate and glucose concentrations , partial pressure of oxygen ( PO2 ) and carbon dioxide ( PCO2 ) , and percent oxygen saturation . RESULTS Pseudoephedrine significantly decreased time to completion of 1500-m time trials in the present study by 2.1 % ( from 279.65 + /- 4.36 s with placebo to 273.86 + /- 4.36 s with pseudoephedrine ) with no reported side effects . No changes in the measured blood parameters were found , suggesting a central effect of pseudoephedrine rather than a metabolic effect . CONCLUSION The finding was that 2.5 mg.kg(-1 ) bw pseudoephedrine ingested 90 min preexercise improves 1500-m running performance The aim of the study was to assess the effect of maximal therapeutic dosing of sympathomimetic amines found in over-the-counter ( OTC ) decongestant preparations on endurance running . Following familiarisation and a grade d exercise test to determine maximal oxygen uptake ( VO2 max ) , trained male runners ( n = 8) completed four exercise sessions each separated by a minimum of one week . Each session was comprised of 20 min of sub-maximal treadmill running ( 70 % VO2 max ) followed by a 5,000-m time trial on the treadmill under drug , placebo or control conditions . Drugs were administered in their commercial format over the 36-hour period prior to testing in the manufacturer 's recommended maximal doses ( i. e. 25 mg of phenylpropanolamine and 60 mg of pseudoephedrine four times daily ) . During sub-maximal endurance running no statistical differences were observed in heart rate , VO2 , minute ventilation , respiratory exchange ratio , blood lactate , glucose or non-esterified fatty acids ( NEFA ) or ratings of perceived exertion with respect to the treatment administered . Similarly there were no statistical differences according to the condition during the 5,000-m running time trial , in terms of heart rate , ratings of perceived exertion , time of completion and pre and post exercise blood lactate , glucose or NEFA . The results indicate that in maximal , multiple therapeutic doses both pseudoephedrine or phenylpropanolamine as present in common OTC decongestant formulations do not affect , nor possess any ergogenic properties with regard to , endurance running OBJECTIVES The purpose of the present study was to examine a possible dose-response between pre-exercise pseudoephedrine intake and cycling time trial performance . DESIGN R and omised , double-blind , crossover trial . METHODS Ten trained male endurance cyclists ( 26.5 ± 6.2 years , 75.1 ± 5.9 kg , 70.6 ± 6.8 mL kg(-1)min(-1 ) ) undertook three cycling time trials in which a fixed amount of work ( 7 kJ kg(-1 ) body mass ) was completed in the shortest possible time . Sixty minutes before the start of exercise , subjects orally ingested either 2.3 mg kg(-1 ) or 2.8 mg kg(-1 ) body mass of pseudoephedrine or a placebo in a r and omised and double-blind manner . Venous blood was sample d at baseline , pre- and post-warm up and post-exercise for the analysis of pH and lactate and glucose concentrations ; plasma catecholamine and pseudoephedrine concentrations were measured at all times except post-warm up . RESULTS Cycling time trial performance ( ∼ 30 min ) was not enhanced by pseudoephedrine ingestion . Plasma pseudoephedrine concentration increased from pre-warm up to post-exercise in both treatment conditions , with the 2.8 mg kg(-1 ) body mass dose producing the highest concentration at both time points ( 2.8 mg kg(-1)>2.3 mg kg(-1)>placebo ; p<0.001 ) . CONCLUSIONS There was large individual variation in plasma pseudoephedrine concentration between subjects following pseudoephedrine administration . A number of factors clearly influence the uptake and appearance of pseudoephedrine in the blood and these are not yet fully understood . Combined with subsequent differences in plasma pseudoephedrine between individuals , this may partially explain the present findings and also the inconsistencies in performance following pseudoephedrine administration in previous studies The ingestion of a combination of caffeine ( C ) and ephedrine ( E ) has been reported to prolong exercise time to exhaustion during cycle ergometry at 85 % VO2max . The present study was undertaken to investigate whether this enhancement would occur in a field setting and if drug ingestion on 1 d would affect performance 1 d later . Two hours after ingesting either a combination of 375 mg of C and 75 mg E ( C+E ) , or a placebo ( P ) , 9 healthy male recreational runners completed six balanced and double-blind trials of the Canadian Forces Warrior Test ( WT ) , a 3.2 km run wearing " fighting order " which weighed about 11 kg . The trials were performed in sets of two runs , i.e. , two runs were done 24 h apart , and these sets were separated by a minimum of 7 d. The sets were : C+E trial on day 1 ( D1 ) , placebo on day 2 ( P2 ) ; placebo first ( P1 ) , C+E second ( D2 ) ; and placebo first ( P3 ) , placebo second ( P4 ) . In addition , 1 wk before the treatment trials the subjects performed a control trial WT . During the WT , heart rates ( HR ) were recorded every minute . Plasma C and E levels immediately before the WT were similar for both C+E trials , but were undetectable for all P trials . Run times ( mean+/-SD ) were 15.3+/-0.6 , 15.4+/-0.9 , 15.5+/-1.2 , 15.4+/-0.9 , 15.4+/-0.9 , 14.8+/-0.7 , and 14.6+/-0.8 min for control , P1 , P2 , P3 , P4 , D1 , D2 trials , respectively . The two C+E trial run times were similar and both were significantly faster ( p < 0.05 ) than control and all placebo trials . HR during the WT was significantly higher ( p < 0.05 ) for the C+E trials compared with the other trials . WT performance was not impaired by C+E ingestion 24 h earlier . In conclusion , performance of the WT was improved by ingestion of Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To investigate the effect of an acute oral administration of pseudoephedrine ( PSE ) on muscle function , fatigue , and anaerobic power output . Design and Material sHealthy males ( N = 10 ) and females ( N = 10 ) were allocated to receive both a placebo and PSE ( 120 mg ) using a r and omized , double-blind , crossover experimental design . Each subject had their maximal voluntary contraction strength and fatigability measured for both h and grip and ankle dorsi-flexion . Following the strength measurements , a 30-second maximal cycle test was performed to determine lower extremity anaerobic power and fatigue . Plasma lactate was measured before and after exercise . Results There were no significant differences in any of the outcome variables between the placebo and PSE trials . Conclusions These results demonstrated that a 120 mg dose of PSE did not enhance force production , time to fatigue , fatigue index , or power output in young men or women . Therefore , there does not appear to be an ergogenic benefit from the ingestion of 120 mg PSE in high-intensity exercise performance In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted This study was design ed to measure whether a single dose of 120 mg pseudoephedrine ingested 120 min before exercise influences performance during 1 h of high-intensity exercise . The effects of exercise on urinary excretion of the drug were also studied . Ten healthy male cyclists were tested on two occasions , separated by at least 7 days , by using a r and omly assigned , double-blind , placebo-controlled , crossover design . Exercise performance was tested during a 40-km trial on a laboratory cycle ergometer , and skeletal muscle function was measured during isometric contractions . On a third occasion , subjects ingested 120 mg pseudoephedrine but did not exercise [ control ( C ) ] . Pseudoephedrine did not influence either time trial performance [ drug ( D ) vs. placebo : 58.1 + /- 1.4 ( SE ) vs. 58.7 + /- 1.5 min ] or isometric muscle function . Urinary pseudoephedrine concentrations were significantly increased 1 h after exercise ( D vs. C : 114.3 + /- 27.2 vs. 35.4 + /- 13.1 micrograms/ml ; P < 0.05 ) . Peak plasma pseudoephedrine concentrations ( P < 0.05 ) but not time taken to reach peak plasma concentrations or the area under the plasma pseudoephedrine concentration vs. time curve was significantly increased in the total group with exercise ( D vs. C ) . In three subjects , plasma pseudoephedrine concentrations were not influenced by exercise . Only these subjects showed increased urinary pseudoephedrine excretion during exercise . We conclude that a single therapeutic dose of pseudoephedrine did not have a measurable ergogenic effect during high-intensity exercise of 1-h duration , but plasma drug concentrations and urinary excretion were altered by exercise . These findings have practical relevance to doping control regulations in international sporting competitions Objective To study the effects of over-the-counter dosages of the pure α1–agonists pseudoephedrine ( PSE ) and phenylpropanolamine ( PPA ) on selected parameters of exercise performance , and to establish a range of corresponding drug levels in the urine of the athletes who use these drugs . Design Placebo-controlled , r and omized , double-blinded , multiple-dose trial . Setting The National Institute of Fitness and Sport , the Department of Family Medicine , Indiana University , and the Sports Medicine Lab , Department of Pathology , Indiana University , Indianapolis , Indiana . Participants A convenience sample of 20 male cyclists , aged 18–35 , from the local cycling community . Inclusion criteria required cycling at least 50 miles a week , no chronic medical problems , and not taking any medications . Subjects were recruited by local ads and word of mouth . Intervention Patients were r and omized to one of two groups of 10 subjects . Each subject in both groups performed three separate bicycle ergometer tests after ingestion of varying dosages of α1–agonists . One group performed tests after receiving placebo , 0.33 mg/kg PPA , and 0.66 mg/kg PPA , whereas the other group received placebo , 1 mg/kg PSE , and 2 mg/kg PSE . A minimum 1-week washout period was required between tests . Urine for drug testing was collected 1 h before , immediately afterward , and the next morning after testing . Drug testing was performed by gas GC/MCD at a facility approved by the International Olympic Committee . Main outcome measures Maximum oxygen uptake ( VO2max ) , time to exhaustion , urine drug levels of PSE and PPA , peak blood pressures ( BPs ) , peak pulse , and Borg scale ( rating of perceived exertion or RPE ) . Main Results In the PPA group , the 0.33-mg/kg dose result ed in insignificant changes in peak systolic BP ( + 5.4 mm Hg , p = 0.260 ) , peak diastolic BP ( −1.6 mm Hg , p = 0.622 ) , peak pulse ( −2.2 beats/min , p = 0.12 ) , peak Borg ( RPE = −0.10 ( p = 0.823 ) , time to exhaustion ( −16.9 s , p = 0.287 ) , and Vo2max ( + 0.50 ml/kg/min , p = 0.71 ) . No significant change was noted in any study variable at the 0.66-mg/kg PPA dose , and some effects were dissimilar to the lower PPA dose effects . Peak systolic BP increased 2.8 mm Hg ( p = 0.617 ) , diastolic BP decreased 1.6 mm Hg ( p = 0.634 ) , peak pulse increased 1.4 beats/min ( p = 0.504 ) , peak Borg RPE decreased 0.80 ( p = 0.210 ) , time to exhaustion decreased 2.6 s ( p = 0.861 ) , and Vo2max decreased 2.92 ml/kg/min ( p = 0.14).In the 1-mg/kg PSE group , there was a significant increase in peak systolic BP ( + 10.6 mm Hg , p = 0.029 ) . No significant changes occurred in peak diastolic BP ( + 2.4 mm Hg , p = 0.333 ) , peak pulse ( + 2.2 beats/min , p = 0.306 ) , peak RPE ( + 0.2 , p = 0.62 ) , time to exhaustion ( + 21.4 s , p = 0.289 ) , and Vo2max ( + 2.29 ml/kg/min , p = 0.31 ) . In the 2-mg/kg PSE dose trial , there were insignificant changes in peak systolic BP of + 2.4 mm Hg ( p = 0.559 ) , + 3.8 mm Hg in peak diastolic BP ( p = 0.106 ) , + 1.6 beats/min in peak pulse ( p = 0.586 ) , −0.1 in peak Borg RPE scales ( p = 0.76 ) , −10.4 s in time to exhaustion ( p = 0.41 ) , and + 1.79 ml/kg/min in Vo2max ( p = 0.43).Urine drug levels in those subjects receiving 1 mg/kg PSE ranged from 7–55 μg/ml before performance and 30–128 μg/ml after performance to 7–35 μg/ml the next morning . Levels in those receiving 2 mg/kg ranged from 5–160 μg/ml before performance and 44–200 μg/ml after performance to 8–44 μg/ml the next day . In the PPA 0.33-mg/kg dose trials , the levels ranged 1–36 μg/ml before performance and 9–50 μg/ml after performance to < 1–14 μg/ml the next morning . In the PPA 0.66-mg/kg dose trials , the levels were 4–52 μg/ml before performance , 8–80 μg/ml after performance , and 6–74 μg/ml the next day . Conclusions We found no significant differences between trials in maximum oxygen uptake ( Vo2max ) , peak or progression of Borg Scale ( RPE ) , maximum systolic and diastolic BPs , peak pulse , or time to exhaustion among the athletes tested at the dosages studied . Urine drug levels in athletes taking one and two times the over-the-counter dosages of PPA and PSE in all cases exceeded allowable limits according to International Olympic Committee drug-testing st and ards PURPOSE To study the effects of a therapeutic dose of pseudoephedrine on anaerobic cycling power and aerobic cycling efficiency . METHODS Eleven healthy moderately trained males ( VO ( 2peak ) 4.4 + /- 0.8 L x min(-1 ) participated in a double-blinded crossover design . Subjects underwent baseline ( B ) tests for anaerobic ( Wingate test ) and aerobic ( VO ( 2peak ) test ) cycling power . Subjects ingested either 60 mg of pseudoephedrine hydrochloride ( D ) or a placebo ( P ) and , after 90 min of rest , a Wingate and a cycling efficiency test were performed . During the cycling efficiency test , heart rate ( HR ) and VO(2 ) were averaged for the last 5 min of a 10-min cycle at 40 % and 60 % of the peak power achieved during the VO ( 2peak ) test . RESULTS There were no significant differences in peak power ( B = 860 + /- 154 , D = 926 + /- 124 , P = 908 + /- 118 W ) , total work ( B = 20 + /- 3 , D = 21 + /- 3 , P = 21 + /- 3 kJ ) , or fatigue index ( B = 39 + /- 8 , D = 45 + /- 5 , P = 43 + /- 5 % ) . There were no significant differences in HR at 40 % power ( D = 138 + /- 10 , P = 137 + /- 10 beats.min-1 ) or 60 % power ( D = 161 + /- 11 , P = 160 + /- 11 beats x min(-1 ) . There were no significant differences in cycling efficiency at 40 % power ( D = 18.8 + /- 1.8 , P = 18.5 + /- 1.8 % ) or 60 % power ( D = 20.3 + /- 2.0 , P = 20.1 + /- 2.1 % ) . CONCLUSION A therapeutic dose of pseudoephedrine hydrochloride does not affect anaerobic cycling performance or aerobic cycling efficiency The aim of the current study was to investigate the effect of 180 mg of pseudoephedrine ( PSE ) on cycling time-trial ( TT ) performance . Six well-trained male cyclists and triathletes ( age 33 + /- 2 yr , mass 81 + /- 8 kg , height 182.0 + /- 6.7 cm , VO2max 56.8 + /- 6.8 ml x kg(-1 ) x min(-1 ) ; M + /- SD ) underwent 2 performance trials in which they completed a 25-min variable-intensity ( 50 - 90 % maximal aerobic power ) warm-up , followed by a cycling TT in which they completed a fixed amount of work ( 7 kJ/kg body mass ) in the shortest possible time . Sixty minutes before the start of exercise , they orally ingested 180 mg of PSE or a cornstarch placebo ( PLA ) in a r and omized , crossover , double-blind manner . Venous blood was sample d immediately pre- and postexercise for the analysis of pH plus lactate , glucose , and norepinephrine ( NE ) . PSE improved cycling TT performance by 5.1 % ( 95 % CI 0 - 10 % ) compared with PLA ( 28:58.9 + /- 4:26.5 and 30:31.7 + /- 4:36.7 min , respectively ) . There was a significant Treatment x Time interaction ( p = .04 ) for NE , with NE increasing during the PSE trial only . Similarly , blood glucose also showed a trend ( p = .06 ) for increased levels postexercise in the PSE trial . The ingestion of 180 mg of PSE 60 min before the onset of high-intensity exercise improved cycling TT performance in well-trained athletes . It is possible that changes in metabolism or an increase in central nervous system stimulation is responsible for the observed ergogenic effect of PSE BACKGROUND Ingesting a combination of caffeine and ephedrine ( C+E ) has been shown to raise metabolic heat production and body temperature . This side effect of C+E ingestion may be positive during a cold stress scenario , however , during heat stress it could prove to be detrimental . Thus , the purpose of this study was to clarify the effect of C+E ingestion on body temperature regulation during moderate exercise in a hot dry environment . METHODS Ten , healthy , non heat acclimated , males exercised at 50 % VO2peak in a 40 degrees C and 30 % RH environment until rectal temperature reached 39.3 degrees C ; heart rate ( HR ) remained at 95 % of peak value or greater for 3 min , dizziness or nausea precluded further exercise , or 3 h had elapsed . They did this four times at weekly intervals : familiarization ( Fam ) , control ( Cont ) , placebo , and C+E ( 5 mg . kg(-1 ) caffeine + 1 mg . kg(-1 ) ephedrine ) trials . The Fam and Cont treatments were done first and sequentially while the placebo and C+E treatments were balanced and double-blind . Tolerance times , mean skin temperature ( Tsk ) , rectal temperature ( Tre ) , Vo2 , Vco2 , VE , sweat rate ( SR ) , HR , and sensation of thermal comfort were measured . RESULTS Tolerance times ( mean+/-SD in minutes ) were similar for the placebo ( 120.0+/-28.4 ) and C+E ( 121.3+/-33.9 ) trials and both times were significantly longer than Cont ( 106.6+/-24.0 ) trial . C+E did not affect Tsk , initial TrC , delta Tre , SR or the sensation of thermal comfort . VO2 and VF , were significantly increased by C+E. HR was elevated by C+E compared with the other trials , but only during the initial 20 min of exercise . CONCLUSION Although the metabolic rate was slightly increased with C+E treatment , it was sufficiently offset by increased heat loss mechanisms so that internal body temperature was not increased during moderate exercise in a hot , dry environment AIMS Pseudoephedrine ( PSE ) is a readily available over-the-counter nasal decongestant which is structurally similar to amphetamine and is included on the International Olympic Committee 's list of banned substances . However to date , little research has supported its putative ergogenic effect . This study investigated whether a 180 mg dose of PSE ingested 45 min prior to exercise enhanced short-term maximal exercise performance and /or altered related physiological variables . METHODS A r and omised , double-blind , crossover study in 22 healthy male athletes . RESULTS Maximum torque ( mean + /- s.d . , n = 22 ) produced in an isometric knee extension exercise was 321.1+/-62.0 Nm ( PSE ) and 295.7+/-72.4 Nm ( placebo ) , and peak power obtained on the ' all-out ' 30 s cycle test was 1262.5+/-48.5 W ( PSE ) and 1228.4+/-47.1 W ( placebo ) ( P<0.01 , P<0.03 , respectively ) . Subjects were estimated to be producing 96.9+/-2.4 % of their maximal possible isometric leg extension force after PSE ingestion , but only 95.3+/-2.4 % when PSE was not ingested . Bench press tasks and total work during the cycle test were not affected by the ingestion of PSE . Lung function was altered following ingestion of PSE ( P<0.05 ) with FEV1 and FVC significantly increased ( P<0.02 , P<0.01 , respectively ) although the FEV1/FVC ratio was not altered . Heart rate was significantly elevated by the ingestion of PSE immediately following the 30 s cycle sprint ( P<0.01 ) however , lactate concentration was not altered by the ingestion of PSE . CONCLUSIONS The administration of a 180 mg dose of PSE increased maximum torque , produced in an isometric knee extension and produced an improvement in peak power during maximal cycle performance , as well as improving lung function Due to its stimulatory effects on the central nervous system , and its structural similarity to banned stimulants such as ephedrine and methamphetamine , pseudoephedrine ( PSE ) at high doses is considered as an ergogenic aid for boosting athletic performance . However , the status of PSE in the International St and ard of the Prohibited List as established under the World Anti-Doping Code has changed over the years , being prohibited until 2003 at a urinary cut-off value of 25 µg/ml , and then subsequently removed from the Prohibited List during the period 2004 - 2009 . The re-consideration of this position by the World Anti-Doping Agency ( WADA ) List Expert Group has led to the re introduction of PSE in the Prohibited List in 2010 . In this manuscript , we present the results of two WADA-sponsored clinical studies on the urinary excretion of PSE and its metabolite cathine ( CATH ) following the oral administration of different PSE formulations to healthy individuals at therapeutic regimes . On this basis , the current analytical urinary threshold for the detection of PSE as a doping agent in sport has been conservatively established at 150 AIMS To study the elimination of ephedrines with reference to the International Olympic Committee ( IOC ) doping control cut-off levels , following multiple dosing of over-the-counter decongestant preparations . METHODS A double-blind study was performed in which 16 healthy male volunteers were administered either pseudoephedrine or phenylpropanolamine in maximal recommended therapeutic doses over a 36-h period . Urine was collected every two hours between 08:00 and 24:00 h and at 04:00 h throughout the testing period of three days . Urine drug levels were quantified using high performance liquid chromatography . Side-effects were assessed , including heart rate and blood pressure , every four hours between 08:00 and 20:00 h. RESULTS Mean ( 95 % CI ) total phenylpropanolamine and pseudoephedrine eliminated unchanged was 75 ( 88 , 61 ) and 81 ( 92 , 71)% , respectively . Maximum urine concentrations of phenylpropanolamine and pseudoephedrine were 112.1 ( 164.2 , 59.9 ) and 148.5 ( 215.0 , 82.1 ) mg.l(-1 ) , respectively . A peak in drug urine concentration occurred four hours following the final dose . There were no adverse cardiovascular effects and only mild CNS stimulation was evident . CONCLUSIONS Following therapeutic , multiple dosing , drug levels remain above the IOC cut-off levels for a minimum of 6 h and 16 h following final doses of phenylpropanolamine and pseudoephedrine , respectively . Athletes require informed advice on this from their healthcare professionals |
1,138 | 21,454,329 | Even small financial incentives were found to be effective in improving nurse survey participation .
Token nonmonetary incentives , in contrast , were much less effective .
In terms of design strategies , postal and telephone strategies have generally been more successful than have fax or web-based approaches , with evidence also supporting use of mixed-mode surveys in this population .
In addition , use of first-class stamps on return envelopes as well as question naires personalized and endorsed by legitimizing professional associations were also more likely to be successful . | While surveys of nurses are an important tool in health services and policy research , they are often characterized by low response rates . | Background Postal surveys are a frequently used method of data collection in health services research . Low response rates increase the potential for bias and threaten study validity . The objectives of this study were to estimate current response rates , to assess whether response rates are falling , to explore factors that might enhance response rates and to examine the potential for non-response bias in surveys mailed to healthcare professionals . Methods A r and om sample of postal or electronic surveys of healthcare workers ( 1996 - 2005 ) was identified from Medline , Embase or Psycinfo data bases or Biomed Central . Outcome measures were survey response rate and non response analysis . Multilevel , multivariable logistic regression examined the relationship between response rate and publication type , healthcare profession , country and number of survey participants , question naire length and use of reminders . Results The analysis included 350 studies . Average response rate in doctors was 57.5 % ( 95%CI : 55.2 % to 59.8 % ) and significantly lower than the estimate for the prior 10 year period . Response rates were higher when reminders were sent ( adjusted OR 1.3 ; 95%CI 1.1 - 1.6 ) but only half the studies did this . Response rates were also higher in studies with fewer than 1000 participants and in countries other than US , Canada , Australia and New Zeal and . They were not significantly affected by publication type or healthcare profession ( p > 0.05 ) . Only 17 % of studies attempted assessment of possible non-response bias . Conclusion Response rates to postal surveys of healthcare professionals are low and probably declining , almost certainly leading to unknown levels of bias . To improve the informativeness of postal survey findings , research ers should routinely consider the use of reminders and assess potential for non-response bias Background Monetary incentives in survey research may provide important gains from a method ological perspective in the control and reduction of survey error associated with potential nonresponse of participants . However , few studies have systematic ally investigated the use of monetary incentives or other methods to improve the response rates in the nonphysician clinician population . Objective To investigate differences in response rates to a mailed self-administered survey of nonphysician clinicians who were r and omized to receive a prepaid monetary incentive , a postsurvey prize drawing , or no incentive . Methods A r and omized controlled trial of financial incentives was conducted from November 2002 to February 2003 . Nonphysician clinicians ( nurse practitioners [ NPs ] and physician assistants [ PAs ] ; N = 3,900 ) r and omly selected to participate in a national ethics-related study were assigned r and omly in equal allocations ( n = 1,300 [ 650 NPs , 650 PAs ] ) to three incentive groups : ( a ) no incentive ; ( b ) a $ 5 prepaid token incentive in the initial mailing ; or ( c ) a chance to win one of ten $ 100 prize drawings upon completion and return of a self-administered survey . Results A $ 5 cash incentive increased survey response rates to an adjusted 64.2 % : a 19.5 percentage point increase over the lottery group ( 44.7 % response rate ) , and a 22 percentage point increase over the control group ( 42.2 % response rate ) . Discussion A nominal cash incentive of $ 5 yields a significantly higher response rate from nonphysician providers than receiving either a lottery option or no incentive Background Given the increasingly stressful environment due to manpower shortages in the healthcare system in general , substance induced impairment among some healthcare professions is anticipated to grow . Though recent studies suggest that the prevalence of substance abuse is no higher in healthcare professionals ( HPs ) than the general population , given the responsibility to the public , any impairment could place the public at increased risk for errors . Few studies have ever reported predictors or risk factors for alcohol and other drug use ( AOD ) across a sample of HPs . Methods The study used a cross-sectional , descriptive self-report survey in a small northeastern state . A 7-page survey was mailed to a stratified r and om sample of 697 dentists , nurses , pharmacists and physicians registered in a northeastern state . The main outcome measures were demographic characteristics , lifetime , past year and past month prevalence of AOD use , the frequency of use , drug related dysfunctions , drug misuse and abuse potential . Six contacts during the summer of 2002 result ed in a 68.7 % response rate ( 479/697 ) . Results Risk factors contributing to any reported past year AOD use , as well as significant ( defined as the amount of AOD use by the top 25 % of respondents ) past year AOD use by HPs were examined using logistic regression . Risk factors of any self-reported past year AOD use included moderate or more frequency of alcohol use , being in situations when offered AODs , feeling immune to the addictive effects of drugs ( pharmaceutical invincibility ) and socializing with substance abusers . Risk factors of significant past year AOD use were HPs with younger licensees , a moderate pattern of alcohol use and not socializing with substance abusers . Conclusion National and state organizations need to develop policies that focus on prevention , treatment , and rehabilitation of alcohol and other drug-using healthcare professionals . The results of this study may help to delineate the characteristics of HPs abusing drugs , leading to the development of more effective policies design ed to protect the public , and move toward more tailored and effective intervention strategies for HPs The purpose of this research was to study the effect of various direct mail techniques on professional nurses ' response rates to question naires . A r and om sample of 700 registered professional nurses consisting of five groups who were members of New York State Nurses Association ( NYSNA ) were mailed a question naire with 22 items . The study demonstrated that the response rates were directly attributable to techniques used . Providing information about the association was related to significantly decreased response rates and monetary incentives with significantly increased response rates . A combined direct mailing for question naire completion and membership solicitation was not effective for either purpose The purpose was to examine the effectiveness of a modest monetary incentive ( $ 1 ) and none in increasing the response rate of a mail survey to 600 nurse practitioners . The response rate in the incentive group was 81 % and 66 % in the control group , significant by chi-square test . The most cost effective survey technique for increasing the response rate of nurse practitioners was to code the envelopes and eliminate the monetary incentive The past 20 years have seen an overall decline in survey response rates and an even more pronounced decline in sample s of health care professionals . The authors tested the use of a “ thank you ” or “ reminder ” postcard as a method by which to stem the tide of declining response rates . The authors conducted a mail and telephone survey of 49,605 registered nurses for the 2000 National Sample Survey of Registered Nurses and sent an extra mailing to a r and om sub sample ( n= 4,968 ) . They then compared response rates for both groups . Contrary to prior research , this study found that reminder postcards did not improve response rates or rates of return . There may be several reasons for this finding , including the general familiarity with , and high saliency of , this research project for the nursing community . These results suggest that even widely accepted best practice s for survey methods deserve scrutiny when applied to special sub population OBJECTIVE To examine response rate information from mailed physician question naires reported in published articles . DATA SOURCES / STUDY SETTING Citations for articles published between 1985 and 1995 were obtained using a key word search of the Medline , PsychLit , and Sociofile data bases . STUDY DESIGN A 5 percent r and om sample of relevant citations was selected from each year . DATA COLLECTION / EXTRACTION METHODS Citations found to be other than physician surveys were discarded and replaced with the next r and omly assigned article . Selected articles were abstract ed using a st and ardized variable list . PRINCIPAL FINDINGS The average response rate for mailed physician question naires was 61 percent . The average response rate for large sample surveys ( > 1,000 observations ) was 52 percent . In addition , only 44 percent of the abstract ed articles reported a discussion of response bias , and only 54 percent reported any type of follow-up . CONCLUSIONS ( 1 ) Response rates have remained somewhat constant over time , and ( 2 ) research ers need to document the efforts used to increase response rates to mailed physician question naires Background : Achieving acceptable response rates from health care providers via postal question naires is an ongoing challenge . The use of monetary incentives is one of the most effective strategies for increasing response rates . However , the effect and cost of such an incentive on retail pharmacists ’ response rates has not been well studied . Methods : A sample of 700 pharmacies was selected at r and om from the electronic Yellow Pages in NSW Australia and mailed a brief survey regarding pharmacotherapies and advice for smoking cessation . Half of the sample was r and omly allocated to receive an offer of an US$ 14 gift voucher . Results : The response rates were 65.9 % for the voucher group and 53.5 % for the no-voucher group . The odds of response from the voucher group was 1.68 ( 95%CI = 1.23 , 2.30 ) times greater than for the no-voucher group . The cost per additional respondent was US$ 67.95 . The incentive also reduced follow up costs by 10 % . Conclusions : A moderately sized monetary incentive is able to achieve a significant increase in response rates for retail pharmacists , thereby reducing potential bias in the sample Two major obstacles encountered when surveying nursing practice in institutional setting s are obtaining a representative sample and collecting an adequate number of observations at a reasonable cost . Past efforts to deal with these problems are review ed briefly , and results are reported from a two-stage mail survey of a national sample of critical-care nurses . The first stage involved attempts to procure a list of staff nurses from head nurses of critical-care units at 240 r and omly selected institutions . An 86 % response rate was obtained . The second stage involved mailing question naires to a r and om sample of 600 critical-care nurses listed . Completed , mailed question naires were obtained from 87 % . Little evidence of bias due to administrative selection and /or volunteerism was found in the lists of staff nurses . An analysis of membership in professional nursing organizations indicates that more than one half of the nurses who responded to this survey would not have been included had the sample been selected from organizational membership lists Background : Recent experiences of survey research ers suggest that physicians are becoming less willing to complete surveys . Objective : To compare response rates to a mailed physician survey with a prepaid check incentive of $ 20 versus $ 50 . Research Design : R and omized controlled trial . Subjects : Five hundred seventy-eight physicians caring for patients with lung or colorectal cancer in northern California . Measures : Proportion of physicians responding to the survey . Results : Overall , 60.0 % of physicians responded to the survey . The response rate was 52.1 % for physicians who received a $ 20 check versus 67.8 % for physicians who received a $ 50 check ( P < 0.001 ) . Similar differences in response rates were seen in strata by physician sex , year graduated from medical school , and survey version ( all P < 0.001 ) . More than 42 % of physicians who received a $ 50 check responded to the first mailing , compared with only 30.8 % of those who received a $ 20 check ( P < 0.001 ) . Conclusions : Among physicians caring for patients with lung cancer or colorectal cancer in northern California , a $ 50 check incentive was much more effective than a $ 20 check incentive at increasing response rates to a mailed survey . As physicians become increasingly burdened with surveys , larger incentives may be necessary to engage potential respondents and thus maximize response rates We conducted a pilot study to determine the most efficient mailing strategy for a postal question naire study among nurses in Ontario , Canada . Five mailing strategies involving types of stamps on the return envelopes were considered : no stamp , business-reply stamp , metered stamp , small regular stamp , and large commemorative stamp . We found that paper stamps , especially large commemorative stamps , on return envelopes increased the response rate and reduced the response time , as compared with other mailing strategies . Business-reply stamps had the lowest cost per response received and a low total cost This study assessed differences in response rates to a series of three-wave mail surveys when amiable or insistently worded postcards were the third wave of the mailing . Three studies were conducted ; one with a sample of 600 health commissioners , one with a sample of 680 vascular nurses , and one with 600 elementary school secretaries . The combined response rates for the first and second wave mailings were 65.8 % , 67.6 % , and 62.4 % , respectively . A total of 308 amiable and 308 insistent postcards were sent r and omly to nonrespondents as the third wave mailing . Overall , there were 41 amiable and 52 insistent postcards returned , not significantly different by chi-square test . However , a separate chi-square test for one of the three studies , the nurses ' study , did find a significant difference in favor of the insistently worded postcards To determine whether academic physicians ' response rates to a mail survey depend on the envelope used to mail the survey , we r and omized 901 internists affiliated with a university department of medicine to receive a survey in either a university envelope or a Veterans Affairs envelope . The response rate among those receiving the Veterans Affairs envelope ( 41 % ) was 20 % higher than the response rate among those receiving the university envelope ( 34 % ) . We conclude that the packaging of a mail survey can influence the response rate Background : More patients are receiving healthcare services from nurse practitioners ( NPs ) and physician assistants ( PAs ) . These providers are likely to be confronted with a variety of ethical issues as they balance quality care with their patients ' rising cost concerns . However , very little is known about the ethical conflicts and causes of these conflicts experienced by these clinicians in their daily practice . Objective : To identify ethical concerns and conflicts NPs and PAs encounter related to managed care in the delivery of primary care to patients and the factors that influence ethical conflict . Methods : A cross-sectional self-administered mailed question naire was sent to 3,900 NPs and PAs r and omly selected from primary care and primary care subspecialties in the United States ( adjusted response rate , 50.6 % ) . Respondents were surveyed on ethical issues and concerns , ethics preparedness , and ethical conflict . Bivariate and multiple linear regression analyses were used to evaluate predictors of ethical conflict . Results : Insurance constraints were reported to have interfered with the ability to provide quality patient care by 72 % of respondents , with 55.3 % reporting daily to weekly interferences . Nearly half of respondents ( 47 % ) have been asked by a patient to mislead insurers to assist them in receiving care . A perceived obligation to advocate for patients , even if it means exaggerating the severity of a patient 's condition , was the single most significant predictor of ethical conflict , explaining 25 % of the variance . Discussion : NPs and PAs are experiencing ethical conflict often associated with their perceived professional obligations to advocate for patients . Being well-prepared in ethics and having sufficient professional independence help clinicians balance the ethical complexities and dem and s of meeting patients ' needs within a constrained healthcare system We assessed the prevalence of licit ( e.g. alcohol ) and illicit ( e.g. cocaine ) drug use , as well as prescription ( e.g. tranquillizers ) and over-the-counter medications ( e.g. analgesics ) , in a regional sample of female nurses . Surveys were mailed to a r and om sample of 4000 nurses in Western New York . The survey focused on lifetime and current use of substances , negative consequences of alcohol consumption and dependence . Three mailings result ed in a return of 2400 ( 60 % ) surveys , of which 1951 ( 49 % ) were usable . We examined lifetime and current use in each of the four classes of substances in the context of nursing related-factors ( e.g. type of nurse , nursing specialty , work setting ) and demographic characteristics ( e.g. age , marital status ) . There were significant differences within each of the different groupings . Lifetime experience of negative consequences were relatively rare and few nurses reported dependence on substances other than tobacco and caffeine Improvement of hospital unit work environments is key to quality patient care , productivity , nurse retention , and job satisfaction . Accurate measurement of such environments is necessary prior to introduction and evaluation of improvement structures and strategies . Characteristics and attributes of work environments are group level phenomena . Accurate assessment of these phenomena requires survey response rates of sufficient size to ensure sample representativeness and data that can reliably be aggregated to group level . What is the sufficient response rate ? This question was answered through psychometric testing of five r and om sample s from the population of 23 M.D. And erson Cancer Center clinical units that had 100 % response rates on an environmental survey . Response rates of 40 % or more had acceptable psychometric properties for unit-specific scales OBJECTIVE To assess the effects of two different mixed-mode ( mail and web survey ) combinations on response rates , response times , and nonresponse bias in a sample of primary care and specialty internal medicine physicians . DATA SOURCES / STUDY SETTING Primary data were collected from 500 physicians with an appointment in the Mayo Clinic Department of Medicine ( DOM ) between February and March 2005 . STUDY DESIGN Physicians were r and omly assigned to receive either an initial mailed survey evaluating the Electronic Medical Record ( EMR ) with a web survey follow-up to nonrespondents or its converse-an initial web survey followed by a mailed survey to nonrespondents . Response rates for each condition were calculated using st and ard formula . Response times were determined as well . Nonresponse bias was measured by comparing selected characteristics of survey respondents to similar characteristics in the full sample frame . In addition , the distributions of results on key outcome variables were compared overall and by data collection condition and phase . PRINCIPAL FINDINGS Overall response rates were somewhat higher in the mail/web condition ( 70.5 percent ) than in the web/mail condition ( 62.9 percent ) ; differences were more pronounced before the mode switch prior to the mailing to nonrespondents . Median response time was 2 days faster in the web/mail condition than in the mail/web ( median=5 and 7 days , respectively ) but there was evidence of under-representation of specialist physicians and those who used the EMR a half a day or less each day in the web/mail condition before introduction of the mailed component . This did not translate into significant inconsistencies or differences in the distributions of key outcome variables , however . CONCLUSIONS A methodology that uses an initial mailing of a self-administered form followed by a web survey to nonrespondents provides slightly higher response rates and a more representative sample than one that starts with web and ends with a mailed survey . However , if the length of the data collection period is limited and rapid response is important , perhaps the web survey followed by a mailed question naire is to be preferred . Key outcome variables appear to be unaffected by the data collection method |
1,139 | 14,584,018 | Vitamin B12 deficiency produces both an anaemia identical to that of folate deficiency but also causes irreversible damage to the central and peripheral nervous systems .
Folic acid will correct the anaemia of vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage .
REVIEW ER 'S CONCLUSIONS There was no beneficial effect of 750 mcg of folic acid per day on measures of cognition or mood in older healthy women .
In patients with mild to moderate cognitive decline and different forms of dementia there was no benefit from folic acid on measures of cognition or mood .
Folic acid plus vitamin B12 was effective in reducing the serum homocysteine concentrations .
Folic acid was well tolerated and no adverse effects were reported . | BACKGROUND Folates are vitamins essential to the development of the central nervous system .
Insufficient folate activity at the time of conception and early pregnancy can result in congenital neural tube defects .
In adult life folate deficiency has been known for decades to produce a characteristic form of anaemia ( " megaloblastic " ) .
More recently degrees of folate inadequacy , not severe enough to produce anaemia , have been found to be associated with high blood levels of the amino acid homocysteine .
Such degrees of folate inadequacy can arise because of insufficient folates in the diet or because of inefficient absorption or metabolic utilisation of folates due to genetic variations .
Conventional criteria for diagnosing folate deficiency may be inadequate for identifying people capable of benefiting from dietary supplementation .
High blood levels of homocysteine have been linked with the risk of arterial disease , dementia and Alzheimer 's disease .
There is therefore interest in whether dietary supplements of folic acid ( an artificial chemical analogue of naturally occurring folates ) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia , whether by affecting homocysteine metabolism or through other mechanisms .
There is a risk that if folic acid is given to people who have undiagnosed deficiency of vitamin B12 it may lead to neurological damage .
OBJECTIVES To examine the effects of folic acid supplementation , with or without vitamin B12 , on elderly healthy and demented people , in preventing cognitive impairment or retarding its progress . | Abstract 5′-Methyltetrahydrofolic acid ( 5′- MTHF ) in addition to st and ard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency , and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment . In this equivalence study the effect of 5′- MTHF on depressive symptoms and cognitive status was compared to Trazodone ( TRZ ) in normofolatemic elderly patients with mild to moderate dementia and depression . Ninety-six patients with dementia , scoring 12–23 at the Mini Mental State Examination ( MMSE ) and ≥18 at the Hamilton Depression Rating Scale ( HDRS ) after a 2-week placebo run-in , were r and omized to receive either 5′-MTHF ( 50 mg/day p.o . ) ( 47 patients ) or TRZ ( 100 mg/day p.o . ) ( 49 patients ) in a double-blind design for 8 weeks . HDRS was assessed before , after 4 weeks and at the end of treatment ; Rey ’s Verbal Memory ( RVM ) test for immediate and delayed recall was evaluated before and after treatment . After 4 weeks of treatment HDRS score was reduced from 23±5 to 20±6 in the 5′-MTHF ( p<0.05 vs baseline ) , and from 23±3 to 21±4 in the TRZ group ( p<0.05 vs baseline ) . p]A further significant decrease to 18±6 and 19±5 respectively was obtained at the end of the treatment period ( p<0.05 vs week 4 ) with 5′-MTHF and TRZ . HDRS was administered again after a 4-week , drug-free , follow-up period : no change vs the post treatment scores was observed either in the 5′-MTHF or in the TRZ group ( 18±7 and 19±5 respectively ) . RVM test for immediate recall was significantly improved ( p<0.05 ) at week 8 vs baseline in the 5′-MTHF group whereas no significant change occurred in the TRZ group . No change in delayed recall was observed after treatment in either group . Tolerability was good for both treatments . This study shows that 5′-MTHF and TRZ are equally effective in improving depressive symptoms in patients with mild to moderate dementia and suggests that pharmacological doses of 5′-MTHF may exert psychotropic effects irrespective of folate status . ( Aging Clin . Exp . Res . 1 : 63–71 , 1993 Based on research demonstrating associations between folate , B-12 and B-6 vitamins and cognition and mood , we investigated the effects of short-term supplementation in 211 healthy younger , middle-aged and older women who took either 750 microg of folate , 15 microg of vitamin B-12 , 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition , we examined associations between dietary intake of these vitamins and cognition and mood . Usual dietary intake status was estimated using a retrospective , self-report , quantified food frequency question naire . Participants completed alternate forms of st and ardized tests of cognitive processing re sources , memory , executive function , verbal ability and self-report mood measures before and after supplementation . Supplementation had a significant positive effect on some measures of memory performance only , and no effect on mood . Dietary intake status was associated with speed of processing , recall and recognition and verbal ability BACKGROUND Frail elders are at risk of suboptimal micronutrient status , functional decline , and neurologic disorders . The influence of oral multimicronutrients in physiologic doses and of moderately intense physical exercise on homocysteine ( Hcy ) , methylmalonic acid ( MMA ) , and neurologic functioning have not yet been investigated . OBJECTIVE Our goal was to determine the effects of enriched foods and exercise on blood vitamins , Hcy , MMA , and neuropsychological functioning in the frail . DESIGN A 17-wk r and omized controlled intervention trial was used to study 1 ) enriched foods plus a social program , 2 ) regular foods plus exercise , 3 ) enriched foods plus exercise , and 4 ) regular foods plus a social program . Enriched foods contained multiple micronutrients ( 25 - 100 % of the Dutch recommended dietary allowances ) ; exercises focused on strength , coordination , flexibility , and endurance . Vitamin ( cobalamin , red blood cell folate , and pyridoxal 5'-phosphate ) , Hcy , and MMA concentrations were measured and 2 neuropsychological tests were conducted . RESULTS Vitamin concentrations were higher in the supplemented groups than in the unsupplemented groups ( P < 0.001 ; total n = 130 ) . Compared with baseline , cobalamin in the supplemented groups was increased by 22 % , plasma folate by 101 % , red blood cell folate by 87 % , and pyridoxal 5'-phosphate by 68 % . Concentrations in the unsupplemented groups changed by -2 % , -6 % , 1 % , and -13 % , respectively . Hcy decreased by 25 % and MMA by 30 % in the supplemented groups , compared with a small increase in Hcy ( 2 % ) and decrease in MMA ( 9 % ) in the unsupplemented groups . Exercise did not significantly affect vitamin , Hcy , or MMA concentrations . No significant effect of either intervention was observed on the neuropsychological tests . CONCLUSIONS The decrease in Hcy and MMA in frail elders confirms a sub clinical metabolic deficiency state . Enriched foods containing physiologic amounts of micronutrients have a beneficial effect on these metabolites . No effects of B vitamins on mental health were identified OBJECTIVE The main hypothesis was that subtle vitamin B12 deficiencies occur more commonly in senile dementia of Alzheimer type ( SDAT ) that in healthy elderly individuals , and may be revealed by elevated total serum homocysteine ( tHcy ) . A subsidiary hypothesis was that such deficiencies would be nutritionally independent as determined by retinol binding protein ( RBP ) . DESIGN A prospect i ve case-controlled survey . SETTING A Welsh urban psychogeriatric assessment centre and local general practice . PATIENTS Thirty patients , aged 65 or over , seen consecutively in 1994 with features compatible with DSM-III-R criteria for primary degenerative dementia of Alzheimer type and 30 cognitively intact age-matched control subjects . MEASURES Diagnosis was assessed using the CAMDEX . Cognitive scores were evaluated with the CAMCOG scale for patients and MMSE scores for control subjects . THcy was measured using high performance liquid chromatography ( HPLC ) , and RBP assayed by a radial immunodiffusion method . RESULTS Patients had a highly significant elevation of tHcy compared with control ( p < 0.0001 ) . Multiple regression highlighted the interrelated effects of tHcy and total serum cobalamin on cognitive scores . RBP did not differ between groups . Macrocytosis was absent , and neutrophil hypersegmentation uncommon , in hyperhomocysteinaemic patients . CONCLUSIONS SDAT patients have significantly elevated tHcy . This is independent of RBP determined nutritional status . ' Classical ' haematological changes of cobalamin or folate deficiency are poor predictors of tHcy in these patients . Aberrant cobalamin tissue delivery appears to contribute to SDAT cognitive decline . Relative contributions of other tHcy determinants require further investigation Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration OBJECTIVES To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels ; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia . SUBJECTS People with dementia or mild cognitive impairment . DESIGN AND INTERVENTION In a 2 x 2 x 2 factorial design trial , 149 people at high-risk of dementia were r and omized to receive either low-dose aspirin ( 81 mg ) or placebo ; and folic acid ( 2 mg ) plus vitamin B12 ( 1 mg ) or placebo ; and vitamins E ( 500 mg ) plus C ( 200 mg ) or placebo . Participants were seen twice before and once after 12 weeks of treatment . MAIN OUTCOME MEASURES At each visit , participants had their cognitive function assessed and had blood collected for homocysteine , folate and vitamin B12 determination and urine collected for markers of platelet activation ( 11-dehydro-thromboxane B2 ) and reactive oxygen species ( 8-epi-PGF2 alpha ) . RESULTS Prior to treatment , cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane , and these associations were independent of age . Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73 % ( P < 0.001 ) . B-vitamins lowered plasma homocysteine concentration by 30 % ( P < 0.0001 ) and antioxidant vitamins lowered isoprostane excretion by 26 % ( P < 0.1 ) . No effect of treatment on cognitive function was detected . CONCLUSIONS Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia . Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia Moderate hyperhomocysteinaemia is common in the general population and has been linked with cardiovascular disease . However , there are no data from prospect i ve , population -based studies . We examined the association between serum total homocysteine ( tHcy ) concentration and stroke in a nested case-control study within the British Regional Heart Study cohort . Between 1978 and 1980 serum was saved from 5661 men , aged 40 - 59 years , r and omly selected from the population of one general practice in each of 18 towns in the UK . During follow-up to December , 1991 , there were 141 incident cases of stroke among men with no history of stroke at screening . Serum tHcy was measured in 107 cases and 118 control men ( matched for age-group and town , without a history of stroke at screening , who did not develop a stroke or myocardial infa rct ion during follow-up ) . tHcy concentrations were significantly higher in cases than controls ( geometric mean 13.7 [ 95 % CI 12.7 - 14.8 ] vs 11.9 [ 11.3 - 12.6 ] mumol/L ; p = 0.004 ) . There was a grade d increase in the relative risk of stroke in the second , third , and fourth quarters of the tHcy distribution ( odds ratios 1.3 , 1.9 , 2.8 ; trend p = 0.005 ) relative to the first . Adjustment for age-group , town , social class , body-mass index , hypertensive status , cigarette smoking , forced expiratory volume , packed-cell volume , alcohol intake , diabetes , high-density-lipoprotein cholesterol , and serum creatinine did not attenuate the association . These findings suggest that tHcy is a strong and independent risk factor for stroke BACKGROUND Elevated plasma homocysteine levels are a risk factor for coronary heart disease , but the prognostic value of homocysteine levels in patients with established coronary artery disease has not been defined . METHODS We prospect ively investigated the relation between plasma total homocysteine levels and mortality among 587 patients with angiographically confirmed coronary artery disease . At the time of angiography in 1991 or 1992 , risk factors for coronary disease , including homocysteine levels , were evaluated . The majority of the patients subsequently underwent coronary-artery bypass grafting ( 318 patients ) or percutaneous transluminal coronary angioplasty ( 120 patients ) ; the remaining 149 were treated medically . RESULTS After a median follow-up of 4.6 years , 64 patients ( 10.9 percent ) had died . We found a strong , grade d relation between plasma homocysteine levels and overall mortality . After four years , 3.8 percent of patients with homocysteine levels below 9 micromol per liter had died , as compared with 24.7 percent of those with homocysteine levels of 15 micromol per liter or higher . Homocysteine levels were only weakly related to the extent of coronary artery disease but were strongly related to the history with respect to myocardial infa rct ion , the left ventricular ejection fraction , and the serum creatinine level . The relation of homocysteine levels to mortality remained strong after adjustment for these and other potential confounders . In an analysis in which the patients with homocysteine levels below 9 micromol per liter were used as the reference group , the mortality ratios were 1.9 for patients with homocysteine levels of 9.0 to 14.9 micromol per liter , 2.8 for those with levels of 15.0 to 19.9 micromol per liter , and 4.5 for those with levels of 20.0 micromol per liter or higher ( P for trend=0.02 ) . When death due to cardiovascular disease ( which occurred in 50 patients ) was used as the end point in the analysis , the relation between homocysteine levels and mortality was slightly strengthened . CONCLUSIONS Plasma total homocysteine levels are a strong predictor of mortality in patients with angiographically confirmed coronary artery disease Folic acid deficiency is common in the elderly population , result ing in anaemia , dementia , many neurological sequelae and an indirect role in atheromatous disease . An increase in natural food folate is relatively ineffective at increasing folate status and the use of folate fortification of foodstuffs is recommended . The aim of our study was to assess the benefits of folic acid-fortified milk to the folate status of an elderly institutionalised population . 49 subjects received fortified milk as part of their daily diet for at least 6 months ( active group ) and 40 subjects received unfortified milk ( control group ) . Our results showed a mean serum folate level in the active group of 5.81 ( 1.1–17.6 ) µg/l compared to the control group mean of 2.16 ( 0.5–9.4 ) µg/l ( p < 0.001 ; normal range for serum folate 2.7–20 µg/l ) . Similarly the mean red cell folate level in the active group of 316.5 ( 130–905 ) µg/l was significantly higher than the control group mean of 196.1 ( 95–490 ) µg/l ( p < 0.001 ; normal range for red cell folate 150–1,000 µg/l ) . Our results suggest that folic acid-fortified milk is an efficacious and acceptable method of administration of folic acid in the elderly population and we recommend the use of folic acid-fortified milk in the regular daily diet of the elderly population |
1,140 | 23,007,881 | The best evidence was for brief ( 10- to 15-minute ) multicontact interventions .
Evidence was insufficient to draw conclusions about accidents , injuries , or alcohol-related liver problems .
Trials enrolling young adults or college students showed reduced consumption and fewer heavy drinking episodes ( moderate strength of evidence ) .
Little or no evidence of harms was found .
CONCLUSION Behavioral counseling interventions improve behavioral outcomes for adults with risky drinking . | BACKGROUND Alcohol misuse , which includes the full spectrum from risky drinking to alcohol dependence , is a leading cause of preventable death in the United States .
PURPOSE To evaluate the benefits and harms of behavioral counseling interventions for adolescents and adults who misuse alcohol . | BACKGROUND Brief interventions for problem drinking in medical setting s are effective but rarely conducted , mainly due to insufficient time . A stepped care approach ( starting with a very brief intervention and intensifying efforts in case of no success ) could save re sources and enlarge effectiveness ; however , research is lacking . The present study compares a full care brief intervention for patients with at-risk drinking , alcohol abuse or dependence with a stepped care approach in a r and omized controlled trial . METHODS Participants were proactively recruited from general practice s in two northern German cities . In total , 10,803 screenings were conducted ( refusal rate : 5 % ) . Alcohol use disorders according to DSM-IV were assessed with the Munich-Composite International Diagnostic Interview ( M-CIDI ) . Eligible participants were r and omly assigned to one of three conditions : ( 1 ) stepped care ( SC ) : a computerized intervention plus up to three 40-min telephone-based interventions depending on the success of the previous intervention ; ( 2 ) full-care ( FC ) : a computerized intervention plus a fixed number of four 30-min telephone-based interventions that equals the maximum of the stepped care intervention ; ( 3 ) an untreated control group ( CG ) . Counseling effort in the intervention conditions and quantity/frequency of drinking were assessed at 12-month follow-up . RESULTS SC participants received roughly half of the amount of intervention in minutes compared to FC participants . Both groups did not differ in drinking outcomes . Compared to CG , intervention showed small to medium effect size for at-risk drinkers . CONCLUSIONS Study results reveal that a stepped care approach can be expected to increase cost-effectiveness of brief interventions for individuals with at-risk drinking Background Alcohol screening and brief intervention for unhealthy alcohol use has not been consistently delivered in primary care as part of preventive healthcare . Objective To explore whether telephone-based intervention delivered by a health educator is efficacious in reducing at-risk drinking among older adults in primary care setting s. Design Secondary analyses of data from a r and omized controlled trial . Participants Subjects r and omized to the intervention arm of the trial ( n = 310 ) . Interventions Personalized risk reports , advice from physicians , booklet about alcohol and aging , and up to three telephone calls from a health educator . All interventions were completed before the three-month follow-up . Measurements Risk outcomes ( at-risk or not at-risk ) at 3 and 12 months after enrollment . Main results In univariate analyses , compared to those who remained at risk , those who achieved not at-risk outcome at 3 months were more likely to be women , Hispanic or non-white , have lower levels of education , consume less alcohol , drink less frequently , and have lower baseline number of risks . In mixed-effects logistic regression models , completing all three health educator calls increased the odds of achieving not at-risk outcome compared to not completing any calls at 3 months ( OR 5.31 ; 95 % CI 1.92–14.7 ; p = 0.001 ) , but not at 12 months ( OR 2.01 ; 95 % CI 0.71–5.67 ; p = 0.18 ) . Conclusions Telephone-based intervention delivered by a health educator was moderately efficacious in reducing at-risk drinking at 3 months after enrollment among older adults receiving a multi-faceted intervention in primary care setting s ; however , the effect was not sustained at 12 months OBJECTIVE : To test the effectiveness of a brief intervention in the reduction of prenatal alcohol consumption by women when a partner is included . METHODS : R and omized trial of a single session brief intervention given by the study nurse or principal investigator for 304 pregnant women and their partners . The women had positive T-ACE ( Tolerance , Annoyed , Cut down , Eye-opener , an alcohol screening test ) results and were at risk for alcohol consumption while pregnant . All completed initial diagnostic and postpartum interviews . RESULTS : Fewer than 20 % of participants ( median 11.5 weeks of gestation ) were abstinent at study enrollment , averaging more than 1.5 drinks per episode . Nearly 30 % had 2 or more drinks at a time while pregnant . Prenatal alcohol use declined in both the treatment and control groups after study enrollment , based on a 95 % follow-up rate . Factors associated with increased prenatal alcohol use after r and omization included more years of education , extent of previous alcohol consumption , and temptation to drink in social situations . Brief interventions for prenatal alcohol reduced subsequent consumption most significantly for the women with the highest consumption initially ( regression coefficient , b = −0.163 , st and ard error ( b ) = 0.063 , P < .01 ) . Moreover , the effects of the brief intervention were significantly enhanced when a partner participated ( b = −0.932 , st and ard error ( b ) = 0.468 ) , P < .05 ) . CONCLUSION : Pregnant women with the highest levels of alcohol use reduced their drinking most after a brief intervention that included their partners . Recommendations include consistent screening for prenatal alcohol use followed by diagnostic assessment when indicated , and if confirmed by other studies , a patient-partner brief intervention for the heaviest drinkers . LEVEL OF EVIDENCE : Purpose The purpose of this study is to determine the effect at 48 months of a screening and brief patient-centered physician- and nurse practitioner-delivered intervention implemented during a routine primary care visit on the reduction of alcohol consumption by high-risk drinkers . Methods Participants seen in primary care practice s previously r and omized to special intervention ( SI ) or usual care ( UC ) were reconsented for long-term follow-up . From the initial cohort , 63 % reconsented to participate and provided follow-up at 48 months between November 1996 and March 2002 . The data for this paper were analyzed in June 2004 . Results At 48 months , SI participants maintained significant reductions in drinks per week seen at 6 and 12 months . However , there were no longer significant differences in drinks per week , binges per month , percentage of low-risk drinking , relapse rates , and new quits between the SI and UC groups at 48 months that had been seen at earlier follow-up . There was a significant effect of prior low-risk drinking status at 12 months ; those who were low-risk drinkers at 12 months were more likely to stay low-risk drinkers at 48 months regardless of treatment group . Conclusions With a single brief intervention , SI participants had significantly greater reductions in their drinking levels at 6 and 12 months compared to UC participants and maintained the lower-risk levels at 48 months result ing in a reduction in health risk exposure time . However , the significant group differences in treatment effect seen in earlier follow-ups were not maintained Seventy two women drinking 21 units ( 210 g ) or more of alcohol per week were recruited from an opportunistic screening programme in eight English general practice s. The women were r and omized into control and treatment groups . Women in the treatment group received ten minutes advice from their general practitioner to reduce alcohol consumption . At one year follow-up , when analyzed by intention to treat , women in the treatment group had reduced their alcohol consumption from an average of 35 - 24 units per week . Similar reductions were found in the control group ( from 37 - 27 units per week ) . The lack of evidence for a treatment effect may be explained by contamination of the control group by informal interventions In a controlled evaluation of general practitioner (GP)-based brief intervention , 378 excessive drinkers identified opportunistically by screening in 40 group practice s in metropolitan Sydney were assigned to groups receiving : ( i ) a five-session intervention by the GP ( the Alcoholscreen Program ) ; ( ii ) a single session of 5 minutes ' advice by the GP plus a self-help manual ( minimal intervention ) ; ( iii ) an alcohol-related assessment but no intervention ; ( iv ) neither intervention nor assessment . Among all patients allocated to receive it , the Alcoholscreen Program did not result in a significantly greater reduction in consumption at follow-up than control conditions but patients offered Alcoholscreen reported a significantly greater reduction in alcohol-related problems in the period to 6 months follow-up . A greater proportion of patients who returned for the second Alcoholscreen visit were drinking below recommended levels at follow-up than in the remainder of the sample . There was no evidence that minimal intervention or alcohol-related assessment were effective in reducing alcohol consumption or problems . Implication s for further research into GP-based brief interventions are discussed Home visitation interventions show promise for helping at-risk mothers , yet few programs have been developed and evaluated specifically for alcohol and drug-abusing pregnant women . This study examines outcomes among 216 women enrolled in the Washington State Parent-Child Assistance Program , a three-year intervention program for women who abuse alcohol and drugs during an index pregnancy . Pretest-posttest comparison was made across three sites : the original demonstration ( 1991–1995 ) , and the Seattle and Tacoma replications ( 1996–2003 ) . In the original demonstration , the client group performed significantly better than controls . Compared to the original demonstration , outcomes at replication sites were maintained ( for regular use of contraception and use of reliable method ; and number of subsequent deliveries ) , or improved ( for alcohol/drug treatment completed ; alcohol/drug abstinence ; subsequent delivery unexposed to alcohol/drugs ) . Improved outcomes at replication sites are not attributable to enrolling lower-risk women . Public policies and programs initiated over the study period may have had a positive effect on outcomes . Study findings suggest that this community-based intervention model is effective over time and across venues OBJECTIVE : To determine effectiveness of advice from general practitioners to heavy drinkers to reduce their excessive alcohol consumption ( 35 U or more a week for men , 21 U or more for women ) . DESIGN : R and omised , controlled double blind trial over 12 months with interim assessment at six months . SETTING : Group practice s ( n = 47 ; list size averaging 10,000 ) recruited from Medical Research Council 's general practice research framework , mostly in rural or small urban setting s. PATIENTS : Patients recruited after question naire survey . Of total of 2571 ( 61.2 % ) of 4203 patients invited for interview who attended , 909 ( 35.4 % ) stated that in past seven days they had drunk above the limits set for study and had not received advice ; they were r and omised to control and treatment groups . INTERVENTIONS : Patients in treatment group were interviewed by general practitioner ( who had had a training session ) and received advice and information about how to reduce consumption and also given a drinking diary . END POINT : Study aim ed at detecting a reduction in proportion of men with excessive alcohol consumption of 30 % in treatment group and 20 % in control group ( for women 40 % and 20 % , respectively ) with a power of 90 % at 5 % level of significance . In addition , corroborative measures such as estimation of gamma-glutamyltransferase activity were included . MEASUREMENTS AND MAIN RESULTS : At one year a mean reduction in consumption of alcohol of 18.2 ( SE 1.5 ) U/week had occurred in treated men compared with a reduction of 8.1 ( 1.6 ) U/week in controls ( p less than 0.001 ) . The proportion of men with excessive consumption at interview had dropped by 43.7 % in the treatment group compared with 25.5 % in controls ( p less than 0.001 ) . A mean reduction in weekly consumption of 11.5 ( 1.6 ) U occurred in treated women compared with 6.3 ( 2.0 ) U in controls ( p less than 0.05 ) , with proportionate reductions of excessive drinkers in treatment and control groups of 47.7 % and 29.2 % respectively . Reduction in consumption increased significantly with number of general practitioner interventions . At one year the mean value for gamma-glutamyltransferase activity had dropped significantly more in treated men ( -2.4 (0.9)IU/l ) than in controls ( + 1.1(1.0)IU/l ; t = 2.7 , p less than 0.01 ) . Reduction in gamma-glutamyltransferase activity tended to increase with number of intervention sessions in men . Changes in gamma-glutamyltransferase activity in women and changes in other indicators in both sexes did not differ significantly between treatment and control groups . CONCLUSIONS : If the results of this study were applied to the United Kingdom intervention by general practitioners could each year reduce to moderate levels the alcohol consumption of some 250000 men and 67500 women who currently drink to excess . General practitioners and other members of the primary health care team should therefore be encouraged to include counselling about alcohol consumption in their preventive activities AIM To analyse gender differences in the efficacy of stepped care brief interventions for general practice patients with alcohol problems . METHODS Data are part of " Stepped Interventions for Problem Drinkers , " in which 10,803 patients from 85 general practitioners were screened using alcohol related question naires ; 408 patients were r and omized ( 32 % were female ) to a control ( booklet only ) or two different intervention groups : stepped care ( feedback , manual , and up to three counselling sessions depending on the success of the previous intervention ) and fixed care ( four sessions ) . Response rate for the 12 months follow-up was 91.7 % . RESULTS Regression analysis revealed a significant effect size only in women ( P = 0.039 ) . After excluding alcohol dependents and binge drinkers , an effect size ( R(2 ) ) of 0.031 ( P = 0.050 ) in women and an effect size ( R(2 ) ) of 0.069 ( P = 0.057 ) in men was obtained . Among the patients in stepped care who , by the first assessment point , had reduced drinking to within safe-drinking limits , there was a tendency for females to have achieved this more often than males ( 40 % vs. 24 % ; P = 0.089 ) . CONCLUSIONS In a heterogeneous sample , the intervention was only effective for women . Women tended to profit more from the first , less intensive intervention than men . When analysis was limited to those reporting " at risk " average daily consumption and " alcohol abuse , " the gender differences in efficacy appeared to be less , but the study was not sufficiently powered to affirm that OBJECTIVE To evaluate the correspondence among measures of self-reported drinking , st and ard biological indicators and the reports of collateral informants , and to identify patient characteristics associated with observed discrepancies among these three sources of research data . METHOD Using data collected from a large-scale clinical trial of treatment matching with alcoholics ( N = 1,726 ) , these three alternative outcome measures were compared at the time of admission to treatment and at 12 months after the end of treatment . RESULTS Patient self-reports and collateral reports agreed most ( 97.1 % ) at treatment admission when heavy drinking was unlikely to be denied . In contrast , liver function tests were relatively insensitive , with positive serum gamma-glutamyl transpeptidase ( GGTP ) values obtained from only 39.7 % of those who admitted to heavy drinking . At 15-month follow-up the correspondence between client self-report and collateral report decreased to 84.7 % , but agreement with blood chemistry values increased to 51.6 % . When discrepancies occurred , they still indicated that the client ' s self-report is more sensitive to the amount of drinking than the biochemical measures . Patients who presented discrepant results tended to have more severe drinking problems , more previous treatments , higher levels of pretreatment drinking and significantly greater levels of cognitive impairment , all of which could potentially interfere with accurate recall . CONCLUSIONS In clinical trials using self-selected research volunteers , biochemical tests and collateral informant reports do not add sufficiently to self-report measurement accuracy to warrant their routine use . Re sources devoted to collecting these alternative sources of outcome data might be better invested in interview procedures design ed to increase the validity of self-report information AIMS To examine whether a multi-faceted intervention among older at-risk drinking primary care patients reduced at-risk drinking and alcohol consumption at 3 and 12 months . DESIGN R and omized controlled trial . SETTING Three primary care sites in southern California . PARTICIPANTS Six hundred and thirty-one adults aged ≥ 55 years who were at-risk drinkers identified by the Comorbidity Alcohol Risk Evaluation Tool ( CARET ) were assigned r and omly between October 2004 and April 2007 during an office visit to receive a booklet on healthy behaviors or an intervention including a personalized report , booklet on alcohol and aging , drinking diary , advice from the primary care provider and telephone counseling from a health educator at 2 , 4 and 8 weeks . MEASUREMENTS The primary outcome was the proportion of participants meeting at-risk criteria , and secondary outcomes were number of drinks in past 7 days , heavy drinking ( four or more drinks in a day ) in the past 7 days and risk score . FINDINGS At 3 months , relative to controls , fewer intervention group participants were at-risk drinkers [ odds ratio ( OR ) 0.41 ; 95 % confidence interval ( CI ) 0.22 - 0.75 ] ; they reported drinking fewer drinks in the past 7 days [ rate ratio ( RR ) 0.79 ; 95 % CI 0.70 - 0.90 ] , less heavy drinking ( OR 0.46 ; 95 % CI 0.22 - 0.99 ) and had lower risk scores ( RR 0.77 95 % CI 0.63 - 0.94 ) . At 12 months , only the difference in number of drinks remained statistically significant ( RR 0.87 ; 95 % CI 0.76 - 0.99 ) . CONCLUSIONS A multi-faceted intervention among older at-risk drinkers in primary care does not reduce the proportions of at-risk or heavy drinkers , but does reduce amount of drinking at 12 months BACKGROUND Alcohol use in older adults is common . It is associated with depression , hypertension , diabetes , drug interactions , accidents , and increased rates of emergency department visits and hospitalizations . METHODS A controlled clinical trial ( Project GOAL --Guiding Older Adult Lifestyles ) tested the efficacy of brief physician advice in reducing the alcohol use and use of health care services of older adult problem drinkers . Twenty-four community-based primary care practice s in Wisconsin ( 43 family physicians and internists ) participated in the trial . Of the 6073 patients screened , 105 men and 53 women met inclusion criteria and were r and omized into a control group ( n = 71 ) or an intervention group ( n = 87 ) . Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions that included advice , education , and contracting using a scripted workbook . A total of 146 patients ( 92.4 % ) participated in the 12-month follow-up procedure . RESULTS No significant differences were found between the control and intervention groups at baseline in alcohol use , age , socioeconomic status , depression , onset of alcohol use , smoking status , activity level , or use of mood-altering drugs . The older adults who received the physician intervention demonstrated a significant reduction in 7-day alcohol use , episodes of binge drinking , and frequency of excessive drinking ( P < .005 ) compared with the control group at 3 , 6 , and 12 months after the intervention . There was a 34 % reduction in 7-day alcohol use , 74 % reduction in mean number of binge-drinking episodes , and 62 % reduction in the percentage of older adults drinking more than 21 drinks per week in the intervention group compared with the control group . There were no significant changes in health status . Patterns of health care utilization were not extensively analyzed because of the small number of events . CONCLUSIONS This study provides the first direct evidence that brief physician advice can decrease alcohol use by older adults in community-based primary care practice About 20 % of pregnant women will drink alcohol , even though no universally safe level of prenatal alcohol consumption has been established . This study of 123 alcohol screen-positive pregnant women receiving a brief intervention in the 16th week of gestation examines the relationship of drinking goals , reasons for the goals , recognition of situations increasing risk of drinking , and subsequent antepartum consumption . While women who named abstinence as their antepartum drinking goal were more likely not to be consuming alcohol at the time of study enrollment ( chi(2 ) = 16.80 , df = 1 , p = .001 ) , current drinkers who named abstinence as their goal did reduce subsequent prenatal alcohol use ( chi(2 ) = 10.04 , df = 1 , p = .002 ) . All current drinkers who indicated fetal alcohol syndrome as a reason not to drink reduced their subsequent alcohol consumption ( chi(2 ) = 11.04 , df = 1 , p = .001 ) . Future efforts may include the partners and support systems of pregnant women in education or intervention programs to reduce prenatal alcohol consumption to enhance their effectiveness OBJECTIVE This study tested the effectiveness of brief primary care provider interventions delivered in a college student health center to a sample of college students who screened positive for high-risk drinking . METHOD Between November 2005 and August 2006 , 8,753 students who presented as new patients to the health service at a large public university were screened for high-risk drinking , and 2,484 students ( 28 % ) screened positive on the 5/4 gender-specific high-risk drinking question ( i.e. , five or more drinks per occasion for men and four or more for women ) . Students who screened positive for high-risk drinking and consented to participate ( N= 363 ; 52 % female ) were r and omly assigned either to a control group ( n = 182 ) or to an experimental group ( n = 181 ) . Participants in the experimental group received two brief intervention sessions that were founded in motivational interviewing techniques and delivered by four specially trained providers within the student health center . Data on alcohol use and related harms were obtained from a Web-based Healthy Lifestyle Question naire , 30-day Timeline Followback alcohol-use diaries , the Rutgers Alcohol Problem Index ( RAPI ) , and eight items from the Drinker Inventory of Consequences-2L . RESULTS Repeated measures analysis showed that , compared with the control group ( C ) , the intervention group ( I ) had significant reductions in typical estimated blood alcohol concentration ( BAC ) ( C = .071 vs I = .057 at 3 months ; C = .073 vs I = .057 at 6 months ) , peak BAC ( C = . 142 vs I = .112 at 3 months ; C = .145 vs I = .108 at 6 months ) , peak number of drinks per sitting ( C = 8.03 vs I = 6.87 at 3 months ; C = 7.98 vs I = 6.52 at 6 months ) , average number of drinks per week ( C = 9.47 vs I = 7.33 at 3 months ; C = 8.90 vs I = 6.16 at 6 months ) , number of drunk episodes in a typical week ( C = 1.24 vs I = 0.85 at 3 months ; C = 1.10 vs I = 0.71 at 6 months ) , number of times taken foolish risks ( C = 2.24 vs I = 1.12 at 3 months ) , and RAPI sum scores ( C = 6.55 vs I = 4.96 at 6 months ; C = 6.17 vs I = 4.58 at 9 months ) . CONCLUSIONS Brief interventions delivered by primary care providers in a student health center to high-risk-drinking students may result in significantly decreased alcohol consumption , high-risk drinking , and alcohol-related harms BACKGROUND Studies suggest that 14 % of women age 18 to 40 drink alcohol above recommended limits . Of special concern is the increasing use of alcohol by women during pregnancy . This article reports 48 month follow-up data from a sub analysis of a trial for early alcohol treatment ( Project TrEAT ) focused on women of childbearing age . METHODS Project TrEAT was conducted in the offices of 64 primary care , community-based physicians from 10 Wisconsin counties . Of 5979 female patients ages 18 to 40 who were screened for problem drinking , 205 were r and omized into an experimental group ( n = 103 ) or control group ( n = 102 ) . The intervention consisted of two 15 min , physician-delivered counseling visits that included advice , education , and contracting by using a scripted workbook . A total of 174 subjects ( 85 % ) completed the 48 month follow-up procedures . RESULTS No significant differences were found between the experimental and control groups at baseline for alcohol use , age , socioeconomic status , smoking , depression or anxiety , conduct disorder , lifetime drug use , or health care utilization . The trial found a significant treatment effect in reducing both 7 day alcohol use ( p = 0.0039 ) and binge drinking episodes ( p = 0.0021 ) over the 48 month follow-up period . Women in the experimental group who became pregnant during the follow-up period had the most dramatic decreases in alcohol use . A logistic regression model based on a 20 % or greater reduction in drinking found an odds ratio of 1.93 ( confidence interval 1.07 - 3.46 ) in the sample exposed to physician intervention . Age , smoking , depression , conduct disorder , antisocial personality disorder , and illicit drug use did not reduce drinking significantly . No significant differences were found in health care utilization and health status between groups . CONCLUSIONS This trial provides the first direct evidence that brief intervention is associated with sustained reductions in alcohol consumption by women of childbearing age . The results have enormous implication s for the U.S. health care system BACKGROUND There is compelling evidence supporting screening and brief intervention ( SBI ) for hazardous drinking , yet it remains underused in primary health care . Electronic ( computer or Web-based ) SBI ( e-SBI ) offers the prospect s of ease and economy of access . We sought to determine whether e-SBI reduces hazardous drinking . METHODS We conducted a r and omized controlled trial in a university primary health care service . Participants were 975 students ( age range , 17 - 29 years ) screened using the Alcohol Use Disorders Identification Test ( AUDIT ) . Of 599 students who scored in the hazardous or harmful range , 576 ( 300 of whom were women ) consented to the trial and were r and omized to receive an information pamphlet ( control group ) , a Web-based motivational intervention ( single-dose e-SBI group ) , or a Web-based motivational intervention with further interventions 1 and 6 months later ( multidose e-SBI group ) . RESULTS Relative to the control group , the single-dose e-SBI group at 6 months reported a lower frequency of drinking ( rate ratio [ RR ] , 0.79 ; 95 % confidence interval [ CI ] , 0.68 - 0.94 ) , less total consumption ( RR , 0.77 ; 95 % CI , 0.63 - 0.95 ) , and fewer academic problems ( RR , 0.76 ; 95 % CI , 0.64 - 0.91 ) . At 12 months , statistically significant differences in total consumption ( RR , 0.77 ; 95 % CI , 0.63 - 0.95 [ equivalent to 3.5 st and ard drinks per week ] ) and in academic problems ( RR , 0.80 ; 95 % CI , 0.66 - 0.97 ) remained , and the AUDIT scores were 2.17 ( 95 % CI , -1.10 to -3.24 ) points lower . Relative to the control group , the multidose e-SBI group at 6 months reported a lower frequency of drinking ( RR , 0.85 ; 95 % CI , 0.73 - 0.98 ) , less total consumption ( RR , 0.79 ; 95 % CI , 0.64 - 0.97 [ equivalent to 3.0 st and ard drinks per week ] ) , reduced episodic heavy drinking ( RR , 0.65 ; 95 % CI , 0.45 - 0.93 ) , and fewer academic problems ( RR , 0.78 ; 95 % CI , 0.65 - 0.93 ) . At 12 months , statistically significant differences in academic problems remained ( RR , 0.75 ; 95 % CI , 0.62 - 0.90 ) , while the AUDIT scores were 2.02 ( 95 % CI , -0.97 to -3.10 ) points lower . CONCLUSIONS Single-dose e-SBI reduces hazardous drinking , and the effect lasts 12 months . Additional sessions seem not to enhance the effect . Trial Registration www.anzctr.org.au Identifier : ACTRN012607000103460 BACKGROUND The prevention and treatment of alcohol use disorders among women of reproductive age have been well described . However , there is limited information on women specifically during the postpartum period . This period in a woman 's life is a time of transition and it provides an ideal opportunity for primary care providers to intervene . PURPOSE The goal of this report was to present the results of a brief alcohol intervention conducted in 34 obstetrical practice s with women seeking routine postpartum care . METHODS A r and omized clinical trial was conducted from 2002 to 2005 in a diverse sample of women located in 15 Wisconsin counties . This report presents 6-month follow-up data . RESULTS A total of 8,706 women were screened for high-risk alcohol use during routine postpartum care with 997 ( 12 % ) of these women testing positive for at-risk drinking . A total of 235 women met inclusion criteria and were r and omized to either " usual care " or " brief intervention . " The 4-session intervention was delivered by outpatient obstetrical nurses and research staff . The mean age of the women in the sample was 28 , 19.3 % were from minority groups , 60.8 % were married , 53.2 % reported current tobacco use , and 17.9 % had used marijuana in the previous 30 days . At the 6 month follow-up appointment , there were significant reductions in mean number of total drinks in the previous 28 days ( p < 0.013 ) , number of drinking days ( p < 0.024 ) and heavy drinking days ( p < 0.019 ) . In addition to a statistical difference between groups , there was a 19 % difference in the mean number of drinks and number of drinking days , and a 36 % difference in the number of heavy drinking days in favor of the intervention group . CONCLUSION The findings of the Healthy Moms Trial support the implementation of brief alcohol intervention during the postpartum period BACKGROUND : The objective of this study was to determine the effects of a brief primary care provider-delivered counseling intervention on the reduction of alcohol consumption by high-risk drinkers . The intervention was implemented as part of routine primary care medical practice . METHODS : We performed a controlled clinical trial with 6- and 12-month follow-up . Three primary care practice s affiliated with an academic medical center were r and omly assigned to special intervention ( SI ) or usual care ( UC ) . A total of 9,772 primary care patients were screened for high-risk drinking . A fourth site was added later . From the group that was screened , 530 high-risk drinkers entered into the study , with 447 providing follow-up at 12 months . The intervention consisted of brief ( 5–10 minute ) patient-centered counseling plus an office system that cued providers to intervene and provided patient educational material s. RESULTS : At 12-month follow-up , after controlling for baseline differences in alcohol consumption , SI participants had significantly larger changes ( P=.03 ) in weekly alcohol intake compared to UC ( SI=−5.7 drinks per week ; UC=−3.1 drinks per week ) , and of those who changed to safe drinking at 6 months more SI participants maintained that change at 12 months than UC . CONCLUSIONS : Project Health provides evidence that screening and very brief ( 5–10 minute ) advice and counseling delivered by a patient ’s personal physician or nurse practitioner as a routine part of a primary care visit can reduce alcohol consumption by high-risk drinkers BACKGROUND Strong evidence exists for the efficacy of screening and brief intervention for reducing hazardous drinking . However , problems have been highlighted with respect to its implementation in health-care systems , not least of which is a reluctance of some doctors to discuss alcohol proactively with their patients . AIMS To determine the efficacy of a novel web-based screening and brief intervention ( e-SBI ) to reduce hazardous drinking . DESIGN A double-blind r and omized controlled trial . SETTING A university student health service . PARTICIPANTS A total of 167 students ( 17 - 26 years ) were recruited in the reception area and completed a 3-minute web-based screen including the Alcohol Use Disorder Identification Test ( AUDIT ) question naire . Of these , 112 tested positive , and 104 ( 52 females ) who consented to follow-up were included in the trial . MEASUREMENTS Drinking frequency , typical occasion quantity , total volume , heavy episode frequency ( females > 80 g ethanol , males > 120 g ethanol ) , number of personal problems , an academic problems score . INTERVENTION Participants were r and omized to 10 - 15 minutes of web-based assessment and personalized feedback on their drinking ( intervention , n = 51 ) or to a leaflet-only control group ( n = 53 ) . FINDINGS Mean baseline AUDIT scores for control and intervention groups were 16.6 ( SD = 6.0 ) and 16.6 ( SD = 5.7 ) . At 6 weeks , participants receiving e-SBI reported significantly lower total consumption ( geometric mean ratio = 0.74 ; 95 % confidence interval : 0.56 - 0.96 ) , lower heavy episode frequency ( 0.63 ; 0.42 - 0.92 ) and fewer personal problems ( 0.70 ; 0.54 - 0.91 ) . At 6 months personal problems remained lower ( 0.76 ; 0.60 - 0.97 ) , although consumption did not differ significantly . At 6 months , academic problems were lower in the intervention group relative to controls ( 0.72 ; 0.51 - 1.02 ) . CONCLUSIONS e-SBI reduced hazardous drinking among university students , to an extent similar to that found for practitioner-delivered brief interventions in the general population . e-SBI offers promise as a strategy to reduce alcohol-related harm in a way that is non-intrusive , appealing to the target group , and capable of being incorporated into primary care . Research is required to replicate the findings , to determine the duration of intervention effects , and to investigate the mechanisms by which the intervention operates AIMS To determine the effectiveness of Motivational Enhancement Therapy ( MET ) for hazardous drinkers in Primary Care Unit ( PCU ) setting s in rural Thail and . METHODS A r and omized controlled trial was conducted in eight PCUs in Ubonratchatanee and Chachoengsao provinces in Thail and . Hazardous drinkers were identified using the World Health Organization-recommended Alcohol Use Disorder Identification Test . Of 117 eligible participants ( 91 % male ) , 59 were r and omized to the intervention group to receive MET in three individual appointments with a trained nurse and 58 to an assessment -only control group . Outcome evaluations were carried out after 6 weeks , 3 months and 6 months . RESULTS Follow-up data were available on 84 , 94 and 91 % of subjects , respectively , at the three intervals . Self-reported drinks per drinking day , frequency of hazardous drinking assessed either on a daily or weekly basis , and of binge drinking sessions were reduced in the intervention group more than in the control group ( P < 0.05 ) after both 3 and 6 months . The groups did not generally differ at 6 weeks . However , although self-reported consumption in both groups fell from baseline to 6-month follow-up , serum gamma-glutamyl transferase increased in both groups , which raises doubts about the validity of this marker in this sample and /or the validity of the self-reported data in this study . CONCLUSION MET delivered by nurses in PCUs in Thail and appears to be an effective intervention for male hazardous drinkers . Uncertainties about the validity of self-reported data jeopardize the safety of this conclusion BACKGROUND Prenatal alcohol exposure is a leading preventable cause of birth defects and developmental disabilities in the United States . DESIGN A r and omized controlled trial ( 2002 - 2005 ; data analyzed 2005 - 2006 ) of a brief motivational intervention to reduce the risk of an alcohol-exposed pregnancy ( AEP ) in preconceptional women by focusing on both risk drinking and ineffective contraception use . SETTING / PARTICIPANTS A total of 830 nonpregnant women , aged 18 - 44 years , and currently at risk for an AEP were recruited in six diverse setting s in Florida , Texas , and Virginia . Combined setting s had higher proportions of women at risk for AEP ( 12.5 % overall ) than in the general population ( 2 % ) . INTERVENTIONS Participants were r and omized to receive information plus a brief motivational intervention ( n=416 ) or to receive information only ( n=414 ) . The brief motivational intervention consisted of four counseling sessions and one contraception consultation and services visit . MAIN OUTCOME MEASURES Women consuming more than five drinks on any day or more than eight drinks per week on average , were considered risk drinkers ; women who had intercourse without effective contraception were considered at risk of pregnancy . Reversing either or both risk conditions result ed in reduced risk of an AEP . RESULTS Across the follow-up period , the odds ratios ( ORs ) of being at reduced risk for AEP were twofold greater in the intervention group : 3 months , 2.31 ( 95 % confidence interval [CI]=1.69 - 3.20 ) ; 6 months , 2.15 ( CI=1.52 - 3.06 ) ; 9 months , 2.11 ( CI=1.47 - 3.03 ) . Between-groups differences by time phase were 18.0 % , 17.0 % , and 14 . 8 % , respectively . CONCLUSIONS A brief motivational intervention can reduce the risk of an AEP BACKGROUND High-risk alcohol use in persons 18 to 30 years of age is a critical public health problem . It is the number 1 cause of death in this population . This article reports the results of a sub analysis of young adults ( aged 18 to 30 years ) who participated in Project TrEAT ( Trial of Early Alcohol Treatment ) conducted in the offices of 64 primary care physicians located in 10 counties in southern Wisconsin . METHODS Project TrEAT was a r and omized clinical trial design ed to test the efficacy of a brief intervention protocol to reduce alcohol use , improve health status , and decrease health care utilization . A total of 226 young adults were r and omly assigned to either a usual care or brief intervention group . RESULTS There were no significant differences between the 2 groups at baseline on a number of potential confounders . During the 4-year follow-up period , there were significant reductions in number of persons drinking more than 3 drinks per day , average 7-day alcohol use , number of persons drinking 6 or more drinks per occasion , and number of binge drinking episodes in the previous 30 days ( P < .01 to P < .001 ) . There were also significant differences ( P < .05 ) in emergency department visits ( 103 vs 177 ) , motor vehicle crashes ( 9 vs 20 ) , total motor vehicle events ( 114 vs 149 ) , and arrests for controlled substance or liquor violation ( 0 vs 8) . CONCLUSION In this 4-year sub analysis of young adults who participated in Project TrEAT , we found long-term reductions in high-risk drinking behaviors and consequences . The findings of this study support more widespread implementation of brief interventions in primary care setting OBJECTIVE Problem alcohol use among elderly persons can have a variety of health-related consequences , complicating management of chronic illnesses and increasing health care utilization and costs . This study evaluates the economic cost and benefits of brief intervention for at-risk drinking older adults . METHOD A controlled clinical trial with 24-month follow-up tested effectiveness of brief physician advice in reducing alcohol use , health care utilization and other consequences among older ( age 65 or older ) adult problem drinkers . Of 6,073 patients screened for problem drinking in 24 community-based primary care practice s in Wisconsin , 158 patients met inclusion criteria and were r and omized into control ( n = 71 ) or intervention ( n = 87 ) groups . Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions including professional advice , education and contracting using scripted workbooks . RESULTS The intervention group demonstrated significant reductions in alcohol use ( p = 0.001 ) and frequency of excessive drinking ( p = 0.03 ) compared with the control group over 24 months , but no significant differences emerged in economic outcomes , including hospital days , emergency department visits , office visits , medications , lab and x-ray procedures , injuries , legal events or mortality . CONCLUSIONS Although the clinical benefits of brief alcohol interventions with older adults are clear , the economic results in this age group are less certain . Older adult problem drinkers may require more intensive and costly interventions to achieve economic benefits similar to those seen in younger adult problem drinkers . Method ological issues , such as statistical power , outcome measures , outlier cases and follow-up periods , are identified for future evaluations INTRODUCTION The study was design ed to test a brief intervention for reducing alcohol consumption among moderate to heavy ( hazardous ) drinkers in a busy HMO primary care setting . METHODS In a r and omized controlled trial , hazardous drinkers ( n = 516 ) were identified by the AUDIT screening question naire . Intervention included brief clinician advice ( 30 seconds ) , a 15-minute motivational session by counselors , and printed material s. RESULTS At six-month follow-up , intervention subjects reported fewer total st and ard drinks in the past three months ( 176 versus 216 , P = .04 , one-tailed ) and fewer drinking days per week ( 2.8 versus 3.3 , P = .02 ) than controls , but similar drinks per drinking day ( 3.3 versus 3.5 ; P = .13 ) . At 12 months , intervention subjects again reported fewer drinking days per week ( 2.7 versus 3.1 ; P = .04 ) than controls , but similar numbers of st and ard drinks ( 157 versus 179 ; P = .13 ) and drinks per drinking day ( 3.6 versus 3.3 ; P = .20 ) . Intervention subjects were somewhat more likely than controls to report drinking within daily recommended limits ( < or = 3 for men , < or = 2 for women ) at both six months ( 79 % versus 71 % ; P = .06 ) and 12 months ( 80 % versus 73 % ; P = .07 ) , but did not differ significantly from controls on other drinking outcomes ( percent abstinent , frequency of drinking > or = 6 drinks per drinking occasion , estimated peak blood alcohol concentration ) , or use of medical care in the year following intervention . CONCLUSIONS A one-time , brief motivational intervention using minimal clinician time supplemented by trained counselors result ed in a modest reduction in frequency of alcohol consumption in a busy primary care population . Future research should focus on strengthening and maintaining intervention effects AIMS To assess the impact of a brief intervention on antepartum alcohol consumption . DESIGN A r and omized clinical trial . SETTING The obstetrics practice s of the Brigham and Women 's Hospital in Boston , MA , USA . PARTICIPANTS Two hundred and fifty eligible women initiating prenatal care . INTERVENTION A comprehensive assessment of alcohol use ( assessment only , AO ) or the same comprehensive assessment with a brief intervention ( BI ) . MEASUREMENT Demographic background and obstetric history of subjects , current and lifetime use of alcohol and substances , composite Addiction Severity Index scores , and antepartum alcohol use . FINDINGS Of the 250 , 247 ( 99 % ) subjects provided information on their antepartum drinking . Both the AO and BI groups had reductions in antepartum alcohol consumption , but differences in reductions by group were not statistically significant ( p > 0.05 ) . Risk of antepartum drinking after either the AO or BI was increased nearly threefold if the subject had any prenatal alcohol consumption before assessment ( p = 0.0001 ) . For the 143 subjects who were abstinent pre- assessment , however , those who received the BI maintained higher rates of abstinence ( 86 % versus 72 % , p = 0.04 ) . CONCLUSIONS After a comprehensive assessment of alcohol use , subjects in both the AO and BI groups reduced their antepartum alcohol consumption . The importance of screening for prenatal alcohol use is underscored by the findings that any prenatal alcohol consumption increases the risk of continued antepartum drinking OBJECTIVE Project TrEAT ( Trial for Early Alcohol Treatment ) was design ed to test the efficacy of brief physician advice in reducing alcohol use and health care utilization in problem drinkers . DESIGN R and omized controlled clinical trial with 12-month follow-up . SETTING A total of 17 community-based primary care practice s ( 64 physicians ) located in 10 Wisconsin counties . PARTICIPANTS Of the 17695 patients screened for problem drinking , 482 men and 292 women met inclusion criteria and were r and omized into a control ( n=382 ) or an experimental ( n=392 ) group . A total of 723 subjects ( 93 % ) participated in the 12-month follow-up procedures . INTERVENTION The intervention consisted of two 10- to 15-minute counseling visits delivered by physicians using a scripted workbook that included advice , education , and contracting information . MAIN OUTCOME MEASURES Alcohol use measures , emergency department visits , and hospital days . RESULTS There were no significant differences between groups at baseline on alcohol use , age , socioeconomic status , smoking status , rates of depression or anxiety , frequency of conduct disorders , lifetime drug use , or health care utilization . At the time of the 12-month follow-up , there were significant reductions in 7-day alcohol use ( mean number of drinks in previous 7 days decreased from 19.1 at baseline to 11.5 at 12 months for the experimental group vs 18.9 at baseline to 15.5 at 12 months for controls ; t=4.33 ; P<.001 ) , episodes of binge drinking ( mean number of binge drinking episodes during previous 30 days decreased from 5.7 at baseline to 3.1 at 12 months for the experimental group vs 5.3 at baseline to 4.2 at 12 months for controls ; t=2.81 ; P<.001 ) , and frequency of excessive drinking ( percentage drinking excessively in previous 7 days decreased from 47.5 % at baseline to 17.8 % at 12 months for the experimental group vs 48.1 % at baseline to 32.5 % at 12 months for controls ; t=4.53 ; P<.001 ) . The chi2 test of independence revealed a significant relationship between group status and length of hospitalization over the study period for men ( P<.01 ) . CONCLUSIONS This study provides the first direct evidence that physician intervention with problem drinkers decreases alcohol use and health re source utilization in the US health care system OBJECTIVE Cost-effective interventions are needed for counseling pregnant drinkers , in order to reduce risk of fetal alcohol effects . METHOD 42 pregnant women who reported alcohol consumption participated in this pilot study of motivational interviewing . Following a comprehensive alcohol use assessment , the participants were r and omly assigned to receive either written information about the risks related to drinking during pregnancy or a one-hour motivational interview . The motivational interview was an empathic , client-centered , but directive session focusing on the health of the participants ' unborn babies . RESULTS At the end of a 2-month follow-up period , the 34 women ( 81 % ) who remained in the study showed a significant reduction in alcohol consumption and peak intoxication levels . Women who had reported the highest blood alcohol concentration ( BAC ) levels during early pregnancy showed a significantly greater reduction in their estimated BACs at follow-up ( during later pregnancy ) if assigned to the treatment rather than the control condition . CONCLUSIONS Motivational interviewing shows promise as a specific intervention for initiating a reduction in drinking among pregnant women who are at greatest risk . Simpler assessment and advice may suffice for women with lower initial consumption levels OBJECTIVE Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support . The purpose of this study was to ( 1 ) evaluate the effects of brief advice ( BA ) and motivational enhancement ( ME ) interventions on alcohol consumption . In addition , a hindsight matching design was used to ( 2 ) study the moderator effects of patient readiness to change ( alcohol use ) on alcohol consumption . METHOD The subjects ( N = 301 , 70 % men ) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics . After screening for eligibility and providing consent to participate in the study , the patients completed a baseline assessment and were r and omly assigned to the BA , ME or st and ard care ( SC ) interventions condition . Follow-up assessment s were completed at 1- , 3- , 6- , 9- and 12-months postbaseline assessment . RESULTS Evaluation of the first hypothesis ( n = 232 for these analyses ) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessment s. In addition , evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months , such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness . Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions . CONCLUSIONS The results confirm that , among primary care patients , substantial changes in alcohol consumption are possible . They further suggest that matching studies of patient readiness to change their alcohol use , as well as other variables , are warranted Purpose : To report on secondary results from the Healthy Moms Study , a clinical trial to test the efficacy of brief intervention on reducing alcohol use and alcohol-related harms in postpartum women . Study Design and Methods : Data from a r and omized clinical trial conducted between 2002 and 2005 with a sample of Wisconsin women was analyzed . This report presents comparison data on depressive symptomatology between postpartum women drinking above recommended levels who received a brief alcohol intervention and those who received no intervention . Results : At 6-month follow-up , there was a significant reduction in mean depression scores compared to baseline in the women who received the alcohol intervention ( p < .001 ) . There was no significant reduction in depressive symptomatology in the control group . Mean level of depression at 6 months was significantly predicted by baseline depression and the alcohol intervention ( p = .018 ) . Alcohol use at either baseline or follow-up was not a predictive factor in determining mean depressive symptomatology . Clinical Implication s : The results of the Healthy Moms Study support the importance of both alcohol and depression screening during the postpartum period . Brief alcohol intervention during this time may also positively affect depressive symptomatology The objective of the study was to determine the effectiveness of advice from general practitioners to heavy drinking men ( consuming 350 - 1050 grams of alcohol per week ) to reduce their alcohol consumption . One hundred and fifty-four men recruited from eight general practice s were allocated r and omly to treatment and control groups . Men in the treatment group received advice from their own general practitioner . At one year follow-up , when analyzed according to intention to treat , the treatment group had reduced their consumption by an excess of 65 grams of alcohol per week when compared with the control group ( p less than 0.05 ) . General practitioners should be recommended to screen for alcohol consumption amongst their patients and to give advice to those found to be at risk because of their drinking In clinical trials of brief interventions for alcohol use , individuals typically are defined as eligible for the research through meeting quantity-frequency ( QF ) of alcohol consumption criteria , alcohol-related problems criteria , or both . The purpose of this study was to evaluate preintervention and posttreatment differences among three groups of research participants eligible for participation in a brief intervention clinical trial by meeting the AUDIT total score criterion only , the QF criterion only , or both . The participants were 301 men and women 21 years of age or older who presented for medical treatment at one of twelve primary care clinics and were screened for participation in the clinical trial . Participants completed an assessment protocol at preintervention and 1 , 3 , 6 , 9 , and 12 months postintervention . The analyses showed statistical differences among the three subgroups on three outcome dimensions of alcohol consumption , related consequences and behaviors , and medical complications ; for both consumption and complications , the AUDIT + QF participants showed greater severity than participants in either of the other two groups . For consequences , AUDIT + QF participants scored higher than the QF participants on one variable constituting this dimension . The overall subgroup differences were maintained at six months in the consumption and consequences data . The implication s of these findings for sensitivity of brief intervention trial design , the discovery of patient moderators of intervention effectiveness , and clinical practice are discussed CONTEXT The concept that assessment of a person 's health status without subsequent intervention has beneficial effects in itself has stimulated much interest in underlying psychological mechanisms , method ological implication s and its public health potential . There have , however , been few experimental studies of assessment effects . AIM To test the hypothesis that assessment in itself produces a reduction in hazardous drinking . DESIGN AND SETTING Two conditions ( group A , leaflet only and group B , leaflet and assessment but no intervention ) of a four-arm r and omized controlled trial with enrollment in March-April 2003 . PARTICIPANTS A total of 975 students ( 17 - 29 years ) attending a primary health-care clinic completed a web-based Alcohol Use Disorders Identification Test ( AUDIT ) question naire . Of 599 who scored > or= 8576 consented to follow-up and were included in the full four-arm trial , of whom 293 ( 153 women ) were assigned to groups A and B. INTERVENTION Group A received an information leaflet at baseline . Group B received the information leaflet and 10 minutes of web-based assessment 4 weeks later . MEASUREMENTS Drinking frequency , typical quantity , heavy episode frequency , personal problems and academic problems . FINDINGS Baseline mean AUDIT scores were 15.0 ( SD = 5.4 ) and 14.9 ( SD = 5.0 ) in groups A and B , respectively . Twelve months after baseline , relative to group A , group B reported lower overall consumption ( geometric means ratio 0.82 , 95 % CI : 0.68 - 0.98 ) , fewer heavy drinking episodes ( 0.66 , 0.47 - 0.91 ) , fewer problems ( 0.81 , 0.67 - 0.99 ) and lower AUDIT scores ( beta = -1.63 , -0.62 to -2.65 ) . CONCLUSIONS Brief assessment appeared to reduce hazardous drinking . Controlled trials that rely on assessment may therefore underestimate treatment effects . Limitations include the possibility of measurement artefact due to social desirability bias This study tested a cognitive-behavioral intervention for reducing alcohol consumption among economically disadvantaged pregnant women . The intervention included a 10-minute educational session and a nine-step self-help manual . Women attending public health maternity clinics completed a screening question naire , a pretest question naire , were r and omly assigned to receive the self-help intervention or usual clinic care , and completed a posttest question naire . A higher alcohol quit rate was observed among the intervention participants ( 88 % ) than controls ( 69 % ) . The effect was strongest for " light " drinkers , African-Americans , and non-Protestants . This approach may be useful in clinics where staff time is limited This study examined whether a brief intervention to reduce hazardous alcohol consumption among primary care patients reduced use of medical care . In a parent , r and omized controlled trial , at-risk drinkers identified in HMO outpatient waiting rooms were r and omly assigned to receive usual care or brief clinician advice plus a 15-minute motivational counseling session . The current study ( n=514 ) examined the groups ' use of outpatient and inpatient medical services during two years after intervention . Although the intervention reduced alcohol consumption at six-month follow-up , intervention and control groups made similar numbers of outpatient visits ( M=17.7 vs. 18.3 , respectively;p=.47 ) , were equally likely to be hospitalized ( 21.2 % vs. 22.0%;p=.81 ) , and , among those hospitalized , had similar lengths of stay ( 4.7 vs. 6.6 days;p=.37 ) . Although brief interventions to reduce hazardous drinking may potentially reduce medical care utilization , more evidence is needed to substantiate their practicality and cost-effectiveness Context Brief interventions can reduce problem drinking , but physicians infrequently use them . Contribution This r and omized trial , from an academic primary care setting , tested whether prompting physicians with positive alcohol screening results that are linked to specific management recommendations works . Prompted faculty , but not residents , tended to discuss alcohol problems and counsel patients more often than did their counterparts who were not prompted . At 6 months , however , only patients of prompted residents had reduced their drinking . Implication s Prompting physicians with positive alcohol screening results and recommendations for action may or may not be effective , depending on patient , physician , and setting characteristics . The Editors Alcohol use disorders are a leading cause of disability and are as common and costly as coronary artery disease and depression ( 1 - 6 ) . Primary care setting s are ideal for alcohol screening and intervention ( 7 ) . Valid , brief , practical screening tools exist , and brief interventions can reduce drinking and improve health when delivered to primary care patients with alcohol problems ( 8 - 11 ) . However , alcohol problems are often unrecognized and untreated in primary care setting s ( 12 - 16 ) . Barriers to screening and intervention include issues related specifically to addictions ( such as patient readiness and physician discomfort , frustration , lack of confidence or skills , or pessimism about efficacy of intervention ) and issues related to the delivery of preventive services in general ( such as cost , acceptability , priorities , and time ) ( 17 , 18 ) . Physician prompting can improve the likelihood of cancer screening , administration of immunizations , and smoking cessation interventions ( 19 - 21 ) . Screening and intervention for alcohol problems , however , involve more complex assessment and intervention . The effectiveness of providing physicians with screening results and a prompt without training is unknown . Such a systems intervention would be easier and less costly to implement than training all physicians about addressing alcohol problems . We tested the hypotheses that providing physicians with patients ' alcohol screening results and simple individualized recommendations would increase physician alcohol counseling and decrease patient drinking . Methods Study Description The study was a cluster r and omized trial at the physician level because r and omization at the patient level would have risked contamination . The institutional review board of the Boston University Medical Center in Boston , Massachusetts , approved the study . Patients gave informed consent and were told that the physician may be given the results of alcohol screening questions . We obtained a Certificate of Confidentiality from the federal government . Participants Physicians were recruited , enrolled , and r and omly assigned before patients were enrolled . All faculty and resident primary care physicians in an urban academic practice ( excluding the authors ) were eligible . Physicians who had seen fewer than 80 patients in the previous 3 years or who anticipated leaving the practice within 6 months were excluded . We informed physicians that we would conduct a health screening study . We used a self-administered question naire to screen and enroll patients who spoke English or Spanish ( staff were available to assist ) ( 22 ) . This was done before a visit with one of the enrolled physicians . Eligible patients were current hazardous drinkers [ 23 ] , which was defined as having consumed alcohol in the past month and either 1 ) answered yes to one or more of the CAGE ( 24 - 26 ) alcohol screening questions ( modified to refer to the past year rather than lifetime ) [ 27 ] or 2 ) drank hazardous amounts in the past month ( 28 , 29 ) . Hazardous amounts for men and women , respectively , were defined as more than 4 st and ard drinks per occasion or 14 drinks per week and as more than 3 st and ard drinks per occasion or 7 drinks per week in the past 30 days ( 26 , 30 ) . Assessment s Before patients were enrolled , physicians completed a confidential written survey ( July 1997 ) . They were asked about their attitudes toward patients with addictions ; their professional satisfaction when caring for patients with alcohol problems ; whether they or someone they knew had an alcohol or drug problem ; and other issues related to alcohol and physicians , including the physician 's usual practice s ( 18 ) . A trained staff research er interviewed enrolled patients before and after their visits with a physician ( between February 1998 and August 1999 ) . All questions not available in Spanish ( 31 ) were translated , back-translated , and checked for accuracy . The assessment visit that occurred before the physician visit addressed demographic characteristics , previous counseling for alcohol problems , and readiness to change ( 32 , 33 ) . Patients were also asked about medication use , medical comorbidity ( 34 , 35 ) , psychiatric comorbidity ( 36 , 37 ) , and tobacco and other drug use . Immediately after the physician visit , patients were interviewed to determine whether counseling had occurred , drinking amounts ( 38 , 39 ) , the quality of communication with the physician ( 40 ) , alcohol dependence symptoms ( 41 ) , and alcohol problems ( Short Inventory of Problems [ SIP-2R ] ) ( 42 ) . Six months later , patients were interviewed by telephone to determine alcohol consumption in the past 30 days ; the vali date d Timeline Followback method was used ( 43 ) . Patients and staff research ers were not blinded to group assignment ( in addition , patients were not necessarily given this information ) ; at follow-up , interviews were done without knowledge of group assignment . R and omization and Intervention Physicians were stratified by level of training ( resident or faculty ) and were r and omly assigned to the intervention or control group at the start of the study . The computer-generated r and omization was done by off-site data management personnel who had no patient or physician contact . The staff research er attached the intervention , a sheet of paper , to the encounter record the physician routinely received immediately before each patient visit . One side of the paper provided the patient 's alcohol screening results , a preliminary assessment , and specific recommendations . The screening results included answers to each of the CAGE questions , reports of usual weekly and per occasion maximum drinking amounts , and the patient 's report of readiness to change on a 10-point scale ( 44 ) ( see Appendix Figure ) . For patients reporting hazardous drinking amounts but no affirmative CAGE question naire responses , the assessment was drinking hazardous amounts and the recommendation was consider advising safe drinking limits and consider providing patients with a pamphlet provided by the study titled How to Cut Down on Your Drinking ( 27 ) . For patients reporting any affirmative CAGE responses but no hazardous drinking amounts , the assessment was possible alcohol problems and recommendations were consider advising abstinence , provide the pamphlet , and referral to addiction treatment . For patients reporting affirmative CAGE question naire responses and hazardous drinking amounts , the assessment was both possible alcohol problems and drinking hazardous amounts and recommendations were consider advising abstinence and referral to addiction treatment . The other side of the paper provided the predictive value of CAGE based on the prevalence of alcohol abuse or dependence in the practice ( 26 , 31 ) , definitions of hazardous drinking , an approach for patients who are not ready to change , a list of abuse or dependence symptoms , and referral information . To increase counseling rates ( not for data collection ) , we attached a Post-it note to the encounter form asking physicians to indicate whether alcohol was discussed and , if not , why ( 45 ) . Physicians in the control group did not receive any information from the study . Statistical Analysis All analyses were performed by using SAS software , version 8.1 [ SAS Institute , Inc. , Cary , North Carolina ] . The primary prespecified outcomes of the study were the occurrence of physician discussion s regarding alcohol problems during the physicianpatient encounter and a decrease in patient drinking . Patients were asked whether they had 1 ) received alcohol counseling , defined as advice on safe drinking limits , advice to cut down or abstain , or referral to an alcohol specialist or treatment program ; 2 ) received any advice [ including counseling ] ; or 3 ) participated in any discussion about alcohol ( including advice ) . An example question was : Did the doctor give you any advice about your drinking habits ? Drinks per drinking day was the primary drinking outcome . We examined additional measures in secondary analyses : days drinking ( any day on which a drink was taken ) , days binge drinking ( any day on which per occasion amounts noted previously were exceeded ) , proportion drinking hazardous amounts , proportion binge drinking , and proportion abstinent . We compared sociodemographic characteristics , level of training , and mean number of patients enrolled for physicians in the intervention and control groups by using the two independent sample s t-test and the Fisher exact test , as applicable . We then compared patients who were seen by physicians in the intervention and control groups with respect to measured characteristics . We compared patients who were available and unavailable at the 6-month follow-up by r and omized group , physician level of training , and sociodemographic characteristics . Outcomes were compared between physicians in the intervention and control groups by using an intention-to-treat analysis ( physicians were analyzed in the groups to which they were r and omly assigned ) . Generalized estimating equations ( GEE ) were used to adjust for clustering of patients by physician ( PROC GENMOD , SAS software , version 8.1 ) ( 46 ) . For continuous outcomes , we specified the identity link function ; for dichotomous outcomes , we specified the logit link OBJECTIVE The aim of this study was to test the efficacy of brief physician advice in reducing alcohol use and related harm in college students . METHOD The College Health Intervention Projects ( CHIPs ) is a r and omized , controlled clinical trial with 12-month follow-up conducted in five college health clinics in Wisconsin ; Washington state ; and Vancouver , Canada . Of the 12,900 students screened for high-risk drinking , 484 men and 502 women met inclusion criteria and were r and omized into a control ( n = 493 ) or intervention ( n = 493 ) group . Ninety-six percent of students participated in the follow-up procedures . The intervention consisted of two 15-minute counseling visits and two follow-up phone calls , and used motivational interviewing , contracting , diary cards , and take-home exercises . RESULTS No significant differences were found between groups at baseline on alcohol use , age , socioeconomic or smoking status , rates of depression , or measures of alcohol-related harm . At 12 months , the experimental subjects reduced their 28-day drinking totals by 27.2 % , and the control group reduced their totals by 21 % . A mixed effects repeated measures model found a statistical difference in favor of the brief-intervention group ( beta = 4.7 , SE = 2.0 , p = .018 ) in 28-day drinking totals . The total Rutgers Alcohol Problem Index score was also significantly different during the 12-month follow-up period ( beta = 0.8 , SE = 0.4 , p = .033 ) . There was no difference on the other outcome measures of interest , such as frequency of excessive heavy drinking , health care utilization , injuries , drunk driving , depression , or tobacco use . CONCLUSIONS The study supports re source allocation and implementation of alcohol screening and brief physician advice in primary care-based college health clinics We sought to determine if Brief Interventions [ BIs , Motivational Enhancement ( ME ) , and Brief Advice ( BA ) ] reduced alcohol consumption among hazardous alcohol drinking elderly ( 65 years or older ) and whether the elderly responded similarly to younger population s. In 12 primary care offices from 10 1995 to 12 1997 , we screened 13,438 patients of whom 2702 were elderly ( 180 were hazardous drinkers ) . Forty-five elderly enrollees were r and omized to receive ME ( n = 18 ) , BA ( n = 12 ) , and St and ard Care ( SC , n = 12 ) . At baseline , the elderly drank more alcohol and abstained fewer days than the younger cohort ( p<0.05 ) . During the year , the elderly in ME , BA , and SC intervention arms increased the number of days abstained , decreased the number of drinks per day , and reduced the number of total days per month drinking . There were trends toward decreases in the alcohol consumption measures in the ME and BA treatment arms compared to SC . The elderly 's response to all interventions was similar to that of the younger cohort . This study suggests that hazardous alcohol consumption in the elderly is common and that BIs reduce alcohol consumption in the elderly similar to younger population BACKGROUND There is a need for primary care providers to have brief effective methods to intervene with high-risk drinkers during a regular outpatient visit . OBJECTIVE To determine whether brief physician- and nurse practitioner-delivered counseling intervention is efficacious as part of routine primary care in reducing alcohol consumption by high-risk drinkers . METHODS Academic medical center-affiliated primary care practice sites were r and omized to special intervention or to usual care . From a screened population of 9772 patients seeking routine medical care with their primary care providers , 530 high-risk drinkers were entered into the study . Special intervention included training providers in a brief ( 5- to 10-minute ) patient-centered counseling intervention , and an office support system that screened patients , cued providers to intervene , and made patient education material s available . The primary outcome measures were change in alcohol use from baseline to 6 months as measured by weekly alcohol consumption and frequency of binge drinking episodes . RESULTS Participants in the special intervention and usual care groups were similar on important background variables and potential confounders except that special intervention participants had significantly higher baseline levels of alcohol usage ( P = .01 ) . At 6-month follow-up , in the 91 % of the cohort who provided follow-up information , alcohol consumption was significantly reduced when adjusted for age , sex , and baseline alcohol usage ( special intervention , -5.8 drinks per week ; usual care , -3.4 drinks per week ; P = .001 ) . CONCLUSIONS This study provides evidence that screening and very brief ( 5- to 10-minute ) advice and counseling delivered by a physician or nurse practitioner as part of routine primary care significantly reduces alcohol consumption by high-risk drinkers This r and omized trial evaluated an intervention for reducing at-risk drinking practice s in a sample of 307 patients . Eligible drinking patterns included chronic drinking ( > or = 2 drinks per day in the past month ) , binge drinking ( > or = 5 drinks per occasion at least twice in the past month ) , and drinking and driving ( driving after > 2 drinks in the past month ) . Members of the intervention group received a message from their physician during their regularly scheduled visit , a self-help manual , written personalized feedback , and up to 3 telephone counseling calls . Dropout was significantly higher in the intervention than control group BACKGROUND Binge drinking is a common pattern of alcohol use in the US . However , no studies have evaluated the effectiveness of brief interventions targeting only binge drinkers . METHODS R and omized controlled clinical trial with a 12-month follow-up period conducted from March 1 , 2003 to March 1 , 2006 in Spain . Of a screened population of 15,325 patients seeking routine medical care from their primary care providers , patients who met inclusion criteria were r and omized into an experimental group ( n=371 ) or a control group ( n=381 ) . The primary outcome measures were the frequency of binge drinking episodes and weekly alcohol intake . RESULTS There were no significant differences at baseline between groups in alcohol use and demographic variables . At the end of the 12-month follow-up period , there were significant reductions in binge-drinking status ( 52.2 % vs 67.2 % , P < .001 ) , number of episodes of binge drinking ( 1.14 vs 1.56 , P < .001 ) , number of drinks weekly ( 19.2 vs 22.4 , P < .001 ) , and frequency of excessive alcohol intake in 7 days ( 47.9 % vs 66.6 % , P > .001 ) . CONCLUSIONS This study provided evidence that screening and brief counseling delivered by a primary care physician as part of regular health care significantly reduced binge drinking episodes in binge drinkers BACKGROUND Brief interventions ( BIs ) are effective methods to reduce problematic drinking . It is not known , if the effectiveness of BI differs between patients with or without comorbid depression or anxiety disorders . METHODS In a r and omized controlled BI study with two intervention groups and one control condition , data were collected from 408 general practice ( GP ) patients with alcohol use disorders , at-risk drinking or binge drinking . 88 participants were diagnosed with comorbid anxiety and /or depressive disorders . The effectiveness of BI was assessed at a 12-month follow-up in relation to the presence and absence of comorbidity . Reduction of drinking in six ordered categories ( g/alcohol ) between baseline and follow-up served as the outcome variable . RESULTS BI were significantly related to reduction of drinking in the non-comorbid ( -2.64 g/alcohol vs. -8.61 g/alcohol ; p=.03 ) but not in the comorbid sub sample ( -22.06 g/alcohol vs. -22.09 g/alcohol ; p=.76 ) . Compared to non-comorbid participants , a significantly higher reduction of drinking was found for comorbid individuals ( -6.55 g/alcohol vs. -22.08 g/alcohol ; p=.01 ) . An ordinal regression analysis revealed comorbidity to be a positive predictor for reduction of drinking ( estimator=.594 ; CI=.175 - 1.013 ; p<.01 ) . When entering the variables amount of drinking at baseline , intervention and classification of problematic drinking , these became significant predictors , whereas comorbidity showed only a tendency . CONCLUSION BI did not significantly effect a reduction of drinking in comorbid patients . As BI are known to be less effective for dependent drinkers , a larger proportion of dependents among the comorbid might have limited the effectiveness of BI . Future studies with larger sample sizes of comorbid problem drinkers are necessary to confirm the results |
1,141 | 29,986,763 | However , findings on efficacy of repeated doses in co-infection of S. mansoni and S. haematobium were not conclusive .
Praziquantel administrated at 60 mg/kg was slightly more efficacious than the 40 mg/kg st and ard dose .
Minor and transitory side-effects were reported for both regimens . | Background Schistosomiasis is a serious public health burden in sub-Saharan Africa .
Praziquantel is the only drug recommended by the World Health Organization to treat both urogenital and intestinal schistosomiasis .
The reliance on a single drug to treat a disease with such a huge burden has raised concerns of possible drug resistance mainly in endemic areas .
This systematic review was conducted to identify gaps and recent progress on the efficacy of different regimens of praziquantel in treating schistosomiasis among children in sub-Saharan Africa where Schistosoma mansoni and S. haematobium are endemic . | Background Over 650 million people globally are at risk of schistosomiasis infection , while more than 200 million people are infected of which the higher disease rates occur in children . Eighty three students between 6 - 20 years ( mean 12.45 ± 3.2 ) from Quran School for boys in Radwan village , Gezira state were recruited to investigate for the relationship between the genetic diversity of Schistosoma haematobium strains and the severity of the disease . MethodS chistosoma haematobium infection was detected by filtration of urine . Ultrasonography was done on each study subject , while PCR technique was used for genotyping via r and om amplified polymorphic DNA ( RAPD ) with A01 , A02 , A12 , Y20 and A13 primers . A01 primer gave three different genotypes ( A01 - 1 , A01 - 2 and A01 - 3 ) . Results About 54.2 % ( 45/83 ) were S. haematobium egg positive by urine filtration . On assessment of the upper and lower urinary tract by ultrasound technique , 61.4 % ( 51/83 ) were positive and 73.3 % ( 60/83 ) sample s were PCR positive . No significant difference was found when comparing the three different genotypes with severity of the disease . Conclusion This study concludes that no association was found between the different genotypes of S.haemtobium and the severity of the disease . Examination of more sample s from different areas to identify any possible differences between the parasites genes and disease severity was recommended Background Morbidity due to schistosomiasis is currently controlled by treatment of schistosome infected people with the antihelminthic drug praziquantel ( PZQ ) . Children aged up to 5 years are currently excluded from schistosome control programmes largely due to the lack of PZQ safety data in this age group . This study investigated the safety and efficacy of PZQ treatment in such children . Methods Zimbabwean children aged 1–5 years ( n = 104 ) were treated with PZQ tablets and side effects were assessed by question naire administered to their caregivers within 24 hours of taking PZQ . Treatment efficacy was determined 6 weeks after PZQ administration through schistosome egg counts in urine . The change in infection levels in the children 1–5 years old ( n = 100 ) was compared to that in 6–10 year old children ( n = 435 ) . Principal Findings Pre-treatment S. haematobium infection intensity in 1–5 year olds was 14.6 eggs/10 ml urine and prevalence was 21 % . Of the 104 children , 3.8 % reported side effects within 24 hours of taking PZQ treatment . These were stomach ache , loss of appetite , lethargy and inflammation of the face and body . PZQ treatment significantly reduced schistosome infection levels in 1–5 year olds with an egg reduction rate ( ERR ) of 99 % and cure rate ( CR ) of 92 % . This was comparable to the efficacy of praziquantel in 6–10 year olds where ERR was 96 % and CR was 67 % . Interpretation/ Significance PZQ treatment is as safe and efficacious in children aged 1–5 years as it is in older children aged 6–10 years in whom PZQ is the drug of choice for control of schistosome infections Background Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa , yet this age category is not part of the schistosomiasis control program . The objective of this study was to compare the impact of single and double dose praziquantel ( PZQ ) treatment on cure rates ( CRs ) , egg reduction rates ( ERRs ) and re-infection rates 8 months later , in children aged 1 - 5 years living along Lake Victoria , Ug and a. Methodology /Principal Findings Infected children ( n= 1017 ) were r and omized to receive either a single or double dose of PZQ . Initially all children were treated with a single st and ard oral dose 40 mg/kg body weight of PZQ . Two weeks later a second dose was administered to children in the double dose treatment arm . Side effects were monitored at 30 minutes to 24 hours after each treatment . Efficacy in terms of CRs and ERRs for the two treatments was assessed and compared 1 month after the second treatment . Re-infection with S. mansoni was assessed in the same children 8 months following the second treatment . CRs were non-significantly higher in children treated with two 40 mg/kg PZQ doses ( 85.5 % ; 290/339 ) compared to a single dose ( 83.2 % ; 297/357 ) . ERRs were significantly higher in the double dose with 99.3 ( 95%CI : 99.2 - 99.5 ) compared with 98.9 ( 95%CI : 98.7 - 99.1 ) using a single dose , ( P = 0.01 ) . Side effects occurred more frequently during the first round of drug administration and were mild and short-lived ; these included vomiting , abdominal pain and bloody diarrhea . Overall re-infection rate 8 months post treatment was 44.5 % . Conclusions PZQ is efficacious and relatively safe to use in preschool-age children but there is still an unmet need to improve its formulation to suit small children . Two PZQ doses lead to significant reduction in egg excretion compared to a single dose . Re-infection rates with S. mansoni 8 months post treatment is the same among children irrespective of the treatment regimen OBJECTIVE To evaluate the efficacy and side effects of praziquantel ( PZQ ) in the treatment of schistosomiasis in Ethiopia . METHODS In a cross-sectional study , stool specimens were collected from r and omly selected 299 school children in Shesha Kekele Elementary School , Wondo Genet , Southern Ethiopia , in April 2010 . Stool specimens were examined using a single Kato-Katz thick smear for Schistosoma mansoni ( S. mansoni ) ova . Children who were found positive for S. mansoni were treated with a single oral dose of PZQ at 40 mg/kg bw and interviewed for treatment-related symptoms 24 hours after drug administration . Four weeks post-treatment , stool specimens were collected from the same children and examined following the same procedure as in the pre-treatment . Drug efficacy was determined based on cure and egg reduction rates . RESULTS Pre-treatment prevalence of S. mansoni infection was 74.9 % with geometric mean egg count of 268 . The evaluated generic PZQ produced an overall cure rate of 73.6 % ( P<0.000 1 , OR : 8.33 , CI : 5.3 - 13.1 ) and egg reduction rate of 68.2 % ( P=0.03 , F=0.64 ) . The cure rate showed significant association with age ( χ(2)=11 , P=0.004 ) , the highest rate being observed in the 15 - 22 age group . 83 % of S. mansoni infected children showed various treatment-related symptoms , the most frequent being headache , nausea , and abdominal pain . These symptoms were associated with age ( P<0.001 ) and pre-treatment intensity of infection ( P<0.05 ) . CONCLUSIONS The present observations revealed relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ br and s in Ethiopia . Hence , in depth studies are recommended to clarify whether the present relatively lower cure rate is the actual cure rate of the praziquantel evaluated , treatment failure , or reduced susceptibility of the parasite . Treatment-related side effects observed were transient and tolerable Background In 2012 the WHO formally recognised that infants and preschool children are at significant risk of schistosomiasis and qualify for treatment with praziquantel ( PZQ ) . Targeted surveys determining both the performance and safety of this drug are now needed in endemic areas . We have formally assessed parasitological cure and putative side-effects in a prospect i ve cohort of Schistosoma mansoni-infected children ( aged 5 months–7 years old ) in lakeshore setting s of Ug and a. Methodology /Principal Findings From a total of 369 children found to be egg-patent for intestinal schistosomiasis , 305 were followed-up three to four weeks after PZQ treatment and infection status re-assessed . Separately , a previously tested side-effect question naire was employed before and 24 hours after PZQ treatment to assess incidence and amelioration of symptoms in young children and their mothers . While the overall observed parasitological cure was 56.4 % , a significant difference was found between a sub-set of children who had a history of multiple PZQ treatments ( between one and four in an 18 month period ) , where cure rate was 41.7 % , and those who had never received treatment ( cure rate was 77·6 % ) . PZQ proved to be safe , with only mild reported side effects which cleared within a month after treatment . Prevalence of reported symptoms was significantly lower in children than in mothers , and fewer side-effects were reported upon subsequent rounds of PZQ treatment . Conclusion / Significance Our findings show that PZQ treatment of young children result ed in satisfactory cure rates , and marked reduction in egg-output , with only mild and transient reported side-effects . However , the cure rate is clearly lower in younger children and those with history of previous treatment . Cure rate , but not egg reduction rate , was also lower in children with heavier pre-intervention infection intensity . With chemotherapy now recommended as a long-term strategy for disease control in young children , research into optimising the periodicity of targeted treatment strategies is now crucial BACKGROUND The current recommended control strategy for schistosomiasis is annual treatment using 40 mg/kg of praziquantel . However , praziquantel is only effective on adult worms and giving a second dose may increase its efficacy . We assessed the effect of one versus two doses of praziquantel on cure rate and re-infection with Schistosoma mansoni in a high endemic community along Lake Victoria , Ug and a. METHODOLOGY To investigate the effect of the two regimens , 395 infected people were r and omised into two groups ; one received a single st and ard dose of praziquantel ( Distocide ® 600 mg , Shin Poong Pharmaceuticals , Seoul , Republic of Korea ) , 40mg/kg body weight , while the other group received a second dose 2 weeks later . Cure rate and infection intensity were assessed 9 weeks after the first treatment using st and ard parasitological procedures . Re-infection levels were monitored 8 and 24 months after treatment . RESULTS Those who received two doses were more likely to be cured ( 69.7 % ) compared to those who received a single dose ( 47.9 % ) ( χ(2 ) = 18.5 , p < 0.001 ) . Geometric mean intensity ( GMI ) of infection at 9 weeks ( eggs per gram of faeces [ epg ] ) was 12.0 epg ( CI95 : 8.9 - 16.1 ) for individuals who received 2 doses and 22.1 epg ( CI95 : 16.9 - 28.8 ) for those in the single dose arm . Eight months after treatment , prevalence of re-infection for individuals in the double dose arm ( 61.6 % , CI95 : 50.2 - 73.1 ) was not significantly different from that of those in a single dose arm ( 68.3 % , CI95 : 59.9 - 76.8 ) . The difference in GMI of re-infection for individuals in the single dose arm ( 33.8 epg , CI95 : 23.2 - 49.3 ) and those in the double dose arm ( 34.5 epg , CI95 : 24.7 - 48.1 ) was not significant . Twenty four months after treatment , prevalence of re-infection was not significantly different . The difference in GMI of re-infection for those in the single dose arm ( 57.5 epg , CI95 : 33.9 - 97.5 ) and those in the double dose arm ( 42.2 epg , CI95 : 29.9 - 59.6 ) was also insignificant . CONCLUSION Our results suggest that a second dose of praziquantel given 2 weeks after the first dose improves cure rate and reduces S. mansoni infection intensity . However , there is no added advantage on reduction of S. mansoni re-infection by administering two doses of praziquantel . CLINICAL TRIALS.GOV IDENTIFIER : NCT00215267 Disease outcome in persons infected with Schistosoma haematobium varies dramatically , ranging from mild symptoms to severe damage of the kidneys and /or bladder . We used ultrasonography to characterize the extent of urinary tract pathology of infected children in Zimbabwe , and r and om genetic markers to examine the relationship between genetic diversity of S. haematobium and clinical outcome . One hundred thirty-three parasite isolates from 12 students with mild lesions and 13 with severe lesions were compared . Using four r and omly amplified polymorphic DNA ( RAPD ) markers , we scored parasite allelic frequencies at 53 loci . Although parasite heterogeneity did not differ , allelic frequencies at eight loci differed significantly between the mild and severe groups . Parasite isolates were analyzed further using a modified cluster analysis that segregated the population into 13 clusters of associated genotypes . Three clusters were significantly over-represented in children with severe lesions . Our findings , although preliminary , suggest that parasite genetic associations may be important in clinical outcome Preschool children ( aged ≤5 years ) have so far been overlooked by mass treatment campaigns targeting schistosomiasis , even though praziquantel ( PZQ ) has been shown to be well tolerated and effective within this age group . The WHO provided the Ug and an Ministry of Health with a syrup formulation of PZQ with the aim of assessing its safety and efficacy in comparison with crushed PZQ tablets for the treatment of intestinal schistosomiasis in preschool children . This study included 1144 preschool children r and omly assigned to two treatment arms ( PZQ syrup or crushed PZQ tablet ) regardless of infection status for direct comparison . Diagnosis of intestinal schistosomiasis was assessed using single stool sample , double Kato-Katz smear examinations . Parasitological cure was assessed 3 weeks after treatment . The observed cure rate was 80.9 % for the PZQ syrup arm and 81.7 % for the crushed PZQ tablet arm , with egg reduction rates of 86.1 % and 89.0 % , respectively . Pre-treatment infection intensity was observed to influence cure rates significantly , with cure rates of 88.6 % for light infections , 74.5 % for moderate infections and 67.4 % for heavy infections . No significant difference was found in non-compliance between the PZQ syrup ( 11.1 % ) and crushed PZQ tablet ( 14.7 % ) arms . PZQ syrup and crushed PZQ tablets have very similar efficacies in the treatment of intestinal schistosomiasis in preschool children Praziquantel is the current mainstay for morbidity control of schistosomiasis . Artemisinin and its derivatives , widely used for the treatment of malaria , also display antischistosomal properties . The present study is an effort to assess the therapeutic efficacy of artesunate , an artemisinin derivative , in Schistosoma haematobium infections in a human population . The efficacy of artesunate and praziquantel were comparatively studied in primary schoolchildren from two villages , Lampsar ( n=180 ) and Makhana ( n=108 ) , located along the Lampsar river in the delta of the Senegal River Basin in Northern Senegal ( West Africa ) . In each village , half of the infected children were treated with a single oral dose of 40 mg/kg praziquantel and half with artesunate following the recommended malaria monotherapy regimen . For both drugs , cure and egg count reduction rates were , without apparent explanation , higher in Makhana than in Lampsar . In both villages , high and nearly comparable egg count reduction rates were obtained with both drugs at each follow-up after treatment ( 5 , 12 and 24 weeks ) in the heavy infected group of children ( > 50 eggs/10 ml of urine ) . No major adverse effects were observed . The results demonstrate that artesunate is effective against S. haematobium , but the results obtained with praziquantel were consistently better BACKGROUND Chemotherapy with praziquantel is the current strategy of choice to control schistosomiasis . However , in view of concern about praziquantel tolerance or resistance , new drugs are needed . Artemether , a derivative of the antimalarial drug artemisinin , kills immature schistosomes of Schistosoma japonicum , and reduces the incidence of infection in field trials . Laboratory studies have also showed activity by this drug against S. mansoni . We report a r and omised double-blind placebo-controlled clinical trial of artemether to prevent S. mansoni infection . METHODS The trial was done in an area of western Côte d'Ivoire endemic for S. mansoni . 354 schoolchildren were enrolled . Stool specimens were screened over four consecutive days , followed by two mass treatments with praziquantel 4 weeks apart . All S. mansoni negative children were r and omly assigned to placebo ( n=151 ) or artemether 6 mg/kg ( n=138 ) orally six times once every 3 weeks . Adverse events were assessed 24 h after treatment . Perceived illness episodes were recorded once a week by interviewing the children with a st and ardised question naire . 3 weeks after the final medication S. mansoni infections were assessed by screening stool sample s. Blood sample s were examined for Plasmodium falciparum before the first and after the last artemether treatment . FINDINGS Oral artemether showed no adverse reactions . The group that received artemether had a significantly lower incidence of S. mansoni infection ( 31/128 versus 68/140 , relative risk : 0.50 [ 95 % CI 0.35 - 0.71 ] , p=0.00006 ) . The geometric mean egg output among positive children in the artemether group was significantly lower than in placebo recipients ( 19 vs 32 eggs/g stool , p=0.017 ) . There was also a significant reduction in the prevalence of P. falciparum . INTERPRETATION Oral artemether is safe and shows a prophylatic effect against S. mansoni . The use of artemether may be recommended in appropriated situations as an additional tool for more effective schistosomiasis control measures . However the application needs to be carefully assessed especially in view of the concern that it could select for resistant plasmodia |
1,142 | 30,882,699 | Conclusion : Evidence from RCTs in pediatric cardiac surgery , though limited , showed non-inferiority of restrictive thresholds over liberal thresholds in length of ICU stay and other outcomes following red blood cell transfusion . | Background : Restrictive red blood cell transfusion strategy is implemented to minimize risk following allogeneic blood transfusion in adult cardiac surgery .
However , it is still unclear if it can be applied to pediatric cardiac patients .
The purpose of this systematic review and meta- analysis was to determine the effect of postoperative restrictive transfusion thresholds on clinical outcomes based on up-to- date results of r and omized controlled trials ( RCTs ) and observational studies in pediatric cardiac surgery . | BACKGROUND The aim of this study was to investigate the association between red blood cell ( RBC ) transfusion and haematocrit values with outcomes in infants with univentricular physiology undergoing surgery for a modified Blalock-Taussig shunt . MATERIAL AND METHODS This study included infants ≤ 2 months of age who underwent modified Blalock-Taussig shunt surgery at the Arkansas Children 's Hospital ( 2006 - 2012 ) . Infants undergoing a Norwood operation or Damus-Kaye-Stansel operation with modified Blalock-Taussig shunt were excluded . Demographics , pre-operative , operative , daily laboratory data , and post-operative variables were collected . We studied the association between haematocrit and blood transfusion with a composite clinical outcome . Multivariable logistic regression models were fitted to study the probability of study outcomes as a function of haematocrit values and RBC transfusions after operation . RESULTS Seventy-three patients qualified for inclusion . All study patients received blood transfusion within the first 48 hours after heart surgery . The median haematocrit was 44.3 ( interquartile range [ IQR ] 42.5 - 46.2 ) , and the median volume of RBC transfused was 28 mL/kg ( IQR , 10 - 125 ) in the first 14 days after surgery . The overall in-hospital mortality rate was 13.6 % ( 10 patients ) . A multivariable analysis adjusted for risk factors , including weight , prematurity , cardiopulmonary bypass and postoperative need for nitric oxide and dialysis , revealed no association between haematocrit values and RBC transfusion with the composite clinical outcome . DISCUSSION We did not find an association between higher haematocrit values and increasing RBC transfusions with improved outcomes in infants with shunt-dependent pulmonary blood flow and univentricular physiology . The power of our study was small , which prevents any strong statement on this lack of association . Future multi-centre , r and omised controlled trials are needed to investigate this topic in further detail Objective : To determine the impact of a restrictive vs. a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome in children post cardiac surgery . The optimal transfusion threshold after cardiac surgery in children is unknown . Design : R and omized , controlled trial . Setting : Tertiary pediatric intensive care units . Patients : Participants are a subgroup of pediatric patients post cardiac surgery from the TRIPICU ( Transfusion Requirements in Pediatric Intensive Care Units ) study . Exclusion criteria specific to the cardiac surgery subgroup included : age < 28 days and patients remaining cyanotic . Intervention : Critically ill children with a hemoglobin ≤95 g/L within 7 days of pediatric intensive care unit admission were r and omized to receive prestorage leukocyte-reduced red-cell transfusion if their hemoglobin dropped either < 70 g/L ( restrictive ) or 95 g/L ( liberal ) . Measurements and Main Results : Postoperative cardiac patients ( n = 125 ) from seven centers were enrolled . The restrictive ( n = 63 ) and liberal ( n = 62 ) groups were similar at baseline in age ( mean ± st and ard deviation = 31.4 ± 38.1 mos vs. 26.4 ± 39.1 mos ) , surgical procedure , severity of illness ( Pediatric Risk of Mortality score = 3.4 ± 3.2 vs. 3.2 ± 3.2 ) , multiple organ dysfunction syndrome ( 46 % vs. 44 % ) , mechanical ventilation ( 62 % vs. 60 % ) , and hemoglobin ( 83 vs. 80 g/L ) . Mean hemoglobin remained 21 g/L lower in the restrictive group after r and omization . No significant difference was found in new or progressive multiple organ dysfunction syndrome ( primary outcome ) in the restrictive group vs. liberal group ( 12.7 % vs. 6.5 % ; p = .36 ) , pediatric intensive care unit length of stay ( 7.0 ± 5.0 days vs. 7.4 ± 6.4 days ) or 28-day mortality ( 3.2 % vs. 3.2 % ) . Conclusion : In this subgroup analysis of cardiac surgery patients , a restrictive red-cell transfusion strategy , as compared with a liberal one , was not associated with any significant difference in new or progressive multiple organ dysfunction syndrome , but this evidence is not definitive Objective : Perioperative transfusion has adverse effects in adults undergoing cardiac surgery . We sought to investigate whether greater use of blood and blood products might be an independent predictor of prolonged postoperative recovery , indicated by duration of mechanical ventilation ( DMV ) , after reparative infant heart surgery . Design : Secondary analysis of prospect ively collected data from two r and omized trials of hematocrit strategy during cardiopulmonary bypass in infant heart surgery to explore the association of DMV with perioperative transfusion and other variables . Setting : Tertiary pediatric hospital . Patients : Two hundred seventy infants undergoing two ventricle corrective cardiac surgery without aortic arch reconstruction . Measurements and Main Results : In univariable analyses , longer DMV was associated with younger age and lower weight at surgery , diagnostic group , and higher intraoperative and postoperative blood product transfusion ( each p < .001 ) . In multivariable proportional hazard regression , longer total support time and greater intraoperative and early postoperative blood products per kg were the strongest predictors of longer DMV . Patients in the highest tertile of intraoperative blood products per kg had an instantaneous risk of being extubated approximately half that of patients in the lowest tertile ( hazard ratio , 0.51 ; 95 % confidence interval , 0.35 , 0.73 ) . Patients who received any blood products on postoperative day 1 , compared with those who did not , had a hazard ratio for extubation of 0.65 ( 95 % confidence interval , 0.50 , 0.85 ) . Conclusions : In this exploratory secondary analysis of infants undergoing two ventricular repair of congenital heart disease without aortic arch obstruction , greater intraoperative and early postoperative blood transfusion emerged as potential important risk factors for longer DMV . Future prospect i ve clinical trials are needed to determine whether reduction in blood product administration hastens postoperative recovery after infant heart surgery BACKGROUND Blood transfusion in adults is associated with increased mortality and morbidity after cardiac operations . The aim of this study was to identify the main predictors of blood transfusion and explore the relationship between blood transfusion and adverse outcomes in a pediatric population . METHODS We retrospectively analyzed a prospect ively collected data base ( January 2002 to December 2003 ) of 657 consecutive pediatric patients undergoing open heart procedures in a tertiary pediatric cardiac center . Risk models were calculated for each blood product and for the total amount of blood transfused during the operation and in the first 24 hours . Postoperative adverse events were investigated after propensity score adjustment . RESULTS During the postoperative period , 30 patients ( 4.6 % ) died , 80 ( 12.2 % ) sustained nonvascular pulmonary complications , and 113 ( 17.2 % ) had infection . The risk model for the total amount of blood transfusion included weight , preoperative creatinine clearance , preoperative mechanical ventilation , duration of operation and cross-clamp , surgeon , delayed chest closure , inotropic dose , and nitric oxide administration . Univariate analyses demonstrated significant associations between blood transfusion and occurrence of every complication except of neurologic events . After adjustment for propensity score and disease severity , the total amount of blood transfusion was independently associated with an increased risk for infections ( odds ratio , 1.01 ; 95 % confidence interval , 1.002 to 1.02 ; p = 0.01 ) . Transfusion of platelets was associated with lower incidence of nonvascular pulmonary complications ( odds ratio , 0.89 ; 95 % confidence interval , 0.79 to 0.99 ; p = 0.049 ) . CONCLUSIONS The amount of blood transfusion is independently associated with infections but not with mortality The importance and variability of pre‐operative anaemia in cardiac surgical patients across the UK is not known , and there is debate about its association with patient outcomes . The Association of Cardiothoracic Anaesthetists carried out its first national audit on anaemia and transfusion , and analysed data from 19,033 patients operated on in 12 cardiac surgical centres between 2010 and 2012 ; 5895 ( 31 % ) had pre‐operative anaemia . Centre‐specific prevalence of anaemia varied from 23 % to 45 % ; anaemia was associated with older patients , diabetes and surgical risk ( EuroSCORE ) . Nevertheless , controlling for these factors , regional variation remained an independent effect ( p < 0.001 ) . Multivariable analysis demonstrated an independent association of anaemia with transfusion ( odds ratio ( 95 % confidence interval ) 2.75 ( 2.55–2.95 ) , p < 0.001 ) , mortality ( 1.42 ( 1.18–1.71 ) , p < 0.001 ) and hospital stay ( geometric mean ratio ( 95 % confidence interval ) 1.15 ( 1.13–1.17 ) , p < 0.001 ) . Haemoglobin concentration per se was also independently associated with worse outcomes ; a 10 g.l−1 decrease in haemoglobin was associated with a 43 % increase ( 95 % confidence interval 40–46 % ) in the odds of transfusion and a 16 % increase ( 95 % confidence interval 10–22 % ) in the odds of mortality ( both p < 0.001 ) . This large UK‐wide audit has demonstrated marked regional variation in both anaemia and transfusion , with a consistently high incidence of both . The independent association between pre‐operative anaemia and worse outcomes in UK practice has also been confirmed , and robust prospect i ve study of anaemia treatment before cardiac surgery is required ; these data will assist in design ing such trials BACKGROUND Red blood cell ( RBC ) transfusions are common in the pediatric intensive care unit ( PICU ) . However , there are no recent data on transfusion practice s in the PICU . Our objective was to determine transfusion practice in the PICU , to compare this practice with that observed 10 years earlier , and to estimate the compliance to the recommendation of a large r and omized clinical trial , the Transfusion Requirements in Pediatric Intensive Care Unit ( TRIPICU ) study . STUDY DESIGN AND METHODS This was a single-center prospect i ve observational study over a 1-year period . Information was abstract ed from medical charts . Determinants of transfusion were search ed for daily until the first transfusion in transfused cases or until PICU discharge in nontransfused cases . The justifications for transfusions were assessed using a question naire . RESULTS Of 913 consecutive admissions , 842 were included . At least one RBC transfusion was given in 144 patients ( 17.1 % ) . The mean hemoglobin ( Hb ) level before the first transfusion was 77.3 ± 27.2 g/L. The determinants of a first transfusion event retained in the multivariate analysis were young age ( < 12 months ) , congenital cardiopathy , lowest Hb level of not more than 70 g/L , severity of illness , and some organ dysfunctions . The three most frequently quoted justifications for RBC transfusion were a low Hb level , intent to improve oxygen delivery , and hemodynamic instability . The main recommendation of the TRIPICU study was applied in 96.4 % of the first transfusion events . CONCLUSIONS RBC transfusions are frequent in the PICU . Young age , congenital heart disease , low Hb level , severity of illness , and some organ dysfunctions are significant determinants of RBC transfusions in the PICU . Most first transfusion events were prescribed according to recent recommendations Objective : To examine the impact of a restrictive vs. liberal transfusion strategy on arterial lactate and oxygen content differences in children with single-ventricle physiology post cavopulmonary connection . Children with single-ventricle physiology are routinely transfused postoperatively to increase systemic oxygen delivery , and transfusion thresholds in this population have not been studied . Design : Prospect i ve , r and omized , controlled , clinical trial . Setting : Pediatric cardiac intensive care unit in a teaching hospital . Patients : Infants and children ( n = 60 ) with variations of single-ventricle physiology presenting for cavopulmonary connection . Interventions : Subjects were r and omized to a restrictive ( hemoglobin of < 9.0 g/dL ) , or liberal ( hemoglobin of ≥13.0 g/dL ) transfusion strategy for 48 hrs post operation . Primary outcome measures were mean and peak arterial lactate . Secondary end points were arteriovenous ( C(a-v)o2 ) and arteriocerebral oxygen content ( C(a-c)o2 ) differences and clinical outcomes . Measurements and Main Results : A total of 30 children were in each group . There were no significant preoperative differences . Mean hemoglobin in the restrictive and liberal groups were 11 ± 1.3 g/dL and 13.9 ± 0.5 g/dL , respectively ( p < .01 ) . No differences in mean ( 1.4 ± 0.5 mmol/L [ Restrictive ] vs. 1.4 ± 0.4 mmol/L [ Liberal ] ) or peak ( 3.1 ± 1.5 mmol/L [ Restrictive ] vs. 3.2 ± 1.3 mmol/L [ Liberal ] ) lactate between groups were found . Mean number of red blood cell transfusions were 0.43 ± 0.6 and 2.1 ± 1.2 ( p < .01 ) , and donor exposure was 1.2 ± 0.7 and 2.4 ± 1.1 to ( p < .01 ) , for each group , respectively . No differences were found in C(a-v)o2 , C(a-c)o2 , or clinical outcome measures . Conclusion : Children with single-ventricle physiology do not benefit from a liberal transfusion strategy after cavopulmonary connection . A restrictive red blood cell transfusion strategy decreases the number of transfusions , donor exposures , and potential risks in these children . Larger studies with clinical outcome measures are needed to determine the transfusion threshold for children post cardiac repair or palliation for congenital heart disease 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 optimal hemoglobin for infants after cardiac operation is unknown . Red blood cells ( RBCs ) are commonly transfused to maintain high hemoglobin concentrations in the absence of a clinical indication . We hypothesized that infants can be managed with a postoperative conservative RBC transfusion strategy , result ing in lower daily hemoglobin concentrations , without evidence of impaired oxygen delivery ( ie , lactate , arteriovenous oxygen difference [ avO2diff ] ) , or adverse clinical outcomes . METHODS Infants weighing 10 kg or less undergoing biventricular repair or palliative ( nonseptated ) operation were r and omly assigned to either a postoperative conservative or liberal transfusion strategy . Conservative group strategy was RBC transfusion for a hemoglobin less than 7.0 g/dL for biventricular repairs or less than 9.0 g/dL for palliative procedures plus a clinical indication . Liberal group strategy was RBC transfusion for hemoglobin less than 9.5 g/dL for biventricular repairs or less than 12 g/dL for palliative procedures regardless of clinical indication . RESULTS After the operation of 162 infants ( 82 conservative [ 53 biventricular , 29 palliative ] , 80 liberal [ 52 biventricular , 28 palliative ] ) , including 12 Norwood procedures ( 6 conservative , 6 liberal ) , daily hemoglobin concentrations were significantly lower within the conservative group than the liberal group by postoperative day 1 and remained lower for more than 10 days . The percentage of patients requiring a RBC transfusion , number of transfusions , and volume of transfusions were all significantly lower within the conservative group . Despite lower hemoglobin concentrations within the conservative group , lactate , avO2diff , and clinical outcomes were similar . CONCLUSIONS Infants undergoing cardiac operation can be managed with a conservative RBC transfusion strategy . Clinical indications should help guide the decision for RBC transfusion even in this uniquely vulnerable population . Larger multicenter trials are needed to confirm these results , and focus on the highest risk patients would be of great interest Background : Current trends in pediatric cardiac surgery and anesthesiology include goal -directed allogeneic blood transfusion , but few studies address the transfusion of platelets and cryoprecipitate . We report a quality improvement initiative to reduce the transfusion of platelets and cryoprecipitate in infants having cardiac surgery with cardiopulmonary bypass ( CPB ) . Methods : Data from 50 consecutive patients weighing four to ten kilograms having cardiac surgery with CPB were prospect ively collected after the institution of a policy to obtain each patient ’s platelet and fibrinogen levels during the rewarming phase of CPB . Data from 48 consecutive patients weighing four to ten kilograms having cardiac surgery with CPB prior to the implementation of the policy change were retrospectively collected . Demographics , laboratory values and blood product transfusion data were compared between the groups , using the Chi-square/Fisher ’s exact test or the T-Test/Wilcoxon Rank-Sum test , as appropriate . Results : The results showed more total blood product exposures in the control group during the time from bypass through the first twenty-four post-operative hours ( median of 2 units versus 1 unit in study group , p=0.012 ) . During the time period from CPB separation through the first post-operative day , 67 % of patients in the control group received cryoprecipitate compared to 32 % in the study group ( p=0.0006 ) . There was no difference in platelet exposures between the groups . Conclusion : Checking laboratory results during the rewarming phase of CPB reduced cryoprecipitate transfusion by 50 % . This reproducible strategy avoids empiric and potentially unnecessary transfusion in this vulnerable population BACKGROUND Blood utilization has long been suspected to consume more health care re sources than previously reported . Incomplete accounting for blood costs has the potential to misdirect programmatic decision making by health care systems . Determining the cost of supplying patients with blood transfusions requires an in-depth examination of the complex array of activities surrounding the decision to transfuse . STUDY DESIGN AND METHODS To accurately determine the cost of blood in a surgical population from a health system perspective , an activity-based costing ( ABC ) model was constructed . Tasks and re source consumption ( material s , labor , third-party services , capital ) related to blood administration were identified prospect ively at two US and two European hospitals . Process frequency ( i.e. , usage ) data were captured retrospectively from each hospital and used to populate the ABC model . RESULTS All major process steps , staff , and consumables to provide red blood cell ( RBC ) transfusions to surgical patients , including usage frequencies , and direct and indirect overhead costs contributed to per-RBC-unit costs between $ 522 and $ 1183 ( mean , $ 761 + /- $ 294 ) . These exceed previously reported estimates and were 3.2- to 4.8-fold higher than blood product acquisition costs . Annual expenditures on blood and transfusion-related activities , limited to surgical patients , ranged from $ 1.62 to $ 6.03 million per hospital and were largely related to the transfusion rate . CONCLUSION Applicable to various hospital practice s , the ABC model confirms that blood costs have been underestimated and that they are geographically variable and identifies opportunities for cost containment . Studies to determine whether more stringent control of blood utilization improves health care utilization and quality , and further reduces costs , are warranted BACKGROUND The optimal hemoglobin threshold for erythrocyte transfusions in critically ill children is unknown . We hypothesized that a restrictive transfusion strategy of using packed red cells that were leukocyte-reduced before storage would be as safe as a liberal transfusion strategy , as judged by the outcome of multiple-organ dysfunction . METHODS In this noninferiority trial , we enrolled 637 stable , critically ill children who had hemoglobin concentrations below 9.5 g per deciliter within 7 days after admission to an intensive care unit . We r and omly assigned 320 patients to a hemoglobin threshold of 7 g per deciliter for red-cell transfusion ( restrictive- strategy group ) and 317 patients to a threshold of 9.5 g per deciliter ( liberal- strategy group ) . RESULTS Hemoglobin concentrations were maintained at a mean ( + /-SD ) level that was 2.1+/-0.2 g per deciliter lower in the restrictive- strategy group than in the liberal- strategy group ( lowest average levels , 8.7+/-0.4 and 10.8+/-0.5 g per deciliter , respectively ; P<0.001 ) . Patients in the restrictive- strategy group received 44 % fewer transfusions ; 174 patients ( 54 % ) in that group did not receive any transfusions , as compared with 7 patients ( 2 % ) in the liberal- strategy group ( P<0.001 ) . New or progressive multiple-organ dysfunction syndrome ( the primary outcome ) developed in 38 patients in the restrictive- strategy group , as compared with 39 in the liberal- strategy group ( 12 % in both groups ) ( absolute risk reduction with the restrictive strategy , 0.4 % ; 95 % confidence interval , -4.6 to 5.4 ) . There were 14 deaths in each group within 28 days after r and omization . No significant differences were found in other outcomes , including adverse events . CONCLUSIONS In stable , critically ill children a hemoglobin threshold of 7 g per deciliter for red-cell transfusion can decrease transfusion requirements without increasing adverse outcomes . ( Controlled-trials.com number , IS RCT N37246456 [ controlled-trials.com ] . ) Objective To investigate the safety and effects of a restrictive red blood cell ( RBC ) transfusion strategy in pediatric cardiac surgery patients . Design R and omized controlled trial . Setting Pediatric ICU in an academic tertiary care center , Leiden University Medical Center , Leiden , The Netherl and s. Patients One hundred seven patients with non-cyanotic congenital heart defects between 6 weeks and 6 years of age . One hundred three patients underwent corrective surgery on cardiopulmonary bypass . Interventions Prior to surgery patients were r and omly assigned to one of two groups with specific RBC transfusion thresholds : Hb 10.8 g/dl ( 6.8 mmol/l ) and Hb 8.0 g/dl ( 5.0 mmol/l ) . Measurements Length of stay in hospital ( primary outcome ) , length of stay in PICU , duration of ventilation ( secondary outcome ) , incidence of adverse events and complications related to r and omization ( intention to treat analysis ) . Results In the restrictive transfusion group , mean volume of transfused RBC was 186 ( ±70 ) ml per patient and in the liberal transfusion group 258 ( ±87 ) ml per patient , ( 95 % CI 40.6–104.6 ) , p < 0.001 . Length of hospital stay was shorter in patients with a restrictive RBC transfusion strategy : median 8 ( IQR 7–11 ) vs. 9 ( IQR 7–14 ) days , p = 0.047 . All other outcome measures and incidence of adverse effects were equal in both RBC transfusion groups . Cost of blood products for the liberal transfusion group was 438.35 ( ±203.39 ) vs. 316.27 ( ±189.96 ) euros ( 95 % CI 46.61–197.51 ) per patient in the restrictive transfusion group , p = 0.002 . Conclusions For patients with a non-cyanotic congenital heart defect undergoing elective cardiac surgery , a restrictive RBC transfusion policy ( threshold of Hb 8.0 g/dl ) during the entire perioperative period is safe , leads to a shorter hospital stay and is less expensive Background : The aim of this study was to explore the relative clinical and bio material effects of blood transfusions ( Tx ) and novel low-prime , surface-coated circuitry on perioperative outcome in a pediatric population undergoing cardiac surgery with cardiopulmonary bypass ( CPB ) . Methods : Over a 12-month period , 80 patients weighing > 10 kg undergoing ventricular septal defect ( VSD ) repair with CPB were prospect ively r and omized into two groups according to the type of CBP circuit used , then each r and omized group was enrolled into two groups again , according to the need for transfusion ( N=20 ) : Group 1- Tx-free procedures on low-prime , surface-coated extracorporeal circuitry ( FX05 , Terumo ) ; Group 2- procedures requiring Tx on coated circuitry ; Group 3- Tx-free procedures with st and ard uncoated circuitry ( D902 , Sorin ) ; Group 4 (Control)- procedures requiring Tx on uncoated circuitry . Blood sample s were collected at baseline ( T1 ) , at the end of the CPB ( T2 ) and 24 h ( T3 ) postoperatively . rSO2 desaturation risk score > 6000 ( Invos , Somanetics ) was calculated by multiplying rSO2 < 50 % by time . Results : IL-6 levels ( pg/ml ) were significantly lower in Groups 1 and 3 versus control at T2 ( 13±4 ; 17±5 versus 33±8 ; p<0.05 ) . CD11b/CD18 levels ( % ) were significantly lower in Group 1 ( 12±4 ) versus control ( 25±8 ) at T2 ( p<0.05 ) . Respiratory support time ( h ) was significantly less in Group 1 ( 11.4±6 ) versus control ( 19.8±7 ) ( p<0.05 ) . rSO2 desaturation risk > 6000 ( % ) was 15.7±9 in Group 1 and 26.8±11 in control ( p<0.05 ) . Conclusion : Allogenic Tx amplifies the CPB-related inflammatory response . It is feasible to do congenital procedures safely without Tx for patients weighing > 10 kg by using combined blood management strategies BACKGROUND Red blood cell transfusion is an important supportive measure after pediatric cardiac operations . However , no clear hemoglobin threshold has been established . This study characterized anemia development and red blood cell transfusions in the pediatric intensive care unit ( PICU ) after cardiac operations . METHODS A prospect i ve , multicenter , 6-month cohort study on the management of anemia in critically ill pediatric patients was conducted in 30 North American PICUs . This observational study enrolled 977 consecutive children ( aged < 18 years ) who stayed in the PICU for 48 hours or more . We analyzed a subgroup of postcardiac surgical patients from this study . RESULTS Included were 175 cardiac patients , 56 % of whom had cyanotic heart disease . The mean Pediatric Risk of Mortality ( PRISM III ) score was 6.4 ± 5.4 . Fifty-four percent of children were anemic in the PICU ( 20 % on admission , 34 % during PICU stay ) . Most patients ( 79 % ) received at least one red blood cell transfusion in the PICU . Patients who received a transfusion had a significantly longer PICU stay ( 9.3 ± 6.3 vs 6.1 ± 5.4 days , p = 0.01 ) . Pretransfusion hemoglobin was different in acyanotic and cyanotic patients ( mean ± st and ard deviation : 11.1 ± 2.2 g/dL and 11.8 ± 2.1 g/dL , respectively ) . According to the attending physician , a low hemoglobin level was the primary indication for transfusion in only 17 % of cases . CONCLUSIONS Pediatric cardiac surgical patients are at high risk of receiving red blood cell transfusions . This study , which showed great variability in transfusion practice s across North American PICUs , highlights the need for clearer transfusion guidelines in this specific population BACKGROUND We sought to identify risk factors for surgical site infections ( SSI ) in children undergoing cardiac surgery . METHODS A matched case-control study was conducted in the Children 's Hospital Boston Cardiovascular Program . Surgical site infections were identified for 3 years ( 2004 to 2006 ) . We identified two r and omly selected control patients who underwent cardiac surgery within 7 days of each index case . Univariate and multivariate conditional logistic regression analyses were used to identify risk factors for SSI . In a secondary analysis , risk factors for organ space SSI ( mediastinitis ) were sought . Secondary analyses were also conducted using only those variables known preoperatively . RESULTS Seventy-two SSI and 144 controls were included . Independent risk factors for any type of SSI were age younger than 1 year ( adjusted odds ratio , 2.28 ; 95 % confidence interval , 1.18 to 4.39 ) and duration of cardiopulmonary bypass greater than 105 minutes ( adjusted odds ratio , 1.92 ; 95 % confidence interval , 1.02 to 3.62 ) . Independent risk factors for organ space SSI were aortic cross-clamp time greater than 85 minutes ( adjusted odds ratio , 5.61 ; 95 % confidence interval , 1.06 to 29.67 ) and postoperative exposure to at least three separate red blood cell transfusions ( adjusted odds ratio , 7.87 ; 95 % confidence interval , 1.63 to 37.92 ) . When only those potential risk factors known preoperatively were considered , age younger than 1 year independently predicted the subsequent development of any type of SSI , and preoperative hospitalization independently predicted the subsequent development of organ space SSI . CONCLUSIONS Younger patients undergoing longer surgical procedures and those requiring more postoperative blood transfusions are at greatest risk for SSI . Additional preventive strategies , including restrictive blood transfusion policies , warrant further investigation |
1,143 | 31,280,258 | In conclusion , there is evidence that the OHRQoL of children and adolescents improved following caries intervention procedures , but the quality of the evidence was very low .
In spite of that , caries interventions are highly recommended as abstaining from treatment is likely to result in a deterioration of | This systematic review and meta- analysis were undertaken to assess the responsiveness of vali date d oral health-related quality of life ( OHRQoL ) question naires to dental caries interventions in children , adolescents , and young adults . | Purpose : To investigate the perceived clinical outcome and parents ’ satisfaction after dental rehabilitation under general anesthesia over a follow-up period of 2 years . Material s and Methods : A prospect i ve study of question naire data obtained from 352 pediatric patients before and after treatment of early childhood caries with full dental rehabilitation under general anesthesia . Question naires focused on oral symptoms , functional limitations , and emotional and social well-being before and after dental treatment . Cases were followed up for 2 years postoperatively . Results : A dramatic disappearance of symptoms was reported from parents ’ perspective . There was a high satisfaction rate ( 99.14 % ) also among parents of the children included in the study . Conclusion : Children with early childhood caries do not necessarily express it verbally as pain . The disease has a lot of other expressions affecting children 's behavior and habits , including the ability to sleep , thrive , and socialize . This study contributes to the existing literature that full dental rehabilitation under general anesthesia [ dental general anesthesia ( DGA ) ] has an immediate positive impact on the physical and social quality of life of children suffering from early childhood caries as well as on their families . Postoperative preventive care , early diagnosis , and treatment of recurrent caries are key factors to maintain postoperative outcome of DGA OBJECTIVE To compare subjective pain experience and oral health-related quality of life ( OH-QoL ) in treated and untreated subjects over the first 3 months of fixed appliance therapy . SETTING AND SAMPLE POPULATION The Department of Orthodontics , School of Medicine and Dentistry . One hundred and twenty-four subjects aged between 11 and 14 years either commencing or awaiting fixed appliance treatment . MATERIAL & METHODS A prospect i ve controlled longitudinal study design was applied to subjects , over a 3-month observation period , following the placement of fixed appliances . Socio-economic status , OH-QoL , pain experience and analgesic consumption were recorded on question naires at baseline ( T0 ) , 6 weeks ( T1 ) and 3 months ( T2 ) . RESULTS Oral symptoms and functional limitation domains of OH-QoL were found to worsen , during the follow-up period , in the test group ( p = 0.001 and p = 0.002 , respectively ) . In the treated group , pain intensity declined significantly on days 3 and 2 at T1 and T2 , respectively ( p < 0.001 ) . Analgesia was required during both periods in a total of 13 participants ( 24.5 % ) undergoing orthodontic treatment . CONCLUSION Based on this prospect i ve controlled study , the initial stages of fixed appliance treatment results in subjective pain experience , with subsequent reduction , and a significant impact on oral symptoms and functional limitation domains of Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Abstract Our goal was to evaluate how dental treatments under general anesthesia ( GA ) affect the quality of life by a prospect i ve pair-matched design . Pediatric patients , who had received dental treatments under GA , were enrolled and were asked to complete the Early Childhood Oral Health Impact Scale ( ECOHIS ) before the treatment and 1 month after the treatment . To shield the observed impacts , a pair-matched control group was performed . Patients in the control group were also required to complete the ECOHIS at these different points in time . In both groups , the items of troubled sleep and oral/dental pain scored highest , whereas avoiding smiling or laughing and avoiding talking scored lowest before the treatment . The total mean score in the 2 groups was 13.1 and 13.7 , respectively , and there was no significant statistical difference ( P > 0.05 ) . However , the total mean score was 1.9 in the experimental group after the treatment and smaller compared with the control group ( 1.9 vs. 4.7 , P < 0.001 ) . The majority of the items in both groups had an apparent effect size and the total mean effect in the experimental group was greater than that in the control group ( 85.5 % vs. 65.7 % , P < 0.001 ) . Therefore , dental treatment under GA could provide better quality of life restoration compared with treatment over multiple visits We present data from two studies which clarify the relationship between the responsiveness and validity of instruments design ed to measure health status in clinical trials . In a controlled trial of long vs short duration adjuvant chemotherapy for women with Stage II breast cancer , the Breast Cancer Chemotherapy Question naire ( BCQ ) proved valid as a measure of subjective health status and was able to distinguish long vs short arms . Well vali date d measures of physical and emotional function developed by the R and Corporation were unable to distinguish between the two groups . The Eastern Co-operative Oncology Group Criteria ( ECOG ) distinguished the two groups , but failed criteria of clinical sensibility as a measure of subjective health status . In a study of patients with Crohn 's disease and ulcerative colitis , the Inflammatory Bowel Disease Question naire ( IBDQ ) showed small intrasubject variability over time . Gobal ratings of change showed moderate to high correlations with changes in IBDQ score , and patients who reported overall improvement or deterioration showed large changes in IBDQ score . Each of these findings support , in different ways , the reproducibility , validity , and responsiveness of the question naire . While the same data can at times bear on both validity and responsiveness , when assessing evaluative instruments it is useful to make a conceptual distinction between the two OBJECTIVES This study examined the responsiveness of the Early Childhood Oral Health Impact Scale ( ECOHIS ) to dental treatment of early childhood caries ( ECC ) in a primary dental care setting . METHODS Parents of children participating in a r and omized controlled trial completed the ECOHIS at baseline and follow-up , and rated the global oral health transition of their child at follow-up ( ' worsened ' , ' no change ' , ' improved ' ) . Change scores were calculated and longitudinal construct validity assessed by examining the association between change scores and global oral health transition groups . ECOHIS changes from baseline to follow-up within global transition groups were also evaluated . Effect sizes , minimally important difference , and Guyatt 's responsiveness index were calculated to examine the scale 's sensitivity and responsiveness . RESULTS After 11.3 months , complete question naire data were available for 189 participants ; 59 % reported ' improved ' oral health . The follow-up scores were significantly lower in the child psychology , parental distress and family impact section , P < 0.001 , and in the child social interaction , family function and the total ECOHIS scores , P < 0.05 , Wilcoxon signed-rank test . There was a significant difference in changed scores among the global transition groups , P < 0.05 , Kruskal-Wallis test , and the difference was significant between ' worsened ' and ' improved ' groups for the family impact and the total ECOHIS scores , Dunn test , P < 0.05 . Effect sizes were small , 0.17 , 0.33 , 0.30 for the child impact , family impact and total ECOHIS scores , respectively , for those reporting ' improved ' oral health . CONCLUSIONS The responsiveness of the ECOHIS to the treatment of ECC in primary dental care setting s was modest , and its use to measure treatment effects in primary care setting s requires further investigations AIM To assess changes over time and determine the minimally important difference ( MID ) in the Oral Impact on Daily Performances ( OIDP ) index for patients with severe generalized periodontitis receiving periodontal treatment . METHODS This study was nested in a larger r and omized controlled trial and consisted of 45 consecutive subjects of the larger trial ( 17 receiving intensive and 28 receiving conservative periodontal care ) . The OIDP index assessed impacts on quality of life ( QoL ) at baseline and 1 month after treatment . Repeated- measures ANOVA was used for comparison over time and between treatment groups . To estimate the MID , two subjective global transition scales , related to periodontal and oral health , respectively , were used as anchors , whereas the effect size ( ES ) , st and ardized response mean and st and ard error of measurement were also calculated . RESULTS The mean OIDP score after treatment was significantly lower than at baseline , indicating improvement in QoL , but there were no differences between treatment groups . Based on an agreement between different methods , the MID of the OIDP index was around five scale points and corresponded to a moderate ES . CONCLUSION The MID for the OIDP index among patients treated for severe generalized periodontitis provides meaning to change scores and facilitates interpretation of findings This study aim ed to evaluate the impact of dental caries treatment on oral health-related quality of life ( OHRQoL ) among schoolchildren and the responsiveness of the Child Perceptions Question naire ( CPQ8 - 10 ) instrument . Brazilian schoolchildren , 8 - 10 yr of age , were r and omly selected and assigned to two groups -- dental caries treatment ( DCT ) and caries-free (CF)--according to their caries experience [ decayed , missing , or filled primary teeth ( dmft ) and decayed , missing or filled secondary teeth ( DMFT ) values of ≥ 0 ] . The CPQ8 - 10 instrument was administered at baseline and at 4 wk of follow-up ( i.e. 4 wk after completion of dental treatment ) . In the DCT group , increases in CPQ8 - 10 scores were observed between the baseline and follow-up results . However , longitudinal evaluation of the CF group demonstrated no statistically significant difference in CPQ8 - 10 scores . Responsiveness of the CPQ8 - 10 instrument ( magnitude of change in CPQ8 - 10 scores ) in the DCT group was greater ( effect size > 0.7 ) than in the CF group . The findings of this study show that dental caries treatment has an important impact on OHRQoL of children . The CPQ8 - 10 was considered an acceptable instrument for longitudinal measurement of changes in Abstract Objective : Our aim was to analyze longitudinally the impact of young children ’s dental general anaesthesia ( DGA ) treatment on their OHRQoL and to determine their post-operative oral health status at the six-month follow-up together with parental ratings of their children ’s oral health . Material and methods : We conducted a prospect i ve follow-up study of OHRQoL among Lithuanian child patients treated under general anaesthesia ( n = 144 ) . The study consisted of clinical dental examinations performed by two examiners at the time of DGA and at the six-month recall , along with OHRQoL surveys and data collected from the patients ’ files . The dmft index and Silness – Löe plaque index served as clinical measures . The survey tool for assessing the children ’s OHRQoL was the previously tested Lithuanian version of the ECOHIS . The Wilcoxon signed-rank test served for the statistical analysis ( p < 0.05 ) . Results : The ECOHIS scores clearly decreased post-operatively , indicating a significant ( p < 0.001 ) improvement in the children ’s OHRQoL after the DGA treatment . The ECOHIS scores were lower immediately after the DGA treatment and remained low at the six-month recall . Parents rated their child ’s oral health as higher after the DGA treatment ( p < 0.001 ) . The majority ( 75 % ) of the patients had poor or satisfactory oral hygiene at follow-up . Conclusions : This longitudinal study showed a sustained improvement in the children ’s OHRQoL six months after their DGA treatment . Post-operative parental ratings of their child ’s oral health were higher after the DGA treatment , but the children exhibited insufficient oral hygiene and new caries lesions . An appropriate follow-up system for children receiving DGA treatment with special focus on preventive care is needed BACKGROUND The aim of this study was to compare changes in child oral health-related quality of life ( COHRQoL ) after treatment for early childhood caries ( ECC ) using two alternative treatment approaches . METHODS A r and omized control trial with r and om allocation of parent/child dyads with ECC to test ( minimum intervention ) or control ( st and ard care ) . Participating parents completed the Early Childhood Oral Health Impact Scale ( ECOHIS ) at baseline and follow-up . Changes in ECOHIS scores and extent of COHRQoL impacts between and within groups were tested using the chi-squared statistic for groups , Wilcoxon 's rank-sum test , and matched-pairs signed-rank test . RESULTS Two hundred and fifty-four children were r and omized ( test = 127 ; control = 127 ) . At baseline , mean ECOHIS score 11.1 , sd 8.2 ; mean age = 3.8 years , sd 0.90 ; mean dmft = 4.9 , sd 4.0 ; and 59 % male . After a mean interval of 11.4 months , 210 children were followed-up and returned a completed question naire ( test = 111 ; control = 99 ) . There was no significant difference in COHRQoL changes between test and control . For all the children combined , there were significantly fewer impacts at follow-up in the child and family domains and the total ECOHIS , Wilcoxon signed-rank test , p < 0.05 . CONCLUSIONS COHRQoL improved with primary dental care for ECC , and there was no statistically significant difference between test and control in the extent of the improvement BACKGROUND Oral health-related quality of life ( OHRQoL ) measures should be tested for responsiveness to change if they are to be used as outcomes in r and omized clinical trials . AIM To assess the responsiveness of the Brazilian ECOHIS ( B-ECOHIS ) to dental treatment of dental caries . METHODS One hundred parents of 3- to 5-year-old children completed the B-ECOHIS prior to their children 's treatment and 7 - 14 days after completion of treatment . The post-treatment question naire also included a global transition judgment that assessed parent 's perceptions of change in their children 's oral health following treatment . Change scores , longitudinal construct validity , st and ardized effect sizes ( ES ) and st and ardized response mean ( SRM ) were calculated . RESULTS Improvements in children 's oral health after treatment were reflected in mean pre- and post-treatment B-ECOHIS scores . They declined considerably significantly from 17.4 to 1.6 ( P < 0.0001 ) , as did the individual domain scores ( P < 0.0001 ) . There were significant differences in the pre- and post-treatment scores of children who reported little improvement ( P < 0.0001 ) as well as in those who reported large improvements ( P < 0.0001 ) . The ES and SRM based on change scores mean for total scores and for categories of global transitions judgments were large . CONCLUSIONS Dental treatment result ed in significant improvement of the preschool children 's OHRQoL. The B-ECOHIS is responsive During the past decade the research interest in Oral Health-Related Quality of Life ( OHRQoL ) has been prospering . This study was performed to test ( using a r and omized controlled trial design ) the hypothesis that young children 's OHRQoL improves after oral rehabilitation under general anaesthesia ( GA ) . A further aim of this study was to explore whether dental fear also changes . One-hundred and four children ( 54 boys ; mean age 4.08 yr , st and ard deviation = 1.09 ) , who had been referred to a specialized clinic in paediatric dentistry , were r and omly assigned , based on a Solomon four-group design , to two treatment ( GA ) and two control conditions . The Early Childhood Oral Health Impact Scale ( ECOHIS ) and the Children 's Fear Survey Schedule-Dental Subscale ( CFSS-DS ) were used to assess OHRQoL and dental fear , respectively , before and after the rehabilitation procedures . A 2 x 2 analysis of variance revealed that the total ECOHIS score after GA was more positive in the GA group than in the control group . There was no effect found of the pre-test and there was also no interaction between the pre-test and treatment . In the total CFSS-DS scores no effects were found . The results of this study showed that the child 's OHRQoL improved after treatment under GA . Furthermore , children need guidance in reducing dental fear after treatment under GA |
1,144 | 31,655,953 | After stratifying for different criteria for remission , RYGB still tended to result in higher remission rates , but the difference was not statistically significant .
This review demonstrates important remission of T2DM following SG .
Nevertheless , as remission was significantly more often observed following RYGB surgery , the latter procedure remains the gold st and ard for reaching T2DM remission in patients with concurrent obesity | The sleeve gastrectomy ( SG ) has gained popularity which has result ed in a rising number of patients with T2DM to undergo this procedure .
This systematic review and meta- analysis aim ed to compare the long-term effects of SG on T2DM remission with remission seen after Roux-en-Y gastric bypass ( RYGB ) or gastric b and ing ( GB ) . | Background Laparoscopic sleeve gastrectomy ( LSG ) and laparoscopic Roux-en-Y gastric bypass ( LRYGB ) achieve similar type 2 diabetes mellitus ( T2DM ) remission rates . Since a great variability exists in defining T2DM remission , an expert panel proposed partial and complete remission criteria that include the maintenance of fasting plasma glucose ( FPG ) and glycosylated hemoglobin ( A1c ) objectives for at least 1 year . The 2-year T2DM remission rate and time needed to reach it after LSG or LRYGB were compared using different remission criteria . Methods This was a prospect i ve cohort study of 55 T2DM subjects operated on with LSG ( n = 21 ) or LRYGB ( n = 34 ) . Four models for defining remission were used : Buchwald criteria ( FPG < 100 mg/dl or A1c < 6 % ) , American Diabetes Association ( ADA ) complete ( FPG < 100 mg/dl plus A1c < 6 % maintained for at least 1 year ) , ADA partial ( FPG < 125 mg/dl with A1c < 6.5 % maintained for at least 1 year ) , and ADA complete without time requirement . Results Both groups were comparable , except for higher A1c levels in the LSG group . The remission rate ranged from 43.6 % using ADA complete remission to 92.7 % with Buchwald criteria , with no differences between surgical procedures . Differences were found in the time to achieve remission only when ADA complete remission criteria ( 5.1 ± 2.9 months LRYGB and 9.0 ± 3.8 months LSG , p = 0.014 ) and ADA without time requirement criteria ( 4.9 ± 2.7 months LRYGB and 8.4 ± 3.9 months LSG , p = 0.005 ) were used . Conclusions T2DM remission rate varies widely depending on the criteria used for its definition . Remission occurred sooner after LRYGB when the strictest criteria to define remission were used Objective : To present long-term results of a large series of patients su bmi tted to laparoscopic Roux-en-Y gastric bypass ( RYGBP ) for morbid obesity . Background : Reports on long-term results of RYGBP are scarce and focus primarily on weight loss . Our aim is to provide mid- to long-term data of RYGBP , with detailed results on weight loss , evolution of comorbidities and quality of life , also using the BAROS score . Methods : All patients who underwent a primary RYGBP for morbid obesity in our 2 hospitals between 1999 and August 2008 were included . Data were collected prospect ively in a computerized data base , and review ed for the purpose of this study . Results : A total of 379 patients were included in the analysis of long-term results , 282 women , and 97 men , with a mean BMI of 46.3 kg/m2 . After 5 years , 74.9 % of the patients achieved an excess weight loss of at least 50 % , with a mean of 62.7 % and 76.8 % achieved a BMI < 35 kg/m2 . The corresponding figures after 7 years were 64.9 , 58.1 , and 71.9 , respectively . There was a small but significant long-term weight regain . All comorbidities improved markedly in the vast majority of patients , with no significant difference between the 3- and 5-year terms . Quality of life also improved markedly , and more than 95 % of the patients had a good to excellent 5-year overall result according to the BAROS score . Conclusions : Laparoscopic RYGBP for morbid obesity results in good and maintained weight loss up to 7 years in the majority of patients , improves quality of life and markedly improves all the evaluated comorbidities , result ing in good to excellent overall 5-year results in 97 % of the patients according to the BAROS score BACKGROUND Obesity not only increases the chances of developing diabetes-one of the top causes of death in the United States-but it also results in further medical complications . OBJECTIVE To compare the 6-month and 1-year postoperative remission rates of type 2 diabetic ( T2D ) patients after bariatric surgery based on preoperative glycosylated hemoglobin ( A1C ) stratification and pharmacologic therapy : insulin-dependent diabetic ( IDD ) versus noninsulin-dependent diabetic ( NIDD ) . SETTING Academic hospital , United States . METHODS We retrospectively analyzed a prospect ively maintained data base of 186 obese patients with a diagnosis T2D who had undergone either a sleeve gastrectomy or a Roux-en-Y gastric bypass surgery at our hospital . RESULTS At 6 months ( n = 180 ) , patients who were stratified by preoperative A1C levels ( < 6.5 ; ≥6.5 to<8 ; ≥8 ) had 70.5 % , 51.7 % , and 30.0 % remission rates ( P<.001 ) and at 1 year ( n = 118 ) patients had 72.0 % , 54.0 % , and 42.8 % remission rates ( P = .053 ) , respectively . When patients were substratified by preoperative pharmacologic therapy , IDD and NIDD patients had different remission rates within the same A1C level . At 6-months follow-up within A1C ≥6.5 to<8 ( IDD versus NIDD ) , the remission rate was 23.5 % versus 64.1 % ( odds ratio [ OR ] : .173 , confidence interval [ CI ] : .0471 , .6308 , P = .0079 ) , and within A1C ≥8 the remission was 24.0 % versus 37.5 % ( OR : .5263 , CI : .2115 , 1.3096 , P = .1676 ) , respectively . At 1-year follow-up within A1C ≥6.5 to<8 , the remission rate was 30.0 % versus 62.9 % ( OR : .2521 , CI : .0529 , 1.2019 , P = .0838 ) , and within A1C ≥8 the remission was 31.4 % versus 61.9 % ( OR : .2821 , CI : .0908 , .8762 , P = .0286 ) , respectively . Furthermore , when IDD patients were compared between A1C ≥6.5 to<8 and A1C ≥8 the remission rates were nearly identical , and for NIDD patients A1C was not significantly associated with remission regardless of the level , except at 6 months . CONCLUSION While a difference was observed between overall A1C levels-the lower the A1C level , the higher the remission rate-IDD patients had lower remission rates than NIDD patients irrespective of A1C levels ; further , IDD patients performed similarly across A1C levels Importance Sleeve gastrectomy is increasingly used in the treatment of morbid obesity , but its long-term outcome vs the st and ard Roux-en-Y gastric bypass procedure is unknown . Objective To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss , changes in comorbidities , increase in quality of life , and adverse events . Design , Setting , and Participants The Swiss Multicenter Bypass or Sleeve Study ( SM-BOSS ) , a 2-group r and omized trial , was conducted from January 2007 until November 2011 ( last follow-up in March 2017 ) . Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers , 217 patients were enrolled and r and omly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period . Interventions Patients were r and omly assigned to undergo laparoscopic sleeve gastrectomy ( n = 107 ) or laparoscopic Roux-en-Y gastric bypass ( n = 110 ) . Main Outcomes and Measures The primary end point was weight loss , expressed as percentage excess body mass index ( BMI ) loss . Exploratory end points were changes in comorbidities and adverse events . Results Among the 217 patients ( mean age , 45.5 years ; 72 % women ; mean BMI , 43.9 ) 205 ( 94.5 % ) completed the trial . Excess BMI loss was not significantly different at 5 years : for sleeve gastrectomy , 61.1 % , vs Roux-en-Y gastric bypass , 68.3 % ( absolute difference , −7.18 % ; 95 % CI , −14.30 % to −0.06 % ; P = .22 after adjustment for multiple comparisons ) . Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass ( 60.4 % ) than after sleeve gastrectomy ( 25.0 % ) . Gastric reflux worsened ( more symptoms or increase in therapy ) more often after sleeve gastrectomy ( 31.8 % ) than after Roux-en-Y gastric bypass ( 6.3 % ) . The number of patients with reoperations or interventions was 16/101 ( 15.8 % ) after sleeve gastrectomy and 23/104 ( 22.1 % ) after Roux-en-Y gastric bypass . Conclusions and Relevance Among patients with morbid obesity , there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery . Trial Registration clinical trials.gov Identifier : Introduction Bariatric surgery is considered the most effective treatment for obesity . A recent worldwide survey demonstrated that Laparoscopic Sleeve Gastrectomy ( LSG ) is the most commonly performed bariatric procedure , while Laparoscopic Adjustable Gastric B and ing ( LAGB ) has been almost ab and oned . Objectives The aim of this retrospective study was to compare 5-year results of LSG and LAGB at our Institution . Material s and Methods Prospect i ve maintained data base of our Institution was review ed to find all patients who had undergone LSG between January 2009 and December 2011 . Inclusion criteria were BMI of 40–50 kg/m2 and age of 18–60 years old . Patients with Class I and II obesity , superobese subjects , and patients with previous history of bariatric surgery were excluded . Data on sex , age , pre-operative BMI , obesity-related diseases ( diabetes , hypertension , dyslipidemia ) , and early and late complications were collected . Each subject who underwent LSG was matched one-to-one with a patient that had undergone LAGB . Outcomes were analyzed at 1 , 3 , and 5 years of follow-up . Results A total number of 122 patients were included in this study , 61 in each group . Better % EWL was observed in the LSG group at 1 , 3 , and 5 years . Both procedures induced improvements of obesity-related diseases without significant difference . In the LAGB group , ten patients underwent uneventful b and removal . In the LSG group , two patients had serious postoperative complications . Conclusion LSG achieves better % EWL than LAGB within 5 years , but comorbidities improvement is not significantly different . Severity of complication is higher after LSG . LAGB is still a good option for selected patients Background Bariatric surgery is currently the most effective treatment for morbid obesity . It provides not only substantial weight loss , but also resolution of obesity-related comorbidities . Laparoscopic sleeve gastrectomy ( LSG ) has rapidly been gaining in popularity . However , there are limited data on the reduction of obesity-related comorbidities for LSG compared to laparoscopic Roux-en-Y gastric bypass ( LRYGB ) . The aim of this study was to assess the effectiveness of laparoscopic LSG versus LRYGB for the treatment of obesity-related comorbidities . Methods A total of 558 patients who underwent either LSG or LRYGB for morbid obesity at the Westchester Medical Center between April 2008 and September 2010 were included . Data were collected prospect ively into a computerized data base and review ed for this study . Fisher ’s exact test analyses compared 30-day , 6-month , and 1-year outcomes of obesity-related comorbidities . Results A total of 558 patients were included in the analysis of obesity-related comorbidity resolution ; 200 underwent LSG and 358 underwent LRYGB . After 1 year , 86.2 % of the LSG patients had one or more comorbidities in remission compared to 83.1 % LRYGB patients ( P = 0.688 ) . With the exception of GERD ( −0.09 vs. 50 % ; P < 0.001 ) , similar comorbidity remission rates were observed between LSG and LRYGB for sleep apnea ( 91.2 vs. 82.8 % ; P = 0.338 ) , hyperlipidemia ( 63 vs. 55.8 % ; P = 0.633 ) , hypertension ( 38.8 vs. 52.9 % ; P = 0.062 ) , diabetes ( 58.6 vs. 65.5 % ; P = 0.638 ) , and musculoskeletal disease ( 66.7 vs. 79.4 % ; P = 0.472 ) . Conclusions Laparoscopic sleeve gastrectomy markedly improves most obesity-related comorbidities . Compared to LRYGB , LSG may have equal in reducing sleep apnea , hyperlipidemia , hypertension , diabetes , and musculoskeletal disease . LRYGB appears to be more effective at GERD resolution than LSG Aims /hypothesisBariatric surgery is gaining acceptance as a ‘ metabolic surgical intervention ’ for patients with type 2 diabetes . The optimal form of surgery and the mechanism of action of these procedures are much debated . We compared two bariatric procedures for obese patients with type 2 diabetes and evaluated their effects on HbA1c and glucose tolerance . Methods We performed a parallel un-blinded r and omised trial of Roux-en-Y gastric bypass ( RYGB ) vs sleeve gastrectomy ( SG ) in 41 obese patients with type 2 diabetes , who were bariatric surgery c and i date s attending the obesity clinic . HbA1c , body composition and glucose tolerance were evaluated at baseline , and at 3 and 12 months . Results Of the 41 patients , 37 completed the follow-up ( 19 RYGB , 18 SG ) . Both groups had similar baseline anthropometric and biochemical measures , and showed comparable weight loss and fat : fat-free mass ratio changes at 12 months . A similar normalisation of HbA1c levels was observed as early as 3 months post-surgery ( 6.37 ± 0.71 % vs 6.23 ± 0.69 % for RYGB vs SG respectively , p < 0.001 in both groups for baseline vs follow-up ) . Conclusions /interpretationIn this study , RYGB did not have a superior effect in comparison to SG with regard to HbA1c levels or weight loss during 12 months of follow-up . Trial registration Clinical Trials.gov NCT00667706 Funding This work was supported by grant no. 3 - 000 - 8480 from the Israel Ministry of Health Chief Scientist , the Stephen Morse Diabetes Research Foundation and by Johnson & Johnson Background : Bariatric surgery is currently the most effective treatment in morbidly obese patients , leading to durable weight loss . Objective : In this prospect i ve double blind study , we aim to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) with laparoscopic sleeve gastrectomy ( LSG ) on body weight , appetite , fasting , and postpr and ial ghrelin and peptide-YY ( PYY ) levels . Methods : After r and omization , 16 patients were assigned to LRYGBP and 16 patients to LSG . Patients were reevaluated on the 1st , 3rd , 6th , and 12th postoperative month . Blood sample s were collected after an overnight fast and in 6 patients in each group after a st and ard 420 kcal mixed meal . Results : Body weight and body mass index ( BMI ) decreased markedly ( P < 0.0001 ) and comparably after either procedure . Excess weight loss was greater after LSG at 6 months ( 55.5 % ± 7.6 % vs. 50.2 % ± 6.5 % , P = 0.04 ) and 12 months ( 69.7 % ± 14.6 % vs. 60.5 % ± 10.7 % , [ P = 0.05 ] ) . After LRYGBP fasting ghrelin levels did not change significantly compared with baseline ( P = 0.19 ) and did not decrease significantly after the test meal . On the other h and , LSG was followed by a marked reduction in fasting ghrelin levels ( P < 0.0001 ) and a significant suppression after the meal . Fasting PYY levels increased after either surgical procedure ( P ≤ 0.001 ) . Appetite decreased in both groups but to a greater extend after LSG . Conclusion : PYY levels increased similarly after either procedure . The markedly reduced ghrelin levels in addition to increased PYY levels after LSG , are associated with greater appetite suppression and excess weight loss compared with LRYGBP IMPORTANCE Short-term studies show that bariatric surgery causes remission of diabetes . The long-term outcomes for remission and diabetes-related complications are not known . OBJECTIVES To determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery . DESIGN , SETTING , AND PARTICIPANTS The Swedish Obese Subjects ( SOS ) is a prospect i ve matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden . Of patients recruited between September 1 , 1987 , and January 31 , 2001 , 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline . For the current analysis , diabetes status was determined at SOS health examinations until May 22 , 2013 . Information on diabetes complications was obtained from national health registers until December 31 , 2012 . Participation rates at the 2- , 10- , and 15-year examinations were 81 % , 58 % , and 41 % in the control group and 90 % , 76 % , and 47 % in the surgery group . For diabetes assessment , the median follow-up time was 10 years ( interquartile range [ IQR ] , 2 - 15 ) and 10 years ( IQR , 10 - 15 ) in the control and surgery groups , respectively . For diabetes complications , the median follow-up time was 17.6 years ( IQR , 14.2 - 19.8 ) and 18.1 years ( IQR , 15.2 - 21.1 ) in the control and surgery groups , respectively . INTERVENTIONS Adjustable or nonadjustable b and ing ( n = 61 ) , vertical b and ed gastroplasty ( n = 227 ) , or gastric bypass ( n = 55 ) procedures were performed in the surgery group , and usual obesity and diabetes care was provided to the control group . MAIN OUTCOMES AND MEASURES Diabetes remission , relapse , and diabetes complications . Remission was defined as blood glucose < 110 mg/dL and no diabetes medication . RESULTS The diabetes remission rate 2 years after surgery was 16.4 % ( 95 % CI , 11.7%-22.2 % ; 34/207 ) for control patients and 72.3 % ( 95 % CI , 66.9%-77.2 % ; 219/303 ) for bariatric surgery patients ( odds ratio [ OR ] , 13.3 ; 95 % CI , 8.5 - 20.7 ; P < .001 ) . At 15 years , the diabetes remission rates decreased to 6.5 % ( 4/62 ) for control patients and to 30.4 % ( 35/115 ) for bariatric surgery patients ( OR , 6.3 ; 95 % CI , 2.1 - 18.9 ; P < .001 ) . With long-term follow-up , the cumulative incidence of microvascular complications was 41.8 per 1000 person-years ( 95 % CI , 35.3 - 49.5 ) for control patients and 20.6 per 1000 person-years ( 95 % CI , 17.0 - 24.9 ) in the surgery group ( hazard ratio [ HR ] , 0.44 ; 95 % CI , 0.34 - 0.56 ; P < .001 ) . Macrovascular complications were observed in 44.2 per 1000 person-years ( 95 % CI , 37.5 - 52.1 ) in control patients and 31.7 per 1000 person-years ( 95 % CI , 27.0 - 37.2 ) for the surgical group ( HR , 0.68 ; 95 % CI , 0.54 - 0.85 ; P = .001 ) . CONCLUSIONS AND RELEVANCE In this very long-term follow-up observational study of obese patients with type 2 diabetes , bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care . These findings require confirmation in r and omized trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01479452 Objective : Laparoscopic sleeve gastrectomy ( LSG ) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass ( LRYGB ) . We present the 3-year interim results of the 5-year prospect i ve , r and omized trial comparing the 2 procedures ( Swiss Multicentre Bypass Or Sleeve Study ; SM-BOSS ) . Methods : Initially , 217 patients ( LSG , n = 107 ; LRYGB , n = 110 ) were r and omized to receive either LSG or LRYGB at 4 bariatric centers in Switzerl and . Mean body mass index of all patients was 44 ± 11 kg/m2 , mean age was 43 ± 5.3 years , and 72 % of patients were female . Minimal follow-up was 3 years with a rate of 97 % . Both groups were compared for weight loss , comorbidities , quality of life , and complications . Results : Excessive body mass index loss was similar between LSG and LRYGB at each time point ( 1 year : 72.3 ± 21.9 % vs. 76.6 ± 20.9 % , P = 0.139 ; 2 years : 74.7 ± 29.8 % vs. 77.7 ± 30 % , P = 0.513 ; 3 years : 70.9 ± 23.8 % vs. 73.8 ± 23.3 % , P = 0.316 ) . At this interim 3-year time point , comorbidities were significantly reduced and comparable after both procedures except for gastro-esophageal reflux disease and dyslipidemia , which were more successfully treated by LRYGB . Quality of life increased significantly in both groups after 1 , 2 , and 3 years postsurgery . There was no statistically significant difference in number of complications treated by reoperation ( LSG , n = 9 ; LRYGB , n = 16 , P = 0.15 ) or number of complications treated conservatively . Conclusions : In this trial , LSG and LRYGB are equally efficient regarding weight loss , quality of life , and complications up to 3 years postsurgery . Improvement of comorbidities is similar except for gastro-esophageal reflux disease and dyslipidemia that appear to be more successfully treated by LRYGB Background There are very few r and omised , blinded trials comparing laparoscopic sleeve gastrectomy ( LSG ) versus laparoscopic Roux-en-Y gastric bypass ( LRYGB ) in achieving remission of type 2 diabetes ( T2D ) , particularly silastic ring (SR)-LRYGB . We compared the effectiveness of ( LSG ) versus SR-LRYGB among patients with T2D and morbid obesity . Methods Prospect i ve , r and omised , parallel , 2-arm , blinded clinical trial conducted in a single Auckl and ( New Zeal and ) centre . Eligible patients aged 20–55 years , T2D of at least 6 months duration and BMI 35–65 kg/m2 were r and omised 1:1 to LSG ( n = 58 ) or SR-LRYGB ( n = 56 ) using r and om number codes disclosed after anaesthesia induction . Primary outcome was T2D remission defined by different HbA1c thresholds at 1 year . Secondary outcomes included weight loss , quality of life , anxiety and depressive symptoms , post-operative complications and mortality . Results Mean ± st and ard deviation ( SD ) pre-operative BMI was 42.5 ± 6.2 kg/m2 , HbA1c 63 ± 16 mmol/mol ( 30 % insulin-treated , 28 % had diabetes duration over 10 years ) . Proportions achieving HbA1c ≤ 38 mmol/mol , < 42 mmol/mol , < 48 mmol/mol and < 53 mmol/mol without diabetes medication at 1 year in SR-LRYGB vs LSG were 38 vs 43 % ( p = 0.56 ) , 52 vs 49 % ( p = 0.85 ) , 75 vs 72 % ( p = 0.83 ) and 80 vs 77 % ( p = 0.82 ) , respectively . Mean ± SD % total weight loss at 1 year was greater after SR-LRYGB than LSG : 32.2 ± 7.7 vs 27.1 ± 7.5 % , respectively ( p < 0.001 ) . Gastrointestinal complications were more frequent after SR-LRYGB ( including 3 ulcers , 1 anastomotic leak , 1 abdominal bleeding ) . Quality of life and depression symptoms improved significantly in both groups . Conclusion Despite significantly greater weight loss after SR-LRYGB , there was similar T2D remission and psychosocial improvement after LSG and SR-LRYGB at 1 year . Trial Registration Prospect ively registered at Australia and New Zeal and Clinical Trials Register ( ACTRN 12611000751976 ) and retrospectively registered at Clinical Trials ( NCT1486680 ) Objective This report documents that the gastric bypass operation provides long-term control for obesity and diabetes . Summary Background Data Obesity and diabetes , both notoriously resistant to medical therapy , continue to be two of our most common and serious diseases . Methods Over the last 14 years , 608 morbidly obese patients underwent gastric bypass , an operation that restricts caloric intake by ( 1 ) reducing the functional stomach to approximately 30 mL , ( 2 ) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet , and ( 3 ) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy . Even though many of the patients were seriously ill , the operation was performed with a perioperative mortality and complication rate of 1.5 % and 8.5 % , respectively . Seventeen of the 608 patients ( <3 % ) were lost to follow-up . Results Gastric bypass provides durable weight control . Weights fell from a preoperative mean of 304.4 lb ( range , 198 to 615 lb ) to 192.2 lb ( range , 104 to 466 ) by 1 year and were maintained at 205.4 lb ( range , 107 to 512 lb ) at 5 years , 206.5 lb ( 130 to 388 lb ) at 10 years , and 204.7 lb ( 158 to 270 lb ) at 14 years . The operation provides long-term control of non-insulin-dependent diabetes mellitus ( NIDDM ) . In those patients with adequate follow-up , 121 of 146 patients ( 82.9 % ) with NIDDM and 150 of 152 patients ( 98.7 % ) with glucose impairment maintained normal levels of plasma glucose , glycosylated hemoglobin , and insulin . These antidiabetic effects appear to be due primarily to a reduction in caloric intake , suggesting that insulin resistance is a secondary protective effect rather than the initial lesion . In addition to the control of weight and NIDDM , gastric bypass also corrected or alleviated a number of other comorbidities of obesity , including hypertension , sleep apnea , cardiopulmonary failure , arthritis , and infertility Objective : To evaluate the physiologic importance of the satiety gut hormones . Background : Controversy surrounds the physiologic role of gut hormones in the control of appetite . Bariatric surgery remains the most effective treatment option for obesity , and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass . Methods : We correlated peptide YY ( PYY ) and glucagon-like peptide 1 ( GLP-1 ) changes within the first week after gastric bypass with changes in appetite . We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass . Finally , we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake . Results : Postpr and ial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass ( P < 0.05 ) . Changes in appetite are evident within days after gastric bypass surgery ( P < 0.05 ) , and unlike other operations , the reduced appetite continues . However , in patients with poor weight loss after gastric bypass associated with increased appetite , the postpr and ial PYY and GLP-1 responses are attenuated compared with patients with good weight loss ( P < 0.05 ) . Inhibiting gut hormone responses , including PYY and GLP-1 after gastric bypass , results in return of appetite and increased food intake ( P < 0.05 ) . Conclusion : The attenuated appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations , and appetite returns when the release of gut hormones is inhibited . The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implication s for the treatment of obesity BACKGROUND Laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and laparoscopic sleeve gastrectomy ( LSG ) are associated with glucose metabolism improvement although data on insulin resistance remission rates after these procedures are lacking . AIMS Primary aim was to compare insulin resistance remission rates achieved after LRYGB and LSG , using population -specific HOMA-IR cut-off points . Secondary objectives were to analyze factors associated with type 2 diabetes mellitus ( T2DM ) complete remission according to the new American Diabetes Association criteria and to examine changes in HOMA-B during follow-up . METHODS Non-r and omized , prospect i ve cohort study of patients undergoing LRYGB or LSG with a minimal follow-up of 24 months . Patients on insulin therapy were excluded . RESULTS At baseline , 56 ( 48.7 % ) of the 115 LRYGB group and 48 ( 61.5 % ) of the 78 LSG group had insulin resistance , and 29 ( 25.2 % ) and 20 ( 25.6 % ) T2DM , respectively . No differences were detected in insulin resistance remission rate ( 92.9 % LRYGB and 87.5 % LSG , p = 0.355 ) nor in T2DM complete remission at 2 years ( 62.1 vs 60 % respectively , p = 0.992 ) . Factors independently associated with T2DM complete remission were diabetes treatment and a greater decrease in 3-month HOMA-IR index . The HOMA-B index showed a progressive decline during follow-up . CONCLUSION Both surgical techniques are equally effective in achieving insulin resistance normalization in the majority of severely obese patients . Three-month HOMA-IR reduction after surgery was the main predictor of T2DM complete remission Type 2 diabetes ( T2D ) remission after bariatric procedures has been highlighted in many retrospective and some recent prospect i ve studies . However , in the most recent prospect i ve study , more than 50 % of patients did not reach T2D remission at 1 year . Our aim was to identify baseline positive predictors for T2D remission at 1 year after bariatric surgery and to build a preoperative predictive score . We analysed the data concerning 161 obese operated on between June 2007 and December 2010 . Among them , 46 were diabetic and were included in the study —11 laparoscopic adjustable gastric b and ing ( LAGB ) , 26 Roux-en-Y gastric bypass ( RYGB ) and 9 sleeve gastrectomy ( SG ) . We compared anthropometric and metabolic features during 1 year of follow-up . A receiver operating characteristic analysis was performed to predict T2D remission . RYGB and SG were similarly efficient for body weight loss and more efficient than LAGB ; 62.8 % of patients presented with T2DM remission at 1 year , with no significant difference according to the surgical procedure . A 1-year body mass index ( BMI ) < 35 kg m−2 was predictive of T2DM remission whatever the procedure . The preoperative predictive factors of diabetes remission were baseline BMI ≤50 kg m−2 , duration of type 2 diabetes ≤4 years , glycated haemoglobin ≤7.1 % , fasting glucose < 1.14 g/l and absence of insulin therapy . A short duration of diabetes and good preoperative glycaemic control increase the rate of T2DM remission 1 year after surgery . Preoperative metabolic data could be of greater importance than the choice of bariatric procedure BACKGROUND Although laparoscopic sleeve gastrectomy ( LSG ) was initially described as the first step of a 2-stage procedure for high-risk patients requiring laparoscopic Roux-en-Y gastric bypass ( LRYGB ) , it is now being used as a single-stage procedure . Experience with laparoscopic bariatric surgery is growing , such that LRYGB is increasingly feasible for patients with body mass index ( BMI ) ≥ 50 kg/m² . Nevertheless , outcomes for such category of patients following LSG and LRYGB are lacking . OBJECTIVE To compare weight loss and changes in obesity related co-morbidities at one year following LSG with LRYGB in patients with BMI ≥ 50 kg/m² . SETTING S The prospect i ve data base of a single surgery university center was queried for clinical and other relevant data . METHODS From January 2004 to January 2013 , 74 and 285 patients underwent LSG or LRYGB with a BMI ≥ 50 kg/m² . At one year , rate of follow-up was 92.8 % . Success of surgery was defined as % of excess weight loss (%EWL)≥ 50 % at one year . Logistic regression was used to compute odds ratio ( OR ) to evaluate the success at one year of surgery . RESULTS LSG ( N = 74 ) and LGBP ( N = 285 ) groups did not differ for initial BMI ( 57.2 ± 7.1 versus 56.7 ± 5.5 kg/m² ; P = .52 ) , % of female ( 64.6 % versus 73.7 % , P = .13 ) or major adverse postoperative events ( 5.7 % versus 6.7 % ; P = .85 ) . At one year , the mean percentage of weight loss ( % ) ( 22.0 ± 7.6 versus 30.3 ± 7.4 ; P < .0001 ) and percentage of excess weight loss ( % ) ( 40.2 ± 15.2 versus 55.0 ± 14.6 ; P < .0001 ) and rates of remission of diabetes ( 47.5 % versus 70.7 % ; P = .01 ) were greater in the LGBP than LSG group . In multivariate analyses ( OR ) , LSG was an independent factor of failure of weight loss ( .12 ; P < .0001 ) CONCLUSION : After 1 year of follow-up in patients with a BMI ≥ 50 kg/m² , LRYGB provides better weight loss and resolution in diabetes than LSG with similar postoperative morbidity . Further long-term studies are needed to confirm these results The laparoscopic Roux Y gastric bypass ( LRYGB ) and the laparoscopic gastric sleeve resection are frequently used methods for the treatment of morbid obesity . Quality of life , weight loss and improvement of the co-morbidities were examined . Match pair analysis of the prospect ively collected data base of the 47 gastric bypass and 47 gastric sleeve resection patients operated on in our hospital was performed . The quality of life parameters were measured with two st and ard question naires ( SF 36 and Moorehead – Ardelt II ) . The mean preoperative and postoperative BMI was in gastric bypass group 46.1 and 28.1 kg/m2 ( mean follow-up : 15.7 months ) and in gastric sleeve group 50.3 and 33.5 kg/m2 ( mean follow-up : 38.3 months ) . The SF 36 question naire yielded a mean total score of 671 for the bypass and 611 for the sleeve resection patients ( p = 0.06 ) . The Moorehead – Ardelt II test signed a total score of 2.09 for gastric bypass versus 1.70 for gastric sleeve patients ( p = 0.13 ) . Ninety percent of the diabetes was resolved in the bypass and 55 % in the sleeve resection group . Seventy-three percent of the hypertension patients needed no more antihypertensive treatment after gastric bypass and 30 % after sleeve resection . Ninety-two percent of the gastro-oesophageal reflux were resolved in the bypass group and 25 % in the sleeve ( with 33 % progression ) group . Ninety-four percent of the patients were satisfied with the result after gastric bypass and 90 % after sleeve resection . The patients have scored a high level of satisfaction in both study groups . The gastric bypass is associated with a trend toward a better quality of life without reaching statistical significance , pronounced loss of weight and more remarkable positive effects on the co-morbidities comparing with the gastric sleeve resection Gastric bypass ( GBP ) has proved its efficacy 30 years ago in the management of diabetes mellitus ( T2DM ) for severe obese patients . More recently , interesting results have been published after sleeve gastrectomy ( SG ) in the same indication . Between 2005 and 2008 , three bariatric centers have prospect ively collected the data of T2DM patients treated by laparoscopic gastric bypass ( LGBP ) or laparoscopic sleeve gastrectomy ( LSG ) . Effects on hemoglobin A1c ( HbA1c ) , pharmacological treatment and excess weight loss after 1 year of surgery have been analyzed . All patients ( 35 LGBP and 33 LSG ) were treated with oral anti-diabetics ( OAD ) or insulin before surgery ( 32 OAD and three insulin in LGBP group and 27 OAD and six insulin in LSG group ) . The average body mass index ( BMI ) in the LGBP group was 47.9 and 50.6 kg/m² in the LSG group . At 1 year after surgery , the average HbA1c lost was 2,537 in the GBP group and 2,175 in the SG group . T2DM had resolved ( withdrawal of pharmacological treatment ) in 60 % of the LGBP group and 75.8 % of the LSG group . Reduced use of pharmacological therapy was noted in 31.42 % of the LGBP group and 15.15 % of the LSG group . Percentage excess weight loss and BMI lost were 56.35 % and 29.75 % in the LGBP group and 60.11 % and 29.80 % in the LSG group , respectively . During short-term follow-up , the impact on regulation of HbA1c blood level of LGBP or LSG is important . At 1 year after surgery , LSG seems to be as effective as LGBP for the management of T2DM in severely obese patients Importance Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass . Objective To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity . Design , Setting , and Participants The Sleeve vs Bypass ( SLEEVEPASS ) multicenter , multisurgeon , open-label , r and omized clinical equivalence trial was conducted from March 2008 until June 2010 in Finl and . The trial enrolled 240 morbidly obese patients aged 18 to 60 years , who were r and omly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period ( last follow-up , October 14 , 2015 ) . Interventions Laparoscopic sleeve gastrectomy ( n = 121 ) or laparoscopic Roux-en-Y gastric bypass ( n = 119 ) . Main Outcomes and Measures The primary end point was weight loss evaluated by percentage excess weight loss . Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were −9 % to + 9 % excess weight loss . Secondary end points included resolution of comorbidities , improvement of quality of life ( QOL ) , all adverse events ( overall morbidity ) , and mortality . Results Among 240 patients r and omized ( mean age , 48 [ SD , 9 ] years ; mean baseline body mass index , 45.9 , [ SD , 6.0 ] ; 69.6 % women ) , 80.4 % completed the 5-year follow-up . At baseline , 42.1 % had type 2 diabetes , 34.6 % dyslipidemia , and 70.8 % hypertension . The estimated mean percentage excess weight loss at 5 years was 49 % ( 95 % CI , 45%-52 % ) after sleeve gastrectomy and 57 % ( 95 % CI , 53%-61 % ) after gastric bypass ( difference , 8.2 percentage units [ 95 % CI , 3.2%-13.2 % ] , higher in the gastric bypass group ) and did not meet criteria for equivalence . Complete or partial remission of type 2 diabetes was seen in 37 % ( n = 15/41 ) after sleeve gastrectomy and in 45 % ( n = 18/40 ) after gastric bypass ( P > .99 ) . Medication for dyslipidemia was discontinued in 47 % ( n = 14/30 ) after sleeve gastrectomy and 60 % ( n = 24/40 ) after gastric bypass ( P = .15 ) and for hypertension in 29 % ( n = 20/68 ) and 51 % ( n = 37/73 ) ( P = .02 ) , respectively . There was no statistically significant difference in QOL between groups ( P = .85 ) and no treatment-related mortality . At 5 years the overall morbidity rate was 19 % ( n = 23 ) for sleeve gastrectomy and 26 % ( n = 31 ) for gastric bypass ( P = .19 ) . Conclusions and Relevance Among patients with morbid obesity , use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years . Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years , the difference was not statistically significant , based on the prespecified equivalence margins . Trial Registration clinical trials.gov Identifier : BACKGROUND Roux-en-Y gastric bypass ( RYGBP ) and sleeve gastrectomy ( SG ) have been associated with a high remission rate of type 2 diabetes mellitus ( T2DM ) . However , whether such remission is associated with full restoration of postpr and ial glucose profile and /or the potentially nonrestored glycemic profile is associated with altered beta cell function , and relapse of T2DM over time is unknown . METHODS Cross-sectional studies comparing ( 1 ) glucose and proinsulin/insulin response to a st and ardized liquid mixed meal ( SLMM ) challenge ( n = 31 ) , ( 2 ) glucose response in normal living conditions assessed using continuous glucose monitoring ( CGM ) ( n = 16 ) , and prospect i ve observational study comparing ( 3 ) rates of relapse of T2DM after surgery ( n = 232 ) in subjects with remission of T2DM ensuing RYGBP or SG . RESULTS In RYGB individuals , SLMM elicited faster and sharper rise in plasma glucose compared with SG , with 88.2 % and 42.9 % of the study subjects presenting respectively a peak glucose more than 180 mg/dL ( all , P < 0.05 ) . During CGM , average percent time in hyperglycemic and hypoglycemic range was larger in RYGBP ( respectively , 4.6 % and 12.7 % ) compared with SG subjects ( respectively , 0.4 % and 3.2 % ; both P < 0.05 ) . However , ( 1 ) no differences were found in fasting or stimulated proinsulin/insulin ratio , and ( 2 ) higher rates of T2DM relapse were observed after SG ( hazard ratio : 2.339 ; P = 0.034 ) . CONCLUSIONS Remission of T2DM after RYGBP and SG is associated with distinct glycemic profiles . However , longer time spent in hyperglycemia and in hypoglycemia after RYGBP compared with SG is not associated with persistence of altered beta cell function or higher rates of relapse of T2DM over time |
1,145 | 24,895,299 | Aloe vera , either alone or in combination with routine treatment , was more effective than routine treatment alone for improving the symptoms of phlebitis including shortening the time of elimination of red swelling symptoms , time of pain relief at the location of the infusion vein and time of resolution of phlebitis .
There is no strong evidence for preventing or treating infusion phlebitis with external application of Aloe vera . | BACKGROUND Up to 80 % of hospitalised patients receive intravenous therapy at some point during their admission .
About 20 % to 70 % of patients receiving intravenous therapy develop phlebitis .
Infusion phlebitis has become one of the most common complications in patients with intravenous therapy .
However , the effects of routine treatments such as external application of 75 % alcohol or 50 % to 75 % magnesium sulphate ( MgSO4 ) are unsatisfactory .
Therefore , there is an urgent need to develop new methods to prevent and alleviate infusion phlebitis .
OBJECTIVES To systematic ally assess the effects of external application of Aloe vera for the prevention and treatment of infusion phlebitis associated with the presence of an intravenous access device . | Complications of intravenous therapy with steel needles and small-bore Teflon catheters were compared in a r and omized study of 954 cannula insertions . Cannulas were inserted and cared for by an intravenous team following a st and ard protocol . There were no cases of cannula-related septicemia and only one case of local infection , a cellulitis in the group in which Teflon catheters were used . There was a low incidence of positive semiquantitative cannula cultures in both treatment groups ( steel needles 1.5 percent , Teflon catheters 1.4 percent ) . The risk of phlebitis was significantly greater with Teflon catheters ( 18.8 percent with Teflon catheters , 8.8 percent with steel needles , adjusted odds ratio 1.87 ) . Steel needles were significantly associated with infiltration ( 17.9 percent with Teflon catheters , 40.1 percent with steel needles , adjusted odds ratio 0.39 ) . The over-all rate of complications was significantly greater for the group in which steel needles were used ( 53.8 versus 64.0 percent , adjusted odds ratio 0.72 ) , principally due to the increased risk of infiltration with steel needles . Analysis of the per day risk of infiltration and phlebitis revealed that these relationships were present for each day the cannulas remained in place . We conclude ( 1 ) that steel needles and small-bore Teflon catheters can both be used with low risk of infection and ( 2 ) that Teflon catheters more frequently cause phlebitis , whereas steel needles infiltrate more readily OBJECTIVE An examination glove that delivers aloe vera ( AV ) gel to the gloved h and was studied in 30 adult females with bilateral occupational dry skin with or without irritant contact dermatitis ( with or without erythema , fissures , and excoriations ) . METHODS All participants were factory assembly-line workers with repeated superficial skin trauma who attributed their dry , irritated , emollient-dependent skin to a common cause ( occupational exposure ) . Participants were sequentially enrolled ( after written informed consent , n = 29 evaluable participants ) into an open , contralateral comparison study to evaluate efficacy of AV glove use 8 h/day to one h and versus no use to the opposite h and for 30 days , followed by 30 days rest , followed by 10 days of repeated use . Participant 's dorsal h and s were documented by st and ardized photos at baseline , during , and at the end of study . RESULTS Unblinded investigator baseline assessment rated dry skin as mild to moderate ( n = 27 ) , or moderate to severe ( n = 2 ) . Mean time to noticeable improvement for the AV glove h and was 3.5 days ( range : 2 - 6 days ) whereas marked improvement was 10.4 days ( range : 7 - 17 days ) for the AV glove h and . No improvement was detected for nonglove h and s. Blinded photo assessment was rated independently by dermatology research staff . End-of- study mean global assessment of AV glove h and s versus nonglove h and s was 1.3 for AV glove h and ( 0 = no change , 1 = good [ 10%-89 % global improvement ] , 2 = marked improvement [ 90%-100 % global improvement ] ) versus 0 for nonglove h and ( P < .0001 ) . Mean global end-of- study assessment s by the participants = 2.0 for AV glove h and versus 0 for nonglove h and . CONCLUSION Dry-coated AV gloves that provide for gradual delivery of AV gel to skin produced a uniformly positive outcome of improved skin integrity , decreased appearance of fine wrinkling , and decreased erythema in the management of occupational dry skin and irritant contact dermatitis OBJECTIVE To identify risk factors for infusion-related phlebitis with peripheral intravenous catheters . DESIGN A r and omized trial of two catheter material s , with consideration of 21 potential risk factors . SETTING A university hospital . PATIENTS Hospitalized adults without granulocytopenia who received a peripheral intravenous catheter . INTERVENTIONS House officers or ward nurses inserted the catheters , and each insertion was r and omized to a catheter made of tetrafluoroethylene-hexafluoropropylene ( FEP-Teflon ) or a novel polyetherurethane without leachable additives ( PEU-Vialon ) . MEASUREMENTS Research nurses scored insertion sites each day for inflammation and cultured catheters at removal . RESULTS The Kaplan-Meier risk for phlebitis exceeded 50 % by day 4 after catheterization . intravenous antibiotics ( relative risk , 2.00 ) , female sex ( relative risk , 1.88 ) , prolonged ( greater than 48 hours ) catheterization ( relative risk , 1.79 ) , and catheter material ( PEU-Vialon : FEP-Teflon ) ( relative risk , 0.73 ) strongly predicted phlebitis in a Cox proportional hazards model ( each , P less than 0.003 ) . The best-fit model for severe phlebitis identified the same predictors plus catheter-related infection ( relative risk , 6.19 ) , phlebitis with a previous catheter ( relative risk , 1.54 ) , and anatomic site ( h and : forearm , relative risk , 0.71 ; wrist : forearm , relative risk , 0.60 ) . The low incidence of local catheter-related infection was comparable with the two catheter material s ( 5.4 % [ 95 % CI , 3.8 % to 7.6 % ] and 6.9 % [ CI , 4.9 % to 9.6 % ] ) ; none of the 1054 catheters prospect ively studied caused bacteremia . CONCLUSIONS Multiple factors , including the infusate and the duration of cannulation , contribute to the development of infusion-related phlebitis . The use of peripheral intravenous catheters made of PEU-Vialon appears to pose the same risk for catheter-related infection as the use of catheters made of FEP-Teflon , and PEU-Vialon can permit longer cannulation with less risk for phlebitis . The risk for catheter-related bacteremia with FEP-Teflon and PEU-Vialon catheters is sufficiently low that it no longer seems justifiable to recommend the use of small steel needles for most peripheral intravenous therapy STUDY OBJECTIVES To prospect ively assess the relative risk for phlebitis in a series of consecutive patients with pneumonia and to identify risk factors that predict an increased risk for phlebitis . SETTING Internal medicine department of a tertiary teaching hospital . PATIENTS Seven hundred sixty-six consecutive patients with acute pneumonia receiving IV therapy . INTERVENTIONS Only the first catheter was taken into account . There were 308 short lines ( a 51-mm , 18-gauge Teflon catheter ) ; 307 midsized lines ( a 28-cm , 16-gauge polyvinyl chloride catheter ) ; and 151 long lines ( 71-cm , 14-gauge plain polyurethane catheter ) . Eighteen variables were prospect ively evaluated in an open , nonr and omized study for their contribution to the occurrence of phlebitis . RESULTS The overall phlebitis rate was 39 % . Phlebitis developed in 53 % of patients with short lines , in 41 % of patients with midsized lines , and in 10 % of patients with long lines , and these catheters remained in place an average ( + /- SD ) of 3.0+/-2.4 days , 4.6+/-3.4 days , and 7.8+/-6.6 days , respectively . The variables that influenced the development of phlebitis , as determined by multivariate analysis , were the following : type of catheter ; blood hemoglobin levels ; and IV therapy with either corticosteroids or erythromycin . CONCLUSIONS According to our data , when the use of a catheter is expected to be required for < or = 36 h , a short line can be used . If a longer duration is expected , a longer line is warranted . Ours is the first study in which the relationship between blood hemoglobin levels and phlebitis has been reported . Because the use of intravascular devices is increasingly common , a more complete knowledge of the factors that influence their acceptance has become essential Vinorelbine is a moderate vesicant that is well known to cause local venous toxicity such as drug induced-phlebitis . We conducted a prospect i ve r and omized trial to determine whether a 1-min bolus injection ( 1 min bolus ) of vinorelbine reduced the incidence of local venous toxicity compared with a 6-min drip infusion ( 6 min infusion ) . Non-small cell lung cancer patients who were to receive chemotherapy containing vinorelbine were r and omly assigned to receive either 6 min infusion or 1 min bolus of the drug . All infusions were administered through a peripheral vein . Local venous toxicity was evaluated at each infusion up to two cycles . Eighty-three patients were r and omized into the study and 81 of them assessable for analysis . One hundred thirty-eight infusions to 40 patients in 6 min infusion and 135 infusions to 41 patients in 1 min bolus were delivered . Vinorelbine induced-local venous toxicity was observed in 33 % of patients in 6 min infusion and 24 % in 1 min bolus . There was no statistically significant difference between the two arms ( P=0.41 ) . The incidence of local venous toxicity per infusions was 16 % ( 22 of 138 infusions ) in 6 min infusion and 11 % ( 15 of 135 infusions ) in 1 min bolus ( P=0.47 ) . No severe local venous toxicity was seen in either arm . In this study , the administration of in 1 min bolus of vinorelbine did not significantly reduce the incidence of local venous toxicity compared with 6 min infusion . Further studies for the control of local venous toxicity of vinorelbine are warranted Background : The herbal preparation , aloe vera , has been cl aim ed to have anti‐inflammatory effects and , despite a lack of evidence of its therapeutic efficacy , is widely used by patients with inflammatory bowel disease As part of a st and ardized , multi-hospital prospect i ve surveillance system for nosocomial infections in Rhode Isl and , an analysis was undertaken in March 1980-February 1982 to determine the interplay of factors that contribute to the risk of phlebitis in peripheral , non-steel , non-butterfly intravenous catheters . The authors studied 3094 patients with 5161 total episodes of peripheral intravenous catheters from day of admission until day of discharge . The overall rate of phlebitis was 2.3 % ( 118 episodes ) , and the rate of intravenous catheter-associated bacteremia was 0.08 % ( 1 definite episode , 3 possible episodes ) . Factors significantly associated with the occurrence of phlebitis were : underlying risk for any nosocomial infection , duration of the catheter episode , chronological order of the episode and an interaction between the latter two variables . Analysis of day-specific risk of phlebitis indicated that , for patients with low risk diagnoses , initial peripheral intravenous catheters might be left in place with relative safety for up to 96 hours . Over this time period , the day-specific risk for such patients ranged between 0.8 % and 1.4 % , exclusive of the first day . In all other circumstances , the current recommendation of 48 - 72 hours seems appropriate |
1,146 | 28,623,461 | Test specific analyses indicated that verbally-mediated tasks including digit span , verbal fluency , and list learning were not affected by videoconference administration . | The purpose of the current systematic review and meta- analysis was to assess the effect of videoconference administration on adult neurocognitive tests .
We investigated whether the scores acquired during a videoconference administration were different from those acquired during on-site administration . | As the population of older Latinos in the U.S. increases , availability of culturally adapted geriatric psychiatry services is becoming a growing concern . This issue is exacerbated for rural Latino population s. In this study , we assessed whether neurocognitive assessment via telepsychiatry ( TP ) using a Spanish- language battery would be comparable to in-person ( IP ) testing using the same battery in a sample of Spanish-speaking older adults in a rural setting . Patients ( N = 22 ) received IP and TP testing 2 weeks apart . The order of IP and TP test administrations in individual subjects was determined r and omly . Comparison of scores indicated that there were no significant differences between IP and TP test performance though both groups scored non-significantly higher at the second visit . This study demonstrates feasibility and utility of neurocognitive testing in Spanish using TP among older rural Latinos Background It is possible that cross-over studies included in current systematic review s are being inadequately assessed , because the current risk of bias tools do not consider possible biases specific to cross-over design . We performed this study to evaluate whether this was being done in cross-over studies included in Cochrane Systematic Review s ( CSRs ) . Methods We search ed the Cochrane Library ( up to 2013 issue 5 ) for CSRs that included at least one cross-over trial . Two authors independently undertook the study selection and data extraction . A r and om sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane h and book . In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane h and book . Results We identified 688 CSRs that included one or more cross-over studies . We chose a r and om sample of 60 CSRs and these included 139 cross-over studies . None of these CSRs undertook a risk of bias assessment specific for cross-over studies . In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs . When we reassessed the risk of bias , including the 3 items specific to cross-over trials , of these 139 studies , a low risk of bias was judged for appropriate cross-over design in 110(79 % ) , carry-over effects in 48(34 % ) and for reporting data in all stages of the trial in 114(82 % ) . Assessment of biases in cross-over trials could affect the GRADE assessment of a review ’s findings . Conclusion The current Cochrane risk of bias tool is not adequate to assess cross-over studies . Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs . A proposed check list for the evaluation of cross-over trials is provided Accurate underst and ing of practice characteristics , performance stability , and error on neuropsychological tests is essential to both valid clinical assessment and maximization of signal detection for clinical trials of cognitive enhancing drugs . We examined practice effects in 28 healthy adults . As part of a larger study using donepezil and simulating a Phase I trial , participants were r and omized into : placebo , no-treatment and donepezil . Donepezil results are presented elsewhere . Neuropsychological tests were administered in a fixed order for 6 weeks , with alternate forms available for most tests . Despite alternate forms , ANOVAs revealed significant improvements for the pooled control group ( placebo and no-treatment ) on all tests except Letter Number Sequencing and Trails B. Learning occurred principally in the first three to four sessions . PASAT and Stroop interference showed the greatest learning . Thus , serial assessment with alternate forms may attenuate retest effects on some tests , but continued learning occurs on novel tests or those in which an advantageous test-taking strategy can be identified . Alternate forms and baseline practice sessions may help control early , rapid improvements in clinical trials Objectives : To compare in-person versus telehealth ( TH ) assessment of discourse ability in adults with chronic traumatic brain injury ( TBI ) . Design : Repeated- measures design with r and om order of conditions . Participants : Twenty adults with moderate-to-severe TBI . Method : Participants completed conversation , picture description , story-generation , and procedural description tasks . Sessions were video-recorded and transcribed . Measures : Measures of productivity and quality of discourse . Results : Significant differences between conditions were not detected in this sample , and feedback from participants was positive . Conclusions : These preliminary results support the use of TH for the assessment of discourse ability in adults with TBI , at least for individuals with sufficient cognitive skills to follow TH procedures OBJECTIVE Combat veterans returning to society with impairing mental health conditions such as PTSD and major depression ( MD ) report significant barriers to care related to aspects of traditional psychotherapy service delivery ( e.g. , stigma , travel time , and cost ) . Hence , alternate treatment delivery methods are needed . Home-based telehealth ( HBT ) is one such option ; however , this delivery mode has not been compared to in person , clinic-based care for PTSD in adequately powered trials . The present study was design ed to compare relative noninferiority of evidence -based psychotherapies for PTSD and MD , specifically Behavioral Activation and Therapeutic Exposure ( BA-TE ) , when delivered via HBT versus in person , in clinic delivery . METHOD A repeated measures ( i.e. , baseline , posttreatment , 3- , 6-month follow-up ) r and omized controlled design powered for noninferiority analyses was used to compare PTSD and MD symptom improvement in response to BA-TE delivered via HBT versus in person , in clinic conditions . Participants were 232 veterans diagnosed with full criteria or predefined subthreshold PTSD . RESULTS PTSD and MD symptom improvement following BA-TE delivered by HBT was comparable to that of BA-TE delivered in person at posttreatment and at 3- and 12-month follow-up . CONCLUSION Evidence -based psychotherapy for PTSD and depression can be safely and effectively delivered via HBT with clinical outcomes paralleling those of clinic-based care delivered in person . HBT , thereby , addresses barriers to care related to both logistics and stigma OBJECTIVE This study aims to assess the current utilisation of a real-time teleophthalmology service for rural Western Australia ( WA ) . DESIGN Service evaluation by prospect i ve audit . SETTING Includes general practice s , optometrists , hospitals in rural WA and the Lions Eye Institute in Perth . PARTICIPANTS Eighty-five patients from rural WA participating . INTERVENTIONS Video consultation ( VC ) with a general ophthalmologist . MAIN OUTCOME MEASURES Number of referring practitioners and their locations , software and imaging equipment used as well as the presentation , working diagnosis and follow-up plan for each consultation . RESULTS Eighty-five participants took part in a total of 100 VCs in the 5-month data collection period . There were 49 men ( 58 % ) ; age range 7 - 92 years ; 31 identified as Indigenous Australian ( 37 % ) . Participants were referred by optometrists ( 59 % ) , hospital district medical officers ( 23 % ) and GPs ( 18 % ) . Karratha ( 41 % ) , Albany ( 20 % ) and Broome ( 14 % ) were the main VC locations . There were 31 different eye conditions managed ; red eye , acute vision loss , known glaucoma and abnormal retinal photographs were the main presentations . Skype was the commonly used software ( 71 % ) . Images were provided in 63 % of all VCs . The main equipment used included digital retinal cameras ( 56 % ) , smartphones ( 25 % ) and digital slit lamps ( 13 % ) . An outpatient appointment with the ophthalmologist was recommended following 35 VCs . CONCLUSIONS Optometrists used this service most frequently , despite a lack of financial incentive . Digital retinal cameras and smartphones were the most commonly used imaging modalities . Overall , real-time teleophthalmology was used in the management of a broad range of eye conditions and was a useful supplement to outreach ophthalmology services BACKGROUND Dementia is a common but frequently undiagnosed problem in aging . Barriers to early diagnosis include a lack of routine screening for dementia and a lack of access to specialty consultative services . We conducted a pilot study to see if telemedicine could provide reliable , accurate geriatric consultative services to evaluate patients for dementia who were residing at remote sites . METHODS This was a prospect i ve cohort study that compared the diagnostic reliability of telemedicine to an in-person examination for dementia . Eligible subjects were residents of a Washington State Veterans ' Home , age 60 years or older , with no prior diagnosis of dementia . Eligible subjects were screened for dementia using the 7-Minute Screen . Veterans who screened positive and consented to participate in the study received an in-person neuropsychiatric evaluation at baseline , and then both telemedicine and in-person examinations for dementia conducted by experienced geriatric psychiatrists . The accuracy of the telemedicine diagnosis was estimated by comparing it to the diagnosis from the clinical examination . Three geriatric psychiatrists who were blinded to the results of the clinical examination conducted the telemedicine and in-person examinations . We also assessed attitudes of the subjects and geriatric psychiatrists towards the telemedicine sessions . RESULTS Eighteen of 85 subjects screened were ' positive ' for dementia on the 7 Minute Screen . Of these , 16 consented to participate in the telemedicine study . Twelve of the 16 subjects were subsequently diagnosed with dementia by the telemedicine examination . The telemedicine diagnoses were in 100 % agreement with the diagnoses from the in-person clinical examinations . Moreover , the subjects reported a high degree of satisfaction with the telemedicine experience and that they would like to have further care through telemedicine in the future . The geriatric psychiatrists reported technical difficulties with the audio-visual quality of telemedicine in the initial phases of the project that resolved as familiarity with the telemedicine equipment increased . None of these problems had an adverse impact on the diagnostic accuracy of telemedicine . CONCLUSIONS We found that telemedicine was as accurate as an in-person clinical examination in establishing the diagnosis of dementia . In addition , subjects reported a high degree of satisfaction with telemedicine and a willingness to participate in telemedicine clinical care in the future . Given the large increase in the aging population and the shortage of geriatric psychiatrists nationally , it appears that telemedicine may be a promising means to exp and the availability of geriatric psychiatric consultation to remote areas BACKGROUND Recent advances in telehealth have improved access to health care for those in rural areas . It is important that examinations conducted via telehealth are comparable to in-person testing . A rural and remote memory clinic in Saskatoon provided an opportunity to compare scores on the Mini-Mental State Examination ( MMSE ) administered in-person and via telehealth . METHODS After an initial one day assessment in Saskatoon , patients were seen in follow-up at 6 and 12 weeks . Individual patients were r and omly assigned to either in-person follow-up assessment in Saskatoon or telehealth assessment in their home community . Patients who initially received in-person assessment s were seen by telehealth for their next follow-up visit and vice-versa . The same neurologist administered MMSEs at all visits . The first 71 patients with both 6 and 12 week follow-up assessment s were included in this study . The scores of in-person and telehealth MMSE administrations were compared using the methods of Bl and and Altman as well as a paired t-test . RESULTS MMSE scores did not differ significantly between telehealth ( 22.34 + /- 6.35 ) and in-person ( 22.70 + /- 6.51 ) assessment s. CONCLUSION Telehealth provides an acceptable means of assessing mental status of patients in remote areas Mini-Mental State Examination scores were compared in an adult psychiatric population when the test was performed face to face and over a Low-Cost VideoConferencing System ( LCVC ) . The minor changes to the instrument that are required to make it compatible with the LCVC are described . The high correlations achieved between the test scores in the two conditions suggests that this cognitive screening test may be reliably performed in this group of patients over the LCVC |
1,147 | 26,765,068 | Liver enzyme abnormalities were the most commonly observed AE , followed by the symptoms associated with postembolization syndrome . | UNLABELLED Transarterial chemoembolization ( TACE ) using lipiodol-based regimens , including the administration of an anticancer-in-oil emulsion followed by embolic agents , is widely used in the treatment of hepatocellular carcinoma ( HCC ) .
This approach has been supported by meta-analyses of r and omized , controlled trials ( RCTs ) performed more than a decade ago .
We performed a systematic review to underst and current efficacy and safety data of lipiodol TACE in treatment of HCC . | Transcatheter arterial chemoembolization ( TACE ) offers a survival benefit to patients with intermediate hepatocellular carcinoma ( HCC ) . A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge — conventional TACE . Recently , a drug-eluting bead ( DC Bead ® ) has been developed to enhance tumor drug delivery and reduce systemic availability . This r and omized trial compares conventional TACE ( cTACE ) with TACE with DC Bead for the treatment of cirrhotic patients with HCC . Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and /or multinodular , unresectable , N0 , M0 HCCs were r and omized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin . R and omization was stratified according to Child-Pugh status ( A/B ) , performance status ( ECOG 0/1 ) , bilobar disease ( yes/no ) , and prior curative treatment ( yes/no ) . The primary endpoint was tumor response ( EASL ) at 6 months following independent , blinded review of MRI studies . The drug-eluting bead group showed higher rates of complete response , objective response , and disease control compared with the cTACE group ( 27 % vs. 22 % , 52 % vs. 44 % , and 63 % vs. 52 % , respectively ) . The hypothesis of superiority was not met ( one-sided P = 0.11 ) . However , patients with Child-Pugh B , ECOG 1 , bilobar disease , and recurrent disease showed a significant increase in objective response ( P = 0.038 ) compared to cTACE . DC Bead was associated with improved tolerability , with a significant reduction in serious liver toxicity ( P < 0.001 ) and a significantly lower rate of doxorubicin-related side effects ( P = 0.0001 ) . TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease BACKGROUND / AIMS Lipiodol chemoembolization is a widely used method of treatment in patients with unresectable hepatocellular carcinoma , but its efficacy is still debated . The aim of our study was to assess the efficacy of lipiodol chemoembolization in patients with unresectable hepatocellular carcinoma . METHODS Seventy-three patients with unresectable hepatocellular carcinoma , but without severe liver disease or portal vein occlusion , were r and omly assigned to receive either repeated lipiodol chemoembolization ( lipiodol , cisplatin ( 2 mg/kg ) , lecithin , and gelatin sponge injected into the hepatic artery ) plus tamoxifen ( 40 mg ) or tamoxifen alone . The main end-point was survival . RESULTS The 37 patients in the lipiodol chemoembolization group received 104 courses ( median 3 per patient ) . By 1 September 1996 , 58 patients had died : 30 in the lipiodol chemoembolization group and 28 in the tamoxifen group . There was no difference in survival between the two groups ( p=0.77 ) . The relative risk of death in the lipiodol chemoembolization plus tamoxifen group as compared to the tamoxifen group was 0.92 ( 95 % confidence interval 0.55 to 1.56 ) . At 1 year , survival was 51 % and 55 % , respectively . An objective tumoral response was more frequently observed in the lipiodol chemoembolization group than in the tamoxifen group ( 24 versus 5.5 % , respectively , p=0.046 ) . Lipiodol chemoembolization caused two deaths and induced signs of liver failure in 51 % of the patients assigned to this treatment . CONCLUSION In our r and omized study , lipiodol chemoembolization did not improve the survival of patients with unresectable hepatocellular carcinoma treated with tamoxifen A r and omized trial of hepatic arterial chemoembolization was conducted in 42 patients with unresectable hepatocellular carcinoma . These patients represented 41 % of patients with hepatocellular carcinoma seen during the inclusion period . In the remaining 59 % , 9 % had resectable tumours and 50 % had unresectable tumours with contraindication for chemoembolization . Patients received either repeated chemoembolization with gelfoam powder and doxorubicin ( group 1 ) or symptomatic treatment ( group 2 ) . There was no difference in age , prevalence of cirrhosis or staging according to Okuda between the two groups of patients . A complete tumour response ( assessed by arteriography , ultrasonography and serum alphafetoprotein ) was observed in four patients , and a partial response in three other patients from group 1 . Actuarial survival rates were 33 and 24 % in group 1 and 52 and 31 % in group 2 at 6 and 12 months , respectively ( differences were not significant -- logrank test ) . With the treatment used in our study , chemoembolization did not prolong the survival time of patients with unresectable hepatocellular carcinoma . There were , however , some complete or partial responses . The high spontaneous 1-year survival rate of untreated patients was probably due to the exclusion of the most severely ill patients . Our results do not support the use of this method of chemoembolization in the treatment of hepatocellular carcinoma This r and omized , controlled trial assessed the efficacy of transarterial Lipiodol ( Lipiodol Ultrafluide , Laboratoire Guerbet , Aulnay-Sous-Bois , France ) chemoembolization in patients with unresectable hepatocellular carcinoma . From March 1996 to October 1997 , 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and r and omly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery ( chemoembolization group , 40 patients ) or symptomatic treatment ( control group , 40 patients ) . One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis . Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease . Survival was the main end point . The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 ( range , 1 - 15 ) courses per patient . Chemoembolization result ed in a marked tumor response , and the actuarial survival was significantly better in the chemoembolization group ( 1 year , 57 % ; 2 years , 31 % ; 3 years , 26 % ) than in the control group ( 1 year , 32 % ; 2 years , 11 % ; 3 years , 3 % ; P = .002 ) . When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model , the survival benefit of chemoembolization remained significant ( relative risk of death , 0.49 ; 95 % CI , 0.29 - 0.81 ; P = .006 ) . Although death from liver failure was more frequent in patients who received chemoembolization , the liver functions of the survivors were not significantly different . In conclusion , in Asian patients with unresectable hepatocellular carcinoma , transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment BACKGROUND The aim of our study was to compare the efficacy and safety of : 1 ) transarterial chemolipiodolization with gelatin sponge embolization vs chemolipiodolization without embolization , and 2 ) chemolipiodolization with triple chemotherapeutic agents vs epirubicin alone . METHODS A single-blind , three parallel arm , r and omized trial was conducted at three clinical centers with patients with biopsy-confirmed unresectable hepatocellular carcinoma . Arm 1 received triple-drug chemolipiodolization and sponge embolization , whereas Arm 2 received triple-drug chemolipiodolization only . Patients in arm 3 were treated with single-drug chemolipiodolization and sponge embolization . We compared overall survival and time to progression . Event-time distributions were estimated by the Kaplan-Meier method . All statistical tests were two-sided . RESULTS From July 2007 to November 2009 , 365 patients ( Arm 1 : n = 122 ; Arm 2 : n = 121 ; Arm 3 : n = 122 ) were recruited . The median tumor size was 10.9 cm ( range = 7 - 22 cm ) , and 34.5 % had macrovascular invasion . The median survivals and time to progression in Arm 1 , Arm 2 , and Arm 3 were 10.5 and 3.6 months , 10.1 and 3.1 months , and 5.9 and 3.1 months , respectively . Survival was statistically significantly better in Arm 1 than in Arm 3 ( P < .001 ) , whereas there was no statistically significant difference between Arm 1 and Arm 2 ( P = .20 ) . Objective response rates were 45.9 % , 29.7 % , and 18.9 % for Arm 1 , Arm 2 , and Arm 3 , respectively . CONCLUSIONS Chemolipiodolization played an important role in transarterial chemoembolization , and the choice of chemotherapy regimen may largely affect survival outcomes . However , the removal of embolization from chemoembolization might not statistically significantly decrease survival This r and omized , controlled trial assessed the effect of transarterial embolization ( TAE ) ( without associated chemotherapy ) on the survival of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Eighty consecutive patients were r and omized to treatment with embolization ( Group A , n = 40 ) , or to symptomatic treatment ( Group B , n = 40 ) , there being no differences between both groups regarding the degree of liver function impairment and tumor stage . Eighty‐two percent of the patients presented a self‐limited postembolization syndrome , without treatment‐related mortality . Fifty‐five percent of the treated cases exhibited a partial response , which result ed in a lower probability of tumor progression during follow‐up ( 57 % vs. 77 % at 1 year ; P < .005 ) . However , after a median follow‐up of 24 months ( 30 deaths in each group ) , there are no differences in survival ( Group A : 49 % and 13 % ; Group B : 50 % and 27 % , at 2 and 4 years , respectively ; P = .72 ) . The absence of differences was maintained even when dividing patients according to Child‐Pugh 's grade , Okuda stage , or performance status test ( PST ) . Furthermore , there were no differences in the probability of complications or in the need of hospital admissions . In conclusion , TAE has a marked antitumoral effect associated to a slower growth of the tumor , but it does not improve the survival of patients with nonsurgical HCC Background Stimulation of vascular endothelial growth factor ( VEGF ) has been observed following transarterial chemoembolization ( TACE ) in hepatocellular cancer ( HCC ) and may contribute to tumor regrowth . This pilot study examined whether intravenous ( IV ) bevacizumab , a monoclonal antibody against VEGF , could inhibit neovessel formation after TACE . Methods 30 subjects with HCC undergoing TACE at a single academic institution were r and omized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE ( TACE-BEV arm ) or observation ( TACE-O arm ) . Angiography was performed with TACE at day 8 , and again at weeks 10 and 14 . Repeat TACE was performed at week 14 if indicated . TACE-BEV subjects were allowed to continue bevacizumab beyond week 16 . TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease . The main outcome measure was a comparison of neovessel formation by serial angiography . Secondary outcome measures were progression free survival ( PFS ) at 16 weeks , overall survival ( OS ) , bevacizumab safety , and an analysis of VEGF levels before and after TACE with and without bevacizumab . Results Among the 30 subjects enrolled , 9 of 15 r and omized to the TACE-O arm and 14 of 15 r and omized to the TACE-BEV arm completed all 3 angiograms . At week 14 , 3 of 9 ( 33 % ) TACE-O subjects and 2 of 14 ( 14 % ) TACE-BEV subjects demonstrated neovascularity . The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm ( p = 0.021 ) . The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm ( p = 0.21 ) . No life-threatening bevacizumab-related toxicities were observed . There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls . Bevacizumab attenuated the increase in VEGF observed post-TACE . Conclusions IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE , and appeared to diminish neovessel formation at week 14.Trial registration Clinical Trials.gov NCT00049322 Background GIDEON ( Global Investigation of therapeutic DEcisions in hepatocellular carcinoma [ HCC ] and Of its treatment with sorafeNib ) is a global , prospect i ve , non-interventional study undertaken to evaluate the safety of sorafenib in patients with unresectable HCC in real-life practice , including Child-Pugh B patients who were excluded from clinical trials . Methods Patients with unresectable HCC , for whom the decision to treat with sorafenib , based on the approved label and prescribing guidelines , had been taken by their physician , were eligible for inclusion . Demographic data and disease/medical history were recorded at entry . Sorafenib dosing and adverse events ( AEs ) were collected at follow-up visits . The second interim analysis was undertaken when ∼1500 treated patients were followed up for ≥ 4 months . Results Of the 1571 patients evaluable for safety , 61 % had Child-Pugh A status and 23 % Child-Pugh B. The majority of patients ( 74 % ) received the approved 800 mg initial sorafenib dose , regardless of Child-Pugh status ; however , median duration of therapy was shorter in Child-Pugh B patients . The majority of drug-related AEs were grade 1 or 2 , and the most commonly reported were consistent with previous reports . The incidence and nature of drug-related AEs were broadly similar across Child-Pugh , Barcelona Clinic Liver Cancer ( BCLC ) and initial dosing subgroups , and consistent with the overall population . Conclusions Consistent with the first interim analysis , overall safety profile and dosing strategy are similar across Child-Pugh subgroups . Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage . Final analyses in > 3000 patients are ongoing Background : Transcatheter arterial chemoembolisation ( TACE ) is the treatment of choice for intermediate stage hepatocellular carcinoma ( HCC ) . Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE ( cTACE ) . The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression ( TTP ) , adverse events ( AEs ) , and 2-year survival . Methods : Patients were r and omised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death . Transcatheter arterial chemoembolisation was repeated ‘ on-dem and ’ . Results : We enrolled 177 patients : 89 underwent DEB-TACE and 88 cTACE . The median number of procedures was 2 in each arm , and the in-hospital stay was 3 and 4 days , respectively ( P=0.323 ) . No differences were found in local and overall tumour response . The median TTP was 9 months in both arms . The AE incidence and severity did not differ between the arms , except for post-procedural pain , more frequent and severe after cTACE ( P<0.001 ) . The 1- and 2-year survival rates were 86.2 % and 56.8 % after DEB-TACE and 83.5 % and 55.4 % after cTACE ( P=0.949 ) . Eastern Cooperative Oncology Group ( ECOG ) , serum albumin , and tumour number independently predicted survival ( P<0.05 ) . Conclusions : The DEB-TACE and the cTACE are equally effective and safe , with the only advantage of DEB-TACE being less post-procedural abdominal pain BACKGROUND & AIMS Chemoembolization is one of several st and ards of care treatment for hepatocellular carcinoma ( HCC ) . Radioembolization with Yttrium-90 microspheres is a novel , transarterial approach to radiation therapy . We performed a comparative effectiveness analysis of these therapies in patients with HCC . METHODS We collected data from 463 patients who were treated with transarterial locoregional therapies ( chemoembolization or radioembolization ) over a 9-year period . We excluded patients who were not appropriate for comparison and analyzed data from 245 ( 122 who received chemoembolization and 123 who received radioembolization ) . Patients were followed for signs of toxicity ; all underwent imaging analysis at baseline and follow-up time points . Overall survival was the primary outcome measure . Secondary outcomes included safety , response rate , and time-to-progression . Uni- and multivariate analyses were performed . RESULTS Abdominal pain and increased transaminase activity were more frequent following chemoembolization ( P < .05 ) . There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization ( 49 % vs 36 % , respectively , P = .104 ) . Although time-to-progression was longer following radioembolization than chemoembolization ( 13.3 months vs 8.4 months , respectively , P = .046 ) , median survival times were not statistically different ( 20.5 months vs 17.4 months , respectively , P = .232 ) . Among patients with intermediate-stage disease , survival was similar between groups that received chemoembolization ( 17.5 months ) and radioembolization ( 17.2 months , P = .42 ) . CONCLUSIONS Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times . Radioembolization result ed in longer time-to-progression and less toxicity than chemoembolization . Post hoc analyses of sample size indicated that a r and omized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies AIM To conduct a r and omized trial to evaluate the role of using high-dose iodized oil transcatheter arterial chemoembolization ( TACE ) in the treatment of large hepatocellular carcinoma ( HCC ) . METHODS From January 1993 to June 1998 , 473 patients with unresectable hepatocellular carcinoma were divided into two groups : 216 patients in group A received more than 20 mL iodized oil during the first TACE treatment ; 257 patients in group B received 5 - 15 mL iodized oil in the same way . The Child 's classification and ICG-R15 for evaluating the liver function of the patients were done before the treatment . During the TACE procedure the catheters were inserted into the target artery selectively and the tumor vessels were demonstrated with contrast medium in the hepatic angiography . The anticancer drugs mixed with iodized oil ( Lipiodol ) were Epirubicin and Mitomycin . In group A , 112 cases received 20 - 29 mL Lipiodol in the first procedure , 85 cases 30 - 39 mL , 19 cases more than 40 mL. The largest dose was 53 mL and the average dose was 28.3 mL. In group B , 119 cases received 5 - 10 mL Lipiodol,138 cases received 11 - 15 mL and the average dose was 11.8 mL. RESULTS High-dose Lipiodol chemoembolization had tolerable side effects and a little hurt to the liver function in the patients with Child 's A or ICG-R15<20 . But the patients with child 's B or ICG-R15>20 had higher risk of liver failure after high-dose TACE . More type I and type II in CT scan after 4 weeks of TACE were seen in the patients of group A than those in the patients of group B ( P<0.01 ) . The resection rate and complete tumor necrosis rate of group A were higher than those of group B ( P<0.05 ) . The 1-,2- , 3-year survival rates of group A patients with Child 's A were 79.2 , 51.8 and 34.9 , respectively , better than those of group A ( P<0.001 ) . CONCLUSION High-dose Lipiodol can result in more complete tumor necrosis by blocking both arteries and small portal vein of the tumor . High-dose TACE for treatment of large and hypervascular hepatocellular carcinoma is practically acceptable with the better effect than the routine dose . For the patients with large and hypervascular tumor of Child grade A liver function or ICG-R15 less than 20 % , oily chemoembolization with 20 - 40 mL Lipiodol is recommended BACKGROUND There is no st and ard treatment for unresectable hepatocellular carcinoma . Arterial embolisation is widely used , but evidence of survival benefits is lacking . METHODS We did a r and omised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment , of Child-Pugh class A or B and Okuda stage I or II , to assess the survival benefits of regularly repeated arterial embolisation ( gelatin sponge ) or chemoembolisation ( gelatin sponge plus doxorubicin ) compared with conservative treatment . 903 patients were assessed , and 112 ( 12 % ) patients were finally included in the study . The primary endpoint was survival . Analyses were by intention to treat . FINDINGS The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment ( hazard ratio of death 0.47 [ 95 % CI 0.25 - 0.91 ] , p=0.025 ) . 25 of 37 patients assigned embolisation , 21 of 40 assigned chemoembolisation , and 25 of 35 assigned conservative treatment died . Survival probabilities at 1 year and 2 years were 75 % and 50 % for embolisation ; 82 % and 63 % for chemoembolisation , and 63 % and 27 % for control ( chemoembolisation vs control p=0.009 ) . Chemoembolisation induced objective responses sustained for at least 6 months in 35 % (14)of cases , and was associated with a significantly lower rate of portal-vein invasion than conservative treatment . Treatment allocation was the only variable independently related to survival ( odds ratio 0.45 [ 95 % CI 0.25 - 0.81 ] , p=0.02 ) . INTERPRETATION Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma PURPOSE To compare therapeutic effect , adverse events , and embolized hepatic artery impairment in transcatheter arterial chemoembolization between Lipiodol plus insoluble gelatin sponge particles ( Gelpart ) and Lipiodol plus 2-day-soluble gelatin sponge particles ( 2DS-GSPs ) . MATERIAL S AND METHODS In a single-center , prospect i ve , r and omized controlled trial , patients with hepatocellular carcinoma were assigned to the 2DS-GSP group or the Gelpart group . Radiographic response at 3 months per modified Response Evaluation Criteria In Solid Tumors was evaluated as the primary endpoint ; secondary endpoints were safety ( per Common Terminology Criteria for Adverse Events , version 4.0 ) within 3 months and hepatic branch artery impairment at the time of repeat chemoembolization ( grade 0 , no damage ; grade I , mild vessel wall irregularity ; grade II , overt stenosis ; grade III , occlusion of more peripheral branch artery than subsegmental artery ; grade IV , occlusion of subsegmental artery ) . Grade II , III , or IV indicated significant hepatic artery impairment . RESULTS Thirty-seven patients with 143 nodules were r and omized to the 2DS-GSP group and 36 patients with 137 nodules were r and omized to the Gelpart group . No significant differences in patient background existed between groups . Target lesion response and overall tumor response in the 2DS-GSP and Gelpart groups were 77.7 % versus 76.9 % and 78.3 % versus 77.8 % , respectively , with no significant differences . No significant difference in adverse events existed between groups . Hepatic artery impairment was observed in 5 % of patients in the 2DS-GSP group ( n = 32 ) and in 16 % in the Gelpart group ( n = 33 ; P < .001 ) . CONCLUSIONS Transcatheter arterial chemoembolization with 2DS-GSPs result ed in the same therapeutic and adverse effects as chemoembolization with Gelpart while causing significantly less hepatic artery impairment PURPOSE To evaluate the safety and efficacy of transcatheter arterial chemoembolization used for the treatment of unresectable hepatocellular carcinoma ( HCC ) with an Asian cooperative prospect i ve study between Japan and Korea . MATERIAL S AND METHODS Patients with unresectable HCC unsuitable for curative treatment or with no prior therapy for HCC were enrolled . The patients underwent transcatheter arterial chemoembolization with emulsion of Lipiodol and anthracycline agent , followed by embolization with gelatin sponge particles , which was repeated on an as-needed basis . The primary endpoint was 2-year survival rate , and the secondary endpoints were adverse events and response rate . RESULTS The 2-year survival rate of 99 patients was 75.0 % ( 95 % confidence interval , 65.2%-82.8 % ) . The median time-to-progression was 7.8 months , and the median overall survival period was 3.1 years . Of 99 patients , 42 ( 42 % ) achieved a complete response , and 31 ( 31 % ) had a partial response . The response rate was 73 % using modified Response Evaluation Criteria in Solid Tumors . The grade 3 - 4 toxicities included increased alanine aminotransferase level in 36 % , increased aspartate aminotransferase level in 35 % , thrombocytopenia in 12 % , and abdominal pain in 4 % of patients . All other toxicities were generally transient . CONCLUSIONS Asian transcatheter arterial chemoembolization demonstrated sufficient safety and reasonable efficacy as a st and ard treatment for unresectable HCC . These results could be useful as reference data for future trials of transcatheter arterial chemoembolization The oncologic community is faced with a steady increase in the incidence of hepatocellular carcinoma ( HCC ) [ 1 ] . Liver cancer represents the sixth most common cancer in the world ( 749 000 new cases ) and the third cause of cancer-related death ( 692 000 cases ) . The incidence varies from 3 out of 100 000 in Western countries , to more than 15 out of 100 000 in certain areas of the world , mapping the geographical distribution of viral hepatitis B ( HBV ) and hepatitis C ( HCV ) , the most important causes of chronic liver disease and HCC [ 2 ] . Most cases arise in those regions with limited re sources . The incidence of HCC increases progressively with advancing age in all population s , with a strong male preponderance . The association of chronic liver disease and HCC represents the basis for preventive strategies , including universal vaccination at birth against hepatitis B , programs to stop transmission and early antiviral eradication of viral hepatitis B and C [ III , A ] . It is unclear whether HBV vaccination will result in a decline in HCC as was seen in Taiwan , given the importance of other risk factors in Europe , such as alcoholic and non-alcoholic fatty liver disease . The control of other risk factors for chronic liver disease and cancer is more difficult to implement , such as cutting down on the consumption of alcohol and programs aim ing at a healthier lifestyle in the light of the obesity p and emic [ 3 , 4 ] . In Africa , reduction of exposure to aflatoxin B1 , especially in HBV-infected individuals , may lower the risk of HCC . HCC may evolve from subclasses of adenomas , and in < 10 % of cases HCC occurs in a normal liver . Surveillance of HCC involves the repeated application of screening tools in patients at risk for HCC and aims for the reduction in mortality of this patient population . The success of surveillance is influenced by the incidence of HCC in the target population , the availability and acceptance of efficient diagnostic tests and the availability of effective treatment . Costeffectiveness studies suggest surveillance of HCC is warranted in cirrhotic patients irrespective of its etiology [ 5 ] . Surveillance of non-cirrhotic patients is also advocated , especially in HBV carriers with serum viral load > 10 000 copies/ml [ 6 ] or HCVinfected patients with bridging fibrosis ( F3 ) [ III , A ] . Patients with HCV infection and advanced fibrosis remain at risk for HCC even after achieving sustained virological response following antiviral treatment [ III , A ] . Japanese cohort studies have shown that surveillance by abdominal ultrasound result ed in an average size of the detected tumors of 1.6 ± 0.6 cm , with < 2 % of the cases exceeding 3 cm [ 7 ] . In the Western world and in less experienced centers , sensitivity of finding early-stage HCC by ultrasound is considerably less effective [ 8 ] . There are no data to support the use of contrast-enhanced computed tomography ( CT ) or magnetic resonance imaging ( MRI ) for surveillance . In many centers , ultrasound surveillance is complemented with the determination of serum alphafetoprotein ( AFP ) , which can lead to a 6%–8 % gain in the tumor detection rate but at the price of false-positive results . A r and omized , controlled trial ( RCT ) of Chinese patients with chronic hepatitis B infection compared surveillance ( ultrasound and serum AFP measurements every 6 months ) versus no surveillance [ 9 ] . Despite low compliance with the surveillance program ( 55 % ) , HCC-related mortality was reduced by 37 % in the surveillance arm . Considering the most appropriate surveillance interval , a r and omized study comparing a 3versus 6-month based schedule failed to detect any differences [ 10 ] . Therefore , surveillance of patients at risk for HCC should be carried out by abdominal ultrasound every 6 months [ I , A ] BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group ( hazard ratio in the sorafenib group , 0.69 ; 95 % confidence interval , 0.55 to 0.87 ; P<0.001 ) . There was no significant difference between the two groups in the median time to symptomatic progression ( 4.1 months vs. 4.9 months , respectively , P=0.77 ) . The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( P<0.001 ) . Seven patients in the sorafenib group ( 2 % ) and two patients in the placebo group ( 1 % ) had a partial response ; no patients had a complete response . Diarrhea , weight loss , h and -foot skin reaction , and hypophosphatemia were more frequent in the sorafenib group . CONCLUSIONS In patients with advanced hepatocellular carcinoma , median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo . ( Clinical Trials.gov number , NCT00105443 . BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma Hepatocellular carcinoma ( HCC ) is a major and often therapeutically frustrating oncological problem . A total of 100 patients with unresectable HCC were recruited and r and omized to be treated with either transcatheter arterial chemoembolization ( TACE ) or systemic chemotherapy . Fifty patients were treated with TACE using lipiodol , doxorubicin and cisplatin , while 50 patients were treated with systemic doxorubicin alone . Patients treated with TACE achieved a significantly higher response rate , with partial response achieved in 16 patients ( 32 % ) versus five patients ( 10 % ) in the chemotherapy arm ( P = 0.007 ) . A significantly more favourable tumour response to chemoembolization was found in patients with single lesions ( P = 0.02 ) , Child class A ( P = 0.007 ) , Okuda stage 1 ( P = 0.005 ) and alpha-feto protein less than 400 ng/mL ( P < 0.001 ) . The probability of tumour progression was significantly lower in cases treated with TACE where the median progression free survival was 32 weeks ( range , 16 - 70 weeks ) versus 26 weeks ( range , 14 - 54 weeks ) for patients treated with systemic chemotherapy ( P = 0.03 ) . However , the median overall survival did not differ significantly in cases treated with TACE ( 38 weeks ) compared with those treated with chemotherapy ( 32 weeks ) ( P = 0.08 ) , except for patients with serum albumin > 3.3 g/dL ( 60 vs. 36 weeks ; P = 0.003 ) . Multivariate Cox regression analysis showed that a rise of serum albumin by 1 g/dL is associated with a decrease in the risk of death by 33 % ( 95 % confidence interval : 0.12 - 0.94 , P = 0.038 ) . Mortality in the chemoembolization arm was due to tumour progression in 18 patients ( 53 % ) , liver failure in 11 patients ( 32 % ) and gastro intestinal tract ( GIT ) bleeding in 5 patients ( 15 % ) . Mortality in the chemotherapy arm was due to tumour progression in 23 patients ( 64 % ) , liver failure in 9 patients ( 25 % ) and GIT bleeding in 4 patients ( 11 % ) . Treatment-related mortality was 4 % in the TACE arm versus 0 % in the chemotherapy arm . In conclusion , the overall survival benefits of TACE and systemic doxorubicin are similar for patients with unresectable HCC amenable to either treatment . It is crucial to optimize the benefit-risk ratio of TACE . In this setting , serum albumin level is a c and i date marker for selection of cases who may benefit from this procedure A r and omized controlled trial of hepatic arterial embolization was conducted in 63 consecutive patients who had unresectable but still embolizable hepatocellular carcinoma . Patients were r and omized into three groups . Patients in group 1 received multiple hepatic arterial embolizations ; patients in group 2 were given hepatic arterial embolization once , followed by monthly chemotherapy with high doses of 5-fluorouracil ; and patients in group 3 received only monthly chemotherapy with high doses of 5-fluorouracil . Complete response was achieved in only 1 patient who received multiple hepatic arterial embolizations . Partial responses were observed in 13 patients ( 61.9 % ) in group 1 , 10 patients ( 47.6 % ) in group 2 , and 2 patients ( 9.5 % ) in group 3 . The survival rates of patients in group 1 at the end of the ninth , 12th , 15th , 18th , and 21st months were 53.2 % , 42.2 % , 42.2 % , 42.2 % , and 42.2 % , respectively , which were not significantly different from those of patients in group 2 but were better than the survival rates of patients in group 3 . The results suggest that hepatic arterial embolization is an effective palliative treatment that prolongs survival of patients with unresectable hepatocellular carcinoma BACKGROUND There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma . AIM The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group . METHODS Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial . transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions . RESULTS Thirteen patients were r and omised in the amiodarone group , and 14 were r and omised in the control group . The two groups were comparable with respect to their baseline characteristics . The objective response rate according to the EASL criteria was 62 % ( 95 % CI 35 - 88 ) in the amiodarone group and 50 % ( 95 % CI 24 - 76 ) in the control group . At 1 and 2 years , survival rates were 77 % ( 95 % CI 44 - 92 ) and 52 % ( 95 % CI 22 - 75 ) in the amiodarone group , and 57 % ( 95 % CI 28 - 78 ) and 40 % ( 95 % CI 15 - 65 ) in the control group , respectively . There was no difference between the two groups in terms of toxicity . CONCLUSIONS The results of this study suggest that lipiodol transarterial chemoembolisation with anthracycline and amiodarone was safe but did not increase survival compared with lipiodol transarterial chemoembolisation with anthracycline alone in patients with hepatocellular carcinoma BACKGROUND / AIMS Transcatheter arterial chemoembolization ( TACE ) is a combination of transarterial infusion chemotherapy ( TAI ) and embolization , and has been widely used to treat patients with hepatocellular carcinoma ( HCC ) . However , since the impact of adding embolization on the survival of patients treated with TAI had never been evaluated in a phase III study , we conducted a multi-center , open-label trial comparing TACE and TAI to assess the effect of adding embolization on survival . METHODS Patients with newly diagnosed unresectable HCC were r and omly assigned to either a TACE group or a TAI group . Zinostatin stimalamer was injected into the hepatic artery , together with gelatin sponge in the TACE group and without gelatin sponge in the TAI group . Treatment was repeated when follow-up computed tomography showed the appearance of new lesions in the liver or re-growth of previously treated tumors . RESULTS Seventy-nine patients were assigned to the TACE group , and 82 were assigned to the TAI group . The two groups were comparable with respect to their baseline characteristics . At the time of the analysis , 51 patients in the TACE group and 58 in the TAI group had died . The median overall survival time was 646 days in the TACE group and 679days in the TAI group ( p=0.383 ) . CONCLUSIONS The results of this study suggest that treatment intensification by adding embolization did not increase survival over TAI with zinostatin stimalamer alone in patients with HCC PURPOSE To compare the stability of epirubicin-iodized oil emulsions prepared with ionic or nonionic contrast medium and to compare the efficacy of these emulsions in a prospect i ve , r and omized , controlled trial of transarterial chemoembolization ( TACE ) for hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Epirubicin-iodized oil emulsions prepared with ionic and nonionic contrast media was evaluated for stability with light microscopy and magnetic resonance imaging . One hundred ninety-seven patients with inoperable HCC were r and omized to receive TACE with epirubicin , prepared either with ionic ( control group , n = 99 ) or nonionic ( experimental group , n = 98 ) contrast medium . Tumor response was grade d according to iodized oil retention ( grade 1 = > 90 % retention , grade 2 = 50%-90 % retention , and grade 3 = < 50 % retention ) , as characterized with computed tomography . Survival probabilities were calculated with the Kaplan-Meier method . RESULTS The epirubicin-iodized oil emulsions prepared with ionic contrast medium were less stable , exhibiting rapid separation of the oil and aqueous phases , compared with emulsions prepared with nonionic medium . Ninety-one patients in the control group and 87 in the experimental group underwent follow-up CT . Thirty-seven of the 91 patients in the control group ( 41 % ) had grade 1 tumors , 41 ( 45 % ) had grade 2 tumors , and 13 ( 14 % ) had grade 3 tumors . Forty-eight of the 87 patients in the experimental group ( 55 % ) had grade 1 tumors , 22 ( 25 % ) had grade 2 tumors , and 17 ( 20 % ) had grade 3 tumors . The number of patients with grade 1 tumors was significantly higher in the experimental group than in the control group ( P = .02 ) ; however , there was no difference in patient survival ( P = .94 ) . CONCLUSIONS Epirubicin-iodized oil emulsions prepared with nonionic contrast medium are more stable and are associated with lower tumor grade in patients with inoperable HCC . The choice of solvent , however , does not appear to have an effect on patient survival UNLABELLED Transarterial chemoembolization ( TACE ) is the current st and ard of treatment for unresectable intermediate-stage hepatocellular carcinoma ( HCC ) . Brivanib , a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling , may improve the effectiveness of TACE when given as an adjuvant to TACE . In this multinational , r and omized , double-blind , placebo-controlled , phase III study , 870 patients with TACE-eligible HCC were planned to be r and omly assigned ( 1:1 ) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily . The primary endpoint was overall survival ( OS ) . Secondary endpoints included time to disease progression ( TTDP ; a composite endpoint based on development of extrahepatic spread or vascular invasion , deterioration of liver function or performance status , or death ) , time to extrahepatic spread or vascular invasion ( TTES/VI ) , rate of TACE , and safety . Time to radiographic progression ( TTP ) and objective response rate were exploratory endpoints . The trial was terminated after r and omization of 502 patients ( brivanib , 249 ; placebo , 253 ) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives . At termination , median follow-up was approximately 16 months . Intention-to-treat analysis showed no improvement in OS with brivanib versus placebo ( median , 26.4 [ 95 % confidence interval { CI } : 19.1 to not reached ] vs. 26.1 months [ 19.0 - 30.9 ] ; hazard ratio [ HR ] : 0.90 [ 95 % CI : 0.66 - 1.23 ] ; log-rank P=0.5280 ) . Brivanib improved TTES/VI ( HR , 0.64 [ 95 % CI : 0.45 - 0.90 ] ) , TTP ( 0.61 [ 0.48 - 0.77 ] ) , and rate of TACE ( 0.72 [ 0.61 - 0.86 ] ) , but not TTDP ( 0.94 [ 0.72 - 1.22 ] ) versus placebo . Most frequent grade 3 - 4 adverse events included hyponatremia ( brivanib , 18 % vs. placebo , 5 % ) and hypertension ( 13 % vs. 3 % ) . CONCLUSIONS In this study , brivanib as adjuvant therapy to TACE did not improve OS |
1,148 | 29,746,546 | Conclusions Symptomatic aortic stenosis can be lethal without intervention but surgical resection is contraindicated for some patients and high risk for others .
We found that all-cause mortality up to 5 years of follow-up did not differ significantly between TAVI and SAVR in patients surgically operable at a high risk , but favoured TAVI over medical therapy in patients surgically inoperable .
TAVI is a viable life-extending treatment option in these surgical high risk groups | Background Symptomatic aortic stenosis has a poor prognosis .
Many patients are considered inoperable or at high surgical risk for surgical aortic valve replacement ( SAVR ) , reflecting their age , comorbidities and frailty .
The clinical effectiveness and safety of TAVI have not been review ed systematic ally for these high levels of surgical risk .
This systematic review compares mortality and other important clinical outcomes up to 5 years post treatment following TAVI or other treatment in these risk groups . | OBJECTIVES This study sought to examine sex-specific differences in outcomes after surgical aortic valve replacement ( SAVR ) or transcatheter aortic valve replacement ( TAVR ) in high-risk patients with severe aortic stenosis . BACKGROUND The PARTNER ( Placement of Aortic Transcatheter Valve ) trial demonstrated similar 2-year survival with SAVR or TAVR for high-risk patients , but sex-specific outcomes are unknown . METHODS In all , 699 patients ( 300 female ) were r and omly assigned 1:1 to either SAVR or TAVR with a balloon exp and able pericardial tissue valve . Baseline characteristics and 2-year outcomes of TAVR versus SAVR were compared among males and females . RESULTS Baseline characteristics differed between the sexes . Despite higher Society of Thoracic Surgeons mortality risk scores ( 11.9 vs. 11.6 ; p = 0.05 ) , female patients had lower prevalence of coronary artery disease ( 64.4 % vs. 83.7 % ) , prior coronary artery bypass graft surgery ( 19.8 % vs. 61.2 % ) , peripheral vascular disease ( 36.4 % vs. 46.9 % ) , diabetes mellitus ( 35.6 % vs. 45.6 % ) , and elevated creatinine ( 11.7 % vs. 23.9 % ) . Among female patients , procedural mortality trended lower with TAVR versus SAVR ( 6.8 % vs. 13.1 % ; p = 0.07 ) and was maintained throughout follow-up ( hazard ratio [ HR ] : 0.67 ; 95 % confidence interval [ CI ] : 0.44 to 1.00 ; p = 0.049 ) , driven by the transfemoral arm ( HR : 0.55 ; 95 % CI : 0.32 to 0.93 ; p = 0.02 ) . Among male patients , although procedural mortality was lower with TAVR ( 6 % vs. 12.1 % ; p = 0.03 ) , there was no overall survival benefit ( HR : 1.15 ; 95 % CI : 0.82 to 1.61 ; p = 0.42 ) . CONCLUSIONS In this retrospective sub analysis of high-risk , symptomatic aortic stenosis patients in the PARTNER trial , female subjects had lower late mortality with TAVR versus SAVR . This was especially true among patients suitable for transfemoral access and suggests that TAVR may be preferred over surgery for high-risk female patients . A r and omized , controlled trial conducted specifically in female patients is necessary to properly study differences in mortality between treatment modalities . ( THE PARTNER TRIAL : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) BACKGROUND The use of transcatheter aortic-valve replacement has been shown to reduce mortality among high-risk patients with aortic stenosis who are not c and i date s for surgical replacement . However , the two procedures have not been compared in a r and omized trial involving high-risk patients who are still c and i date s for surgical replacement . METHODS At 25 centers , we r and omly assigned 699 high-risk patients with severe aortic stenosis to undergo either transcatheter aortic-valve replacement with a balloon-exp and able bovine pericardial valve ( either a transfemoral or a transapical approach ) or surgical replacement . The primary end point was death from any cause at 1 year . The primary hypothesis was that transcatheter replacement is not inferior to surgical replacement . RESULTS The rates of death from any cause were 3.4 % in the transcatheter group and 6.5 % in the surgical group at 30 days ( P=0.07 ) and 24.2 % and 26.8 % , respectively , at 1 year ( P=0.44 ) , a reduction of 2.6 percentage points in the transcatheter group ( upper limit of the 95 % confidence interval , 3.0 percentage points ; predefined margin , 7.5 percentage points ; P=0.001 for noninferiority ) . The rates of major stroke were 3.8 % in the transcatheter group and 2.1 % in the surgical group at 30 days ( P=0.20 ) and 5.1 % and 2.4 % , respectively , at 1 year ( P=0.07 ) . At 30 days , major vascular complications were significantly more frequent with transcatheter replacement ( 11.0 % vs. 3.2 % , P<0.001 ) ; adverse events that were more frequent after surgical replacement included major bleeding ( 9.3 % vs. 19.5 % , P<0.001 ) and new-onset atrial fibrillation ( 8.6 % vs. 16.0 % , P=0.006 ) . More patients undergoing transcatheter replacement had an improvement in symptoms at 30 days , but by 1 year , there was not a significant between-group difference . CONCLUSIONS In high-risk patients with severe aortic stenosis , transcatheter and surgical procedures for aortic-valve replacement were associated with similar rates of survival at 1 year , although there were important differences in periprocedural risks . ( Funded by Edwards Lifesciences ; Clinical Trials.gov number , NCT00530894 . ) OBJECTIVES We compared the incidence of prosthesis-patient mismatch ( PPM ) between transcatheter aortic valve replacement ( TAVR ) using a self-exp and ing bioprosthesis and surgical aortic valve replacement ( SAVR ) in the CoreValve US High Risk Pivotal Trial . We sought to determine the influence of PPM on clinical outcomes . METHODS Patients with severe aortic stenosis and at increased risk for surgery were r and omized 1:1 to TAVR or SAVR . Postoperative PPM was defined by the effective orifice area index ( EOAi ) as severe PPM ( EOAi ≤ 0.65 cm(2)/m(2 ) ) and no severe PPM ( EOAi > 0.65 cm(2)/m(2 ) ) ; clinical outcomes were analyzed in the TAVR arm ( n = 389 ) and SAVR arm ( n = 353 ) . Left ventricular mass index and regression were analyzed at baseline and 1 year . RESULTS The incidence of severe PPM in the SAVR group at 1 year was 25.7 % versus 6.2 % in the TAVR group ( P < .0001 ) . Left ventricular mass index regression at 1 year was 6.8 % for TAVR and 15.1 % for SAVR in patients with severe PPM . At 1 year the rate of all-cause mortality and acute kidney injury were significantly greater in all patients ( TAVR + SAVR ) with severe PPM compared with no severe PPM ( 20.6 % vs 12.0 % [ P = .0145 ] for death and 19.2 % vs 8.5 % [ P = .0008 ] for acute kidney injury ) . CONCLUSIONS In patients with high surgical risk and severe aortic stenosis , severe PPM is more common in patients treated with SAVR than those treated with TAVR . Patients with severe PPM are a greater risk for death and acute kidney injury than patients without severe PPM OBJECTIVES This study sought to compare health status and quality -of-life outcomes for patients with severe aortic stenosis ( AS ) and high surgical risk treated with either transcatheter aortic valve replacement ( TAVR ) or surgical aortic valve replacement ( AVR ) . BACKGROUND For high-risk patients with severe AS , TAVR has been shown to result in similar 12-month survival but differing adverse events compared with AVR . METHODS We evaluated the health status of 628 patients with severe , symptomatic AS at high risk of surgical complications who were r and omized to either TAVR or AVR in the PARTNER Trial . Health status was assessed at baseline and 1 , 6 , and 12 months using the Kansas City Cardiomyopathy Question naire , the Short Form-12 , and the EuroQol-5D . RESULTS The primary outcome , the Kansas City Cardiomyopathy Question naire summary score , improved more rapidly with TAVR , but was similar for the 2 groups at 6 and 12 months . However , there was a significant interaction between the benefit of TAVR and access site ( transapical vs. transfemoral ) . Patients eligible for transfemoral TAVR demonstrated significant health status benefits with TAVR versus AVR at 1 month ( difference , 9.9 points ; 95 % confidence interval : 4.9 to 14.9 ; p < 0.001 ) , whereas patients treated via the TA approach demonstrated no benefits with TAVR compared with AVR at any time point . Results for Kansas City Cardiomyopathy Question naire subscales and generic measures demonstrated similar patterns . CONCLUSIONS In high-risk patients with severe AS , health status improved substantially between baseline and 1 year after either TAVR or AVR . TAVR via the transfemoral , but not the transapical route , was associated with a short-term advantage compared with surgery . ( Placement of AoRTic TraNscathetER Valve [ PARTNER ] trial ; NCT00530894 ) BACKGROUND We compared transcatheter aortic-valve replacement ( TAVR ) , using a self-exp and ing transcatheter aortic-valve bioprosthesis , with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery . METHODS We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center . Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors . Eligible patients were r and omly assigned in a 1:1 ratio to TAVR with the self-exp and ing transcatheter valve ( TAVR group ) or to surgical aortic-valve replacement ( surgical group ) . The primary end point was the rate of death from any cause at 1 year , evaluated with the use of both noninferiority and superiority testing . RESULTS A total of 795 patients underwent r and omization at 45 centers in the United States . In the as-treated analysis , the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group ( 14.2 % vs. 19.1 % ) , with an absolute reduction in risk of 4.9 percentage points ( upper boundary of the 95 % confidence interval , -0.4 ; P<0.001 for noninferiority ; P = 0.04 for superiority ) . The results were similar in the intention-to-treat analysis . In a hierarchical testing procedure , TAVR was noninferior with respect to echocardiographic indexes of valve stenosis , functional status , and quality of life . Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke . CONCLUSIONS In patients with severe aortic stenosis who are at increased surgical risk , TAVR with a self-exp and ing transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement . ( Funded by Medtronic ; U.S. CoreValve High Risk Study Clinical Trials.gov number , NCT01240902 . ) Background —The Placement of Aortic Transcatheter Valves ( PARTNER ) trial demonstrated similar survival after transcatheter and surgical aortic valve replacement ( TAVR and SAVR , respectively ) in high-risk patients with symptomatic , severe aortic stenosis . The aim of this study was to evaluate the effect of left ventricular ( LV ) dysfunction on clinical outcomes after TAVR and SAVR and the impact of aortic valve replacement technique on LV function . Methods and Results —The PARTNER trial r and omized high-risk patients with severe aortic stenosis to TAVR or SAVR . Patients were stratified by the presence of LV ejection fraction ( LVEF ) < 50 % . All-cause mortality was similar for TAVR and SAVR at 30-days and 1 year regardless of baseline LV function and valve replacement technique . In patients with LV dysfunction , mean LVEF increased from 35.7±8.5 % to 48.6±11.3 % ( P<0.0001 ) 1 year after TAVR and from 38.0±8.0 % to 50.1±10.8 % after SAVR ( P<0.0001 ) . Higher baseline LVEF ( odds ratio , 0.90 [ 95 % confidence interval , 0.86 , 0.95 ] ; P<0.0001 ) and previous permanent pacemaker ( odds ratio , 0.34 [ 95 % confidence interval , 0.15 , 0.81 ] ) were independently associated with reduced likelihood of ≥10 % absolute LVEF improvement by 30 days ; higher mean aortic valve gradient was associated with increased odds of LVEF improvement ( odds ratio , 1.04 per 1 mm Hg [ 95 % confidence interval , 1.01 , 1.08 ] ) . Failure to improve LVEF by 30 days was associated with adverse 1-year outcomes after TAVR but not SAVR . Conclusions —In high-risk patients with severe aortic stenosis and LV dysfunction , mortality rates and LV functional recovery were comparable between valve replacement techniques . TAVR is a feasible alternative for patients with symptomatic severe aortic stenosis and LV dysfunction who are at high risk for SAVR . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00530894 OBJECTIVES This study sought to compare the health status outcomes for patients treated with either self-exp and ing transcatheter aortic valve replacement ( TAVR ) or surgical aortic valve replacement ( AVR ) . BACKGROUND In patients at increased surgical risk , TAVR with a self-exp and ing bioprosthesis is associated with improved 1-year survival compared with AVR . However , elderly patients may be just as concerned with quality -of-life improvement as with prolonged survival as a goal of treatment . METHODS Between 2011 and 2012 , 795 patients with severe aortic stenosis at increased surgical risk were r and omized to TAVR or AVR in the CoreValve US Pivotal Trial . Health status was assessed at baseline , 1 month , 6 months , and 1 year using the Kansas City Cardiomyopathy Question naire , Medical Outcomes Study Short-Form 12 Question naire , and EuroQOL 5-dimension question naire ; growth curve models were used to examine changes over time . RESULTS Over the 1-year follow-up period , disease-specific and generic health status improved substantially for both treatment groups . At 1 month , there was a significant interaction between the benefit of TAVR over AVR and access site . Among surviving patients eligible for iliofemoral ( IF ) access , there was a clinical ly relevant early benefit with TAVR across all disease-specific and generic health status measures . Among the non-IF cohort , however , most health status measures were similar for TAVR and AVR , although there was a trend toward early benefit with TAVR on the Short-Form 12 Question naire 's physical health scale . There were no consistent differences in health status between TAVR and AVR at the later time points . CONCLUSIONS Health status improved substantially in surviving patients with increased surgical risk who were treated with either self-exp and ing TAVR or AVR . TAVR via the IF route was associated with better early health status compared with AVR , but there was no early health status benefit with non-IF TAVR compared with AVR . ( Safety and Efficacy Study of the Medtronic CoreValve ® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) BACKGROUND Little is known about the incidence of prosthesis-patient mismatch ( PPM ) and its impact on outcomes after transcatheter aortic valve replacement ( TAVR ) . OBJECTIVES The objectives of this study were : 1 ) to compare the incidence of PPM in the TAVR and surgical aortic valve replacement ( SAVR ) r and omized control trial ( RCT ) arms of the PARTNER ( Placement of AoRTic TraNscathetER Valves ) I Trial cohort A ; and 2 ) to assess the impact of PPM on regression of left ventricular ( LV ) hypertrophy and mortality in these 2 arms and in the TAVR nonr and omized continued access ( NRCA ) registry cohort . METHODS The PARTNER Trial cohort A r and omized patients 1:1 to TAVR or bioprosthetic SAVR . Postoperative PPM was defined as absent if the indexed effective orifice area ( EOA ) was > 0.85 cm(2)/m(2 ) , moderate if the indexed EOA was ≥0.65 but ≤0.85 cm(2)/m(2 ) , or severe if the indexed EOA was < 0.65 cm(2)/m(2 ) . LV mass regression and mortality were analyzed using the SAVR- RCT ( n = 270 ) , TAVR- RCT ( n = 304 ) , and TAVR-NRCA ( n = 1,637 ) cohorts . RESULTS The incidence of PPM was 60.0 % ( severe : 28.1 % ) in the SAVR- RCT cohort versus 46.4 % ( severe : 19.7 % ) in the TAVR- RCT cohort ( p < 0.001 ) and 43.8 % ( severe : 13.6 % ) in the TAVR-NRCA cohort . In patients with an aortic annulus diameter < 20 mm , severe PPM developed in 33.7 % undergoing SAVR compared with 19.0 % undergoing TAVR ( p = 0.002 ) . PPM was an independent predictor of less LV mass regression at 1 year in the SAVR- RCT ( p = 0.017 ) and TAVR-NRCA ( p = 0.012 ) cohorts but not in the TAVR- RCT cohort ( p = 0.35 ) . Severe PPM was an independent predictor of 2-year mortality in the SAVR- RCT cohort ( hazard ratio [ HR ] : 1.78 ; p = 0.041 ) but not in the TAVR- RCT cohort ( HR : 0.58 ; p = 0.11 ) . In the TAVR-NRCA cohort , severe PPM was not a predictor of 1-year mortality in all patients ( HR : 1.05 ; p = 0.60 ) but did independently predict mortality in the subset of patients with no post-procedural aortic regurgitation ( HR : 1.88 ; p = 0.02 ) . CONCLUSIONS In patients with severe aortic stenosis and high surgical risk , PPM is more frequent and more often severe after SAVR than TAVR . Patients with PPM after SAVR have worse survival and less LV mass regression than those without PPM . Severe PPM also has a significant impact on survival after TAVR in the subset of patients with no post-procedural aortic regurgitation . TAVR may be preferable to SAVR in patients with a small aortic annulus who are susceptible to PPM to avoid its adverse impact on LV mass regression and survival . ( The PARTNER Trial : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) BACKGROUND Many patients with severe aortic stenosis and coexisting conditions are not c and i date s for surgical replacement of the aortic valve . Recently , transcatheter aortic-valve implantation ( TAVI ) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis . METHODS We r and omly assigned patients with severe aortic stenosis , whom surgeons considered not to be suitable c and i date s for surgery , to st and ard therapy ( including balloon aortic valvuloplasty ) or transfemoral transcatheter implantation of a balloon-exp and able bovine pericardial valve . The primary end point was the rate of death from any cause . RESULTS A total of 358 patients with aortic stenosis who were not considered to be suitable c and i date s for surgery underwent r and omization at 21 centers ( 17 in the United States ) . At 1 year , the rate of death from any cause ( Kaplan – Meier analysis ) was 30.7 % with TAVI , as compared with 50.7 % with st and ard therapy ( hazard ratio with TAVI , 0.55 ; 95 % confidence interval [ CI ] , 0.40 to 0.74 ; P<0.001 ) . The rate of the composite end point of death from any cause or repeat hospitalization was 42.5 % with TAVI as compared with 71.6 % with st and ard therapy ( hazard ratio , 0.46 ; 95 % CI , 0.35 to 0.59 ; P<0.001 ) . Among survivors at 1 year , the rate of cardiac symptoms ( New York Heart Association class III or IV ) was lower among patients who had undergone TAVI than among those who had received st and ard therapy ( 25.2 % vs. 58.0 % , P<0.001 ) . At 30 days , TAVI , as compared with st and ard therapy , was associated with a higher incidence of major strokes ( 5.0 % vs. 1.1 % , P=0.06 ) and major vascular complications ( 16.2 % vs. 1.1 % , P<0.001 ) . In the year after TAVI , there was no deterioration in the functioning of the bioprosthetic valve , as assessed by evidence of stenosis or regurgitation on an echocardiogram . CONCLUSIONS In patients with severe aortic stenosis who were not suitable c and i date s for surgery , TAVI , as compared with st and ard therapy , significantly reduced the rates of death from any cause , the composite end point of death from any cause or repeat hospitalization , and cardiac symptoms , despite the higher incidence of major strokes and major vascular events . ( Funded by Edwards Lifesciences ; Clinical Trials.gov number , NCT00530894 . ) The objective of this study was to compare outcomes in women after surgical aortic valve replacement ( SAVR ) versus transcatheter aortic valve replacement ( TAVR ) using a self-exp and ing prosthesis in patients with severe aortic stenosis who were at high risk for SAVR . Although registries and meta-analyses have suggested that TAVR is of considerable benefit in women , perhaps even more so than in men , a rigorous evaluation of TAVR with a self-exp and ing valve versus SAVR in women from a r and omized trial has not been performed . Patients with severe aortic stenosis were r and omized 1:1 to either TAVR or SAVR . Outcomes at 1 year are reported . Treatment was attempted in a total of 353 women ( 183 TAVR and 170 SAVR ) . Baseline characteristics and predicted risk of the 2 groups were comparable , although the frequency of diabetes mellitus was lower in patients undergoing TAVR ( 33.3 % vs 45.3 % ; p = 0.02 ) . TAVR-treated patients experienced a statistically significant 1-year survival advantage compared with SAVR patients ( 12.7 % vs 21.8 % ; p = 0.03 ) . The composite all-cause mortality or major stroke rate also favored TAVR ( 14.9 % vs 24.2 % ; p = 0.04 ) . Quality of life , as measured by the Kansas City Cardiomyopathy Question naire summary score , for both the TAVR and SAVR groups increased significantly from baseline to 1 year . In conclusion , female TAVR patients had lower 1-year mortality and lower 1-year all-cause mortality or major stroke compared with women undergoing SAVR , with both cohorts experiencing improved quality of life . Further studies specifically in women are warranted to vali date these findings BACKGROUND In patients with severe aortic stenosis at increased risk for surgery , self-exp and ing transcatheter aortic valve replacement ( TAVR ) is associated with improved 2-year survival compared with surgery . OBJECTIVES This study sought to determine whether this clinical benefit was sustained over time . METHODS Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were r and omized 1:1 to TAVR or open surgical valve replacement ( SAVR ) . Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure . RESULTS A total of 797 patients underwent r and omization at 45 U.S. centers ; 750 patients underwent an attempted procedure . Three-year all-cause mortality or stroke was significantly lower in TAVR patients ( 37.3 % vs. 46.7 % in SAVR ; p = 0.006 ) . Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients , including all-cause mortality ( 32.9 % vs. 39.1 % , respectively ; p = 0.068 ) , all stroke ( 12.6 % vs. 19.0 % , respectively ; p = 0.034 ) , and major adverse cardiovascular or cerebrovascular events ( 40.2 % vs. 47.9 % , respectively ; p = 0.025 ) . At 3 years aortic valve hemodynamics were better with TAVR patients ( mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR ; p < 0.001 ) , although moderate or severe residual aortic regurgitation was higher in TAVR patients ( 6.8 % vs. 0.0 % in SAVR ; p < 0.001 ) . There was no clinical evidence of valve thrombosis in either group . CONCLUSIONS Patients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery . Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration . ( Safety and Efficacy Study of the Medtronic CoreValve ( ® ) System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) BACKGROUND Based on the early results of the Placement of Aortic Transcatheter Valves ( PARTNER ) trial , transcatheter aortic valve replacement ( TAVR ) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery . However , little information is available about the late clinical outcomes in such patients . METHODS We did this r and omised controlled trial at 21 experienced valve centres in Canada , Germany , and the USA . We enrolled patients with severe symptomatic inoperable aortic stenosis and r and omly assigned ( 1:1 ) them to transfemoral TAVR or to st and ard treatment , which often included balloon aortic valvuloplasty . Patients and their treating physicians were not masked to treatment allocation . The r and omisation was done central ly , and sites learned of the assignment only after a patient had been screened , consented , and entered into the data base . The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population , here we present the prespecified findings after 5 years . This study is registered with Clinical Trials.gov , number NCT00530894 . FINDINGS We screened 3015 patients , of whom 358 were enrolled ( mean age 83 years , Society of Thoracic Surgeons Predicted Risk of Mortality 11·7 % , 54 % female ) . 179 were assigned to TAVR treatment and 179 were assigned to st and ard treatment . 20 patients crossed over from the st and ard treatment group and ten withdrew from study , leaving only six patients at 5 years , of whom five had aortic valve replacement treatment outside of the study . The risk of all-cause mortality at 5 years was 71·8 % in the TAVR group versus 93·6 % in the st and ard treatment group ( hazard ratio 0·50 , 95 % CI 0·39 - 0·65 ; p<0·0001 ) . At 5 years , 42 ( 86 % ) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three ( 60 % ) of five in the st and ard treatment group . Echocardiography after TAVR showed durable haemodynamic benefit ( aortic valve area 1·52 cm(2 ) at 5 years , mean gradient 10·6 mm Hg at 5 years ) , with no evidence of structural valve deterioration . INTERPRETATION TAVR is more beneficial than st and ard treatment for treatment of inoperable aortic stenosis . TAVR should be strongly considered for patients who are not surgical c and i date s for aortic valve replacement to improve their survival and functional status . Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities . FUNDING Edwards Lifesciences OBJECTIVES The goal of this study was to determine whether a less-invasive approach to aortic valve replacement ( AVR ) improves clinical outcomes in diabetic patients with aortic stenosis ( AS ) . BACKGROUND Diabetes is associated with increased morbidity and mortality after surgical AVR for AS . METHODS Among treated patients with severe symptomatic AS at high risk for surgery in the PARTNER ( Placement of Aortic Transcatheter Valve ) trial , we examined outcomes stratified according to diabetes status of patients r and omly assigned to receive transcatheter or surgical AVR . The primary outcome was all-cause mortality at 1 year . RESULTS Among 657 patients enrolled in PARTNER who underwent treatment , there were 275 patients with diabetes ( 145 transcatheter , 130 surgical ) . There was a significant interaction between diabetes and treatment group for 1-year all-cause mortality ( p = 0.048 ) . Among diabetic patients , all-cause mortality at 1 year was 18.0 % in the transcatheter group and 27.4 % in the surgical group ( hazard ratio : 0.60 [ 95 % confidence interval : 0.36 to 0.99 ] ; p = 0.04 ) . Results were consistent among patients treated via transfemoral or transapical routes . In contrast , among nondiabetic patients , there was no significant difference in all-cause mortality at 1 year ( p = 0.48 ) . Among diabetic patients , the 1-year rates of stroke were similar between treatment groups ( 3.5 % transcatheter vs. 3.5 % surgery ; p = 0.88 ) , but the rate of renal failure requiring dialysis > 30 days was lower in the transcatheter group ( 0 % vs. 6.1 % ; p = 0.003 ) . CONCLUSIONS Among patients with diabetes and severe symptomatic AS at high risk for surgery , this post-hoc stratified analysis of the PARTNER trial suggests there is a survival benefit , no increase in stroke , and less renal failure from treatment with transcatheter AVR compared with surgical AVR . ( The PARTNER Trial : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) BACKGROUND The Placement of Aortic Transcatheter Valves ( PARTNER ) trial showed that among high-risk patients with aortic stenosis , the 1-year survival rates are similar with transcatheter aortic-valve replacement ( TAVR ) and surgical replacement . However , longer-term follow-up is necessary to determine whether TAVR has prolonged benefits . METHODS At 25 centers , we r and omly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR . All patients were followed for at least 2 years , with assessment of clinical outcomes and echocardiographic evaluation . RESULTS The rates of death from any cause were similar in the TAVR and surgery groups ( hazard ratio with TAVR , 0.90 ; 95 % confidence interval [ CI ] , 0.71 to 1.15 ; P=0.41 ) and at 2 years ( Kaplan-Meier analysis ) were 33.9 % in the TAVR group and 35.0 % in the surgery group ( P=0.78 ) . The frequency of all strokes during follow-up did not differ significantly between the two groups ( hazard ratio , 1.22 ; 95 % CI , 0.67 to 2.23 ; P=0.52 ) . At 30 days , strokes were more frequent with TAVR than with surgical replacement ( 4.6 % vs. 2.4 % , P=0.12 ) ; subsequently , there were 8 additional strokes in the TAVR group and 12 in the surgery group . Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years . Paravalvular regurgitation was more frequent after TAVR ( P<0.001 ) , and even mild paravalvular regurgitation was associated with increased late mortality ( P<0.001 ) . CONCLUSIONS A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients . The two treatments were similar with respect to mortality , reduction in symptoms , and improved valve hemodynamics , but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality . ( Funded by Edwards Lifesciences ; Clinical Trials.gov number , NCT00530894 . ) BACKGROUND The Placement of Aortic Transcatheter Valves ( PARTNER ) trial showed that mortality at 1 year , 2 years , and 3 years is much the same with transcatheter aortic valve replacement ( TAVR ) or surgical aortic valve replacement ( SAVR ) for high-risk patients with aortic stenosis . We report here the 5-year outcomes . METHODS We did this r and omised controlled trial at 25 hospitals , in Canada ( two ) , Germany ( one ) , and the USA ( 23 ) . We used a computer-generated r and omisation sequence to r and omly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-exp and able bovine pericardial tissue valve by either a transfemoral or transapical approach . Patients and their treating physicians were not masked to treatment allocation . The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year , we present here predefined outcomes at 5 years . The study is registered with Clinical Trials.gov , number NCT00530894 . FINDINGS We screened 3105 patients , of whom 699 were enrolled ( 348 assigned to TAVR , 351 assigned to SAVR ) . Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11·7 % . At 5 years , risk of death was 67·8 % in the TAVR group compared with 62·4 % in the SAVR group ( hazard ratio 1·04 , 95 % CI 0·86 - 1·24 ; p=0·76 ) . We recorded no structural valve deterioration requiring surgical valve replacement in either group . Moderate or severe aortic regurgitation occurred in 40 ( 14 % ) of 280 patients in the TAVR group and two ( 1 % ) of 228 in the SAVR group ( p<0·0001 ) , and was associated with increased 5-year risk of mortality in the TAVR group ( 72·4 % for moderate or severe aortic regurgitation vs 56·6 % for those with mild aortic regurgitation or less ; p=0·003 ) . INTERPRETATION Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes . FUNDING Edwards Lifesciences BACKGROUND Transcatheter aortic-valve replacement ( TAVR ) is the recommended therapy for patients with severe aortic stenosis who are not suitable c and i date s for surgery . The outcomes beyond 1 year in such patients are not known . METHODS We r and omly assigned patients to transfemoral TAVR or to st and ard therapy ( which often included balloon aortic valvuloplasty ) . Data on 2-year outcomes were analyzed . RESULTS A total of 358 patients underwent r and omization at 21 centers . The rates of death at 2 years were 43.3 % in the TAVR group and 68.0 % in the st and ard-therapy group ( P<0.001 ) , and the corresponding rates of cardiac death were 31.0 % and 62.4 % ( P<0.001 ) . The survival advantage associated with TAVR that was seen at 1 year remained significant among patients who survived beyond the first year ( hazard ratio , 0.58 ; 95 % confidence interval [ CI ] , 0.36 to 0.92 ; P=0.02 with the use of the log-rank test ) . The rate of stroke was higher after TAVR than with st and ard therapy ( 13.8 % vs. 5.5 % , P=0.01 ) , owing , in the first 30 days , to the occurrence of more ischemic events in the TAVR group ( 6.7 % vs. 1.7 % , P=0.02 ) and , beyond 30 days , to the occurrence of more hemorrhagic strokes in the TAVR group ( 2.2 % vs. 0.6 % , P=0.16 ) . At 2 years , the rate of rehospitalization was 35.0 % in the TAVR group and 72.5 % in the st and ard-therapy group ( P<0.001 ) . TAVR , as compared with st and ard therapy , was also associated with improved functional status ( P<0.001 ) . The data suggest that the mortality benefit after TAVR may be limited to patients who do not have extensive coexisting conditions . Echocardiographic analysis showed a sustained increase in aortic-valve area and a decrease in aortic-valve gradient , with no worsening of paravalvular aortic regurgitation . CONCLUSIONS Among appropriately selected patients with severe aortic stenosis who were not suitable c and i date s for surgery , TAVR reduced the rates of death and hospitalization , with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of follow-up . The presence of extensive coexisting conditions may attenuate the survival benefit of TAVR . ( Funded by Edwards Lifesciences ; Clinical Trials.gov number , NCT00530894 . ) OBJECTIVES This study sought to compare echocardiographic findings in patients with critical aortic stenosis following surgical aortic valve replacement ( SAVR ) or transcatheter aortic valve replacement ( TAVR ) . BACKGROUND The PARTNER ( Placement of Aortic Transcatheter Valves ) trial r and omized patients 1:1 to SAVR or TAVR . METHODS Echocardiograms were obtained at baseline , discharge , 30 days , 6 months , 1 year , and 2 years after the procedure and analyzed in a core laboratory . For the analysis of post-implantation variables , the first interpretable study ( ≤6 months ) was used . RESULTS Both groups showed a decrease in aortic valve gradients and increase in effective orifice area ( EOA ) ( p < 0.0001 ) , which remained stable over 2 years . Compared with SAVR , TAVR result ed in larger indexed EOA ( p = 0.038 ) , less prosthesis-patient mismatch ( p = 0.019 ) , and more total and paravalvular aortic regurgitation ( p < 0.0001 ) . Baseline echocardiographic univariate predictors of death were lower peak transaortic gradient in TAVR patients , and low left ventricular diastolic volume , low stroke volume , and greater severity of mitral regurgitation in SAVR patients . Post-implantation echocardiographic univariate predictors of death were : larger left ventricular diastolic volume , left ventricular systolic volume and EOA , decreased ejection fraction , and greater aortic regurgitation in TAVR patients ; and smaller left ventricular systolic and diastolic volumes , low stroke volume , smaller EOA , and prosthesis-patient mismatch in SAVR patients . CONCLUSIONS Patients r and omized to either SAVR or TAVR experience enduring , significant reductions in transaortic gradients and increase in EOA . Compared with SAVR , TAVR patients had higher indexed EOA , lower prosthesis-patient mismatch , and more aortic regurgitation . Univariate predictors of death for the TAVR and SAVR groups differed and might allow future refinement in patient selection . ( THE PARTNER TRIAL : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) OBJECTIVES This study sought to identify the incidence , predictors , and prognostic impact of bleeding complications ( BC ) after surgical aortic valve replacement ( SAVR ) compared with transcatheter aortic valve replacement ( TAVR ) . BACKGROUND Bleeding complications after SAVR and TAVR are frequent and may be associated with an unfavorable prognosis . METHODS In the r and omized controlled PARTNER ( Placement of Aortic Transcatheter Valve ) I trial , 657 patients from cohort A ( operable high risk ) were r and omly assigned to SAVR or TAVR ( transfemoral [ TF ] if iliofemoral access was suitable or transapical [ TA ] if not ) and received the design ated treatment . First-generation Edwards SAPIEN valves and delivery systems ( Edwards Lifesciences , Irvine , California ) were used for TAVR , through a 22- or 24-F sheath . The 30-day rates of major BC ( modified Valve Academic Research Consortium definitions ) , predictors of BC , and their association with 1-year mortality were assessed . RESULTS A total of 71 ( 22.7 % ) , 27 ( 11.3 % ) , and 9 ( 8.8 % ) patients had major BC within 30 days of the procedure after SAVR , TF-TAVR , and TA-TAVR , respectively ( p < 0.0001 ) . SAVR was associated with a significantly higher 30-day rate of transfusion ( 17.9 % ) than either TF-TAVR ( 7.1 % ) or TA-TAVR ( 4.8 % ; p < 0.0001 ) . Independent predictors of major BC were the occurrence of major vascular complications and use of intraprocedural hemodynamic support among TF-TAVR patients , severe procedural complications requiring conversion to open surgery among TA-TAVR patients , and the presence of low hemoglobin at baseline among SAVR patients . Major BC was identified as the strongest independent predictor of 1-year mortality among the full cohort . However , risk-adjusted analyses demonstrated a significant interaction between BC and treatment strategy with respect to mortality , suggesting that BC after SAVR have a greater impact on prognosis than after TAVR . CONCLUSIONS Among high-risk aortic stenosis patients enrolled in the PARTNER I r and omized trial , BC were more common after SAVR than after TAVR and were also associated with a worse long-term prognosis . ( THE PARTNER TRIAL : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) BACKGROUND The U.S. pivotal trial for the self-exp and ing valve found that among patients with severe aortic stenosis at increased risk for surgery , the 1-year survival rate was 4.9 percentage points higher in patients treated with a self-exp and ing transcatheter aortic valve bioprosthesis than in those treated with a surgical bioprosthesis . OBJECTIVES Longer-term clinical outcomes were examined to confirm if this mortality benefit is sustained . METHODS Patients with severe aortic stenosis who were at increased surgical risk were recruited . Eligible patients were r and omly assigned in a 1:1 ratio to transcatheter aortic valve replacement with the self-exp and ing transcatheter valve ( transcatheter aortic valve replacement [ TAVR ] group ) or to aortic valve replacement with a surgical bioprosthesis ( surgical group ) . The 2-year clinical and echocardiographic outcomes were evaluated in these patients . RESULTS A total of 797 patients underwent r and omization at 45 centers in the United States . The rate of 2-year all-cause mortality was significantly lower in the TAVR group ( 22.2 % ) than in the surgical group ( 28.6 % ; log-rank test p < 0.05 ) in the as-treated cohort , with an absolute reduction in risk of 6.5 percentage points . Similar results were found in the intention-to-treat cohort ( log-rank test p < 0.05 ) . The rate of 2-year death or major stroke was significantly lower in the TAVR group ( 24.2 % ) than in the surgical group ( 32.5 % ; log-rank test p = 0.01 ) . CONCLUSIONS In patients with severe aortic stenosis who are at increased surgical risk , the higher rate of survival with a self-exp and ing TAVR compared with surgery was sustained at 2 years . ( Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) BACKGROUND All neurologic events in the PARTNER r and omized trial comparing transcatheter aortic valve replacement ( TAVR ) with surgical aortic valve replacement ( AVR ) were analyzed . METHODS High-risk patients with aortic stenosis were stratified into transfemoral ( TF , n = 461 ) or transapical ( TA , n = 196 ) strata based on their arterial anatomy and r and omized : 657 received treatment assigned ( " as treated " ) , 313 underwent AVR , and 344 TAVR . Neurologic events were prospect ively adjudicated by an independent Clinical Events Committee . Multivariable , multiphase hazard analysis eluci date d factors associated with increased likelihood of neurologic events . RESULTS Forty-nine neurologic events ( 15 transient ischemic attacks , 34 strokes ) occurred in 47 patients ( TAVR , n = 31 ; AVR , n = 16 ) . An early peaking high hazard phase occurred within the first week , which declined to a constant late hazard phase out to 2 years . The risk in the early phase was higher after TAVR than AVR , and in the TAVR arm in patients with a smaller aortic valve area index . In the late risk phase , the likelihood of neurologic event was linked to patient-related factors in both arms ( " non-TF c and i date , " history of recent stroke or transient ischemic attack , and advanced functional disability ) , but not by treatment ( TAVR vs AVR ) or any intraprocedural variables . The likelihood of sustaining a neurologic event was lowest in the AVR subgroup in the TF stratum during all available follow-up . CONCLUSIONS After either treatment , there were 2 distinct hazard phases for neurologic events that were driven by different risk factors . Neurologic complications occurred more frequently after TAVR than AVR early , but thereafter the risk was influenced by patient- and disease-related factors |
1,149 | 17,327,526 | In low-bias risk trials , after exclusion of selenium trials , beta carotene ( RR , 1.07 ; 95 % CI , 1.02 - 1.11 ) , vitamin A ( RR , 1.16 ; 95 % CI , 1.10 - 1.24 ) , and vitamin E ( RR , 1.04 ; 95 % CI , 1.01 - 1.07 ) , singly or combined , significantly increased mortality .
Vitamin C and selenium had no significant effect on mortality .
CONCLUSIONS Treatment with beta carotene , vitamin A , and vitamin E may increase mortality . | CONTEXT Antioxidant supplements are used for prevention of several diseases .
OBJECTIVE To assess the effect of antioxidant supplements on mortality in r and omized primary and secondary prevention trials . | BACKGROUND / AIMS The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled r and omized trial . METHODS Twenty-five patients received 1000 I.U. of vitamin E per day , while 26 patients received placebo for 3 months . The patients were followed for 1 year after entry into the trial . RESULTS Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo . Prothrombin time did not change , while serum creatinine remained in the normal range . Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent , regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis , vitamin E treatment decreased serum hyaluronic acid ( P<0.05 ) while serum aminoterminal peptide of type III procollagen did not change in either group . Four patients in the treatment group and five in the placebo group died during the 1-year study . CONCLUSIONS Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis Ageing is associated with impaired immune responses and increased infection-related morbidity . This study assessed the effect of physiological amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness . 96 independently living , healthy elderly individuals were r and omly assigned to receive nutrient supplementation or placebo . Nutrient status and immunological variables were assessed at baseline and at 12 months , and the frequency of illness due to infection was ascertained . Subjects in the supplement group had higher numbers of certain T-cell subsets and natural killer cells , enhanced proliferation response to mitogen , increased interleukin-2 production , and higher antibody response and natural killer cell activity . These subjects were less likely than those in the placebo group to have illness due to infections ( mean [ SD ] 23 [ 5 ] vs 48 [ 7 ] days per year , p = 0.002 ) . Supplementation with a modest physiological amount of micronutrients improves immunity and decreases the risk of infection in old age BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration BACKGROUND The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the effect of daily beta-carotene ( 30 mg ) and retinyl palmitate ( 25,000 IU ) on the incidence of lung cancer , other cancers , and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure . CARET was stopped ahead of schedule in January 1996 because participants who were r and omly assigned to receive the active intervention were found to have a 28 % increase in incidence of lung cancer , a 17 % increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group . METHODS After the intervention ended , CARET participants returned the study vitamins to their study center and provided a final blood sample . They continue to be followed annually by telephone and mail self-report . Self-reported cancer endpoints were confirmed by review of pathology reports , and death endpoints were confirmed by review of death certificates . All statistical tests were two-sided . RESULTS With follow-up through December 31 , 2001 , the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 ( 95 % confidence interval [ CI ] = 0.97 to 1.31 ) and 1.08 ( 95 % CI = 0.99 to 1.17 ) , respectively . Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up . By contrast , the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped . During the post-intervention phase , females had larger relative risks of lung cancer mortality ( 1.33 versus 1.14 ; P = .36 ) , cardiovascular disease mortality ( 1.44 versus 0.93 ; P = .03 ) , and all-cause mortality ( 1.37 versus 0.98 ; P = .001 ) than males . CONCLUSIONS The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant . Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females , and cardiovascular disease mortality primarily to females and to former smokers Patients with chronic hepatitis C virus ( HCV ) infection often develop liver cirrhosis and hepatocellular carcinoma ( HCC ) . The purpose of this study was to test the chemopreventive effect of alpha-tocopherol on hepatocarcinogenesis in patients with liver cirrhosis and a history of HCV infection . Eighty-three patients with liver cirrhosis and with positive history of HCV infection were divided at r and om into two groups . Forty-four patients were treated with alpha-tocopherol ( Vit E group ) while the other 39 were followed as controls . The clinical background ( gender , age , and laboratory data ) was similar in the two groups . Serum levels of alpha-tocopherol , albumin , alanine aminotransferase ( ALT ) , and total cholesterol and platelet count were measured serially over a period of five years . The mean serum concentration of alpha-tocopherol was low in both groups at entry and was significantly higher in the Vit E group than in the control group one month after treatment . Platelet count , serum albumin , ALT , and total cholesterol were not different between the two groups during the five-year period . Cumulative tumor-free survival and cumulative survival rate tended to be higher in the Vit E group than in controls , albeit statistically insignificant . The serum level of alpha-tocopherol was low in patients with liver cirrhosis and positive for HCV . Although the administration of alpha-tocopherol normalized the level one month later , it could neither improve liver function , suppress hepatocarcinogenesis , nor improve cumulative survival . Patients treated with alpha-tocopherol tended to live longer without development of HCC but the difference was not statistically significant BACKGROUND It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer . To date , however , the published results of r and omized , placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect . We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population . METHODS The Supplementation en Vitamines et Mineraux Antioxydants ( SU.VI.MAX ) study is a r and omized , double-blind , placebo-controlled primary prevention trial . A total of 13 017 French adults ( 7876 women aged 35 - 60 years and 5141 men aged 45 - 60 years ) were included . All participants took a single daily capsule of a combination of 120 mg of ascorbic acid , 30 mg of vitamin E , 6 mg of beta carotene , 100 mug of selenium , and 20 mg of zinc , or a placebo . Median follow-up time was 7.5 years . RESULTS No major differences were detected between the groups in total cancer incidence ( 267 [ 4.1 % ] for the study group vs 295 [ 4.5 % ] for the placebo group ) , ischemic cardiovascular disease incidence ( 134 [ 2.1 % ] vs 137[2.1 % ] ) , or all-cause mortality ( 76 [ 1.2 % ] vs 98 [ 1.5 % ] ) . However , a significant interaction between sex and group effects on cancer incidence was found ( P = .004 ) . Sex-stratified analysis showed a protective effect of antioxidants in men ( relative risk , 0.69 [ 95 % confidence interval [ CI ] , 0.53 - 0.91 ] ) but not in women ( relative risk , 1.04 [ 95 % CI , 0.85 - 1.29 ] ) . A similar trend was observed for all-cause mortality ( relative risk , 0.63 [ 95 % CI , 0.42 - 0.93 ] in men vs 1.03 [ 95 % CI , 0.64 - 1.63 ] in women ; P = .11 for interaction ) . CONCLUSIONS After 7.5 years , low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women . Supplementation may be effective in men only because of their lower baseline status of certain antioxidants , especially of beta carotene Background —Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease ( CVD ) risk . In contrast , r and omized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events . Methods and Results —The study population consisted of men and women ≥40 years old with an LDL cholesterol level ≥3.37 mmol/L ( 130 mg/dL ) and no clinical signs or symptoms of CVD . Eligible participants were r and omized to DL-&agr;-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years . The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness ( IMT ) assessed by computer image-processed B-mode ultrasonograms . A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates . Compared with placebo , & agr;-tocopherol supplementation significantly raised plasma vitamin E levels ( P < 0.0001 ) , reduced circulating oxidized LDL ( P = 0.03 ) , and reduced LDL oxidative susceptibility ( P < 0.01 ) . However , vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects r and omized to placebo . Conclusions —The results are consistent with previous r and omized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials We hypothesize that smokers with the null genotype for GSTM1 ( GSTM1 - 0 ) , who thus lack the detoxification enzyme glutathione S-transferase mu-1 , develop atherosclerosis at an increased rate compared to smokers with the positive genotype ( GSTM1 - 1 ) . We used data from a 2-year r and omized placebo-controlled trial on the effect of vitamin E on atherosclerosis among 189 male smokers . Progression of atherosclerosis was measured by 2-year change of the common carotid intima media thickness ( CCA-IMT ) as measured by B-mode ultrasonography . The frequency of GSTM1 - 0 genotype was 0.5 in both the placebo and the vitamin E group . Smokers with GSTM1 - 0 genotype had a tendency to higher baseline CCA-IMT values than those with GSTM1 - 1 ( 0.97 versus 0.92 mm , P=0.09 ) . Within the placebo group , more CCA-IMT progression was found for smokers with the GSTM1 - 0 than for smokers with the GSTM1 - 1 genotype after adjustment for baseline IMT and major CVD risk factors ( 0.050 versus -0.002 mm , P=0.046 ) . In the vitamin E group no effect of GSTM1 genotype on atherosclerosis progression was found . Overall , smokers with GSTM1 - 0 genotype had a higher mean 2-year progression compared to those with GSTM1 - 1 as shown by a difference in increase of 0.042 mm ( 95 % CI 0.006 ; 0.078 , P=0.02 ) . In conclusion , our data suggest that smokers lacking the detoxifying enzyme GST mu-1 develop progression of atherosclerosis at an increased rate Passage of the DSHEA in 1994 created a new “ liminal ” category for the FDA : dietary supplements are regulated as neither food nor drugs . However , there appears to be a significant disconnect between the “ official ” discourse surrounding dietary supplements and supplement users ’ actual practice s. Despite this discrepancy , and the inadequacy of surveys to capture the dynamics of pharmaceutical practice , there is little ethnographic information available on the ways that Americans think about or use dietary supplements . We offer some preliminary observations from a pilot ethnographic study of Americans ’ use of dietary supplements in which we consider not only the reasons why people are using supplements , but how they are using them , and how their experimentation has been influenced by the information they seek and receive from a variety of sources . We illustrate how anthropological studies of supplement related practice can help us better underst and Americans ’ attraction to and use of dietary supplements , and suggest that anthropology can contribute to a more balanced perspective on supplement use — one that moves the study of supplements beyond surveys and r and omized controlled studies of efficacy to considerations of patterns of use in context , user expectations , and measures of perceived effectiveness OBJECTIVE To determine whether vitamin E affects change in cartilage volume in patients with knee osteoarthritis ( OA ) . METHODS In a double blind , placebo controlled trial , 136 patients with knee OA ( American College of Rheumatology clinical and radiographic criteria ) were r and omized to receive vitamin E ( 500 IU ) or placebo for 2 years . Tibial cartilage volume was measured by magnetic resonance imaging at the beginning and end of the study . RESULTS Baseline characteristics were similar in the 2 groups ( 67 vitamin E , 69 placebo ) ; there were more women in the vitamin E group , 42 ( 63 % ) vs 33 ( 48 % ) in the placebo group . One hundred seventeen subjects ( 59 vitamin E , 58 placebo ) completed the study . Loss of medial and lateral tibial cartilage was similar in subjects treated with vitamin E and placebo ( mean + /- SD : medial 157 + /- 209 vs 187 + /- 220 micro m3 placebo , p = 0.51 ; lateral 186 + /- 258 vs 251 + /- 216 micro m3 , p = 0.19 ) . There were no significant differences between the vitamin E and placebo treated groups in improvement of symptoms from baseline . Dietary levels of antioxidants ( vitamin C , beta carotene , retinol equivalents ) had no effect on cartilage volume loss . CONCLUSION Vitamin E does not appear to have a beneficial effect in the management of knee OA : it does not affect cartilage volume loss or symptoms BACKGROUND Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer 's disease . METHODS In a double-blind study , we evaluated subjects with the amnestic subtype of mild cognitive impairment . Subjects were r and omly assigned to receive 2000 IU of vitamin E daily , 10 mg of donepezil daily , or placebo for three years . The primary outcome was clinical ly possible or probable Alzheimer 's disease ; secondary outcomes were cognition and function . RESULTS A total of 769 subjects were enrolled , and possible or probable Alzheimer 's disease developed in 212 . The overall rate of progression from mild cognitive impairment to Alzheimer 's disease was 16 percent per year . As compared with the placebo group , there were no significant differences in the probability of progression to Alzheimer 's disease in the vitamin E group ( hazard ratio , 1.02 ; 95 percent confidence interval , 0.74 to 1.41 ; P=0.91 ) or the donepezil group ( hazard ratio , 0.80 ; 95 percent confidence interval , 0.57 to 1.13 ; P=0.42 ) during the three years of treatment . Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group , the donepezil group had a reduced likelihood of progression to Alzheimer 's disease during the first 12 months of the study ( P=0.04 ) , a finding supported by the secondary outcome measures . Among carriers of one or more apolipoprotein E epsilon4 alleles , the benefit of donepezil was evident throughout the three-year follow-up . There were no significant differences in the rate of progression to Alzheimer 's disease between the vitamin E and placebo groups at any point , either among all patients or among apolipoprotein E epsilon4 carriers . CONCLUSIONS Vitamin E had no benefit in patients with mild cognitive impairment . Although donepezil therapy was associated with a lower rate of progression to Alzheimer 's disease during the first 12 months of treatment , the rate of progression to Alzheimer 's disease after three years was not lower among patients treated with donepezil than among those given placebo Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications result ing in carcinogenesis . Dietary antioxidants trap these species limiting their damage . The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who , because of hypochlorhydria and possible depletion of gastric antioxidants , could be at increased risk of gastric cancer . Patients undergoing surveillance for Barrett 's oesophagus ( n 100 ) , on long-term proton pump inhibitors were r and omized into two groups : vitamin C ( 500 mg twice/d ) and vitamin E ( 100 mg twice/d ) for 12 weeks ( the supplemented group ) or placebo . Those attending for subsequent endoscopy had gastric juice , plasma and mucosal measurements of vitamin levels and markers of DNA damage . Seventy-two patients completed the study . Plasma ascorbic acid , total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance . Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group ( P=0.01 ) but supplementation had no effect on the mucosal level of this vitamin . However , gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group . Mucosal malondialdehyde , chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation . In conclusion , supplementation does not affect DNA damage in this group of patients . This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion Background —Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression , but the evidence from clinical trials is controversial . In the first 3 years of the ASAP trial , the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women . This article examines the 6-year effect of supplementation on common carotid artery ( CCA ) intima-media thickness ( IMT ) . Methods and Results —The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol ≥5.0 mmol/L ( 193 mg/dL ) , 440 ( 84.6 % ) of whom completed the study . Atherosclerotic progression was assessed ultrasonographically . In covariance analysis in both sexes , supplementation reduced the main study outcome , the slope of mean CCA-IMT , by 26 % ( 95 % CI , 5 to 46 , P = 0.014 ) , in men by 33 % ( 95 % CI , 4 to 62 , P = 0.024 ) and in women by 14 % ( not significant ) . In both sexes combined , the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group ( 25 % treatment effect , 95 % CI , 2 to 49 , P = 0.034 ) . In men , this treatment effect was 37 % ( 95 CI , 4 to 69 , P = 0.028 ) . The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques . Vitamin E had no effect on HDL cholesterol . Conclusions —These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes BACKGROUND Selenium is known to be important to the brain . Three small , published studies have suggested an effect of selenium supplementation or deprivation on mood in healthy volunteers . We investigated these findings on a much larger scale . METHODS In this double-blind , placebo-controlled intervention , 501 UK participants aged 60 - 74 were r and omly allocated to receive 100 , 200 or 300 microg selenium/d as high-selenium yeast or placebo yeast . Mood ( Profile of Moods States - Bipolar Form [ POMS-BI ] question naire ) , " quality of life " ( Short Form 36 [ SF-36 ] question naire ) and plasma selenium were measured at baseline and six months . RESULTS Supplementation significantly increased plasma selenium above baseline values : from an overall mean ( SD ) of 90(19 ) ng/g to 91(26 ) , 144(27 ) , 191(41 ) and 227(53 ) ng/g in the placebo , 100 , 200 , 300 microg selenium groups respectively ( p < .001 ) . Four hundred forty-eight participants completed the POMS-BI question naires at both time points , with no significant differences in total mood or mood-subscale scores seen between doses . After six months of supplementation , mean ( SD ) total mood scores for the four doses were 163(36 ) , 161(37 ) , 162(33 ) , 162(34 ) , F(3,443 ) = .25 , p = .86 . Quality of life was similarly unaffected . CONCLUSIONS There was no evidence that selenium supplementation benefited mood or quality of life in these elderly volunteers . Though this is at odds with some previous results , our robust study design , much larger sample size and longer supplementation period , together with the evidence that the brain is a privileged site for selenium retention , suggest that this is a reliable finding The objective of this study was to assess the effects of ascorbic acid supplementation , 500 mg twice daily in the treatment of pressure ulcers as an adjunct to st and ardized treatment . The design consisted of a multicenter blinded r and omized trial . The control group received 10 mg of ascorbic acid twice daily . Patients from 11 nursing homes and 1 hospital participated . Main outcome measures included wound survival , healing rates of wound surfaces , and clinimetric changes over 12 weeks . Eighty-eight patients were r and omized . Intention-to-treat analysis showed that the wound closure probability per unit time ( i.e. , the closure rate ) was not higher in the intervention group than in the control group ( Cox hazard ratio of 0.78 [ 90 % precision interval , 0.44 - 1.39 ] ) . Mean absolute healing rates were 0.21 and 0.27 cm2/week in the intervention and control group , respectively ( PI of the adjusted difference : -0.17 to 0.13 ) . Relative healing rates and healing velocities did not show favorable results of ascorbic acid supplementation , either . A panel scored slides of the ulcers with a report mark between 1 ( bad ) and 10 ( excellent ) . The improvement was 0.45 and 0.72 points per week in the intervention and control group , respectively ( PI of the adjusted difference : -0.50 to 0.20 ) . With another clinimetric index we could not show any differences , either . These data do not support the idea that ascorbic acid supplementation ( 500 vs. 10 mg twice daily ) speeds up the healing of pressure ulcers Thirty elderly long-stay patients were r and omly allocated to receive either placebo or dietary supplementation with vitamins A , C and E for 28 days . Nutritional status and cell-mediated immune function were assessed before and after the period of supplementation . Following vitamin supplementation , cell-mediated immune function improved as indicated by a significant increase in the absolute number of T cells ( p less than 0.05 ) , T4 subsets ( p less than 0.05 ) , T4 to T8 ratio ( p less than 0.01 ) and the proliferation of lymphocytes in response to phytohaemagglutinin ( p less than 0.01 ) . In contrast , no significant changes were noted in the immune function of the placebo group . We conclude that supplementation with the dietary antioxidants vitamins A , C and E can improve aspects of cell-mediated immune function in elderly long-stay patients OBJECTIVE Patients with systemic lupus erythematosus ( SLE ) experience excess morbidity and mortality due to coronary artery disease ( CAD ) that can not be fully explained by the classical CAD risk factors . Among emerging CAD risk factors , oxidative stress is currently being emphasized . We evaluated the effects of longterm antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE . METHODS Patients were r and omized to receive either placebo or vitamins ( 500 mg vitamin C and 800 IU vitamin E daily ) for 12 weeks . Markers of oxidative stress included malondialdehyde ( MDA ) and allantoin . Antioxidants measured included erythrocyte superoxide dismutase and glutathione peroxidase , plasma total antioxidant power ( as FRAP value ) , and ascorbic acid and vitamin E concentrations . Endothelial function was assessed by flow-mediated dilatation ( FMD ) of the brachial artery and plasma concentration of von Willebr and factor ( vWF ) and plasminogen activator inhibitor type 1 ( PAI-1 ) . Primary outcome of the study included the change in lipid peroxidation as revealed by MDA levels . Secondary outcomes included changes in allantoin and antioxidant levels and change in endothelial function . RESULTS After treatment , plasma ascorbic acid and alpha-tocopherol concentrations were significantly ( p < 0.05 ) increased only in the vitamin-treated group , associated with a significant decrease ( p < 0.05 ) in plasma MDA . Other oxidative stress markers and antioxidant levels remained unchanged in both groups . FMD and vWF and PAI-1 levels remained unchanged in both groups . CONCLUSION Combined administration of vitamins C and E was associated with decreased lipid peroxidation , but did not affect endothelial function in patients with SLE after 3 months of therapy We conducted a r and omized , double-blind , controlled trial to examine the efficacy of retinol supplementation on the incidence of first new nonmelanoma skin cancer in moderate-risk subjects . A total of 2297 free-living subjects were enrolled ; subjects resided in Arizona ( median age , 63 years ) and had a history of more than 10 actinic keratoses and at most 2 squamous cell carcinoma ( SCC ) or basal cell carcinoma ( BCC ) skin cancers . Subjects were r and omly assigned to receive oral retinol ( 25,000 IU ) or placebo supplementation daily for up to 5 years . The primary end points for the trial were time to first new SCC or BCC . During a median follow-up time of 3.8 years , we found that 526 subjects had a first new skin cancer . Comparing retinol-supplemented subjects with placebo-supplemented subjects showed a hazard ratio for first new SCC of 0.74 ( 95 % confidence interval , 0.56 - 0.99 ; P = 0.04 ) . The hazard ratio of first new BCC for the retinol-supplemented subjects compared with those receiving placebo was 1.06 ( 95 % confidence interval , 0.86 - 1.32 ; P = 0.36 ) . Potentially adverse symptoms that were judged to be associated with retinol were rare ( approximately 1 % higher in the retinol group than in the control group ) . Therefore , we concluded that daily supplementation with 25,000 IU of retinol was effective in preventing SCC , although it did not prevent BCC AIMS Chronic heart failure ( CHF ) is a common and leading cause of death in industrialized countries . The potential benefits of micronutrient supplementation in CHF are extensive . Therefore , we examined the influence of long-term multiple micronutrient supplementation on left ventricular ( LV ) function , levels of pro-inflammatory cytokines , and quality -of-life ( QoL ) in elderly patients with CHF . METHODS AND RESULTS Thirty CHF patients [ age 75.4 ( 0.7 ) , mean ( SEM ) , LV ejection fraction ( LVEF ) < or = 35 % ] were r and omized to receive capsules containing a combination of high-dose micronutrients ( calcium , magnesium , zinc , copper , selenium , vitamin A , thiamine , riboflavin , vitamin B(6 ) , folate , vitamin B(12 ) , vitamin C , vitamin E , vitamin D , and Coenzyme Q10 ) or placebo for 9 months in a double-blind fashion . All subjects were on stable optimal medical therapy for at least 3 months before enrolment . At r and omization and at study end , tumour necrosis factor-alpha and its soluble receptors TNFR-1 and TNFR-2 were measured and six-minute walk test and QoL were assessed . Cardiac magnetic resonance scanning was performed to evaluate cardiac dimensions and LVEF . Two patients died during follow-up . The remaining patients ( 14 r and omized to placebo and 14 to micronutrients ) were well matched for LV function , symptoms , and exercise capacity . At the end of the follow-up period , LV volumes were reduced in the intervention group with no change in the placebo group [ -13.1 (17.1)% vs. + 3.8 (10.0)% ; P<0.05 ] . LVEF increased by 5.3+/-1.4 % in the intervention group and was unchanged in the placebo group ( P<0.05 ) . Patients taking micronutrients also had a significant improvement in QoL score between enrolment and study end [ + 9.5 (1.6)% ; P<0.05 ] , whereas those taking placebo had a slight deterioration [ -1.1 (0.8)% ; P=0.12 ] . Six-minute walk test and inflammatory cytokine levels remained unchanged in both groups . CONCLUSION Long-term multiple micronutrient supplementation can improve LV volumes and LVEF and QoL scores in elderly patients with heart failure due to LV systolic dysfunction BACKGROUND Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity . However , few large trials in elderly people have been conducted that include end points for clinical variables . OBJECTIVE To determine the effects of long-term daily supplementation with trace elements ( zinc sulfate and selenium sulfide ) or vitamins ( beta carotene , ascorbic acid , and vitamin E ) on immunity and the incidence of infections in institutionalized elderly people . METHODS This r and omized , double-blind , placebo-controlled intervention study included 725 institutionalized elderly patients ( > 65 years ) from 25 geriatric centers in France . Patients received an oral daily supplement of nutritional doses of trace elements ( zinc and selenium sulfide ) or vitamins ( beta carotene , ascorbic acid , and vitamin E ) or a placebo within a 2 x 2 factorial design for 2 years . MAIN OUTCOME MEASURES Delayed-type hypersensitivity skin response , humoral response to influenza vaccine , and infectious morbidity and mortality . RESULTS Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year , during which there was no effect of any treatment on delayed-type hypersensitivity skin response . Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins , whereas the vitamin group had significantly lower antibody titers ( P<.05 ) . The number of patients without respiratory tract infections during the study was higher in groups that received trace elements ( P = .06 ) . Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections . Survival analysis for the 2 years did not show any differences between the 4 groups . CONCLUSIONS Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections BACKGROUND There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer 's disease . METHODS We conducted a double-blind , placebo-controlled , r and omized , multicenter trial in patients with Alzheimer 's disease of moderate severity . A total of 341 patients received the selective monoamine oxidase inhibitor selegiline ( 10 mg a day ) , alpha-tocopherol ( vitamin E , 2000 IU a day ) , both selegiline and alpha-tocopherol , or placebo for two years . The primary outcome was the time to the occurrence of any of the following : death , institutionalization , loss of the ability to perform basic activities of daily living , or severe dementia ( defined as a Clinical Dementia Rating of 3 ) . RESULTS Despite r and om assignment , the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups , and this variable was highly predictive of the primary outcome ( P<0.001 ) . In the unadjusted analyses , there was no statistically significant difference in the outcomes among the four groups . In analyses that included the base-line score on the Mini-Mental State Examination as a covariate , there were significant delays in the time to the primary outcome for the patients treated with selegiline ( median time , 655 days ; P=0.012 ) , alpha-tocopherol ( 670 days , P=0.001 ) or combination therapy ( 585 days , P=0.049 ) , as compared with the placebo group ( 440 days ) . CONCLUSIONS In patients with moderately severe impairment from Alzheimer 's disease , treatment with selegiline or alpha-tocopherol slows the progression of disease Because supplements of vitamins C and E had been associated with reduction of fecal mutagen levels , a double-blind r and omized trial was design ed to examine the effects of these vitamins on the rate of recurrence of colorectal polyps , presumed precursors for colorectal cancer . Two hundred patients believed to be free of polyps after removal of at least one colorectal polyp were r and omized to receive a supplement of 400 mg each of ascorbic acid and alpha-tocopherol , or a placebo . Fifteen patients had to be excluded because a review of pathology indicated that their polyps were not adenomatous . A second colonoscopic examination was planned after 2 yr of supplementation . One hundred thirty-seven people ( 75 % of eligible subjects ) completed the study ; polyps were observed in the second colonoscopy in 41.4 % of 70 subjects on vitamin supplements and in 50.7 % of 67 subjects on placebos . After adjustment for differences between groups in demographic and dietary factors before study entry , the relative risk of polyp occurrence was 0.86 , with 95 % confidence limits from 0.51 to 1.45 , in an analysis of 129 subjects with complete information on demographic and dietary factors who had completed the trial . Of the 48 patients who had not completed the study , 7 had died , 33 had not returned to their physician for an examination , and 8 had had a follow-up colonoscopy or sigmoidoscopy . Inclusion of the three polyps found in these eight examinations led to an estimate of relative risk of 0.86 ( 95 % confidence limits , 0.51 to 1.43 ) . The findings of this investigation suggest that any reduction in the rate of polyp recurrence associated with vitamin supplementation is small , and a larger study would be required to ensure that an effect of this size was not a chance finding Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . BACKGROUND Elevated benzo(a)pyrene [B(a)P]-DNA adducts have been associated with 3-fold increased risk of lung cancer in current smokers . We assessed the chemopreventive effects of antioxidant supplementation using B(a)P-DNA adducts in leukocytes as an intermediate cancer risk marker . METHODS Subjects were r and omized to a double-blinded placebo-controlled clinical trial of antioxidant vitamin supplementation [ 500 mg vitamin C and 400 IU vitamin E ( dl-alpha-tocopherol ) daily ] or placebo . Smokers with > or = 10 cigarettes per day and serum cotinine > or = 25 ng/mL were eligible for the study . B(a)P-DNA adduct level was the outcome . The r and omization was stratified by gender and cigarettes per day ( < or = 20 or > 20 ) . Smoking habits and blood sample s were collected every 3 months during the 15-month treatment period . Sample s were analyzed for B(a)P-DNA adducts ( high-performance liquid chromatography ) , plasma cotinine , vitamin levels , and GSTM1 genotype . The intent-to-treat model adjusted for B(a)P-DNA and cotinine at r and omization . RESULTS Overall and among men , there was no effect of treatment on B(a)P-DNA adduct levels . Among treated women , B(a)P-DNA adducts decreased by 31 % compared with women on placebo ( P = 0.03 ) . Among treated women with the GSTM1 genotype , there was a 43 % decrease in adducts ( P = 0.04 ) . CONCLUSION Our primary hypothesis that the mean level of smoking-related B(a)P-DNA adducts would be lower in all subjects in the vitamin treatment group compared with all placebo-treated subjects was not substantiated . However , our secondary gender-specific analysis found a significant reduction in B(a)P-DNA adducts in women with vitamin treatment , suggesting that antioxidant supplementation maymitigate some of the procarcinogenic effects of exposuretoB(a)P. The effect in GSTM1-null women suggeststhat certain subgroups may derive more benefit fromsupplementation . Although the results of this trial showthe potential chemopreventive role of antioxidants , thebest way for smokers to reduce their cancer risk remains smoking cessation OBJECTIVE Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms . Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases . The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics . PATIENTS AND METHODS 67 subjects were included in this double blind trial ; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year . Each month , the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment . Every 3 months , the patients underwent a medical examination , and blood sample s were taken for clinical laboratory analysis and serum vitamin E measurement . RESULTS Alpha-tocopherol levels were significantly lower in patients with more severe liver disease . This difference was not significant when vitamin E levels were corrected by cholesterol . Oral supplementation significantly increased serum vitamin E levels in the experimental group . Alcohol ingestion and hospitalization rates were similar in both groups . Life table analysis did not show significant differences in mortality between the two groups . DISCUSSION Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters , mortality or hospitalization rates of decompensated alcoholic cirrhotics , although serum levels of the vitamin significantly increased Aging is associated with a progressive decline in the immune system and a greater susceptibility to infection . This double-blind , placebo-controlled study , examined the effect of a vitamin and trace element supplement on immune responses of healthy , noninstitutionalized elderly subjects . Forty-seven subjects aged 61 - 79 years were r and omly assigned to receive placebo or micronutrient supplementation for one year . Thirty-five individuals completed the one-year study . Immune function was assessed before and after the period of supplementation . Cell-mediated immune function assessed by the number of T cells and subsets remained constant in the supplemented group and there was a significant increase in CD57 natural killer cells . In contrast , a significant decrease in T cells , CD4 cells , and CD4 : CD8 ratio was noted in the placebo group . Supplementation with micronutrients can play a crucial role in the maintenance of normal immune function in the elderly We conducted a population ‐based , double‐blind , r and omized controlled trial to examine the effect of vitamin C supplementation on serum pepsinogen ( PG ) level , Helicobacter pylori ( H. pylori ) infection , and cytotoxin‐associated gene A ( Cag A ) status . Subjects aged 40 to 69 years living in one village in Akita prefecture , a high‐risk area for gastric cancer in Japan , were recruited through annual health check‐up programs . Among 635 subjects diagnosed as having chronic gastritis on the basis of serum PG levels , after excluding ineligible cases , 439 subjects were assigned to one of four groups using a 2 × 2 factorial design ( 0 or 15 mg/day β‐carotene and 50 or 500 mg/day vitamin C ) . However , based on the results from two β‐carotene trials in the United States , we discontinued β‐carotene ( vitamin C supplementation was continued ) . Finally , 120 subjects in the low‐dose group ( vitamin C 50 mg ) , and 124 subjects in the high‐dose group ( vitamin C 500 mg ) completed the 5‐year supplementation . The difference in the change of PGI/II ratio between baseline and after 5‐year follow up was statistically significant between the intervention groups among those who completed the supplementation : ‐0.25 for the low‐dose group and ‐0.13 for the high‐dose group ( P=0.046 ) . To conclude , vitamin C supplementation may protect against progression of gastric mucosal atrophy . ( Cancer Sci 2003 ; 94 : 378–382 OBJECTIVE To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment . RESEARCH DESIGN AND METHODS T1DM patients with high cholesterol received Atorvastatin 20 mg with either placebo ( group AP , n = 11 ) or d-alpha-tocopherol 750 IU ( group AE , n = 11 ) daily . They were monitored for blood biochemistry , low-density lipoprotein ( LDL ) subfractions and lipid peroxidation at inclusion and after 3 and 6 months . RESULTS Serum cholesterol and triglycerides decreased to the same extent ( 29 and 21 % respectively ) in both groups . Serum tocopherol decreased by 18 % in AP and increased by 50 % in AE ( P < 0.0001 , between-group comparison by repeated measures ANOVA ) but relative to lipids it increased by 15 % in AP and by 100 % in AE . Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18 % in AP and did not change in AE ( P = 0.02 ) . The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE ( P = 0.028 ) . Plasma malondialdehyde decreased by 35 % in both groups ( P = 0.002 ) but not when adjusted for lipids . CONCLUSIONS In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin . They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs . These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin Background : We have previously reported , in an uncontrolled trial , an improvement in fatigue scores in patients with primary biliary cirrhosis given oral antioxidant supplementation . We now present data from a controlled trial BACKGROUND The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known . Also , there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals , but there is limited evidence of its effect in human beings . METHODS In a community-based r and omised trial with a 2 by 2 factorial design , individuals were assigned to four treatment groups : daily application of a sun protection factor 15-plus sunscreen to the head , neck , arms , and h and s , and betacarotene supplementation ( 30 mg per day ) ; sunscreen plus placebo tablets ; betacarotene only ; or placebo only . Participants were 1621 residents of Nambour in southeast Queensl and , Australia . The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred . Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application . All analyses were by intention to treat . FINDINGS 1383 participants underwent full skin examination by a dermatologist in the follow-up period . 250 of them developed 758 new skin cancers during the follow-up period . There were no significant differences in the incidence of first new skin cancers between groups r and omly assigned daily sunscreen and no daily sunscreen ( basal-cell carcinoma 2588 vs 2509 per 100,000 ; rate ratio 1.03 [ 95 % CI 0.73 - 1.46 ] ; squamous-cell carcinoma 876 vs 996 per 100,000 ; rate ratio 0.88 [ 0.50 - 1.56 ] ) . Similarly , there was no significant difference between the betacarotene and placebo groups in incidence of either cancer ( basal-cell carcinoma 3954 vs 3806 per 100,000 ; 1.04 [ 0.73 - 1.27 ] ; squamous-cell carcinoma 1508 vs 1146 per 100,000 ; 1.35 [ 0.84 - 2.19 ] ) . In terms of the number of tumours , there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group ( 1115 vs 1832 per 100,000 ; 0.61 [ 0.46 - 0.81 ] ) . INTERPRETATION There was no harmful effect of daily use of sunscreen in this medium-term study . Cutaneous squamous-cell carcinoma , but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years . There was no beneficial or harmful effect on the rates of either type of skin cancer , as a result of betacarotene supplementation OBJECTIVES To test the hypothesis that a micronutrient supplement can improve seroconversion after influenza immunization in older institutionalized people . DESIGN : R and omized , double-blind , placebo-controlled study . SETTING Nursing and residential homes in Liverpool , United Kingdom . PARTICIPANTS One hundred sixty-four residents aged 60 and older from 31 homes were initially r and omized ; of these , 119 ( 72.6 % ) completed the study . INTERVENTION Participants were r and omized to receive a micronutrient supplement providing the reference nutrient intake for all vitamins and trace elements or identical placebo . Tablets were taken over an 8-week period during September and October 2000 ; influenza vaccine was administered 4 weeks after their commencement . MEASUREMENTS The hemagglutination-inhibiting antibody response as defined by a fourfold or greater titer rise over 4 weeks and assessed separately for each of the three antigens contained in the 2000/2001 influenza vaccine ( A/New Caledonia/20/99 ( H1N1 ) , A/Moscow/10/99 ( H3N2 ) , B/Beijing/184/93 ( B ) ) . RESULTS Despite a significant increase in serum concentrations of vitamins A , C , D3 , E , folate , and selenium in the supplemented group , there was no significant difference between groups ( supplemented vs placebo , respectively ) in the proportion of participants seroconverting to H1N1 ( 41 % vs 49 % , P=.374 ) , H3N2 ( 49 % vs 58 % , P=.343 ) , or B ( 41 % vs 40 % , P=.944 ) . CONCLUSION A micronutrient supplement providing the reference nutrient intake administered over 8 weeks had no beneficial effect on antibody response to influenza vaccine in older people living in long-term care BACKGROUND Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract . OBJECTIVE To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss . DESIGN The 11-center Age-Related Eye Disease Study ( AREDS ) was a double-masked clinical trial . Participants were r and omly assigned to receive daily oral tablets containing either antioxidants ( vitamin C , 500 mg ; vitamin E , 400 IU ; and beta carotene , 15 mg ) or no antioxidants . Participants with more than a few small drusen were also r and omly assigned to receive tablets with or without zinc ( 80 mg of zinc as zinc oxide ) and copper ( 2 mg of copper as cupric oxide ) as part of the age-related macular degeneration trial . Baseline and annual ( starting at year 2 ) lens photographs were grade d at a reading center for the severity of lens opacities using the AREDS cataract grading scale . MAIN OUTCOME MEASURES Primary outcomes were ( 1 ) an increase from baseline in nuclear , cortical , or posterior subcapsular opacity grade s or cataract surgery , and ( 2 ) at least moderate visual acuity loss from baseline ( > /=15 letters ) . Primary analyses used repeated- measures logistic regression with a statistical significance level of P = .01 . Serum level measurements , medical histories , and mortality rates were used for safety monitoring . RESULTS Of 4757 participants enrolled , 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years . No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities ( odds ratio = 0.97 , P = .55 ) . There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery . For the 1117 participants with no age-related macular degeneration at baseline , no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss . No statistically significant serious adverse effect was associated with treatment . CONCLUSION Use of a high-dose formulation of vitamin C , vitamin E , and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss CONTEXT Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events . Clinical trials have generally failed to confirm benefits , possibly due to their relatively short duration . OBJECTIVE To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer , cancer death , and major cardiovascular events . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled international trial ( the initial Heart Outcomes Prevention Evaluation [ HOPE ] trial conducted between December 21 , 1993 , and April 15 , 1999 ) of patients at least 55 years old with vascular disease or diabetes mellitus was extended ( HOPE-The Ongoing Outcomes [ HOPE-TOO ] ) between April 16 , 1999 , and May 26 , 2003 . Of the initial 267 HOPE centers that had enrolled 9541 patients , 174 centers participated in the HOPE-TOO trial . Of 7030 patients enrolled at these centers , 916 were deceased at the beginning of the extension , 1382 refused participation , 3994 continued to take the study intervention , and 738 agreed to passive follow-up . Median duration of follow-up was 7.0 years . INTERVENTION Daily dose of natural source vitamin E ( 400 IU ) or matching placebo . MAIN OUTCOME MEASURES Primary outcomes included cancer incidence , cancer deaths , and major cardiovascular events ( myocardial infa rct ion , stroke , and cardiovascular death ) . Secondary outcomes included heart failure , unstable angina , and revascularizations . RESULTS Among all HOPE patients , there were no significant differences in the primary analysis : for cancer incidence , there were 552 patients ( 11.6 % ) in the vitamin E group vs 586 ( 12.3 % ) in the placebo group ( relative risk [ RR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.84 - 1.06 ; P = .30 ) ; for cancer deaths , 156 ( 3.3 % ) vs 178 ( 3.7 % ) , respectively ( RR , 0.88 ; 95 % CI , 0.71 - 1.09 ; P = .24 ) ; and for major cardiovascular events , 1022 ( 21.5 % ) vs 985 ( 20.6 % ) , respectively ( RR , 1.04 ; 95 % CI , 0.96 - 1.14 ; P = .34 ) . Patients in the vitamin E group had a higher risk of heart failure ( RR , 1.13 ; 95 % CI , 1.01 - 1.26 ; P = .03 ) and hospitalization for heart failure ( RR , 1.21 ; 95 % CI , 1.00 - 1.47 ; P = .045 ) . Similarly , among patients enrolled at the centers participating in the HOPE-TOO trial , there were no differences in cancer incidence , cancer deaths , and major cardiovascular events , but higher rates of heart failure and hospitalizations for heart failure . CONCLUSION In patients with vascular disease or diabetes mellitus , long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure context Funding surgery worldwide for age-related cataract ( ARC ) , a leading cause of blindness , is a huge economic burden . Non-surgical means of slowing ARC progression could benefit patients and reduce this burden . objective To determine if a mixture of oral antioxidant micronutrients [ mg/day ] ( ß-carotene [ 18 ] , vitamin C [ 750 ] , and vitamin E [ 600 ] ) would modify progression of ARC . design REACT was a multi-centered , prospect i ve , double-masked , r and omized , placebo-controlled , 3-year trial . setting Consecutive adult American and English out patients with early ARC were recruited . patients Four-hundred- and -forty-five patients were eligible ; 297 were r and omized ; 231 ( 78 % ) were followed for two years ; 158 ( 53 % ) were followed for three years ; 36 ( 12 % ) were followed for four years . Twelve patients died during the trial ( 9 on vitamins ; 3 on placebo ( p = 0.07 ) ) . There were no serious safety issues . intervention After a three-month placebo run-in , patients were r and omized by clinical center to the vitamin or placebo groups and followed every four months . main outcome measure Cataract severity was documented with serial digital retroillumination imagery of the lens ; progression was quantified by image analysis assessing increased area of opacity . This measure of area , ‘ increase % pixels opaque ’ ( IPO ) , was the main outcome measure . results There were no statistically significant differences between the treatment groups at baseline . The characteristics of dropouts and the mean follow-up times by treatment group were the same . After two years of treatment , there was a small positive treatment effect in U.S. patients ( p = 0.0001 ) ; after three years a positive effect was apparent ( p = 0.048 ) in both the U.S. and the U.K. groups . The positive effect in the U.S. group was even greater after three years : ( IPO = 0.389 ( vitamin ) vs. IPO = 2.517 ( placebo ) ; p = 0.0001 ) . There was no statistically significant benefit of treatment in the U.K. group . In spite of nearly perfect r and omization into treatment groups , the U.S. and U.K. cohorts differed significantly . conclusion Daily use of the afore-mentioned micronutrients for three years produced a small deceleration in progression of ARC BACKGROUND Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary question naires or blood measurements , and it has had protective effects in some animal models of carcinogenesis . METHODS We tested the possible cancer-preventing effects of beta carotene by r and omly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer . RESULTS Adherence to the prescribed treatment was good , and after one year the actively treated group 's median plasma beta carotene level ( 3021 nmol per liter ) was much higher than that of the control group ( 354 nmol per liter ) . After five years of follow-up , however , there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer ( relative rate , 1.05 ; 95 percent confidence interval , 0.91 to 1.22 ) . In subgroup analyses , active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked . There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year . CONCLUSIONS In persons with a previous nonmelanoma skin cancer , treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation Summary .Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis ( ALS ) . The antioxidant vitamin E ( alpha-tocopherol ) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS . The current study , a double blind , placebo-controlled , r and omised , stratified , parallel-group clinical trial , was design ed to determine whether vitamin E ( 5000 mg per day ) may be efficacious in slowing down disease progression when added to riluzole . Methods . 160 patients in 6 German centres with either probable or definite ALS ( according to the El Escorial Criteria ) and a disease duration of less than 5 years , treated with riluzole , were included in this study and were r and omly assigned to receive either alpha-tocopherol ( 5000 mg per day ) or placebo for 18 months . The Primary outcome measure was survival , calculating time to death , tracheostomy or permanent assisted ventilation , according to the WFN- Criteria of clinical trials . Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales , manual muscle testing ( BMRC ) , spasticity scale , ventilatory function and the Sickness Impact Profile ( SIP ALS/19 ) . Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18 . Vitamin E sample s were taken for compliance check and Quality Control of the trial . For Safety , a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18 . Height and weight were recorded at baseline and weight alone at the follow-up visits . A neurological examination as well as vital signs ( heart rate and blood pressure ) , an ECG and VEP ’s were recorded at each visit . Furthermore , spontaneously reported adverse experiences and serious adverse events were documented and st and ard laboratory tests including liver function tests performed . For Statistical Analysis , the population to be considered for the primary outcome measure was an “ intent-to-treat ” ( ITT ) population which included all r and omised patients who had received at least one treatment dose ( n = 160 patients ) . For the secondary outcome measures , a two way analysis of variance was performed on a patient population that included all r and omised patients who had at least one assessment after inclusion . Results . Concerning the primary endpoint , no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test . The functional assessment s showed a marginal trend in favour of vitamin E , without reaching significance . Conclusion . Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol . Larger or longer studies might be needed . However , administration of this megadose does not seem to have any significant side effects in this patient population The aim of this study was to determine if vitamin A supplementation reduces the incidence of bacterial infections among elderly nursing-home residents . One hundred and nine patients were enrolled into a double-masked , placebo-controlled trial at an academically affiliated nursing home . Fifty-six patients received a single capsule containing 1,000 IU of vitamin A ( placebo ) and 53 received a single capsule containing 200,000 IU of vitamin A. Antibiotic-treated infections were enumerated for 90 days after dosing and infection rates were expressed per 1000 days of follow-up . There were 42 antibiotic-treated infections altogether , 21 in each group . The infection rates in the vitamin A and placebo groups were 4.7 and 4.3 per 1,000 days of follow-up , respectively ( relative risk 1.1 ; 95 % CI 0.6 , 2.0 ) . The findings of this study do not support a role for vitamin A supplements for the prevention of infections among frail elderly nursing-home patients Because their formation is associated with tumor development in specific tissues , DNA adducts have potential usefulness as intermediate end points in chemoprevention studies . To determine the efficacy of a combination of antioxidant vitamins ( vitamins C and E and beta-carotene ) , a r and omized clinical trial was conducted among heavy smokers using DNA damage as the end point . Immunological methods were used to measure polycyclic aromatic hydrocarbon-DNA adducts and oxidative DNA damage ( 8-oxo or hydroxydeoxyguanosine ) in mononuclear and oral cells . A total of 121 subjects were r and omized to the 6-month intervention and received either vitamins or placebo . Dropout rates were higher in the placebo than in the vitamin group ; 65 % of subjects in the vitamin group , but only 47 % in the placebo group , provided specimens at 6 months . Plasma levels of all three antioxidants rose significantly in the vitamin group but not in the placebo group . All four measures of DNA damage decreased in both groups ; the between-group differences were not statistically significant . These data do not provide clear evidence that antioxidant vitamin intake prevents DNA damage . However , the study demonstrates that DNA damage is a useful end point in chemoprevention trials Evidence from both epidemiological and experimental observations have fueled the belief that the high consumption of fruits and vegetables rich in carotenoids may help prevent cancer and heart disease in humans . Because of its well-documented antioxidant and antigenotoxic properties , the carotenoid beta-carotene ( betaCT ) gained most of the attention in the early 1980s and became one of the most extensively studied cancer chemopreventive agents in population -based trials supported by the National Cancer Institute . However , the results of three r and omized lung cancer chemoprevention trials on betaCT supplementation unexpectedly contradicted the large body of epidemiological evidence relating to the potential benefits of dietary carotenoids . Not only did betaCT show no benefit , it was associated with significant increases in lung cancer incidence , cardiovascular diseases , and total mortality . These findings aroused widespread scientific debate that is still ongoing . It also raised the suspicion that betaCT may even possess co-carcinogenic properties . In this review , we summarize the current data on the co-carcinogenic properties of betaCT that is attributed to its role in the induction of carcinogen metabolizing enzymes and the over-generation of oxidative stress . The data presented provide convincing evidence of the harmful properties of this compound if given alone to smokers , or to individuals exposed to environmental carcinogens , as a micronutrient supplement . This has now been directly verified in a medium-term cancer transformation bioassay . In the context of public health policies , while the benefits of a diet rich in a variety of fruits and vegetables should continue to be emphasized , the data presented here point to the need for consideration of the possible detrimental effects of certain isolated dietary supplements , before mass cancer chemoprevention clinical trials are conducted on human subjects . This is especially important for genetically predisposed individuals who are environmentally or occupationally exposed to mutagens and carcinogens , such as those found in tobacco smoke and in industrial setting CONTEXT Respiratory tract infections are prevalent in elderly individuals , result ing in increased morbidity , mortality , and use of health care services . Vitamin E supplementation has been shown to improve immune response in elderly persons . However , the clinical importance of these findings has not been determined . OBJECTIVE To determine the effect of 1 year of vitamin E supplementation on respiratory tract infections in elderly nursing home residents . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled trial was conducted from April 1998 to August 2001 at 33 long-term care facilities in the Boston , Mass , area . A total of 617 persons aged at least 65 years and who met the study 's eligibility criteria were enrolled ; 451 ( 73 % ) completed the study . INTERVENTION Vitamin E ( 200 IU ) or placebo capsule administered daily ; all participants received a capsule containing half the recommended daily allowance of essential vitamins and minerals . MAIN OUTCOME MEASURES Incidence of respiratory tract infections , number of persons and number of days with respiratory tract infections ( upper and lower ) , and number of new antibiotic prescriptions for respiratory tract infections among all participants r and omized and those who completed the study . RESULTS Vitamin E had no significant effect on incidence or number of days with infection for all , upper , or lower respiratory tract infections . However , fewer participants receiving vitamin E acquired 1 or more respiratory tract infections ( 60 % vs 68 % ; risk ratio [ RR ] , 0.88 ; 95 % confidence interval [ CI ] , 0.76 - 1.00 ; P = .048 for all participants ; and 65 % vs 74 % ; RR , 0.88 ; 95 % CI , 0.75 - 0.99 ; P = .04 for completing participants ) , or upper respiratory tract infections ( 44 % vs 52 % ; RR , 0.84 ; 95 % CI , 0.69 - 1.00 ; P = .05 for all participants ; and 50 % vs 62 % ; RR , 0.81 ; 95 % CI , 0.66 - 0.96 ; P = .01 for completing participants ) . When common colds were analyzed in a post hoc subgroup analysis , the vitamin E group had a lower incidence of common cold ( 0.67 vs 0.81 per person-year ; RR , 0.83 ; 95 % CI , 0.68 - 1.01 ; P = .06 for all participants ; and 0.66 vs 0.83 per person-year ; RR , 0.80 ; 95 % CI , 0.64 - 0.98 ; P = .04 for completing participants ) and fewer participants in the vitamin E group acquired 1 or more colds ( 40 % vs 48 % ; RR , 0.83 ; 95 % CI , 0.67 - 1.00 ; P = .05 for all participants ; and 46 % vs 57 % ; RR , 0.80 ; 95 % CI , 0.64 - 0.96 ; P = .02 for completing participants ) . Vitamin E had no significant effect on antibiotic use . CONCLUSIONS Supplementation with 200 IU per day of vitamin E did not have a statistically significant effect on lower respiratory tract infections in elderly nursing home residents . However , we observed a protective effect of vitamin E supplementation on upper respiratory tract infections , particularly the common cold , that merits further investigation OBJECTIVE To determine whether treatment with vitamin E ( 500 IU daily ) reduces either the incidence or rate of progression of age-related cataracts . DESIGN A prospect i ve , r and omized , double-masked , placebo-controlled clinical trial entitled the Vitamin E , Cataract and Age-Related Maculopathy Trial . PARTICIPANTS Of 1906 screened volunteers , 1193 eligible subjects with early or no cataract , aged 55 to 80 years , were enrolled and followed up for 4 years . INTERVENTION Subjects were assigned r and omly to receive either 500 IU of natural vitamin E in soybean oil encapsulated in gelatin or a placebo with an identical appearance . MAIN OUTCOME MEASURES The incidence and progression rates of age-related cataract were assessed annually with both clinical lens opacity gradings and computerized analysis of Scheimpflug and retroillumination digital lens images obtained with a Nidek EAS-1000 lens camera . The analysis was undertaken using data from the eye with the more advanced opacity for each type of cataract separately and for any cataract changes in each individual . RESULTS Overall , 87 % of the study population completed the 4 years of follow-up , with 74 % of the vitamin E group and 76 % of the placebo group continuing on their r and omized treatment allocation throughout this time . For cortical cataract , the 4-year cumulative incidence rate was 4.5 % among those r and omized to vitamin E and 4.8 % among those r and omized to placebo ( P = 0.87 ) . For nuclear cataract , the corresponding rates were 12.9 % and 12.1 % ( P = 0.77 ) . For posterior subcapsular cataract , the rates were 1.7 % and 3.5 % ( P = 0.08 ) , whereas for any of these forms of cataract , they were 17.1 % and 16.7 % , respectively . Progression of cortical cataract was seen in 16.7 % of the vitamin E group and 18.4 % of the placebo group ( P = 0.76 ) . Corresponding rates for nuclear cataract were 11.4 % and 11.9 % ( P = 0.84 ) , whereas those of any cataract were 16.5 % and 16.7 % , respectively . There was no difference in the rate of cataract extraction between the 2 groups ( P = 0.87 ) . Lens characteristics of the participants withdrawn from the r and omized medications were not different from those who continued . CONCLUSIONS Vitamin E given for 4 years at a dose of 500 IU daily did not reduce the incidence of or progression of nuclear , cortical , or posterior subcapsular cataracts . These findings do not support the use of vitamin E to prevent the development or to slow the progression of age-related cataracts BACKGROUND Excess cardiovascular mortality has been documented in chronic haemodialysis patients . Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without , suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis . We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease . METHODS Haemodialysis patients with pre-existing cardiovascular disease ( n=196 ) aged 40 - 75 years at baseline from six dialysis centres were enrolled and r and omised to receive 800 IU/day vitamin E or matching placebo . Patients were followed for a median 519 days . The primary endpoint was a composite variable consisting of : myocardial infa rct ion ( fatal and non-fatal ) , ischaemic stroke , peripheral vascular disease ( excluding the arteriovenous fistula ) , and unstable angina . Secondary outcomes included each of the component outcomes , total mortality , and cardiovascular-disease mortality . FINDINGS A total of 15 ( 16 % ) of the 97 patients assigned to vitamin E and 33 ( 33 % ) of the 99 patients assigned to placebo had a primary endpoint ( relative risk 0.46 [ 95 % CI 0.27 - 0.78 ] , p=0.014 ) . Five ( 5.1 % ) patients assigned to vitamin E and 17 ( 17.2 % ) patients assigned to placebo had myocardial infa rct ion ( 0.3 [ 0.11 - 0.78 ] , p=0.016 ) . No significant differences in other secondary endpoints , cardiovascular disease , or total mortality were detected . INTERPRETATION In haemodialysis patients with prevalent cardiovascular disease , supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infa rct ion BACKGROUND A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals . In humans , epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers . Vitamins and minerals in these foods may contribute to the reduced cancer risk . The people of Linxian , China , have persistently low intake of multiple nutrients and exhibit one of the world 's highest rates of esophageal/gastric cardia cancer , with an exceptionally high risk of esophageal dysplasia . PURPOSE To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia , we conducted a 6-year prospect i ve intervention trial in Linxian . METHODS Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were r and omly assigned to receive , throughout that period , daily supplementation with 14 vitamins and 12 minerals or placebo . Doses were typically two to three times U.S. Recommended Daily Allowances . Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from sample s of individuals r and omly selected without replacement every 3 months throughout the trial . Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years . RESULTS A total of 324 deaths occurred during the 6-year intervention period ; 167 occurred in the control ( placebo ) group and 157 occurred in the supplement group . Cancer was the leading cause of death ( 54 % of all deaths ) ; 18 % were due to cerebrovascular diseases and 29 % to other causes . Cumulative esophageal/gastric cardia death rates were 8 % lower ( relative risk [ RR ] = 0.92 ; 95 % confidence interval [ CI ] = 0.67 - 1.28 ) among individuals receiving supplements rather than placebo , a nonsignificant ( P > .10 ) difference . Risk of total mortality was 7 % lower ( RR = 0.93 ; 95 % CI = 0.75 - 1.16 ; P > .10 ) , total cancer 4 % lower ( RR = 0.96 ; 95 % CI = 0.71 - 1.29 ; P > .10 ) , cerebrovascular disease 38 % lower ( RR = 0.62 ; 95 % CI = 0.37 - 1.06 ; P = .08 ) , and other diseases 12 % higher ( RR = 1.12 ; 95 % CI = 0.74 - 1.69 ; P > .10 ) among the treated group . Cumulative cancer incidence rates were nearly the same in the two groups . CONCLUSIONS No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus . IMPLICATION S Although no statistically significant short-term benefits were observed , longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia BACKGROUND Age-related macular degeneration ( ARMD ) is the leading cause of vision loss in aging Westem societies . The objective of the lutein antioxidant supplementation trial ( LAST ) is to determine whether nutritional supplementation with lutein or lutein together with antioxidants , vitamins , and minerals , improves visual function and symptoms in atrophic ARMD . METHODS The study was a prospect i ve , 12-month , r and omized , double-masked , placebo-controlled trial conducted at an urban midwestern Veterans Administration Hospital from August 1999 to May 2001 . Ninety patients with atrophic ARMD were referred by ophthalmologists at two Chicago-area veterans medical facilities . Patients in Group 1 received lutein 10 mg ( L ) ; in Group 2 , a lutein 10 mg/antioxidants/vitamins and minerals broad spectrum supplementation formula ( L/A ) ; and in Group 3 , a maltodextrin placebo ( P ) over 12 months . RESULTS In Groups 1 L and 2 L/A , mean eye macular pigment optical density increased approximately 0.09 log units from baseline , Snellen equivalent visual acuity improved 5.4 letters for Group 1 L and 3.5 letters for Group 2 L/A , and contrast sensitivity improved . There was a net subjective improvement in Amsler grid in Group 1 L. VFO-14 question naires conceming subjective glare recovery were nearly significant at 4 months for Group 2 L/A. Patients who received the placebo ( Group 3 ) had no significant changes in any of the measured findings . CONCLUSION In this study , visual function is improved with lutein alone or lutein together with other nutrients . Further studies are needed with more patients , of both genders , and for longer periods of time to assess long-term effects of lutein or lutein together with a broad spectrum of antioxidants , vitamins , and minerals in the treatment of atrophic age-related macular degeneration BACKGROUND Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural population s living in the province of Nariño , Colombia , in the And es Mountains . METHODS A r and omized , controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and /or intestinal metaplasia , two precancerous lesions . Individuals were assigned to receive anti-Helicobacter pylori triple therapy and /or dietary supplementation with ascorbic acid , beta-carotene , or their corresponding placebos . Gastric biopsy specimens taken at baseline were compared with those taken at 72 months . Relative risks of progression , no change , and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects . All statistical tests were two-sided . RESULTS All three basic interventions result ed in statistically significant increases in the rates of regression : Relative risks were 4.8 ( 95 % confidence interval [ CI ] = 1.6 - 14.2 ) for anti-H. pylori treatment , 5 . 1 ( 95 % CI = 1.7 - 15.0 ) for beta-carotene treatment , and 5.0 ( 95 % CI = 1.7 - 14.4 ) for ascorbic acid treatment in subjects with atrophy . Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 ( 95 % CI = 1.0 - 9.3 ) , 3.4 ( 95 % CI = 1.1 - 9.8 ) , and 3.3 ( 95 % CI = 1.1 - 9.5 ) . Combinations of treatments did not statistically significantly increase the regression rates . Curing the H. pylori infection ( which occurred in 74 % of the treated subjects ) produced a marked and statistically significant increase in the rate of regression of the precursor lesions ( relative risks = 8.7 [ 95 % CI = 2.7 - 28.2 ] for subjects with atrophy and 5.4 [ 95 % CI = 1.7 - 17.6 ] for subjects with intestinal metaplasia ) . CONCLUSIONS In the very high-risk population studied , effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process , mostly by increasing the rate of regression of cancer precursor lesions , and may be an effective strategy to prevent gastric carcinoma To evaluate the clinical antioxidant effects of vitamin E , 161 healthy volunteers aged 39 to 56 years , were given 100 or 3 mg of d-α-tocopheryl acetate orally daily for 6 years using a r and omized , double-blind design . Among the 147 volunteers who qualified for the analysis , seven of the 73 volunteers receiving 3 mg d-α-tocopheryl acetate daily and none of the 74 volunteers receiving 100 mg had coronary disorders including myocardial damage ( P < 0.02 ) . ST or T wave abnormalities on electrocardiograms were considered to indicate coronary disorders ( four volunteers ) . The mean serum total tocopherol ( TOC ) concentration in the 100-mg group was significantly higher than that in the 3-mg group 6 months after the start of the study , and this raised value was maintained throughout the study ; the level in the 3-mg group did not change significantly from the baseline value . The low-density lipoprotein cholesterol/total TOC ratio , a parameter of the inhibition of peroxidation of low-density lipoprotein cholesterol , was the only serum lipid parameter that was significantly different , at baseline , in the volunteers with coronary disorders compared with the others . These findings indicate that long-term supplementation with 100 mg tocopheryl acetate daily may prevent the early stages of coronary atherosclerosis by decreasing peroxidation of low-density lipoprotein cholesterol BACKGROUND It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease , cancer , and other adverse outcomes . METHODS 20,536 UK adults ( aged 40 - 80 ) with coronary disease , other occlusive arterial disease , or diabetes were r and omly allocated to receive antioxidant vitamin supplementation ( 600 mg vitamin E , 250 mg vitamin C , and 20 mg beta-carotene daily ) or matching placebo . Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants . An average of 83 % of participants in each treatment group remained compliant during the scheduled 5-year treatment period . Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol , increased that of vitamin C by one-third , and quadrupled that of beta-carotene . Primary outcomes were major coronary events ( for overall analyses ) and fatal or non-fatal vascular events ( for subcategory analyses ) , with subsidiary assessment s of cancer and of other major morbidity . FINDINGS There were no significant differences in all-cause mortality ( 1446 [ 14.1 % ] vitamin-allocated vs 1389 [ 13.5 % ] placebo-allocated ) , or in deaths due to vascular ( 878 [ 8.6 % ] vs 840 [ 8.2 % ] ) or non-vascular ( 568 [ 5.5 % ] vs 549 [ 5.3 % ] ) causes . Nor were there any significant differences in the numbers of participants having non-fatal myocardial infa rct ion or coronary death ( 1063 [ 10.4 % ] vs 1047 [ 10.2 % ] ) , non-fatal or fatal stroke ( 511 [ 5.0 % ] vs 518 [ 5.0 % ] ) , or coronary or non-coronary revascularisation ( 1058 [ 10.3 % ] vs 1086 [ 10.6 % ] ) . For the first occurrence of any of these " major vascular events " , there were no material differences either overall ( 2306 [ 22.5 % ] vs 2312 [ 22.5 % ] ; event rate ratio 1.00 [ 95 % CI 0.94 - 1.06 ] ) or in any of the various subcategories considered . There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause . INTERPRETATION Among the high-risk individuals that were studied , these antioxidant vitamins appeared to be safe . But , although this regimen increased blood vitamin concentrations substantially , it did not produce any significant reductions in the 5-year mortality from , or incidence of , any type of vascular disease , cancer , or other major outcome The aim of this study was to assess the effect of vitamin and /or glucose energy supplementation in elderly medical patients on an intention-to-treat basis . One hundred and six elderly medical in- patients were entered into a double-bind placebo-controlled factorial trial of glucose energy and vitamin supplementation . Supplementation was given for 1 month . This trial was design ed to detect a > 2 kg increase in weight and > 3 g/l increase in serum albumin between active and placebo supplementation in 100 patients with 90 % power ( p < 0.05 ) . Other outcome measures included changes in Barthel activities of daily living , length of stay , and mental test score ( MTS ) . No interaction between vitamin and glucose supplementation was demonstrated . Active energy supplementation with glucose alone was associated with a + 0.6 kg change in weight and + 0.7 g/l change in albumin [ 95 % confidence interval ( CI ) -0.8 , + 2.0 and -1.3 , + 2.8 , respectively ] . The respective changes for active vitamin supplementation were -0.6 kg for weight and + 0.5 g/l for albumin ( 95 % CI -2.1 , + 0.8 and -1.5 , + 2.6 , respectively ) . There were no significant differences in mental test score , Barthel score , or length of stay between the two groups . Compliance with the glucose energy supplementation was poor with only one-third of patients consuming more than 50 % of the offered drink . We conclude that the giving of glucose alone and /or vitamin supplementation in elderly patient is of no benefit on an intention-to-treat basis BACKGROUND The experimental design , subjects , procedures and baseline data for the prospect i ve double blind dry ARMD-antioxidant intervention study have been described in Part 1 . METHODS At eight DVA medical centers , 32 patients ( group one ) were assigned a placebo and 39 patients ( group two ) a " broad spectrum " antioxidant capsule . Data was collected in five areas : demographic ; ophthalmic ; dietary analysis of daily food intake ; serum analysis ; and adverse gastrointestinal symptoms . Data was serially acquired at baseline , 6 months , 12 months and 18 months , and was analyzed by univariate repeated factors ANOVA , p = 0.05 . RESULTS Group two ( antioxidant po BID ) maintained their distance LogMAR visual acuity ( p = 0.03 ) , while there was a trend toward both stabilized near M print ( p = 0.07 ) and 6 cycle/degree contrast sensitivity ( p approximately 0.10 ) , in left eyes . However , group two ( antioxidant ) also had increased cortical opacification of the right lens ( p = 0.04 ) , compared to group one ( placebo ) . Self perceived stabilization of vision was reported by subjects in group two and supported the objective data ( Pearson chi square ; p = 0.05 ) . CONCLUSIONS A specific 14 component antioxidant capsule taken twice daily stabilized but did not improve dry ARMD over the study period of 1.5 years . The ARMD stabilized eyes had less advanced disease functionally but not by fundus appearance . Decreased intake of cardioprotective nutrients ( vitamin E , zinc , magnesium , B6 and folate ) in ARMD patients remained constant over the course of the trial BACKGROUND Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers , including cancers of the esophagus and stomach . Vitamins and minerals in these foods may contribute to the reduced cancer risk . The people of Linxian County , China , have one of the world 's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients . PURPOSE We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian . METHODS Individuals of ages 40 - 69 were recruited in 1985 from four Linxian communes . Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period . The subjects were r and omly assigned to intervention groups according to a one-half replicate of a 2(4 ) factorial experimental design . This design enabled testing for the effects of four combinations of nutrients : ( A ) retinol and zinc ; ( B ) riboflavin and niacin ; ( C ) vitamin C and molybdenum ; and ( D ) beta carotene , vitamin E , and selenium . Doses ranged from one to two times U.S. Recommended Daily Allowances . RESULTS A total of 2127 deaths occurred among trial participants during the intervention period . Cancer was the leading cause of death , with 32 % of all deaths due to esophageal or stomach cancer , followed by cerebrovascular disease ( 25 % ) . Significantly ( P = .03 ) lower total mortality ( relative risk [ RR ] = 0.91 ; 95 % confidence interval [ CI ] = 0.84 - 0.99 ) occurred among those receiving supplementation with beta carotene , vitamin E , and selenium . The reduction was mainly due to lower cancer rates ( RR = 0.87 ; 95 % CI = 0.75 - 1.00 ) , especially stomach cancer ( RR = 0.79 ; 95 % CI = 0.64 - 0.99 ) , with the reduced risk beginning to arise about 1 - 2 years after the start of supplementation with these vitamins and minerals . No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc , riboflavin and niacin , or vitamin C and molybdenum . Patterns of cancer incidence , on the basis of 1298 cases , generally resembled those for cancer mortality . CONCLUSIONS The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults , particularly with the combination of beta carotene , vitamin E , and selenium , may effect a reduction in cancer risk in this population . IMPLICATION S The results on their own are not definitive , but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements BACKGROUND & AIMS Esophageal squamous cell carcinoma remains a leading cause of cancer death worldwide . Squamous dysplasia , the accepted histological precursor for esophageal squamous cell carcinoma , represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk population s. METHODS We conducted a r and omized , controlled trial of selenomethionine 200 microg daily and /or celecoxib 200 mg twice daily ( 2 x 2 factorial design ) among residents of Linxian , People 's Republic of China . Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline . Esophagogastroduodenoscopy was performed before and after a 10-month intervention . Per-subject change ( regression , stable , or progression ) in the worst dysplasia grade was defined as the primary end point . Results were compared by agent group ( selenomethionine vs placebo ; celecoxib vs placebo ) . RESULTS Two hundred sixty-seven subjects fulfilled all eligibility criteria , and 238 ( 89 % ) completed the trial . Overall , selenomethionine result ed in a trend toward increased dysplasia regression ( 43 % vs 32 % ) and decreased dysplasia progression ( 14 % vs 19 % ) compared with no selenomethionine ( P = .08 ) . In unplanned stratified analyses , selenomethionine favorably affected a change in dysplasia grade among 115 subjects with mild esophageal squamous dysplasia at baseline ( P = .02 ) , but not among 123 subjects with moderate esophageal squamous dysplasia at baseline ( P = 1.00 ) . Celecoxib status did not influence changes in dysplasia grade overall ( P = .78 ) or by baseline histology subgroup . CONCLUSIONS After a 10-month intervention , neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects . However , among subjects with mild esophageal squamous dysplasia at baseline , selenomethionine did have a protective effect . Although it is based on unplanned stratified analyses , this finding is the first report of a possible beneficial effect for any c and i date esophageal squamous cell carcinoma chemopreventive agent in a r and omized controlled trial Because of previous reports of the beneficial effect of vitamin E in angina pectoris patients , 48 patients , with both stable angina and positive ( chest pain plus ishemic ST depression ) maximal exercise treadmill tests , participated in a double-blind cross-over study of 6 months of vitamin E and 6 months of placebo therapy , separated by a 2 month no treatment period . All 48 patients had positive selective coronary arteriograms ( 75 per cent obstruction of at least a major coronary artery ) and /or Q wave ECG evidence of previous myocardial infa rct ion ( Minnesota criteria ) . Evaluation of drug effectiveness was based on performance of serial maximal exercise treadmill tests , serial systolic time interval measurements , and daily angina diaries . No statistically significant differences between the two treatment studied . It is concluded that a large dose of vitamin E ( 1,600 I.U. of d-alpha-tocopherol succinate daily ) for 6 months in patients with stable angina pectoris fails to increase the exercise capacity , improve left ventricular function , or reduce the frequency of chest pain To determine the impact of a trace element and vitamin supplementation on infectious morbidity , a double-blind controlled trial was performed on 81 elderly subjects in a geriatric center during a 2-year period . Subjects were r and omly assigned to one of four treatment groups , and received daily : placebo ; trace elements/zinc 20 mg ; selenium 100 micrograms ) ; vitamins ( vitamin C 120 mg ; beta-carotene 6 mg ; alpha-tocopherol 15 mg ) ; or a combination of trace elements and vitamins at equal doses . ( 1 ) Before supplementation , low serum values in vitamin C , folate , zinc and selenium were observed in more than two thirds of the patients . ( 2 ) After 6 months of supplementation , a significant increase in vitamin and trace element serum levels was obtained in the corresponding treatment groups : a plateau was then observed for the whole study . ( 3 ) Subjects who received trace elements ( zinc and selenium ) alone or associated with vitamins had significantly less infectious events during the 2 years of supplementation . These results indicate that supplementation with low doses of vitamins and trace elements is able to rapidly correct corresponding deficiencies in the institutionalized elderly . Moreover , zinc and selenium reduced infectious events |
1,150 | 23,173,657 | The results reveal that implementation of the team nursing model of care result ed in significantly decreased incidence of medication errors and adverse intravenous outcomes , as well as lower pain scores among patients ; however , there was no effect of this model of care on the incidence of falls .
Wards that used a hybrid model demonstrated significant improvement in quality of patient care , but no difference in incidence of pressure areas or infection rates .
There were no significant differences in nursing outcomes relating to role clarity , job satisfaction and nurse absenteeism rates between any of the models of care .
Based on the available evidence , a predominance of team nursing within the comparisons is suggestive of its popularity .
Patient outcomes , nurse satisfaction , absenteeism and role clarity/confusion did not differ across model comparisons .
Little benefit was found within primary nursing comparisons and the cost effectiveness of team nursing over other models remains debatable .
Nonetheless , team nursing does present a better model for inexperienced staff to develop , a key aspect in units where skill mix or experience is diverse | OBJECTIVE This review investigated the effect of the various models of nursing care delivery using the diverse levels of nurses on patient and nursing outcomes . | Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising studies for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding . Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the appraisal process involves a detailed assessment of the patients ( for example , high , medium , or low risk ) , the study interventions ( for example , frequency , degree , and duration ) , and the outcome measurements ( for example , definitions and degree of surveillance ) Cluster r and omized controlled trial ( RCT ) , in which groups or clusters of individuals rather than individuals themselves are r and omized , are increasingly common . Indeed , for the evaluation of certain types of intervention ( such as those used in health promotion and educational interventions ) a cluster r and omized trial is virtually the only valid approach . However , cluster trials are generally more difficult to design and execute than individually r and omized studies , and some design features of a cluster trial may make it particularly vulnerable to a range of threats that can introduce bias . In this paper we discuss the issues that can lead to bias in cluster r and omized trials and conclude with some suggestions for avoiding these problems The employment of unlicensed personnel in Canadian acute care hospitals has been undertaken without clear evidence of outcomes for patients , caregivers , and hospital organizations . This quasi-experimental evaluation study was completed in a metropolitan Toronto acute care hospital to examine the effects of a new nursing care delivery system which included unlicensed assistive personnel . Most of the expected benefits of the newly implemented nursing care delivery system did not material ize leading to the conclusion that the employment of unlicensed assistive personnel in acute care hospital systems may not offer additional benefits for patients , caregivers , or hospital organizations . The processes and results of this study provide useful information for nurse administrators who are seeking effective and innovative care delivery systems that are design ed to optimize patient , caregiver , and hospital outcomes BACKGROUND Many studies have examined predictors of nurses ' intention to work in their job , including desire to quit . Intent has been a good predictor of actual turnover . Few longitudinal studies exist that consider regional variables . OBJECTIVES To extend the conceptual framework of turnover research to the whole nursing workforce and determine : ( 1 ) how do demographics , region ( metropolitan statistical area : MSA ) , movement opportunities , and work setting variables affect registered nurses ' ( RNs ) intent to work and desire to quit ; and ( 2 ) how do demographics , MSA variables , movement opportunities , and work setting variables affect RNs ' work behavior at time 2 ? DESIGN Panel study using Dillman 's design method . SETTING S AND PARTICIPANTS R and omly selected national cluster sample from 40 urban geographic regions ( MSAs ) in 29 states of the United States . METHODS Four thous and surveys were sent . There were 1907 female RNs under 65 ( 48 % response rate ) from year 1 of which 1348 responded at year 2 ( 70 % response rate ) . RESULTS The first analyses used desire to quit ( explained 65 % of the variance ) and intent to work from year 1 as dependent variables . Satisfaction and organizational commitment were significant negative predictors of desire to quit . In the logistic regression on intent to work , the work motivation and work-family conflict were positive and significant as well as wages ( negative ) and three benefit variables . In year 2 , the dependent variable was working or not and if working , full-time or not . For this bivariate probit regression no attitudes influenced the work/not work decision , but MSA level variables , wages ( positive ) and benefits ( positive ) did . Organizational commitment and higher workload increased the probability of working FT . CONCLUSIONS Regional differences across markets need to be controlled and their influence investigated . In addition , attitudes as well as wages and benefits were important in certain decisions : these factors are clearly under the influence of employers Day Surgery ( DS ) and prehospitalization emerged in Italy -- as it had previously in the United States and other European countries -- as able to improve healthcare and reduce costs . The purpose of this study was to evaluate the impact of the Nurse Case Manager ( NCM ) Model on patients undergoing DS procedures . The study assessed the intensity of pain , anxiety , and stress factors , and the level of discomfort experienced . The quasi-experimental study design involved two groups of patients ( at two different DS hospital centers ) : one using the NCM model ( Ward A ) the other based on team nursing ( Ward B ) . All patients undergoing DS for ( a ) varicose veins , ( b ) inguinal hernia , ( c ) breast biopsy , and ( d ) hemorrhoids were included . A valid question naire interview based on 22 questions was used ( 1 ) the morning before surgery , ( 2 ) the evening after surgery , and ( 3 ) 48 hr after the operation , by telephone . Of the 145 patients that were involved , 66 were from Ward A ( 45.5 % ) and 79 from Ward B ( 54.5 % ) . When patient care was based on the NCM Model ( Ward A ) , it seemed that ( a ) the pathway before DS was more efficient ; ( b ) they perceived lower levels of perioperative anxiety and pain ; and ( c ) they recognized the DS center as a unique point of reference for all postoperative problems |
1,151 | 20,122,137 | The results suggest that combining educational and environmental components that focus on both sides of the energy balance give better and more relevant effects .
Furthermore , computer-tailored personalized education in the classroom showed better results than a generic classroom curriculum . | It is the purpose of this study to systematic ally review the evidence of school-based interventions targeting dietary and physical activity behaviour in primary ( 6 - 12 years old ) and secondary school ( 12 - 18 years old ) children in Europe . | Abstract Objective : To assess if a school based intervention was effective in reducing risk factors for obesity . Design : Group r and omised controlled trial . Setting : 10 primary schools in Leeds . Participants : 634 children aged 7 - 11 years . Intervention : Teacher training , modification of school meals , and the development of school action plans targeting the curriculum , physical education , tuck shops , and playground activities . Main outcome measures : Body mass index , diet , physical activity , and psychological state . Results : Vegetable consumption by 24 hour recall was higher in children in the intervention group than the control group ( weighted mean difference 0.3 portions/day , 95 % confidence interval 0.2 to 0.4 ) , representing a difference equivalent to 50 % of baseline consumption . Fruit consumption was lower in obese children in the intervention group ( −1.0 , −1.8 to −0.2 ) than those in the control group . The three day diary showed higher consumption of high sugar foods ( 0.8 , 0.1 to 1.6 ) ) among overweight children in the intervention group than the control group . Sedentary behaviour was higher in overweight children in the intervention group ( 0.3 , 0.0 to 0.7 ) . Global self worth was higher in obese children in the intervention group ( 0.3 , 0.3 to 0.6 ) . There was no difference in body mass index , other psychological measures , or dieting behaviour between the groups . Focus groups indicated higher levels of self reported behaviour change , underst and ing , and knowledge among children who had received the intervention . Conclusion : Although it was successful in producing changes at school level , the programme had little effect on children 's behaviour other than a modest increase in consumption of vegetables . What is already known on this topic Obesity is increasing among school children and dem and s preventive strategies R and omised controlled trials of school based primary prevention programmes have all used a prescriptive approach What this study adds Behavioural changes were disappointing with this programme based on the health promoting schools philosophy , despite changes at school level The only positive outcome was a modest increase in vegetable consumption The discrepancy between changes achieved at the individual and school level raises issues regarding the problems inherent in such 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 CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs A health education intervention was carried out for three consecutive years on primary school Cretan children . Baseline measures were obtained from 962 pupils ( 509 boys and 453 girls ) registered in first grade in 1992 . The health education intervention programme was directed at both the children of the intervention group and their parents , and has a projected duration of 6 years . After the completion of the 3 years of intervention and while pupils were in fourth grade , measures were obtained for evaluation purpose s on a r and om sub sample of 393 pupils of the original cohort . Statistically greater improvements in the intervention , as opposed to the control group , were observed for both children 's and parents ' health knowledge , and children 's st and ing broad jump , sit-ups ( SUP ) , sit- and -reach , h and grip and endurance run test ( ERT ) . Furthermore , time spent on moderate to vigorous physical activities out of school significantly increased for intervention group children compared to the control group . Statistically smaller increases in the intervention as opposed to the control group were observed in suprailiac skinfold and body mass index . The degree of improvement in both SUP and ERT related positively to parent 's baseline physical activity score . Finally , the parental attitude of health-related hedonism related negatively to SUP improvement OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents would be successful in influencing body composition and aerobic fitness . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 978 adolescents ( mean age , 12.7 years ) . INTERVENTION An interdisciplinary multicomponent intervention program with an adapted curriculum for 11 biology and physical education lessons and environmental change options , including additional lessons on physical education and advice on the school canteen selection . MAIN OUTCOME MEASURES Body height and weight , hip and waist circumference , 4 skinfold thickness measurements , and aerobic fitness . RESULTS Multilevel analyses showed significant differences in changes after the 8-month intervention period in favor of the intervention group with regard to hip circumference ( mean difference , 0.53 cm ; 95 % confidence interval , 0.07 to 0.98 ) and sum of skinfolds among girls ( mean difference , -2.31 mm ; 95 % confidence interval , -4.34 to -0.28 ) . In boys , the intervention result ed in a significant difference in waist circumference ( mean difference , -0.57 cm ; 95 % confidence interval , -1.10 to -0.05 ) . No significant intervention effects were found related to aerobic fitness . CONCLUSIONS The multicomponent Dutch Obesity Intervention in Teenagers program positively influenced several measures of body composition among both girls and boys . Our results indicate that secondary prevocational school curriculum changes may contribute to excessive weight gain prevention among adolescents OBJECTIVE To examine the effects of a health and nutrition intervention , implemented in primary schools of Crete , on health knowledge , nutrient intakes and physical activity of the intervention population . METHODS The intervention group consisted of 24 schools while the control group consisted of 16 schools . The overall duration of the intervention was six years , while the topics of the intervention primarily focused on children ' dietary habits , physical activity and fitness . RESULTS After the completion of the intervention period , the changes observed in health knowledge , nutrient intakes and physical activity were in favour of the intervention group pupils . CONCLUSION The encouraging findings of the study indicate the potential of the programme in health promotion and disease prevention without involving substantial new school re sources and time The effectiveness of a health and nutrition education programme , in changing certain chronic disease risk factors , was assessed after the 6 years intervention period was completed . The school-based intervention programme was applied to all children registered in the first grade ( age 5.5 - 6.5 years ) in 1992 in two counties of Crete , while the children from a third county served as a control group . In order to assess the effectiveness of the intervention , a variety of biological and behavioural parameters were measured before and following completion of the intervention in a r and omly selected school-based sample of 602 intervention group ( IG ) and 444 control group ( CG ) pupils . At the end of the 6-year period , it was found that biochemical indices generally improved significantly more in the IG compared with the CG ( mean change for IG v. CG was -0.27 v. -0.12 mmol/l for total cholesterol ( TC ) ; -0.07 v. + 0.24 for TC : HDL and -0.13 v. + 0.14 for LDL : HDL ) . Similarly , the changes observed in the anthropometric variables in the two groups were in favour of the IG ( + 3.68 v. + 4.28 kg/m2 for BMI ; + 2.97 v. + 4.47 mm for biceps skinfold ) . Total energy intake and consumption of total fat and saturated fat increased significantly less in the IG compared with the CG ( + 747.7 v. 1534.7 kJ ( + 178.7 v. + 366.8 kcal ) ; + 5.9 v. + 18.8 g and + 0.8 v. + 5.1 g respectively ) , while time devoted to leisure time physical activity and cardiovascular run test performance increased significantly more in the IG ( + 281 v. + 174 min/week and + 2.5 v. + 1.2 stages respectively ) . The findings of the present study underline the importance of such programmes in health promotion and disease prevention . Although the long-term effects of these programmes can only be assessed by tracking this population through to adolescence and adulthood , these programmes seem to have the potential to lead to a healthier lifestyle and thus a reduction in risk factor levels OBJECTIVES To evaluate the effects of a middle-school healthy eating promotion intervention combining environmental changes and computer-tailored feedback , with and without an explicit parent involvement component . DESIGN Clustered r and omised controlled trial . SETTING Fifteen West-Flemish ( Belgian ) middle schools . SUBJECTS A r and om sample of 15 schools with 2991 pupils in 7th and 8th grade s was r and omly assigned to an intervention group with parental support ( n = 5 ) , an intervention group without parental support ( n = 5 ) and a control group ( n = 5 ) . In these 15 schools an intervention combining environmental changes with computer-tailored feedback was implemented . Fat and fruit intake , water and soft drinks consumption were measured with food-frequency question naires in the total sample of children . RESULTS In girls , fat intake and percentage of energy from fat decreased significantly more in the intervention group with parental support , compared with the intervention alone group ( all F>3.9 , P < 0.05 ) and the control group ( all F>16.7 , P < 0.001 ) . In boys , there were no significant decreases in fat intake ( F = 1.4 , not significant ( NS ) ) or percentage of energy from fat ( F = 0.7 , NS ) as a result of the intervention . No intervention effects were found in boys or in girls for fruit ( F = 0.5 , NS ) , soft drinks ( F = 2.6 , NS ) and water consumption ( F = 0.3 , NS ) . CONCLUSIONS Combining physical and social environmental changes with computer-tailored feedback in girls and their parents can induce lower fat intake in middle-school girls . However , to have an impact on the consumption of soft drinks and water , governmental laws that restrict the at-school availability of low-nutritive products may be necessary Background Only limited data are available on the development , implementation , and evaluation processes of weight gain prevention programs in adolescents . To be able to learn from successes and failures of such interventions , integral written and published reports are needed . Methods Applying the Intervention Mapping ( IM ) protocol , this paper describes the development , implementation , and evaluation of the Dutch Obesity Intervention in Teenagers ( DOiT ) , a school-based intervention program aim ed at the prevention of excessive weight gain . The intervention focussed on the following health behaviours : ( 1 ) reduction of the consumption of sugar-sweetened beverages , ( 2 ) reduction of energy intake derived from snacks , ( 3 ) decrease of levels of sedentary behaviour , and ( 4 ) increase of levels of physical activity ( i.e. active transport behaviour and sports participation).The intervention program consisted of an individual classroom-based component ( i.e. an educational program , covering 11 lessons of both biology and physical education classes ) , and an environmental component ( i.e. encouraging and supporting changes at the school canteens , as well as offering additional physical education classes).We evaluated the effectiveness of the intervention program using a r and omised controlled trial design . We assessed the effects of the intervention on body composition ( primary outcome measure ) , as well as on behaviour , behavioural determinants , and aerobic fitness ( secondary outcome measures ) . Furthermore , we conducted a process evaluation . Discussion The development of the DOiT-intervention result ed in a comprehensive school-based weight gain prevention program , tailored to the needs of Dutch adolescents from low socio-economic background Introduction Prevention of obesity and overweight is an important target for health promotion . Early prevention requires an intervention during childhood and adolescence . At these stages , the game could be an appropriate means to teach nutrition knowledge and to influence dietary behaviour . To this end , the authors developed Kalèdo , a new board-game . Objective The aim of the present study was to test the efficacy of Kalèdo on changes in nutrition knowledge and dietary behaviour in a pilot study conducted in three middle schools in Naples , Italy . Material s and Methods A simple two-group design ( treatment and control ) with pre- and post- assessment was employed . The classroom was the unit of recruitment and r and om assignment to groups . All students ( 307 ) in the participating schools were invited to participate . Data analysis was performed on 241 subjects . During 24 weeks , a group of 153 children from 8 classrooms ( 11–14 year old Caucasian subjects ; 78 male , 75 female ) was involved in 15–30 minute-long play sessions once a week . A question naire was given to the participants at the beginning and at the end of the study to evaluate nutrition knowledge ( 31 questions ) , physical activity ( 8 questions ) and food intake ( 34 questions ) . Anthropometric measurements were also carried out . A second group of 88 children from 5 classrooms ( same age and ethnicity ; 55 male , 33 female ) was investigated at the same times with the same question naire and anthropometric measures but they did not receive any play sessions with Kalèdo . ObservationChildren playing Kalèdo showed a significant increase in nutrition knowledge ( p<0.05 ) and in weekly vegetable intake ( p<0.01 ) with respect to the control . Conclusion The results suggest that Kalèdo could be an effective instrument to teach children about healthy diet . More research is needed to study the long term effect of this intervention OBJECTIVE To evaluate the effects of a 2-year middle school physical activity and healthy food intervention , including an environmental and computer-tailored component on BMI and BMI z-score in boys and girls . RESEARCH METHODS AND PROCEDURES A r and om sample of 15 schools with seventh and eighth grade rs was r and omly assigned to three conditions : an intervention with parental support group , an intervention-alone group , and a control group . Weight and height were measured at the beginning and end of each school year to assess BMI and BMI z-score . A physical activity and healthy food program was implemented over 2 school years . RESULTS In girls , BMI and BMI z-score increased significantly less in the intervention with parental support group compared with the control group ( p < 0.05 ) or the intervention-alone group ( p = 0.05 ) . In boys , no significant positive intervention effects were found . DISCUSSION This was the first study evaluating the effectiveness of an intervention combining environmental changes with personal computer-tailored feedback on BMI and BMI z-score in middle school children . After 2 school years , BMI and BMI z-score changed in a more positive direction in girls as a result of the intervention with parental support Abstract Objectives : To implement a school based health promotion programme aim ed at reducing risk factors for obesity and to evaluate the implementation process and its effect on the school . Design : Data from 10 schools participating in a group r and omised controlled crossover trial were pooled and analysed . Setting : 10 primary schools in Leeds . Participants : 634 children ( 350 boys and 284 girls ) aged 7 - 11 years . Main outcome measures : Response rates to question naires , teachers ' evaluation of training and input , success of school action plans , content of school meals , and children 's knowledge of healthy living and self reported behaviour . Results : All 10 schools participated throughout the study . 76 ( 89 % ) of the action points determined by schools in their school action plans were achieved , along with positive changes in school meals . A high level of support for nutrition education and promotion of physical activity was expressed by both teachers and parents . 410 ( 64 % ) parents responded to the question naire concerning changes they would like to see implemented in school . 19 out of 20 teachers attended the training , and all reported satisfaction with the training , re sources , and support . Intervention children showed a higher score for knowledge , attitudes , and self reported behaviour for healthy eating and physical activity . Conclusion : This programme was successfully implemented and produced changes at school level that tackled risk factors for obesity . What is already known on this topic Prevention of obesity is an increasingly important aspect of health promotion Few trials have investigated school based primary prevention programmes directed at obesity What this study adds The programme was successful in producing school level changes to tackle risk factors for obesity High levels of participation indicated support from schools , staff , parents , and pupils Positive changes were seen in school meals , tuck shops , and playground PURPOSE To evaluate the effects of a middle school physical activity intervention , new in combining an environmental and computer tailored component ; and to evaluate the effects of parental involvement . METHODS A clustered r and omized controlled design was used . A r and om sample of 15 schools with 7th and 8th grade rs was r and omly assigned to one of three conditions : ( a ) intervention with parental support , ( b ) intervention alone , and ( c ) control group . The intervention was new in combining environmental strategies with computer-tailored feedback to increase levels of moderate to vigorous physical activity . The intervention was implemented by the school staff . Physical activity was measured through a question naire in the total sample and with accelerometers in a sub sample of adolescents . RESULTS The intervention with parental support led to an increase in self-reported school-related physical activity of , on average , 6.4 minutes per day ( p < or = .05 , d = .40 ) . Physical activity of light intensity measured with accelerometers decreased with , on average , 36 minutes per day as a result of the intervention with parental support ( p < or = .05 , d = .54 ) . Physical activity of moderate to vigorous intensity measured with accelerometers significantly increased with on average 4 minutes per day in the intervention group with parental support , while it decreased with almost 7 minutes per day in the control group ( p < or = .05 , d = .46 ) . CONCLUSIONS The physical activity intervention , implemented by the school staff , result ed in enhanced physical activity behaviors in both middle school boys and girls . The combination of environmental approaches with computer-tailored interventions seemed promising This paper describes the development , implementation and evaluation of a school- and family-based intervention to prevent obesity in children aged 5 - 7 years . In addition , the efficacy of three different intervention programmes was compared . Children aged 5 - 7 years ( n=213 ) were recruited from three primary schools in Oxford and r and omly allocated to a control group or one of three intervention groups : nutrition group , physical activity group , and combined nutrition and physical activity group . The setting for the interventions was lunchtime clubs , where an interactive and age-appropriate nutrition and /or physical activity curriculum was delivered . The intervention lasted for 20 weeks over four school terms ( approximately 14 months ) . Children 's growth , nutrition knowledge , diet and physical activity were assessed at baseline and at the end of the intervention . Significant improvements in nutrition knowledge were seen in all children ( p<0.01 ) between baseline and post-intervention , and results were highly significant in the nutrition and combined group ( p<0.001 ) . Overall , fruit and vegetable intake increased significantly ( p<0.01 and < 0.05 , respectively ) , with changes seen in fruit consumption in the nutrition group ( p<0.05 ) and the control group ( p<0.05 ) in particular . No significant changes in the rates of overweight and obesity were seen as a result of the intervention . Gender differences were not detected in the majority of assessment s and there was no clear effect of programme type per se . This pilot study has demonstrated that school may be a suitable setting for the promotion of healthy lifestyles in children , but requires replication in other social setting s. Future initiatives should be long-lasting , multi-faceted and sustainable , involving all children in a school , and should target the whole environment and be behaviourally focused . The ultimate goal of any such programme is to lead to positive behaviour change which will have a beneficial effect on long-term health . Successful targeting of the family remains a challenge to such interventions This paper examines how the concept of the ' evidence -based ' approach has transferred from clinical medicine to public health and has been applied to health promotion and policy making . In policy making evidence has always been interpreted broadly to cover all types of reasoned enquiry and after some debate the same is now true for health promotion . Taking communities rather than individuals as the unit of intervention and the importance of context means that frequently r and omized controlled trials are not appropriate for study of public health interventions . Further , the notion of a ' best solution ' ignores the complexity of the decision making process . Evidence ' enlightens ' policy makers shaping how policy problems are framed rather than providing the answer to any particular problem . There are lessons from the way that evidence -based policy is being applied in public health that could usefully be taken back into medicine BACKGROUND No national policy for health education in schools exists to date in Greece . The first attempt to apply a school-based health education intervention program was launched in 1992 on all 4,171 pupils registered in the first grade in two counties of Crete . The 1,510 pupils registered in a third county served as controls . METHODS The school-based intervention and the seminars organized for parents were primarily aim ed at improving children 's diet , fitness , and physical activity . Pupils in the first grade in a representative sample of 40 schools were examined prior to the intervention program on a variety of health knowledge , dietary , physical activity , fitness , anthropometric , and biochemical indices . The same measurements were taken after 3 years of the program on 288 intervention group and 183 control group pupils . RESULTS Positive serum lipid level changes occurred to a greater extent in the intervention group than the control group . BMI increased less in the intervention group than for controls . The increase in health knowledge and physical activity and fitness levels occurred to a higher extent in the intervention group compared to controls . CONCLUSIONS The short-term changes observed in the present study are markedly encouraging and indicate great potential for progressive improvement . Continuation and expansion of such a program may prove to be beneficial in initiating long-term changes OBJECTIVE To evaluate the 4-year outcome of a school-based health promotion on weight status as part of the Kiel Obesity Prevention Study ( KOPS ) . RESEARCH METHODS AND PROCEDURES Within a cluster- sample d quasi-r and omized controlled trial , 1764 children at 6 and 10 years of age were assessed between 1996 and 2005 in 32 primary schools in Kiel , North Germany . Six nutrition units followed by 20-minute running games were performed within the first year at school . Prevalence , incidence , and remission of overweight were main outcome measures . RESULTS The 4-year change in BMI was + 11.6 % , with increases in prevalence of overweight and obesity from 5.2 % to 11.1 % and 3.9 % to 5.1 % , respectively . Cumulative 4-year incidence of overweight and obesity was 9.2 % and 3.1 % , respectively . Intervention had no effect on mean BMI . The effect on prevalence was significant in children from families with high socioeconomic status [ odds ratio ( OR ) , 0.35 ; 95 % confidence interval ( CI ) , 0.14 to 0.91 ] and marginally significant in children of normal-weight mothers ( OR , 0.57 ; 95 % CI , 0.33 to 1.00 ) . Cumulative 4-year incidence of overweight was lower only in intervention children from families with high socioeconomic status ( OR , 0.26 ; 95 % CI , 0.07 to 0.87 ) . Remission of overweight was most pronounced in children of normal-weight mothers ( OR , 5.43 ; 95 % CI , 1.28 to 23.01 ) . Prevalence of underweight was unchanged . The intervention had minor but favorable effects on lifestyle . DISCUSSION A school-based health promotion has sustainable effects on remission and incidence of overweight ; it was most pronounced in children of normal-weight mothers and children from families with high socioeconomic status . There was no effect on obesity . The data argue in favor of additional measures of prevention The aim of the present study was to evaluate the effects of a middle school physical activity and healthy eating intervention , including an environmental and computer-tailored component , and to investigate the effects of parental involvement . A r and om sample of 15 schools with seventh and eight grade rs was r and omly assigned to one of three conditions : ( i ) intervention with parental involvement , ( ii ) intervention alone and ( iii ) control group . In 10 schools , an intervention , combining environmental changes with computer-tailored feedback , was implemented over 2 school years . In five intervention schools , increased parental support was added . Physical activity was measured with question naires in the total sample and with accelerometers in a sub- sample of children . Fat intake , fruit , water and soft drink consumption were measured using food-frequency question naires . Results showed significant positive intervention effects on physical activity in both genders and on fat intake in girls . Parental involvement did not increase intervention effects . It can be concluded that physical activity and eating behaviours of middle school children can be improved by school-based strategies combining environmental and personal interventions . The use of personalized computer-tailored interventions seems to be a promising tool for targeting adolescents but needs to be further explored Obesity in childhood is increasing worldwide . To combat overweight and obesity in childhood , the school-based Children 's Health InterventionaL Trial ( CHILT ) project combines health education and physical activity . This paper examines the effect of intervention on the body mass index ( BMI ) and motor abilities after 20.8 ± 1.0 months in 12 r and omly selected primary schools compared with 5 r and omly selected control schools . The anthropometric data were assessed , BMI was calculated . Coordination was determined by lateral jumping and endurance performance by a 6-minute run . No difference in the prevalence of overweight and obesity was found between the intervention ( IS ) and control schools ( CS ) either at baseline or following intervention ( each p > 0.05 ) . The increase in the number of lateral jumps was significantly higher in the IS than in the CS ( p < 0.001 ) . For the 6-minute run the increase in distance run was significantly improved in IS ( p = 0.020 ) . All variables were controlled for gender and age . Overweight and obese children in both IS and CS produced significantly lower scores in coordination and endurance tasks than normal and underweight children during both examinations ( each p ≤ 0.001 ) , adjusted for gender and age . Preventive intervention in primary schools offers an effective means to improve motor skills in childhood and to break through the vicious circle of physical inactivity - motor deficits - frustration - increasing inactivity possibly combined with an excess energy intake and weight gain . To prevent overweight and obesity these measures have to be intensified . Key PointsSchool-based prevention improves motor abilities in primary school children . The incidence of obesity is not influenced by school-based intervention . To prevent obesity in early childhood the measures have to be intensified and parents should be included |
1,152 | 20,332,307 | Paracervical local anaesthetic injection is the best method of pain control for women undergoing hysteroscopy as out patients | OBJECTIVE To compare the effects of different types of local anaesthetic for pain control during outpatient hysteroscopy . | STUDY OBJECTIVE To determine whether the pain and discomfort of routine hysteroscopy with endometrial biopsy to diagnose infertility and endometrial pathology can be minimized by topical application of mepivacaine . DESIGN Prospect i ve , r and omized , double-blind study . SETTING The Department of Obstetrics and Gynecology at a teaching hospital in Rome , Italy . PATIENTS Eighteen women undergoing diagnostic hysteroscopy . INTERVENTIONS Hysteroscopy and endometrial biopsy were performed after transcervical injection of 5 ml 2 % mepivacaine or 5 ml saline solution into the uterine cavity . MEASUREMENTS AND MAIN RESULTS Difficulty introducing the hysteroscope was rated by the operator on a scale of 1 to 3 . An observer scored visible signs of each woman 's distress using a three-point scale . The patients reported their pain 15 , 30 , 60 , 120 minutes after the procedure on a visual analog scale . Mepivacaine was more effective than placebo according to all measurements . CONCLUSIONS Topical mepivacaine reduced the pain experienced during and after hysteroscopy and endometrial biopsy BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences Outpatient hysteroscopy is now regarded as the investigation of choice for abnormal uterine bleeding as there is no longer any doubt that hysteroscopy is more effective than conventional curettage at identifying intrauterine pathology ( Gimpelson , 1984 ; Goldrath & Sherman , 1985 ; Gimpelson & Rappold , 1988 ; Loffer 1989 ) as it allows direct inspection of the uterine cavity , directed biopsy and appropriate therapeutic management . Another important advantage of hysteroscopy is that it can be performed without general anaesthesia and , in our experience , only 28.5 % of patients required local anaesthesia ; this was significantly associated with the need to dilate the cervix ( Hill et al. 1992 ) . In order to assess the role and efficacy of local anaesthesia before hysteroscopy , a r and omized placebo controlled double blind trial was performed comparing intracervical lignocaine with saline Objective To compare saline with and without added lignocaine and carbon dioxide distension for out patient hysteroscopy with regards to patient discomfort and hysteroscopic view OBJECTIVE To assess the efficacy of lignocaine spray during outpatient hysteroscopy in reducing the need for additional anesthesia and reducing the discomfort of the procedure . DESIGN A r and omized double-blind , placebo-controlled trial . SETTING An undergraduate university teaching hospital in London . PATIENT(S ) One hundred twenty patients undergoing outpatient hysteroscopy . INTERVENTION(S ) Application of lignocaine spray to the cervix , cervical canal , and uterine cavity during outpatient hysteroscopy . MAIN OUTCOME MEASURE(S ) The need to use additional anesthesia and the pain experienced at various steps of the procedure . RESULT ( S ) Women treated with active spray experienced significantly less pain when the cervix was grasped with a tenaculum at the start of hysteroscopy . There were no other significant differences in the outcome of hysteroscopy between the placebo and lignocaine groups , although there was a significant reduction in the use of additional anesthesia in both groups compared with historical controls . CONCLUSION ( S ) Lignocaine spray has beneficial effects on cervical but not uterine sensation . Pretreatment with either lignocaine or placebo seems to reduce the need for additional intracervical anesthesia during hysteroscopy OBJECTIVE : To compare a “ no touch ” approach to diagnostic hysteroscopy without anesthesia with traditional diagnostic hysteroscopy after intracervical injection of mepivacaine hydrochloride 3 % . METHODS : A total of 130 women undergoing diagnostic hysteroscopy were included in the study and were r and omized , using a computer-generated r and omization list to one of two treatment groups in a ratio of 2:1 . Eighty-three women underwent hysteroscopy without speculum , tenaculum , or anesthesia . Forty-seven women received intracervical anesthesia with 10 mL of 3 % mepivacaine hydrochloride solution injected at two sites ( 3:00 and 9:00 positions ) and underwent traditional hysteroscopy . Hysteroscopy was performed using a rigid 3.7-mm hysteroscope and a medium of 0.9 % saline , and the image was transmitted to a screen visible to the patient . A visual analog scale ( VAS ) consisting of a 10-cm line was used to assess the intensity of pain experienced during and after the procedure . Overall patient satisfaction was assessed during , immediately after , 15 minutes later , and 3 days after hysteroscopy . RESULTS : The mean pain score was significantly lower in the group without the use of speculum , tenaculum , or anesthesia ( VAS1 : 3.8±2.7 versus 5.34±3.23 , P=.01 ; VAS2 : 3.02±2.50 versus 4.57±3.30 , P=.008 ) . Patient satisfaction rate was similar in both groups . CONCLUSION : Patients reported significantly less pain with the altered approach to diagnostic hysteroscopy compared with patients undergoing the traditional procedure with anesthesia . This new approach can therefore be considered as a useful hysteroscopic technique . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00319410 LEVEL OF EVIDENCE : BACKGROUND The study was design ed to compare local anaesthesia and conscious sedation for outpatient bipolar operative hysteroscopy in terms of pain control and patients ' satisfaction . METHODS A prospect i ve multicentre r and omized study was carried out in university hospitals and in a private endoscopy unit . A total of 166 women with surgically treatable lesions associated with infertility or abnormal uterine bleeding was considered eligible for the study . Patients were r and omized , using a computer-generated r and omization list , into two groups . Group A ( 82 patients ) underwent operative hysteroscopy with local anaesthesia . Group B ( 84 patients ) received conscious sedation . Operative hysteroscopy was performed with a bipolar electrosurgical device to cut , vaporize and coagulate . Main outcome measures were pain control during the procedure , the post-operative pain score at 15 and 60 min , and at 24 h after the procedure , and patients ' satisfaction rate . RESULTS All procedures were completed within 35 min , the amount of saline used varied from 400 - 1200 ml . There were no significant differences between local anaesthesia and conscious sedation in terms of pain control during the procedure and in postoperative pain at different intervals . Satisfaction rate was similar in the two groups . CONCLUSIONS Both local anaesthesia and conscious sedation can be used for operative hysteroscopy using a bipolar electrosurgical system without significant differences in terms of pain control and patients ' satisfaction STUDY OBJECTIVE To evaluate the amount of pain during office hysteroscopy and endometrial biopsy with and without intrauterine anesthesia . DESIGN Prospect i ve r and omized study ( Canadian Task Force classification I ) . SETTING Academic teaching center . PATIENTS A total of 82 women underwent outpatient hysteroscopy for evaluation of their uterine cavity . INTERVENTIONS R and omization to local cervical or combined cervical and intrauterine anesthesia . MEASUREMENTS AND MAIN RESULTS Amount of pain experienced during the procedure ; 10 , 30 , and 60 minutes after the procedure ; and during endometrial biopsy . We used a visual analog scale ranging from 0 to 10 ( 0 : no pain , 10 : excruciating pain ) . Of 82 patients , 4 patients were excluded , 36 patients underwent hysteroscopy using local cervical anesthesia , and 42 others with combined cervical and intrauterine anesthesia . The mean age of the patients in the local group was 37.4 + /- 0.8 years and in the combined group was 38.3 + /- 0.7 years . In both groups , patients experienced significantly more pain during and 10 minutes after the procedure than 30 and 60 minutes after . No significant differences occurred in the pain scores during the hysteroscopy , and 10 , 30 , and 60 minutes after between the 2 anesthesia groups . The pain score in the local group during endometrial biopsy was significantly higher than during ( p < .05 ) , 10 minutes after ( p < .001 ) , 30 minutes after ( p < .001 ) , and 60 minutes after ( p < .001 ) the procedure , respectively . In the combined group , compared with the pain score during endometrial biopsy , the scores during the hysteroscopy ( p < .05 ) , 10 minutes after ( p < .01 ) , 30 minutes after ( p < .001 ) , and 60 minutes after ( p < .001 ) the procedure were also less , respectively . CONCLUSION Intrauterine anesthesia with medicated saline as a distending medium is ineffective . Endometrial biopsy is associated with more pain than hysteroscopy OBJECTIVE To determine the feasibility and patient satisfaction of female sterilisation using the Essure system in an outpatient hysteroscopy clinic without conscious sedation or general anaesthesia . DESIGN Prospect i ve cohort study . SETTING Outpatient hysteroscopy clinic in a large teaching hospital . POPULATION Women undergoing outpatient hysteroscopic sterilisation using the Essure system for permanent fertility control . METHODS Demographic and procedural data were prospect ively collected from 112 consecutive women undergoing outpatient hysteroscopic sterilisation without sedation or general anaesthesia . A hysterosalpingogram ( HSG ) was performed routinely in all women 3 months after the procedure to confirm bilateral tubal occlusion . Postal question naires were sent at this time enquiring about patient satisfaction and experience with the outpatient procedure . Multivariable logistic regression was used to identify factors independently predictive of successful completion of the procedure . MAIN OUTCOME MEASURES Technical feasibility , predictive factors for technical success ( operator , body mass index , uterine size , axis , menstrual phase and cervical stenosis ) , complications , tubal occlusion on HSG , patient satisfaction and procedure-related experience . RESULTS Successful bilateral tubal placement of the Essure microinserts was achieved in 103/112 ( 92 % , 95 % CI 85 - 96 % ) women . Nonsecretory phase of the menstrual cycle ( P = 0.04 ) and a clinical ly normal-sized uterus ( P = 0.003 ) were independently predictive for successful completion of the outpatient procedure on multivariable modelling . There were no major procedure-related complications recorded , but transient vasovagal reactions occurred in 5/112 ( 5 % ) women . Of the original cohort of 112 women with successful procedures , 84 women were 3 months postprocedure and had undergone a HSG . Bilateral tubal occlusion was confirmed in 83/84 ( 99 % , 95 % CI 94 - 100 % ) women at 3 months and in 100 % at 6 months . Seventy-six of 84 ( 91 % ) had returned the question naires , and 70/73 ( 96 % , 95 % CI 88 - 99 % ) were satisfied with their overall experience of the procedure including radiological follow up , with most reporting being ' very satisfied ' ( 64/73 , 88 % , 95 % CI 78 - 94 % ) . CONCLUSIONS Outpatient hysteroscopic sterilisation using the Essure system without sedation or general anaesthesia is a successful and safe procedure associated with high rates of patient satisfaction . If practical , women should be scheduled to have their procedures in the proliferative phase of the menstrual cycle to optimise successful placement of Essure devices , especially if the uterus is clinical ly enlarged OBJECTIVE To evaluate the efficiency of paracervical anesthesia in reducing pain and the incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women . STUDY DESIGN A r and omized , placebo-controlled , double-blind study . Seventy-two postmenopausal women underwent diagnostic hysteroscopy and endometrial biopsy . Hysteroscopies were performed by using a lens-based endoscope with a diameter of < 4 mm and endometrial biopsies by using a 3-mm Novak 's curette . Ten milliliters of 1.5 mepivacaine or saline solution was injected at the junction of the cervix and vagina ( at the 4 and 8 o'clock positions ) by means of an appropriate needle before performing the intrauterine procedures . Referred pain was evaluated by means of a visual analogue scale ; continuous monitoring of heart rate and blood pressure was also performed . RESULTS Paracervical anesthesia significantly reduced pain at hysteroscopy and biopsy . The incidence of vasovagal reactions was also significantly lower in the anesthetized group . CONCLUSION Paracervical anesthesia is effective for hysteroscopy and endometrial biopsy in postmenopausal women and may be indicated particularly for patients with cervical stenosis , for very anxious subjects and in all situations where pain stimulation could trigger threatening side effects due to systemic pathologies OBJECTIVE To assess the efficacy of lignocaine gel in reducing the overall pain and pain of individual steps during outpatient hysteroscopy in comparison with placebo ( no anesthesia ) . DESIGN A prospect i ve , r and omized , double-blind , placebo-controlled trial . SETTING Outpatient hysteroscopy clinic in a regional hospital in Hong Kong . PATIENT(S ) A total of 500 Chinese patients undergoing outpatient hysteroscopy . INTERVENTION(S ) Application of lignocaine gel to the cervix during outpatient hysteroscopy . MAIN OUTCOME MEASURE(S ) Mean pain score using present pain intensity , overall pain score measured by total area under the curve , and the pain score of individual steps in the procedure in patients receiving lignocaine gel were compared with those of patients having no anesthesia . The failure rate and poor-view rate in both groups were also compared . RESULT ( S ) There were no statistically significant differences in mean pain score , overall pain score , and pain score of individual steps between the lignocaine group and controls . The failure rate and poor-view rate also showed no statistically significant differences . CONCLUSION ( S ) Outpatient hysteroscopy without anesthesia is acceptable to most Chinese women , and the local application of lignocaine gel is not effective in reducing pain One hundred seventy-seven women aged 41 + /- 8 ( mean + /- SD ) years , referred for evaluation of excessive uterine bleeding , were enrolled in an open-label r and omized trial to evaluate the efficacy of local anesthesia before hysteroscopy in an outpatient population . The patients underwent hysteroscopy and endometrial biopsy with paracervical block by 10 mL of 1 % mepivacaine hydrochloride solution ( n = 87 ) or no local anesthesia ( n = 90 ) and assessed lower abdominal and pelvic pain according to a 10-point linear analog scale . The mean + /- SD pain score was 4.5 + /- 2.0 at hysteroscopy and 5.2 + /- 2.1 at endometrial biopsy in the 87 subjects given a paracervical block versus 4.9 + /- 2.2 and 5.7 + /- 2.4 in the 90 women not given local anesthesia , without statistically significant differences . Paracervical anesthesia for routine outpatient hysteroscopy in premenopausal women may be superfluous OBJECTIVE To determine the feasibility ( safety , potential efficacy and cost effectiveness ) of a miniature endoscopic bipolar electrosurgical intrauterine system in the treatment of symptomatic submucous fibroids . STUDY DESIGN A total of 37 women with symptomatic submucous fibroids were identified on outpatient hysteroscopy . All underwent hysteroscopic excision or ablation using a bipolar intrauterine system ( Versapoint ) . The main outcomes measures were change in uterine bleeding symptoms measured on a continuous and ordinal scale , patient satisfaction , time of work and use of health service re sources at 6 months following treatment . RESULTS 36/37 ( 97 % ) women returned completed outcome question naires . The mean amount of abnormal uterine bleeding was reduced at 6 months compared to immediately prior to treatment ( P=0.0001 ) . Improvement in bleeding symptoms was reported by 28/36 ( 78 % ) women and satisfaction with treatment by 33/36 ( 92 % ) women . All procedures were successfully completed , there were no serious operative complications and at 6 months no repeat hysteroscopic procedures were necessary . The mean cost of diagnosis and treatment of submucous fibroids using an endoscopic bipolar intrauterine system was 40 % cheaper at 6 months follow-up than a hysterectomy or open myomectomy ( pound 1266 versus pound 2123 ) . CONCLUSION Hysteroscopic treatment of symptomatic submucous fibroids appears to be safe , efficacious and cost effective . It seems feasible to launch a r and omised controlled trial to confirm these provisional results in both the short and longer term Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor STUDY OBJECTIVE To compare the amount of pain during and after hysteroscopy using local intracervical and combined local and paracervical anesthesia . DESIGN Prospect i ve r and omized trial ( Canadian Task Force classification I ) . SETTING University teaching hospital . PATIENTS Eighty-four women who underwent outpatient hysteroscopy for evaluation of the uterine cavity at McGill University Health Center . INTERVENTIONS R and omization to local intracervical or combined local and paracervical anesthesia . MEASUREMENTS AND MAIN RESULTS Amount of pain experienced during the procedure and at 10 , 30 , and 60 minutes after the procedure was measured using a visual analog scale ranging from zero to 10 ( zero = no pain ; 10 = excruciating pain ) . The mean age of the patients in the local anesthesia group was 36.1 + /- 0.7 years and in the combined local and paracervical anesthesia group was 35.2 + /- 0.7 years . Patients experienced significantly more pain during than after the procedure . The mean pain scores in the local anesthesia group were significantly higher than in the combined anesthesia group during the procedure ( 3.2 + /- 0.3 vs 2.1 + /- 0.2 ; p < .01 ; 95 % CI 0 - 2 ) , 10 minutes after the procedure ( 1.9 + /- 0.2 vs 1.5 + /- 0.3 ; p = .03 ; 95 % CI 0 - 1 ) , and 30 minutes after the procedure ( 1.7 + /- 0.2 vs 1.0 + /- 0.2 ; p = .02 ; 95 % CI 0 - 1 ) . However , there was no significant difference in pain scores at 60 minutes after the procedure between the local anesthesia and combined anesthesia groups ( 0.9 + /- 0.2 and 0.7 + /- 0.1 , respectively ) . CONCLUSIONS Outpatient hysteroscopy with local or combined local and paracervical anesthesia was well tolerated by patients . However , combined anesthesia was associated with less pain during and at 10 and 30 minutes after the procedure . Most patients considered the pain as mild OBJECTIVE To evaluate the efficacy and safety of topical anaesthesia in reducing pain and incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women . DESIGN R and omised placebo-controlled double-blind study . SETTING University hospital . PARTICIPANTS Eighty postmenopausal women undergoing diagnostic hysteroscopy and endometrial biopsy . INTERVENTIONS Two millilitres of 2 % mepivacaine or saline solution were injected transcervically into the uterine cavity before performing the procedures . MAIN OUTCOME MEASURES Evaluation of pain reduction on a visual analogue scale and continuous monitoring of heart rate and blood pressure . RESULTS The use of the anaesthetic significantly reduced the pain experienced at hysteroscopy and endometrial biopsy . The occurrence of vasovagal reactions was significantly lower in the anaesthetised group . CONCLUSIONS Topical anaesthesia attenuated pain and effectively prevented the occurrence of vasovagal reactions during hysteroscopy and endometrial biopsy in postmenopausal women Objective To assess the efficacy of lidocaine spray during outpatient hysteroscopy for reducing procedure-related pain and to identify risk factors for discomfort . Methods One hundred twenty-one women were assigned r and omly to have application of lidocaine spray or placebo to the uterine cervix during outpatient hysteroscopy . The main outcome measure was pain during hysteroscopy , assessed on a visual analog scale . Results There was no statistically significant difference between study and control groups in mean age , rate of nulliparity , postmenopausal state , need for cervical dilation , or percentage of women who used hormone replacement therapy . Indications for diagnostic hysteroscopy were similar between groups . Women in the lidocaine group had statistically significantly less pain during the procedure than women in the placebo group ( 2.2 ± 1.9 and 3.7 ± 2.5 , respectively ; P < .001 ) . Women with abnormal uterine findings ( submucous myoma , endometrial polyps , or intrauterine adhesions ) had significantly higher pain scores than women with normal cavities ( 2.2 ± 1.9 and 3.2 ± 2.4 , respectively ; P < .002 ) . Aerosol anesthesia and normal uterine findings were independently associated with less pain . No procedure had to be ab and oned because of excessive pain or complications , and no women required hospitalization . Conclusion Women treated with lidocaine spray had significantly less pain . Uterine cavity abnormality might be associated with a higher degree of pain during hysteroscopy Background . Three methods of diagnostic hysteroscopy have been tested for both women 's compliance and feasibility of procedures in postmenopause Objective To assess whether transcervical intrauterine instillation of local anaesthetic agent reduces pain during diagnostic outpatient hysteroscopy and endometrial biopsy EDITORIAL COMMENT : We accepted this paper for publication to inform readers who perform hysteroscopy that the procedure can be done under local analgesia with minimal patient discomfort . This is important now that we must increase the number of patients managed as day cases and because in many major institutions hysteroscopies are still done under general anaesthesia |
1,153 | 28,469,722 | Conclusion : Obtaining TBB sample s for histopathological diagnosis is enhanced by the addition of EBUS to conventional fluoroscopic guidance ; this is , especially important for patients with small peripheral lung lesions who benefit greatly from early diagnosis | Background : We report a meta- analysis of recent studies comparing the diagnostic yields of endobronchial ultrasonography plus fluoroscopically-guided transbronchial biopsy ( EBUS + TBB ) with that of conventional fluoroscopically-guided TBB for peripheral pulmonary lesions ( PPLs ) . | INTRODUCTION Fluoroscopy-guided bronchoscopy is usually performed for the diagnosis of peripheral pulmonary lesions ( PPL ) , but the diagnostic yield varies widely among studies . Endobronchial ultrasound ( EBUS ) can increase the diagnostic yield of bronchoscopic diagnosis of PPL . OBJECTIVE To compare the diagnostic yield of fluoroscopy-guided bronchoscopy and EBUS with fluoroscopy-guided bronchoscopy in the study of PPL . METHODS All patients who underwent bronchoscopy to study PPL from January 2009 to December 2012 were prospect ively included . 145 consecutive patients were r and omly distributed in two groups : EBUS and fluoroscopy ( 50 patients , 71.3 ± 8.2 years ) or fluoroscopy alone ( 95 patients , 68 ± 10.5 years ) . The mean diameter of the lesions was 41.97 ± 19.22 mm . Cytological brushing and transbronchial biopsies were obtained . All procedures were performed under fluoroscopic guidance with intravenous conscious sedation . EBUS was performed using an endoscopic ultrasound system equipped with a 20-MHz radial miniprobe introduced via a guide-sheath . Bronchoscopist , cytologist , study protocol , techniques and tools were the same throughout the whole study . RESULTS 129 ( 89 % ) patients had malignant disease . A diagnosis with bronchoscopy was established in 105 ( 72.4 % ) patients . EBUS plus fluoroscopy obtained a diagnostic yield in 78 % of patients and fluoroscopy alone in 69.5 % ( non-significant ) . In contrast , for lesions smaller than 30 mm , EBUS plus fluoroscopy guidance provided significantly greater diagnostic performance than fluoroscopy alone ( 90 vs. 52 % ; P=.05 ) . CONCLUSIONS Bronchoscopy under EBUS plus fluoroscopy guidance is a technique that has become useful for the diagnostic of LPPs , especially those smaller than 30 mm in diameter STUDY OBJECTIVE To assess the ability of endobronchial ultrasonography ( EBUS ) using a guide sheath ( EBUS-GS ) to diagnose peripheral pulmonary lesions . METHOD We devised a technique for EBUS-GS covering a miniature probe , and 150 lesions were evaluated in a prospect i ve open study . In this procedure , the probe covered by a guide sheath is introduced into the lesion via the working channel of a bronchoscope . The probe is withdrawn , while the guide sheath is left in situ . A brush or biopsy forceps is introduced through the guide sheath into the lesion . RESULTS One hundred sixteen of 150 EBUS-GS procedures ( 77 % ) were diagnostic . Cases in which the probe was located within the lesion had a significantly higher diagnostic yield ( 105 of 121 cases , 87 % ) than when the probe was located adjacent to it ( 8 of 19 cases , 42 % ) [ p < 0.0001 , chi(2 ) ] . The diagnostic yield from EBUS-GS in lesions < /= 10 mm ( 16 of 21 lesions , 76 % ) , > 10 to < /= 15 mm ( 19 of 25 lesions , 76 % ; p = 0.99 , chi(2 ) ) , > 15 to < /= 20 mm ( 23 of 35 lesions , 66 % ; p = 0.41 , chi(2 ) ) , and > 20 to < /= 30 mm ( 33 of 43 lesions , 77 % ; p = 0.96 , chi(2 ) ) were similar , demonstrating the efficacy of EBUS-GS even in lesions < /= 10 mm in diameter . In 54 of 81 lesions < /= 20 mm , fluoroscopy was not able to confirm whether the forceps reached the lesion . However , the yield was the same with ( 67 % , 18 of 27 lesions ) and without ( 74 % , 40 of 54 lesions ) successful fluoroscopy ( p = 0.96 , chi(2 ) ) . Moderate bleeding occurred in two patients ( 1 % ) ; there were no other complications . CONCLUSIONS EBUS-GS is a useful method for collecting sample s from peripheral pulmonary lesions , even those too small to be visualized under fluoroscopy Transbronchial biopsy ( TBBX ) for peripheral lung lesions is usually performed with the help of fluoroscopy , but the yield varies widely . This feasibility study aim ed to assess the ability of endobronchial ultrasound ( EBUS ) to provide imaging guidance for TBBX . In a prospect i ve study , 50 consecutive patients referred for TBBX for peripheral lesions underwent fluoroscopy-guided and EBUS-guided TBBX in r and om order . Diagnostic yields were compared for both modalities and feasibility was assessed for EBUS . Diagnostic material was obtained in 80 % of patients with EBUS and 76 % of patients with fluoroscopy . There was a nonsignificant trend for EBUS to be better than fluoroscopy for lesions <3 cm in diameter . Four lesions could not be visualised with EBUS . There were no significant complications associated with the use of EBUS . Endobronchial ultrasound-guided transbronchial biopsy is feasible . It appears to be at least equivalent to fluoroscopy without the accompanying radiation exposure . Further large-scale studies are indicated to assess the possible role of endobronchial ultrasound as a potential imaging method of choice for the biopsy of peripheral lung lesions RATIONALE Endobronchial ultrasound ( EBUS ) and electromagnetic navigation bronchoscopy ( ENB ) have increased the diagnostic yield of bronchoscopic diagnosis of peripheral lung lesions . However , the role of combining these modalities to overcome each individual technique 's limitations and , consequently , to further increase the diagnostic yield remains untested . OBJECTIVES A prospect i ve r and omized controlled trial involving three diagnostic arms : EBUS only , ENB only , and a combined procedure . METHODS All procedures were performed via flexible bronchoscopy and transbronchial forceps biopsies were obtained without fluoroscopic guidance . In the combined group , after electromagnetic navigation , the ultrasound probe was passed through an extended working channel to visualize the lesion . Biopsies were taken if ultrasound visualization showed that the extended working channel was within the target . Primary outcome was diagnostic yield . The reference " gold st and ard " was a surgical biopsy if bronchoscopic biopsy did not reveal a definite histological diagnosis compatible with the clinical presentation . Secondary outcomes were yields by size , lobar distribution , and lesion pathology . Complication rates were also documented . MEASUREMENTS AND MAIN RESULTS Of the 120 patients recruited , 118 had a definitive histological diagnosis and were included in the final analysis . The diagnostic yield of the combined procedure ( 88 % ) was greater than EBUS ( 69 % ) or ENB alone ( 59 % ; p = 0.02 ) . The combined procedure 's yield was independent of lesion size or lobar distribution . The pneumothorax rates ranged from 5 to 8 % , with no significant differences between the groups . CONCLUSIONS Combined EBUS and ENB improves the diagnostic yield of flexible bronchoscopy in peripheral lung lesions without compromising safety RATIONALE Advanced bronchoscopy techniques such as electromagnetic navigation ( EMN ) have been studied in clinical trials , but there are no r and omized studies comparing EMN with st and ard bronchoscopy . OBJECTIVES To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions . Secondary outcomes included diagnostic yield of different sampling techniques , complications , and practice pattern variations . METHODS We used the AQuIRE ( ACCP Quality Improvement Registry , Evaluation , and Education ) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy ( TBBx ) for evaluation of peripheral lesions . MEASUREMENTS AND MAIN RESULTS Fifteen centers with 22 physicians enrolled 581 patients . Of the 581 patients , 312 ( 53.7 % ) had a diagnostic bronchoscopy . Unadjusted for other factors , the diagnostic yield was 63.7 % when no radial endobronchial ultrasound ( r-EBUS ) and no EMN were used , 57.0 % with r-EBUS alone , 38.5 % with EMN alone , and 47.1 % with EMN combined with r-EBUS . In multivariate analysis , peripheral transbronchial needle aspiration ( TBNA ) , larger lesion size , nonupper lobe location , and tobacco use were associated with increased diagnostic yield , whereas EMN was associated with lower diagnostic yield . Peripheral TBNA was used in 16.4 % of cases . TBNA was diagnostic , whereas TBBx was nondiagnostic in 9.5 % of cases in which both were performed . Complications occurred in 13 ( 2.2 % ) patients , and pneumothorax occurred in 10 ( 1.7 % ) patients . There were significant differences between centers and physicians in terms of case selection , sampling methods , and anesthesia . Medical center diagnostic yields ranged from 33 to 73 % ( P = 0.16 ) . CONCLUSIONS Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused . The diagnostic yields of EMN and r-EBUS were lower than expected , even after adjustment AIM To determine diagnostic rate , complications and patient tolerability of endobronchial ultrasound-guide sheath ( EBUS-GS ) and computed tomography (CT)-guided percutaneous core biopsy for peripheral lung lesions . METHODS Lesions > 1 cm diameter on CT were r and omised to either EBUS-GS or CT-guided biopsy . Excluded were patients with severe chronic obstructive airway disease , lesions touching visceral pleura or hilum , and patients with symptoms needing bronchoscopic evaluation . Patients completed preprocedure and postprocedure question naires on tolerability . RESULTS Of 64 participants ( mean lesion size 29 ± 16 mm ) , 57 completed the study . Diagnostic sensitivity was 67 % for EBUS-GS and 78 % for CT-guided biopsy ( P = not significant ) . In those with negative results , in the EBUS group , nine had a CT-guided biopsy as a cross-over , seven of which were positive . In the CT group , four had cross-over EBUS-GS of which three were diagnostic . Sensitivity for malignancy was 17/23 for EBUS-GS ( 74 % ) and 23/26 ( 88 % , P = not significant ) . For lesions < 2 cm , CT-guided biopsy had a significantly better diagnostic yield ( 80 % vs 50 % , P = 0.05 ) . In EBUS-GS cases , for lesions with an air bronchogram , sensitivity was 89 % . Pneumothorax and intercostal catheter insertion occurred in three and two cases , respectively , for EBUS , and 10 and 3 cases for CT-guided biopsy ( P = 0.02 for pneumothorax ) . Nine unexpected admissions occurred after CT-guided biopsy compared with three after EBUS-GS . Overall , tolerability was high for both groups ; however three patients had moderate-to-severe pain after CT-guided biopsy . CONCLUSIONS In lesions < 2 cm , CT-guided biopsy had higher yields ; however , EBUS-GS had better tolerability and fewer complications Background : Peripheral lung lesions are increasing in numbers . Endoscopic diagnosis is essential for the prevention of unnecessary operations . Conventional diagnostic procedures have limitations in availability and results . Objectives : Endobronchial ultrasonography ( EBUS ) was investigated as a means to guide transbronchial lung biopsy , to reduce the discomfort during the procedure and to improve diagnostic accuracy . Methods : In 50 cases , we performed transbronchial lung biopsy combined with EBUS and fluoroscopic guidance . The results were compared to 42 controls assessed by fluoroscopy only . Results : In 38 cases ( 76 % ) , EBUS could describe the peripheral lesion ( 33 from inside , including 9 cases with difficulties in fluoroscopic observation , and 5 from an adjacent bronchus , indicating the correct location of the lesion ) . If successfully placed inside , a change in the patient ’s position was not required , which helped to reduce patient discomfort . Lung cancer was diagnosed in 24 patients and benign disease in 25 patients ; in 1 case diagnosis remained unknown . When the EBUS probe could be introduced inside the lesion , the sensitivity for cancer diagnosis and specificity for cancer exclusion were 100 % , respectively ( 15/15 , 18/18 ) . Compared to the controls in whom the biopsy site was determined by fluoroscopy only , the sensitivity tended to be superior by EBUS , although it did not reach statistical significance ( p = 0.06 ) . However , specificity and accuracy were statistically significant ( both p = 0.02 ) . Conclusions : When the lesion can be correctly described by EBUS from inside the lesion , EBUS is useful to guide transbronchial lung biopsy , can contribute to a reduction in patient discomfort and improves the accuracy of diagnosis . Additional navigation tools to increase correct positioning of the EBUS probe are desirable |
1,154 | 22,502,681 | High levels of TS expression were associated with a poorer OS for advanced GC patients compared with low levels .
In the adjuvant setting , high TS expression was also associated with a worse EFS . | PURPOSE The relationship between thymidylate synthase ( TS ) expression and outcomes in gastric cancer ( GC ) patients remains controversial , although most studies reported poor survival and reduced response to fluoropyrimidine were related to high TS in tumors .
We carried out a systematic review of the literature with meta- analysis to estimate the predictive value of TS expression from published studies . | AIM To investigate the prognostic role of thymidylate synthase ( TS ) and thymidine phosphorylase ( TP ) mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouracil-based adjuvant chemotherapy . METHODS Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouracil-based adjuvant chemotherapy , and intratumoral expression of TS and TP in 51 gastric cancer tissue sample s was tested by real-time quantitative PCR . RESULTS The median disease-free survival ( DFS ) time was 10.2 mo in the patients . There were no significant differences in DFS between the groups with high and low levels of TP . However , the group with low level of TS had a longer DFS ( 14.4 mo vs 8.3 mo , P = 0.017 ) . The median overall survival ( OS ) time was 18.5 mo , and there were significant differences in OS between the groups with high and low levels of TS or TP ( for TS , 17.0 mo vs 21.3 mo , P = 0.010 ; for TP , 16.6 mo vs 22.5 mo , P = 0.009 ) . Moreover , the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene . CONCLUSION Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracil-based adjuvant chemotherapy Purpose : We evaluated the expression of seven therapy-related genes to predict the clinical outcome of advanced gastric cancer patients treated with a neoadjuvant chemotherapeutic protocol . Experimental Design : Pretherapeutic , formalin-fixed , and paraffin-embedded biopsies of 61 patients , who received a 5-fluorouracil (5-FU)– and cisplatin-based chemotherapy were studied . The expressions of the 5-FU – related genes TS , DPD , and TP and of the cisplatin-related genes ERCC1 , ERCC4 , KU80 , and GADD45A were analyzed by quantitative real-time PCR . The expression levels of single genes and of various combinations were tested for an association with response and overall survival . Results : High DPD levels were more frequently found in nonresponding patients and were associated with worse survival . GADD45A and TP levels showed weak associations with response , but GADD45A expression correlated with survival . There was no association with response for TS expression , but tumors with a high TS level were associated with worse survival . The combination of GADD45A and TP revealed the strongest predictive effect . High expression values of TP and /or GADD45A were exclusively found in nonresponding patients ( P = 0.002 ) and were associated with a significantly poorer survival ( P = 0.04 ) . Conclusions : Combined gene expression levels of TP and GADD45A represent a new variable to predict the clinical outcome after neoadjuvant chemotherapy in gastric cancer . The association of DPD expression with response and survival underlines a predominant role of DPD to predict 5-FU sensitivity . The association of TS expression levels with survival but not with response suggests an importance of this gene for tumor progression We evaluated the expression of thymidylate synthase ( TS ) in locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection and investigated the association between TS expression and clinicopathologic characteristics including prognosis of the patients . TS expression was evaluated by immunohistochemical staining using TS106 monoclonal antibody in 103 locally advanced gastric cancer patients ( stage IB – IV ) who underwent 5-fluorouracil ( 5-FU ) and doxorubicin-based adjuvant chemotherapy after curative resection . 65 patients ( 63 % ) had primary tumours with high TS expression ( ≥ 25 % of tumour cells positive ) , and 38 patients ( 37 % ) demonstrated low TS expression ( < 25 % of tumour cells positive or no staining ) . High TS expression was associated with male gender ( P=0.002 ) , poorly differentiated histology ( P=0.015 ) , and mixed type in Lauren 's classification ( P=0.027 ) . There were no statistically significant differences in 4-year disease-free survival ( 60.0 % vs 57.2 % , P=0.548 ) and overall survival ( 59.6 % vs 59.3 % , P=0.792 ) between high-TS group and low-TS group . In conclusion , although high TS expression was associated with poorly differentiated histology and mixed type in Lauren 's classification , it did not predict poor disease-free and overall survival in gastric cancer patients treated with 5-FU and doxorubicin-based adjuvant chemotherapy after curative resection . Further prospect i ve studies including the evaluation of other biological markers associated with the resistance to 5-FU and doxorubicin are necessary . © 2001 Cancer Research Campaign The predictive values of thymidylate synthase ( TS ) and dihydropyrimidine dehydrogenase ( DPD ) gene expressions were retrospectively evaluated in patients with gastric cancer treated by a regimen containing S-1 . The study population consisted of 53 patients registered into different two phase II studies for metastatic gastric cancer ; 27 patients treated by S-1-alone study : 26 patients treated with S-1 combined with irinotecan ( CPT-11 ) . TS and DPD gene expressions in primary tumours were measured by the real-time reverse transcription PCR method . There was no statistical difference in DPD gene expression in terms of response in cases treated with S-1 alone and those treated with S-1 plus CPT-11 . TS mRNA of responding tumours was lower than that of nonresponding ones when treated with S-1 ( P<0.005 ) . In the S-1-alone group , taking TS cutoff as the median values , the response rate in the low TS group was 50 % , but only 8 % in the high TS group ( P<0.05 ) . Patients with low TS gene expression survived longer than those with high TS gene expression ( P<0.0001 ) . However , there was no statistically significant difference in response rate and survival between patients with low TS tumours and those with high TS tumours , when the cutoff was taken as the median value of TS gene expression in the group treated with S-1 plus CPT-11 . In conclusion , treatment effects of S-1 monotherapy for gastric cancer were determined by the status of TS gene expression , regardless of DPD gene expression . TS predictive power was overcome by CPT-11 combination therapy with S-1 We investigated the utility of examining biological markers to predict chemoresponse and survival . The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum . The expression of p53 , bcl-2 , thymidylate synthase ( TS ) , glutathione S-transferase pi ( GST-pi ) , and vascular endothelial growth factor ( VEGF ) in the formalin-fixed biopsy sample s of primary tumors before chemotherapy was examined immunohistochemically . The positive rate for VEGF , bcl-2 , TS , p53 , and GST-pi was 51 , 10 , 46 , 38 , and 69 % , respectively . VEGF-positive cases showed a higher response rate than did negative cases ( 11 of 20 versus 2 of 19 cases ; P = 0.0057 ) . The cases that were negative for p53 , TS , bcl-2 , and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers . The 10 cases having 4 or 5 favorable phenotypes ( VEGF positive , p53 negative , bcl-2 negative , TS negative , and GST-pi negative ) survived longer than the remaining 29 cases ( P = 0.0069 ) . Multivariate analysis revealed that the number of favorable phenotypes ( > or = 4 versus < or = 3 ) had a greater impact on survival than performance status ( 0 versus 1 or 2 ) , age ( > 60 years versus < or = 60 years ) , macroscopic type ( scirrhous versus nonscirrhous ) , histological type ( intestinal versus diffuse ) , or tumor extent ( locally advanced versus metastatic ) . Immunohistochemical examination of biological markers in biopsy sample s may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum PURPOSE We have previously shown that relative thymidylate synthase ( TS ) mRNA levels in primary gastric adenocarcinomas treated with fluorouracil ( 5-FU ) and cisplatin are inversely associated with response and survival . This is a presumed function of TS as a target for 5-FU activity . We now test the hypotheses that the relative mRNA level of the excision repair cross-complementing ( ERCC1 ) gene is inversely associated with response and survival as an independent function of cisplatin efficacy . PATIENTS AND METHODS Patients had intact , untreated , primary gastric adenocarcinoma cancer and were evaluated for eligibility on a preoperative cisplatin infusion-5-FU protocol . cDNA , derived from primary gastric tumors before chemotherapy , was used to determine ERCC1 mRNA levels , expressed as the ratio of polymerase chain reaction ( PCR ) product of the ERCC1 gene and the beta-actin gene . RESULTS The median ERCC1 mRNA level from 38 primary gastric cancers ( 33 assessable for response ) was 5.8 x 10(-3 ) ( range , 1.8 x 10(-3 ) to 19.5 x 10(-3 ) ) . Of 17 responding patients , 13 ( 76 % ) were less than or equal to 5.8 x 10(-3 ) and four were greater than 5.8 x 10(-3 ) ( P = .003 ) . The median survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3 ) has not been reached , whereas for those greater than 5.8 x 10(-3 ) it was 5.4 months ( P = .034 ) . The median TS mRNA level , 3.7 x 10(-3 ) ( range , 0.9 to 18.9 ) also segregated responsive versus resistant tumors ( P = .024 ) . With both ERCC1 and TS mRNA levels below their medians , 11 of 13 patients ( 85 % ) responded ; with both ERCC1 and TS mRNA levels above their medians , two of 10 patients ( 20 % ) responded ( P = .003 ) . CONCLUSION Considered separately , either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response . ERCC1 mRNA levels have a statistically significant association with survival ; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication . Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined In the past 4 years , the weekly 24‐hour infusion of high dose 5‐fluorouracil ( 5‐FU ) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospect ively studied at the authors ' institution . This has enabled them to explore the possibility that the level of expression of thymidylate synthase ( TS ) , the target enzyme of 5‐FU , is related to the drug sensitivity of gastric carcinoma to 5‐FU‐based chemotherapy Purpose We investigated whether the intensity of thymidylate synthase ( TS ) staining in tissue sample s obtained from gastric cancer ( GC ) patients undergoing gastrectomy could predict response to 5-FU-based adjuvant chemotherapy after gastrectomy . Method and material sClinicopathological features of 124 patients with histologically proven GC who underwent radical gastrectomy were retrospectively review ed . Tissue sample s obtained from these patients were immunohistochemically stained for assessing TS expression . We arbitrarily classified the TS staining results as low ( < 20 % cytoplasmic immunostaining ) and high ( ≥20 % cytoplasmic immunostaining ) TS expression . Results The clinicopathological features of the low TS expression group patients were typically similar to those of the high TS expression group patients . However , multivariate forward stepwise logistic regression analysis revealed that low TS expression was independently associated with females and responders to 5-FU-based adjuvant chemotherapy . The median follow-up duration for the 124 GC patients who had undergone curative resection was 41.3 months . The GC patients who showed poor tumor differentiation and high TS expression had short disease-free survival ( DFS ) and overall survival ( OS ) . Conclusions Low TS expression is significantly associated with female GC patients and responders to 5-FU-based adjuvant chemotherapy . It predicts longer DFS and OS in selected GC patients treated with 5-FU-based adjuvant chemotherapy after curative resection . The results suggest that prospect i ve assessment of TS staining intensity in tissue sample s obtained from GC patients undergoing gastrectomy would be useful to predict the patients who would be benefited from 5-FU-based adjuvant chemotherapy after gastrectomy BACKGROUND Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated . In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer ( SPIRITS ) trial , we aim ed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone . METHODS In this phase III trial , chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26 , 2002 , and Nov 30 , 2004 , at 38 centres in Japan , and r and omly assigned to S-1 plus cisplatin or S-1 alone . In patients assigned to S-1 plus cisplatin , S-1 ( 40 - 60 mg depending on patient 's body surface area ) was given orally , twice daily for 3 consecutive weeks , and 60 mg/m(2 ) cisplatin was given intravenously on day 8 , followed by a 2-week rest period , within a 5-week cycle . Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks , followed by a 2-week rest period , within a 6-week cycle . The primary endpoint was overall survival . Secondary endpoints were progression-free survival , proportions of responders , and safety . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00150670 . FINDINGS 305 patients were enrolled ; seven patients were ineligible or withdrew consent , therefore , 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone . Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin ( 13.0 months [ IQR 7.6 - 21.9 ] ) than in those assigned to S-1 alone ( 11.0 months [ 5.6 - 19.8 ] ; hazard ratio for death , 0.77 ; 95 % CI 0.61 - 0.98 ; p=0.04 ) . Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone ( median progression-free survival 6.0 months [ 3.3 - 12.9 ] vs 4.0 months [ 2.1 - 6.8 ] ; p<0.0001 ) . Additionally , of 87 patients assigned S-1 plus cisplatin who had target tumours , one patient had a complete response and 46 patients had partial responses , ie , a total of 54 % ( range 43 - 65 ) . Of 106 patients assigned S-1 alone who had target tumours , one patient had a complete response and 32 had partial responses , ie , a total of 31 % ( 23 - 41 ) . We recorded more grade 3 or 4 adverse events including leucopenia , neutropenia , anaemia , nausea , and anorexia , in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone . There were no treatment-related deaths in either group . INTERPRETATION S-1 plus cisplatin holds promise of becoming a st and ard first-line treatment for patients with advanced gastric cancer PURPOSE We tested the hypothesis that polymerase chain reaction ( PCR ) quantitation of the enzyme thymidylate synthase ( TS ) within a primary adenocarcinoma of the stomach , has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy . PATIENTS AND METHODS Before systemic chemotherapy , the genetic expression of TS ( TSmRNA level ) was determined using a PCR method . Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene . Chemotherapy consisted of two cycles of protracted infusion ( PI ) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w . Cisplatin 100 mg/m2 was administered on day 1 . RESULTS Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3 ) ( range , 0.9 to 20.1 x 10(-3 ) ) . Thirty-five percent of patients had measurable responses in their primary tumors . The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant ( P < .001 ) . The median survival time was 43 + months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median ( P = .003 ) . CONCLUSION The genetic expression of TS ( TSmRNA level ) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer . Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor PURPOSE In the r and omized , multinational phase II/III trial ( V325 ) of untreated advanced gastric cancer patients , the phase II part selected docetaxel , cisplatin , and fluorouracil ( DCF ) over docetaxel and cisplatin for comparison against cisplatin and fluorouracil ( CF ; reference regimen ) in the phase III part . PATIENTS AND METHODS Advanced gastric cancer patients were r and omly assigned to docetaxel 75 mg/m2 and cisplatin 75 mg/m2 ( day 1 ) plus fluorouracil 750 mg/m2/d ( days 1 to 5 ) every 3 weeks or cisplatin 100 mg/m2 ( day 1 ) plus fluorouracil 1,000 mg/m2/d ( days 1 to 5 ) every 4 weeks . The primary end point was time-to-progression ( TTP ) . RESULTS In 445 r and omly assigned and treated patients ( DCF = 221 ; CF = 224 ) , TTP was longer with DCF versus CF ( 32 % risk reduction ; log-rank P < .001 ) . Overall survival was longer with DCF versus CF ( 23 % risk reduction ; log-rank P = .02 ) . Two-year survival rate was 18 % with DCF and 9 % with CF . Overall response rate was higher with DCF ( chi2 P = .01 ) . Grade 3 to 4 treatment-related adverse events occurred in 69 % ( DCF ) v 59 % ( CF ) of patients . Frequent grade 3 to 4 toxicities for DCF v CF were : neutropenia ( 82 % v 57 % ) , stomatitis ( 21 % v 27 % ) , diarrhea ( 19 % v 8 % ) , lethargy ( 19 % v 14 % ) . Complicated neutropenia was more frequent with DCF than CF ( 29 % v 12 % ) . CONCLUSION Adding docetaxel to CF significantly improved TTP , survival , and response rate in gastric cancer patients , but result ed in some increase in toxicity . Incorporation of docetaxel , as in DCF or with other active drug(s ) , is a new therapy option for patients with untreated advanced gastric cancer Thymidylate synthase ( TS ) , dihydropyrimidine dehydrogenase ( DPD ) , and vascular endothelial growth factor ( VEGF ) are associated with the effect of 5-fluorouracil ( 5-FU ) based adjuvant chemotherapy . However , very few studies have investigated the relationship between these factors and 5-FU neoadjuvant chemotherapy for primary gastric cancer patients . In this study , we studied the correlation between these markers and the histological chemotherapeutic effect in advanced gastric cancer with neoadjuvant chemotherapy . Methods : Sixty-two primary advanced gastric cancer patients were recruited into the study . One cycle of continuous infusion of 5-FU ( 300 mg/m2/day , 14 days ) plus drip infusion of cisplatin ( 15 mg/m2/day , Day one and Day two ) was performed as neoadjuvant chemotherapy . Histological chemotherapeutic responses of the resected specimens were classified into responders and nonresponders . TS , DPD , VEGF expressions both before and after neoadjuvant chemotherapy were examined immunohistochemically . Results : There was an association between the TS-low group and the responders ( p < 0.05 ) ; the DPD-low group and the responders in both biopsy and surgical specimens ( p < 0.01 ) . A combination of the low-TS and low-DPD group was further associated with responders ( p < 0.01 ) . The immunoexpressions of biopsied and surgical specimens were significantly associated with each other . Conclusion : Neoadjuvant chemotherapy for primary gastric cancer with one cycle of 5-FU and cisplatin was associated with histological findings in patients with low baseline TS and DPD . This dual determination may predict for efficacy of neoadjuvant treatment with these drugs Many reports have demonstrated that thymidylate synthase ( TS ) and dihydropyrimidine dehydrogenase ( DPD ) are biomarkers for the response and prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy . A newly developed orally administered drug , fluoropyrimidine ( S-1 ) , has been developed with clinical efficacy when combined with an inhibitor of DPD . In this study , the relationship between immunoreactivity to TS and DPD in biopsy specimens and the effects of chemotherapy was investigated in 41 patients treated with S-1 therapy for advanced gastric cancer . Response rates were 54 % ( 13/24 ) in TS(+ ) and 53 % ( 9/17 ) in TS(- ) patients ( p=0.938 ) , and those of DPD(+ ) and ( - ) patients were 61 % ( 11/18 ) and 48 % ( 11/23 ) ( p=0.397 ) , respectively . The median survival time of all the subjects was 253 days . There was no significant difference in median survival time between TS(+ ) patients ( 284 days ) and ( - ) patients ( 189 days : p=0.670 ) . The 18 DPD(+ ) patients had median survival times slightly longer ( 338 days ) than the 23 patients with DPD(- ) ( 207 days : p=0.206 ) . This study indicates that S-1 may be effective in the treatment of gastric cancer patients , regardless of intratumoral TS and DPD immunoreactivity status . Further studies are needed to confirm these results with larger numbers of patients BACKGROUND Advanced gastric cancer can respond to S-1 , an oral fluoropyrimidine . We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer . METHODS Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended ( D2 ) lymph-node dissection were r and omly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only . In the S-1 group , administration of S-1 was started within 6 weeks after surgery and continued for 1 year . The treatment regimen consisted of 6-week cycles in which , in principle , 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks . The primary end point was overall survival . RESULTS We r and omly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004 . The trial was stopped on the recommendation of the independent data and safety monitoring committee , because the first interim analysis , performed 1 year after enrollment was completed , showed that the S-1 group had a higher rate of overall survival than the surgery-only group ( P=0.002 ) . Analysis of follow-up data showed that the 3-year overall survival rate was 80.1 % in the S-1 group and 70.1 % in the surgery-only group . The hazard ratio for death in the S-1 group , as compared with the surgery-only group , was 0.68 ( 95 % confidence interval , 0.52 to 0.87 ; P=0.003 ) . Adverse events of grade 3 or grade 4 ( defined according to the Common Toxicity Criteria of the National Cancer Institute ) that were relatively common in the S-1 group were anorexia ( 6.0 % ) , nausea ( 3.7 % ) , and diarrhea ( 3.1 % ) . CONCLUSIONS S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer . ( Clinical Trials.gov number , NCT00152217 [ Clinical Trials.gov ] . ) |
1,155 | 23,440,799 | There was evidence that LASIK gives a faster visual recovery than PRK and is a less painful technique .
Results at one year after surgery were comparable : most analyses favoured LASIK but they were not statistically significant .
LASIK gives a faster visual recovery and is a less painful technique than PRK .
The two techniques appear to give similar outcomes one year after surgery . | BACKGROUND Myopia ( also known as short-sightedness or near-sightedness ) is an ocular condition in which the refractive power of the eye is greater than is required , result ing in light from distant objects being focused in front of the retina instead of directly on it .
The two most commonly used surgical techniques to permanently correct myopia are photorefractive keratectomy ( PRK ) and laser-assisted in-situ keratomileusis ( LASIK ) .
OBJECTIVES To compare the effectiveness and safety of LASIK and PRK for correction of myopia by examining post-treatment uncorrected visual acuity , refractive outcome , loss of best spectacle-corrected visual acuity , pain scores , flap complications in LASIK , subepithelial haze , adverse events , quality of life indices and higher order aberrations . | PURPOSE To evaluate the safety and efficacy of laser in situ keratomileusis ( LASIK ) compared to photorefractive keratectomy ( PRK ) for the correction of low or moderate myopia ( -0.50 to -6.00 D ) at 6 months after surgery . METHODS The study population comprised a non-r and omized consecutive series of 622 eyes of 392 patients who were treated with the Nidek EC-5000 excimer laser . LASIK was performed using the ACS Chiron microkeratome on 314 eyes and surface PRK on 308 eyes . All patients were treated using a st and ard protocol , then assessed at 1 , 3 , and 6 months postoperatively . RESULTS Forty-four percent of the LASIK group and 67 % of the PRK group attended their 6-month examination . Eighty percent of patients ( 111 eyes ) after LASIK and 65 % ( 136 eyes ) after PRK had an uncorrected visual acuity of 20/20 or better . Spherical equivalent refraction was within + /-0.50 D of intended refraction in 78 % ( 109 eyes ) for LASIK and 82 % ( 170 eyes ) for PRK . Loss of two more lines of best spectacle-corrected visual acuity at 6 months occurred in 1.4 % ( 2 eyes ) of the LASIK group and 1.0 % ( 2 eyes ) of the PRK group . CONCLUSION At 1 month follow-up , the percentage of eyes that achieved 20/20 uncorrected visual acuity was greater in the LASIK group than in the PRK group . At 6 months , visual and refractive outcomes of LASIK and PRK were similar . Although flap related complications occurred only after LASIK , the overall risk of loss of best spectacle-corrected visual acuity was not significantly greater than for PRK OBJECTIVE This report presents patient-reported optical symptoms after photorefractive keratectomy ( PRK ) and laser in situ keratomileusis ( LASIK ) . DESIGN Preoperative and postoperative patient surveys in a prospect i ve , multicenter , r and omized clinical trial . PARTICIPANTS Two hundred twenty eyes of 220 patients entered the study ; 105 were r and omized to PRK and 115 were r and omized to LASIK . INTERVENTION All patients received a one-pass , multizone excimer laser ablation as part of either a PRK or LASIK procedure . Attempted corrections ranged from 6.00 to 15.00 diopters ( D ) . MAIN OUTCOME MEASURES Glare , halo , and monocular diplopia symptoms as reported by patients on question naires before surgery and at the 6-month follow-up . Comparison was made between symptoms when using optical correction before surgery and symptoms without correction after surgery . RESULTS For both the PRK and LASIK groups analyzed individually , the difference in average glare index before surgery and after surgery was not statistically significant ( P = 0.54 for PRK ; P = 0.15 for LASIK ; t test ) . Twenty-four PRK patients ( 41.4 % ) reported worsening of glare symptoms from baseline compared with 11 LASIK patients ( 21.6 % ) ; however , the difference between the two groups was not statistically significant ( P = 0.086 , chi-square test ) . Within the PRK group , the difference in average halo index before and after surgery was statistically significant ( P = 0.0003 , t test ) ; in the LASIK group , it was not statistically significant ( P = 0.1 1 , t test ) . Thirty-four PRK patients ( 58.6 % ) reported worsening of halo symptoms from baseline compared with 26 LASIK patients ( 50.0 % ) ; this difference was not statistically significant ( P = 0.086 , chi-square test ) . For both the PRK and LASIK groups , the difference in average diplopia index before and after surgery was statistically significant ( P < 0.0001 for PRK ; 0.047 for LASIK ; t test ) . Twenty-six PRK patients ( 44.8 % ) reported a worsening of monocular diplopia symptoms from baseline compared with 19 LASIK patients ( 35.8 % ) ; this difference was not statistically significant ( P = 0.39 , chi-square test ) . When changes in glare and halo from before surgery to after surgery were pooled as a glare-halo index , however , the PRK group did show a significantly greater likelihood of demonstrating an increase in symptoms compared with the LASIK group ( P = 0.048 , chi-square test ) . CONCLUSIONS Optical sequelae of glare , halo , and monocular diplopia may occur in some patients after either both PRK or LASIK for moderate to high myopia ; in contradistinction , many other patients ' preoperative symptoms improve after surgery . On average , PRK patients show an increase in halo and diplopia symptoms , but not glare , after surgery , and LASIK patients show an increase in diplopia , but not glare and halo symptoms . There is a suggestion of a somewhat lesser tendency toward postoperative optical symptoms in LASIK compared with PRK treated eyes OBJECTIVE Determine the outcomes of single-zone photorefractive keratectomy ( SZPRK ) , aspherical photorefractive keratectomy ( ASPRK ) , and laser in-situ keratomileusis ( LASIK ) for the correction of myopia between -6 and -12 diopters . DESIGN Two simultaneous prospect i ve , r and omized , multi-center clinical trials . PARTICIPANTS 286 first-treated eyes of 286 patients enrolled in one of two studies . In Study I , 134 eyes were r and omized to SZPRK ( 58 eyes ) or ASPRK ( 76 eyes ) . In Study II , 152 eyes were r and omized to ASPRK ( 76 eyes ) or to LASIK ( 76 eyes ) . INTERVENTION All eyes received spherical one-pass excimer laser ablation as part of PRK or LASIK performed with the Summit Technologies Apex laser under an investigational device exemption , with attempted corrections between -6 and -12 diopters . MAIN OUTCOME MEASURES Data on uncorrected and best spectacle-corrected visual acuity , predictability and stability of refraction , and complications were analyzed . Follow-up was 12 months . RESULTS At 1 month postoperatively , more eyes in the LASIK group achieved 20/20 and 20/25 or better uncorrected visual acuity than PRK-treated eyes ; at the 20/25 or better level , the difference was significant for LASIK ( 29/76 eyes , 38 % ) over SZPRK ( 10/58 eyes , 17 % ) ( P = .0064 ) . At all subsequent postoperative intervals , no difference was seen between treatment groups . Similarly , best corrected visual acuities were better for LASIK than all PRK eyes at 1 month postoperatively , and LASIK was better than SZPRK at 3 months follow-up ( e.g. , for 20/20 or better at 1 month , LASIK 50/76 eyes ( 66 % ) versus SZPRK 24/57 eyes ( 42 % ) , P = .0066 ) . PRK eyes had a mean loss of BCVA through 6 months , while LASIK eyes had a slight gain of mean BCVA through month 6 ; at 12 months , both ASPRK groups but not SZPRK continued to have a small mean loss of BCVA ( e.g. , compared to preoperative , mean BCVA at 12 months for SZPRK was + 0.3 , LASIK was + .21 , ASPRK I was -0.11 , and ASPRK II -0.31 ( SZPRK versus ASPRK II , P = .0116 ) . Predictability was better for PRK than LASIK at all follow-up intervals ( e.g. , for manifest refraction spherical equivalent + /- 1.0 diopters at 6 months , ASPRK I 42/62 eyes ( 68 % ) versus LASIK 29/72 eyes ( 40 % ) , P = .0014 % ) . Stability was slightly but insignificantly less in the LASIK eyes compared to PRK eyes . All visual outcome measures were better for eyes with preoperative myopia between -6 and -8.9 D compared with eyes with myopia between -9 and -12 D. No consistent differences in refractive outcomes or postoperative corneal haze were seen between aspherical and single-zone ablations ; haze diminished over 12 months and was judged to be vision-impairing in only one ASPRK eye . Microkeratome and flap complications occurred in 4 eyes , result ing in delay of completion of the procedure in 3 eyes but not causing long-term impairment . CONCLUSIONS Improvement in uncorrected visual acuity and return of best corrected visual acuity was more rapid for LASIK than PRK , but efficacy outcomes in the longer term through 12 months were similar for all treatment groups . LASIK eyes tended toward undercorrection with the nomogram employed in this study compared to PRK , but the scatter was similar , suggesting little difference between these procedures for most patients by 6 months and thereafter . No consistent advantage was demonstrated between aspherical and single-zone ablation patterns . Predictability was much better for all procedures for corrections of -6 to -8.9 D compared with -9 to -12 D. Sporadic loss of best corrected vision in the PRK eyes not found in the LASIK eyes and other measures of visual function require further study PURPOSE To review cases of corneal ectasia after laser in situ keratomileusis ( LASIK ) , identify preoperative risk factors , and evaluate methods and success rates of visual rehabilitation for these cases . DESIGN Retrospective nonr and omized comparative trial . PARTICIPANTS Ten eyes from seven patients identified as developing corneal ectasia after LASIK , 33 previously reported ectasia cases , and two control groups with uneventful LASIK and normal postoperative courses : 100 consecutive cases ( first control group ) , and 100 consecutive cases with high myopia ( > 8 diopters [ D ] ) preoperatively ( second control group ) . METHODS Retrospective review of preoperative and postoperative data for each case compared with that of previously reported cases and cases with uneventful postoperative courses . MAIN OUTCOME MEASURES Preoperative refraction , topographic features , residual stromal bed thickness ( RSB ) , time to the development of ectasia , number of enhancements , final best-corrected visual acuity ( BCVA ) , and method of final correction . RESULTS Length of follow-up averaged 23.4 months ( range , 6 - 48 months ) after LASIK . Mean time to the development of ectasia averaged 16.3 months ( range , 1 - 45 months ) . Preoperative refraction averaged -8.69 D compared with -5.37 D for the first control group ( P = 0.005 ) . Preoperatively , 88 % of ectasia cases met criteria for forme fruste keratoconus , compared with 2 % of the first control group ( P < 0.0000001 ) and 4 % of the second control group ( P = 0.0000001 ) . Seven eyes ( 70 % ) had RSB < 250 microm , as did 16 % of eyes in the first control group and 46 % of the second control group . The mean RSB for ectasia cases ( 222.8 microm ) was significantly less than that for the first control group ( 293.6 micro m , P = 0.0004 ) and the second control group ( 256.5 microm ; P = 0.04 ) . Seven eyes ( 70 % ) had enhancements . Only 10 % of eyes lost more than one line of BCVA , and all patients eventually achieved corrected vision of 20/30 or better . One case required penetrating keratoplasty ( 10 % ) , while all others required rigid gas-permeable contact lenses for correction . CONCLUSIONS Significant risk factors for the development of ectasia after LASIK include high myopia , forme fruste keratoconus , and low RSB . All patients had at least one risk factor other than high myopia , and significant differences remained even when controlling for myopia . Multiple enhancements were common among affected cases , but their causative role remains unknown . We did not identify any patients who developed ectasia without recognizable preoperative risk factors Purpose : To compare differences in visual acuity , contrast sensitivity , complications , and higher-order ocular aberrations ( HOAs ) in eyes with stable myopia undergoing either photo-refractive keratectomy ( PRK ) or thin-flap laser in situ keratomileusis ( LASIK ) ( intended flap thickness of 90 μm ) using the VISX Star S4 CustomVue excimer laser and the IntraLase FS60 femtosecond laser at 1 , 3 , and 6 months postoperatively . Methods : In this prospect i ve , masked , and r and omized pilot study , refractive surgery was performed contralaterally on 52 eyes : 26 with PRK and 26 with thin-flap LASIK . Primary outcome measures were uncorrected distance visual acuity ( UDVA ) , corrected distance visual acuity ( CDVA ) , contrast sensitivity , and complications . Results : At 6 months , mean values for UDVA ( logMAR ) were −0.043 ± 0.668 and −0.061 ± 0.099 in the PRK and thin-flap LASIK groups , respectively ( n = 25 , P = 0.466 ) . UDVA of 20/20 or better was achieved in 96 % of eyes undergoing PRK and 92 % of eyes undergoing thin-flap LASIK , whereas 20/15 vision or better was achieved in 73 % of eyes undergoing PRK and 72 % of eyes undergoing thin-flap LASIK ( P > 0.600 ) . Significant differences were not found between treatment groups in contrast sensitivity ( P ≥ 0.156 ) or CDVA ( P = 0.800 ) at postoperative 6 months . Types of complications differed between groups , notably 35 % of eyes in the thin-flap LASIK group experiencing complications , including microstriae and 2 flap tears . Conclusion : Under well-controlled surgical conditions , PRK and thin-flap LASIK refractive surgeries achieve similar results in visual acuity , contrast sensitivity , and induction of HOAs , with differences in experienced complications PURPOSE A prospect i ve study was conducted to compare the effectiveness , safety , and stability of photorefractive keratectomy ( PRK ) and laser in situ keratomileusis ( LASIK ) for correction of low to moderate myopia . METHODS Forty-five patients with a manifest refraction ( PRK , -4.54 + /- 0.80 ; LASIK , -4.82 + /- 1.10 ) from -1.50 to -6.00 diopters ( D ) were treated and followed-up for 6 months . In each case , 1 eye received PRK and the other LASIK . The first eye treated , and the surgical method used in the first eye , were r and omized . Uncorrected and corrected visual acuity , manifest refraction , corneal haze , and topographic analysis of ablation decentration were examined . RESULTS The uncorrected visual acuity was 20/20 or better in 35 PRK eyes ( 77.8 % ) and 28 LASIK eyes ( 62.2 % ) at 6 months ( P = .107 ) . At 6 months , 28 eyes ( 62.2 % ) that received PRK showed a spherical equivalent of within + /-0.5 D as compared with 24 eyes ( 53.4 % ) that received LASIK ( P = .393 ) . The amount of ablation decentration was 0.37 + /- 0.25 mm in PRK eyes and 0.49 + /- 0.38 mm in LASIK eyes at 3 months ( P = .36 ) . CONCLUSIONS In our study , PRK and LASIK were found to be similarly effective and predictive of correction in low to moderate myopia . PRK has the advantage of less ablation decentration and is safer than LASIK , so we recommend PRK for eyes with low to moderate myopia Purpose : To measure and compare the changes in objective wavefront aberration and subjective manifest refraction after laser in situ keratomileusis ( LASIK ) flap creation with a mechanical microkeratome and a femtosecond laser . Setting : Private practice refractive surgery center , Irvine , California , USA . Methods : This r and omized prospect i ve study comprised 9 patients ( 18 eyes ) treated with a 2‐step LASIK procedure : lamellar keratectomy with a Hansatome microkeratome ( Bausch & Lomb ) or the IntraLase femtosecond laser in fellow eyes followed by non‐wavefront‐guided ( st and ard ) excimer laser treatment with the Technolas 217A ( Bausch & Lomb ) excimer laser 10 weeks later . Fellow eyes were matched to within 0.75 diopter ( D ) sphere and 0.50 D cylinder . Patients were followed for 3 months after excimer laser treatment . Preoperative and post‐flap creation wavefront aberrometry using a Hartmann‐Shack aberrometer and manifest refraction were compared between the 2 groups . The same tests were performed 3 months after excimer laser ablation . Results : Statistically significant changes were seen in defocus wavefront aberrations after Hansatome ( P = .004 ) and IntraLase ( P = .008 ) flap creation . A hyperopic shift in manifest refraction was noted in the Hansatome group after the creation of the corneal flap ( P = .04 ) ; no statistically significant changes in manifest refraction were seen in the IntraLase group . Statistically significant changes in total higher‐order aberrations ( HOAs ) ( trefoil and quadrafoil Zernike terms ) were seen after flap creation in the Hansatome group ( P = .02 ) . No significant changes in HOAs were noted after flap creation in the IntraLase group . After the flap was relifted and st and ard excimer laser ablation was performed , a statistically significant increase in coma occurred in the Hansatome group ( P = .008 ) . St and ard refractive outcomes in the 2 groups were similar . Conclusions : The creation of the LASIK flap alone can modify the eye 's optical characteristics in low‐order aberrations and HOAs . A significant increase in HOAs was seen in the Hansatome group but not in the IntraLase group . This may have significant clinical implication s in wavefront‐guided LASIK treatments , which are based on measurements made before flap creation Purpose : To compare the outcomes of wavefront‐guided laser in situ keratomileusis ( LASIK ) performed using the IntraLase femtosecond laser with the outcomes using the Hansatome mechanical microkeratome . Setting : Private clinic , Overl and Park , Kansas , USA . Methods : In a prospect i ve contralateral‐eye study performed under institutional review board supervision , 51 consecutive patients ( 102 eyes ) had bilateral wavefront‐guided LASIK for myopia using the Alcon LADARVision laser . One eye of each patient was r and omized to have the flap created with the IntraLase femtosecond laser and the other flap using a st and ard compression head Hansatome microkeratome . All other treatment parameters were the same . Results : The IntraLase group had significantly better mean uncorrected visual acuity ( UCVA ) at all intervals from 1 day to 3 months postoperatively . The mean spheroequivalent at 3 months was more myopic with the Hansatome ( −0.34 diopter [ D ] ± 0.28 [ SD ] ) than with the IntraLase ( −0.19 ± 0.24 D ) ( P<.01 ) . The mean residual astigmatism at 3 months was also significantly higher in the Hansatome group than in the IntraLase group ( 0.32 ± 0.25 D and 0.17 ± 0.20 D , respectively ) ( P<.01 ) . The differences in UCVA persisted after spheroequivalent outcomes were controlled for but equilibrated when the analysis was modified to control for manifest postoperative astigmatism . Aberrometry showed significantly higher astigmatism and trefoil in the Hansatome group . Recovery of corneal sensation and epithelial integrity was similar between groups . Conclusions : The statistically better UCVA and manifest refractive outcomes after LASIK with the IntraLase femtosecond laser may be the result of differences in postoperative astigmatism and trefoil . These findings are consistent with previous findings of better astigmatic outcomes with the IntraLase laser and may have clinical significance for wavefront‐guided treatments OBJECTIVE To compare laser in situ keratomileusis ( LASIK ) with photorefractive keratectomy ( PRK ) in the correction of myopia from -2.00 to -5.50 diopters . DESIGN Prospect i ve , r and omized , paired clinical trial . PARTICIPANTS Fifty-two eyes of 26 myopic patients were enrolled in the study . INTERVENTION Each patient received PRK on one eye ( PRK eye ) and LASIK on the other ( LASIK eye ) ; the procedure assigned to each eye , and the sequence of surgeries for each patient was r and omized . MAIN OUTCOME MEASURES Slit-lamp microscopy , manifest refraction , uncorrected and spectacle-corrected visual acuity , and videokeratography were done before operation , and 2 weeks , 6 weeks , 3 months , 6 months , and 12 months after operation . Patient satisfaction and preference were assessed by a subjective question naire . RESULTS All LASIK eyes had fast , painless recovery . At 1 year , 24 patients ( 92.3 % ) were examined , the mean spherical equivalent refraction was -0.08 + /- 0.38 diopter in the PRK eyes and -0.14 + /- 0.31 diopter in the LASIK eyes , and the uncorrected visual acuity was 20/20 or better in 15 PRK eyes ( 62.5 % ) and 19 LASIK eyes ( 79.2 % ) ; no eye lost 2 or more Snellen lines of spectacle-corrected visual acuity . Both procedures were stable throughout the first year . One PRK eye developed dense subepithelial corneal haze . The strongest correlate to spectacle-corrected visual acuity after the two procedures was the coefficient of variation of corneal power over the pupil . Nineteen patients ( 79.2 % ) preferred the LASIK procedure because of the fast , painless recovery . CONCLUSIONS In the current study , PRK and LASIK were found to be similarly effective , predictable , stable , and reasonably safe for the correction of myopia between -2.00 and -5.50 diopters . Laser in situ keratomileusis has the advantage of fast , painless recovery . Patients prefer LASIK PURPOSE To compare changes in the corneal wavefront aberrations after photorefractive keratectomy and laser in situ keratomileusis . METHODS In a prospect i ve r and omized study , 22 patients with bilateral myopia received photorefractive keratectomy on one eye and laser in situ keratomileusis on the other eye . The procedure assigned to each eye and the sequence of surgery for each patient were r and omized . Corneal topography measurements were performed preoperatively , 2 and 6 weeks , 3 , 6 , and 12 months after surgery . The data were used to calculate the wavefront aberrations of the cornea for both small ( 3-mm ) and large ( 7-mm ) pupils . RESULTS Both photorefractive keratectomy and laser in situ keratomileusis significantly increased the total wavefront aberrations for 3- and 7-mm pupils , and values did not return to the preoperative level throughout the 12-month follow-up period . For a 3-mm pupil , there was no statistically significant difference between photorefractive keratectomy and laser in situ keratomileusis at any postoperative point . For a 7-mm pupil , the post-laser in situ keratomileusis eyes exhibited significantly larger total aberrations than the post-photorefractive keratectomy eyes , where a significant intergroup difference was observed for spherical-like aberration , but not for coma-like aberration . This discrepancy seemed to be attributable to the smaller transition zone of the laser ablation in the laser in situ keratomileusis procedure . Before surgery , simulated pupillary dilation from 3 to 7 mm caused a five- to six-fold increase in the total aberrations . After surgery , the same dilation result ed in a 25- to 32-fold increase in the photorefractive keratectomy group and a 28- to 46-fold increase in the laser in situ keratomileusis group . For a 3-mm pupil , the proportion of coma-like aberration increased after both photorefractive keratectomy and laser in situ keratomileusis . For a 7-mm pupil , coma-like aberration was dominant before surgery , but spherical-like aberration became dominant postoperatively . CONCLUSIONS Both photorefractive keratectomy and laser in situ keratomileusis increase the wavefront aberrations of the cornea and change the relative contribution of coma- and spherical-like aberrations . For a large pupil , laser in situ keratomileusis induces more spherical aberrations than photorefractive keratectomy . This finding could be attributable to the smaller transition zone of the laser ablation in the laser in situ keratomileusis procedure OBJECTIVE To determine the incidence and severity of complications from laser in situ keratomileusis ( LASIK ) for the correction of myopia by experienced and inexperienced surgeons . DESIGN Prospect i ve , observational clinical study . PARTICIPANTS Fourteen surgeons and 1062 eyes of 574 myopic patients who desired surgical correction of myopia ranging from -2.00 to -22.50 diopters ( D ; mean , -7.57 D ) and astigmatism no greater than 4.00 D participated in this study . INTERVENTION Myopia was corrected with LASIK . Astigmatism was corrected with arcuate keratotomy at the same time as the initial procedure or subsequently . MAIN OUTCOME MEASURES Primary outcome measures were change in best spectacle-corrected visual acuity ( BSCVA ) and the incidence of complications . RESULTS Eyes were followed for a mean of 9.5 months after their last surgical procedure ( range , 2 weeks-21 months ) . Three hundred eighty-one eyes ( 36 % ) underwent 468 enhancement procedures 3 months or more after the initial treatment . There were 27 ( 2.1 % ) intraoperative and 40 ( 3.1 % ) postoperative complications . Laser ablation was not performed during the initial treatment of 17 ( 1.6 % ) eyes because of intraoperative complications . Seventy-four eyes gained 2 or more lines of BSCVA , while 50 eyes lost 2 or more lines of BSCVA . Only three eyes lost two or more lines of BSCVA to a level worse than 20/40 . One eye with a flap buttonhole ( BSCVA 20/50 ) also had an epiretinal membrane . The second eye ( BSCVA 20/60 ) had a flap buttonhole that may have been related to a previous corneal transplant . The third eye ( -22.50 D before surgery ) had a rhegmatogenous retinal detachment develop , reducing BSCVA from 20/60 to 20/200 . The incidence of intraoperative complications decreased from 3.1 % during the first 3 months to 0.7 % during the last 9 months of the study ( P = 0.02 ) . CONCLUSIONS LASIK is acceptably safe for the correction of myopia . Although complications occur in approximately 5 % of cases , these rarely lead to visual loss of more than two Snellen lines and postoperative acuity below 20/40 . Flap buttonholes were more likely to cause loss of BSCVA than free or incomplete flaps ( P = 0.02 ) ; flap buttonholes may be more likely in eyes that have undergone previous surgery . Complication rates can be reduced as the surgical team gains experience OBJECTIVE This study aim ed to assess the long-term stability and efficacy of excimer laser photorefractive keratectomy . DESIGN Patients who participated in the first United Kingdom photorefractive keratectomy clinical trial were asked to attend a 6-year follow-up assessment . PARTICIPANTS Eighty-three patients ( 68 % ) of the original cohort of 120 participants were observed for 6 years . A Summit Technology UV200 excimer laser with a 4-mm ablation zone had been used with patients allocated to one of six groups according to their preoperative refraction . Each group received one of the following spherical corrections : -2 , -3 , -4 , -5 , -6 , or -7 diopters ( D ) . Within each group , all patients received an identical treatment , and thus emmetropia was not the goal in all patients . INTERVENTION The induced refractive change , objective corneal haze , glare , and halo measurements , together with possible late-phase complications , were analyzed . MAIN OUTCOME MEASURES All groups achieved a refractive undercorrection , and the magnitude of the undercorrection was related to the size of the attempted correction . The induced refraction stabilized by 6 to 12 months and has been maintained up to the 6-year follow-up stage . RESULTS Ninety-one percent of patients who underwent a -2.00-D correction and 76 % of patients who received a -3.00-D correction were within + /- 1 D of the intended refraction at 6 years . Fifty-seven percent of the -4.00-D group and 50 % of those in the -5.00-D group were within + /- 1 D , and this was reduced further to 43 % in the -6.00-D group and 19 % in the -7.00-D group . Six patients ( 7 % ) had evidence of residual corneal haze , which was visually significant in two patients ( 3 % ) . Ten patients ( 12 % ) had significant night halos due to the small 4-mm ablation zone that was used in this early treatment trial . CONCLUSIONS There was no further regression of the refraction after 1 year , and , more important , there was no sign of hyperopic shift or diurnal fluctuation in the patients ' refraction . In addition , corneal haze appeared to reduce further with time , with no intraocular or retinal side effects being noted . Night halos remain a significant reported problem in a small number of patients who were treated with the 4-mm ablation zone PURPOSE To explain the basic science and clinical evidence that has led to the development of a new technique in corneal refractive surgery -- sub-Bowman 's keratomileusis ( SBK ) . METHODS A comprehensive review of the literature and report of a contralateral eye study of 50 patients ( 100 eyes ) enrolled at 2 sites ( 25 patients per site ) and r and omized according to the dominant eye was conducted . All eyes underwent a wavefront-guided refractive correction using the Alcon LADARVision4000 System . In one eye , an 8.5-mm , ETOH-assisted photorefractive keratectomy ( PRK ) was performed . In the second eye , an 8.5-mm , 100-microm flap was attempted using a 60 kHz IntraLase FS femtosecond laser . Pre- and postoperative tests included best spectacle-corrected visual acuity , uncorrected visual acuity , corneal topography , wavefront aberrometry , retinal image quality , contrast sensitivity , and biomechanical response of the cornea . Patients completed subjective question naires at each follow-up . RESULTS Clinical results demonstrate that SBK provides quicker visual recovery , although the data suggest that the 3- and 6-months results are similar in terms of visual outcomes . Reichert Ocular Response Analyzer results demonstrate that its impact on the cornea is similar to PRK . CONCLUSIONS This study indicates that SBK provides the visual recovery of a LASIK procedure with the Optical Response Analyzer results similar to PRK PURPOSE To evaluate the 24-month refractive outcome of excimer laser photorefractive keratectomy ( PRK ) performed on normal , sighted myopic eyes ; and to assess the evolution of postoperative refraction , the accuracy of predicted correction , and the results in terms of uncorrected visual acuity . METHODS Photorefractive keratectomy was performed on 495 eyes , with a preoperative refraction ranging from -1.25 to -7.50 diopters ( D ) . Ablation zone diameters of 4.3 and 4.5 mm were used . All patients were treated with a st and ard topical steroid regimen postoperatively . Minimum follow-up time was 24 months . RESULTS Mean refraction ( spherical equivalent + /- st and ard deviation ) at 24 months was -0.27 + /- 0.74 D , which was significantly ( P < 0.01 ) different from the mean at 12 months ( 0.01 + /- 0.78 D ) . There was also a significant ( P = 0.01 ) difference between the 12- and 18-month ( -0.15 + /- 0.82 D ) mean refractions . But there was no significant difference between the means at 18 and 24 months postoperatively . Subgroup analysis at 24 months showed that patients with low to moderate myopia ( up to -3.90 D ) had significantly better refractive outcomes than those with higher myopia . Also at 24 months , 91 % of the eyes had an uncorrected visual acuity of at least 20/40 , and 81.5 % had an uncorrected visual acuity of at least 20/30 . Correspondingly , 87.5 % of the eyes were within 1.00 D of emmetropia , and 71.7 % were within 0.50 D. Only 0.4 % lost one line of best-corrected visual acuity , no eye lost two lines or more . CONCLUSIONS Refraction after PRK is slow to stabilize , but appears to reach stability by 18 to 24 months after surgery . The refractive results are reasonably predictable and compare well with those achieved with radial keratotomy OBJECTIVE This study aim ed to compare qualitative patterns of corneal topography early in the postoperative course after excimer laser photorefractive keratectomy ( PRK ) and laser in situ keratomileusis ( LASIK ) when used for the treatment of myopia of 6.0 to 15.0 diopters . DESIGN The study design was a prospect i ve , multicenter , r and omized clinical trial . PARTICIPANTS A total of 64 eyes were treated with PRK and 54 eyes were treated with LASIK . INTERVENTION Using the Summit Apex excimer laser , patients received either PRK or LASIK using a single pass , multizone excimer laser ablation . Computer-assisted videokeratography was performed at design ated postoperative examinations . MAIN OUTCOME MEASURES Videokeratography maps at 1 and 3 months after surgery were classified using a st and ard classification scheme . The association of topography patterns to loss of spectacle-corrected visual acuity was tested . RESULTS At 1 month , for the PRK ( n = 60 ) and LASIK ( n = 51 ) groups , respectively , 63.3 % and 19.6 % of eyes fell into one of the four optically irregular groups ( central isl and , keyhole , semicircular , or irregularly irregular ; P < 0.001 ) . At 3 months , for the PRK ( n = 49 ) and LASIK ( n = 39 ) groups , respectively , 36.7 % and 10.3 % of eyes fell into one of the optically irregular groups ( P = 0.004 ) . Comparing the 1- and 3-month examination results in the PRK and LASIK groups , respectively , 19 ( 42 % ) of 45 eyes and 11 ( 31 % ) of 36 eyes had a change in topography , generally to an optically smoother pattern . The irregular groups , taken together , were associated with a greater tendency toward loss of spectacle-corrected visual acuity of two or more Snellen lines ( P = 0.01 ) . There also was greater tendency toward loss of spectacle-corrected visual acuity in the PRK group that diminished with time ( P < 0.01 at 1 month , P = 0.05 at 3 months ) . CONCLUSIONS After treatment for moderate-to-high myopia , LASIK topography patterns generally are more regular than are PRK patterns . This may be a result either of masking of underlying topography perturbations by the lamellar corneal flap , thus mitigating induced topography changes , or differences in surface wound healing . This study suggests that more rapid return of spectacle-corrected visual acuity found in patients treated with LASIK may be a result of more regular topography patterns early in the postoperative course OBJECTIVE To compare effectiveness , safety , and stability of excimer laser in situ keratomileusis ( LASIK ) and photorefractive keratectomy ( PRK ) for low-to-moderate myopia . DESIGN Prospect i ve , r and omized , bilateral study . PARTICIPANTS Thirty-three patients with a manifest refraction of -2.50 to -8.00 diopters ( D ) participated . INTERVENTION For each patient , one eye received LASIK and the other received PRK . The first eye treated , and surgical method in the first eye , were r and omized . Both eyes were treated by the same surgeon during the same operative session with a Summit Omnimed I laser ( 6-mm-diameter ablation ) and a Chiron Automated Corneal Shaper . Follow-up was 90 % at 1 and 2 years . RESULTS At baseline , mean ( + /-st and ard deviation ) spherical equivalent manifest refraction was -4.80 + /- 1.60 D in LASIK-treated eyes and -4.70 + /- 1.50 D in PRK-treated eyes . At 1 day after surgery , 81 % of patients ( 21 eyes ) reported no pain in the LASIK-treated eye , whereas no patient ( 0 % ) reported being pain-free in the PRK-treated eye . At 3 to 4 days after surgery , 18 ( 80 % ) LASIK-treated eyes either improved or remained within 1 line of baseline spectacle-corrected visual acuity ; only 10 ( 45 % ) PRK-treated eyes achieved this result . At 2 years after surgery , 18 ( 61 % ) LASIK- and 10 ( 36 % ) PRK-treated eyes achieved an uncorrected visual acuity of 20/20 or better , with no statistically significant difference in refractive outcome between the two techniques . Quantitative videokeratography showed more regularity after LASIK . Complications were similar in the two groups . Patients preferred LASIK by a margin of 2 to 1 at 1 year but showed no preference at 2 years . CONCLUSIONS Using a 6-mm-diameter single-pass , large area ablation and an automated microkeratome to treat myopia of -2.50 to -8.00 D with 1.00 D or less astigmatism in 1994 , the authors used LASIK to produce a higher percentage of eyes with an uncorrected visual acuity of 20/20 or better , more regular postoperative corneal topography , less postoperative pain , and more rapid recovery of baseline spectacle-corrected visual acuity than PRK . Both LASIK and PRK achieved successful correction of low-to-moderate myopia at 1 and 2 years after surgery OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) PURPOSE To evaluate and compare the recovery of postoperative corneal sensitivity after laser in situ keratomileusis and photorefractive keratectomy for the correction of low myopia . METHODS In a prospect i ve study , 17 consecutive eyes ( 17 patients ) underwent laser in situ keratomileusis to correct myopia ranging from -3.25 to -6.75 diopters , and another 18 consecutive eyes ( 18 patients ) underwent photorefractive keratectomy to correct myopia from -3.12 to -7.00 diopters . Corneal sensitivity was tested preoperatively and 1 week and 1 , 3 , and 6 months postoperatively using the Cochet-Bonnet esthesiometer . Corneal sensitivity was tested at the center of the cornea , and in four additional central points 2 mm from the corneal center ( nasal , inferior , temporal , and superior ) . RESULTS Corneal sensitivity after laser in situ keratomileusis was reduced at the ablated zone during the first 3 months after surgery ( Wilcoxon rank sum test , P < .05 ) , and only after 6 months it returned to its preoperative values . However , corneal sensitivity recovered its preoperative values 1 month after photorefractive keratectomy ( Wilcoxon rank sum test , P > .05 ) , except for the central corneal point , where 3 months were required . Comparing both groups , corneal sensitivity was more depressed after laser in situ keratomileusis than after photorefractive keratectomy during the first 3 months ( Mann-Whitney test , P < .05 ) , except for the nasal central point , although no differences were found between both groups at 6 months ( P > .05 ) . CONCLUSIONS In the correction of low myopia , corneal sensitivity at the ablated zone was more depressed after laser in situ keratomileusis than after photorefractive keratectomy during the first 3 months after surgery . Only after 6 months were corneal sensitivity values similar in both groups PURPOSE To compare the safety and efficacy of wavefront-guided laser in situ keratomileusis ( LASIK ) vs photorefractive keratectomy ( PRK ) in a prospect i ve r and omized clinical trial . METHODS A cohort of 68 eyes of 34 patients with -0.75 to -8.13 diopters ( D ) of myopia ( spherical equivalent ) were r and omized to receive either wavefront-guided PRK or LASIK in the fellow eye using the VISX CustomVue laser . Patients were evaluated at 1 day , 1 week , and months 1 , 3 , 6 , and 12 . RESULTS At 1 month , uncorrected visual acuity ( UCVA ) , best spectacle-corrected visual acuity ( BSCVA ) , 5 % and 25 % contrast sensitivity , induction of higher-order aberrations ( HOAs ) , and subjective symptoms of vision clarity , vision fluctuation , ghosting , and overall self- assessment of vision were worse ( P<0.05 ) in the PRK group . By 3 months , these differences had resolved ( P>0.05 ) . At 1 year , mean spherical equivalent was reduced 94 % to -0.27 ± 0.31 D in the LASIK group and reduced 96 % to -0.17 ± 0.41 D in the PRK group . At 1 year , 91 % of eyes were within ±0.50 D and 97 % were within ±1.0 D in the PRK group . At 1 year , 88 % of eyes were within ±0.50 D and 97 % were within ±1.0 D in the LASIK group . At 1 year , 97 % of eyes in the PRK group and 94 % of eyes in the LASIK group achieved an UCVA of 20/20 or better ( P=0.72 ) . Refractive stability was achieved in both PRK and LASIK groups after 1 month . There were no intraoperative or postoperative flap complications in the LASIK group . There were no instances of corneal haze in the PRK group . CONCLUSIONS Wavefront-guided LASIK and PRK are safe and effective at reducing myopia . At 1 month postoperatively , LASIK demonstrates an advantage over PRK in UCVA , BSCVA , low-contrast acuity , induction of total HOAs , and several subjective symptoms . At postoperative month 3 , these differences between PRK and LASIK results had resolved OBJECTIVE To evaluate long-term refractive stability of excimer laser myopic photorefractive keratectomy ( PRK ) . DESIGN A long-term ( 12 years ) prospect i ve follow-up study . PARTICIPANTS Sixty-eight patients ( 56.6 % ) of the original cohort of 120 who participated in the first United Kingdom excimer laser clinical trial underwent detailed clinical assessment at 12 years after myopic PRK . INTERVENTION Myopic PRK was performed using the Summit Technology UV 200 excimer laser with a 4-mm ablation zone . Patients were allocated to 1 of 6 treatment groups based on their preoperative refraction . Each group received one of the following spherical corrections : -2 , -3 , -4 , -5 , -6 , or -7 diopters ( D ) . Patients in each group received an identical treatment , and therefore , emmetropia was not the primary aim . MAIN OUTCOME MEASURES Refractive stability , refractive predictability , best spectacle-corrected visual acuity ( BSCVA ) , and corneal haze . RESULTS The postoperative refraction remained stable at 12 years , with no significant change in mean spherical equivalent refraction between 1 , 6 , and 12 years . Seventy-five percent of patients who underwent a -2-D correction and 65 % of patients who received a -3-D correction were within 1 D of intended correction at 12 years . Fifty-seven percent of the -4-D group and 50 % of the -5-D group were within 1 D , and this was further reduced to 25 % and 22 % in the -6-D and -7-D groups , respectively . Four percent had residual corneal haze , and 12 % had persistent nighttime halos at 12 years . Dry eyes were encountered in 3 % of patients , and none of the eyes developed corneal ectasia in the long term . CONCLUSIONS In myopic PRK , refractive stability achieved at 1 year was maintained up to 12 years with no evidence of hyperopic shift , diurnal fluctuation , or late regression in the long term . Corneal haze decreased with time , with complete recovery of BSCVA . Night halos remained a significant problem in a subset of patients due to the small ablation zone size OBJECTIVE This document describes laser in situ keratomileusis ( LASIK ) for myopia and astigmatism and examines the evidence to answer key questions about the efficacy and safety of the procedure . METHODS A literature search conducted for the years 1968 to 2000 retrieved 486 citations and an up date search conducted in June 2001 yielded an additional 243 articles . The panel members review ed 160 of these articles and selected 47 for the panel method ologist to review and rate according to the strength of evidence . A Level I rating is assigned to properly conducted , well- design ed , r and omized clinical trials ; a Level II rating is assigned to well- design ed cohort and case-control studies ; and a Level III rating is assigned to case series and poorly design ed prospect i ve and retrospective studies , including case-control studies . RESULTS The assessment describes r and omized controlled trials published in 1997 or later ( Level I evidence ) and more recent comparative and noncomparative case series ( Level II and Level III evidence ) , focusing on results for safety and effectiveness . It is difficult to extrapolate results from these studies that are comparable to current practice s with the most recent generation lasers because of the rapid evolution of LASIK technology and techniques . It is also difficult to compare studies because of variations in the range of preoperative myopia , follow-up periods , lasers , nomograms , microkeratomes and techniques , the time frame of the study , and the investigators ' experience . CONCLUSIONS For low to moderate myopia , results from studies in the literature have shown that LASIK is effective and predictable in terms of obtaining very good to excellent uncorrected visual acuity and that it is safe in terms of minimal loss of visual acuity . For moderate to high myopia ( > 6.0 D ) , the results are more variable , given the wide range of preoperative myopia . The results are similar for treated eyes with mild to moderate degrees of astigmatism ( < 2.0 D ) . Serious adverse complications leading to significant permanent visual loss such as infections and corneal ectasia probably occur rarely in LASIK procedures ; however , side effects such as dry eyes , night time starbursts , and reduced contrast sensitivity occur relatively frequently . There were insufficient data in prospect i ve , comparative trials to describe the relative advantages and disadvantages of different lasers or nomograms PURPOSE To compare the axis and magnitude of surgically induced astigmatism in photorefractive keratectomy ( PRK ) and laser in situ keratomileusis ( LASIK ) . SETTING Multicenter clinical trial . METHODS In this prospect i ve r and omized trial , 220 eyes of 220 patients entered the study cohort : 105 r and omized to PRK and 115 to LASIK . All patients received a single-pass , multizone excimer laser ablation as part of a PRK or LASIK procedure . Attempted corrections ranged from -6.00 to -15.00 diopters ( D ) . The LASIK procedures were performed with nasal hinges . Absolute changes in astigmatism and axis and magnitude of surgically induced astigmatism were analyzed . Patients were followed for up to 6 month . RESULTS In the PRK group , the mean change in absolute astigmatism was + 0.14 , + 0.16 and + 0.32 D at 1 , 3 , and 6 months , respectively ; in the LASIK group , the mean change was -0.15 , -0.08 , and -0.03 D , respectively . At all time points , a greater proportion of PRK than LASIK eyes had an increase in absolute magnitude of astigmatism . In the PRK group , the axis of vectoral-induced astigmatism was significantly different from r and om at 3 and 6 months ( P = .01 , P < .001 ) , respectively ) with a tendency for induced with-the-rule shifts postoperatively . In the LASIK group , the axis of vectoral-induced astigmatism was significantly different from r and om at only 1 month ( P = .04 ) , and there was no preponderant direction of axis shift . Despite these findings , other analyses showed no statistically significant between-group differences in vectoral axis or magnitude of surgically induced astigmatism . CONCLUSIONS Induced astigmatism was generally less and more r and om in axis in LASIK than in PRK ; a general trend for induced with-the-rule astigmatism in PRK was not seen in LASIK . Hypothetically , the lamellar corneal flap in LASIK may counteract the tendency toward steepening at 90 degrees seen in PRK by retracting toward the hinge , by masking underlying induced astigmatism in the ablation zone , or by its mitigating influence on postoperative corneal healing PURPOSE To compare photorefractive keratectomy ( PRK ) with prophylactic use of mitomycin C ( MMC ) and LASIK in custom surgeries for myopic astigmatism . METHODS Eighty-eight eyes of 44 patients with a minimum estimated ablation depth of 50 microm were r and omized to receive PRK with MMC 0.002 % for 1 minute in one eye and LASIK in the fellow eye . Uncorrected visual acuity ( UCVA ) , best spectacle-corrected visual acuity ( BSCVA ) , cycloplegic refraction , slit-lamp microscopy , contrast sensitivity , specular microscopy , aberrometry , and a subjective question naire were evaluated . Forty-two patients completed 6-month follow-up . RESULTS Mean spherical equivalent refraction error before surgery and mean ablation depth were -3.99+/-1.20 diopters ( D ) and 73.09+/-14.55 microm in LASIK eyes , and -3.85+/-1.12 D and 70.7+/-14.07 microm in PRK with MMC eyes , respectively . Uncorrected visual acuity was significantly better in PRK with MMC eyes 3 months ( P=.04 ) and 6 months ( P=.01 ) after surgery . Best spectacle-corrected visual acuity and spherical equivalent refraction did not differ significantly in the groups during follow-up ( P>.05 ) . Significant haze was not observed in any PRK with MMC eye . Mean higher order aberration was lower in PRK with MMC eyes postoperatively compared with LASIK eyes ( P=.01 ) . Better contrast sensitivity was observed in PRK with MMC eyes than LASIK eyes ( P<.05 ) . The endothelial cell count did not differ significantly between groups ( P=.65 ) . In terms of visual satisfaction , PRK with MMC eyes were better rated . CONCLUSIONS Photorefractive keratectomy with MMC appears to be more effective than LASIK in custom surgery for moderate myopia . During 6-month follow-up , no toxic effects of MMC were evident . Long-term follow-up is necessary to attest its safety PURPOSE To examine long-term changes in corneal power and aberrations in myopic patients r and omized to photorefractive keratectomy ( PRK ) or laser in situ keratomileusis ( LASIK ) . METHODS Forty-five patients with myopia from -6 to -8 diopters ( spherical equivalent refraction ) were r and omized to PRK ( n = 20 ) or LASIK ( n = 25 ) . Patients were examined preoperatively and for up to 7 years after surgery . Measurements included refraction , topography ( TMS-1 ) , and ultrasound pachymetry . By 3 years , 16 PRK and 15 LASIK patients were examined and by 7 years , 9 PRK and 7 LASIK subjects were available . Only patients who had not been reoperated and attended the two late controls were included in data analyses . Optical analysis of topographic data was used to calculate corneal power and wavefront aberrations . RESULTS PRK and LASIK caused a similar reduction in corneal power . During the first year after PRK , corneal power increased , but remained stable from 1 to 7 years . In contrast , corneal power continued to increase from 1 to 7 years after LASIK . Both PRK and LASIK caused an increase in coma-like and spherical aberrations that remained constant for 7 years . No significant changes in other higher-order aberrations were observed . CONCLUSIONS The cornea may not be stable even 7 years after LASIK , as indicated by the continuing increase in corneal power . In contrast , PRK appears stable from 1 year post surgery . Coma-like and spherical aberrations are permanently increased after PRK and LASIK . ( Clinical Trials.gov number , NCT00404105 . ) PURPOSE To compare intraocular straylight measurements and contrast sensitivity after wavefront-guided LASIK ( WFG LASIK ) in one eye and wavefront-guided photorefractive keratectomy ( WFG PRK ) in the fellow eye for myopia and myopic astigmatism correction . METHODS A prospect i ve , r and omized study of 22 eyes of 11 patients who underwent simultaneous WFG LASIK and WFG PRK ( contralateral eye ) . Both groups were treated with the NIDEK Advanced Vision Excimer Laser System , and a microkeratome was used for flap creation in the WFG LASIK group . High and low contrast visual acuity , wavefront analysis , contrast sensitivity , and retinal straylight measurements were performed preoperatively and at 3 , 6 , and 12 months postoperatively . A third-generation straylight meter , C-Quant ( Oculus Optikgeräte GmbH ) , was used for measuring intraocular straylight . RESULTS Twelve months postoperatively , mean uncorrected distance visual acuity was -0.06 + /- 0.07 logMAR in the WFG LASIK group and -0.10 + /- 0.10 logMAR in the WFG PRK group . Mean preoperative intraocular straylight was 0.94 + /- 0.12 logs for the WFG LASIK group and 0.96 + /- 0.11 logs for the WFG PRK group . After 12 months , the mean straylight value was 1.01 + /- 0.1 log s for the WFG LASIK group and 0.97 + /- 0.12 log s for the WFG PRK group . No difference was found between techniques after 12 months ( P = .306 ) . No significant difference in photopic and mesopic contrast sensitivity between groups was noted . CONCLUSIONS Intraocular straylight showed no statistically significant increase 1 year after WFG LASIK and WFG PRK . Higher order aberrations increased significantly after surgery for both groups . Nevertheless , WFG LASIK and WFG PRK yielded excellent visual acuity and contrast sensitivity performance without significant differences between techniques Purpose : To compare the short‐ , medium‐ , and long‐term changes in corneal optical power and corneal aberrations , central corneal thickness , and corneal “ stiffness ” assessed by pneumotonometry readings in patients having laser in situ keratomileusis ( LASIK ) or photorefractive keratectomy ( PRK ) for myopia . Setting : Department of Ophthalmology , Århus University Hospital , Århus , Denmark . Methods : One eye of each of 45 patients with myopia ranging from −6.00 to −8.00 diopters ( D ) ( spherical equivalent spectacle refraction [ SER ] ) was r and omized to LASIK ( n = 25 ; mean SER −7.12 D ± 0.57 [ SD ] ) or PRK ( n = 20 ; mean SER −6.91 ± 0.57 D ) . Data were collected prospect ively before and 1 , 3 , 6 , 12 , and 36 months after surgery . Measurements included corneal topography ( TMS‐1 , Tomey ) , corneal thickness ( ultrasound pachymetry ) , and apparent intraocular pressure ( IOP ) ( pneumotonometry ) . Retreatments were not performed during the first year , and retreated eyes were excluded from the 3‐year follow‐up . Changes in corneal power and aberrations , thickness , and apparent IOP were calculated in a pair‐wise manner for 3 time periods : short term ( preoperative to 1 month after surgery ) , medium term ( 1 to 12 months after surgery ) , and long term ( 1 to 3 years after surgery ) . Results : In the short term , corneal power decreased equally in LASIK and PRK eyes . Spherical aberrations and coma‐like aberrations increased equally , while corneal thickness decreased significantly less in LASIK eyes than in PRK eyes . The apparent IOP decreased more in LASIK eyes than in PRK eyes . In the medium term , corneal power increased significantly in both groups . Spherical aberrations decreased significantly in PRK eyes but not in LASIK eyes . From 1 to 12 months , corneal thickness increased more in PRK eyes than in LASIK eyes . During this period , the apparent IOP increased significantly in LASIK eyes . In the long term , corneal power and corneal aberrations did not change significantly in either group . Corneal thickness increased slightly but significantly in both groups . The apparent IOP increased significantly more in PRK eyes . Conclusions : Differences between LASIK and PRK related to time‐dependent events affecting corneal shape and structural integrity were present . Peripheral changes in flap hydration in LASIK eyes and epithelial and /or stromal thickening in PRK eyes appeared to be the most important factors in optical power changes in the first year after treatment . The changes in apparent IOP suggest that some interlamellar healing occurred during the first year after LASIK . After LASIK and PRK , corneal bending stiffness seemed permanently decreased , although some restiffening may occur in PRK eyes in the long term Purpose : To compare the outcome of low‐contrast visual acuity and glare sensitivity after photorefractive keratectomy ( PRK ) and laser in situ keratomileusis ( LASIK ) . Setting : Department of Ophthalmology , Cantonal Hospital of Lucerne , Lucerne , Switzerl and . Methods : In this prospect i ve study , patients selected PRK or LASIK after the advantages and disadvantages of both had been described . Snellen visual acuity and disability glare were measured with the Berkeley glare test preoperatively and 1 year postoperatively . At the 1‐year follow‐up , haze was grade d and patients had to assess their quality of vision subjectively . Results : One‐year follow‐up of 58 patients in the PRK group and 64 patients in the LASIK group was achieved . In both groups , the mean uncorrected visual acuity was 20/32 ( P = .63 ) and the mean best corrected visual acuity , 20/20 with no statistically significant difference ( P = .20 ) . There were no preoperative or postoperative differences between the 2 groups in low‐contrast visual acuity under 4 glare conditions . At 1 year , LASIK eyes had significantly lower postoperative haze scores than PRK eyes ( P = .0013 ) . The number of eyes with visually moderate and disturbing halos or disturbances in night vision did not differ considerably between the groups ( P = .88 ) . Conclusions : Efficacy outcomes were generally similar in the PRK and LASIK groups . Both achieved good objective and subjective results after treatment with a second‐generation excimer laser Purpose : To evaluate and compare tear secretion and tear film instability following photorefractive keratectomy ( PRK ) and laser in situ keratomileusis ( LASIK ) . Setting : Department of Ophthalmology , Yonsei University School of Medicine , Seoul , Korea . Methods : In a prospect i ve study , 36 eyes ( 21 patients ) had PRK and 39 eyes ( 25 patients ) had LASIK to correct myopia . Tear secretion and tear film instability were tested preoperatively and 3 and 6 months postoperatively using Schirmer test values , tear breakup time ( BUT ) scores , and tear osmolarity . Results : Six months after surgery , the change in Schirmer test values from preoperative levels was –14.57 % ± 6.39 % ( SD ) in the PRK eyes and –23.40 % ± 5.94 % in the LASIK eyes and the change in BUT scores , –12.54 % ± 8.28 % and –18.79 % ± 13.01 % , respectively . The change in tear osmolarity was 14.95 % ± 6.46 % and 35.63 % ± 8.51 % , respectively . Conclusions : The decrease in tear secretion was greater after LASIK than after PRK at 6 months . Proper treatment of dry eye is required after LASIK and PRK , particularly in the LASIK postoperative period PURPOSE To prospect ively evaluate inflammatory response by measuring aqueous flare in the anterior chamber after photorefractive keratectomy ( PRK ) , laser in situ keratomileusis ( LASIK ) , and intracorneal ring segments ( ICRS ) implantation . METHODS Aqueous flare was measured pre- and postoperatively at days 1 , 7 , and 21 with a laser flare meter ( Kowa FM 500 ) . Thirty-one patients ( 58 eyes ) were r and omized , only for low myopia , in three groups treated with PRK ( myopia < -4.50 D ) , LASIK ( myopia range between -4.00 and -12.00 D ) , and ICRS ( myopia < -4.50 D ) . RESULTS Mean preoperative flare intensities were similar in the three groups ( p < or = 0.05 ; mean , 4.6 photons/ms ) . In the PRK group , flare increased significantly ( mean day 2 , 9.5 photons/ms ) , as it did in the LASIK group ( mean day 1 , 23.8 photons/ms ) . In the ICRS group , there was no significant difference between pre- and postoperative levels of flare at any time ( mean day 1 , 4.9 photons/ms ) . In all three groups , flare intensity returned to baseline at day 7 , except in the LASIK group , which remained at a significantly higher level ( mean day 7 , 7.7 photons/ms ) than the preoperative one . CONCLUSIONS According to this method , the blood-aqueous barrier seems to be altered in laser procedures , particularly in LASIK , probably in correlation with the depth of photoablation . ICRS implantation did not increase the postoperative flare significantly |
1,156 | 24,408,888 | Among HIV-infected individuals , the prevalence of CVD risk factors and the risk for CVD is higher compared with HIV negatives .
Antiretroviral drugs may induce dyslipidaemia , reduce insulin sensitivity , and promote body fat redistribution that additionally contributes to CVD risk .
Some antiretroviral drugs may increase risk for CVD events , but the absolute risk increase is moderate and has to be put into perspective with the massive HIV-related benefits .
Sustained HIV suppression reduces systemic inflammatory markers and is associated with a moderate reduction in CVD events .
Statins are effective for the treatment of dyslipidaemia in HIV infection , but drug interactions with ART need to be considered .
Human immunodeficiency virus-infected individuals are at increased risk for CVD .
Timely initiation of ART with consequent viral suppression is likely to reduce CVD events and to offset potential side effects from ART-induced metabolic changes . | AIMS With the success of antiretroviral therapy ( ART ) , non-human immunodeficiency virus (HIV)-related comorbidities like cardiovascular diseases ( CVDs ) are of increasing concern .
We describe important recent research developments on the epidemiology of CVD in HIV infection , ART-related metabolic changes , and cardioprotective anti-inflammatory mechanisms , and summarize management strategies for CVD risk reduction . | CONTEXT Cardiovascular disease is increased in patients with human immunodeficiency virus ( HIV ) , but the specific mechanisms are unknown . OBJECTIVE To assess arterial wall inflammation in HIV , using 18fluorine-2-deoxy-D-glucose positron emission tomography ( 18F-FDG-PET ) , in relationship to traditional and nontraditional risk markers , including soluble CD163 ( sCD163 ) , a marker of monocyte and macrophage activation . DESIGN , SETTING , AND PARTICIPANTS A cross-sectional study of 81 participants investigated between November 2009 and July 2011 at the Massachusetts General Hospital . Twenty-seven participants with HIV without known cardiac disease underwent cardiac 18F-FDG-PET for assessment of arterial wall inflammation and coronary computed tomography scanning for coronary artery calcium . The HIV group was compared with 2 separate non-HIV control groups . One control group ( n = 27 ) was matched to the HIV group for age , sex , and Framingham risk score ( FRS ) and had no known atherosclerotic disease ( non-HIV FRS-matched controls ) . The second control group ( n = 27 ) was matched on sex and selected based on the presence of known atherosclerotic disease ( non-HIV atherosclerotic controls ) . MAIN OUTCOME MEASURE Arterial inflammation was prospect ively determined as the ratio of FDG uptake in the arterial wall of the ascending aorta to venous background as the target-to- background ratio ( TBR ) . RESULTS Participants with HIV demonstrated well-controlled HIV disease ( mean [ SD ] CD4 cell count , 641 [ 288 ] cells/μL ; median [ interquartile range ] HIV-RNA level , < 48 [ < 48 to < 48 ] copies/mL ) . All were receiving antiretroviral therapy ( mean [ SD ] duration , 12.3 [ 4.3 ] years ) . The mean FRS was low in both HIV and non-HIV FRS-matched control participants ( 6.4 ; 95 % CI , 4.8 - 8.0 vs 6.6 ; 95 % CI , 4.9 - 8.2 ; P = .87 ) . Arterial inflammation in the aorta ( aortic TBR ) was higher in the HIV group vs the non-HIV FRS-matched control group ( 2.23 ; 95 % CI , 2.07 - 2.40 vs 1.89 ; 95 % CI , 1.80 - 1.97 ; P < .001 ) , but was similar compared with the non-HIV atherosclerotic control group ( 2.23 ; 95 % CI , 2.07 - 2.40 vs 2.13 ; 95 % CI , 2.03 - 2.23 ; P = .29 ) . Aortic TBR remained significantly higher in the HIV group vs the non-HIV FRS-matched control group after adjusting for traditional cardiovascular risk factors ( P = .002 ) and in stratified analyses among participants with undetectable viral load , zero calcium , FRS of less than 10 , a low-density lipoprotein cholesterol level of less than 100 mg/dL ( < 2.59 mmol/L ) , no statin use , and no smoking ( all P ≤ .01 ) . Aortic TBR was associated with sCD163 level ( P = .04 ) but not with C-reactive protein ( P = .65 ) or D-dimer ( P = .08 ) among patients with HIV . CONCLUSION Participants infected with HIV vs noninfected control participants with similar cardiac risk factors had signs of increased arterial inflammation , which was associated with a circulating marker of monocyte and macrophage activation BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Background Therapy with a HIV protease inhibitor is associated with elevations in cholesterol and triglycerides . HMG-CoA reductase inhibitors ( ` statins ' ) are the established therapy for persons with primary hypercholesterolaemia . Because of drug interactions , pravastatin may represent the preferred choice in those taking HIV protease inhibitors . Design A r and omized , open-label comparative 24 week trial of dietary advice alone or with pravastatin in 31 male patients established on protease inhibitor-based regimens for greater than 12 weeks with viral load < 500 copies/ml and cholesterol > 6.5 mmol/l . Results There were no significant clinical or laboratory events and no patient discontinuation secondary to adverse effects . Viral rebound did not occur . Relative to baseline , total cholesterol at week 24 fell significantly in the pravastatin ( 1.2 mmol/l ; 17.3 % ) ( P < 0.05 ) but not in the dietary advice ( 0.3 mmol/l ; 4 % ) group . The difference between the two groups approached significance at week 24 ( P = 0.051 ) . This fall was accounted for entirely by a reduction in low density lipoprotein [ calculated change 1.24 mmol/l ( 19 % ) and 0.07 mmol ( 5.5 % ) in pravastatin and dietary advice groups , respectively ] as high density lipoprotein rose non-significantly by 0.6 mmol/l in both groups . Weight , basal metabolic rate , fasting glucose and triglycerides did not change significantly in either group . Conclusions Dietary advice plus pravastatin significantly reduced total cholesterol in HIV-positive individuals taking protease inhibitors , without significant adverse effects . The inclusion of pravastatin substantially increases the magnitude of the change , which is comparable with changes achieved in endogenous hyperlipidaemia Background : The effect of specific antiretrovirals on inflammation is unclear . Methods : A5224s was a sub study of A5202 , which r and omized HIV-infected treatment-naïve patients to blinded abacavir/lamivudine ( ABC/3TC ) or tenofovir/emtricitabine ( TDF/FTC ) with open-label efavirenz ( EFV ) or atazanavir/ritonavir ( ATV/r ) in a factorial design . Our analysis compared changes in inflammation markers from baseline to week 24 between ABC/3TC and TDF/FTC . Secondary analyses included changes at week 96 and comparisons of EFV vs. ATV/r . Results : Analyses included 244 patients ( 85 % male , 48 % white non-Hispanic ) , median age 39 years , HIV-1 RNA 4.6 log10 copies/ml , CD4 240 cells/&mgr;l . TNF-&agr ; , soluble receptors of TNF-&agr ; (sTNFR)-I and II , soluble vascular cellular adhesion molecule (sVCAM)-1 and soluble intercellular adhesion molecule (sICAM)-1 decreased significantly at weeks 24 and 96 , without significant differences between components ( P ≥ 0.44 ) . At week 24 , ABC/3TC had a greater high-sensitivity C-reactive protein ( hsCRP ) mean fold change than TDF/FTC { 1.43 vs. 0.88 , estimated mean fold change percentage difference [ & Dgr ; ] 61.5 % [ 95 % confidence interval ( CI ) 13.6 % , 129.5 % ] ; P = 0.008}. Similar results were seen at week 96 ( P = 0.021 ) . At week 24 ( but not 96 ) , EFV had a greater hsCRP mean fold change than ATV/r [ 1.41 vs. 0.88 ; & Dgr ; = 60.2 % ( 12.6 % , 127.7 % ) ; P = 0.009 ] . IL-6 decreased significantly at week 24 with TDF/FTC but not with ABC/3TC ( between-components P = 0.019 ) . At week 96 , IL-6 decreased significantly in both nucleoside reverse transcriptase inhibitor components ( between-components P = 0.11 ) . IL-6 changes were not significantly different between ATV/r and EFV at either time point ( P ≥ 0.89 ) . Conclusions : Soluble TNF-receptors and adhesion molecules decreased following treatment initiation and did not differ by regimens . Differences were seen on hsCRP and IL-6 changes with ABC/3TC vs. TDF/FTC and on hsCRP with EFV vs. ATV/r Objectives : To evaluate simplified protease inhibitor (PI)-sparing antiretroviral treatment versus lipid-lowering therapy for the management of highly active antiretroviral therapy (HAART)-induced hyperlipidaemia . Design : R and omized , open-label clinical trial assessing the efficacy on hyperlipidaemia of a switching therapy from PI to non-nucleoside reverse transcriptase inhibitor ( NNRTI ) nevirapine or efavirenz versus a hypolipidaemic treatment ( with pravastatin or bezafibrate ) added to current , unchanged antiretroviral combination . Methods : All HIV-infected patients on their first HAART regimen , with stable immuno-virological features , naive to all NNRTIs , and with mixed hyperlipidaemia , were r and omized to replace PI with nevirapine ( arm A ) or efavirenz ( arm B ) , or to receive pravastatin ( arm C ) or bezafibrate ( arm D ) with unchanged HAART regimen , and were followed-up for 12 months . Results : One hundred and thirty patients were evaluated : 29 patients were r and omized to arm A , 34 to arm B , 36 to arm C , and 31 to arm D. At the end of the 12-month follow-up , a reduction of 25.2 , 9.4 , 41.2 and 46.6 % in mean triglyceridaemia versus respective baseline values was reported in groups A , B , C and D , respectively , with statistically significant difference between arms A – B and C – D ( P < 0.01 ) . Similar results were reported for total and low-density lipoprotein cholesterol levels . Viro-immunological efficacy and tolerability profile were comparable in all considered arms . Conclusion : Pravastatin and bezafibrate proved significantly more effective in the management of HAART-related hyperlipidaemia than the switching therapy from PI to nevirapine or efavirenz CONTEXT A syndrome of lipodystrophy , characterized by fat redistribution and insulin resistance , has been estimated to affect the majority of human immunodeficiency virus (HIV)-infected individuals who are treated with combination antiretroviral therapy . There are no proven therapies for the metabolic disturbances associated with HIV lipodystrophy syndrome . OBJECTIVE To determine the safety and efficacy of metformin therapy in HIV-infected patients with fat redistribution and abnormal glucose homeostasis . DESIGN AND SETTING R and omized , double-blind , placebo-controlled pilot study conducted in a university hospital between December 1998 and January 2000 . PATIENTS Twenty-six HIV-infected , nondiabetic patients with fat redistribution and abnormal oral glucose tolerance test ( OGTT ) results , hyperinsulinemia , or both . INTERVENTIONS Patients were r and omly assigned to receive metformin , 500 mg twice daily ( n = 14 ) , or identical placebo ( n = 12 ) , for 3 months . MAIN OUTCOME MEASURES Insulin area under the curve ( AUC ) , calculated 120 minutes following a 75-g OGTT at baseline vs at 3-month follow-up and compared between treatment groups . RESULTS Patients treated with metformin demonstrated significant reductions in mean ( SEM ) insulin AUC 120 minutes after OGTT ( -2930 [ 912 ] vs -414 [ 432 ] microIU/mL [ -20349 6334 vs -2875 3000 pmol/L ] ; P = .01 ) , weight ( -1.3 [ 0.6 ] vs 1.1 [ 0.4 ] kg ; P = .005 ) , and diastolic blood pressure ( -5 [ 4 ] vs 5 [ 2 ] mm Hg ; P = .009 ) vs controls , respectively . Metformin therapy was associated with a decrease in visceral abdominal fat ( VAT ; -1115 [ 819 ] vs 1191 [ 699 ] mm(2 ) ; P = .08 ) and a proportional reduction in subcutaneous abdominal fat ( SAT ) ; the VAT-SAT ratio was unchanged in metformin-treated vs placebo-treated patients . No increase in lactate or liver transaminase levels was observed with metformin treatment . Mild diarrhea was the most common adverse effect of metformin . No patient discontinued therapy because of adverse effects . CONCLUSIONS This study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy . JAMA . 2000;284:472 - Objective : To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment ( cART ) in 1997–1999 and followed up to 2009 . Design : Prospect i ve study of 1046 patients at 47 French clinical sites . Methods : Potential determinants of diabetes occurrence , defined by confirmed increased glycemia and /or initiation of antidiabetic treatment , were assessed by a proportional hazards model , including time-up date d metabolic parameters and ART exposure . Results : Among the cohort , representing 7846 person-years of follow-up ( PYFU ) , 54 % received indinavir , 75 % stavudine and 52 % didanosine . Overall , 111 patients developed diabetes , with an incidence of 14.1/1000 PYFU ( 14.6 in men , 12.6 in women ) . Incidence peaked in 1999–2000 ( 23.2/1000 PYFU ) and decreased thereafter . The incidence of diabetes was associated [ adjusted hazard ratio ( aHR ) , all P < 0.02 ] with older age ( hazard ratio = 2.13 when 40–49 years , hazard ratio = 3.63 when ≥50 years ) , overweight ( hazard ratio = 1.91 for a BMI 25–29 kg/m2 , hazard ratio = 2.85 > 30 kg/m2 ) , waist-to-hip ratio ( hazard ratio = 3.87 for ≥0.97 male/0.92 female ) , time-up date d lipoatrophy ( hazard ratio = 2.14 ) and short-term exposure to indinavir ( 0–1year : hazard ratio = 2.53 ) , stavudine ( 0–1year : hazard ratio = 2.56 , 1–2years : hazard ratio = 2.65 ) or didanosine ( 2–3years : hazard ratio = 3.16 ) . Occurrence of diabetes was not associated with HIV-related markers , hepatitis C , hypertension or family history of diabetes . Insulin resistance was predictive for incident diabetes . Conclusions : In this nationwide cohort , followed for 10 years after cART initiation , diabetes incidence peaked in 1990–2000 , was markedly higher than that reported for European uninfected or other HIV-infected population s ( 4–6/1000 PYFU ) and linked with age and adiposity . Adiposity and glycemic markers should be monitored in aging HIV-infected patients BACKGROUND Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infa rct ion or heart failure . We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infa rct ion . METHODS In this double-blind , placebo-controlled clinical trial , we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy . Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infa rct ion . Patients were r and omly assigned to n-3 fatty acids ( 1 g daily ) or placebo ( olive oil ) . The initially specified primary end point was the cumulative rate of death , nonfatal myocardial infa rct ion , and nonfatal stroke . At 1 year , after the event rate was found to be lower than anticipated , the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes . RESULTS Of the 12,513 patients enrolled , 6244 were r and omly assigned to n-3 fatty acids and 6269 to placebo . With a median of 5 years of follow-up , the primary end point occurred in 1478 of 12,505 patients included in the analysis ( 11.8 % ) , of whom 733 of 6239 ( 11.7 % ) had received n-3 fatty acids and 745 of 6266 ( 11.9 % ) had received placebo ( adjusted hazard ratio with n-3 fatty acids , 0.97 ; 95 % confidence interval , 0.88 to 1.08 ; P=0.58 ) . The same null results were observed for all the secondary end points . CONCLUSIONS In a large general- practice cohort of patients with multiple cardiovascular risk factors , daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity . ( Funded by Società Prodotti Antibiotici and others ; Clinical Trials.gov number , NCT00317707 . ) BACKGROUND In patients with established cardiovascular disease , residual cardiovascular risk persists despite the achievement of target low-density lipoprotein ( LDL ) cholesterol levels with statin therapy . It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein ( HDL ) cholesterol is superior to simvastatin alone in reducing such residual risk . METHODS We r and omly assigned eligible patients to receive extended-release niacin , 1500 to 2000 mg per day , or matching placebo . All patients received simvastatin , 40 to 80 mg per day , plus ezetimibe , 10 mg per day , if needed , to maintain an LDL cholesterol level of 40 to 80 mg per deciliter ( 1.03 to 2.07 mmol per liter ) . The primary end point was the first event of the composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , hospitalization for an acute coronary syndrome , or symptom-driven coronary or cerebral revascularization . RESULTS A total of 3414 patients were r and omly assigned to receive niacin ( 1718 ) or placebo ( 1696 ) . The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy . At 2 years , niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter ( 0.91 mmol per liter ) to 42 mg per deciliter ( 1.08 mmol per liter ) , lowered the triglyceride level from 164 mg per deciliter ( 1.85 mmol per liter ) to 122 mg per deciliter ( 1.38 mmol per liter ) , and lowered the LDL cholesterol level from 74 mg per deciliter ( 1.91 mmol per liter ) to 62 mg per deciliter ( 1.60 mmol per liter ) . The primary end point occurred in 282 patients in the niacin group ( 16.4 % ) and in 274 patients in the placebo group ( 16.2 % ) ( hazard ratio , 1.02 ; 95 % confidence interval , 0.87 to 1.21 ; P=0.79 by the log-rank test ) . CONCLUSIONS Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter ( 1.81 mmol per liter ) , there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period , despite significant improvements in HDL cholesterol and triglyceride levels . ( Funded by the National Heart , Lung , and Blood Institute and Abbott Laboratories ; AIM -HIGH Clinical Trials.gov number , NCT00120289 . ) Aims HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications , potentially increasing their risk of cardiovascular diseases ( CVDs ) . Furthermore , exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk . We aim ed to develop cardiovascular risk- assessment models tailored to HIV-infected patients . Methods and results Prospect i ve multinational cohort study . The data set included 22 625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection on Adverse Effects of Anti-HIV Drugs Study . Using cross-validation methods , separate models were developed to predict the risk of myocardial infa rct ion , coronary heart disease , and a composite CVD endpoint . Model performance was compared with the Framingham score . The models included age , sex , systolic blood pressure , smoking status , family history of CVD , diabetes , total cholesterol , HDL cholesterol and indinavir , lopinavir/r and abacavir exposure . The models performed well with area under the receiver operator curve statistics of 0.783 ( range 0.642–0.820 ) for myocardial infa rct ion , 0.776 ( 0.670–0.818 ) for coronary heart disease and 0.769 ( 0.695–0.824 ) for CVD . The models estimated more accurately the outcomes in the subgroups than the Framingham score . Conclusion Risk equations developed from a population of HIV-infected patients , incorporating routinely collected cardiovascular risk parameters and exposure to individual antiretroviral therapy drugs , might be more useful in estimating CVD risks in HIV-infected persons than conventional risk prediction models Background — To test formally the inflammatory hypothesis of atherothrombosis , an agent is needed that reduces inflammatory biomarkers such as C-reactive protein , interleukin-6 , and fibrinogen but that does not have major effects on lipid pathways associated with disease progression . Methods and Results — We conducted a double-blind , multinational phase IIb trial of 556 men and women with well-controlled diabetes mellitus and high cardiovascular risk who were r and omly allocated to subcutaneous placebo or to subcutaneous canakinumab at doses of 5 , 15 , 50 , or 150 mg monthly and followed over 4 months . Compared with placebo , canakinumab had modest but nonsignificant effects on the change in hemoglobin A1c , glucose , and insulin levels . No effects were seen for low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , or non – high-density lipoprotein cholesterol , although triglyceride levels increased ≈10 % in the 50-mg ( P=0.02 ) and 150-mg ( P=0.03 ) groups . By contrast , the median reductions in C-reactive protein at 4 months were 36.4 % , 53.0 % , 64.6 % , and 58.7 % for the 5- , 15- , 50- , and 150-mg canakinumab doses , respectively , compared with 4.7 % for placebo ( all P values ⩽0.02 ) . Similarly , the median reductions in interleukin-6 at 4 months across the canakinumab dose range tested were 23.9 % , 32.5 % , 47.9 % , and 44.5 % , respectively , compared with 2.9 % for placebo ( all P⩽0.008 ) , and the median reductions in fibrinogen at 4 months were 4.9 % , 11.7 % , 18.5 % , and 14.8 % , respectively , compared with 0.4 % for placebo ( all P values ⩽0.0001 ) . Effects were observed in women and men . Clinical adverse events were similar in the canakinumab and placebo groups . Conclusions — Canakinumab , a human monoclonal antibody that neutralizes interleukin-1&bgr ; , significantly reduces inflammation without major effect on low-density lipoprotein cholesterol or high-density lipoprotein cholesterol . These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00900146 Background In the Strategies for Management of Anti-Retroviral Therapy trial , all-cause mortality was higher for participants r and omized to intermittent , CD4-guided antiretroviral treatment ( ART ) ( drug conservation [ DC ] ) than continuous ART ( viral suppression [ VS ] ) . We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways , thrombosis , and fibrinolysis . Methods and Findings Stored sample s were used to measure six biomarkers : high sensitivity C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , amyloid A , amyloid P , D-dimer , and prothrombin fragment 1 + 2 . Two studies were conducted : ( 1 ) a nested case – control study for study ing biomarker associations with mortality , and ( 2 ) a study to compare DC and VS participants for biomarker changes . For ( 1 ) , markers were determined at study entry and before death ( latest level ) for 85 deaths and for two controls ( n = 170 ) matched on country , age , sex , and date of r and omization . Odds ratios ( ORs ) were estimated with logistic regression . For each biomarker , each of the three upper quartiles was compared to the lowest quartile . For ( 2 ) , the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following r and omization . Higher levels of hsCRP , IL-6 , and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality . Unadjusted ORs ( highest versus lowest quartile ) were 2.0 ( 95 % confidence interval [ CI ] , 1.0–4.1 ; p = 0.05 ) , 8.3 ( 95 % CI , 3.3–20.8 ; p < 0.0001 ) , and 12.4 ( 95 % CI , 4.2–37.0 ; p < 0.0001 ) , respectively . Associations were significant after adjustment , when the DC and VS groups were analyzed separately , and when latest levels were assessed . IL-6 and D-dimer increased at 1 mo by 30 % and 16 % in the DC group and by 0 % and 5 % in the VS group ( p < 0.0001 for treatment difference for both biomarkers ) ; increases in the DC group were related to HIV-RNA levels at 1 mo ( p < 0.0001 ) . In an exp and ed case – control analysis ( four controls per case ) , the OR ( DC/VS ) for mortality was reduced from 1.8 ( 95 % CI , 1.1–3.1 ; p = 0.02 ) to 1.5 ( 95 % CI , 0.8–2.8 ) and 1.4 ( 95 % CI , 0.8–2.5 ) after adjustment for latest levels of IL-6 and D-dimer , respectively . Conclusions IL-6 and D-dimer were strongly related to all-cause mortality . Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels . Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation . Trial Registration : Clinical Trials.gov ( NCT00027352 ) OBJECTIVE —The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs ( D : A : D ) cohort , to identify demographic , HIV-related , and combination antiretroviral therapy (cART)-related factors associated with the onset of diabetes , and to identify possible mechanisms for any relationships found . RESEARCH DESIGN AND METHODS —D : A : D is a prospect i ve observational study of 33,389 HIV-infected patients ; diabetes is a study end point . Poisson regression models were used to assess the relation between diabetes and exposure to cART after adjusting for known risk factors for diabetes , CD4 count , lipids , and lipodystrophy . RESULTS —Over 130,151 person-years of follow-up ( PYFU ) , diabetes was diagnosed in 744 patients ( incidence rate of 5.72 per 1,000 PYFU [ 95 % CI 5.31–6.13 ] ) . The incidence of diabetes increased with cumulative exposure to cART , an association that remained significant after adjustment for potential risk factors for diabetes . The strongest relationship with diabetes was exposure to stavudine ; exposures to zidovudine and didanosine were also associated with an increased risk of diabetes . Time-up date d measurements of total cholesterol , HDL cholesterol , and triglycerides were all associated with diabetes . Adjusting for each of these variables separately reduced the relationship between cART and diabetes slightly . Although lipodystrophy was significantly associated with diabetes , adjustment for this did not modify the relationship between cART and diabetes . CONCLUSION —Stavudine and zidovudine are significantly associated with diabetes after adjustment for risk factors for diabetes and lipids . Adjustment for lipodystrophy did not modify the relationship , suggesting that the two thymidine analogs probably directly contribute to insulin resistance , potentially through mitochondrial toxicity CONTEXT HIV patients on antiretroviral therapy ( ART ) have a unique dyslipidemia [ elevated triglycerides and non-high-density lipoprotein-cholesterol ( HDL-C ) , low HDL-C ] with insulin resistance ( characterized by hypoadiponectinemia ) . OBJECTIVE The aim was to test a targeted , comprehensive , additive approach to treating the dyslipidemia . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled , 24-wk trial of lifestyle modification , fenofibrate , and niacin in multiethnic HIV clinics at an academic center . PARTICIPANTS Hypertriglyceridemic adult patients were stratified on three combinations of ART classes . Subjects retained at the first measurement ( 2 wk ) after entry were included in the analysis ( n = 191 ) . INTERVENTIONS Subjects were r and omized into five treatment groups : usual care ( group 1 ) ; low-saturated-fat diet and exercise ( D/E ; group 2 ) ; D/E + fenofibrate ( group 3 ) ; D/E + niacin ( group 4 ) ; or D/E + fenofibrate + niacin ( group 5 ) . MAIN OUTCOME MEASURES We measured changes in fasting triglycerides , HDL-C , and non-HDL-C ( primary ) , and in insulin sensitivity , glycemia , adiponectin , C-reactive protein , energy expenditure , and body composition ( secondary ) . Data were analyzed as a factorial set of treatment combinations using a mixed repeated measures model , last observation carried forward , and complete case approaches ( groups 2 - 5 ) , and as an unstructured set of treatments ( groups 1 - 5 ) . RESULTS Fenofibrate improved triglycerides ( P = 0.002 ) , total cholesterol ( P = 0.02 ) , and non-HDL-C ( P = 0.003 ) , whereas niacin improved HDL-C ( P = 0.03 ) , and both drugs decreased the total cholesterol-to-HDL-C ratio ( P = 0.005 - 0.01 ) . The combination of D/E , fenofibrate , and niacin provided maximal benefit , markedly reducing triglycerides ( -52 % compared to usual care ; P = 0.003 ) , increasing HDL-C ( + 12 % ; P < 0.001 ) , and decreasing non-HDL-C ( -18.5 % ; P = 0.003 ) and total cholesterol-to-HDL-C ratio ( -24.5 % ; P < 0.001 ) . Niacin doubled adiponectin levels . CONCLUSIONS A combination of fenofibrate and niacin with low-saturated-fat D/E is effective and safe in increasing HDL-C , decreasing non-HDL-C and hypertriglyceridemia , and ameliorating hypoadiponectinemia in patients with HIV/ART-associated dyslipidemia Objective : To determine the prevalence of risk factors for cardiovascular disease ( CVD ) among HIV-infected persons , and to investigate any association between such risk factors , stage of HIV disease , and use of antiretroviral therapies . Design : Baseline data from 17 852 subjects enrolled in DAD , a prospect i ve multinational cohort study initiated in 1999 . Methods : Cross-sectional analyses of CVD risk factors at baseline . The data collected includes data on demographic variables , cigarette smoking , diabetes mellitus , hypertension , dyslipidaemia , body mass index , stage of HIV infection , antiretroviral therapy . Results : Almost 25 % of the study population were at an age where there is an appreciable risk of CVD , with those receiving a protease inhibitor ( PI ) and /or non-nucleoside reverse transcriptase inhibitor ( NNRTI ) tending to be older . 1.4 % had a previous history of CVD and 51.5 % were cigarette smokers . Increased prevalence of elevated total cholesterol ( ⩾ 6.2 mmol/l ) was observed among subjects receiving an NNRTI but no PI [ odds ratio ( OR ) , 1.79 ; 95 % confidence interval ( CI ) , 1.45–2.22 ] , PI but no NNRTI ( OR , 2.35 ; 95 % CI , 1.92–2.87 ) , or NNRTI + PI ( OR , 5.48 ; 95 % CI , 4.34–6.91 ) compared to the prevalence among antiretroviral therapy (ART)-naive subjects . Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects . Higher CD4 cell count , lower plasma HIV RNA levels , clinical signs of lipodystrophy , longer exposure times to NNRTI and PI , and older age were all also associated with elevated total cholesterol level . Conclusion : HIV-infected persons exhibit multiple known risk factors for CVD . Of specific concern is the fact that use of the NNRTI and PI drug classes ( alone and especially in combination ) , particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication , was associated with a lipid profile known to increase the risk of coronary heart disease Objectives : Plasma soluble inflammatory molecules are associated with the risk of ischaemic cardiovascular events . We investigated whether HIV replication modified the levels of these proteins in a combination antiretroviral therapy ( cART ) interruption trial . Method and results : In 145 HIV-infected Thai patients ( 62 % women , median CD4 cell count 271 cells/μl , median plasma HIV-RNA 4.66 log10 copies/ml ) included in the Swiss – Thai – Australia Treatment Interruption Trial ( STACCATO ) trial , leptin , adiponectin , C-reactive protein , soluble vascular cell adhesion molecule-1 ( s-VCAM-1 ) , P-selectin , chemokine lig and 2 , chemokine lig and 3 , interleukin (IL)-6 , IL-10 , granulocyte macrophage colony-stimulating factor and D-dimer were measured before cART was initiated , after cART had suppressed HIV replication to less than 50 copies/ml plasma ( median 8 months ) and again 12 weeks after r and omization to continued cART ( n = 48 ) or interrupted cART ( n = 97 ) . Multiple linear regression and logistic regression were used to investigate the association between each cardiovascular marker and plasma HIV-RNA . Initiation of cART result ed in significant declines in s-VCAM-1 , P-selectin , leptin and D-dimer , whereas mediators with anti-inflammatory properties , such as adiponectin and IL-10 , increased . At 12 weeks after r and omization , we found positive associations between levels of s-VCAM-1 and chemokine lig and 2 with an increase in plasma HIV-RNA ( r = 0.271 , P = 0.001 and r = 0.24 , P = 0.005 , respectively ) , whereas levels of adiponectin decreased for each 1 log increase in plasma HIV-RNA ( r = −0.24 , P = 0.002 ) . Detectable IL-10 was less likely ( odds ratio = 0.64 , 95 % confidence interval = 0.43–0.96 ) for each 1 log increase in plasma HIV-RNA . Conclusion : Plasma levels of several inflammatory , anti-inflammatory and endothelial activation markers of cardiovascular disease are associated with HIV-RNA replication Abstract Purpose : The objectives of the study were to assess the effects of pravastatin on plasma HIV RNA , lipid parameters , and protease inhibitor ( PI ) concentrations in patients treated with PI-containing regimens and with total cholesterol ( TC ) ⩾5.5 mmol/L. Method : A clinical trial including patients r and omized to receive pravastatin or matching placebo for 12 weeks was implemented . Results : Twelve patients were included in the pravastatin group and 9 in the placebo group . At week 12 ( W12 ) , no patient had experienced virological failure . Between week 0 ( W0 ) and W12 , the median differences for TC were –1.4 mmol/L in the pravastatin group and + 0.2 mmol/L in the placebo group ( p = .005 ) ; for LDL , they were –1.0 mmol/L and + 0.3 ( p = .007 ) , respectively . A significant decrease of the PI concentration ( 12 hours after administration ) ratio W12 – W0/W0 was noticed in the pravastatin group ( –0.2 [ interquartile range , –0.3 to –0.1 ] as compared with the placebo group ( 0.1 [ IQR , 0.0 to 0.3 ] ) ( p = .03 ) . When the study was restricted to patients treated with lopinavir/ritonavir , a decrease from 3.8 μg/mL at baseline to 2.9 μg/mL at W12 was noticed in the pravastatin arm ( p = .04 ) but not in the control arm ( p = 1.00 ) . No clinical adverse event reached a severity of grade 3 . Conclusion : We observed in this study that the use of pravastatin in PI – treated patients was not associated with major change in the plasma HIV RNA on 12 weeks of follow-up . However , we found a trend of decrease of the trough PI concentration at W12 , suggesting a possible drug – drug interaction of pravastatin on PI metabolism CONTEXT Antiretroviral therapy can be associated with visceral adiposity and metabolic complications , increasing cardiovascular risk , and reduced growth hormone ( GH ) secretion may be a contributing factor . OBJECTIVE To investigate the effects of low-dose physiological GH administration on body composition , glucose , and cardiovascular parameters in patients with human immunodeficiency virus ( HIV ) having abdominal fat accumulation and relative GH deficiency . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled trial of 56 patients with HIV , abdominal fat accumulation , and reduced GH secretion ( peak GH < 7.5 ng/mL ) conducted at a US academic medical center between November 2003 and October 2007 . INTERVENTION Patients were r and omly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 ( IGF-1 ) range for 18 months . Starting dose was 2 microg/kg/d and increased to maximum dose of 6 microg/kg/d ( average dose , 0.33 mg/d ) . MAIN OUTCOME MEASURES Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry . Secondary outcomes included glucose , IGF-1 , blood pressure ( BP ) , and lipids . Treatment effect was the difference in the change between GH and placebo groups , using all available data . RESULTS Fifty-five patients ( 26 with GH and 29 with placebo ) were included in the safety analyses and 52 patients ( 25 with GH and 27 with placebo ) were included in the efficacy analyses . Visceral adipose tissue area ( treatment effect [ last-value-carried-forward analysis { n = 56 } , -19 cm(2 ) ; 95 % confidence interval { CI } , -37 to -0.3 cm(2 ) ] , -19 cm(2 ) ; 95 % CI , -38 to -0.5 cm(2 ) ; P = .049 ) ; trunk fat ( -0.8 kg ; 95 % CI , -1.5 to -0.04 kg ; P = .04 ) ; diastolic BP ( -7 mm Hg ; 95 % CI , -11 to -2 mm Hg ; P = .006 ) ; and triglycerides ( -7 mg/dL , P = .002 ) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group ( treatment effect , 22 mg/dL ; 95 % CI , 6 - 37 mg/dL ; P = .009 ) . The IGF-1 levels increased ( treatment effect , 129 ng/mL ; 95 % CI , 95 - 164 ng/mL ; P < .001 ) . Adverse events were not increased for GH vs placebo ( 23 % ; 95 % CI , 9%-44 % vs 28 % ; 95 % CI , 13%-47 % ; P = .70 ) . CONCLUSIONS In HIV-associated abdominal fat accumulation and relative GH deficiency , low-dose GH received for 18 months result ed in significantly reduced visceral fat and truncal obesity , triglycerides , and diastolic BP , but 2-hour glucose levels on glucose tolerance testing were increased . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00100698 Background : Once-daily atazanavir/ritonavir demonstrated similar antiviral efficacy to twice-daily lopinavir/ritonavir over 48 weeks , with less gastrointestinal disturbance and a better lipid profile , in treatment-naive patients . Methods : International , multicenter , open-label , 96-week noninferiority r and omized trial of atazanavir/ritonavir 300/100 mg once daily vs lopinavir/ritonavir 400/100 mg twice daily , each in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily , in antiretroviral-naive , HIV-1-infected patients . The primary end point was the proportion of patients with HIV RNA < 50 copies/mL at 48 weeks . Results through 96 weeks are reported . Results : Of 883 patients enrolled , 440 were r and omized to atazanavir/ritonavir and 443 to lopinavir/ritonavir . At week 96 , more patients receiving atazanavir/ritonavir achieved HIV RNA < 50 copies/mL ( 74 % vs 68 % , P < 0.05 ) in the intent-to-treat analysis . On both regimens , 7 % of subjects were virologic failures by 96 weeks . Bilirubin-associated disorders were greater in patients taking atazanavir/ritonavir . Treatment-related gastrointestinal adverse events were greater in patients taking lopinavir/ritonavir . Mean changes from baseline in fasting total cholesterol , non-high-density lipoprotein cholesterol , and triglycerides at week 96 were significantly higher with lopinavir/ritonavir ( P < 0.0001 ) . Conclusions : Noninferiority of atazanavir/ritonavir to lopinavir/ritonavir was confirmed at 96 weeks . Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir BACKGROUND Blood lipid abnormalities in patients on highly active antiretroviral therapy ( HAART ) have been associated with exposure to protease inhibitors ( PIs ) , particularly ritonavir . First therapy with a non-nucleoside reverse transcriptase inhibitor ( NNRTI ) leads to relatively favourable lipid profiles . We report on medium-term lipid profiles ( up to 5 years ) for antiretroviral-naive patients starting NNRTI- and PI-based HAART in the Swiss HIV Cohort Study . METHODS Since April 2000 , blood sample s taken at visits scheduled every 6 months have been analysed for cholesterol and triglyceride concentrations . For 1065 antiretroviral-naive patients starting HAART after April 2000 , we estimated changes in concentration over time using multivariate linear regression with adjustment for baseline covariates , use of lipid-lowering drugs and whether the sample was taken in a fasting state . RESULTS Non-high density lipoprotein ( HDL ) cholesterol levels increase with increasing exposure to either PI- or NNRTI-based therapy , HDL cholesterol levels increase and triglyceride levels decrease with increasing exposure to NNRTI-based therapy , whereas triglyceride levels increase with increasing exposure to PI-based therapy . Between NNRTI-based therapies , there is a slight difference in triglyceride levels , which tend to increase with increasing exposure to efavirenz and to decrease with increasing exposure to nevirapine . Of the three common PI-based therapies , nelfinavir appears to have a relatively favourable lipid profile , with little change with increasing exposure . Of the other two PI therapies , lopinavir with ritonavir has a more favourable profile than indinavir with ritonavir , with smaller increases in both non-HDL cholesterol and triglycerides and an increase in HDL cholesterol . Increasing exposure to abacavir is associated with a decrease in the level of triglycerides . CONCLUSION In general , NNRTI-based therapy is associated with a more favourable lipid profile than PI-based therapy , but different PI-based therapies are associated with very different lipid profiles . Nelfinavir appears to have a relatively favourable lipid profile . Of the two boosted PI therapies , lopinavir appears to have a more favourable lipid profile than indinavir Introduction : Fish oil has been shown to reduce serum triglyceride ( TG ) concentrations . In HIV-infected patients on antiretroviral therapy , high TG concentrations likely contribute to increased risk of cardiovascular disease . AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels ≤200 mg/dL with either agent alone . Methods : One hundred subjects on highly active antiretroviral therapy with serum TG concentrations ≥400 mg/dL and low-density lipoprotein cholesterol ≤160 mg/dL were r and omized to 3 g of fish oil twice daily or 160 mg of fenofibrate daily for 8 weeks . Subjects with a fasting TG level > 200 mg/dL at week 8 received a combination of fish oil and fenofibrate in the same doses from week 10 to week 18 . Results : Median baseline TG was 662 mg/dL in the fish oil group and 694 mg/dL in the fenofibrate group ( P = not significant ) . Fish oil reduced TG levels by a median of 283 mg/dL ( 46 % ) , fenofibrate reduced them by 367 mg/dL ( 58 % ) , and combination therapy reduced them by 65.5 % . Combination therapy achieved TG levels of ≤200 mg/dL in 22.7 % subjects . Fish oil had no measurable effect on immunologic parameters or the pharmacokinetics of lopinavir . Conclusions : Fish oil was safe when administered alone or combined with fenofibrate and significantly reduced TG levels in HIV-infected subjects with hypertriglyceridemia CONTEXT Alterations in serum lipid values have been widely reported among persons infected with human immunodeficiency virus ( HIV ) type 1 treated with highly active antiretroviral therapy ( HAART ) , but no data have yet been reported on changes from preseroconversion lipid values . OBJECTIVE To describe changes in serum cholesterol levels associated with HIV infection and antiretroviral medication exposure , and 1-time assessment of triglyceride levels post-HAART initiation . DESIGN , SETTING , AND PARTICIPANTS The Multicenter AIDS Cohort Study , a prospect i ve study in which homosexual and bisexual men were enrolled and from which 50 of 517 HIV seroconverters were drawn for the analysis herein , who later initiated HAART , involving measurements of stored serum sample s obtained between 1984 and 2002 . MAIN OUTCOME MEASURES Changes in levels of total cholesterol ( TC ) , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) at 6 time points during an average of 12 years ; 1-time assessment of triglyceride levels from the third post-HAART clinic visit . RESULTS Among the 50 men , notable declines in mean serum TC ( -30 mg/dL [ -0.78 mmol/L ] ) , HDL-C ( -12 mg/dL [ -0.31 mmol/L ] ) , and LDL-C values ( -22 mg/dL [ -0.57 mmol/L ] ) were observed after HIV infection . Following HAART initiation , there were large increases in mean TC and LDL-C values ( 50 and 21 mg/dL [ 1.30 and 0.54 mmol/L ] , respectively ) ; however , the mean changes from the preseroconversion values were 20 mg/dL ( 0.52 mmol/L ) ( 95 % confidence interval [ CI ] , -1 to 41 ) and -1 mg/dL ( -0.03 mmol/L ) ( 95 % CI , -25 to 22 ) , respectively . Mean HDL-C remained below baseline levels throughout follow-up . The median value ( interquartile range ) of triglycerides was 225 mg/dL ( 2.54 mmol/L ) ( 147 - 331 mg/dL ) . CONCLUSIONS Before treatment , HIV infection results in substantial decreases in serum TC , HDL-C , and LDL-C levels . Subsequent HAART initiation is associated with increases in TC and LDL-C but little change in HDL-C. Increases in TC and LDL-C observed after about 3 years of HAART possibly represent a return to preinfection serum lipid levels after accounting for expected age-related changes |
1,157 | 29,847,694 | When ranking the MAO-B inhibitors given in combination with levodopa , selegiline was the most effective and rasagiline was the second best .
All of the included MAO-B inhibitors were effective compared to placebo when given as monotherapy .
Combination therapy with MAO-B inhibitors and levodopa showed that all three MAO-B inhibitors were effective compared to placebo , but selegiline was the most effective drug | AIMS To the best of our knowledge , there are no systematic review s or meta-analyses that compare rasagiline , selegiline and safinamide .
Therefore , we aim ed to perform a drug class review comparing all available monoamine oxidase type B ( MAO-B ) inhibitors in a multiple treatment comparison . | BACKGROUND AND PURPOSE Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist ( DA ) therapy for early Parkinson 's disease ( PD ) . METHODS Study 017 was a 12-month , r and omized , double-blind , placebo-controlled pre-planned extension study to the previously reported Study 015 . Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD . The primary efficacy endpoint was the time from baseline ( Study 015 r and omization ) to ' intervention ' , defined as increase in DA dose ; addition of another DA , levodopa or other PD treatment ; or discontinuation due to lack of efficacy . Safinamide groups were pooled for the primary efficacy endpoint analysis ; post hoc analyses were performed on each separate dose group . RESULTS Of the 269 patients r and omized in Study 015 , 227 ( 84 % ) enrolled in Study 017 and 187/227 ( 82 % ) patients completed the extension study . Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups , respectively ( log-rank test ; P = 0.3342 ) . In post hoc analyses , patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo ( 25 % vs. 51 % , respectively ) and a delay in median time to intervention of 9 days ( P < 0.05 ; 240- to 540-day analysis ) . CONCLUSIONS The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention . Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD CONTEXT Monotherapy with rasagiline mesylate may be useful in early Parkinson disease ( PD ) . OBJECTIVE To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline . DESIGN Multicenter , 26-week , parallel-group , r and omized , double-blind , placebo-controlled clinical trial . SETTING Academically based movement disorders clinics . PATIENTS Patients with early PD not requiring dopaminergic therapy ( n = 404 ) . INTERVENTION Research participants were r and omized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo . A 1-week escalation period was followed by a 25-week maintenance period . MAIN OUTCOME MEASURE The primary prespecified measure of efficacy was the change in the total Unified Parkinson 's Disease Rating Scal score between baseline and 26 weeks of treatment , comparing each active treatment group with the placebo group . RESULTS Monotherapy with rasagiline was effective in this 26-week study . The adjusted effect size for the total Unified Parkinson 's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo ( 95 % confidence interval , -5.66 to -2.73 units ; P<.001 ) and -3.56 units comparing a 2-mg dosage and placebo ( 95 % confidence interval , -5.04 to -2.08 units ; P<.001 ) . There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups . CONCLUSIONS Rasagiline is effective as monotherapy for patients with early PD . The 2 dosages in this trial were both effective relative to placebo . Further study is warranted to evaluate the longer-term effects of rasagiline in PD Background and purpose Depressed mood is a common psychiatric problem associated with Parkinson ’s disease ( PD ) , and studies have suggested a benefit of rasagiline treatment . Methods ACCORDO ( see the 1 ) was a 12-week , double-blind , placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms . The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory ( BDI-IA ) total score . Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery ; Parkinson ’s disease quality of life question naire ( PDQ-39 ) scores ; Apathy Scale scores ; and Unified Parkinson ’s Disease Rating Scale ( UPDRS ) subscores . Results One hundred and twenty-three patients were r and omized . At week 12 there was no significant difference between groups for the reduction in total BDI-IA score ( primary efficacy variable ) . However , analysis at week 4 did show a significant difference in favour of rasagiline ( marginal means difference ± SE : rasagiline −5.46 ± 0.73 vs. placebo −3.22 ± 0.67 ; P = 0.026 ) . There were no significant differences between groups on any cognitive test . Rasagiline significantly improved UPDRS Parts I ( P = 0.03 ) and II ( P = 0.003 ) scores versus placebo at week 12 . Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item ( P = 0.04 ) and PDQ-39 mobility ( P = 0.007 ) and cognition domains ( P = 0.026 ) . Conclusions Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms . Although limited by lack of correction for multiple comparisons , post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes A median safinamide ( SAF ) dose of 70 mg/day ( range 40 to 90 mg/day ) increased the percentage of parkinsonian patients improving their motor scores by ≥30 % from baseline ( responders ) after 3 months from 21.4 % ( placebo ) to 37.5 % ( p < 0.05 , calculated by logistic regression analysis ) . In a subgroup of 101 patients under stable treatment with a single dopamine agonist , addition of SAF magnified the response ( 47.1 % responders , mean 4.7-point motor score decrease ; p ≥ 0.05 ) . These results suggest that doses of SAF exerting ion channel block and glutamate release inhibition add to its symptomatic effect and warrant exploration of higher doses Dopamine agonists ( DA ) are often used as first-line monotherapy for the symptomatic control of Parkinson 's disease ( PD ) . However , DA monotherapy typically becomes inadequate within a few years , at which time the DA dosage must be increased or other antiparkinsonian medications added . Adding a monoamine oxidase-B ( MAO-B ) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability . We conducted an 18-week , r and omized , double-blind , placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy ( ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d ) in early PD patients whose conditions were not adequately controlled on their current treatment regimen . The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale ( UPDRS ) score ( sum of parts I , II , and III ) from baseline to week 18 , comparing rasagiline and placebo groups . The modified intent-to-treat ( ITT ) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7 , and duration of PD was 2.1 ± 2.1 years . Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group ( least squares [ LS ] mean difference ± SE , -2.4 ± 0.95 ; 95 % confidence interval [ CI ] , -4.3 , -0.5 ; P = 0.012 ) . Mean improvement ( LS mean ± SE ) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 0.68 in the placebo group . Rasagiline was well tolerated , and the most common adverse events ( AEs ; rasagiline vs. placebo ) were dizziness ( 7.4 % vs. 6.1 % ) , somnolence ( 6.8 % vs. 6.7 % ) , and headache ( 6.2 % vs. 4.3 % ) . Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated In a 6-month double-blind , placebo-controlled study of Parkinson 's disease patients with motor fluctuations , safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia . Further long-term safinamide use in these patients was evaluated over an additional 18 months . Patients continued on their r and omized placebo , 50 , or 100 mg/d safinamide . The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months . Other efficacy endpoints included change in ON-time without troublesome dyskinesia , changes in individual diary categories , depressive symptoms , and quality of life measures . Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups , despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo . Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline ( 36 % of patients ) showed a decrease with safinamide 100 mg/d compared with placebo ( P = 0.0317 ) . Improvements in motor function , activities of daily living , depressive symptoms , clinical status , and quality of life at 6 months remained significant at 24 months . Adverse events and discontinuation rates were similar with safinamide and placebo . This 2-year , controlled study of add-on safinamide in mid-to-late Parkinson 's disease with motor fluctuations , although not demonstrating an overall difference in dyskinesias between patients and controls , showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline . The study additionally demonstrated significant clinical benefits in ON-time ( without troublesome dyskinesia ) , OFF-time , activities of daily living , motor symptoms , quality of life , and symptoms of depression To confirm the clinical utility of selegiline ( L-deprenyl ) , a selective inhibitor of monoamine oxidase B , as an anti-Parkinson 's disease ( PD ) agent , the first Japanese multi-center , double-blind comparative study of this drug was conducted . The subjects were patients who had responded poorly or suffered with other problems related to L-dopa treatment . A total of 112 patients in two groups , one given selegiline at a dose of 7.5 mg/day ( Group D , n = 60 ) and another given a placebo ( Group P , n = 52 ) , were compared over an 8-week treatment period . The percentage patients showing " moderate improvement " or better was 34.5 % in Group D , while that in Group P was 11.5 % ( P < 0.01 ) . In the assessment of overall safety , 66.7 % in Group D showed no adverse reactions , which was not significantly different from the result of 78.9 % for Group Rasagiline ( N-propargyl-1(R)-aminoindan ) mesylate is a potent , selective , and irreversible monoamine oxidase-B inhibitor . This study was design ed to evaluate the safety , tolerability , and preliminary efficacy of rasagiline monotherapy in early Parkinson 's disease ( PD ) patients not receiving levodopa . The study was performed as a multicenter , parallel-group , double-blind , r and omized , placebo-controlled , 10-week study . Fifty-six PD patients were r and omly assigned to rasagiline mesylate 1 , 2 , or 4 mg once daily , or placebo . A 3-week dose-escalation period was followed by a 7-week maintenance phase . At week 10 , the mean ( + /-SE ) changes from baseline in total Unified Parkinson 's Disease Rating Scale ( UPDRS ) score were -1.8 ( + /-1.3 ) , -3.6 ( + /-1.7 ) , -3.6 ( + /-1.2 ) , and -0.5 ( + /-0.8 ) in the rasagiline 1 , 2 , and 4 mg/day and placebo groups , respectively . Analysis of responders showed that 28 % of patients ( 12 of 43 ) receiving rasagiline had an improvement in total UPDRS score of greater than 30 % , compared with none of the patients receiving placebo ( P < 0.05 , Fisher 's exact test ) . The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar . These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD Levodopa is effective for the motor symptoms of Parkinson 's disease ( PD ) , but is associated with motor fluctuations and dyskinesia . Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia . The objective of this Phase III , multicenter , double-blind , placebo-controlled , parallel-group study was to evaluate the efficacy and safety of safinamide , an α-aminoamide with dopaminergic and nondopaminergic mechanisms , as add-on to l-dopa in the treatment of patients with PD and motor fluctuations . Patients were r and omized to oral safinamide 100 mg/day ( n = 224 ) , 50 mg/day ( n = 223 ) , or placebo ( n = 222 ) for 24 weeks . The primary endpoint was total on time with no or nontroublesome dyskinesia ( assessed using the Hauser patient diaries ) . Secondary endpoints included off time , Unified Parkinson 's Disease Rating Scale ( UPDRS ) Part III ( motor ) scores , and Clinical Global Impression-Change ( CGI-C ) . At week 24 , mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day , 1.37 ± 2.745 hours for safinamide 50 mg/day , and 0.97 ± 2.375 hours for placebo . Least squares means differences in both safinamide groups were significantly higher versus placebo . Improvements in off time , UPDRS Part III , and CGI-C were significantly greater in both safinamide groups versus placebo . There were no significant between-group differences for incidences of treatment-emergent adverse events ( TEAEs ) or TEAEs leading to discontinuation . The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia , decreased off time , and improved parkinsonism , indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia BACKGROUND Fatigue affects 40 % to 50 % of all PD patients and is a leading cause of disability , with no clearly established or efficacious established treatments . METHODS In this double-blinded , placebo-controlled , pilot trial , we investigated whether rasagiline improved fatigue among PD patients . Subjects were r and omized to 1 mg daily of rasagiline or placebo for 12 weeks . The primary endpoint was a change in the Modified Fatigue Impact Scale from baseline to week 12 . RESULTS Thirty PD subjects ( 16 men ) , with Modified Fatigue Impact Scale baseline score of 67 ± 15 , were r and omized ( 16 to rasagiline vs. 14 to placebo ) . Significant improvement was noted in the mean Modified Fatigue Impact Scale score of the rasagiline group ( 12 points ) as compared to placebo ( 8.5 points ) from baseline to week 12 ( P = 0.003 ) . CONCLUSION In this pilot study , rasagiline at a dose of 1 mg per day improved fatigue . Larger r and omized studies are needed to confirm this finding The French Selegiline Multicenter Trial was carried out in 1990 to investigate whether the disability of de novo patients with parkinsonism could be improved during the first 3 months by monotherapy with selegiline ( 10 mg/day ) . A double-blind , r and omized , placebo-controlled clinical trial was conducted over 3 months with 93 patients from 13 centers . Symptomatology was assessed on various disease rating scales , including Hoehn and Yahr , Hamilton Depression Rating Scale , Unified Parkinson 's Disease rating scale , and Schwab and Engl and scores , as well as self- assessment . Biological and clinical parameters were measured for tolerability , and efficacy was investigated with special reference to the point at which therapy with L-dopa had to be started . Selegiline was significantly superior to placebo on the various motor rating scores , and depressive scores were significantly improved at the end of 3 months . Adverse effects were rare and minor . Therefore , selegiline could be the therapy of choice for the treatment of de novo parkinsonian patients The objective of this study was to examine the effect of long‐term treatment with selegiline on the progression of Parkinson 's disease ( PD ) . One hundred and sixty‐three patients with early PD were treated with levodopa and benserazide , combined with selegiline or placebo in a five‐year r and omized , placebo‐controlled , double‐blind , parallel group study followed by a one‐month wash‐out of selegiline or placebo . The main outcome measures were assessment s of the severity of parkinsonism , levodopa requirements and the development of end‐of‐dose motor fluctuations over time and after wash‐out at the end of the study period . Results indicated that patients treated with the combination of selegiline and levodopa developed markedly less severe parkinsonism and required lower doses of levodopa during the five‐year study period than patients treated with levodopa and placebo . There was no trend towards worsening during wash‐out among patients previously treated with selegiline . The results can not easily be explained by a symptomatic effect of selegiline BACKGROUND Rasagiline ( n-propargyl-1[R]-aminoindan ) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor , previously demonstrated to improve symptoms in early Parkinson disease ( PD ) . OBJECTIVE To determine the safety , tolerability , and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations . DESIGN Multicenter , r and omized , placebo-controlled , double-blind , parallel-group study . PATIENTS Parkinson disease patients ( N = 472 ) with at least 21/2 hours of daily " off " ( poor motor function ) time , despite optimized treatment with other anti-PD medications . INTERVENTIONS Rasagiline , 1.0 or 0.5 mg/d , or matching placebo . MAIN OUTCOME MEASURES Change from baseline in total daily off time measured by patients ' home diaries during 26 weeks of treatment , percentage of patients completing 26 weeks of treatment , and adverse event frequency . RESULTS During the treatment period , the mean adjusted total daily off time decreased from baseline by 1.85 hours ( 29 % ) in patients treated with 1.0 mg/d of rasagiline , 1.41 hours ( 23 % ) with 0.5 mg/d rasagiline , and 0.91 hour ( 15 % ) with placebo . Compared with placebo , patients treated with 1.0 mg/d rasagiline had 0.94 hour less off time per day , and patients treated with 0.5 mg/d rasagiline had 0.49 hour less off time per day . Prespecified secondary end points also improved during rasagiline treatment , including scores on an investigator-rated clinical global impression scale and the Unified Parkinson 's Disease Rating Scale ( activities of daily living in the off state and motor performance in the " on " state ) . Rasagiline was well tolerated . CONCLUSIONS Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated PD patients . In light of recently reported benefits in patients with early illness , rasagiline is a promising new treatment for PD Rasagiline mesylate is a highly potent , selective and irreversible monoamine oxidase type B ( MAOB ) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson 's disease ( PD ) . However , few studies have evaluated the efficacy and safety of rasagiline in the Chinese population . This study was design ed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients . This was a r and omized , double-blind , placebo-controlled , parallel-group , multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations . Participants were r and omly assigned to oral rasagiline mesylate ( 1 mg ) or placebo , once daily . Altogether , 219 patients completed the trial . Rasagiline showed significantly greater efficacy compared with placebo . During the treatment period , the primary efficacy variable -- mean adjusted total daily off time -- decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo ( p < 0.05 ) . Scores using the Unified Parkinson 's Disease Rating Scale also improved during rasagiline treatment . Rasagiline was well tolerated . This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations Objective : To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease ( PD ) . Methods : One hundred fifty-seven de novo PD patients were r and omized in a double-blind , placebo-controlled study of 7 years ’ duration . In the monotherapy part , selegiline significantly delayed the initiation of levodopa therapy vs placebo . The authors now report the results from the combination part of the study , in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy . Results : Compared with placebo , selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale ( UPDRS ) total score ( p = 0.003 ) or by motor ( p = 0.002 ) and Activities of Daily Living ( p = 0.0002 ) subscores . After 5 years in combination therapy , the mean difference in the UPDRS total score was nearly 10 points , with patients receiving placebo having 35 % higher scores . Simultaneously , patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline ; after 5 years , the mean dosage of levodopa was 19 % higher with placebo than with selegiline ( p = 0.0002 ) . Considering the entire ( monotherapy and combination therapy ) 7-year study time , there was a trend for selegiline to delay the start of wearing-off fluctuations ( hazard ratio 0.55 , p = 0.08 ) . In both phases of the study , selegiline was safe and well tolerated . Conclusions : The results of this long-term study confirm earlier findings indicating that selegiline delays the progression of the signs and symptoms of Parkinson disease Rasagiline mesylate ( TVP-1012 ) is a potent , selective , non-reversible MAO-B inhibitor , without the tyramine-potentiating effect and with neuroprotective activities . The benefit of rasagiline as monotherapy in patients with early Parkinson 's disease ( PD ) has already been reported . To evaluate the safety , tolerability , and clinical effect of rasagiline as adjunctive therapy to levodopa , a multicenter , double-blind , r and omized , placebo-controlled , parallel-group study ( 0.5 , 1 , and 2 mg/d ) was conducted for 12 weeks in 70 patients with PD ( mean age , 57.4 y ; mean disease duration , 5.7 y ; 32 patients had motor fluctuations ) . A beneficial clinical effect was observed in fluctuating patients treated with rasagiline ( all doses ) , expressed as a decrease in total Unified Parkinson 's Disease Rating Scale ( UPDRS ) score ( 23.0 % vs 8.5 % in the placebo group ) . The treatment effect was still evident 6 weeks after drug discontinuation ( in all doses ) . The safety and tolerability of rasagiline were good . Adverse events were no different than those of patients taking placebo . Almost complete platelet MAO-B inhibition was obtained at all rasagiline doses . This study has demonstrated that rasagiline ( up to 2 mg/day ) has a good safety profile and a beneficial clinical effect in fluctuating patients with PD when given as an add-on to chronic levodopa therapy BACKGROUND Rasagiline mesylate is a novel drug for Parkinson 's disease with selective , irreversible monoamine oxidase B ( MAO-B ) inhibitor activity , and is effective as monotherapy in early disease . This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson 's disease and motor fluctuations . METHODS In an 18-week , double-blind , multicentre ( 74 hospitals and academic centres in Israel , Argentina , and Europe ) trial , 687 out patients were r and omly assigned to oral rasagiline ( 231 individuals ; 1 mg once daily ) , entacapone ( 227 ; 200 mg with every levodopa dose ) , or placebo ( 229 ) . Primary outcome was change in total daily off-time ( intention-to-treat population ) . Other measures included the clinical global improvement ( CGI ) score and unified Parkinson 's disease rating scale ( UPDRS ) scores . Analysis was by intention to treat . FINDINGS 88 ( 13 % ) patients who were assigned treatment did not complete the study ( 23 rasagiline , 30 entacapone , 35 placebo ) , mainly because of withdrawal of consent ( n=34 ) and adverse events ( n=34 ) . Both rasagiline and entacapone reduced mean daily off-time ( -1.18 h rasagiline and -1.2 h entacapone vs placebo -0.4 h ; p=0.0001 , p<0.0001 , respectively ) and increased daily on-time without troublesome dyskinesia ( 0.85 h vs placebo 0.03 h ; p=0.0005 for both ) . We recorded significant mean improvements in CGI scores ( -0.86 rasagiline and -0.72 entacapone vs -0.37 placebo ; p<0.0001 , p=0.0002 , respectively ) . Changes in UPDRS scores also significantly improved for activities of daily living during off-time ( -1.71 and -1.38 vs placebo ; p<0.0001 , p=0.0006 , respectively ) and motor function during on-time ( -2.94 and -2.73 vs placebo ; both p<0.0001 ) . Frequency of adverse events was similar for all treatments . INTERPRETATION Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson 's disease in levodopa-treated patients with motor fluctuations , an effect similar to that of entacapone In a clinical trial that is still in progress , we studied the ability of deprenyl and tocopherol , antioxidative agents that act through complementary mechanisms , to delay the onset of disability necessitating levodopa therapy ( the primary end point ) in patients with early , untreated Parkinson 's disease . Eight hundred subjects were r and omly assigned in a two-by-two factorial design to receive deprenyl , tocopherol , a combination of both drugs , or placebo , and were followed up to determine the frequency of development of the end point . The interim results of independent monitoring prompted a preliminary comparison of the 401 subjects assigned to tocopherol or placebo with the 399 subjects assigned to deprenyl , alone or with tocopherol . Only 97 subjects who received deprenyl reached the end point during an average 12 months of follow-up , as compared with 176 subjects who did not receive deprenyl ( P less than 10(-8 ) . The risk of reaching the end point was reduced by 57 percent for the subjects who received deprenyl ( Cox hazard ratio , 0.43 ; 95 percent confidence limits , 0.33 and 0.55 ; P less than 10(-10 ] . The subjects who received deprenyl also had a significant reduction in their risk of having to give up full-time employment ( P = 0.01 ) . We conclude from these preliminary results that the use of deprenyl ( 10 mg per day ) delays the onset of disability associated with early , otherwise untreated cases of Parkinson 's disease Deprenyl ( selegiline ) delays the need for levodopa therapy in patients with early Parkinson 's disease , but the long‐term benefits of this treatment remain unclear . During 1987 to 1988 , 800 patients with early Parkinson 's disease were r and omized in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial to receive deprenyl , tocopherol , combined treatments , or a placebo and were then placed on active deprenyl ( 10mg/day ) . A second , independent r and omization was carried out in early 1993 for 368 subjects who by that time had required levodopa and who had consented to continuing the deprenyl treatment ( D subjects ) or changing to a matching placebo ( P subjects ) under double‐blind conditions . The first development of wearing off , dyskinesias , or on – off motor fluctuations was the prespecified primary outcome measure . During the average 2‐year follow‐up , there were no differences between the treatment groups with respect to the primary outcome measure ( hazard ratio , 0.87 ; 95 % confidence interval , 0.63 , 1.19 ; p = 0.38 ) , withdrawal from the study , death , or adverse events . Although 34 % of D subjects developed dyskinesias and only 19 % of P subjects did ( p = 0.006 ) , only 16 % of D subjects developed freezing of gait but 29 % of P subjects did ( p = 0.0003 ) . Decline in motor performance was less in D subjects than P subjects . Levodopa‐treated Parkinson 's disease patients who had been treated with deprenyl for up to 7 years , compared with patients who were changed to a placebo after about 5 years , experienced slower motor decline and were more likely to develop dyskinesias but less likely to develop freezing of gait IMPORTANCE Preladenant is an adenosine 2A receptor antagonist that reduced " off " time in a placebo-controlled phase 2b trial in patients with Parkinson disease ( PD ) . We sought to confirm its efficacy in phase 3 trials . OBJECTIVE To evaluate preladenant as an adjunct to levodopa in patients with PD and motor fluctuations . DESIGN , SETTING , AND PARTICIPANTS Two 12-week , phase 3 , r and omized , placebo-controlled , double-blind trials performed from July 15 , 2010 , to April 16 , 2013 . The setting included neurology clinics , clinical research centers , and hospitals in the Americas , the European Union , Eastern Europe , India , and South Africa . Participants included patients with moderate to severe PD taking levodopa who were experiencing motor fluctuations . INTERVENTIONS In trial 1 , a total of 778 eligible patients were r and omized to the addition of preladenant ( 2 mg , 5 mg , or 10 mg twice daily ) , placebo , or rasagiline mesylate ( 1 mg/d ) in a 1:1:1:1:1 ratio . In trial 2 , a total of 476 eligible patients were r and omized to the addition of preladenant ( 2 mg or 5 mg twice daily ) or placebo in a 1:1:1 ratio . MAIN OUTCOMES AND MEASURES The primary outcome measure was change in off time from baseline to week 12 . RESULTS In trial 1 , neither preladenant nor rasagiline was superior to placebo in reducing off time from baseline to week 12 . The differences vs placebo were -0.10 hour ( 95 % CI , -0.69 to 0.46 hour ) for preladenant 2 mg twice daily , -0.20 hour ( 95 % CI , -0.75 to 0.41 hour ) for preladenant 5 mg twice daily , -0.00 hour ( 95 % CI , -0.62 to 0.53 hour ) for preladenant 10 mg twice daily , and -0.30 hour ( 95 % CI , -0.90 to 0.26 hour ) for rasagiline mesylate 1 mg/d . In trial 2 , preladenant was not superior to placebo in reducing off time from baseline to week 12 . The differences vs placebo were -0.20 hour ( 95 % CI , -0.72 to 0.35 hour ) for preladenant 2 mg twice daily and -0.30 hour ( 95 % CI , -0.86 to 0.21 hour ) for preladenant 5 mg twice daily . Preladenant was well tolerated , with the most common adverse event that showed an increase over placebo in both trials being constipation ( 6%-8 % for preladenant vs 1%-3 % for placebo ) . CONCLUSIONS AND RELEVANCE In these phase 3 trials , preladenant did not significantly reduce off time compared with placebo . That the active control rasagiline also failed to demonstrate a significant reduction in off time suggests that issues of study design or conduct may have affected these trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01155466 and NCT01227265 Safinamide is an α-aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add-on to dopamine agonist ( DA ) therapy in early-stage PD . In this 24-week , double-blind study , patients with early PD receiving a stable dose of a single DA were r and omized to once-daily safinamide 100 mg , safinamide 200 mg , or placebo . The primary efficacy variable was UPDRS part III ( motor examination ) total score . Analysis was hierarchical : 200 mg of safinamide versus placebo was tested first ; the success of safinamide 100 mg versus placebo was contingent on this . Two hundred sixty-nine patients received safinamide 100 mg ( n = 90 ) , safinamide 200 mg ( n = 89 ) , or placebo ( n = 90 ) ; 70 , 81 , and 81 patients , respectively , completed the study . Mean improvements from baseline to week 24 in UPDRS III total scores were -3.90 for safinamide 200 mg , -6.0 for safinamide 100 mg and -3.60 for placebo . The difference between safinamide 200 mg and placebo was not significant [ point estimate : -0.4 ; 95 % confidence interval ( CI ) : -2.3 - 1.4 ; P = 0.6504 ] . Although the difference between 100 mg/day and placebo was significant ( point estimate : -1.9 ; 95 % CI : -3.7 to -0.1 ; P = 0.0419 ) , these results are considered exploratory . No clinical ly meaningful differences from placebo were observed for any safety variables . This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day . Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation The effects of MPTP ( 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ) , a neurotoxin that produces the symptoms of Parkinson 's disease , can be fully prevented in experimental animals by inhibiting monoamine oxidase B. On the basis of this observation , a double-blind , placebo-controlled study in patients with early Parkinson 's disease was initiated to determine whether deprenyl ( a selective monoamine oxidase B inhibitor ) would delay the need for L-dopa therapy by slowing the progression of the disease . Fifty-four patients were r and omly assigned to deprenyl ( 10 mg/day ) or placebo treatment groups and followed until L-dopa therapy was indicated or until the patient had been in the study for 3 years . Analysis of Kaplan-Meier survival curves for each group showed that deprenyl delayed the need for L-dopa therapy ; the average time until L-dopa was needed was 312.1 days for patients in the placebo group and 548.9 days for patients in the deprenyl group . Disease progression , as monitored by five different assessment scales , was slowed ( by 40 to 83 % per year ) in the deprenyl group compared to placebo . Therefore , early deprenyl therapy delays the requirement for antiparkinsonian medication , possibly by slowing progression of the disease Cognitive impairment can occur at all stages of Parkinson 's disease . Rasagiline is a selective monoamine oxidase type-B inhibitor that enhances central dopaminergic transmission . Dopamine is thought to be involved in certain cognitive processes such as working memory . We assessed the effects of rasagiline on cognitive deficits in cognitively impaired , nondemented patients with Parkinson 's disease . This was a r and omized , double-blind , placebo-controlled prospect i ve study . Patients with Parkinson 's disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months . Patients were eligible if they had impairment in 2 of 4 cognitive domains ( attention , executive functions , memory , visuospatial functions ) in the screening neuropsychological tests , yet did not fulfill criteria for Parkinson 's disease dementia . Fifty-five patients were r and omized ; 48 patients completed the study . Patients in the rasagiline group showed significant improvement in digit span-backward compared with the placebo group ( P = .04 ) , with trends favoring rasagiline in digit span total and digit-ordering tests . Verbal fluency total score showed a significant difference in favor of rasagiline ( P = .038 ) , with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections . The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score ( P < .005 ) . There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores . The monoamine oxidase type-B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinson 's disease with cognitive impairment Objective : To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease ( PD ) when given as monotherapy . Methods : This was a r and omized , 26-week , placebo- and active-controlled , parallel-group , multicenter , double-blind trial conducted in adults diagnosed with PD for < 5 years who were not yet receiving l-dopa or dopamine agonists . Patients with a Unified Parkinson ’s Disease Rating Scale ( UPDRS ) part 3 ( motor function ) score ≥10 and Hoehn & Yahr score ≤3 were r and omized 1:1:1:1:1 to preladenant 2 , 5 , or 10 mg twice daily , rasagiline 1 mg ( active-control ) once daily , or placebo . The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 ( activities of daily living ) and 3 scores ( UPDRS2 + 3 ) . Results : The number of patients treated was 1,007 . Neither preladenant nor rasagiline was superior to placebo after 26 weeks . The differences vs placebo ( 95 % confidence interval ) in UPDRS2 + 3 scores ( with a negative difference indicating improvement vs placebo ) were preladenant 2 mg = 2.60 ( 0.86 , 4.30 ) , preladenant 5 mg = 1.30 ( −0.41 , 2.94 ) , preladenant 10 mg = 0.40 ( −1.29 , 2.11 ) , and rasagiline 1 mg = 0.30 ( −1.35 , 2.03 ) . Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial . Preladenant was generally well-tolerated with few patients discontinuing due to adverse events ( preladenant 7 % , rasagiline 3 % , placebo 4 % ) . Conclusions : No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial . The lack of efficacy of the active control rasagiline makes it difficult to interpret the results . Clinical trial registration : Clinical trials.gov : NCT01155479 . Classification of evidence : This study provides Class I evidence that for patients with early PD , preladenant is not effective as monotherapy at the doses studied ( 2 , 5 , 10 mg ) We have performed a 14‐month , prospect i ve , r and omized , double‐blind , placebo‐controlled study to evaluate the effect of deprenyl and levodopa/carbidopa ( Sinemet ) on the progression of signs and symptoms in patients with mild Parkinson 's disease ( PD ) . One hundred one untreated PD patients were r and omly assigned to one of the following four treatment groups : Group I , deprenyl + Sinemet ; Group II , placebo‐deprenyl + Sinemet ; Group III , deprenyl + bromocriptine ; and Group IV , placebo‐deprenyl + bromocriptine . The final visit was performed at 14 months , i.e. , 2 months after withdrawal of deprenyl or its placebo and 7 days after withdrawal of Sinemet or bromocriptine . Deterioration in Unified Parkinson 's Disease Rating Score ( UPDRS ) between untreated baseline and final visits was used as an index of disease progression . Placebo‐treated patients deteriorated by 5.8 ± 1.4 points , while deprenyl‐treated patients deteriorated by 0.4 ± 1.3 points ( p < 0.001 ) . This effect was sufficiently powerful that a significant deprenyl effect could be detected in the subgroup of 41 patients r and omized to Sinemet ( p < 0.01 ) as well as in the 23 patients who completed a 14‐day washout of Sinemet or bromocriptine ( p < 0.05 ) . No difference in the extent of deterioration was detected in patients r and omized to Sinemet versus bromocriptine . This study demonstrates that deprenyl attenuates deterioration in UPDRS score in patients with early PD . These findings are not readily explained by the drug 's symptomatic effects and are consistent with the hypothesis that deprenyl has a neuroprotective effect BACKGROUND A therapy that slows disease progression is the major unmet need in Parkinson 's disease . METHODS In this double-blind trial , we examined the possibility that rasagiline has disease-modifying effects in Parkinson 's disease . A total of 1176 subjects with untreated Parkinson 's disease were r and omly assigned to receive rasagiline ( at a dose of either 1 mg or 2 mg per day ) for 72 weeks ( the early-start group ) or placebo for 36 weeks followed by rasagiline ( at a dose of either 1 mg or 2 mg per day ) for 36 weeks ( the delayed-start group ) . To determine a positive result with either dose , the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson 's Disease Rating Scale ( UPDRS , a 176-point scale , with higher numbers indicating more severe disease ) : superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36 , superiority to delayed-start treatment in the change in the score between baseline and week 72 , and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72 . RESULTS Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis : a smaller mean ( + /-SE ) increase ( rate of worsening ) in the UPDRS score between weeks 12 and 36 ( 0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group , P=0.01 ) , less worsening in the score between baseline and week 72 ( 2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group , P=0.02 ) , and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 ( 0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group , P<0.001 ) . All three end points were not met with rasagiline at a dose of 2 mg per day , since the change in the UPDRS score between baseline and week 72 was not significantly different in the two groups ( 3.47+/-0.50 points in the early-start group and 3.11+/-0.50 points in the delayed-start group , P=0.60 ) . CONCLUSIONS Early treatment with rasagiline at a dose of 1 mg per day provided benefits that were consistent with a possible disease-modifying effect , but early treatment with rasagiline at a dose of 2 mg per day did not . Because the two doses were associated with different outcomes , the study results must be interpreted with caution . ( Clinical Trials.gov number , NCT00256204 . BACKGROUND Monoamine oxidase type B ( MAO-B ) inhibitors exhibit neuroprotective effects in pre clinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients . OBJECTIVE To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline . METHODS The primary outcome measure was the Global Outcome ( GO ) , comprised of 5 measures : change from baseline in the Schwab and Engl and ( ADL ) scale , the 39-item Parkinson 's Disease Question naire ( PDQ-39 ) , the UPDRS Ambulatory Capacity Scale , the Symbol Digit Modalities Test , and the most recent Modified Rankin Scale . A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO , adjusting for necessary factors and confounders . Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually . RESULTS 1616 participants comprised the analytic sample . Mean observation was 4.1 ( SD = 1.4 ) years , and 784 ( 48.5 % ) participants received an MAO-B inhibitor . The regression coefficient of cumulative duration of MAO-B inhibitor exposure ( in years ) on the GO was - 0.0064 ( SE = 0.002 , p = 0.001 ) . Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL ( p < 0.001 ) , Ambulatory Capacity ( p < 0.001 ) , and the Rankin ( p = 0.002 ) . CONCLUSIONS Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline . These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospect i ve trial should be considered |
1,158 | 29,974,508 | Successful CTO PCI is associated with a statistically significant improvement in LV ejection fraction and decrease in LV end-systolic volume , that may reflect a beneficial effect of CTO recanalization on LV remodeling . | BACKGROUND We sought to examine the impact of coronary chronic total occlusion ( CTO ) percutaneous coronary intervention ( PCI ) on left ventricular ( LV ) function . | Background —Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation . It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium . Accordingly , the time courses of functional recovery in hibernating and stunned myocardium were compared . Methods and Results — Patients ( n=26 ) with ischemic cardiomyopathy undergoing surgical revascularization were studied ; regional perfusion ( resting 201Tl single-photon emission CT ) , glucose utilization ( 18F-2-deoxyglucose single-photon emission CT ) , and contractile function ( 2D echocardiography ) were assessed before revascularization . Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned , and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating . Contractile function was reevaluated 3 months ( early ) and 14 months ( late ) after revascularization . Of the 266 dysfunctional segments , 57 ( 22 % ) were stunned , 62 ( 23 % ) were hibernating , and 147 ( 55 % ) were scar tissue . In stunned myocardium , contractile function improved significantly at 3 months , without further improvement at 14 months ; 61 % of the stunned segments improved at 3 months , and 9 % improved at 14 months . In hibernating myocardium , contractile function improved at 3 months , with a further improvement at 14 months ; 31 % of the hibernating segments improved at 3 months , and 61 % showed ( additional ) recovery at 14 months . Conclusions —Stunned myocardium is likely to demonstrate early recovery of function , whereas hibernating myocardium may take a longer time to ( fully ) recover in function after revascularization BACKGROUND In 10 % to 15 % of patients with ST-segment elevation myocardial infa rct ion ( STEMI ) , concurrent coronary chronic total occlusion ( CTO ) in a non-infa rct -related artery is present and is associated with increased morbidity and mortality . OBJECTIVES The EXPLORE ( Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Elevation Myocardial Infa rct ion ) trial evaluated whether patients with STEMI and concurrent CTO in a non-infa rct -related artery benefit from additional percutaneous coronary intervention ( PCI ) of CTO shortly after primary PCI . METHODS From November 2007 through April 2015 , we enrolled 304 patients with acute STEMI who underwent primary PCI and had concurrent CTO in 14 centers in Europe and Canada . A total of 150 patients were r and omly assigned to early PCI of the CTO ( CTO PCI ) , and 154 patients were assigned to conservative treatment without PCI of the CTO ( no CTO PCI ) . Primary outcomes were left ventricular ejection fraction ( LVEF ) and left ventricular end diastolic volume ( LVEDV ) on cardiac magnetic resonance imaging after 4 months . RESULTS The investigator-reported procedural success rate in the CTO PCI arm of the trial was 77 % , and the adjudicated success rate was 73 % . At 4 months , mean LVEF did not differ between the 2 groups ( 44.1 ± 12.2 % vs. 44.8 ± 11.9 % , respectively ; p = 0.60 ) . Mean LVEDV at 4 months was 215.6 ± 62.5 ml in the CTO PCI arm versus 212.8 ± 60.3 ml in the no-CTO PCI arm ( p = 0.70 ) . Subgroup analysis revealed that patients with CTO located in the left anterior descending coronary artery who were r and omized to the CTO PCI strategy had significantly higher LVEF compared with patients r and omized to the no-CTO PCI strategy ( 47.2 ± 12.3 % vs. 40.4 ± 11.9 % ; p = 0.02 ) . There were no differences in terms of 4-month major adverse coronary events ( 5.4 % vs. 2.6 % ; p = 0.25 ) . CONCLUSIONS Additional CTO PCI within 1 week after primary PCI for STEMI was feasible and safe . In patients with STEMI and concurrent CTO , we did not find an overall benefit for CTO PCI in terms of LVEF or LVEDV . The finding that early CTO PCI in the left anterior descending coronary artery subgroup was beneficial warrants further investigation . ( Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Segment Elevation Myocardial Infa rct ion ; NTR1108 ) OBJECTIVES This study explored whether cardiac magnetic resonance ( CMR ) could help select patients who could benefit from revascularization by identifying inducible myocardial ischemia and viability in the perfusion territory of the artery with chronic total occlusion ( CTO ) . BACKGROUND The benefit of revascularization using percutaneous coronary intervention ( PCI ) in CTO is controversial . CMR offers incomparable left ventricular ( LV ) systolic function assessment in addition to potent ischemic burden quantification and reliable myocardial viability analysis . Whether CMR guided CTO revascularization would be helpful to such patients has not yet been explored fully . METHODS A prospect i ve study of 50 consecutive CTO patients was conducted . Of 50 patients undergoing baseline stress CMR , 32 ( 64 % ) were selected for recanalization based on the presence of significant inducible perfusion deficit and myocardial viability within the CTO arterial territory . Patients were rescanned 3 months after successful CTO recanalization . RESULTS At baseline , myocardial perfusion reserve ( MPR ) in the CTO territory was significantly reduced compared with the remote region ( 1.8 ± 0.72 vs. 2.2 ± 0.7 ; p = 0.01 ) . MPR in the CTO region improved significantly after PCI ( to 2.3 ± 0.9 ; p = 0.02 vs. baseline ) with complete or near-complete resolution of CTO related perfusion defect in 90 % of patients . Remote territory MPR was unchanged after PCI ( 2.5 ± 1.2 ; p = NS vs. baseline ) . The LV ejection fraction increased from 63 ± 13 % to 67 ± 12 % ( p < 0.0001 ) and end-systolic volume decreased from 65 ± 38 to 56 ± 38 ml ( p < 0.001 ) 3 months after CTO PCI . Importantly , despite minimal post-procedural infa rct ion due to distal embolization and side branch occlusion in 8 of 32 patients ( 25 % ) , the total Seattle Angina Question naire score improved from a median of 54 ( range 45 to 74 ) at baseline to 89 ( range 77 to 98 ) after CTO recanalization ( p < 0.0001 ) . CONCLUSIONS In this small group of patients showing CMR evidence of significant myocardial inducible perfusion defect and viability , CTO recanalization reduces ischemic burden , favors reverse remodeling , and ameliorates quality of life AIMS The aim of the present study was to investigate the effects of successful PCI CTO on absolute myocardial blood flow ( MBF ) and functional recovery . METHODS AND RESULTS Patients with a documented CTO were prospect ively examined for ischaemia and viability with [15O]H2O positron emission tomography ( PET ) and late gadolinium enhancement cardiac magnetic resonance imaging ( LGE-CMR ) . Sixty-nine consecutive patients , in whom PCI was successful , underwent follow-up PET and CMR after approximately 12 weeks to evaluate potential improvement of MBF as well as systolic function . After PCI , stress MBF in the CTO area increased from 1.22±0.36 to 2.40±0.90 mL·min-1·g-1 ( p<0.001 ) , whilst stress MBF in the remote area also increased significantly between baseline and follow-up PET ( 2.58±0.68 to 2.77±0.77 mL·min-1·g-1 , p=0.01 ) . The ratio of stress MBF between CTO and remote area was 0.49±0.13 at baseline and increased to 0.87±0.24 at follow-up ( p<0.001 ) . The MBF defect size of the CTO area decreased from 5.12±1.69 to 1.91±1.75 myocardial segments after PCI ( p<0.001 ) . Left ventricular ejection fraction ( LVEF ) increased significantly ( 46.4±11.0 vs. 47.5±11.4 % , p=0.01 ) at follow-up . CONCLUSIONS The vast majority of CTO patients with documented ischaemia and viability showed significant improvement in stress MBF and a reduction of ischaemic burden after successful percutaneous revascularisation with only minimal effect on LVEF The present study aim ed to assess the mechanisms of effects of percutaneous coronary intervention ( PCI ) for chronic total occlusion ( CTO ) from two different aspects : left ventricular ( LV ) systolic function assessed by two-dimensional speckle tracking echocardiography ( 2D-STE ) and electrical stability evaluated by late potential on signal-averaged electrocardiogram ( SAECG ) . We conducted a prospect i ve observational study with consecutive CTO-PCI patients . 2D-STE and SAECG were performed before PCI , and after 1-day and 3-months of procedure . 2D-STE computed global longitudinal strain ( GLS ) and regional longitudinal strain ( RLS ) in CTO area , collateral blood-supplying donor artery area , and non-CTO/non-donor area . A total of 37 patients ( 66 ± 11 years , 78 % male ) were analyzed . RLS in CTO and donor areas and GLS were significantly improved 1-day after the procedure , but these improvements diminished during 3 months . The improvement of RLS in donor area remained significant after 3-months the index procedure ( pre-PCI −13.4 ± 4.8 % vs. post-3 M −15.1 ± 4.5 % , P = 0.034 ) . RLS in non-CTO/non-donor area and LV ejection fraction were not influenced . Mitral annulus velocity was improved at 3-month follow-up ( 5.0 ± 1.4 vs. 5.6 ± 1.7 cm/s , P = 0.049 ) . Before the procedure , 12 patients ( 35 % ) had a late potential . All components of the late potential ( filtered QRS duration , root-mean-square voltage in the terminal 40 ms , and duration of the low amplitude signal < 40 μV ) were not improved . CTO-PCI improved RLS in the donor area at 3-month follow-up without changes of LV ejection fraction . Although higher prevalence of late potential in the current population compared to healthy population was observed , late potential as a surrogate of arrhythmogenic substrate was not influenced by CTO-PCI Background In congestive heart failure patients , a single measurement of left ventricular ejection fraction ( LVEF ) provides important prognostic information . The importance , if any , of improvement or worsening in serial LVEF has not been defined . The Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials ( V-HeFT ) data base was analyzed to determine the prognostic importance of LVEF changes . Methods and Results The data bases for V-HeFT I ( n = 642 ) and V-HeFT II ( n=804 ) were analyzed . All patients had heart failure with documented exercise intolerance and abnormal LVEF or cardiac dilatation by chest x-ray or echocardiography . Radionuclide LVEF was obtained at baseline , within 6 months , and at least yearly after r and omization to treatment . Cumulative survival subsequent to LVEF follow-up measurements was calculated for strata defined by LVEF change from baseline . In V-HeFT I , patients treated with hydralazine/isosorbide dinitrate ( H-I ) experienced a significant ( P < O.OOl ) increase in LVEF and a survival advantage over those treated with placebo and prazosin . In V-HeFT II , both treatment groups showed significant improvements in LVEF , with the increase with H-I greater than that with enalapril , and enalapril provided a significant survival advantage overH-L. Change ( > 5 ) in LVEF from baseline at 6 months ( V-HeFT I ) and 1 year ( V-HeFT II ) were the strongest predictors of mortality among the serial measurements and were significant after adjustment for therapy and baseline LVEF . Baseline clinical variables were not helpfulin predicting the patients who would experience an improvement in LVEF . Conclusions In patients with heart failure , serial measurements of LVEF provide additional important prognostic information . Vasodilator therapy with H-I is associated with an improvement in LVEF and prognosis . Vasodilator therapy with enalapril improves LVEF less than H-I but provides an additional survival benefit In recent years , several clinical trials conducted on selected middle-aged patients have documented the positive effects of new pharmacologic and nonpharmacologic treatment on chronic heart failure ( HF ) . More recently , some investigators reported cases of elderly patients who had improved clinical conditions and left ventricular ( LV ) systolic function , but neither the prevalence nor the clinical variables associated with this phenomenon have ever been characterized in this population . To assess the prevalence and the predictors of " improvement " of HF , we prospect ively analyzed 87 patients with a recent diagnosis of HF and LV systolic dysfunction , aged > 70 years , who were consecutively admitted to our center for functional class impairment ( New York Heart Association class III and IV ) . After discharge , patients underwent clinical and echocardiographic evaluations every 6 months . During follow-up ( 17 + /- 9 months ) improvement was documented in 31 subjects ( 36 % ) . The variables associated with improvement in the multivariate analysis were the absence of diabetes ( odds ratio [ OR ] 5.1 , 95 % confidence interval [ CI ] 1.3 to 19.9 , p = 0.007 ) , history of arterial hypertension ( OR 3.9 , CI 1.3 to 11.1 , p = 0.01 ) , and beta-blocker therapy ( OR 3.4 , CI 1.1 to 10.8 , p = 0.03 ) . An improvement in clinical status and LV systolic function is not infrequently observed in patients > 70 years of age who have a recent diagnosis of HF . This behavior occurs prevalently in patients receiving beta-blocker therapy who have a history of arterial hypertension , and is inversely related to the presence of diabetes mellitus BACKGROUND The safety of percutaneous coronary intervention ( PCI ) for chronic total occlusion ( CTO ) lesions in remote hospitals without surgical facilities remains unknown . This study aim ed to evaluate three-year outcomes after CTO for PCI in ten centers around China where no on-site coronary artery bypass grafting ( CABG ) support was available . METHODS A total of 152 patients from 10 Chinese hospitals without on-site surgical facilities were prospect ively studied . Intra-procedural and in-hospital events were assessed . Angiographic follow-up was indexed eight months after the initial procedure . Clinical follow-up was extended to three years . The primary outcome was the rate of major adverse cardiac events ( MACE ) , defined as cardiac death , myocardial infa rct ion and target-vessel revascularization ( TVR ) . RESULTS The incidence of CTO was 7.9 % in patients who underwent PCI . Successful recanalization was achieved in 132 patients ( 86.8 % ) . Compared with patients in the PCI success group , patients with PCI procedural failure had longer lesion lengths ( ( 42.32 + /- 22.08 ) mm vs ( 27.61 + /- 22.85 ) mm , P = 0.023 ) , a higher rate of perforation ( 25.0 % vs 0 , P = 0.014 ) , and a greater need for pericardial puncture . There were significant differences in MACE in-hospital and at one year and three years between the failure ( 10.0 % , 30.0 % and 35.0 % ) and the success ( 3.0 % , 12.1 % and 14.4 % ) groups ( P = 0.037 , 0.034 and 0.040 , respectively ) . These led to a significant decrease in the MACE-free survival rate at one and three years in the failure group , compared with the success group ( P = 0.031 and 0.023 , respectively ) . Stump was the only predictor of recanalization success ( HR 0.158 , 95 % CI 0.041 - 0.612 , P = 0.008 ) , whereas procedural failure ( OR 13.023 , 95 % CI 6.67 - 13.69 , P = 0.002 ) , incomplete revascularization ( OR 9.71 , 95 % CI 2.93 - 5.59 , P = 0.005 ) , and total stent length ( OR 6.02 , 95 % CI 1.55 - 11.93 , P = 0.027 ) were three independent predictors of MACE . CONCLUSIONS PCI for CTO was unsafe in remote hospitals without CABG facilities . Paying attention to coronary perforation is important for successful procedures BACKGROUND The Total Occlusion Study of Canada ( TOSCA ) is a multicenter , r and omized trial evaluating the effect of stenting with > = 1 heparin-coated stent on long-term patency after percutaneous coronary intervention by balloon angioplasty of occluded coronary arteries . The purpose of the current study was to compare the effect of stenting and balloon angioplasty on global left ventricular ejection fraction ( LVEF ) and regional wall motion and to examine what clinical and angiographic factors may have an effect on left ventricular function in this setting . METHODS AND RESULTS Analysis at the core angiographic laboratory of paired baseline and follow-up left ventricular angiograms , as well as target vessel patency , was possible in 244 of 410 cases . An improvement in LVEF was observed in the entire group ( 59.4 % + /- 11 % to 61.0 % + /- 11 % , P = .003 ) . The LVEF change was + 1.84 + /- 7.54 in the stent group ( P = .009 ) and 1.28 + /- 8.16 in the percutaneous transluminal coronary angioplasty group ( P = .085 ) . There was no significant intergroup difference . Patients with duration of occlusion < or = 6 weeks had an improvement in LVEF ( + 2.98 + /- 8.68 , P = .0006 ) , whereas those with an occlusion duration of > 6 weeks had no improvement ( + 0.48 + /- 7.01 , P not significant ) . Multivariate analysis revealed baseline LVEF < 60 % , duration of occlusion < or = 6 weeks , and Canadian Cardiology Society angina class I or II to be independent predictors of improvement in LVEF . CONCLUSIONS The restoration of coronary patency of nonacute occluded coronary arteries is associated with a small but significant improvement in regional and global left ventricular function , especially in patients with recent occlusions and depressed left ventricular function . In spite of significant effect on long-term patency , stenting of nonacute coronary occlusions does not result in significantly better left ventricular function compared with balloon angioplasty in this setting BACKGROUND The improvement of regional and global ventricular function following percutaneous coronary intervention ( PCI ) with reperfusion of the artery supplying the infa rct area in acute myocardial infa rct ion is well-described . However , little is known of the potential effects of late recanalization of chronic coronary artery occlusion on left ventricular function . OBJECTIVE To determine whether PCI improves regional and global left ventricular function in patients with chronic coronary artery occlusions . PATIENTS AND METHODS Thirty-five patients having at least one coronary artery occluded for six weeks or longer were included in the present prospect i ve study . Exercise thallium-201 myocardial perfusion scintigraphy , multiple-gated acquisition ventriculography and two-dimensional echocardiography were performed in 19 patients ( 16 men ; mean age of 58+/-5 years ) who underwent a successful PCI to assess both regional and global left ventricular function before and six weeks following the procedure . RESULTS The mean ejection fractions before and after reperfusion were 51+/-7 % and 58+/-6 % using Simpson 's method ( P<0.001 ) by echocardiography , and 45+/-1 % and 53+/-1 % ( P=0.01 ) by multiple-gated acquisition ventriculography , respectively . The echocardiographic wall motion score was 24+/-9 before and 15+/-6 after PCI ( P<0.001 ) . The exercise perfusion score ( 21+/-1 and 14+/-1 [ P=0.01 ] ) , rest perfusion score ( 15+/-1 and 12+/-1 [ P=0.02 ] ) and reinjection perfusion score ( 14+/-1 and 11.1+/-1 [ P=0.07 ] ) also improved after PCI . The presence of angina was strongly associated with an improvement in left ventricular function and wall motion score ( P<0.01 ) . CONCLUSIONS PCI significantly improved the regional and global left ventricular function in patients with chronic total coronary occlusion . This procedure may provide symptom benefits in selected patients The clinical benefit of late recanalization of complete coronary occlusion is debated . Left ventricular ( LV ) function and volumes are major prognostic determinants in patients with coronary artery disease . We sought to assess comprehensively the evolution of global and regional LV function and LV volumes after percutaneous recanalization of chronic complete coronary artery occlusions . A consecutive series of 55 patients who underwent successful percutaneous recanalization of a chronic ( > or = 10 days ) , total ( Thrombolysis in Myocardial Infa rct ion trial flow grade 0 ) occlusion of the left anterior descending or dominant right coronary arteries , and in whom a complete angiographic evaluation was available before angioplasty and at follow-up was studied . At follow-up , 38 patients had a patent artery ( group 1 ) and 17 had a reocclusion ( group 2 ) . Baseline parameters were similar in the 2 groups . In group 1 , LV ejection fraction increased from 55 + /- 14 % to 62 + /- 13 % ( p < 0.001 ) , with an increase in fractional shortening in the occluded artery territory ( 0.43 + /- 0.30 to 0.71 + /- 0.34 , p < 0.001 ) , while LV end-diastolic volume remained unchanged . In group 2 , ejection fraction and regional wall motion were unchanged , while LV end-diastolic volume index increased ( 86 + /- 22 ml/m2 to 99 + /- 34 ml/m2 , p < 0.02 ) . The evolution in LV global and regional function was similar in patients with or without previous myocardial infa rct ion ; however , prevention of LV remodeling was observed only in patients with previous infa rct ion . Maintained potency after successful recanalization of totally occluded coronary arteries improves global and regional LV function and , in patients with previous myocardial infa rct ion , avoids LV remodeling |
1,159 | 30,932,011 | Differences in ADMA concentrations between controls and RDs patients were not significantly associated with inflammatory markers , increasing age , lipid concentrations , body mass index , blood pressure , or methodology used to assess ADMA .
This meta- analysis showed that , in the context of significant between- study heterogeneity , circulating concentrations of ADMA are positively related to RDs | Raised circulating concentrations of asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of nitric oxide synthase ( NOS ) , have been reported in several rheumatic diseases ( RDs ) .
However , the strength of this relationship is unclear .
Therefore , the aim of this systematic review and meta- analysis was to evaluate the magnitude and the robustness of the association between ADMA concentrations and RDs . | Early detection of pulmonary hypertension ( PH ) in patients with systemic sclerosis ( SSc ) is essential as it leads to substantial morbidity and mortality irrespective of its etiology . The aim of our study was to determine whether noninvasive biochemical and /or echocardiographic indices can predict the presence of PH in these patients . We prospect ively studied 66 patients ( mean age of 57.7 ± 12.1 years , 63 women ) with SSc without clinical manifestations of heart failure . All patients underwent st and ard and tissue Doppler echocardiography . Plasma N-terminal pro-B type natriuretic peptide ( NT-proBNP ) and asymmetric dimethylarginine ( ADMA ) levels were also measured . In 24 ( 36 % ) patients , the diagnosis of PH was established by echocardiography ( systolic pulmonary artery pressure value ≥40 mmHg ) . Left atrial ( LA ) volume , NT-proBNP , ADMA , ratio of early transmitral filling velocity to early diastolic velocity of the mitral annulus ( mitral E/Em ) , and right ventricular myocardial performance index ( MPI ) were univariate predictors of PH . In multivariate analysis , NT-proBNP , LA volume , and right ventricular MPI were independent predictors of PH in SSc patients . LA volume and NT-proBNP may be useful noninvasive markers for the prediction of elevated pulmonary artery pressure in patients with SSc . These parameters should be considered when assessing this population for risk stratification and for identification of patients dem and ing further investigation and institution of specific therapy for the disease at the time when it is most likely to be effective 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 BACKGROUND Asymmetric dimethylarginine ( ADMA ) is associated with endothelial injury . Increased ADMA levels are found in rheumatoid arthritis ( RA ) and ankylosing spondylitis ( AS ) . We set out to assess the ADMA and symmetric dimethylarginine ( SDMA ) levels in AS , RA , and healthy controls , and in the anti-TNF treated patients with active AS . METHODS In 78AS patients and 29 RA patients who were anti-TNF treatment naive at baseline , along with 23 healthy control subjects , we assessed erythrocyte sedimentation rate ( ESR ) , high-sensitivity C-reactive protein ( hsCRP ) , ADMA , and SDMA . For AS patients , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , back pain VAS and patient 's global activity of disease were calculated . After 6 months , we repeated the assessment in 30 out of the 78 AS patients in whom the anti-TNF treatment was initiated . RESULTS The baseline mean ( SD ) plasma ADMA concentration of AS patients was 0.64 ( 0.19 ) μmol/l and did not differ from controls ( 0.65 [ 0.19 ] μmol/l , p > 0.05 ) . In the RA group , ADMA concentration was higher than in controls ( 0.77 vs. 0.65 μmol/l , p < 0.05 ) . Both at baseline and at follow-up , ADMA levels correlated positively with BASDAI ( R = 0.52 , p = 0.02 , and R = 0.47 , p = 0.04 , baseline and follow-up , respectively ) . Six months of anti-TNF treatment did not influence ADMA concentration ( 0.51 [ 0.12 ] vs. 0.51 [ 0.11 ] μmol/l , p = 0.70 ) . CONCLUSION An absence of changes in plasma ADMA levels in the anti-TNF treated AS group despite the improvement in disease activity ( BASDAI ) and inflammation ( ESR , CRP ) may suggest either a lack of effect , or , even if such an effect were to take place , it needs not imply measurable changes in blood ADMA We explored the role of asymmetrical dimethylarginine ( ADMA ) as a cause of endothelial dysfunction induced by systemic inflammation . In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli , but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans . In study 1 we recruited 351 patients with coronary artery disease ( CAD ) and 87 healthy controls . In study 2 we recruited 69 CAD , 69 healthy , and 10 patients with rheumatoid arthritis , whereas in study 3 , 22 healthy and 70 CAD subjects were r and omly assigned to Salmonella typhii vaccination ( n=11 healthy and n=60 CAD ) or placebo ( n=11 healthy and n=10 CAD ) . Circulating interleukin 6/ADMA and flow-mediated dilation ( FMD ) were measured at 0 and 8 hours . In study 1 , ADMA was inversely correlated with FMD in healthy individuals and CAD patients ( P<0.0001 for both ) . However , interleukin 6 was inversely correlated with FMD ( P<0.0001 ) in healthy subjects but not in CAD patients . The positive correlation between ADMA and interleukin 6 was stronger in healthy ( r=0.515 ; P<0.0001 ) compared with CAD ( r=0.289 ; P=0.0001 ) subjects . In study 2 , both patients with rheumatoid arthritis and CAD had higher interleukin 6 ( P<0.0001 ) and ADMA ( P=0.004 ) but lower FMD ( P=0.001 ) versus healthy subjects . In study 3 , vaccination increased interleukin 6 in healthy ( P<0.001 ) and CAD ( P<0.001 ) subjects . FMD was reduced in healthy subjects ( P<0.05 ) , but its reduction in CAD was borderline . Vaccination increased ADMA only in healthy subjects ( P<0.001 ) . Systemic , low- grade inflammation leads to increased ADMA that may induce endothelial dysfunction . This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans BACKGROUND Asymmetric dimethylarginine ( ADMA ) is an endogenous competitive inhibitor of nitric oxide ( NO ) synthase . Because endothelial NO elaboration is impaired in hypercholesterolemia , we investigated whether plasma concentrations of ADMA are elevated in young , clinical ly asymptomatic hypercholesterolemic adults . We further studied whether such elevation of ADMA levels was correlated with impaired endothelium-dependent , NO-mediated vasodilation and urinary nitrate excretion . In a r and omized , double-blind , placebo-controlled study , we investigated whether these changes could be reversed with exogenous L-arginine . METHODS AND RESULTS We measured plasma levels of L-arginine , ADMA , and symmetrical dimethylarginine ( SDMA ) by high-performance liquid chromatography in 49 hypercholesterolemic ( HC ) and 31 normocholesterolemic ( NC ) humans . In 8 HC subjects , endothelium-dependent forearm vasodilation was assessed before and after an intravenous infusion of L-arginine or placebo and compared with 8 NC control subjects . ADMA levels were significantly elevated by > 100 % ( 2.17+/-0.15 versus 1.03+/-0.09 micromol/L ; P<0.05 ) in HC subjects compared with NC adults . L-Arginine levels were similar , result ing in a significantly decreased L-arginine/ADMA ratio in HC subjects ( 27.7+/-2.4 versus 55 . 7+/-5.4 ; P<0.05 ) . In 8 HC subjects , intravenous infusion of L-arginine significantly increased the L-arginine/ADMA ratio and normalized endothelium-dependent vasodilation and urinary nitrate excretion . ADMA levels were inversely correlated with endothelium-mediated vasodilation ( R=0.762 , P<0.01 ) and urinary nitrate excretion rates ( R=0.534 , P<0.01 ) . CONCLUSIONS We find that ADMA is elevated in young HC individuals . Elevation of ADMA is associated with impaired endothelium-dependent vasodilation and reduced urinary nitrate excretion . This abnormality is reversed by administration of L-arginine . ADMA may be a novel risk factor for endothelial dysfunction in humans Objectives . Impaired endothelial function represents the early stage of atherosclerosis , which is typically associated with systemic inflammatory diseases like rheumatoid arthritis ( RA ) . As modulators of endothelial nitric oxide synthase expression , asymmetric-dimethylarginine ( ADMA ) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes . We conducted a prospect i ve , case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA ( ERA ) before and after disease-modifying antirheumatic drug ( DMARD ) therapy . Methods . We enrolled 20 consecutively diagnosed , treatment-naïve patients with ERA and 20 matched healthy controls . Serum ADMA and apelin levels and the 28-joint disease activity scores ( DAS28 ) were assessed before and after 12 months of DMARDs treatment . All patients underwent ultrasonographic assessment for intima-media tickness ( IMT ) evaluation . Results . In the ERA group , ADMA serum levels were significantly higher than controls at baseline ( P = 0.007 ) and significantly decreased after treatment ( P = 0.012 versus controls ) . Baseline serum apelin levels were significantly decreased in this group ( P = 0.0001 versus controls ) , but they were not significantly altered by treatment . IMT did not show significant changes . Conclusions . ERA is associated with alterations of serum ADMA and apelin levels , which might be used as biomarkers to detect early endothelial dysfunction in these patients Background Heart and pulmonary involvement is a leading cause of systemic sclerosis (SSc)-related deaths . Objectives The aim of our study was to assess if biochemical markers of right ventricular ( RV ) overload , endothelial function and collagen metabolism can predict RV dysfunction assessed by Doppler echocardiography in SSc patients . Methods We prospect ively studied 111 consecutive patients ( 101 F , 10 M , age 54.2 ± 13.8 years ) with diagnosed SSc ( mean disease duration 9.4 ± 11.4 years ) and a group of 21 age-matched subjects ( 18 F , 3 M , age 49.3 + 10.5 years ) . We performed transthoracic echocardiography ( Phillips iE 33 ) and measured serum endothelin-1 ( ET-1 ) , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , asymmetric dimethylarginine ( ADMA ) , endoglin and human tissue inhibitor of matrix metalloproteinase ( TIMP-1 ) concentration . Results Median serum NT-proBNP level in SSc patients was 133.5 ( range 21.86–17,670 pg/ml ) and was significantly higher than in controls ( p = 0.0002 ) . Moreover , the median serum ET-1 level of 1.49 ( range 0.26–8.75 pg/ml ) was higher in SSc patients ( p = 0.002 ) . However , no significant differences in ADMA , TIMP-1 and endoglin serum concentration between SSc patients and controls were observed . Serum NT-proBNP concentration correlated positively with echocardiographic signs of RV overload : tricuspid regurgitation pressure gradient ( r = 0.38 , p = 0.0004 ) and RV Tei index ( r = 0.25 , p = 0.01 ) . ET-1 serum level correlated negatively with tricuspid annular plane systolic excursion ( r = −0.4 , p = 0.01 ) and positively with inferior vena cava diameter measured at expiration ( r = 0.38 , p = 0.0002 ) . The echocardiographic signs of RV overload were significantly more pronounced in the highest NT-proBNP tertile ( > 195 pg/ml ) group than in the lowest one ( < 88 pg/ml ) . Conclusions Serum ET-1 and NT-proBNP , but not endoglin , ADMA and TIMP-1 levels correlating with the echocardiographic parameters of RV overload , can be considered as noninvasive indicators of RV dysfunction in SSc patients OBJECTIVES To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients . METHODS Endothelin-1 ( ET-1 ) , asymmetric dimethylarginine ( ADMA ) , vascular endothelial growth factor ( VEGF ) , endostatin and endoglin were measured in an observational prospect i ve cohort of 77 SSc patients . The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up . RESULTS After the 3-year follow-up , 40 patients developed new digital ulcers . Logistic regression confirmed VEGF ( HR 1.128 , 95 % CI 1.010 - 1.260 , p=0.033 ) and ADMA ( HR 0.995 , 95 % CI 0.991 - 0.998 , p=0.006 ) as independent predictors of new digital ulcers . Patients with serum levels of ET-1>11.9 pmol/ml ( p<0.001 ) and VEGF<422.47 pg/ml ( p=0.028 ) had significantly more DU in the 3-year follow-up . Although not significant , a trend towards increased serum levels of endoglin>4.215 ng/ml ( p=0.053 ) was associated to a new DU episode . No predictive serum value was found for ADMA ( p=0.075 ) and endostatin ( p=0.130 ) . CONCLUSIONS Endothelial dysfunction and angiogenic vascular biomarkers have an important role in the underlying and in the progression of microvascular disease in systemic sclerosis . Increased serum levels of ET-1 , ADMA and VEGF are strong predictors of severe microangiopathy complications , namely ischaemic digital ulcers Objective . Cardiopulmonary complications are common in patients with systemic sclerosis ( SSc ) . We assessed cardiac involvement in patients with SSc using echocardiography and investigated the association of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) and asymmetric dimethylarginine ( ADMA ) with echocardiographic measures of myocardial function in sera of patients with SSc who had no symptoms of heart failure . Methods . We prospect ively studied 52 patients with SSc ( mean age 55.7 ± 10.1 yrs , 51 women ) , with conventional and tissue-Doppler echocardiography . Plasma NT-proBNP and ADMA levels were measured in all patients . Data were compared with those obtained from 25 healthy controls comparable for age and sex . Results . Patients with SSc had impaired left ventricular ( LV ) and right ventricular diastolic function expressed by inverted ratio of peak early to peak late transmitral ( Mit E/A ) and transtricuspid velocity and increased left atrial diameter compared with controls . Peak systolic mitral lateral annular motion velocity and peak early diastolic mitral lateral annular motion velocity ( LV Em ) were lower , while LV E/Em ratio was higher , in patients with SSc compared to controls . ADMA was significantly related with LV Em and E/Em ratio . NT-proBNP was associated with Mit E , Mit E/A ratio and mitral deceleration time . Significant correlation was also observed between NT-proBNP and ADMA levels . Conclusion . Depressed cardiac function is common , even in asymptomatic patients with SSc . NT-proBNP and ADMA are significantly correlated with echocardiographic abnormalities , providing a potent link for cardiac function , neuroendocrine derangement , and endothelial dysfunction in patients with SSc who have cardiac disease |
1,160 | 31,112,492 | Several models of care can prevent delirium .
The diverse models of care included here explored interventions adapted to specific care setting s , especially by addressing setting -specific delirium risk factors . | BACKGROUND Each hospital day of delirium incurs greater healthcare costs , higher levels of care , greater staff burden , and higher complication rates .
Accordingly , administrators are incentivized to identify models of care that reduce delirium rates and associated costs .
PURPOSE We present a systematic review and meta- analysis of delirium prevention models of care . | BACKGROUND Hospital-acquired delirium is a known risk factor for negative outcomes in patients admitted to the surgical intensive care unit ( SICU ) . Outcomes worsen as the duration of delirium increases . The purpose of this study was to evaluate the efficacy of a delirium prevention program and determine whether it decreased the incidence and duration of hospital-acquired delirium in older adults ( age>50 y ) admitted to the SICU . METHODS A prospect i ve pre- or post-intervention cohort study was done at an academic level I trauma center . Older adults admitted to the SICU were enrolled in a delirium prevention program . Those with traumatic brain injury , dementia , or 0 d of obtainable delirium status were excluded from analysis . The intervention consisted of multidisciplinary education , a pharmacologic protocol to limit medications associated with delirium , and a nonpharmacologic sleep enhancement protocol . Primary outcomes were incidence of delirium and delirium-free days/30 . Secondary outcomes were ventilator-free days/30 , SICU length of stay ( LOS ) , daily and cumulative doses of opioids ( milligram , morphine equivalents ) and benzodiazepines ( milligram , lorazepam equivalents ) , and time spent in severe pain ( greater than or equal to 6 on a scale of 1 - 10 ) . Delirium was measured using the Confusion Assessment Method for the ICU . Data were analyzed using Chi-squared and Wilcoxon rank sum analysis . RESULTS Of 624 patients admitted to the SICU , 123 met inclusion criteria : 57 preintervention ( 3/12 - 6/12 ) and 66 postintervention ( 7/12 - 3/13 ) . Cohorts were similar in age , gender , ratio of trauma patients , and Injury Severity Score . Postintervention , older adults experienced delirium at the same incidence ( pre 47 % versus 58 % , P=0.26 ) , but for a significantly decreased duration as indicated by an increase in delirium-free days/30 ( pre 24 versus 27 , P=0.002 ) . After intervention , older adults with delirium had more vent-free days ( pre 21 versus 25 , P=0.03 ) , shorter SICU LOS ( pre 13 [ median 12 ] versus 7 [ median 6 ] , P=0.01 ) and were less likely to be treated with benzodiazepines ( pre 85 % versus 63 % , P=0.05 ) with a lower daily dose when prescribed ( pre 5.7 versus 3.6 mg , P=0.04 ) . After intervention , all older adults spent less time in pain ( pre 4.7 versus 3.1 h , P=0.02 ) , received less total opioids ( pre 401 versus 260 mg , P=0.01 ) , and had shorter SICU LOS ( pre 9 [ median 5 ] versus 6 [ median 4 ] , P=0.04 ) . CONCLUSIONS Although delirium prevention continues to be a challenge , this study successfully decreased the duration of delirium for older adults admitted to the SICU . Our simple , cost-effective program led to improved pain and sedation outcomes . Older adults with delirium spent less time on the ventilator and all patients spent less time in the SICU Background : Delirium after acute stroke is a serious complication . Numerous studies support a benefit of multicomponent interventions in minimizing delirium-related complications in at-risk patients , but this has not been reported in acute stroke patients . The purpose of this study was to explore the feasibility of conducting a r and omized ( delirium care ) versus usual st and ardized stroke care ( usual care ) in reducing delirium in acute stroke . Objective : This pilot study assessed the feasibility of ( 1 ) enrollment within the 48-hour window when delirium risk is greatest , ( 2 ) measuring cognitive function using the Montreal Cognitive Assessment , ( 3 ) delivering interventions 7 days per week , and ( 4 ) determining delirium incidence in stroke-related cognitive dysfunction . Methods : A 2-group r and omized controlled trial was conducted . Patients admitted with ischemic and hemorrhagic strokes and 50 years or older , English speaking , and without delirium on admit were recruited , consented , and r and omized to usual care or delirium care groups . Results : Data from 125 subjects ( delirium care , n = 59 ; usual care , n = 66 ) were analyzed . All Montreal Cognitive Assessment subscales were completed by 86 % of subjects ( delirium care , mean [ SD ] , 18.14 [ 6.03 ] ; usual care , mean [ SD ] , 17.61 [ 6.29 ] ) . Subjects in the delirium care group received a mean of 6.10 therapeutic activities ( range , 2–23 ) and daily medication review by a clinical pharmacist using anticholinergic drug calculations . Delirium incidence was 8 % ( 10/125 ) , 3 in the delirium care group and 7 in the usual care group . Conclusion : Findings support the feasibility of delivering a multicomponent delirium prevention intervention in acute stroke and warrants testing intervention effects on delirium outcomes and anticholinergic medication administration OBJECTIVE To develop and vali date a new st and ardized confusion assessment method ( CAM ) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk setting s. DESIGN Prospect i ve validation study . SETTING Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University ( site 1 ) and in general medicine wards at the University of Chicago ( site 2 ) . PATIENTS The study included 56 subjects , ranging in age from 65 to 98 years . At site 1 , 10 patients with and 20 without delirium participated ; at site 2 , 16 patients with and 10 without delirium participated . MEASUREMENTS AND MAIN RESULTS An expert panel developed the CAM through a consensus building process . The CAM instrument , which can be completed in less than 5 minutes , consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders ( DSM-III-R ) . An a priori hypothesis was established for the diagnostic value of four criteria : acute onset and fluctuating course , inattention , disorganized thinking , and altered level of consciousness . The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion . At both sites , the diagnoses made by the CAM were concurrently vali date d against the diagnoses made by psychiatrists . At sites 1 and 2 values for sensitivity were 100 % and 94 % , respectively ; values for specificity were 95 % and 90 % ; values for positive predictive accuracy were 91 % and 94 % ; and values for negative predictive accuracy were 100 % and 90 % . The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium . The CAM was shown to have convergent agreement with four other mental status tests , including the Mini-Mental State Examination . The interobserver reliability of the CAM was high ( kappa = 0.81 - 1.0 ) . CONCLUSIONS The CAM is sensitive , specific , reliable , and easy to use for identification of delirium OBJECTIVE To determine the long-term effects on total healthcare costs of the Improving Mood : Promoting Access to Collaborative Treatment ( IMPACT ) program for late-life depression compared with usual care . STUDY DESIGN R and omized controlled trial with enrollment from July 1999 through August 2001 . The IMPACT trial , conducted in primary care practice s in 8 delivery organizations across the United States , enrolled 1801 depressed primary care patients 60 years or older . Data are from the 2 IMPACT sites for which 4-year cost data were available . Trial enrollment across these 2 health maintenance organizations was 551 patients . METHODS Participants were r and omly assigned to the IMPACT intervention ( n = 279 ) or to usual primary care ( n = 272 ) . Intervention patients had access to a depression care manager who provided education , behavioral activation , support of antidepressant medication management prescribed by their regular primary care provider , and problem-solving treatment in primary care for up to 12 months . Care managers were supervised by a psychiatrist and a primary care provider . The main outcome measures were healthcare costs during 4 years . RESULTS IMPACT participants had lower mean total healthcare costs ( $ 29 422 ; 95 % confidence interval , $ 26 479-$32 365 ) than usual care patients ( $ 32 785 ; 95 % confidence interval , $ 27 648-$37 921 ) during 4 years . Results of a bootstrap analysis suggested an 87 % probability that the IMPACT program was associated with lower healthcare costs than usual care . CONCLUSION Compared with usual primary care , the IMPACT program is associated with a high probability of lower total healthcare costs during a 4-year period Background and objectives : delirium is a distressing but potentially preventable condition common in older people in long-term care . It is associated with increased morbidity , mortality , functional decline , hospitalization and significant healthcare costs . Multicomponent interventions , addressing delirium risk factors , have been shown to reduce delirium by one-third in hospitals . It is not known whether this approach is also effective in long-term care . In previous work , we design ed a bespoke delirium prevention intervention , called ‘ Stop Delirium ! ’ In preparation for a definitive trial of Stop Delirium , we sought to address key aspects of trial design for the particular circumstances of care homes . Design : a cluster r and omized feasibility study with an embedded process evaluation . Setting and participants : residents of 14 care homes for older people in one metropolitan district in the UK . Intervention : Stop Delirium ! : a 16-month-enhanced educational package to support care home staff to address key delirium risk factors . Control homes received usual care . Measurements : we collected data to determine the following : recruitment and attrition ; delirium rates and variability between homes ; feasibility of measuring delirium , re source use , quality of life , hospital admissions and falls ; and intervention implementation and adherence . Results : two-thirds ( 215 ) of eligible care home residents were recruited . One-month delirium prevalence was 4.0 % in intervention and 7.1 % in control homes . Proposed outcome measurements were feasible , although our approach appeared to underestimate delirium . Health economic evaluation was feasible using routinely collected data . Conclusion : a definitive trial of delirium prevention in long-term care is needed but will require some further design modifications and pilot work OBJECTIVE Delirium is a highly prevalent and deleterious disorder in terminally ill cancer patients . We assessed whether a multicomponent preventive intervention was effective in decreasing delirium incidence and severity among cancer patients receiving end-of-life care . METHODS A cohort of 1516 patients was followed from admission to death at seven Canadian palliative care centers . In two of these centers , routine care included a delirium preventive intervention targeting physicians ( written notice on selective delirium risk factors and inquest on intended medication changes ) , patients , and their family ( orientation to time and place , information about early delirium symptoms ) . Delirium frequency and severity were compared between patients at the intervention ( N = 674 ) and usual-care ( N = 842 ) centers based on thrice-daily symptom assessment s with the Confusion Rating Scale . RESULTS The overall rate of adherence to the intervention was 89.7 % . The incidence of delirium was 49.1 % in the intervention group , compared with 43.9 % in the usual-care group ( odds ratio [ OR ] 1.23 , P = 0.045 ) . When confounding variables were controlled for , no difference was observed between the intervention and the usual-care groups in delirium incidence ( OR 0.94 , P = 0.66 ) , delirium severity ( 1.83 vs. 1.92 ; P = 0.07 ) , total days in delirium ( 4.57 vs. 3.57 days ; P = 0.63 ) , or duration of first delirium episode ( 2.9 vs. 2.1 days ; P = 0.96 ) . Delirium-free survival was similar in the two groups . CONCLUSION A simple multicomponent preventive intervention was ineffective in reducing delirium incidence or severity among cancer patients receiving end-of-life care . Delirium prevention remains a difficult challenge in terminally ill cancer patients CONTEXT In the intensive care unit ( ICU ) , delirium is a common yet underdiagnosed form of organ dysfunction , and its contribution to patient outcomes is unclear . OBJECTIVE To determine if delirium is an independent predictor of clinical outcomes , including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001 . Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale . MAIN OUTCOME MEASURES Primary outcomes included 6-month mortality , overall hospital length of stay , and length of stay in the post-ICU period . Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge . RESULTS Of 275 patients , 51 ( 18.5 % ) had persistent coma and died in the hospital . Among the remaining 224 patients , 183 ( 81.7 % ) developed delirium at some point during the ICU stay . Baseline demographics including age , comorbidity scores , dementia scores , activities of daily living , severity of illness , and admission diagnoses were similar between those with and without delirium ( P>.05 for all ) . Patients who developed delirium had higher 6-month mortality rates ( 34 % vs 15 % , P = .03 ) and spent 10 days longer in the hospital than those who never developed delirium ( P<.001 ) . After adjusting for covariates ( including age , severity of illness , comorbid conditions , coma , and use of sedatives or analgesic medications ) , delirium was independently associated with higher 6-month mortality ( adjusted hazard ratio [ HR ] , 3.2 ; 95 % confidence interval [ CI ] , 1.4 - 7.7 ; P = .008 ) , and longer hospital stay ( adjusted HR , 2.0 ; 95 % CI , 1.4 - 3.0 ; P<.001 ) . Delirium in the ICU was also independently associated with a longer post-ICU stay ( adjusted HR , 1.6 ; 95 % CI , 1.2 - 2.3 ; P = .009 ) , fewer median days alive and without mechanical ventilation ( 19 [ interquartile range , 4 - 23 ] vs 24 [ 19 - 26 ] ; adjusted P = .03 ) , and a higher incidence of cognitive impairment at hospital discharge ( adjusted HR , 9.1 ; 95 % CI , 2.3 - 35.3 ; P = .002 ) . CONCLUSION Delirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma , sedatives , and analgesics in patients receiving mechanical ventilation BACKGROUND Since in hospitalized older patients delirium is associated with poor outcomes , we evaluated the effectiveness of a multicomponent strategy for the prevention of delirium . METHODS We studied 852 patients 70 years of age or older who had been admitted to the general-medicine service at a teaching hospital . Patients from one intervention unit and two usual-care units were enrolled by means of a prospect i ve matching strategy . The intervention consisted of st and ardized protocol s for the management of six risk factors for delirium : cognitive impairment , sleep deprivation , immobility , visual impairment , hearing impairment , and dehydration . Delirium , the primary outcome , was assessed daily until discharge . RESULTS Delirium developed in 9.9 percent of the intervention group as compared with 15.0 percent of the usual-care group , ( matched odds ratio , 0.60 ; 95 percent confidence interval , 0.39 to 0.92 ) . The total number of days with delirium ( 105 vs. 161 , P=0.02 ) and the total number of episodes ( 62 vs. 90 , P=0.03 ) were significantly lower in the intervention group . However , the severity of delirium and recurrence rates were not significantly different . The overall rate of adherence to the intervention was 87 percent , and the total number of targeted risk factors per patient was significantly reduced . Intervention was associated with significant improvement in the degree of cognitive impairment among patients with cognitive impairment at admission and a reduction in the rate of use of sleep medications among all patients . Among the other risk factors per patient there were trends toward improvement in immobility , visual impairment , and hearing impairment . CONCLUSIONS The risk-factor intervention strategy that we studied result ed in significant reductions in the number and duration of episodes of delirium in hospitalized older patients . The intervention had no significant effect on the severity of delirium or on recurrence rates ; this finding suggests that primary prevention of delirium is probably the most effective treatment strategy Background and aims : Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs . We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures . Methods : One hundred and ninety-nine patients , aged 70 years and over ( mean age±SD , 82±6 , 74 % women ) , were r and omly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward . The intervention consisted of staff education focusing on the assessment , prevention and treatment of delirium and associated complications . The staff worked as a team , applying comprehensive geriatric assessment , management and rehabilitation . Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale , and delirium was diagnosed according to DSM-IV criteria . Results : The number of days of postoperative delirium among intervention patients was fewer ( 5.0±7.1 days vs 10.2±13.3 days , p=0.009 ) compared with controls . A lower proportion of intervention patients were delirious postoperatively than controls ( 56/102 , 54.9 % vs 73/97 , 75.3 % , p=0.003 ) . Eighteen percent in the intervention ward and 52 % of controls were delirious after the seventh postoperative day ( p<0.001 ) . Intervention patients suffered from fewer complications , such as decubitus ulcers , urinary tract infections , nutritional complications , sleeping problems and falls , than controls . Total postoperative hospitalization was shorter in the intervention ward ( 28.0±17.9 days vs 38.0±40.6 days , p=0.028 ) . Conclusions : Patients with postoperative delirium can be successfully treated , result ing in fewer days of delirium , fewer other complications , and shorter length of hospitalization OBJECTIVES To evaluate whether an early multidisciplinary geriatric intervention in elderly patients with hip fracture reduced length of stay , morbidity , and mortality and improved functional evolution . DESIGN R and omized , controlled intervention trial . SETTING Orthopedic ward in a university hospital . PARTICIPANTS Three hundred nineteen patients aged 65 and older hospitalized for hip fracture surgery . INTERVENTION Participants were r and omly assigned to a daily multidisciplinary geriatric intervention ( n=155 ) or usual care ( n=164 ) during hospitalization in the acute phase of hip fracture . MEASUREMENTS Primary endpoints were in-hospital length of stay and incidence of death or major medical complications . Secondary endpoints were the rate of recovery of previous activities of daily living and ambulation ability at 3 , 6 , and 12 months . RESULTS Median length of stay was 16 days in the geriatric intervention group and 18 days in the usual care group ( P=.06 ) . Patients assigned to the geriatric intervention showed a lower in-hospital mortality ( 0.6 % vs 5.8 % , P=.03 ) and major medical complications rate ( 45.2 % vs 61.7 % , P=.003 ) . After adjustment for confounding variables , geriatric intervention was associated with a 45 % lower probability of death or major complications ( 95 % confidence interval=7 - 68 % ) . More patients in the geriatric intervention group achieved a partial recovery at 3 months ( 57 % vs 44 % , P=.03 ) , but there were no differences between the groups at 6 and 12 months . CONCLUSION Early multidisciplinary daily geriatric care reduces in-hospital mortality and medical complications in elderly patients with hip fracture , but there is not a significant effect on length of hospital stay or long-term functional recovery Background : Delirium research is poorly studied in postacute care , a growing setting due to aging population s , as well as in dementia , a critical risk factor for delirium and particularly prevalent in postacute care . We investigated risk factors for delirium and its outcomes in older adults with and without dementia admitted to a subacute care unit ( SCU ) after exacerbated chronic conditions . Methods : This is a prospect i ve cohort study including patients ≥65 years old admitted to an SCU for 12 months . We collected demographics , comprehensive geriatric assessment s , and presence of dementia and delirium at admission . Outcomes included discharge to previous living situation , mortality , and functional evolution . Due to the high prevalence of dementia , a subgroup analysis was performed to investigate specific risk factors for delirium and related outcomes . Results : Of 909 patients ( mean age [ ±SD ] 85.8 ± 6.7 ; 60 % women , 47.5 % with dementia ) , 352 ( 38.7 % ) developed delirium . The main risk factor for delirium was dementia ( HR [ 95 % CI ] 5.2 [ 3.5–7.7 ] ) ; age , functional status , and urinary tract infections were also independently associated with delirium . In dementia patients , only age ( HR [ 95 % CI ] 1.0 [ 1.004–1.1 ] ) and being male ( HR [ 95 % CI ] 1.7 [ 1.04–2.6 ] ) were associated with delirium . Delirium was associated with greater mortality ( 10.8 vs. 3.9 % ; p < 0.001 ) and greater functional decline in the entire sample ( –12.3 vs. –6.4 Barthel index points ; p < 0.001 ) . In the dementia subgroup , patients with delirium experienced greater functional loss ( p = 0.013 ) and less functional recovery ( p = 0.025 ) . Conclusions : In older patients admitted to postacute care , dementia is the main risk factor for delirium , and delirium carries worse clinical and functional outcomes . In patients with dementia , delirium is also relevant , since it entails a functional loss at admission and lower functional recovery OBJECTIVES To investigate whether an education program and a reorganization of nursing and medical care improved the outcome for older delirious patients . DESIGN Prospect i ve intervention study . SETTING Department of General Internal Medicine , Sundsvall Hospital , Sweden . PARTICIPANTS Four hundred patients , aged 70 and older , consecutively admitted to an intervention or a control ward . INTERVENTION The intervention consisted of staff education focusing on the assessment , prevention , and treatment of delirium and on caregiver-patient interaction . Reorganization from a task-allocation care system to a patient-allocation system with individualized care . MEASUREMENTS The patients were assessed using the Organic Brain Syndrome Scale and the Mini-Mental State Examination on Days 1 , 3 , and 7 after admission . Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS Delirium was equally common on the day of admission at the two wards , but fewer patients remained delirious on Day 7 on the intervention ward ( n=19/63 , 30.2 % vs 37/62 , 59.7 % , P=.001 ) . The mean length of hospital stay+/-st and ard deviation was significantly lower on the intervention ward then on the control ward ( 9.4+/-8.2 vs 13.4+/-12.3 days , P<.001 ) especially for the delirious patients ( 10.8+/-8.3 vs 20.5+/-17.2 days , P<.001 ) . Two delirious patients in the intervention ward and nine in the control ward died during hospitalization ( P=.03 ) . CONCLUSION This study shows that a multifactorial intervention program reduces the duration of delirium , length of hospital stay , and mortality in delirious patients OBJECTIVES To ( 1 ) reduce deep sedation and delirium to permit mobilization , ( 2 ) increase the frequency of rehabilitation consultations and treatments to improve patients ' functional mobility , and ( 3 ) evaluate effects on length of stay . DESIGN Seven-month prospect i ve before/after quality improvement project . SETTING Sixteen-bed medical intensive care unit ( MICU ) in academic hospital . PARTICIPANTS 57 patients mechanically ventilated 4 days or longer . INTERVENTION A multidisciplinary team focused on reducing heavy sedation and increasing MICU staffing to include full-time physical and occupational therapists with new consultation guidelines . MAIN OUTCOME MEASURES Sedation and delirium status , rehabilitation treatments , functional mobility . RESULTS Compared with before the quality improvement project , benzodiazepine use decreased markedly ( proportion of MICU days that patients received benzodiazepines [ 50 % vs 25 % , P=.002 ] ) , with lower median daily sedative doses ( 47 vs 15 mg midazolam equivalents [ P=.09 ] and 71 vs 24 mg morphine equivalents [ P=.01 ] ) . Patients had improved sedation and delirium status ( MICU days alert [ 30 % vs 67 % , P<.001 ] and not delirious [ 21 % vs 53 % , P=.003 ] ) . There were a greater median number of rehabilitation treatments per patient ( 1 vs 7 , P<.001 ) with a higher level of functional mobility ( treatments involving sitting or greater mobility , 56 % vs 78 % , P=.03 ) . Hospital administrative data demonstrated that across all MICU patients , there was a decrease in intensive care unit and hospital length of stay by 2.1 ( 95 % confidence interval : 0.4 - 3.8 ) and 3.1 ( 0.3 - 5.9 ) days , respectively , and a 20 % increase in MICU admissions compared with the same period in the prior year . CONCLUSIONS Using a quality improvement process , intensive care unit delirium , physical rehabilitation , and functional mobility were markedly improved and associated with decreased length of stay OBJECTIVES To compare rates of 30-day readmission between hospital units with a Hospital Elder Life Program ( HELP ) and control units without HELP . DESIGN Retrospective cohort study . SETTING The study took place from July 1 , 2013 , to June 30 , 2014 , at the University of Pittsburgh Medical Center Shadyside , a 520-bed community teaching hospital that has used HELP since 2002 . Eight medical and surgical units with HELP were compared with 10 medical and surgical units without HELP . PARTICIPANTS During the study period , HELP units , had 4,794 patients aged 70 and older , and usual care units had 2,834 . INTERVENTION HELP is a multifactorial , multidisciplinary program that provides targeted interventions for delirium risk factors in at-risk individuals in collaboration with bedside staff . MEASUREMENTS Mixed-effects Poisson regression models were used to estimate the adjusted incident risk ratio for 30-day readmission between HELP and usual care units for the overall cohort and for the subgroup of individuals discharged home , with or without services . RESULTS Patients on HELP units were more likely than those in usual care units to be older , female , and black and had an unadjusted readmission rate of 16.9 % , versus 18.9 % for patients on control units . The adjusted risk of readmission was 0.83 ( 95 % confidence interval ( CI ) = 0.73 - 0.94 , P = .003 ) for HELP unit patients overall and 0.74 ( 95 % CI = 0.63 - 0.87 , P < .001 ) for HELP unit patients discharged to home with or without services . CONCLUSION The HELP program is associated with lower risk of 30-day hospital readmission overall and for the subgroup of individuals discharged to home . Prospect i ve studies are needed to confirm these observations OBJECTIVES To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients . DESIGN Controlled study comparing an intervention in a geriatric unit ( GI ) with usual care in two internal medicine services ( UC ) . SETTING University hospital in Madrid , Spain . PARTICIPANTS Five hundred forty-two consecutive patients ( 170 GI , 372 UC ) , aged 70 and older , with any of the risk criteria for delirium ( cognitive impairment , visual impairment , acute disease severity , dehydration ) . INTERVENTION Educational measures and specific actions in seven risk areas ( orientation , sensory impairment , sleep , mobilization , hydration , nutrition , drug use ) . Daily monitoring of adherence . MEASUREMENTS Baseline characteristics , risk factors for delirium , and quality care indicators were analyzed . The primary endpoint was incidence of delirium assessed daily . The secondary endpoint was functional decline , defined as loss of independence in any of the activities of daily living . The intervention effect was evaluated using logistic regression analysis . RESULTS Delirium affected 11.7 % of the GI group and 18.5 % of the UC group ( P=.04 ) . After adjustment for confounders , the intervention was associated with lower incidence of delirium ( odds ratio=0.4 , 95 % confidence interval=0.24 - 0.77 ; P=.005 ) . In the patients who experienced delirium , severity , length , and recurrence of episodes were similar in both groups . Adherence to the intervention protocol s was 75.7 % . The intervention reduced the rate of functional decline ( 45.5 % in GI vs 56.3 % in UC , P=.03 ) and improved other quality indicators ( e.g. , mobilization and physical restraints reduction ) . CONCLUSION A multicomponent , nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients , improves quality of care , and can be implemented without additional re sources in a public healthcare system Objective To develop and vali date an instrument for use in the intensive care unit to accurately diagnose delirium in critically ill patients who are often nonverbal because of mechanical ventilation . Design Prospect i ve cohort study . Setting The adult medical and coronary intensive care units of a tertiary care , university-based medical center . Patients Thirty-eight patients admitted to the intensive care units . Measurements and Main Results We design ed and tested a modified version of the Confusion Assessment Method for use in intensive care unit patients and called it the CAM-ICU . Daily ratings from intensive care unit admission to hospital discharge by two study nurses and an intensivist who used the CAM-ICU were compared against the reference st and ard , a delirium expert who used delirium criteria from the Diagnostic and Statistical Manual of Mental Disorders ( fourth edition ) . A total of 293 daily , paired evaluations were completed , with reference st and ard diagnoses of delirium in 42 % and coma in 27 % of all observations . To include only interactive patient evaluations and avoid repeat-observer bias for patients studied on multiple days , we used only the first-alert or lethargic comparison evaluation in each patient . Thirty-three of 38 patients ( 87 % ) developed delirium during their intensive care unit stay , mean duration of 4.2 ± 1.7 days . Excluding evaluations of comatose patients because of lack of characteristic delirium features , the two critical care study nurses and intensivist demonstrated high interrater reliability for their CAM-ICU ratings with kappa statistics of 0.84 , 0.79 , and 0.95 , respectively ( p < .001 ) . The two nurses ’ and intensivist ’s sensitivities when using the CAM-ICU compared with the reference st and ard were 95 % , 96 % , and 100 % , respectively , whereas their specificities were 93 % , 93 % , and 89 % , respectively . Conclusions The CAM-ICU demonstrated excellent reliability and validity when used by nurses and physicians to identify delirium in intensive care unit patients . The CAM-ICU may be a useful instrument for both clinical and research purpose s to monitor delirium in this challenging patient population BACKGROUND A decreased incidence of delirium following the application of non-pharmacologic intervention protocol s to several patient population s has been previously reported . However , few studies have been conducted to examine the effects of their application to intensive care unit ( ICU ) patients . OBJECTIVES To examine the effects of applying a tailored delirium preventive protocol , developed by the authors , to ICU patients by analyzing its effects on delirium incidence , in-hospital mortality , ICU readmission , and length of ICU stay in a Korean hospital . DESIGN A single-blind r and omized controlled trial . SETTING S A 1049-bed general hospital with a 105-bed ICU . PARTICIPANTS Sixty and 63 ICU patients were r and omly assigned to the intervention and control groups , respectively . METHODS The research ers applied the delirium prevention protocol to the intervention group every day for the first 7 days of ICU hospitalization . Delirium incidence , mortality , and re-admission to the ICU during the same hospitalization period were analyzed by logistic regression analysis ; the 7- and 30-day in-hospital mortality by Kaplan-Meier survival and Cox proportional hazard regression analysis ; and length of ICU stay was assessed by linear regression analysis . RESULTS Application of the protocol had no significant effect on delirium incidence , in-hospital mortality , re-admission to the ICU , or length of ICU stay . Whereas the risk of 30-day in-hospital mortality was not significantly lower in the intervention than in the control group ( OR : 0.33 ; 95 % CI : 0.10 - 1.09 ) , we found a significantly decreased 7-day in-hospital mortality in the intervention group after protocol application ( HR : 0.09 ; 95 % CI : 0.01 - 0.72 ) . CONCLUSIONS Application of a tailored delirium prevention protocol to acute stage patients during the first 7 days of ICU hospitalization appeared to reduce the 7-day in-hospital risk of mortality only for this patient population |
1,161 | 31,551,866 | Results : To our knowledge , this is the first systematic review focused on the comparison of twins ' and singletons ' linguistic environments .
Differences between the groups were found in all of the included studies .
Data against twins were generally identified regarding all the considered linguistic environment 's features .
Conclusion : The disadvantaged linguistic environment of twins is likely due to limited parental re sources and dem and s associated with the management of two children of the same age .
However , the limited and conflicting data found did not allow for a firm conclusion to be drawn on the differences in the twins ' and singletons ' linguistic environments . | Background : Among twins , lower linguistic skills emerged when compared with singletons .
Considering the association found between parental linguistic input and children 's language development , exploring the differences between twins and singletons ' linguistic environments could find variables that are potentially associated with the lower linguistic skills of twins .
Aim : The current systematic review aims to analyze and systematize the existing literature focused on the comparison of twins ' and singletons ' linguistic environments within their first 3 years of life .
Method ological issues ( i.e. , the procedure used to assess the linguistic environment , the coding of the linguistic environment 's features , the computational method employed to assess the parental linguistic input , and participant characteristics ) and differences found among twins and singletons regarding their linguistic environment ( i.e. , linguistic input quantity , linguistic input complexity , linguistic features of child-directed speech , parental responsiveness , and directiveness , joint attention , and book reading ) were highlighted . | Objective : To determine , in a community-based sample of slow-to-talk toddlers , the extent to which specific maternal responsive behaviors at 24 months predict child language at 24 and 36 months . Methods : Mother-child dyads were recruited for this prospect i ve longitudinal study from 3 local government areas spanning low , middle , and high socioeconomic status in Melbourne , Australia . At child age 18 months , 1138 parents completed a 100-word expressive vocabulary checklist ; the 251 ( 22.1 % ) children scoring ⩽20th percentile were then followed up to comprise this study . Predictors : Six maternal responsive behaviors ( imitations , interpretations , labels , expansions , supportive directives and responsive questions ) were derived from mother-child free-play videos collected at 24 months of age and coded using the Observer XT system . Outcomes : Expressive and receptive language measured at 24 and 36 months of age ( Preschool Language Scale-4 ) , blind to maternal responsiveness ratings . Results : Two hundred and twenty-six of the 251 ( 90.0 % ) mother-child dyads were followed up at 36 months . In confounder-adjusted linear regression analyses , expansions , imitations , and responsive questions were strongly associated with better receptive and expressive language at 24 and 36 months . Labels unexpectedly predicted poorer expressive language at 36 months . Expansions were the only maternal behavior that predicted improvement in language between 24 and 36 months . Conclusions : Maternal responsive behaviors , particularly expansions , offer promise in enhancing early language learning in slow-to-talk toddlers . Parent-child interactions characterized by frequent use of maternal labels at 24 months could also be a predictive marker of those slow-to-talk toddlers at greater risk of persistent language problems PURPOSE The aim of this study was to investigate the language outcomes of 7-year-old children with and without a history of late language emergence at 24 months . METHOD One hundred twenty-eight children with a history of late language emergence ( LLE ) at 24 months and 109 children with a history of normal language emergence ( NLE ) at 24 months participated in direct behavioral assessment of multiple dimensions of language at 7 years . The children were recruited from a prospect i ve cohort study of 1,766 epidemiologically ascertained 24-month-old singleton children . RESULTS The group mean for the LLE children was within the typical range on an omnibus measure of general language ability and measures of specific dimensions of language . However , a greater percentage of LLE children , relative to NLE children , performed below normative expectations on a measure of general language ability ( 20 % versus 11 % ) , speech ( 7 % versus 2 % ) , syntax ( 18 % versus 8 % ) , and morphosyntax ( 9%-23 % versus 2%-14 % ) , but not vocabulary or semantics . CONCLUSION The results provide support for growth models of language impairment that predict that late onset of language foretells a protracted growth difference for some LLE children relative to NLE children , particularly for syntax and morphosyntax OBJECTIVE To examine psychosocial and obstetric outcomes at 1 year postpartum in first-time mothers who conceived after IVF . DESIGN Prospect i ve cohort study . SETTING University medical center in the United Kingdom . PATIENT(S ) One hundred twenty-nine mothers with a single naturally conceived birth , 95 mothers with a single IVF birth , and 36 mothers with a twin or triplet IVF birth . MAIN OUTCOME MEASURE(S ) General Health Question naire and Parenting Stress Index . RESULT ( S ) Twenty-two percent of mothers of multiples had Parenting Stress Index scores indicating severe parenting stress , compared with 5 % of mothers of IVF singletons ( odds ratio , 5.14 [ 95 % confidence interval ( CI ) , 1.55 - 16.99 ] ) and 9 % of mothers of naturally conceived singletons ( odds ratio , 2.76 [ 95 % CI , 1.03 - 7.4 ] ) . Mothers of multiple children conceived by IVF did not have poorer mental health but were less likely to be in paid employment at follow-up than were mothers of singletons conceived by IVF ( odds ratio , 0.3 [ 95 % CI , 0.13 - 0.67 ] ) or naturally ( odds ratio , 0.27 [ 95 % CI , 0.12 - 0.59 ] ) . Multiple births were more premature , had lower birth weights , and had more medical complications . They were more likely to have been admitted to special care than were singletons conceived by IVF ( odds ratio , 14.6 [ 95 % CI , 5.1 - 42.0 ) ] or those conceived naturally ( odds ratio , 10.59 [ 95 % CI , 3.67 - 30.57 ] ) CONCLUSION ( S ) Clinicians should ensure that couples making decisions about embryo transfer have considered the potential psychosocial burden of a multiple birth BACKGROUND The aim of the present study was to determine language levels in twins and singletons born after at least 34 weeks gestation and without identifiable neurological abnormality and to evaluate whether in vitro fertilization ( IVF ) affects language development in twin pregnancies . METHODS A prospect i ve study of a large cohort of all children born between 1 January 2001 and 31 December 2003 was carried out at Gazi University Hospital . All live-born twin pairs in which both twins survived were identified , and a comparable sample of families with pairs of singletons were chosen . The Stanford-Binet Intelligence Scale Form and the translated Turkish form of the Peabody Picture Vocabulary Test were completed at 60 months . RESULTS Even after excluding the most premature twins and those with diagnosable neurological damage , twins performed worse than singletons on language development tests . Twin girls had better scores than twin boys . A statistically significant difference was found between the scores of term and preterm twins . No significant difference was noted when compared according to birth order . Appropriate for gestational age ( AGA ) twins did better than small for gestational age ( SGA ) twins in the test scores . All twin girls did not differ from singleton girls , but all twin boys performed worse than singleton boys . Term twins had similar results with term singletons , but preterm twins had lower scores than preterm singletons . SGA singletons had better scores than SGA twins , while AGA twins and singletons did not differ . When the children were compared with regard to method of conception , IVF children had significantly lower scores on the tests than those in the spontaneous conception group . CONCLUSION It is hoped that the present findings could lead to a more precise assessment of children for speech impairment and , above all , to more efficient preventive intervention . Whatever mechanisms are involved , the present results indicate that twins born as a result of IVF , are at a disadvantage in terms of language development in comparison with spontaneously conceived twins OBJECTIVE To establish the nature and extent of difficulties in parenting and child development in families with twins conceived by assisted reproduction . DESIGN Comparisons were carried out between a representative sample of 344 families with 2- to 5-year-old twins conceived by IVF/intracytoplasmic sperm injection ( ICSI ) and a matched comparison group of 344 families with singletons from IVF/ICSI . One twin was r and omly selected for data analysis to avoid the bias associated with nonindependence of measures . SETTING A general population sample of IVF/ICSI families . PATIENT(S ) Mothers and children . INTERVENTION(S ) Mothers completed a question naire booklet . MAIN OUTCOME MEASURE(S ) St and ardized measures of the mother 's psychological well-being ( parenting stress , depression , and quality of marriage ) and st and ardized measures of the child 's psychological development ( emotional/behavioral problems and cognitive development ) . RESULT ( S ) Mothers of twins showed significantly higher levels of parenting stress and depression than mothers of singletons and were significantly more likely to find parenting difficult and significantly less likely to obtain pleasure from their child . Regarding the children , there was no difference in the level of emotional or behavioral problems between twins and singletons . However , twins showed significantly lower levels of cognitive functioning . CONCLUSION ( S ) Greater difficulties in parenting and child development were experienced by IVF/ICSI families with twins than by IVF/ICSI families with singletons |
1,162 | 31,555,967 | The indirect comparison revealed no statistically differences for OS , PFS and ORR across trials , while safety profile differed between the three couples of agents .
This indirect adjusted meta- analysis suggests a similar efficacy and a slightly different safety profile , related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM | Synergistic combinations between BRAF and MEK inhibitors , such as dabrafenib plus trametinib , vemurafenib plus cobimetinib or encorafenib plus binimetinib , represent the current st and ard of care in metastatic or locally advanced BRAF V600 mutated malignant melanomas ( MM ) .
However , no studies explored the direct head-to-head comparison between the three different combinations .
In this paper , we performed a network meta- analysis to evaluate their efficacy in terms of overall survival ( OS ) , progression-free survival ( PFS ) , overall response rate ( ORR ) and safety profile . | AIM Underst and ing predictors of long-term benefit with currently available melanoma therapies is the key for optimising individualised treatments . A prior pooled analysis of dabrafenib plus trametinib ( D + T)-r and omised trials ( median follow-up , 20.0 months ) identified baseline lactate dehydrogenase ( LDH ) and number of organ sites with metastasis as predictive factors for progression-free ( PFS ) and overall ( OS ) survival . However , longer-term follow-up analyses are needed to confirm which patients treated with D + T can achieve maximum benefit . METHODS Three-year l and mark data were retrospectively pooled for D + T patients in phase 3 trials ( COMBI-d [ NCT01584648 ] ; COMBI-v [ NCT01597908 ] ) . Univariate and multivariate analyses assessed prognostic values of predefined baseline factors ; regression tree analysis determined hierarchy and interactions between variables . RESULTS Long-term pooled outcomes were consistent with individual trial results ( N = 563 ; 3-year PFS , 23 % ; 3-year OS , 44 % ) . Baseline LDH level and number of organ sites remained strongly associated with and /or predictive of PFS and OS . In addition , baseline sum of lesion diameters ( SLD ) was identified as a predictor for progression . In the most favourable prognostic group ( normal LDH , SLD < 66 mm , <3 organ sites ; n = 183/563 [ 33 % ] ) , 3-year PFS was 42 % . Baseline number of organ sites was also predictive of outcomes in patients with PFS ≥ 6 months . CONCLUSION Using the largest phase 3 data set available for BRAF/MEK inhibitor combination therapy in melanoma , these results demonstrate that durable responses lasting ≥3 years are possible in subsets of patients with BRAF-mutant melanoma receiving D + T. Although the best predictive model evolved with longer follow-up , factors predicting clinical outcomes with the combination remained consistent with previous analyses BACKGROUND The combination of cobimetinib with vemurafenib improves progression-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF(V600)-mutant advanced melanoma , as previously reported in the coBRIM study . In this Article , we report up date d efficacy results , including overall survival and safety after longer follow-up , and selected biomarker correlative studies . METHODS In this double-blind , r and omised , placebo-controlled , multicentre study , adult patients ( aged ≥18 years ) with histologically confirmed BRAF(V600 ) mutation-positive unresectable stage IIIC or stage IV melanoma were r and omly assigned ( 1:1 ) using an interactive response system to receive cobimetinib ( 60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle ) or placebo , in combination with oral vemurafenib ( 960 mg twice daily ) . Progression-free and overall survival were primary and secondary endpoints , respectively ; all analyses were done on the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01689519 , and is ongoing but no longer recruiting participants . FINDINGS Between Jan 8 , 2013 , and Jan 31 , 2014 , 495 eligible adult patients were enrolled and r and omly assigned to the cobimetinib plus vemurafenib group ( n=247 ) or placebo plus vemurafenib group ( n=248 ) . At a median follow-up of 14·2 months ( IQR 8·5 - 17·3 ) , the up date d investigator-assessed median progression-free survival was 12·3 months ( 95 % CI 9·5 - 13·4 ) for cobimetinib and vemurafenib versus 7·2 months ( 5·6 - 7·5 ) for placebo and vemurafenib ( HR 0·58 [ 95 % CI 0·46 - 0·72 ] , p<0·0001 ) . The final analysis for overall survival occurred when 255 ( 52 % ) patients had died ( Aug 28 , 2015 ) . Median overall survival was 22·3 months ( 95 % CI 20·3-not estimable ) for cobimetinib and vemurafenib versus 17·4 months ( 95 % CI 15·0 - 19·8 ) for placebo and vemurafenib ( HR 0·70 , 95 % CI 0·55 - 0·90 ; p=0·005 ) . The safety profile for cobimetinib and vemurafenib was tolerable and manageable , and no new safety signals were observed with longer follow-up . The most common grade 3 - 4 adverse events occurring at a higher frequency in patients in the cobimetinib and vemurafenib group compared with the vemurafenib group were γ-glutamyl transferase increase ( 36 [ 15 % ] in the cobimetinib and vemurafenib group vs 25 [ 10 % ] in the placebo and vemurafenib group ) , blood creatine phosphokinase increase ( 30 [ 12 % ] vs one [ < 1 % ] ) , and alanine transaminase increase ( 28 [ 11 % ] vs 15 [ 6 % ] ) . Serious adverse events occurred in 92 patients ( 37 % ) in the cobimetinib and vemurafenib group and 69 patients ( 28 % ) in the vemurafenib group . Pyrexia ( six patients [ 2 % ] ) and dehydration ( five patients [ 2 % ] ) were the most common serious adverse events reported in the cobimetinib and vemurafenib group . A total of 259 patients have died : 117 ( 47 % ) in the cobimetinib and vemurafenib group and 142 ( 58 % ) in the vemurafenib group . The primary cause of death was disease progression in most patients : 109 ( 93 % ) of 117 in the cobimetinib and vemurafenib group and 133 ( 94 % ) of 142 in the vemurafenib group . INTERPRETATION These data confirm the clinical benefit of cobimetinib combined with vemurafenib and support the use of the combination as a st and ard first-line approach to improve survival in patients with advanced BRAF(V600)-mutant melanoma . FUNDING F Hoffmann-La Roche-Genentech BACKGROUND Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib ( PLX4032 ) have shown response rates of more than 50 % in patients with metastatic melanoma with the BRAF V600E mutation . METHODS We conducted a phase 3 r and omized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated , metastatic melanoma with the BRAF V600E mutation . Patients were r and omly assigned to receive either vemurafenib ( 960 mg orally twice daily ) or dacarbazine ( 1000 mg per square meter of body-surface area intravenously every 3 weeks ) . Co primary end points were rates of overall and progression-free survival . Secondary end points included the response rate , response duration , and safety . A final analysis was planned after 196 deaths and an interim analysis after 98 deaths . RESULTS At 6 months , overall survival was 84 % ( 95 % confidence interval [ CI ] , 78 to 89 ) in the vemurafenib group and 64 % ( 95 % CI , 56 to 73 ) in the dacarbazine group . In the interim analysis for overall survival and final analysis for progression-free survival , vemurafenib was associated with a relative reduction of 63 % in the risk of death and of 74 % in the risk of either death or disease progression , as compared with dacarbazine ( P<0.001 for both comparisons ) . After review of the interim analysis by an independent data and safety monitoring board , crossover from dacarbazine to vemurafenib was recommended . Response rates were 48 % for vemurafenib and 5 % for dacarbazine . Common adverse events associated with vemurafenib were arthralgia , rash , fatigue , alopecia , keratoacanthoma or squamous-cell carcinoma , photosensitivity , nausea , and diarrhea ; 38 % of patients required dose modification because of toxic effects . CONCLUSIONS Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation . ( Funded by Hoffmann-La Roche ; BRIM-3 Clinical Trials.gov number , NCT01006980 . ) BACKGROUND Combined BRAF-MEK inhibitor therapy is the st and ard of care for BRAFV600-mutant advanced melanoma . We investigated encorafenib , a BRAF inhibitor with unique target-binding properties , alone or in combination with the MEK inhibitor binimetinib , versus vemurafenib in patients with advanced BRAFV600-mutant melanoma . METHODS COLUMBUS was conducted as a two-part , r and omised , open-label phase 3 study at 162 hospitals in 28 countries . Eligible patients were aged 18 years or older and had histologically confirmed locally advanced ( American Joint Committee on Cancer [ AJCC ] stage IIIB , IIIC , or IV ) , unresectable or metastatic cutaneous melanoma , or unknown primary melanoma ; a BRAFV600E or BRAFV600 K mutation ; an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 ; and were treatment naive or had progressed on or after previous first-line immunotherapy . In part 1 of the study , patients were r and omly assigned ( 1:1:1 ) via interactive response technology to receive either oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily ( encorafenib plus binimetinib group ) , oral encorafenib 300 mg once daily ( encorafenib group ) , or oral vemurafenib 960 mg twice daily ( vemurafenib group ) . The primary endpoint was progression-free survival by blinded independent central review for encorafenib plus binimetinib versus vemurafenib . Efficacy analyses were by intention-to-treat . Safety was analysed in patients who received at least one dose of study drug and one postbaseline safety assessment . The results of part 2 will be published separately . This study is registered with Clinical Trials.gov , number NCT01909453 , and EudraCT , number 2013 - 001176 - 38 . FINDINGS Between Dec 30 , 2013 , and April 10 , 2015 , 577 of 1345 screened patients were r and omly assigned to either the encorafenib plus binimetinib group ( n=192 ) , the encorafenib group ( n=194 ) , or the vemurafenib group ( n=191 ) . With a median follow-up of 16·6 months ( 95 % CI 14·8 - 16·9 ) , median progression-free survival was 14·9 months ( 95 % CI 11·0 - 18·5 ) in the encorafenib plus binimetinib group and 7·3 months ( 5·6 - 8·2 ) in the vemurafenib group ( hazard ratio [ HR ] 0·54 , 95 % CI 0·41 - 0·71 ; two-sided p<0·0001 ) . The most common grade 3 - 4 adverse events seen in more than 5 % of patients in the encorafenib plus binimetinib group were increased γ-glutamyltransferase ( 18 [ 9 % ] of 192 patients ) , increased creatine phosphokinase ( 13 [ 7 % ] ) , and hypertension ( 11 [ 6 % ] ) ; in the encorafenib group they were palmoplantar erythrodysaesthesia syndrome ( 26 [ 14 % ] of 192 patients ) , myalgia ( 19 [ 10 % ] ) , and arthralgia ( 18 [ 9 % ] ) ; and in the vemurafenib group it was arthralgia ( 11 [ 6 % ] of 186 patients ) . There were no treatment-related deaths except for one death in the combination group , which was considered possibly related to treatment by the investigator . INTERPRETATION Encorafenib plus binimetinib and encorafenib monotherapy showed favourable efficacy compared with vemurafenib . Overall , encorafenib plus binimetinib appears to have an improved tolerability profile compared with encorafenib or vemurafenib . Encorafenib plus binimetinib could represent a new treatment option for patients with BRAF-mutant melanoma . FUNDING Array BioPharma , Novartis BACKGROUND Combined BRAF and MEK inhibition , as compared with BRAF inhibition alone , delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600 K mutations . METHODS In this phase 3 trial , we r and omly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600 K mutation to receive a combination of dabrafenib ( 150 mg orally twice daily ) and trametinib ( 2 mg orally once daily ) or dabrafenib and placebo . The primary end point was progression-free survival . Secondary end points included overall survival , response rate , response duration , and safety . A preplanned interim overall survival analysis was conducted . RESULTS The median progression-free survival was 9.3 months in the dabrafenib-trametinib group and 8.8 months in the dabrafenib-only group ( hazard ratio for progression or death in the dabrafenib-trametinib group , 0.75 ; 95 % confidence interval [ CI ] , 0.57 to 0.99 ; P=0.03 ) . The overall response rate was 67 % in the dabrafenib-trametinib group and 51 % in the dabrafenib-only group ( P=0.002 ) . At 6 months , the interim overall survival rate was 93 % with dabrafenib-trametinib and 85 % with dabrafenib alone ( hazard ratio for death , 0.63 ; 95 % CI , 0.42 to 0.94 ; P=0.02 ) . However , a specified efficacy-stopping boundary ( two-sided P=0.00028 ) was not crossed . Rates of adverse events were similar in the two groups , although more dose modifications occurred in the dabrafenib-trametinib group . The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib-trametinib group than in the dabrafenib-only group ( 2 % vs. 9 % ) , whereas pyrexia occurred in more patients ( 51 % vs. 28 % ) and was more often severe ( grade 3 , 6 % vs. 2 % ) in the dabrafenib-trametinib group . CONCLUSIONS A combination of dabrafenib and trametinib , as compared with dabrafenib alone , improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600 K mutations . ( Funded by GlaxoSmithKline ; Clinical Trials.gov number , NCT01584648 . ) BACKGROUND In the BRIM-3 trial , vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF(V600 ) mutation-positive melanoma . We present an extended follow-up analysis of the total population and in the BRAF(V600E ) and BRAF(V600 K ) mutation subgroups . METHODS Patients older than 18 years , with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF(V600 ) mutations were eligible . Patients also had to have a life expectancy of at least 3 months , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , and adequate haematological , hepatic , and renal function . Patients were r and omly assigned by interactive voice recognition system to receive either vemurafenib ( 960 mg orally twice daily ) or dacarbazine ( 1000 mg/m(2 ) of body surface area intravenously every 3 weeks ) . Co primary endpoints were overall survival and progression-free survival , analysed in the intention-to-treat population ( n=675 ) , with data censored at crossover . A sensitivity analysis was done . This trial is registered with Clinical Trials.gov , NCT01006980 . FINDINGS 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4 , 2010 , and Dec 16 , 2010 . 337 patients were r and omly assigned to receive vemurafenib and 338 to receive dacarbazine . Median follow-up was 12·5 months ( IQR 7·7 - 16·0 ) on vemurafenib and 9·5 months ( 3·1 - 14·7 ) on dacarbazine . 83 ( 25 % ) of the 338 patients initially r and omly assigned to dacarbazine crossed over from dacarbazine to vemurafenib . Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group ( 13·6 months [ 95 % CI 12·0 - 15·2 ] vs 9·7 months [ 7·9 - 12·8 ] ; hazard ratio [ HR ] 0·70 [ 95 % CI 0·57 - 0·87 ] ; p=0·0008 ) , as was median progression-free survival ( 6·9 months [ 95 % CI 6·1 - 7·0 ] vs 1·6 months [ 1·6 - 2·1 ] ; HR 0·38 [ 95 % CI 0·32 - 0·46 ] ; p<0·0001 ) . For the 598 ( 91 % ) patients with BRAF(V600E ) disease , median overall survival in the vemurafenib group was 13·3 months ( 95 % CI 11·9 - 14·9 ) compared with 10·0 months ( 8·0 - 14·0 ) in the dacarbazine group ( HR 0·75 [ 95 % CI 0·60 - 0·93 ] ; p=0·0085 ) ; median progression-free survival was 6·9 months ( 95 % CI 6·2 - 7·0 ) and 1·6 months ( 1·6 - 2·1 ) , respectively ( HR 0·39 [ 95 % CI 0·33 - 0·47 ] ; p<0·0001 ) . For the 57 ( 9 % ) patients with BRAF(V600 K ) disease , median overall survival in the vemurafenib group was 14·5 months ( 95 % CI 11·2-not estimable ) compared with 7·6 months ( 6·1 - 16·6 ) in the dacarbazine group ( HR 0·43 [ 95 % CI 0·21 - 0·90 ] ; p=0·024 ) ; median progression-free survival was 5·9 months ( 95 % CI 4·4 - 9·0 ) and 1·7 months ( 1·4 - 2·9 ) , respectively ( HR 0·30 [ 95 % CI 0·16 - 0·56 ] ; p<0·0001 ) . The most frequent grade 3 - 4 events were cutaneous squamous-cell carcinoma ( 65 [ 19 % ] of 337 patients ) and keratoacanthomas ( 34 [ 10 % ] ) , rash ( 30 [ 9 % ] ) , and abnormal liver function tests ( 38 [ 11 % ] ) in the vemurafenib group and neutropenia ( 26 [ 9 % ] of 287 patients ) in the dacarbazine group . Eight ( 2 % ) patients in the vemurafenib group and seven ( 2 % ) in the dacarbazine group had grade 5 events . INTERPRETATION Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF(V600E ) mutation and in patients with the less common BRAF(V600 K ) mutation . FUNDING F Hoffmann-La Roche-Genentech BACKGROUND Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAFV600-mutant melanoma in the COLUMBUS trial . Here , we report the results of the secondary endpoint of overall survival . METHODS COLUMBUS was a two-part , r and omised , open-label , phase 3 study done at 162 hospitals in 28 countries . Eligible patients were aged at least 18 years with histologically confirmed , locally advanced , unresectable , or metastatic cutaneous melanoma , or unknown primary melanoma , BRAFV600E or BRAFV600 K mutation , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , and were treatment naive or had progressed on or after first-line immunotherapy . In part 1 of the study , patients were r and omly assigned ( 1:1:1 ) by use of interactive response technology to receive oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily ( encorafenib plus binimetinib group ) , oral encorafenib 300 mg once daily ( encorafenib group ) , or oral vemurafenib 960 mg twice daily ( vemurafenib group ) . R and omisation was stratified by the American Joint Committee on Cancer stage , ECOG performance status , and BRAF mutation status . The primary outcome of the trial , progression-free survival with encorafenib plus binimetinib versus vemurafenib , was reported previously . Here we present the prespecified interim overall survival analysis . Efficacy analyses were by intent to treat . Safety was analysed in patients who received at least one dose of study drug . Part 2 of the study was initiated at the request of the US Food and Drug Administration to better underst and the contribution of binimetinib to the combination therapy by comparing encorafenib 300 mg once daily plus binimetinib 45 mg twice daily with encorafenib 300 mg once daily alone . Results of part 2 will be published separately . This trial is ongoing and is registered with Clinical Trials.gov , number NCT01909453 , and EudraCT , number 2013 - 001176 - 38 . FINDINGS Between Dec 30 , 2013 , and April 10 , 2015 , 577 of 1345 screened patients were r and omly assigned to receive encorafenib plus binimetinib ( n=192 ) , encorafenib ( n=194 ) , or vemurafenib ( n=191 ) . Median follow-up for overall survival was 36·8 months ( 95 % CI 35·9 - 37·5 ) . Median overall survival was 33·6 months ( 95 % CI 24·4 - 39·2 ) with encorafenib plus binimetinib and 16·9 months ( 14·0 - 24·5 ) with vemurafenib ( hazard ratio 0·61 [ 95 % CI 0·47 - 0·79 ] ; two-sided p<0·0001 ) . The most common grade 3 or 4 adverse events did not change substantially from the first report ; those seen in more than 5 % of patients treated with encorafenib plus binimetinib were increased γ-glutamyltransferase ( 18 [ 9 % ] of 192 patients ) , increased blood creatine phosphokinase ( 14 [ 7 % ] ) , and hypertension ( 12 [ 6 % ] ) ; those seen with encorafenib alone were palmar-plantar erythrodysaesthesia syndrome ( 26 [ 14 % ] of 192 patients ) , myalgia ( 19 [ 10 % ] ) , and arthralgia ( 18 [ 9 % ] ) ; and with vemurafenib the most common grade 3 or 4 adverse event was arthralgia ( 11 [ 6 % ] of 186 patients ) . One death in the combination treatment group was considered by the investigator to be possibly related to treatment . INTERPRETATION The combination of encorafenib plus binimetinib provided clinical ly meaningful efficacy with good tolerability as shown by improvements in both progression-free survival and overall survival compared with vemurafenib . These data suggest that the combination of encorafenib plus binimetinib is likely to become an important therapeutic option in patients with BRAFV600-mutant melanoma . FUNDING Array BioPharma , Novartis BACKGROUND Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors . METHODS We performed a molecular analysis to identify oncogenic mutations ( HRAS , KRAS , NRAS , CDKN2A , and TP53 ) in the lesions from patients treated with the BRAF inhibitor vemurafenib . An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed . RESULTS Among 21 tumor sample s , 13 had RAS mutations ( 12 in HRAS ) . In a validation set of 14 sample s , 8 had RAS mutations ( 4 in HRAS ) . Thus , 60 % ( 21 of 35 ) of the specimens harbored RAS mutations , the most prevalent being HRAS Q61L . Increased proliferation of HRAS Q61L-mutant cell lines exposed to vemurafenib was associated with mitogen-activated protein kinase (MAPK)-pathway signaling and activation of ERK-mediated transcription . In a mouse model of HRAS Q61L-mediated skin carcinogenesis , the vemurafenib analogue PLX4720 was not an initiator or a promoter of carcinogenesis but accelerated growth of the lesions harboring HRAS mutations , and this growth was blocked by concomitant treatment with a MEK inhibitor . CONCLUSIONS Mutations in RAS , particularly HRAS , are frequent in cutaneous squamous-cell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib . The molecular mechanism is consistent with the paradoxical activation of MAPK signaling and leads to accelerated growth of these lesions . ( Funded by Hoffmann-La Roche and others ; Clinical Trials.gov numbers , NCT00405587 , NCT00949702 , NCT01001299 , and NCT01006980 . ) BACKGROUND The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600 K mutations . Combining dabrafenib and the MEK inhibitor trametinib , as compared with dabrafenib alone , enhanced antitumor activity in this population of patients . METHODS In this open-label , phase 3 trial , we r and omly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of dabrafenib ( 150 mg twice daily ) and trametinib ( 2 mg once daily ) or vemurafenib ( 960 mg twice daily ) orally as first-line therapy . The primary end point was overall survival . RESULTS At the preplanned interim overall survival analysis , which was performed after 77 % of the total number of expected events occurred , the overall survival rate at 12 months was 72 % ( 95 % confidence interval [ CI ] , 67 to 77 ) in the combination-therapy group and 65 % ( 95 % CI , 59 to 70 ) in the vemurafenib group ( hazard ratio for death in the combination-therapy group , 0.69 ; 95 % CI , 0.53 to 0.89 ; P=0.005 ) . The prespecified interim stopping boundary was crossed , and the study was stopped for efficacy in July 2014 . Median progression-free survival was 11.4 months in the combination-therapy group and 7.3 months in the vemurafenib group ( hazard ratio , 0.56 ; 95 % CI , 0.46 to 0.69 ; P<0.001 ) . The objective response rate was 64 % in the combination-therapy group and 51 % in the vemurafenib group ( P<0.001 ) . Rates of severe adverse events and study -drug discontinuations were similar in the two groups . Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1 % of patients in the combination-therapy group and 18 % of those in the vemurafenib group . CONCLUSIONS Dabrafenib plus trametinib , as compared with vemurafenib monotherapy , significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600 K mutations , without increased overall toxicity . ( Funded by GlaxoSmithKline ; Clinical Trials.gov number , NCT01597908 . ) |
1,163 | 24,937,099 | Including only studies with low risk of bias reduced the heterogeneity but had little impact on the overall effect size of average clinical score ( SMD -0.22 , 95 % CI -0.41 to -0.03).Sub-analyses limited to nebulized albuterol or salbutamol among out patients ( nine studies ) showed no effect on oxygen saturation ( MD -0.19 , 95 % CI -0.59 to 0.21 , n = 572 ) , average clinical score ( SMD -0.36 , 95 % CI -0.83 to 0.11 , n = 532 ) or hospital admission after treatment ( OR 0.77 , 95 % CI 0.44 to 1.33 , n = 404).Adverse effects included tachycardia , oxygen desaturation and tremors .
AUTHORS ' CONCLUSIONS Bronchodilators such as albuterol or salbutamol do not improve oxygen saturation , do not reduce hospital admission after outpatient treatment , do not shorten the duration of hospitalization and do not reduce the time to resolution of illness at home . | BACKGROUND Bronchiolitis is an acute , viral lower respiratory tract infection affecting infants and is sometimes treated with bronchodilators .
OBJECTIVES To assess the effects of bronchodilators on clinical outcomes in infants ( 0 to 12 months ) with acute bronchiolitis .
Given the adverse side effects and the expense associated with these treatments , bronchodilators are not effective in the routine management of bronchiolitis . | OBJECTIVE In previously well infants hospitalized with acute viral bronchiolitis , the effectiveness of repeated nebulized therapy with epinephrine ( EPI ) was compared with treatment with albuterol ( ALB ) or saline placebo ( PLAC ) . STUDY DESIGN In this r and omized , double-blind , parallel-group , controlled trial , infants received study nebulizations every 1 to 6 hours and were assessed twice daily by the research team . The primary outcome was length of hospital stay ( LOS ) . Secondary outcomes included the time from admission until the infant had normal hydration , oxygenation , and minimal respiratory distress . RESULTS A total of 149 infants were r and omized ; 50 were allocated to receive racemic EPI , 51 were given ALB , and 48 received PLAC . Baseline characteristics and pre-enrollment symptoms , signs , and therapy were similar between groups . There were no group differences in the primary outcome measure , mean LOS (hours)(+/- SD ) : EPI = 59.8 ( 62 ) , ALB = 61.4 ( 54 ) , and PLAC = 63.3 ( 47 ) ; P = .95 by intent-to-treat analysis . Group differences were not statistically significant in any of the secondary outcomes . CONCLUSIONS There were no group differences in the effectiveness of therapy for infants hospitalized with bronchiolitis . Based on these results , we do not recommend routine use of either nebulized EPI or ALB in this patient group Objective To compare the length of hospital stay ( primary ) and improvement in clinical severity scores ( secondary ) among children with bronchiolitis nebulized with 3 % hypertonic saline or 0.9 % saline . Design R and omized double blind controlled trial . Setting Tertiary care teaching hospital . Patients Hospitalized children ( 1–24 months ) with acute bronchiolitis of moderate severity . InterventionNebulization of 4 ml of 3 % hypertonic saline or 4 mL of 0.9 % saline , along with 2.5 mg salbutamol , at 4-hourly intervals till the patient was ready for discharge . Results Baseline characteristics were similar in two groups . Median clinical severity score at admission was 6 ( IQR-1 ) in both the groups . Clinical severity scores monitored afterwards 12-hourly till discharge ( 132 h ) did not show statistically significant differences in 3 % and 0.9 % saline groups . Mean length of hospital stay ( time to reach predefined clinical severity score<3 ) was 63.93 ± 22.43 h in 3 % saline group and 63.51 ± 21.27 h in 0.9 % saline group ( P=0.878 ) . No adverse events were reported by the parents , caregivers or treating medical attendants in both groups . Conclusion Nebulized 3 % saline is not superior to 0.9 % saline in infants with clinical ly diagnosed acute bronchiolitis Objective An appropriate treatment of acute viral bronchiolitis can reduce the symptoms , hospitalization duration and exorbitant costs which is imposed on the families and insurance organizations . This study was conducted to determine the efficacy of epinephrine in comparison with salbutamol in the treatment of the disease . Methods Forty infants aged one month to 2 years with acute bronchiolitis in Amin and Al-Zahra hospitals , during 2008 , were enrolled in this study . The participants were r and omized in two treatment groups to receive epinephrine 0.1 ml/kg or salbutamol 0.15 mg/kg . Three doses of each medication were prescribed at intervals of 20 minutes and continued every 10 minutes after the third dose . The patients in both groups were monitored and rated by RDAI , number of the hospitalized days in the hospital , level of oxygen saturation and vital signs . Findings Mean hospitalization duration was 3.3±1.1 and 3±0.9 in the patients receiving salbutamol and epinephrine , respectively ( P=0.03 ) . There was a significant difference in assessing RDAI index between the two groups ( P=0.03 ) . There were no differences in SPO2 , PR , or RR variables in the studied intervals in both groups ( P>0.05 ) . Conclusion Regarding the effect of epinephrine on reduction of hospitalization duration and the RDAI index in patients with acute bronchiolitis , it seems that using epinephrine instead of salbutamol could be more effective in the management of the disease OBJECTIVE To investigate whether nebulized racemic epinephrine or albuterol improves respiratory distress in infants with acute bronchiolitis . DESIGN A r and omized , placebo-controlled , double-blind study . SETTING A university hospital providing primary hospital care for all pediatric patients in a defined area . PATIENTS One hundred consecutive infants younger than 24 months treated in the hospital for acute bronchiolitis . INTERVENTION The patients received two inhalations at 30-minute intervals : racemic epinephrine followed by physiologic saline ( REP group ; n = 24 ) , albuterol followed by physiologic saline ( AP group ; n = 27 ) , physiologic saline followed by racemic epinephrine ( PRE group ; n = 24 ) , and physiologic saline followed by albuterol ( PA group ; n = 25 ) . All patients received intramuscular epinephrine 60 minutes after the beginning of the study . MAIN OUTCOME MEASURES Oxygen saturation , respiratory rate , and two clinical scores were used : one based on wheezing and retractions ( Respiratory Distress Assessment Instrument ) and the other based on changes in wheezing , retractions , and respiratory rate ( Respiratory Assessment Change Score ) . MAIN RESULTS During the study , there were no significant differences among the four groups in clinical scores , oxygen saturations , and respiratory rates . Mean Respiratory Distress Assessment Instrument scores improved significantly within the REP , PRE , and AP groups 15 minutes after the first inhalation . In only the REP group , which received racemic epinephrine , the confidence limits did not overlap . A comparison of paired data of each patient revealed that the difference in Respiratory Assessment Change Score was significant between racemic epinephrine and physiologic saline , but not between albuterol and physiologic saline . Intramuscular epinephrine significantly improved Respiratory Distress Assessment Index scores in those groups treated earlier with racemic epinephrine ( REP and PRE groups ) . No significant adverse effects were seen in any group or at any phase of the study . CONCLUSIONS Elimination of hypoxia by supplemental oxygen and moistening of inspired air relieve the symptoms of acute bronchiolitis . Nebulized racemic epinephrine and albuterol are safe and useful in the treatment of acute bronchiolitis . Improvements in symptom scores at 15 minutes favor the use of racemic epinephrine . As the action of epinephrine is short , the effect can be increased by repeated inhalations To evaluate combination therapy of mild to moderate bronchiolitis with bronchiodilators and corticosteroids , we treated 51 young children with first-time wheezing and symptoms of respiratory tract infection with albuterol plus either prednisolone or placebo for 5 days . Disease severity was scored on days 0 , 2 , 3 , and 6 . On day 2 , prednisolone result ed in significantly lower scores ( 2.7 ±1.4 vs. 4.0 ±1.5 in all patients evaluated , p<0.05 ) than placebo , whereas there was no detectable difference on day 6 , suggesting that addition of prednisolone to albuterol transiently accelerates recovery from bronchiolitis . The clinical significance of this effect needs to be evaluated in further studies OBJECTIVE To determine the utility of inhaled hypertonic saline solution to treat ambulatory infants with viral bronchiolitis . DESIGN R and omized , double-blind , controlled trial . Sixty-five ambulatory infants ( mean + /- SD age , 12.5 + /- 6 months ) with viral bronchiolitis received either of the following : inhalation of 0.5 mL ( 5 mg ) terbutaline added to 2 mL of 0.9 % saline solution as a wet nebulized aerosol ( control ; group 1 ; n = 32 ) or 0.5 mL ( 5 mg ) terbutaline added to 2 mL of 3 % saline solution administered in the same manner as above ( treatment ; group 2 ; n = 33 ) . This therapy was repeated three times every day for 5 days . RESULTS The clinical severity ( CS ) scores at baseline on the first day of treatment were 6.4 + /- 1.8 in group 1 and 6.6 + /- 1.5 in group 2 ( not significant ) . After the first day , the CS score was significantly lower ( better ) in group 2 as compared to group 1 on each of the treatment days ( p < 0.005 ; Fig 1 ) . On the first day , the percentage decrease in the CS score after inhalation therapy was significantly better for group 2 ( 33 % ) than for group 1 ( 13 % ) [ p < 0.005 ; Fig 1 ] . On the second day , the percentage improvement was better in the hypertonic saline solution-treated patients ( group 2 ) as compared to the 0.9 % saline solution-treated patients ( group 1 ) [ p = 0.01 ; Fig 1 ] . CONCLUSIONS We conclude that in nonasthmatic , nonseverely ill ambulatory infants with viral bronchiolitis , aerosolized 3 % saline solution plus 5 mg terbutaline is effective in decreasing symptoms as compared to 0.9 % saline solution plus 5 mg terbutaline OBJECTIVE To determine the utility of inhaled hypertonic saline solution to treat infants hospitalized with viral bronchiolitis . DESIGN R and omized , double-blind , controlled trial . Fifty-two hospitalized infants ( mean + /- SD age , 2.9 + /- 2.1 months ) with viral bronchiolitis received either inhalation of epinephrine , 1.5 mg , in 4 mL of 0.9 % saline solution ( group 1 ; n = 25 ) or inhalation of epinephrine , 1.5 mg , in 4 mL of 3 % saline solution ( group 2 ; n = 27 ) . This therapy was repeated three times every hospitalization day until discharge . RESULTS The percentage improvement in the clinical severity scores after inhalation therapy was not significant in group 1 on the first , second , and third days after hospital admission ( 3.5 % , 2 % , and 4 % , respectively ) . In group 2 , significant improvement was observed on these days ( 7.3 % , 8.9 % , and 10 % , respectively ; p < 0.001 ) . Also , the improvement in clinical severity scores differed significantly on each of these days between the two groups . Using 3 % saline solution decreased the hospitalization stay by 25 % : from 4 + /- 1.9 days in group 1 to 3 + /- 1.2 days in group 2 ( p < 0.05 ) . CONCLUSIONS We conclude that in nonasthmatic , nonseverely ill infants hospitalized with viral bronchiolitis , aerosolized 3 % saline solution/1.5 mg epinephrine decreases symptoms and length of hospitalization as compared to 0.9 % saline solution/1.5 mg epinephrine OBJECTIVES Bronchiolitis is the most common disease of the lower respiratory tract in the first year of life . Treatment is controversial , with studies giving conflicting views on the benefits of bronchodilators and steroids . The objectives of this study were 1 ) to characterize the management of bronchiolitis in pediatric emergency departments ( PEDs ) in Canada , 2 ) to determine patient outcomes following emergency department ( ED ) visits , and 3 ) to provide descriptive data regarding bronchiolitis symptoms and family/personal medical history of these patients . METHODS A prospect i ve consecutive cohort of children with bronchiolitis presenting to seven Canadian PEDs was enrolled during a seven-to-21-day period . St and ardized interviews with parents provided data regarding symptoms , previous treatment , and past history . Charts were review ed for treatment , investigations , and disposition . Telephone follow-up at two to three weeks collected information regarding duration of illness and return visits . RESULTS Two hundred thirty-seven ( 91 % ) of 260 eligible patients were enrolled . One hundred eighty-nine patients ( 80 % ) had both an interview and chart review , and 48 ( 20 % ) had only chart review s ; follow-up was completed for 163 ( 69 % ) patients . One hundred fifteen ( 63 % ) had seen their primary care provider during their illness prior to the ED visit . Seventy-three percent of patients ( range per site 59 - 100 % ) were treated in the ED with bronchodilators ( usually salbutamol or epinephrine ) and 5 % ( range per site 0 - 14 % ) with oral steroids . Twenty-four percent ( 58/237 ) were prescribed bronchodilators on discharge , 3 % ( 7/237 ) inhaled steroids , and 2 % ( 5/237 ) oral steroids . Chi-square tests indicated significant practice variation by site in ED bronchodilator use ( p < 0.001 ) and bronchodilator use at discharge ( p = 0.0003 ) . Admission rate was 31 % ( range by site 22 - 43 % ) , 17 % of patients had more than one ED visit , and 1 % were admitted more than once . Admission rates were increased in younger children , children with comorbidities , and children with lower oxygen saturation . Viral studies were obtained in 53 % , with 76 % of these positive for respiratory syncytial virus ( RSV ) . Median duration of cough was 12 days , poor sleeping and irritability eight days , and wheeze and poor feeding seven days . CONCLUSIONS This study prospect ively describes the treatment of bronchiolitis in the pediatric ED . The findings are consistent with the literature regarding the reported use of bronchodilators ; however , use of steroids was found to be much lower than reported in other studies . Bronchodilator use in the ED and at discharge varied significantly by site . The results capture variation in treatment practice s in Canadian PEDs , which may be the result of discordant r and omized controlled trial evidence . Further research is needed to establish best practice We have measured total work of breathing before and after the inhalation of water , salbutamol , and ipratropium bromide , given as nebulised solutions , in 39 studies on 25 infants with acute , severe bronchiolitis . Twenty minutes after nebulised water , mean work of breathing per minute was increased by 4 % and work per litre by 10 % with 2 infants having significant improvement and 2 others showing deterioration . After salbutamol , mean work of breathing per minute showed a 22 % increase and work per litre a 0.5 % rise . The condition of only one child improved by greater than 25 % after this drug . Ipratropium bromide led to significant improvement in 6 out of 15 studies and no corresponding deterioration . The group results showed a fall in work of breathing , 18 % in work per minute and 16 % in work per litre STUDY OBJECTIVE To compare the safety and efficacy of metered-dose inhaler ( MDI ) albuterol to nebulized ( NEB ) albuterol administration . DESIGN A r and omized , triple-blinded , crossover study . SETTING A pediatric ICU in a tertiary care children 's hospital . PATIENTS Eleven intubated infants with bronchiolitis . INTERVENTIONS Subjects received four puffs of MDI albuterol ( 360 microg ) and 3 mL of NEB saline solution placebo or 0.3 mL of NEB albuterol ( 1.5 mg ) and MDI saline solution placebo . Each set of albuterol and saline solution placebo was administered after direct attachment of delivery device to the endotracheal tube and bag-valve system . Subjects received the opposite sequence 4 h after the initial sequence . The second sequence was given first the next day , and the first sequence was administered 4 h later . MEASUREMENTS AND RESULTS Respiratory system compliance and resistance were measured at baseline and 30 min , 1 h , 2 h , and 4 h after each set of placebo and albuterol . There was an appreciable improvement in compliance and resistance for up to 2 h following both methods of administration . However , the degree of improvement was not significantly different ( p>0.05 ) between the two methods . Neither method caused a significant change in resistance when measured at 4 h after albuterol/placebo administration . No evidence of toxicity was detected . CONCLUSIONS MDI-administered albuterol is as safe and efficacious as nebulized-administered albuterol in intubated infants with bronchiolitis . Generalizability of these results is limited by differences in drug delivery with different br and s of nebulizers and spacers and sites of attachment OBJECTIVES To determine the efficacy of oral salbutamol for providing symptomatic relief in mild bronchiolitis . DESIGN R and omized double-blind placebo controlled trial . SETTING Pediatric Outpatient Department of a tertiary care hospital . SUBJECTS 140 infants ( of 310 approached ) with a clinical diagnosis of acute bronchiolitis with respiratory rate < or= 70 breath/min , heart rate < or= 200 beats/min , hemoglobin oxygen saturation ( SpO2 ) > or= 95 % in room air , no or mild accessory muscle use , and respiratory distress assessment instrument ( RDAI ) score < or=10 . Children were followed up for 14 days . INTERVENTION Oral salbutamol ( 0.1 mg/kg/dose ) ( n=70 ) or placebo ( n=70 ) three times a day for 7 days or till complete resolution of symptoms , whichever was earlier . OUTCOME VARIABLES Time for resolution of illness ( ROI ) , duration of fever , cough , coryza , noisy breathing , time to achieve normal feeding and normal sleep , and frequency of hospitalization and adverse effects . RESULTS Median ( SE , 95 % CI ) duration of resolution of overall illness was similar in the two groups [ 6 ( 0 , 5 to 7 ) d in the salbutamol group vs. 5 ( 1 , 4 to 6 ) days in placebo group ; P=0.21 ] . There was no significant difference in mean duration of fever , cough , coryza , noisy breathing , time to achieve normal feeding and normal sleep ; and frequency of hospitalization or adverse effects , between the two groups . However , tremors were observed in 5 infants in the salbutamol group . CONCLUSION Oral salbutamol is not superior to placebo in reducing the duration of symptoms in mild cases of acute bronchiolitis in children BACKGROUND The role of bronchodilators in the treatment of bronchiolitis remains controversial . METHODS A double-blind , placebo controlled trial was performed to evaluate the clinical response to nebulized salbutamol . One hundred and fifty-six infants aged between 7 weeks and 24 months who had had an episode of wheezing and other signs and symptoms of bronchiolitis were r and omized to three groups as follows : ( i ) nebulized salbutamol was administered to 52 patients in group I at a dose of 0.15 mg/kg in 2 mL saline ; ( ii ) saline was nebulized to 52 patients in group II and ( iii ) in group III 52 patients received mist in a tent . All three groups were administered oxygen during the procedures . Treatment was repeated with the same agent after 30 min if the respiratory score was 5 or more . Respiratory rate , heart rate , oxygen saturation and presence of cyanosis , wheezing , retractions were recorded before and after each treatment . RESULTS The decrease in the respiratory score was 5.2 + /- 1.8 , 0.82 + /- 2.4 and 1.7 + /- 1.3 in group I , II and III , respectively . The decrease in group I was significantly higher than in the other groups . Heart rate was similar between groups . Oxygen saturation decreased in group I without reaching statistical significance . CONCLUSIONS Salbutamol was shown to be effective and safe in the treatment of acute bronchiolitis This r and omized , double-blind trial compared the efficacy of nebulized epinephrine with salbutamol in the treatment of infants with acute bronchiolitis . The mean percent oxygen saturation at 60 minutes was significantly higher in the epinephrine group . Thirty-three percent of the patients in epinephrine group were admitted to the hospital compared with 81 % of the salbutamol group ( p = 0.003 ) . We conclude that nebulized epinephrine is more efficacious than salbutamol for infants with acute bronchiolitis seen in an emergency department OBJECTIVE The primary objective of this study was to establish the validity and reliability of 2 respiratory scores , the Respiratory Distress Assessment Instrument ( RDAI ) and the Children 's Hospital of Wisconsin Respiratory Score ( CHWRS ) , in bronchiolitis . A secondary objective was to identify the respiratory score components that most determine overall respiratory status . METHODS This was a prospect i ve cohort study in infants aged < 1 year seen at Children 's Hospital of Wisconsin for bronchiolitis . We evaluated : ( 1 ) discriminative validity ( the score 's ability to discriminate between 2 different outcomes ) of the respiratory scores to identify emergency department ( ED ) disposition by using receiver operating characteristic curves ; and ( 2 ) construct validity ( the score 's ability to measure what it is thought to measure , overall respiratory status ) by using length of stay ( LOS ) as a proxy for disease severity and comparing correlations between changes in respiratory scores and LOS . Interrater reliability was established by using intraclass correlation . The contribution of individual respiratory score components to determine ED disposition was studied by using multivariate logistic regression . RESULTS A total of 195 infants were included . The area under the receiver operating characteristic curve was 0.68 for CHWRS versus 0.51 for RDAI in predicting disposition . There was no correlation between initial respiratory scores or change in respiratory scores over the first 24 hours and LOS . Item analysis revealed that oxygen delivery , subcostal retractions , and respiratory rate were independently correlated with ED disposition . The CHWRS was more reliable than the RDAI . CONCLUSIONS The CHWRS had modest discriminative validity in predicting ED disposition . Neither the CHWRS nor the RDAI had good construct validity . Respiratory rate , oxygen need , and presence of retractions were most useful in predicting ED disposition To test the efficacy of a combined alpha- and beta-receptor agonist in acute bronchiolitis , we compared inhaled racemic epinephrine with salbutamol in a double-blind , crossover , r and omized protocol . Twenty-four infants , 4.6 + /- 0.5 ( mean + /- SEM ) months of age , with their first episode of bronchiolitis were tested . After sedation with chloral hydrate , a clinical score and pulmonary mechanics measurements using simultaneous signals of airflow volume and transpulmonary pressure were recorded . After baseline measurements , infants received either nebulized salbutamol , 0.03 ml/kg , or racemic epinephrine , 0.1 ml/kg . Thirty minutes later , there was a significant decrease in clinical score after treatment with racemic epinephrine compared with the baseline score ( p < 0.001 ) ; this difference was not present after salbutamol inhalation ( p = 0.42 ) . Only 13 patients had a decrease in clinical score after salbutamol therapy , in comparison with 20 infants treated with racemic epinephrine ( p < 0.01 ) . Both drug decreased respiratory rate , but the decrease was greater after the use of racemic epinephrine ( p < 0.001 ) . There was a significant decrease in inspiratory , expiratory , and total pulmonary resistance after treatment with racemic epinephrine compared with baseline values ( p < 0.01 ) but no significant change after salbutamol inhalation . There was no significant correlation between the clinical score and pulmonary mechanics either at baseline or after drug treatment . We conclude that racemic epinephrine is superior to salbutamol in the treatment of infants with their first episode of acute bronchiolitis OBJECTIVE To assess the relation between age and bronchodilator responsiveness in infants with bronchiolitis . STUDY DESIGN In 41 infants ( age , 2 to 18 months ) with bronchiolitis , lung function was measured with the raised volume rapid thoracoabdominal compression technique before and after salbutamol inhalation . Lung function was quantified in terms of timed volumes ( FEV(0.5 ) , FEV(0.75 ) , and FEV(1.0 ) ) . A significant change was defined as a postbronchodilator value that differed from baseline by more than twice the within-subject coefficient of variation . RESULTS For the group , postbronchodilator values did not differ significantly from baseline ( DeltaFEV(0.5 ) , 3.8 % + /- 9.3 % ; DeltaFEV(0.75 ) , 3.5 % + /- 9.5 % ; and DeltaFEV(1.0 ) , 4.0 + /- 9.8 % ) . Eleven subjects showed significantly increased timed volumes ; 3 presented with a decreased lung function ; the remaining patients failed to show a significant change . The mean age of subjects with improved lung function did not differ significantly from the mean age of those with no or paradoxical responses ( 9.7 + /- 4.7 vs 8.1 + /- 4.1 months ) ; there was no correlation of age with the size of the bronchodilator response . CONCLUSIONS The results of the current study indicate that bronchodilator responsiveness in infants with bronchiolitis is not age-dependent Background Bronchiolitis is the most common cause of lower respiratory tract illness in infancy , and hospital admission rates appear to be increasing in Canada and the United States . Inhaled beta agonists offer only modest short-term improvement . Trials of racemic epinephrine have shown conflicting results . We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress , was safe , and shortened length of stay . Methods The study was a r and omized , double-blind controlled trial of aerosolized racemic epinephrine compared to salbutamol every one to 4 hours in previously well children aged 6 weeks to ≤ 2 years of age hospitalized with bronchiolitis . The primary outcome was symptom improvement as measured by the Respiratory Distress Assessment Instrument ( RDAI ) ; secondary outcomes were length of stay in hospital , adverse events , and report of symptoms by structured parental telephone interview one week after discharge . Results 62 children with a mean age of 6.4 months were enrolled ; 80 % of children had Respiratory Syncytial Virus ( RSV ) . Racemic epinephrine result ed in significant improvement in wheezing and the total RDAI score on day 2 and over the entire stay ( p < 0.05 ) . The mean LOS in the epinephrine arm was 2.6 days ( 95 % CI 2 , 3.2 ) v. 3.4 days in those in the salbutamol group ( 95 % CI 2.6 , 4.2 ) ( p > 0.05 ) . Adverse events were not significantly different in the two arms . At one week post-discharge , over half of parents reported that their child still had a respiratory symptom and 40 % had less than normal feeding . Conclusion Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay . Morbidity associated with bronchiolitis as identified by parents persists for at least one week after hospital discharge in most infants Objectives To evaluate the effect of nebulized albuterol on tidal breathing flow-volume loops in infants with bronchiolitis due to respiratory syncytial virus . Design A r and omized , double-blind , control study . Setting Pediatric unit in a community teaching hospital . Participants Twenty infants younger than 1 year of age ( mean age , 5.8 ± 2.8 months ) with a first episode of wheezing due to respiratory syncytial virus bronchiolitis . Interventions Chloral hydrate ( 50 mg/kg ) was administered orally for sedation . One dose each of nebulized albuterol ( 0.15 mg/kg in 3 ml saline ) and saline ( 3 ml ) were given at 6 hour intervals in a r and om order . Measurements Tidal breathing flow-volume loops were obtained before and after each aerosol treatment with a Neonatal/Pediatric Pulmonary Testing System ( Model 2600 ; Sensor Medics , Anaheim , CA , USA ) . At the same time , the fraction of tidal volume exhaled at peak tidal expiratory flow ( PTEF ) to total tidal volume ( VPTEF/VE ) , and the fraction of exhaled time at PTEF to total expiratory time ( tPTEF/tE ) were measured . The PTEF , the tidal expiratory flows at 10 % , 25 % , and 50 % of the remaining tidal volume ( TEF10 , TEF25 , and TEF50 ) , and the wheeze score were also determined . Results There were no significant changes in VPTEF/VE and tPTEF/tE after albuterol or saline treatment . PTEF increased significantly both after albuterol and saline treatments but the difference between the two treatments was not significant ( P = 0.6 ) . Both TEF10 and the ratio of the tidal expiratory flow at 25 % of the remaining tidal volume to PTEF ( 25/PT ) decreased significantly ( P < 0.05 ) after administration of albuterol . All other investigated variables were not significantly affected by aerosol administration . Conclusions Nebulized albuterol in infants with mild bronchiolitis due to respiratory syncytial virus did not improve VPTEF/VE and tPTEF/tE but did decrease TEF10 and 25/PT Objectives To compare the effect of nebulized racemic epinephrine to nebulized racemic albuterol on successful discharge from the emergency department ( ED ) . Methods Children up to their 18th month of life presenting to two teaching hospital EDs with a clinical diagnosis of bronchiolitis who were ill enough to warrant treatment but did not need immediate intubation were eligible for this double-blind r and omized controlled trial ( RCT ) . Patients received either three doses of racemic albuterol or one dose of racemic epinephrine plus two saline nebulizers . Disposition was decided 2 hours after the first nebulizer . Successful discharge was defined as not requiring additional bronchodilators in the ED after study drug administration and not subsequently admitted within 72 hours . Adjusted relative risks ( aRR ) were estimated using the modified Poisson regression with successful discharge as the dependent variable and study drug and severity of illness as exposures . Secondary analysis was performed for patients aged less than 12 months and first presentation . Results The authors analyzed 703 patients ; 352 patients were given albuterol and 351 epinephrine . A total of 173 in the albuterol group and 160 in the epinephrine group were successfully discharged ( crude RR = 1.08 , 95 % confidence interval [ CI ] = 0.92 to 1.26 ) . When adjusted for severity of illness , patients who received albuterol were significantly more likely than patients receiving epinephrine to be successfully discharged ( aRR = 1.18 , 95 % CI = 1.02 to 1.36 ) . This was also true among those with first presentation and in those less than 12 months of age . Conclusions In children up to the 18th month of life , ED treatment of bronchiolitis with nebulized racemic albuterol led to more successful discharges than nebulized epinephrine . ACADEMIC EMERGENCY MEDICINE 2008 ; 15:305–313 © 2008 by the Society for Academic Emergency Abstract Aim We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis . Methods Computerized lung sounds analysis with quantification of wheezing and crackles and a clinical score were used during a double blind , r and omized , controlled nebulized treatment pilot study . Infants were r and omized to receive a single dose of 1 mgr nebulized l-epinephrine or 2.5 mgr nebulized albuterol . Computerized quantification of wheezing and crackles ( PulmoTrack ® ) and a clinical score were performed prior to , 10 minutes post and 30 minutes post treatment . Results were analyzed with Student 's t-test for independent sample s , Mann-Whitney U test and Wilcoxon test . Results 15 children received albuterol , 12 received epinephrine . The groups were identical at baseline . Satisfactory lung sounds recording and analysis was achieved in all subjects . There was no significant change in objective quantification of wheezes and crackles or in the total clinical scores either within the groups or between the groups . There was also no difference in oxygen saturation and respiratory distress . Conclusion Computerized lung sound analysis is feasible in young infants with RSV bronchiolitis and provides a non-invasive , quantitative measure of wheezing and crackles in these infants . Trial registration number : Clinical Trials.gov BACKGROUND : Respiratory syncytial virus ( RSV ) infection is a leading cause of hospitalization among infants . However , estimates of the RSV hospitalization burden have varied , and precision has been limited by the use of age strata grouped in blocks of 6 to ≥12 months . METHODS : We analyzed data from a 5-year , prospect i ve , population -based surveillance for young children who were hospitalized with laboratory-confirmed ( reverse-transcriptase polymerase chain reaction ) RSV acute respiratory illness ( ARI ) during October through March 2000–2005 . The total population at risk was stratified by month of age by birth certificate information to yield hospitalization rates . RESULTS : There were 559 ( 26 % ) RSV-infected children among the 2149 enrolled children hospitalized with ARI ( 85 % of all eligible children with ARI ) . The average RSV hospitalization rate was 5.2 per 1000 children < 24 months old . The highest age-specific rate was in infants 1 month old ( 25.9 per 1000 children ) . Infants ≤2 months of age , who comprised 44 % of RSV-hospitalized children , had a hospitalization rate of 17.9 per 1000 children . Most children ( 79 % ) were previously healthy . Very preterm infants ( < 30 weeks ’ gestation ) accounted for only 3 % of RSV cases but had RSV hospitalization rates 3 times that of term infants . CONCLUSIONS : Young infants , especially those who were 1 month old , were at greatest risk of RSV hospitalization . Four-fifths of RSV-hospitalized infants were previously healthy . To substantially reduce the burden of RSV hospitalizations , effective general preventive strategies will be required for all young infants , not just those with risk factors BACKGROUND The mainstay of treatment in bronchiolitis includes oxygenation , aspiration of secretions from the respiratory tract and maintenance of hydration . The first choice medical agent in clinical practice is nebulized bronchodilators , although their place in treatment is controversial . OBJECTIVES We investigated the therapeutic benefit of nebulized hypertonic ( 3 % ) saline ( HS ) , by comparing four different nebulized regimens in the treatment of bronchiolitis in the emergency department . METHODS A total of 120 infants were included in this r and omized , double-blind , prospect i ve study . Infants were grouped according to the nebulized treatment they received : group 1 - salbutamol + normal saline ( NS ) , group 2 - salbutamol + HS , group 3 - HS , group 4 - NS . Heart beat , Clinical Bronchiolitis Severity Score ( CBSS ) and oxygen saturation of the patients were determined before and after the nebulizations and at 48 - 72 h after admission by the design ated study physician . RESULTS Post-treatment mean CBSS were significantly lower than pre-treatment scores in all groups ( p = 0.0001 ) with no significant difference within groups . Improvement percentages for CBSSs were significantly higher in infants without a history of atopy treated with HS and NS ( p = 0.023 , p = 0.0001 , respectively ) . CONCLUSIONS The CBSSs of all the infants improved after three doses of nebulized therapy regardless of the treatment regimens . The combination of salbutamol with hypertonic saline did not lead to an additive effect in the improvement of CBSSs compared to the st and ard salbutamol + NS combination . Atopic children benefited from salbutamol/NS combination whereas non-atopic children improved with HS and NS nebulizations based on improvement percentages of CBSS Acute bronchiolitis is a common , potentially life-threatening condition with few therapeutic options . In the present r and omized study , we compared the clinical efficacies of nebulized epinephrine and salbutamol in the emergency room management of acute bronchiolitis . Primary outcome measures were improvement in mean respiratory rate , mean oxygen saturation value and severity score . Secondary outcome measures were length of hospital stay , hospitalization and relapse rates . A total of 75 patients were analyzed ( 36 epinephrine , 39 salbutamol ) . Both groups experienced a similar pattern of clinical improvement . Hospitalization rates were 8.3 % for epinephrine and 5.1 % for salbutamol ( p > 0.05 ) , whereas relapse rates were 80 % for epinephrine and 20 % for salbutamol groups ( p < 0.001 ) . Respiratory syncytial virus was the most common virus identified ( 41 % ) . We did not find a difference between salbutamol and epinephrine in terms of clinical improvement , but salbutamol can be a drug of choice due to its lower relapse and hospitalization rates compared to epinephrine UNLABELLED Bronchiolitis is a common respiratory infection affecting young children . Much controversy revolves around the efficacy of bronchodilators in the treatment of bronchiolitis . This study was conducted to address this issue . AIM To determine the efficacy of bronchodilators in the treatment of bronchiolitis . METHOD All children less than 2 years old with bronchiolitis were r and omly assigned to receive nebulisations of Salbutamol , Ipratropium bromide or normal saline . A fourth group given only humidified oxygen without nebulisation were used as a control . RESULTS Data were obtained for 120 patients . Fifty-one ( 42 % ) had respiratory syncytial virus ( RSV ) isolated from their nasopharyngeal aspirates . The demographic characteristics of the 4 groups were similar . There was no significant difference between the groups in terms of severity score , number of nebulisations required in the nebulised groups and the outcome as measured by the length of hospitalisation . CONCLUSION The use of bronchodilators did not alter the course of the disease and is therefore not effective in the treatment of bronchiolitis To test whether nebulized salbutamol ( albuterol ) is safe and efficacious for the treatment of young children with acute bronchiolitis , we enrolled 83 children ( median age 6 months , range 1 to 21 months ) in a r and omized , double-blind clinical trial . Participants received two treatments at 30-minute intervals of either nebulized salbutamol ( 0.10 mg/kg in 2 ml 0.9 % saline solution ) or a similar volume of 0.9 % saline solution placebo . Outcome measures were the respiratory rate , pulse oximetry , and a clinical score based on the degree of wheezing and retractions . Patients in the salbutamol arm had significantly greater improvement in clinical scores after the initial treatment ( p = 0.04 ) . There was no difference between the groups in oxygen saturation ( p = 0.74 ) ; patients treated with salbutamol had a small increase in heart rate after two treatments ( 159 + /- 16 vs 151 + /- 16 ; p = 0.03 ) . We conclude that salbutamol is safe and effective for the initial treatment of young children with acute bronchiolitis BACKGROUND The treatment of infants with bronchiolitis is largely supportive . The role of bronchodilators is controversial . Most studies of the use of bronchodilators have enrolled small numbers of subjects and have examined only short-term outcomes , such as clinical scores . METHODS We conducted a r and omized , double-blind , controlled trial comparing nebulized single-isomer epinephrine with placebo in 194 infants admitted to four hospitals in Queens-l and , Australia , with a clinical diagnosis of bronchiolitis . Three 4-ml doses of 1 percent nebulized epinephrine or three 4-ml doses of normal saline were administered at four-hour intervals after hospital admission . Observations were made at admission and just before , 30 minutes after , and 60 minutes after each dose . The primary outcome measures were the length of the hospital stay and the time until the infant was ready for discharge . The secondary outcome measures were the degree of change in the respiratory rate , the heart rate , and the respiratory-effort score and the time that supplemental oxygen was required . RESULTS There were no significant overall differences between the groups in the length of the hospital stay ( P=0.16 ) or the time until the infant was ready for discharge ( P=0.86 ) . Among infants who required supplemental oxygen and intravenous fluids , the time until the infant was ready for discharge was significantly longer in the epinephrine group than in the placebo group ( P=0.02 ) . The need for supplemental oxygen at admission had the greatest influence on the score for severity of illness and strongly predicted the length of the hospital stay and the time until the infant was ready for discharge ( P<0.001 ) . There were no significant changes in the respiratory rate , blood pressure , or respiratory-effort scores from before each treatment to after each treatment . The heart rate was significantly increased after each treatment with epinephrine ( P=0.02 to P<0.001 ) . CONCLUSIONS The use of nebulized epinephrine did not significantly reduce the length of the hospital stay or the time until the infant was ready for discharge among infants admitted to the hospital with bronchiolitis OBJECTIVE To describe differences in patients hospitalized with respiratory syncytial virus ( RSV ) lower respiratory tract infection ( LRI ) at nine Canadian tertiary care hospitals . In addition , this study describes the variation in use of drug and other interventions . METHODS Data on patients hospitalized with RSV LRI and their outcomes were prospect ively collected . Demographic data were obtained on enrollment by center study nurses . Data recorded daily included clinical assessment , oxygen saturation determination , and interventions ( bronchodilators , steroids , ribavirin , antibiotics , intensive care , and mechanical ventilation ) received during the day . Patients were divided into those with underlying diseases including congenital heart disease , chronic lung disease , immunodeficiency , or multiple congenital anomalies and those who were previously healthy . Mean RSV-associated length of stay and the proportion of patients receiving each intervention in each group were determined by hospital . RESULTS A total of 1516 patients were enrolled at nine hospitals during January 1 to June 30 , 1993 , and January 1 to April 30 , 1994 . Significant differences were observed among hospitals in the proportion of patients with underlying disease , postnatal age less than 6 weeks , hypoxia , and pulmonary infiltrate on chest radiograph . The mean length of stay varied among hospitals from 8.6 to 11.8 days and 4.6 to 6.7 days in compromised and previously healthy patients , respectively . Except for receipt of bronchodilators , compromised patients were significantly more likely to receive interventions than previously healthy patients . There was variation among hospitals in receipt of most interventions in compromised and previously healthy patients . This variation was statistically significant for previously healthy patients but not statistically significant in those with underlying disease , because the numbers of patients in the latter group were much smaller . The magnitude of the variation for each intervention , however , was not different between those with underlying disease compared with previously healthy patients . CONCLUSION Differences exist among tertiary pediatric hospitals in the nature of the patients admitted with RSV LRI . Variation occurred in the use of five interventions among the hospitals , regardless of whether the patient had underlying illness or was previously healthy . Given their current widespread use , high cost , and potential side effects , r and omized clinical trials are needed to determine the efficacy of different drug treatments used to treat infants hospitalized with RSV Use of both l-epinephrine and racemic epinephrine ( adrenaline ) has improved clinical symptoms and composite respiratory scores in acute bronchiolitis . The objective of this r and omized double-blind placebo-controlled study was to assess whether there was sufficient improvement in clinical state to reduce hospital admissions . Seventy-five infants aged 1 month to 1 year with a clinical diagnosis of acute bronchiolitis were treated with either 2 ml of 1:1000 nebulized adrenaline or 2 ml of nebulized normal saline administered after baseline assessment and 30 min later . Clinical respiratory parameters were recorded at 15-min intervals for a period of 2 h following the baseline assessment . Admission to hospital was the primary end-point and changes in respiratory parameters were secondary end-points . Fifty percent ( 19/38 ) of infants treated with adrenaline were discharged home compared with 38 percent ( 14/37 ) of those treated with saline . This 12 percent reduction in rate of admission is not statistically significant ( 95 % CI of difference : -10 % to 35 % ) . There was no difference between treated and placebo groups in respiratory rate , oxygen saturation , heart rate or a composite respiratory distress score at 30 , 60 or 120 min post-treatment . In this study , nebulized epinephrine did not confer a significant advantage over nebulized saline in the emergency room treatment of acute bronchiolitis As the efficacy of combined nebulized salbutamol & ipratropium bromide as well as L-adrenaline to treat acute bronchiolitis is not well studied among the Bangladeshi infants , this study was carried out to see their efficacy in acute bronchiolitis and to compare their effectiveness . This r and omized clinical trial was done among 60 children aged less than 02 years , admitted in the department of Pediatrics , Dhaka Medical College Hospital , during January through December 2005 with acute bronchiolitis . After a quick initial assessment , nebulization were done twice at 6 hours interval with the mentioned drugs , group wise ( one group with salbutamol plus ipratropium bromide and other group with L-adrenaline alone ) and the outcomes were assessed after 30 minutes of each nebulization in respect to oxygen saturation and clinical modified respiratory distress assessment instrument ( MRDAI ) scores . The results were analyzed by using SPSS version 10.0 and at a p value of < /=0.05 , the test was considered significant . The clinical characteristics were similar in both the groups . After 02 doses of nebulizations by the studied drugs , a significant improvement in respect to oxygen saturation and MRDAI score were noted among the children in both the groups , compared to their baseline status ( p=0.000 ) . However , L-adrenaline showed more efficacy ( MRDAI , p=0.021 ; SaO2 , p=0.034 ) than combined Salbutamol & Ipratropium bromide . Both L-adrenaline and combined salbutamol & ipratropium bromide were found effective in acute bronchiolitis but L-adrenaline was found more effective . A large multi-centre clinical trial is recommended Using a double-blind , placebo-controlled protocol , we evaluated the efficacy of nebulized albuterol in the treatment of infants aged 0 to 24 months who presented to the emergency department with wheezing . Twenty-five infants were r and omly assigned to receive two identical treatments of either nebulized albuterol ( 0.15 mg/kg ) or placebo ( saline ) . Assessment after each treatment included a wheeze and retraction score , respiratory and heart rates , and pulse oximetry . After two treatments , there was a significant improvement in the wheeze scores ( P less than 0.05 ) and total scores ( P less than 0.05 ) of the albuterol group compared with the placebo group . After one treatment , there was an initial decrease in oxygen saturation in the albuterol group , which improved after the second treatment . There were no significant differences between the two groups in heart rate or respiratory rate . This study supports the use of nebulized albuterol in the treatment of wheezing infants in the emergency department The objective of this study was to investigate the effectivenesses of nebulized salbutamol , epinephrin , 3 % saline , and normal saline ( 0.9 % NaCl ) in the treatment of mildly affected infants with acute bronchiolitis . We enrolled 186 children ( mean age 9.5 + /- 5.3 months , range 1.5 - 24 months , 65.1 % male ) with a first episode of wheezing diagnosed as mild bronchiolitis in emergency department . Patients were r and omized in a double-blind fashion to receive 4 ml dose either of 1.5 mg epinephrine plus normal saline ( group 1 ; n = 38 ) or 1.5 mg epinephrine plus 3 % saline ( group 2 ; n = 39 ) or 2.5 mg salbutamol plus normal saline ( group 3 ; n = 36 ) or 2.5 mg salbutamol plus 3 % saline ( group 4 ; n = 36 ) or normal saline alone ( group 5 ; n = 37 ) at 0 and 30 min . Thus , all treatment modalities included high amount of NaCl ( 72 - 240 mg ) . Clinical score , oxygen saturation and heart rate were assessed at 0 , 30 , 60 , and 120 min . After discharge , patients were reassessed by telephone contact at 48 hr and 6 months . The baseline characteristics were similar in all groups ( P > 0.05 ) . The outcome of patients at 120 min was found significantly better than the baseline values ( P < 0.05 ) . There were no significant differences between the outcome variables of the groups ( P > 0.05 ) . No adverse effects attributable to nebulized therapy were seen . In conclusion , all treatment modalities used in this study , including a total of 8 ml normal saline inhalation at 30-min interval showed clinical ly significant and swift improvement in mildly affected ambulatory infants with acute bronchiolitis We enrolled 30 infants ( median age 3 months , range 1 - 12 months ) , hospitalized for bronchiolitis in a r and omized double-blind trial , to examine the efficacy and safety of nebulized epinephrine compared to salbutamol . Once admitted , patients were treated with either nebulized 0.5 mg of an 0.1 % epinephrine solution ( 0.5 mL in 3.5 mL normal saline ( NS ) ) or 2.5 mg nebulized salbutamol ( 0.5 mL in 3.5 mL NS ) . They were evaluated daily before and after nebulization until discharge . The outcome measures used were : baseline clinical score ( based on respiratory rate , subcostal retraction , presence of wheezing , and O2 requirement ) , change in clinical O2 score after nebulization , duration of O2 therapy , and duration of hospitalization . A significant improvement in the clinical score was noted on the first day of hospitalization in subjects receiving epinephrine ( P = 0.025 ) ; that change was not seen in those on salbutamol ( P = 0.6 ) . Nebulized epinephrine decreased the baseline clinical score faster than salbutamol ( P = 0.02 ) , though on the fourth study day there was no significant difference between the two scores . On the fourth and fifth days of study there were more patients hospitalized in the salbutamol group than in the epinephrine group ( P = 0.03 vs. P = 0.025 ) . No adverse effects were associated with nebulized therapy . We conclude that nebulized epinephrine is a more effective agent than salbutamol in the initial treatment of bronchiolitis and is equally safe Background : A wide range of drugs are commonly used to treat bronchiolitis , but evidence of their effectiveness is limited . Objectives : To investigate the efficacy of ipratropium bromide and salbutamol in the treatment of patients with moderate-severe bronchiolitis . Methods : Sixty-nine infants with moderate-severe bronchiolitis hospitalized at their first episode of wheezing or crepitations in the chest were enrolled in a prospect i ve , double-blind , placebo-controlled trial . Patients were r and omly assigned to receive nebulized salbutamol , ipratropium bromide or placebo . Main outcome measures were changes in oxygen saturation rates and clinical scores and duration of hospitalization . Results : In the bronchodilator groups , clinical scores were better compared to the placebo group at 30 min ( 8.4 ± 1.3 vs. 7.5 ± 0.8 , p < 0.05 ) . Bronchodilator groups had also significantly lower clinical scores ( 7.3 ± 1.2 vs. 5.9 ± 1.1 , p < 0.0001 , and 5.3 ± 1.4 vs. 4.5 ± 1.6 , p = 0.006 , respectively ) and higher oxygen saturation rates compared to the placebo group at 8 and 24 h ( 89.6 ± 2.4 vs. 94.3 ± 4.4 , and 92.2 ± 2.6 vs. 95.9 ±4.4 , respectively , p < 0.0001 ) . Improvement rates and duration of hospitalization were not statistically different among groups . Conclusions : Clinical scores and oxygen saturation levels improved more rapidly in the bronchodilator groups than in the placebo group up to 24 h , but these drugs did not have a sufficient effect to change the natural course of the disease Objective : To study patients with respiratory syncytial virus bronchiolitis in respiratory failure to make specific measurements reflecting airway resistance before and after treatment with commonly used agents . We hypothesized that racemic epinephrine would decrease airways resistance more effectively than levalbuterol , and levalbuterol would decrease airways resistance more effectively than racemic albuterol . Normal saline was used as a control . Design : Prospect i ve , r and omized , controlled , blinded study . Setting : Tertiary Pediatric Intensive Care Unit in a University affiliated hospital in the northeastern United States . Patients : Twenty-two patients with respiratory syncytial virus bronchiolitis and in respiratory failure were enrolled . All were intubated and ventilated in a volume control mode and se date d. Interventions : In a r and omized , blinded fashion patients were given four agents : norepinephrine , levalbuterol , racemic albuterol , and normal saline at 6 hr intervals . Measurements : As indicators of bronchodilation , peak inspiratory pressure and inspiratory respiratory system resistance were measured before and 20 mins after each agent was given . Thus , each patient acted as his/her own control . Main Results : There were small but statistically significant decreases in peak inspiratory pressure after racemic epinephrine treatment , levalbuterol , and racemic albuterol . There was no change in peak inspiratory pressure after inhaled normal saline . Inspiratory respiratory system resistance fell significantly after all treatments , including saline . Heart rate rose significantly after inhaled bronchodilator treatments ( p < 0.05 for all treatments ) . Conclusions : Similar statistically significant bronchodilation occurred after all three bronchodilators as indicated by a decrease in peak inspiratory pressure and respiratory system resistance , but these changes were small and probably clinical ly insignificant . However , side effects of bronchodilators , such as tachycardia , also occurred , and these may be clinical ly significant . Thus the benefit of bronchodilator treatment in these patients is small , does not differ among the drugs we studied and of question able value OBJECTIVES To determine the current management of bronchiolitis by five major New Zeal and hospitals and to identify areas for improvement . METHODS Lists of infants under 1 year of age admitted with bronchiolitis during 1998 were obtained from the casemix offices of the five largest New Zeal and hospitals with paediatric services . Hospital records from a r and om sample of these admissions were review ed . RESULTS Out of the 409 infants admitted overnight , 8 % had been born less than or=32 weeks gestation and 53 % were aged younger than 6 months . Overall , 59 % received oxygen , 21 % had nasogastric fluids , 22 % had intravenous fluids , 34 % were prescribed antibiotics , 42 % received bronchodilators and 60 % had a chest radiograph . Respiratory secretions were collected for viral studies from 58 % of infants and , in 59 % , respiratory syncytial virus was detected . Significant variations in management were detected between hospitals . The overall proportion of infants requiring oxygen , intravenous or nasogastric fluids ( 65 % ) was significantly higher than that found in a 1986 - 1988 Christchurch study where only 25 % received one or more of these interventions ( P < 0.001 ) . CONCLUSIONS Opportunities exist to rationalize bronchiolitis management in New Zeal and with potential cost savings , particularly by reducing the number of chest radiographs and prescribing of unnecessary antibiotics and bronchodilators The treatment of infants aged 1.5 - 11.0 months suffering from acute bronchiolitis with a combination of inhaled albuterol and systemic corticosteroids or inhaled albuterol and placebo was compared in 50 infants in a double blind study . The mean initial clinical score and the rate of improvement was similar in the two groups . The mean + /- SD hospital stay was 5.0 + /- 1.2 days for the steroid group and 5.2 + /- 1.7 days for the placebo group . Lung function was measured in 14 infants ( 7 from each group ) and showed evidence of increased lung volumes and severe airway obstruction in the acute stage ( the mean values for the steroid group were : TGV , 31 mL/kg ; SGaw , 0.104 L/s.cmH2O ; VmaxFRC , 12.9 mL/s/kg ; for the placebo group : TGV , 35 mL/kg ; SGaw , 0.104 L/s.cmH2O ; VmaxFRC , 8.5 mL/s/kg ) which had improved 2 - 4 weeks later ( steroid group : TGV , 25 mL/kg ; SGaw , 0.168 L/s.cmH2O ; VmaxFRC , 21.6 mL/s/kg ; -placebo group : TGV , 24 mL/kg , SGaw , 0.198 L/s.cmH2O , VmaxFRC , 17.5 mL/s/kg ) . There were no significant differences of thoracic gas volume , specific airway conductance , and forced expiratory flow at resting lung volume between the two groups , either in the acute or convalescent stages . We conclude that corticosteroids do not change the rate of clinical improvement in acute bronchiolitis , nor do they effect lung function 2 - 4 weeks later Nebulized epinephrine has been advocated as a treatment for airway obstruction in infants with bronchiolitis ; however , its effect on respiratory mechanics and gas exchange has been poorly documented to date . We performed a preinterventional and postinterventional study with primary outcome measures of mechanics ( measured by single-breath occlusion passive deflation ) and oxygenation and ventilation indices in order to measure the effects of nebulized epinephrine in infants requiring mechanical ventilation for RSV-positive bronchiolitis . A two-compartment model was used to describe respiratory mechanics in patients with nonlinear flow-volume curves . Nebulized epinephrine ( 0.5 mg/kg ) was administered to 15 patients ( median age , 0.19 yr ; weight , 4.4 kg ) . Resistance decreased significantly in slow and fast compartments in 87 and 70 % of patients , respectively . Median resistance in the slow compartment decreased from 0.427 to 0.198 cm H2O/ml/s ( p = 0.0015 ) and in the fast compartment from 0.167 to 0.116 cm H2O/ ml/s ( p = 0.018 ) . Compliance , oxygenation index , and ventilation index were not significantly changed after administration of epinephrine . We conclude that nebulized epinephrine substantially improves respiratory system resistance but not oxygenation or ventilation indices . This may be because of the effects of epinephrine on oxygen consumption or ventilation-perfusion matching The response of bronchiolitis to bronchodilator drugs is controversial . The present study was design ed to evaluate the efficacy of oral or metered dose inhaler ( MDI ) salbutamol using a coffee cup as a spacer device in bronchiolitis . In the trial , 31 hospitalized patients between 6 and 24 months of age , who exhibited the first episode of acute bronchiolitis without any other predisposing illness such as cystic fibrosis , congenital heart disease etc . , were r and omly assigned to receive oral salbutamol ( n = 11 , 0.1 mg/kg per dose , four times a day ) , or MDI salbutamol ( n = 12 , 200 micrograms per dose , every 3 h ) or formed the control group without any bronchodilator therapy ( n = 8) . All of the patients were given supplemental oxygen as needed and adequate hydration was maintained . The patients were evaluated with clinical symptom scores . There were no differences in the beneficial or side effects of salbutamol , or the number of days in hospital between the treatment groups and the control group . It was concluded that there is no beneficial effect in using bronchodilators in infants with bronchiolitis . Supplemental oxygen and maintenance of normal hydration may be adequate The effect of inhaled nebulised racemic adrenaline upon symptoms of acute bronchiolitis was investigated in 29 infants and toddlers aged 2 - 17.5 months by transcutaneous oxygen tension ( TcPO2 ) , oxygen saturation , transcutaneous carbon dioxide tension ( TcPCO2 ) , and clinical evaluation in a double blind placebo controlled study . Clinical score and TcPO2 improved significantly at 30 , 45 , and 60 minutes after inhalation of racemic adrenaline , with an increase in TcPO2 > or = 0.5 kPa in 72 % of the children < 1 year of age . No significant improvement was observed after inhalation of placebo . No significant changes in heart rate or TcPCO2 were observed from before to after inhalation , but a small increase in mean systolic blood pressure was observed immediately and 45 minutes after racemic adrenaline inhalation . This study demonstrates that treatment with nebulised racemic adrenaline improved oxygenation and clinical signs in hospitalised children aged less than 18 months with bronchiolitis OBJECTIVE Recent studies have demonstrated that a single intramuscular injection of dexamethasone ( 0.6 mg/kg ) shortens the duration and severity of illness in hospitalized patients with acute viral laryngotracheitis ( croup ) . Our objective was to determine if dexamethasone has a role in the outpatient management of patients with acute viral croup of moderate severity . METHODS Patients , 6 months to 5 years of age , who came to the emergency department ( ED ) with acute viral croup , a croup score of at least 2 ( range 0 to 17 ) , and a disposition of discharge were r and omized in a double-blind fashion to receive a single intramuscular injection of dexamethasone , 0.6 mg/kg , or an equal volume of normal saline before discharge from the ED . Patients were excluded if they had any structural abnormalities , had received any steroids in the preceding 24 hours , or if they required beta-agonist therapy , more than one racemic epinephrine treatment , or hospitalization . Patients were followed up by telephone 24 hours and 7 to 10 days after discharge to determine whether additional medical attention was sought for perceived lack of improvement or worsening of symptoms . Secondary outcome included the parents ' perception of how the child was doing at 24 hours , based on a 4-point ordinal scale : worse ( 1 ) , same ( 2 ) , improved ( 3 ) , symptoms resolved ( 4 ) , and the number of days it took for complete recovery . RESULTS Of the 38 patients comprising the study group , 19 received dexamethasone . The median age was 19 months ( range 6 to 66 months ) , and median pretreatment croup score was 3 ( range 2 to 5 ) for both groups . The number of patients requiring racemic epinephrine was similar in both groups . Five patients sought additional medical attention within 48 hours . Four of the five patients had received placebo ( 21 % of the placebo group ) and one had received dexamethasone ( 5 % of the steroid group ) ( not statistically significant ) . At the 24-hour telephone follow-up , significantly more patients in the dexamethasone group had a score consistent with improvement compared with placebo ( 84 % vs 42 % , P = .003 ) . There was no difference in the number of days for symptoms to completely resolve between the two groups . CONCLUSION The use of dexamethasone in the outpatient management of viral croup was associated with a reduction in severity of illness within 24 hours after treatment . Patients with viral croup of moderate severity should be considered as c and i date s for the use of dexamethasone before discharge from the ED OBJECTIVE To determine whether oral albuterol is effective in reducing symptomatology of acute viral bronchiolitis in infants with mild-to-moderate illness . STUDY DESIGN In a r and omized , double-blind trial , previously well infants were r and omized upon discharge from the emergency department to receive either albuterol ( 0.1 mg/kg/dose ) three times per day or placebo three times per day for 7 days . Daily st and ardized telephone interviews were conducted for as long as 14 days . The primary outcome was the time to resolution of illness . Secondary outcomes included time to normal feeding , normal sleeping , quiet breathing , resolved cough , and coryza . RESULTS We studied 129 infants ( albuterol , n = 64 ; placebo , n = 65 ) . Baseline characteristics were similar between groups . The overall mean age was 5.3 months , 60 % were male , and 49 of 61 tested infants were positive for respiratory syncytial virus . The median ( 95 % confidence interval ) time to resolution of illness ( days ) was similar : albuterol , 9.0 ( 8 - 13 ) ; placebo , 8.0 ( 7 - 9 ) ; P = .3 ) ( log-rank test ) . There were no significant group differences in any secondary outcome . Health care revisit and admission rates were similar between groups . CONCLUSIONS No significant group differences in either primary or secondary outcomes in infants treated with oral albuterol versus placebo were found . The widespread use of oral albuterol in this patient group is not recommended In a double blind r and omised trial , we found no evidence that nebulised ipratropium bromide was of clinical benefit in acute bronchiolitis Inhaled sympathomimetic agents are often used in bronchiolitis with little objective evidence of benefit . The arterial oxygen saturation ( SaO2 ) reflects the adequacy of ventilation-perfusion balance . The aim of the current study was to determine the effect of inhaled salbutamol on SaO2 . In a r and omised , double blind study , 21 infants , admitted with bronchiolitis positive for respiratory syncytial virus , had continuous SaO2 measurements made before and after nebulised salbutamol or placebo . SaO2 was recorded over 30 minutes for a baseline , then during the 10 minutes of first nebulisation with either salbutamol or saline , then over 30 minutes after nebulisation , the 10 minutes of second nebulisation with the alternate regime , and another 30 minutes after this second nebulisation . Desaturation occurred after salbutamol and saline nebulisation . The fall in SaO2 with salbutamol was seen whether infants received it as the first or second nebulisation . The fall in SaO2 after saline was seen when given first , but not when given after salbutamol . The decrease in SaO2 was greater and more prolonged with salbutamol than with saline . Routine nebulised aerosol sympathomimetic treatment during acute bronchiolitis can not be recommended To evaluate the effect of nebulized budesonide on acute , young , wheezing patients , a total of 73 patients , aged below 24 months , who were hospitalized due to bronchiolitis were r and omly enrolled into this study according to age . They were divided into four groups and treated with four kinds of nebulized solutions . Group I consisted of 18 patients under 12 months old who were treated with budesonide ( 1 mg/2 ml ) diluted with 2 ml isotonic sodium chloride . Group II consisted of 18 patients under 12 months old who were treated with 4 ml isotonic sodium chloride . Group III included 16 patients between 12 and 24 months old who were treated with terbutaline ( 5 mg/2 ml ) diluted with 2 ml isotonic sodium chloride . Group IV included 21 patients between 12 and 24 months old who were treated with budesonide ( 1 mg/2 ml ) and terbutaline ( 5 mg/2 ml ) . Clinical data on respiratory rate , wheezing score , cyanosis score and accessory respiratory muscle utilization score were recorded in all patients before and after treatment throughout the entire hospitalization . The results of this study showed no benefits from nebulized budesonide in infants with bronchiolitis either younger than 12 months old or between 12 and 24 months of age . The duration of admission also showed no significant differences among the groups BACKGROUND Salbutamol is the st and ard recommendation in bronchial asthma . However , the use of bronchodilators in wheeze associated respiratory infections including bronchiolitis continues to be controversial . The aim of this study was to compare the efficacy of nebulised salbutamol versus epinephrine in ' first time ' wheezy children using clinical parameters and airway resistance . METHODS Sixty children between two months to 60 months were recruited , 30 in each treatment group . Children received periodic ( 0 , 20 , 40 minutes ) doses of either salbutamol ( 0.15mg/kg with 3ml saline subject to a minimum of 2.5 mg ) or laevo- epinephrine ( 1:1000 , 0.5ml/kg subject to a max of 2.5ml with 3ml saline ) via nebuliser along with oxygen . Changes in heart rate ( HR ) , oxygen saturation ( SpO2 ) , respiratory rate ( RR ) and respiratory distress assessment instrument ( RDAI ) were assessed along with measurement of airway resistance using interrupter method ( H and held spirometer-Microloop with MicroRint module ) . RESULT The respiratory status was better in the epinephrine group with significant improvement in RR , RDAI score , SpO2 and fall of airway resistance . There were no significant side effects noted in either group . CONCLUSION Nebulised epinephrine is a useful and safe drug for wheezy children and is superior to salbutamol . This needs validation by large multicentric r and omized blinded studies OBJECTIVE To determine if nebulized epinephrine is more efficacious than nebulized albuterol in the emergency department ( ED ) treatment of moderately ill infants with bronchiolitis . METHODS Sixty-six patients between 0 and 12 months of age with new-onset wheezing , an antecedent upper respiratory tract infection , and a clinical score ( Respiratory Distress Assessment Instrument ) of 8 to 15 were r and omized in a double-blind fashion to receive either 0.9 mg/kg of nebulized 2.25 % racemic epinephrine ( n = 34 ) or 0.15 mg/kg of nebulized 0.5 % albuterol sulfate ( n = 32 ) at 0 , 30 , and 60 minutes . MAIN OUTCOME MEASURES Primary outcome measures were clinical score and respiratory rate . Secondary outcome measures were room air oxygen saturation , elapsed time to meeting clinical criteria for ED discharge , hospitalization rate , and proportion of patients relapsed within 72 hours of ED discharge ( relapse rate ) . RESULTS Both treatment groups experienced a similar pattern of change in mean clinical score , respiratory rate , and room air saturation over time . There were no significant differences between the groups by these same measures at any time . The median time at which infants were well enough for ED discharge was 90 minutes in the epinephrine-treated group vs 120 minutes in the albuterol-treated group ( P = .01 ) . Sixteen infants ( 47.1 % ) in the epinephrine-treated group were hospitalized compared with 12 infants ( 37.5 % ) in the albuterol-treated group ( relative risk , 1.25 ; 95 % confidence interval , 0.71 - 2.22 ) . Relapse rate was 18.8 % ( 3/16 ) in the epinephrine-treated group and 42.1 % ( 8/19 ) in the albuterol-treated group ( relative risk , 0.45 ; 95 % confidence interval , 0.14 - 1.41 ) . Adverse effects occurred infrequently . CONCLUSIONS Although the patients treated with epinephrine were judged well enough for ED discharge significantly earlier than the patients treated with albuterol , epinephrine was not found to be more efficacious than albuterol in treating moderately ill infants with bronchiolitis Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma . Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone , the following study was undertaken . In this double-blind , placebo-controlled trial , 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were r and omly assigned to receive either nebulized albuterol ( 0.15 mg/kg per dose ) and ipratropium bromide ( 250 micrograms per dose ) ( group A , n = 36 ) or nebulized albuterol and normal saline ( placebo ) ( group B , n = 33 ) for two doses , 1 hour apart . The two groups were comparable at baseline . Both therapies result ed in clinical ly significant improvement . However , the addition of ipratropium result ed in no additional benefit with respect to decrease in the respiratory rate ( mean decreases 10.6/min vs decreases 8.6/min , P = .86 ) , accessory muscle score ( range 0 through 3 ) ( decreases 0.92 vs decreases 0.82 , z = -0.44 ) , wheeze score ( range 0 through 3 ) ( decreases 0.94 vs 0.85 , z = -0.20 ) , oxygen saturation ( increases 0.25 % vs increases -0.33 % , P = .86 ) , or hospitalization rate ( 17 vs 10 ) . The number of " nonresponders " and " clear responders " was also very similar in both groups . No toxicity was noted . The increase in heart rate was mild and similar in both groups ( increases 6.7 vs increases 11.1 ) . The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90 % . ( ABSTRACT TRUNCATED AT 250 WORDS Objectives . To determine whether the use of albuterol by nebulization enhances physiologic or clinical recovery in hospitalized infants with moderate bronchiolitis . Methods . This prospect i ve , double-blind , placebo-controlled , r and omized clinical trial was performed from December 1995 to March 1996 . A total of 52 patients < 24 months of age with a diagnosis of moderately severe , acute viral bronchiolitis were enrolled and assigned to receive nebulized albuterol or normal saline placebo for 72 hours under a st and ardized protocol . Primary outcome measures included improvement in oxygen saturation ( Sao 2 ) during hospitalization and survival analysis to assess the time required to reach preestablished discharge criteria on three measures : Sao 2 , accessory muscle use , and wheezing . An additional secondary outcome measure was actual length of hospital stay . Adverse outcomes also were compared between treatment groups . Results . There was no significant difference in mean Sao 2 between albuterol and placebo at baseline , 24 hours , or maximum Sao 2 achieved during hospitalization . Both groups showed significant improvement in oxygen saturation over time , but there was no significant difference in improvement between the two groups . The study had a power of 90 % to detect a difference in mean percentage point improvement of 2 % Sao 2 . There was no difference in time to reach discharge criteria as defined by Sao 2 , accessory muscle use , or wheezing . There was no difference in length of hospital stay or in the frequency of adverse outcomes . Conclusions . Nebulized albuterol therapy does not appear to enhance recovery or attenuate severity of illness in infants hospitalized with acute , moderate bronchiolitis , as evidence d by improvement in oxygen saturation , time to meet st and ardized discharge criteria , or length of hospital stay Wheezy infants , less than 6 months of age , were given either inhaled salbutamol or saline in a double-blind study . A significant change in maximal flow at functional residual capacity ( VmaxFRC ) was defined as being greater than twice the coefficient of variation of the baseline measurements . There was no difference in the infants ' response to saline or salbutamol . Wheezy infants , less than 6 months of age , do not have an increase in VmaxFRC following a single dose of inhaled salbutamol BACKGROUND The objective of this study was to determine the efficacy and safety of nebulized 3 % hypertonic saline solution and salbutamol in the treatment of mild to moderate bronchiolitis . METHODS In a r and omized controlled trial , 93 infants with mild to moderate bronchiolitis were divided into two groups . The infants received inhalation of 2.5 mg ( 0.5 mL ) salbutamol dissolved in either 4.0 mL normal ( 0.9 % ) saline ( control group , n= 43 ) or 4.0 mL hypertonic ( 3 % ) saline ( treatment group , n= 50 ) . The therapy was repeated three times daily until discharge . Cough , wheezing , pulmonary physical signs , and the length of hospital stay were recorded . RESULTS Wheezing remission time was 3.8 + or - 1.1 days in the control group and 2.7 + or - 0.9 days in the treatment group ( P < 0.01 ) . Cough remission time was 6.3 + or - 0.9 days in the control group and 5.3 + or - 0.8 days in the treatment group ( P < 0.01 ) . The moist crackles disappeared at 5.4 + or - 0.8 days in the treatment group versus 6.2 + or - 0.9 days in the control group ( P < 0.01 ) . Furthermore , the average length of hospital stay decreased from 7.4 + or - 1.5 days in the control group to 6.0 + or - 1.2 days in the treatment group ( P < 0.01 ) . No obvious adverse effects were observed . CONCLUSIONS Inhalation of nebulized 3 % hypertonic saline solution and salbutamol is a safe and effective therapy for patients with mild to moderate bronchiolitis A r and omised double blind trial was conducted to determine the efficacy of inhaled bronchodilators , salbutamol and ipratropium bromide , compared with placebo in the treatment of bronchiolitis . Patients , who were 2 months to 2 years of age and without underlying cardiac or pulmonary disease , received drug 1 ( salbutamol or saline placebo ) followed one hour later by drug 2 ( ipratropium bromide or placebo ) . Both agents were administered every four hours . The patients were allocated to one of four groups according to a factorial design . The four groups were similar in demographic characteristics , initial oxygenation , and clinical score . The change in oxygen saturation of recipients of both agents was significantly better than that of recipients of salbutamol alone or ipratropium bromide alone . This change , however , was not statistically different from that of the control group . No difference was observed in the clinical score or hospital duration . Inhaled bronchodilators did not improve the condition of hospitalised mild bronchiolitis The main purpose of this study was to evaluate four different forms of treatment in young infants admitted for acute wheezing ( AW ) . Seventy-nine infants less than one year of age were r and omly assigned to one of five groups . Group 1 received nebulized fenoterol plus ipratropium bromide , group 2 fenoterol , group 3 fenoterol plus steroids , and group 4 aminophylline , IV , plus steroids and oral fenoterol ; the control group , or group 5 , received nebulized normal saline solution . Clinical evaluation was done by means of a scoring system . The effectiveness of treatments was estimated by a score decrease in the first 24 hours , by the percentage of patients whose scores did not decrease during the same period , and by the number of days in the hospital . All infants had significantly decreased scores , except those in the control group ; the aminophylline group included a greater percentage of patients who did not abate their scores , and they stayed in the hospital for more days than those in the other groups . The fenoterol group had the shortest hospital stay . All four treatments produced objective clinical improvement in bronchial obstruction . However , the nebulized bronchodilator treatments were more effective than aminophylline IV in decreasing scores on the first day , and they result ed in shorter hospitalization There is significant controversy about the role of bronchodilator therapy for wheezing in infants . A double-blind , r and omized trial of subcutaneous epinephrine upsilon normal saline was conducted in children less than 24 months of age evaluated at Yale-New Haven Hospital . Respiratory assessment s using a newly developed Respiratory Distress Assessment Instrument were made at baseline and 15 minutes after each of two injections . Relief of respiratory distress was assessed using strict a priori criteria based on changes in respiratory rate , wheezing , and retractions as scored in the Respiratory Distress Assessment Instrument . Significantly more children improved their respiratory status with epinephrine ( nine of 16 ) than placebo ( one of 14 ) ( Fisher exact test , P = .0067 ) . Paired data in individuals receiving placebo and then epinephrine confirmed this ( Wilcoxon signed ranks test , P less than .01 ) . Sixty-three percent of patients less than 12 months and 92 % of those 12 to 24 months improved with epinephrine , as did seven of ten children with respiratory syncytial virus bronchiolitis . In many children , response to the initial epinephrine injection was not indicative of final response . Results of this study demonstrate the effectiveness of epinephrine in the treatment of acute wheezing in children less than 24 months of age Our objective was to determine if nebulized racemic epinephrine is more efficacious than nebulized albuterol or saline placebo in the treatment of bronchiolitis in the outpatient setting when dosing is equivalent in terms of beta-2 agonist potency . Sixty-five patients between ages 6 weeks and 24 months with a diagnosis of bronchiolitis , defined as first-time wheezing , upper respiratory symptoms and /or fever , and a Respiratory Distress Assessment Instrument score of at least 4 , were r and omized to receive 5 mg nebulized albuterol , 5 mg nebulized racemic epinephrine , or an equivalent volume of placebo at 0 , 30 , and 60 min . The primary outcome measure was need for hospital admission or home oxygen . Secondary outcome measures were changes in clinical scores and oxygen saturations . There were no significant statistical differences between groups in terms of need for hospital admission or outpatient management with home oxygen therapy . There were no differences between groups in terms of changes in clinical scores or oxygen saturations . Racemic epinephrine and albuterol at equivalent doses had no effect on the need for hospitalization or supplemental oxygen in bronchiolitis in the outpatient setting compared to nebulized saline placebo , though this study may have missed less dramatic clinical effects due to small sample size OBJECTIVE Asess the efficacy of nebulized salbutamol and dexamethasone compared with nebulized salbutamol , in patients with bronchiolitis . MATERIAL AND METHODS A blinded clinical trial was performed with 49 patients between 1 - 18 months diagnosed with bronchiolitis with three days or less of disease evolution . Participant 's parents signed an informed consent and patients did not receive prior medication . Patients were r and omly assigned to two groups : nebulized salbutamol or salbutamol plus dexamethasone , which they received every four hours during twenty-four hours . We measured heart and respiratory rate ; respiratory distress index , oxygen saturation , and Silverman And ersen scores . RESULTS No significant differences were found between groups for treatment response ; but the frequency of hospital release at 24 hrs was significant among groups ; 75 vs 96 % respectively ( p = 0.04 ) . CONCLUSIONS The administration of salbutamol plus dexamethasone is more effective in the control of respiratory distress in children with bronchiolitis compared with the use of salbutamol alone Thirty-two infants , aged 1 to 12 months , hospitalized with acute wheezing , were studied . They were r and omly divided into four treatment groups of eight patients each . The treatments were intramuscular dexamethasone or placebo ( double-blind ) , and salbutamol ( oral and inhaled ) , or none ( open ) , in all four possible combinations . The study was carried out as a r and omized block design with eight blocks of four infants each , matched by age and clinical score . Average daily improvements , as reflected by changes in the clinical score and length of hospital stay , was essentially the same for infants treated with placebo , salbutamol alone , and dexamethasone alone . However , combined salbutamol-dexamethasone treatment result ed in more than twice the rate of improvement of the other treatments . The difference was statistically highly significant ( P less than .01 ) . Furthermore , the response of this combined treatment was observed within 24 hours ; none of the ten infants in whom there was no significant improvement within 48 hours and neither of the two patients who developed respiratory failure received the combined salbutamol-dexamethasone treatment . A potentiating effect of corticosteroids on the beta-adrenergic responsiveness is a possible explanation for the advantage of this combined treatment in the management of acute wheezing in infancy OBJECTIVE ( i ) To assess the efficacy of bronchodilators in wheeze associated respiratory tract infection ( WRTI ) ; and ( ii ) To compare L-adrenaline with salbutamol in wheeze associated respiratory tract infection . DESIGN R and omized controlled trial . METHOD Ninety one children in age group of 2 months to 2 years with their 1st or 2nd episode of wheezing in association with fever and /or coryza were enrolled . Of these , 45 received L-adrenaline ( 0.1ml/kg/dose in 1 in 10,000 solution ) ( Group A ) and 46 received salbutamol ( 0.1mg/kg/dose ) ( Group B ) . Three doses of each drug were given , nebulized with oxygen at 20 minutes intervals . Respiratory rate , RDAI score , clinical status and pulse oxymetry was recorded before intervention and 10 minutes after each dose . Patients who showed significant relief were discharged after an observation period of three hours while those who did not were admitted . RESULTS Both L-adrenaline and salbutamol caused significant improvement in mean symptom score and oxygenation . However , the adrenaline group showed a significantly better improvement in the study parameters than the salbutamol group . More children in the adrenaline group could be sent home after the emergency treatment . CONCLUSION Adrenergic agonists both specific and non specific are beneficial in WRTI . Adrenaline is more effective than salbutamol and is thus a better , inexpensive and relatively safe alternative OBJECTIVE To compare nebulized racemic epinephrine delivered by 70 % helium and 30 % oxygen or 100 % oxygen followed by helium-oxygen inhalation therapy via high-flow nasal cannula ( HFNC ) vs oxygen inhalation via HFNC in the treatment of bronchiolitis . DESIGN Prospect i ve , r and omized , controlled , single-blind trial . SETTING This study was conducted from October 1 , 2004 , through May 31 , 2008 , in the emergency department of an urban , tertiary care children 's hospital . Patients Infants aged 2 to 12 months with a Modified Wood 's Clinical Asthma Score ( M-WCAS ) of 3 or higher . INTERVENTIONS Patients initially received nebulized albuterol treatment driven by 100 % oxygen . Patients were r and omized to the helium-oxygen or oxygen group and received nebulized racemic epinephrine via a face mask . After nebulization , humidified helium-oxygen or oxygen was delivered by HFNC . After 60 minutes of inhalation therapy , patients with an M-WCAS of 2 or higher received a second delivery of nebulized racemic epinephrine followed by helium-oxygen or oxygen delivered by HFNC . Main Outcome Measure Degree of improvement of M-WCAS for 240 minutes or until emergency department discharge . RESULTS Of 69 infants enrolled , 34 were r and omized to the helium-oxygen group and 35 to the oxygen group . The mean change in M-WCAS from baseline to 240 minutes or emergency department discharge was 1.84 for the helium-oxygen group compared with 0.31 for the oxygen group ( P < .001 ) . The mean M-WCAS was significantly improved for the helium-oxygen group compared with the oxygen group at 60 minutes ( P = .005 ) , 120 minutes ( P < .001 ) , 180 minutes ( P < .001 ) , and 240 minutes ( P < .001 ) . CONCLUSION Nebulized racemic epinephrine delivered by helium-oxygen followed by helium-oxygen inhalation therapy delivered by HFNC was associated with a greater degree of clinical improvement compared with that delivered by oxygen among infants with bronchiolitis . Trial Registration clinical trials.gov Identifier : NCT00116584 The efficacy of albuterol in the management of infants with first-time wheezing is controversial . This double-blind , placebo-controlled trial involved 128 Egyptian infants with first-time wheezing ( mean age 5.9 months ) who were r and omly separated into four equivalent therapy groups : nebulized albuterol , nebulized saline solution , orally administered albuterol , and orally administered placebo . The nebulized therapy groups received two treatments 30 minutes apart ; the oral therapy groups received one treatment . In addition , 41 infants with recurrent wheezing comprised an open-label control group who received two albuterol nebulizations . Chest radiographs , leukocyte counts , blood culture specimens , and nasal aspirate for viral antigen detection were obtained to confirm the clinical diagnosis of viral bronchiolitis . Respiratory and heart rates , clinical score , and oxygen saturation were recorded at baseline and 30 and 60 minutes after treatment . There was no difference among the four r and omized groups in any of the outcomes except for an increase in heart rate of 10 beats/min in the nebulized albuterol group compared with a decrease in heart rate of 8 beats/min in the oral placebo group . No differences in the need for additional treatment were observed . Nebulized albuterol significantly improved the clinical score and reduced the respiratory rate of those with recurrent wheezing relative to those in the r and omized groups . We conclude that nebulized albuterol is effective in the treatment of infants with recurrent wheezing , but there was no demonstrable efficacy of orally administered or nebulized albuterol in relieving the respiratory distress of infants with bronchiolitis in Egypt In a double-blind , placebo-controlled trial , 40 infants between 6 weeks and 24 months of age who had a first episode of wheezing and other signs and symptoms of bronchiolitis were r and omly assigned to receive either nebulized albuterol ( 0.15 mg/kg/dose ) or placebo ( saline solution ) for two administrations 1 hour apart . The albuterol therapy result ed in a significantly greater improvement in the accessory muscle score ( decreases 0.70 vs decreases 0.30 ; p = 0.03 ) , oxygen saturation ( increases 0.71 % vs decreases 0.47 % ; p = 0.01 ) after one dose , and in the accessory muscle score ( decreases 0.86 vs decreases 0.37 ; p = 0.02 ) , respiratory rate ( decreases 19.6 % vs decreases 8.0 % ; p = 0.016 ) , and oxygen saturation ( increases 0.76 % vs decreases 0.79 % ; p = 0.015 ) after two doses of the drug . The response to therapy was similar in infants younger and those older than 6 months of age . The heart rate rose slightly more in the albuterol group ( increases 7.76 from baseline ) versus the placebo group ( decreases 6.79 ) . There were no other side effects of the treatment . Of the 34 children from whom nasal specimens were obtained by swab for viral identification , 24 had positive test results ( 21 for respiratory syncytial virus , 1 for parainfluenza , 1 for paramyxovirus , and 1 for influenza A ) . We conclude that nebulized albuterol constitutes a safe and effective treatment of infants with bronchiolitis A r and omized clinical trial was conducted on young children with bronchiolitis admitted to hospital with moderate illness to determine the efficacy of the bronchodilators Salbutamol and ipratropium bromide , either as a single drug or in combination , given as a nebulized solution , compared with a normal saline placebo . Eighty-nine patients , aged from 23 days to 11 months , were r and omized into four groups , depending on administered drug or placebo , as follows : group 1 - -Salbutamol ( n = 20 ) ; group 2 - -ipratropium bromide ( n = 23 ) ; group 3 - -combined Salbutamol and Ipratropium bromide ( n = 24 ) ; group 4 - -normal saline ( n = 22 ) . The groups were identical with respect to age , sex , family history of atopy , respiratory syncytial virus ( RSV ) positivity and enrollment score . They were scored using the clinical parameters of wheezing , retractions and respiratory rate at enrollment , at 30 and 60 minutes after the first nebulization , and after 60 minutes following completion of subsequent nebulization at 6 , 12 , 24 and 36 hours . We did not find any significant difference in the rate of improvement and the final score ( p = 0.49 ) in the four groups . The same finding was also noted in children aged more than 3 months ( p = 0.35 ) and in those positive for RSV infection ( p = 0.18 ) . The lengths of hospitalization in the four groups were also similar ( p = 0.79 ) . It is concluded that there is no role for the nebulized bronchodilators Salbutamol and Ipratropium bromide , either as a single agent or in combination , compared with normal saline placebo in treating young children in hospital with bronchiolitis BACKGROUND The primary role of respiratory syncytial virus ( RSV ) in causing infant hospitalizations is well recognized , but the total burden of RSV infection among young children remains poorly defined . METHODS We conducted prospect i ve , population -based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties . We enrolled hospitalized children from 2000 through 2004 and children presenting as out patients in emergency departments and pediatric offices from 2002 through 2004 . RSV was detected by culture and reverse-transcriptase polymerase chain reaction . Clinical information was obtained from parents and medical records . We calculated population -based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits . RESULTS Among 5067 children enrolled in the study , 919 ( 18 % ) had RSV infections . Overall , RSV was associated with 20 % of hospitalizations , 18 % of emergency department visits , and 15 % of office visits for acute respiratory infections from November through April . Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age . Most of the children had no coexisting illnesses . Only prematurity and a young age were independent risk factors for hospitalization . Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments . Out patients had moderately severe RSV-associated illness , but few of the illnesses ( 3 % ) were diagnosed as being caused by RSV . CONCLUSIONS RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient setting s. Most children with RSV infection were previously healthy , suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection Objectives : Bronchiolitis is the most frequent reason for admission in infants . We set out to compare clinical practice guideline ( CPG ) recommendations and physician management of bronchiolitis at Paediatric Research in Emergency Departments International Collaborative ( PREDICT ) sites in Australia and New Zeal and as a baseline for prospect i ve trials . Methods : ( i ) Review of bronchiolitis CPGs from PREDICT sites . ( ii ) Survey of senior pediatric emergency physicians at PREDICT sites to determine management strategies in bronchiolitis . Results : All 11 PREDICT sites participated . Ten sites used a specific bronchiolitis CPG . & bgr;-agonists were not recommended unless the child was older or asthma was suspected . Eight sites did not and 2 sites only recommended corticosteroids for older infants in whom asthma was likely . For rehydration , 7 sites recommended intravenous ( IV ) fluids exclusively or in the acute phase , with 3 recommending nasogastric ( NG ) fluids in the recovery phase or for difficult vascular access . Two sites recommended NG fluids for moderate and IV fluids for severe bronchiolitis . Physician response rate was 78/83 ( 94 % ) . No medications were used for mild ( 94 % ) or moderate ( 83 % ) bronchiolitis . Inhaled & bgr;-agonists were used by 5 % for moderate and 18 % for severe bronchiolitis . Steroids were not used by any physicians for mild or moderate and was used by only 3 % for severe bronchiolitis . The preferred mode of rehydration was IV in 45 % , NG in 49 % , and either one depending on disease severity in 6 % . Conclusions : Management of bronchiolitis was similar across PREDICT sites . Practice is equally split between IV and NG rehydration . This reflects a lack of evidence which should be addressed through a multicenter comparative trial |
1,164 | 28,939,239 | We hypothesized that QoL is consistently better in patients treated with minimally invasive surgery than in those treated with a more traditional and invasive approach .
Although global health , social function , and emotional function improved more commonly after minimally invasive surgery compared with open surgery , physical function and role function , as well as symptoms including choking , dysphagia , eating problems , and trouble swallowing saliva , declined for both surgery types .
Cognitive function was equivocal across both groups . | Although esophageal cancer is rare in the United States , 5-year survival and quality of life ( QoL ) are poor following esophageal cancer surgery .
Although esophageal cancer has been surgically treated with esophagectomy through thoracotomy , an open procedure , minimally invasive surgical procedures have been recently introduced to decrease the risk of complications and improve QoL after surgery .
The current study is a systematic review of the published literature to assess differences in QoL after traditional ( open ) or minimally invasive esophagectomy . | Background The aims of this prospect i ve study were to analyze the predictors of postoperative sleep disturbance after esophagectomy for cancer and to identify patients at risk for postoperative hypnotic administration . Methods Sixty two consecutive patients who underwent cancer-related esophagectomy were enrolled in this study from May 2011 to February 2012 . Data about perioperative management , postoperative complications , ICU stay , and vasopressor , hypnotic , and painkiller administration were retrieved . The EORTC QLQ-C30 was used and global quality of life ( QL2 item ) and sleep disturbance ( SL item ) were the primary endpoints . Univariate and multivariate analyses were performed . Results Postoperative request of hypnotics independently predicted bad quality of life outcome . Sleep disturbance after esophagectomy was independently predicted by the duration of dopamine infusion in the ICU and the daily request of benzodiazepines . Even in this case , only sleep disturbance at diagnosis revealed to be an independent predictor of hypnotic administration need . ROC curve analysis showed that sleep disturbance at diagnosis was a good predictor of benzodiazepine request ( AUC = 73 % , P = 0.02 ) . Conclusions The use of vasopressors in the ICU affects sleep in the following postoperative period and the use of hypnotics is neither completely successful nor lacking in possible consequences . Sleep disturbance at diagnosis can successfully predict patients who can develop sleep disturbance during the postoperative period Background In patients with esophageal cancer , evidence for prognostic significance of preoperative quality of life ( QoL ) is limited , while the prognostic significance of postoperative QoL has not been investigated at all . Aim To determine whether preoperative and postoperative QoL measurements can predict survival independently from clinical and pathological factors , in patients with potentially curable esophageal adenocarcinoma . Methods A r and omized controlled trial was performed from 1994 to 2000 in two academic medical centres , comparing transthoracic and transhiatal esophagectomy . QoL question naires were sent before and 3 months after surgery ( Medical Outcome Study Short Form-20 and Rotterdam Symptom Checklist ) . Uni- and multivariate Cox regression analyses were used to examine firstly the prognostic value of preoperative QoL and several clinical factors , and secondly of postoperative QoL , several clinical factors , and pathological staging . Results Out of 220 r and omized patients , 199 participated in the QoL- study . In the multivariate preoperative model physical symptom scale ( p = 0.021 ) , tumor length ( p = 0.034 ) , and endosonographic T-stage ( p = 0.003 ) were predictive for overall survival . In the postoperative multivariate analysis , social functioning ( p = 0.035 ) , pain ( p = 0.026 ) , and activity level ( p = 0.037 ) predicted survival , besides pathological T-stage ( p < 0.001 ) and N-stage ( p < 0.001 ) . Conclusion In the present paper the first large consecutive series of potentially curable esophageal cancer patients is presented in whom prospect ively collected QoL data before and after potentially curative surgical resection were used to predict survival . Both preoperative ( physical symptoms ) and postoperative ( social functioning , pain , and activity level ) QoL subscales are independent predictors of survival in potentially curable patients with esophageal adenocarcinoma Background For patients undergoing oncologic surgery , the quality of life ( QoL ) is generally accepted as an important outcome parameter in addition to long-term survival , mortality , and complication rates . Our study focused on outcome in terms of QoL in patients with esophageal cancer , comparing the sites of anastomosis ( cervical versus thoracic anastomosis ) . Methods In a prospect i ve longitudinal single-center study from 1998 to 2005 , 105 patients underwent surgery for esophageal cancer . To assess QoL the EORTC-QLQ-C-30 and a tumor-specific module were administered before surgery , at discharge , and three , six , 12 , and 24 months after surgery . Clinical data were collected prospect ively and follow-up was performed every six months . Results The histological type was squamous cell carcinoma in 51.4 % of the cases , adenocarcinoma in 41.9 % , and some other type in 6.7 % . There was no significant difference between cervical and thoracic anastomosis with regard to morbidity , mortality , and survival rates ( 30 % five-year survival rate ) , whereas tumor stage was a significant ( p < 0.001 ) prognostic factor . Most QoL scores dropped significantly below baseline in the early postoperative period . Even though they recovered slowly during the follow-up period , they never reached preoperative levels again . There was no statistically significant difference in any of the QoL scales between patients with a cervical or a thoracic anastomosis . Conclusions Esophageal resections are associated with significant deterioration of QoL , which persists during the follow-up period . The surgical technique and position of the esophagogastrostomy did not affect QoL deterioration Although several studies have reported the impact of oesophagectomy on health-related quality of life ( HRQOL ) , none has objective ly assessed its impact on physical fitness . This study aim ed to evaluate the impact of oesophagectomy on physical fitness and HRQOL in patients with oesophageal cancer . In this prospect i ve study , we investigated 30 consecutive patients with newly diagnosed resectable oesophageal cancer who were scheduled to receive either neoadjuvant chemotherapy followed by surgery or surgery alone . The primary end-points were change from baseline in two measures of physical fitness ( knee-extensor muscle strength and 6-min walking distance ) after oesophagectomy . The secondary end-point was change from baseline in HRQOL measured with the European Organization for the Research and Treatment of Cancer Quality of Life Core Question naire with 30 items ( EORTC QLQ-C30 ) . Physical fitness was significantly lower after oesophagectomy than before oesophagectomy ( P < 0.001 ) . With regard to HRQOL , there was a significant pre- to post-oesophagectomy change in most of the scales . In the multiple regression analysis , the change in 6-min walking distance was the only significant variable affecting the change in physical functional score on the EORTC QLQ-C30 ( P = 0.032 ) . In conclusion , oesophagectomy adversely affects physical fitness and HRQOL in patients with oesophageal cancer . Six-minute walking distance may be a good indicator of HRQOL shortly after oesophagectomy Objective : The aim of this study was to compare the 2-year functional performance and quality of life in patients with operable squamous cell carcinoma of the esophagus , who have received either surgery or definitive chemoradiation ( CRT ) . Summary Background Data : The functional outcomes and quality of life in patients receiving esophagectomy or definitive CRT is uncertain . Methods : Data were extracted from the data base of a prospect i ve r and omized controlled trial that included patients with resectable mid or lower thoracic esophageal cancers . The patients were r and omized to either st and ard esophagectomy or definitive CRT . Quality of life assessment s were performed using the EORTC QLQ-C30 and QLQ-OES24 modules . Other functional assessment s included pulmonary and eating functions . Results : From July 2000 to December 2004 , a total of 81 patients were enrolled into the study . No significant longitudinal changes were detected in the global health status in both groups upon available follow-up . Surgery was associated with worsened physical functioning and fatigue symptoms up to 6 months after treatment ( P < 0.001 and P = 0.021 , respectively ) and these scales improved at 2 years . In terms of pulmonary function , dyspnoic and coughing symptoms were significantly worsened 3 months after surgery ( P = 0.024 and P = 0.036 , respectively ) whereas symptoms in the CRT group progressively deteriorated over time . Concerning the eating function , both groups had improvements in dysphagia but there were frequent need for endoscopic intervention . This study has been registered with clinical trials.gov and the clinical trials.gov ID number is NCT01032967 . Conclusion : Neither surgery nor definitive CRT significantly impaired the global health status of patients . Surgery was associated with a short-term negative impact in some aspects of health related quality of life assessment s but these changes became insignificant 2 years after treatment . However , CRT was associated with progressive deteriorations in pulmonary function in the longer term PURPOSE To assess 3 years of quality of life in patients with esophageal cancer in a r and omized trial comparing limited transhiatal resection with extended transthoracic resection . PATIENTS AND METHODS Quality -of-life question naires were sent at baseline and at 5 weeks ; 3 , 6 , 9 , and 12 months ; and 1.5 , 2 , 2.5 , and 3 years after surgery . Physical and psychological symptoms , activity level , and global quality of life were assessed with the disease-specific Rotterdam Symptom Checklist . Generic quality of life was measured with the Medical Outcomes Study Short Form-20 . RESULTS A total of 199 patients participated . Physical symptoms and activity level declined after the operation and gradually returned toward baseline within the first year ( P < .01 ) . Psychological well-being consistently improved after baseline ( P < .01 ) , whereas global quality of life showed a small initial decline followed by continuous gradual improvement ( P < .01 ) . Quality of life stabilized in the second and third year . Three months after the operation , patients in the transhiatal esophagectomy group ( n = 96 ) reported fewer physical symptoms ( P = .01 ) and better activity levels ( P < .01 ) than patients in the transthoracic group ( n = 103 ) , but no differences were found at any other measurement point . For psychological symptoms and global quality of life , no differences were found at any follow-up measurement . A similar pattern was found for generic quality of life . CONCLUSION No lasting differences in quality of life of patients who underwent either transhiatal or transthoracic resection were found . Compared with baseline , quality of life declined after the operation but was restored within a year in both groups Purpose Improving survival after esophagectomy is an important issue in treating patients with esophageal cancer ( EC ) . In addition to st and ard hospitalization management , periodic assessment of quality -of-life ( QOL ) measures may be useful to detect disease progression from patients ’ subjective reports . Therefore , this prospect i ve longitudinal study was undertaken to identify prognostic factors for 3-year survival of EC patients after esophagectomy and to evaluate the impact of QOL measures on these prognostic factors . Methods Patients with EC ( n = 67 ) who had a complete tumor resection and were alive 6 months after esophagectomy were followed in this study for 3 years . Data were collected on patients ’ sociodemographics , cancer characteristics , adjuvant therapy , general QOL and EC-specific QOL ( before esophagectomy and 6 months afterward ) , cancer recurrence , and death . Patients ’ independent risk factors for 3-year survival were investigated by multivariate Cox regression analysis . Results Of the 67 participants with EC , 26 had late mortality , with a median survival for the whole cohort of 38.2 months ( 95 % CI 31.97–44.35 ) . Independent predictors of early death were early cancer recurrence ( within 6 months after surgery ) , poor cognitive function ( 95 % CI 1.020–1.041 ) , and worse dyspnea ( 95 % CI 1.007–1.034 ) . Conclusions The most predictive factor for early death in EC patients after esophagectomy was cancer recurrence within 6 months after surgery . However , QOL measures could be a tool to provide clinical information from patients ’ perspective suggesting cancer recurrence Health‐related quality of life ( HRQL ) outcomes are important in assessing new approaches to the treatment of cancer . Neoadjuvant therapy is being used increasingly before surgery in patients with localized oesophageal cancer . This prospect i ve non‐r and omized study evaluated HRQL in patients treated by preoperative chemotherapy and radiation therapy followed by surgery ( multimodal therapy ) or by surgery alone Objective : The aim of this study was to assess long-term health-related quality of life ( HRQL ) in patients after thoracoscopic and open esophagectomy . Summary of Background Data : Trials comparing minimally invasive with open transthoracic esophagectomy have shown improved short-term outcomes ; however , long-term HRQL data are lacking . This prospect i ve nonr and omized study compared HRQL and survival after thoracoscopically assisted McKeown esophagectomy ( TAMK ) and open transthoracic Ivor Lewis esophagectomy ( TTIL ) for esophageal or gastroesophageal junction ( GEJ ) cancer . Methods : Patients with esophageal or GEJ cancer selected for TAMK or TTIL completed baseline and follow-up HRQL assessment s for up to 24 months using the EORTC generic and disease-specific measures , QLQ-C30 and QLQ-OES18 . Baseline clinical variables were examined between the treatment groups and changes in mean HRQL scores over time estimated and tested using generalised estimating equations with propensity score ( generated by boosted regression ) adjustment . Results : Of the 487 patients , 377 underwent TAMK and 110 underwent TTIL . Most clinical variables were similar in the 2 groups ; however , there were significantly more patients with AJCC stage 3 disease who underwent TTIL than TAMK ( 54 % vs 32 % , P < 0.01 ) and this was reflected in the survival data . Mean symptom scores for pain were significantly higher in the TTIL group than in TAMK for 2 years postoperatively ( P = 0.036 ) . In addition , mean constipation scores were significantly higher for the TTIL group , with a 15-point difference in mean score at 3 months postoperatively ( P = 0.037 ) . Conclusions : This large comprehensive nonr and omized analysis of longitudinal HRQL shows that TTIL is associated with more pain and constipation than TAMK In a prospect i ve study of 69 patients being treated for oesophageal carcinoma , quality of life was assessed with the Rotterdam Symptom Checklist , a dysphagia score and an activities of daily living question naire . Significant correlations were found between the results of the Rotterdam Symptom Checklist , the dysphagia score and most aspects of the activities of daily living question naire . Eighteen patients underwent surgery , 43 radiotherapy or intubation , and eight a combination of surgery and other therapy . Patients undergoing surgery were significantly younger and had better scores in all parameters examined before operation , including significantly better scores in ‘ knowledge and communication ’ and ‘ mobility and fatigue ’ . The dysphagia score fell significantly after intervention both in patients undergoing surgery alone and in those receiving palliative therapy . The activities of daily living question naire showed significant improvements in two parameters in the surgical group ( ‘ self‐care ’ and ‘ eating and drinking ’ ) and in none of the parameters assessed in the palliation group in 16 weeks . Quality ‐of‐life assessment is useful in assessing quality of care and patient well‐being after the diagnosis and treatment of oesophageal carcinoma Background / Aim : To compare the quality of life ( QOL ) in patients undergoing transhiatal esophagectomy ( THE ) with or without chemotherapy , who were admitted to the Post Graduate Institute of Medical Education and Research , Ch and igarh and enrolled in the study , from July 2004 to October 2005 . Patients and Methods : Thirty patients of esophageal carcinoma by purposive sampling were r and omized into two groups i.e. , patients undergoing THE after chemotherapy and patients undergoing THE without chemotherapy . Two QOL question naires , one generic i.e. , EORTC-QLQ C-30 ( European Organization for Research and Treatment of Cancer ) and other esophageal cancer-specific i.e. , EORTC OES-18 were utilized to assess the QOL . Result : Physical functional scales were better in patients , who received neoadjuvant chemotherapy . The role and social aspects of functional scales deteriorated after completion of treatment in both groups . This was primarily due to the effect of surgery . However , they were better from an emotional and cognitive point of value after surgery and radiotherapy . Fourteen out of 30 patients experienced vomiting and diarrhea due to radiotherapy . Conclusion : THE in esophageal carcinoma improves global health scales and majority of symptom scales in all patients . QOL improvement in general was better in patients who were administered neoadjuvant chemotherapy along with surgery In recent years , the number of quality -of-life ( QOL ) studies on patients with esophageal cancer has increased ; however , the number of studies related to the effects of self-care education programs on QOL of these patients is scarce . This article reports on the effects of a self-care education program on QOL for patients with esophageal cancer in Babol , Iran . The quasi-experimental study had a convenience sample of 105 patients with esophageal cancer referred to oncology centers in Babol City . A quasi-r and om allocation technique was used to divide the sample into experimental ( n = 55 ) and control ( n = 50 ) groups . Appropriate instruments were used to measure QOL ( European Organization for Research and Treatment of Cancer Quality of Life Question naire-30 and Quality of Life Question naire-Oesophageal 18 ) . Question naires were completed by the respondents before and 3 months after implementing the educational program that consisted of group discussion , lectures , and pamphlets . There was no significant difference between QOL mean score of both groups before the intervention ; however , after implementing the educational program , the QOL significantly improved in the experimental group ( p = .001 ) , whereas QOL decreased in the controls . We conclude that self-care education programs have positive effects on the QOL of patients with esophageal cancer . Planning and implementing such self-care education programs , when patients are under treatment , can help them improve their QOL Background : Little is known regarding the short-term quality of life ( QoL ) and predictive factors for QoL after esophagectomy for cancer in Eastern countries . Objective : The aims of this study were to assess QoL and symptoms within 1 and 6 months after surgery for esophageal cancer ( EC ) and to identify factors predictive of QoL within 6 months after esophagectomy in Taiwan . Methods : A longitudinal , prospect i ve design was used , where convenience sample s of 99 patients who had undergone esophagectomy for cancer were recruited from 2 medical centers in northern Taiwan . All participants responded to a question naire with a QLQ-C30 ( Quality of Life Question naire – Cancer ) core and a QLQ-OES18 ( esophageal module of the European Organization for Research and Treatment [ EORTC ] QLQ-C30 ) module in structured interviews at baseline and 1 and 6 months after surgery . Results : The results showed significant decline in social function and global QoL ; fatigue , insomnia , eating problems , reflux , and dry mouth were major problems within 6 months . Body mass index , body weight loss before surgery , activity performance status , and anastomosis site showed no significant association with the function and symptom aspect of QoL. Surgical complications , advanced cancer , neoadjuvant therapy before surgery , and tumor location other than at the EC junction had significant deleterious effects on several aspects of QoL. Conclusions : This study describes the demographics of EC and short-term changes in QoL and also the predictive impact factor for QoL after surgery for EC . Implication s for Practice : Knowledge of risk factors for poor postoperative QoL would be useful for health providers in detecting and prioritizing problems and treatment options in a busy clinical site PURPOSE Because of the trade-off between the potentially negative quality -of-life ( QoL ) effects and uncertain favorable survival effect of neoadjuvant chemoradiotherapy ( CRT ) in patients with resectable esophageal cancer , we assessed heath-related QoL ( HRQoL ) for up to 1 year postoperatively in these patients treated with preoperative CRT with a non-platinum-based outpatient regimen followed by esophagectomy . METHODS AND MATERIAL S Patients undergoing neoadjuvant paclitaxel and carboplatin therapy concurrent with radiotherapy followed by surgery completed st and ardized HRQoL question naires before and after CRT and at regular times up to 1 year postoperatively . We analyzed differences in generic Qol core question naire [ QLQ-C30 ] and condition-specific ( esophageal site-specific [ OES-18 ] ) HRQoL scores over time by using a linear mixed-effects model . RESULTS Mean scores of most HRQoL scales deteriorated significantly during neoadjuvant CRT . The largest deterioration was observed for physical and role-functioning scales . All except two symptom scores worsened significantly . Postoperatively , most mean HRQoL scores improved until recovery to baseline level . Speed of improvement varied . Average taste score returned to baseline 3 months postoperatively , whereas it took 1 year for the average role-functioning score to restore . The emotional-functioning score showed a different pattern ; it was worst at baseline and increased over time during CRT and postoperatively . Dysphagia and pain scores worsened considerably during CRT , restored to baseline 3 months postoperatively , and were even significantly better 1 year postoperatively . CONCLUSIONS Preoperative CRT with paclitaxel and carboplatin for patients with resectable esophageal cancer had a considerable temporary negative effect on most aspects of HRQoL. Nonetheless , all HRQoL scores were restored or even improved 1 year postoperatively BACKGROUND AND OBJECTIVES Neoadjuvant chemoradiation ( nCRT ) followed by esophagectomy is a treatment with curative intent for resectable esophageal cancer . The aim of this study was to measure activities of daily living ( ADL ) and quality of life ( QoL ) , and to examine correlates of changes in ADL and QoL. METHODS A prospect i ve study was performed with three time points ( baseline , 1 week after the end of nCRT , 3-months post-surgery ) together with a cross-sectional post-treatment study . ADL was measured with the Amsterdam Linear Disability Score ( ALDS ) , and QoL with the EORTC QLQ-C30 and the OES-18 . Regression analysis was performed to identify factors associated with changes in ADL and QoL. RESULTS Seventy-six patients were included in the prospect i ve study , 79 in the cross-sectional study . After nCRT , ALDS decreased from 90 to 88 ( P < 0.01 ) and remained stable after surgery . Global QoL decreased from 75 to 61 ( P < 0.01 ) ; no significant changes were observed after surgery . Only timing of the measurement of ALDS was negatively associated with non-maximum ALDS ( n = 155 , based on both studies ) and QoL ( n = 76 ) ( P < 0.01 ) . CONCLUSIONS Patients who undergo nCRT plus surgery should be prepared to experience a short-term decline in ADL and QoL. The findings of this study can support patients and healthcare workers to guide expectations . J. Surg . Oncol . 2016;114:684 - 690 . © 2016 Wiley Periodicals , Although , minimally invasive oesophagectomy was first described in the early 1990s , there is a paucity of high quality data on the relative merits of minimally-invasive versus open oesophagectomy ( 1,2 ) . This is contrast to colorectal surgery where a number of r and omised control trials have conclusively demonstrated the efficacy of laparoscopic colorectal resections ( 3 ) . The reason for this disparity in evidence base lies in the relative rarity of oesophageal cancers combined with the variety of potential surgical approaches for resection oesophageal cancers ( e.g. , transhiatal , 2 stage , 3 stage and hybrid laparoscopic approaches ) . The paper by Beire et al. ( 4 ) is therefore very significant addition to the literature on the topic of minimally invasive oesophagectomies Esophageal cancer is one of the leading causes of cancer-related mortality and surgery is currently the main treatment modality for resectable esophageal cancer . To assess health-related quality of life ( HRQL ) of patients with esophageal squamous cell carcinoma ( ESCC ) following esophagectomy , 62 consecutive patients with middle ESCC were r and omly assigned into h and video-assisted thoracoscopic surgery ( HVATS ) ( n=33 ) and Ivor-Lewis surgery ( ILS ) ( n=29 ) groups . Quality of life question naires (QLQ)-C30 and QLQ-OES18 , published by the European Organization for Research and Treatment of Cancer , were used prior to treatment and at regular intervals until 6 months following surgery . The results of QLQ-C30 and QLQ-OES18 demonstrated that i ) patients with comorbidities and advanced tumor stage ( III-IV ) exhibited increased risk of poor HRQL , while their gender , age , body mass index and anastomosis location were not associated with HRQL at 6 months after surgery ; ii ) all the patients had worse functional , symptom and global scores within 6 months after surgery ; iii ) patients in the HVATS group had similar baseline functional and symptom scores to those of patients in the ILS group ; however , their functional and global scores were higher and their symptom scores were lower compared to those of patients in the ILS group ; iv ) the HRQL of patients in the HVATS group returned to preoperative levels within a shorter time period compared to patients in the ILS group . There were significant differences in global health , physical functioning , fatigue and pain scales between the two groups . In QLQ-OES18 , the dysphagia and gastroesophageal reflux scales were improved in both the HVATS and ILS groups , but no significant differences were observed between the two groups . In addition , the overall survival rate was similar in the two groups . Taken together , our findings indicated that HVATS is a safe procedure , associated with less disturbance to short-term HRQL compared to ILS . Therefore , it appears reasonable to select HVATS for patients with early-stage middle esophageal cancer Cancer of the esophagus is often diagnosed at a late stage and is related to severe morbidity and a low 5-year survival rate . Previous studies have reported low health-related quality of life and high suicide rates for these patients . The occurrence of psychiatric morbidity and thus the potential need for psychological support may vary over time after diagnosis . This has not been adequately studied in patients with newly diagnosed cancer of the esophagus or gastro-esophageal junction . The present study therefore aim ed to prospect ively evaluate the prevalence of psychiatric morbidity in 94 consecutive patients ( median age 66 , range 45 - 88 years ) with all stages of disease . Psychiatric morbidity was evaluated with the Hospital Anxiety and Depression Scale ( HADS ) question naire at inclusion and 1 , 2 , 3 , 6 and 12 months later . At inclusion , 42 % of the patients had HADS scores indicating possible or probable anxiety disorder and /or depression . At all follow-ups except at 3 months , proportions of patients with possible/probable anxiety disorder were significantly lower than at inclusion . Among patients with a duration of tumor-specific symptoms exceeding 6 months pre-diagnosis , larger proportions of patients with a possible/probable anxiety disorder were found at the 1- and 6-month follow ups . The prevalence of possible/probable depression was greater among patients treated with a palliative intent than among those with a curative intent at inclusion . Patients who died during the study period scored worse for depression compared to the survivors . Apart from this , the proportion of patients with possible/probable psychiatric morbidity ( anxiety and /or depression ) was relatively stable over time and was unrelated to patient characteristics or clinical background , including the treatment regime . In conclusion , psychiatric morbidity is common among esophageal cancer patients , both at inclusion and over time , regardless of the cancer therapy given . The findings stress the importance of monitoring the patients ' mental health and of offering adequate psychological care when needed Background The main outcome parameters in oesophageal surgery have traditionally been morbidity and mortality , but quality of life ( QL ) has become an important consideration in view of the severity and persistence of postoperative symptoms . The aim of this study was to analyse QL before and after oesophagectomy for oesophageal cancer and to explore possible association with patient ’s and disease characteristics . Patients and Methods One hundred twenty-six consecutive patients presenting with oesophageal cancer to the Oncological Surgery Unit of the Veneto Institute of Oncology between 2009 and 2011 were enrolled in this prospect i ve study . The patients were asked to answer three QL question naires ( the Italian versions of the QLQ-C30 , the QLQ-OES18 , and the IN-PATSAT32 modules developed by the European Organization for Research and Treatment of Cancer ) at the time of disease diagnosis , after neoadjuvant therapy , immediately after surgery and at 1 , 3 , 6 and 12 months postoperatively . Results Global quality of life ( QL2 item ) seemed to improve after neoadjuvant therapy but it dropped markedly after surgery . It then rose to a value in between the one registered after neoadjuvant therapy and the one at diagnosis . Emotional function and dysphagia were associated to QL2 at diagnosis . After neoadjuvant therapy , age , oesophageal stenosis , emotional function and dysphagia were associated to good quality of life at that stage . After surgery , pain was associated to quality of life at that stage . During the early follow-up phase ( 1–3 months after surgery ) , role function and postoperative urinary complications were associated to QL2 . In the long-term follow-up ( 6–12 months ) , adjuvant therapy , eating disorders and postoperative complications were associated to poor quality of life . Conclusions Postoperative complications are associated to long-term emotional and physical function impairment which can lead to a significantly impaired global quality of life . Postoperative pain relief plays a key role in achieving a good postoperative quality of life . Finally , HRQL after oesophagectomy seems to be a function of therapeutic efficacy rather than of the specific surgical procedure used OBJECTIVE We sought to determine the effect of neoadjuvant chemoradiotherapy followed by surgical intervention on health-related quality of life in patients with esophageal cancer . METHODS Health-related quality of life was evaluated in a prospect i ve phase II study of neoadjuvant chemoradiotherapy followed by esophagectomy in 52 patients with carcinoma of the esophagus . Esophagectomy was performed 6 weeks after completion of induction . Functional Assessment of Cancer Therapy-Esophageal scoring was performed before treatment , 7 weeks after initiation of neoadjuvant therapy , before resection , and at 1 , 3 , and 6 months and 1 year after resection . RESULTS Forty-three patients completed the entire treatment protocol . Functional Assessment of Cancer Therapy-Esophageal scores decreased significantly after chemoradiation at week 7 ( 120 vs 127 at baseline , P = .04 ) but returned to baseline levels before surgical intervention ( 127 ) . Similarly , scores decreased significantly after surgical intervention ( 115 at 1 month , P = .02 ) but returned to baseline levels by 3 months postoperatively ( 127 ) . At 1 year postoperatively , there was a statistically significant improvement in scores compared with those at baseline ( 139 , P = .003 ) . Functional Assessment of Cancer Therapy-Esophageal scores continued to increase over time for patients who were alive at least 1 year after the operation with or without disease but were observed to significantly decrease in those who died within 1 year after the operation ( P = .0001 ) . An increase in quality of life was associated with a significantly lower risk of death ( P = .04 ) . CONCLUSION Neoadjuvant therapy has a significant effect on health-related quality of life , but this is transient , with recovery to baseline within 5 to 7 weeks after completion of induction therapy . Health-related quality of life decreases again after surgical intervention but returns to baseline levels within 3 months BACKGROUND The aim of the study was to compare the longitudinal quality of life ( QoL ) between chemoradiation with or without surgery in patients with locally advanced squamous resectable esophageal cancer included in a r and omized multicenter phase III trial ( FFCD 9102 ) . MATERIAL S AND METHODS All patients with locally advanced resectable ( T3 - 4 N0 - 1 M0 ) epidermoid or gl and ular esophageal cancer ( n = 451 ) received induction chemoradiation . Responders ( n = 259 ) were r and omized between surgery ( arm A ) and continuation of chemoradiation ( arm B ) . The Spitzer QoL Index was scored ( 0 - 10 ) at inclusion and at each follow-up , every 3 months during 2 years . QoL at baseline and longitudinal changes were respectively compared with univariate ANOVA and mixed-model analysis of variance for repeated measurements . The time interval between the follow-up was assessed and the same analyses were performed among survivors with 2 years of follow-up . RESULTS The squamous histology was predominant in both arms . The mean QoL score decreased between baseline and the first follow-up and between the first and the second follow-ups . QoL scores at the first follow-up were comparatively worse in arm A than in arm B ( 7.52 versus 8.45 , P < 0.01 ) , whereas the longitudinal QoL study showed no difference between treatments ( adjusted P = 0.26 ) . Furthermore , the longitudinal QoL was not different ( adjusted P = 0.23 ) among survivors with 2 years of follow-up . CONCLUSIONS Among patients responding to induction chemoradiation , surgery and continuation of chemoradiation had the same impact on QoL in patients with locally advanced , resectable esophageal cancer although a significantly greater decrease in the Spitzer Index was observed in the postoperative period Objective : There are few prospect i ve data on the effects of prolonged intensive care unit stay on the quality of life and long-term survival of a homogeneous patient population . Therefore , the aims of this prospect i ve study were a ) to describe the quality of life in patients after having a transthoracic esophageal resection ; and b ) to analyze the influences of a prolonged intensive care unit stay on quality of life and survival in patients after esophageal cancer resection who survived to hospital discharge . Design : Prospect i ve study . Setting : Medical center . Patients : The study population consisted of 109 patients undergoing a transthoracic resection for adenocarcinoma of the middistal esophagus or gastric cardia between April 1994 and February 2000 . Interventions : None . Measurements and Main Results : A comparison was made between patients staying ≤5 days vs. ≥6 days in the intensive care unit and also ≤2 days vs. ≥14 days . Quality of life was assessed in all patients by mailed self-report question naires at baseline ( preoperatively ) , at 5 wks , and at 3 , 6 , 9 , 12 , 18 , 24 , 30 , and 36 months after surgery . Daily physical , emotional , and social functioning was assessed with the generic Medical Outcome Studies Short Form-20 . Disease-specific quality of life was measured by an adapted Rotterdam Symptom Check List . Quality of life data were gathered between July 1994 and March 2003 . Five of the 109 patients died in the hospital and were excluded from the analysis . All five of them were in the intensive care unit ≥6 days . Of the remaining 104 patients , 92 provided baseline scores . The data of the 92 patients were used for the quality of life analyses . For the clinicopathologic and survival analysis , the data of 104 hospital survivors were used . Patients spent a median of 5.5 days ( range 0–71 ) in the intensive care unit . The Medical Outcome Studies Short Form-20 and the Rotterdam Symptom Check List measurements showed no clear differences in long-term quality of life between patients after a short vs. a prolonged postoperative intensive care unit period . The median overall survival in all patients was 2.0 yrs ( range 0.1–8.0 ) . Median overall survival in patients staying in the intensive care unit ≤5 days was 1.9 yrs ( range 0.3–7.4 yrs ) vs. 2.7 yrs ( range 0.9–7.2 yrs ) in patients staying ≥6 days ( p = .9 , log-rank test ) . Median overall survival in patients staying in the intensive care unit ≤2 days was 1.7 yrs ( range 1.2–2.6 yrs ) vs. 2.0 yrs ( range 0.2–3.8 yrs ) in patients staying ≥14 days ( p = .74 , log-rank test ) . Conclusions : For patients who survived to hospital discharge after transthoracic esophagectomy , there was no difference in long-term quality of life or survival between those su bmi tted to the intensive care unit for a short period vs. a long period Purpose The authors evaluated the efficacy of extended radical ( three-field ) lymphadenectomy for esophageal cancer compared with less radical ( two-field ) lymphadenectomy . Study Subjects and Analytic Methods The mortality and morbidity rates , postoperative courses , and survival rates were compared between 63 patients who underwent three-field lymph node dissection and 65 who underwent two-field lymph node dissection at Kurume University Hospital from 1986 to 1991 . Long-term quality of life after surgery was compared between 37 patients who underwent three-field dissection and 35 who underwent two-field dissection from 1980 to 1991 . Results Three-field dissection result ed in better survival for patients with positive lymph node metastasis from a carcinoma in the upper thoracic or midthoracic esophagus compared with two-field dissection . The mortality rates , postoperative courses and quality of life were the same for both procedures . Conclusions Three-field dissection is preferred for upper thoracic or midthoracic esophageal cancer because of improved survival , acceptable mortality and morbidity rates , and good postoperative course and quality of life BACKGROUD AND OBJECTIVES Health-related quality of life ( HRQL ) is of great importance in cancer management . The aim was to identify factors that influence postoperative HRQL in esophageal carcinoma patients . METHODS A prospect i ve cohort study was conducted to enroll 196 patients with esophageal carcinoma from November 2012 to June 2013 . Sociademographic and clinicopathological parameters were recorded in detail . EORTC-QLQ C30 and ES18 were used to assess HRQL before surgery , at discharge , 1 and 6 months after discharge . Logistic regression models were used to identify factors independently influencing quality of life at 6 months after discharge . RESULTS HRQL dramatically decreased after esophagectomy , but restored within 6 months in the most scales . Multivariate logistic regression analysis showed that gender ( P = 0.002 ) and anastomotic stricture ( P = 0.001 ) were the independent predictors of poor global quality -of-life 6 months after discharge . Anastomotic stricture occurred in 22 patients ( 11.2 % ) , and their performance in social function ( P = 0.04 ) , problems with eating ( P = 0.006 ) , choking when swallowing ( P < 0.001 ) were significantly poorer at 6 months after discharge . There were not significant differences in global quality -of-life between patients with and without anastomotic leakage at three postoperative assessment s. CONCLUSIONS Postoperative HRQL is restored within 6 months after discharge . Occurrence of anastomotic stricture significantly decreases HRQL after esophagectomy |
1,165 | 25,609,236 | The definitions of healthy controls in studies of functional bowel diseases such as IBS are inconsistent . | BACKGROUND Case-control studies are vital for underst and ing the pathophysiology of gastrointestinal disease .
While the definition of disease is clear , the definition of healthy control is not .
This is particularly relevant for functional bowel diseases such as irritable bowel syndrome ( IBS ) .
In this study , a systematic review formed the basis for a prospect i ve study evaluating the effectiveness of commonly used techniques for defining healthy controls in IBS . | OBJECTIVES The aim of the study was to assess prevalence , incidence , recovery , and risk factors of irritable bowel syndrome according to different definitions in a large r and om population . DESIGN A 5 year follow-up study of a sex- and age-stratified r and om sample of 4581 Danes interviewed about abdominal symptoms . SETTING The Glostrup Population s Studies Unit at Glostrup County Hospital . MAIN OUTCOME MEASURES Prevalence , incidence , recovery , and the association of risk factors to irritable bowel syndrome ( IBS ) . The percentage of subjects common to the population s selected by the various definitions of IBS . RESULTS According to various definitions , the prevalence of IBS varied from 5 to 65 % and the incidence varied from 1 to 36 % . At the 5 year follow-up only 5 % of subjects with IBS were completely free of all symptoms . Psychological vulnerability and the experience of having problems were strongly associated with prevalence and incidence of IBS , whereas lifestyle factors only showed a very weak or no relationship to IBS . Population s defined as suffering from IBS according to the various definitions had less than 50 % of the subjects in common . CONCLUSIONS Irritable bowel syndrome is frequent but fluctuating in the general population . Psychological factors seem to be of greater aetiological importance to IBS than lifestyle factors . However , a generally accepted and precise definition is essential to make future studies comparable and to allow general conclusions to be drawn . Furthermore , it still needs to be verified whether the syndrome is a disease entity or just an acceptable , common life-condition Alosetron is a 5‐hydroxytryptamine‐3 receptor antagonist reducing symptoms in female patients with diarrhoea‐predominant irritable bowel syndrome , and is known to increase the colonic transit time Functional gastrointestinal disorders , including the irritable bowel syndrome , account for up to 40 % of referrals to gastroenterologists , but accurate data on the natural history of these disorders in the general population are lacking . Using a reliable and valid question naire , the authors estimated the onset and disappearance of symptoms consistent with functional gastrointestinal disorders . An age- and sex-stratified r and om sample of 1,021 eligible residents of Olmsted County , Minnesota , aged 30 - 64 years were initially mailed the question naire ; 82 % responded ( n = 835 ) . In a remailing to responders 12 - 20 months later , 83 % responded again ( n = 690 ) . The age- and sex-adjusted prevalence rates per 100 for irritable bowel syndrome , chronic constipation , chronic diarrhea , and frequent dyspepsia were 18.1 ( 95 % confidence interval ( CI ) 15.1 - 21.1 ) , 14.7 ( 95 % CI 11.9 - 17.4 ) , 7.3 ( 95 % CI 5.3 - 9.3 ) , and 14.1 ( 95 % CI 11.5 - 16.8 ) , respectively , on the second mailing . Symptoms were not significantly associated with nonresponse to the second mailing ; moreover , the estimated prevalence rates were not significantly different from the first mailing . Among the 582 subjects free of the irritable bowel syndrome on the first survey , 9 % developed symptoms during 795 person-years of follow-up , while 38 % of the 108 who initially had the irritable bowel syndrome did not meet the criteria after 146 person-years of follow-up . Similar onset and disappearance rates were observed for the other main symptom categories . While functional gastrointestinal symptoms are common in middle-aged persons and overall prevalence appears relatively stable over 12 - 20 months , substantial turnover is implied by the observed onset and disappearance rates ; several potential sources of bias do not seem to account for this variation Background Flatulence is a common symptom in patients with irritable bowel syndrome ( IBS ) . This may be due to production of hydrogen by intestinal flora . With the presence of methanogenic flora , 4 mol of hydrogen ( H2 ) are used with 1 mol of carbon dioxide ( CO2 ) to produce 1 mol of methane ( CH4 ) , a process greatly reducing the volume of gas in the colon . However , the prevalence of methanogenic flora has not yet been reported in healthy and IBS patients from North India . Therefore , this study was planned . Methods This study was conducted prospect ively and included 345 patients with irritable bowel syndrome ( fulfilling Rome II criteria ) and 254 age- and gender-matched apparently healthy controls . Each subject underwent a hydrogen breath test using 10 g lactulose after an overnight fast . An SC Microlyser from Quintron , USA , was used to measure methane and hydrogen at baseline and at every 30 min for 4 h. Subjects with fasting methane concentration < 10 p.p.m . were labeled as low methane producers ( LMPs ) and > 10 p.p.m . as predominant methane producers ( PMPs ) . Results The IBS and control groups included 66.78 % and 67.53 % men , respectively . Mean age in the two groups was 48.52 ± 30.54 years ( range 15–68 years ) and 45.67 ± 30.54 years ( range 15–78 years ) , respectively . Prevalence of predominant methanogenic flora in IBS and control groups was 14.5 % ( 50/345 ) and 34.6 % ( 88/254 ) , respectively ( P < 0.001 ) . Fifty-two out of 254 ( 20.6 % ) were PMPs and 36 out of 254 ( 14.0 % ) were LMPs in controls . In contrast to this , IBS patients had 17 out of 354 ( 4.9 % ) that were PMPs and 33 out of 345 ( 9.6 % ) that were LMPs . Conclusion Methanogenic flora was significantly lower in IBS patients from North India than in apparently healthy subjects . This may be one of the causes of flatulence in IBS patients & NA ; Visceral pain processing is abnormal in a majority of irritable bowel syndrome ( IBS ) patients . Aberrant endogenous nociceptive modulation and anticipation are possible underlying mechanisms investigated in the current study . Twelve IBS patients and 12 matched healthy controls underwent brain fMRI scanning during the following r and omised stimuli : sham and painful rectal distensions by barostat without and with simultaneous activation of endogenous descending nociceptive inhibition using ice water immersion of the foot for heterotopic stimulation . Heterotopic stimulation decreased rectal pain scores from 3.7 ± 0.2 to 3.1 ± 0.3 ( mean ± SE , scale 0–5 ) in controls ( p < 0.01 ) , but not significantly in IBS . Controls differed from IBS patients in showing significantly greater activation bilaterally in the anterior insula , SII and putamen during rectal stimulation alone compared to rectal plus heterotopic stimulation . Greater activation during rectal plus heterotopic versus rectal stimulation was seen bilaterally in SI and the right superior temporal gyrus in controls and in the right inferior lobule and bilaterally in the superior temporal gyrus in IBS . Rectal pain scores were similarly low during sham stimulation in both groups , but brain activation patterns differed . In conclusion , IBS patients showed dysfunctional endogenous inhibition of pain and concomitant aberrant activation of brain areas involved in pain processing and integration . Anticipation of rectal pain was associated with different brain activation patterns in IBS involving multiple interoceptive , homeostatic , associative and emotional areas , even though pain scores were similar during sham distension . The aberrant activation of endogenous pain inhibition appears to involve circuitry relating to anticipation as well as pain processing itself OBJECTIVE : Little is known about the natural history of functional GI symptoms , including what factors influence GI symptom patterns and health care seeking for them over the long term . We aim ed to determine whether psychological factors play a role in the development and long-term course of these symptoms . METHODS : A r and om sample of community subjects ( n = 361 ) who reported having unexplained abdominal pain for ≥1 month in a previous population survey were included in the study . Controls ( n = 120 ) were defined as not having abdominal pain for ≥1 month from this initial survey . Subjects were prospect ively followed up via a question naire every 4 months over a 12-month period . The question naire asked about the presence of GI symptoms over the past week and psychological distress over the past 3 wk ( psychological caseness being defined as a score of ≥2 of 12 on the General Health Question naire ) . The number of visits made to a physician or medical specialist over the past 4 months was evaluated . RESULTS : GI symptoms were common among community controls and subjects with abdominal pain . Similar onset and disappearance rates were observed for the majority of GI symptom categories , accounting for the stability of the prevalence rates over a 1-yr period . Changes in a state measure of psychological distress were not significantly associated with changes in GI symptom status between the 4- and 8-month ( r= 0.14 , p= 0.08 ) and 8- and 12-month ( r= 0.02 , p= 0.77 ) follow-ups . Baseline psychological distress , however , was an independent predictor of having persistent GI symptoms , including abdominal pain , bloating , and constipation , and frequently seeking health care for GI symptoms over 1 yr . CONCLUSIONS : Psychological distress levels do not seem to be important in explaining GI symptom change over a 1-yr period . Psychological distress , however , is linked to having persistent GI symptoms and frequently seeking health care for them over time . Clinicians should consider psychological factors in the treatment of this subset of irritable bowel syndrome patients BACKGROUND : While symptom question naires provide a snapshot of bowel habits , they may not reflect day-to-day variations or the relationship between bowel symptoms and stool form . AIM : To assess bowel habits by daily diaries in women with and without functional bowel disorders . METHOD : From a community-based survey among Olmsted County , MN , women , 278 r and omly selected subjects were interviewed by a gastroenterologist , who completed a bowel symptom question naire . Subjects also maintained bowel diaries for 2 wk . RESULTS : Among 278 subjects , question naires revealed diarrhea ( 26 % ) , constipation ( 21 % ) , or neither ( 53 % ) . Asymptomatic subjects reported bowel symptoms ( e.g. , urgency ) infrequently ( i.e. , < 25 % of the time ) and generally for hard or loose stools . Urgency for soft , formed stools ( i.e. , Bristol form = 4 ) was more prevalent in subjects with diarrhea ( 31 % ) and constipation ( 27 % ) than in normals ( 16 % ) . Stool form , straining to begin ( odds ratio [ OR ] 4.1 , 95 % confidence interval [ CI ] 1.7–10.2 ) and end ( OR 4.7 , 95 % CI 1.6–15.2 ) defecation increased the odds for constipation . Straining to end defecation ( OR 3.7 , 95 % CI 1.2–12.0 ) , increased stool frequency ( OR 1.9 , 95 % CI 1.02–3.7 ) , incomplete evacuation ( OR 2.2 , 95 % CI 1.04–4.6 ) , and rectal urgency ( OR 3.1 , 95 % CI 1.4–6.6 ) increased the odds for diarrhea . In contrast , variations in stool frequency and form were not useful for discriminating between health and disease . CONCLUSIONS : Bowel symptoms occur in association with , but are only partly explained by , stool form disturbances . These observations support a role for other pathophysiological mechanisms in functional bowel disorders Objectives The role of melatonin in regulating gut motility in human subjects is not clear . The aim of this study was to investigate the effects of exogenous melatonin on colonic transit time ( CTT ) in healthy subjects and in patients with irritable bowel syndrome ( IBS ) . Methods Colonic transit time was measured in 17 healthy controls using the radio-opaque , blue dye , and Bristol stool form score method before and after 30 days of melatonin treatment 3 mg daily . A double blind cross-over study aim ed at measuring CTT was also performed in 17 matched IBS patients using the blue dye and Bristol stool form score methods . The patients were r and omized and received either melatonin 3 mg or placebo daily for 8 weeks , followed by a 4-week washout , and then placebo or melatonin in the reverse order for a second 8-week period . Results The melatonin treatment of the control subjects caused an increase in CTT ( mean ± SD ) from 27.4 ± 10.5 to 37.4 ± 23.8 h ( P = 0.04 ) . Compared with the CTT of the controls ( 25.2 ± 7.7 ) , that of the constipation-predominant IBS patients appeared prolonged—65.2 ± 33.3 h ( P < 0.01 ) . The CTT did not change significantly in IBS patients after melatonin treatment . Conclusion Melatonin may be a promising c and i date for the future research of agents that can modulate bowel motility Modern methods of diagnosing diarrhea-predominant irritable bowel syndrome ( D-IBS ) require a “ diagnosis of exclusion ” approach . In this study we aim to test the diagnostic ability of using the fluctuation of frequency and consistency of bowel patterns in IBS to discriminate it from other causes of diarrhea . Eligible subjects were asked to complete a question naire on the changes in form and frequency of bowel habits by time . The primary endpoint was to evaluate the diagnostic effectiveness of having irregularly irregular bowel function and form as more characteristic of IBS versus non-IBS causes . Patients were prospect ively recruited from a tertiary care GI clinic . Subjects had to have diarrhea as their primary complaint . In the case of IBS , D-IBS subjects were recruited . Subjects with celiac disease , Crohn ’s and ulcerative colitis were recruited for comparison and were categorically called “ non-IBS . ” Non-IBS subjects could not have a recent history of blood in stool or a history of bowel surgery , fistulae or narcotic use . Sixty-two IBS and 37 non-IBS subjects were recruited . Among the 62 IBS subjects , 49 ( 79 % ) stated that their bowel habits varied in form and frequency on a daily basis compared to 35 % in non-IBS subjects ( OR = 8.9,CI = 3.5–22.5 , P < 0.00001 ) . When subjects were compared by the number of different stool forms they had witnessed in the prior week , IBS subjects noted 3.58 ± 0.19 types and non-IBS reported 2.35 ± 0.16 ( P < 0.00001 ) . Using ≥3 stool forms per week as a method of discriminating IBS from non-IBS , 50 out of 62 subjects with IBS ( 81 % ) reported this greater number of forms compared to 15 out of 37 ( 41 % ) non-IBS subjects ( sensitivity = 0.81 ; specificity = 0.60 ) . The use of this simple tool that identifies an irregularly irregular bowel form and function is successful in separating D-IBS from non-IBS subjects OBJECTIVES : Do gastrointestinal symptoms in patients with inflammatory bowel disease ( IBD ) in apparent remission reflect the coexistence of irritable bowel syndrome ( IBS ) or sub clinical inflammation ? The aims of this study were as follows : ( i ) to prospect ively determine the prevalence of IBS symptoms in IBD patients in remission ; and ( ii ) to determine whether IBS symptoms correlate with levels of fecal calprotectin . METHODS : Remission was defined by physician assessment : Crohn 's disease ( CD ) activity index ≤150 and ulcerative colitis disease activity index ≤3 , and serum C-reactive protein < 10 , while off corticosteroids or biologics . Quality of life ( QOL ) ( by inflammatory bowel disease question naire ) , the hospital anxiety and depression scale ( HAD ) , and fecal calprotectin were measured . RESULTS : Rome II criteria for IBS were fulfilled in 37/62 ( 59.7 % ) of CD patients and by 17/44 ( 38.6 % ) of those with ulcerative colitis ( UC ) . However , fecal calprotectin was significantly elevated above the upper limit of normal in both IBD patient groups , indicating the presence of occult inflammation . Furthermore , calprotectin levels were significantly higher in CD and UC patients with criteria for IBS than in those without IBS-type symptoms . QOL scores were lower and HAD scores higher among UC patients with IBS symptoms in comparison to those who did not have IBS symptoms . CONCLUSIONS : IBS-like symptoms are common in patients with IBD who are thought to be in clinical remission , but abnormal calprotectin levels suggest that the mechanism in most cases is likely to be occult inflammation rather than coexistent IBS Background Postpr and ial symptoms in irritable bowel syndrome ( IBS ) have been associated with increased bowel contractility . Aim To compare ileocolonic and colonic responses to feeding in health and IBS . Methods We prospect ively analyzed data from separate research trials in 122 IBS patients and 41 healthy volunteers . Ileocolonic transit ( ICT ) was evaluated before ( colonic filling [CF]3h ) and immediately after ( CF4h ) a st and ard lunch at 3 h 45 min , and 2 h thereafter . The colonic geometric center ( GC ) was calculated 2 h ( GC6h ) after lunch ingested at 4 h ( GC4h ) and directly after ( GC8h ) a st and ard dinner ingested at 7 h 45 min . Results ICT immediately after eating was higher in IBS diarrhea predominant ( IBS-D ) patients than in the healthy cohort ( 23.1 ± 2.4 vs. 17.5 ± 2.8 % , P = 0.059 ) . ICT 2 h after lunch was similar between groups ( P = 0.55 ) . There was significant overall group differences in colonic transit 2 h post-lunch ( P = 0.045 ) , particularly in the IBS constipation predominant ( IBS-C ; GC6–GC4 , Δ0.29 ± 0.08 ) patients versus healthy volunteers ( Δ0.56 ± 0.12 GC units ) . Conclusions After feeding , ICT is increased in IBS-D , whereas colonic transit is blunted in Our aim was to compare rectal perception of patients with diarrhea-predominant irritable bowel syndrome ( IBS-D ) , constipation-predominant irritable bowel syndrome ( IBS-C ) , functional constipation ( FC ) , and healthy controls and to evaluate the therapeutic effect of acupoint transcutaneous electric nerve stimulation ( TENS ) . Age- and sex-matched patients ( 24 IBS-D , 20 IBS-C , and 30 FC ) were selected , and 30 volunteers served as healthy controls . Rectal sensory thresholds were evaluated by rectal balloon distension . Short- and long-term acupoint TENS was given respectively . IBS-D patients had significantly lower rectal sensory thresholds of the first sensation of stool , urgency of defecation , and pain than IBS-C or FC patients or healthy controls ( P < 0.05 ) , but there were no differences in rectal sensory thresholds among IBS-C and FC patients and healthy controls . In each group , females had significantly lower rectal sensory thresholds than males ( P < 0.05 ) , but there was no difference between younger ( ≤50 years old ) and older ( > 50 years old ) patients . Short-term acupoint TENS increased rectal sensory thresholds of IBS-D patients . After 2-month acupoint TENS treatment in IBS-D patients , rectal sensory thresholds were significantly increased , stool times and the intensity of abdominal pain were decreased , and psychological scores were relieved to normal . Lowered rectal perception threshold is a hallmark of IBS-D patients . Females have significantly lower rectal sensory thresholds than males . Acupoint TENS is effective to treat OBJECTIVES : Despite a lack of supportive data , stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients . The aim of this study was to assess the correlation between stool characteristics ( form and frequency ) and gut transit in constipated and healthy adults . METHODS : A post hoc analysis was performed on 110 subjects ( 46 chronic constipation ) from nine US sites recording stool form ( Bristol Stool Scale ) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule ( WMC ) and radio-opaque marker ( ROM ) tests . Stool form and frequency were correlated with transit times using Spearman 's rank correlation . Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis . RESULTS : In the constipated adults ( 42 females , 4 males ) , moderate correlations were found between stool form and whole-gut transit measured by WMC ( r=−0.61 , P<0.0001 ) or ROM ( −0.45 , P=0.0016 ) , as well as colonic transit measured by WMC ( −0.62 , P<0.0001 ) . A Bristol stool form value <3 predicted delayed whole-gut transit with a sensitivity of 85 % and specificity of 82 % and delayed colonic transit with a sensitivity of 82 % and specificity of 83 % . No correlation between stool form and measured transit was found in healthy adults , regardless of gender . No correlation was found between stool frequency and measured transit in constipated or healthy adults . The correlation between stool frequency and measured transit remained poor in constipated adults with <3 bowel movements per week . CONCLUSIONS : Stool form predicts delayed vs. normal transit in adults . However , only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults . In contrast , stool frequency is a poor surrogate for transit , even in those with reduced stool frequency BACKGROUND Stool form scales are a simple method of assessing intestinal transit rate but are not widely used in clinical practice or research , possibly because of the lack of evidence that they are responsive to changes in transit time . We set out to assess the responsiveness of the Bristol stool form scale to change in transit time . METHODS Sixty-six volunteers had their whole-gut transit time ( WGTT ) measured with radiopaque marker pellets and their stools weighed , and they kept a diary of their stool form on a 7-point scale and of their defecatory frequency . WGTT was then altered with senna and loperamide , and the measurements were repeated . RESULTS The base-line WGTT measurements correlated with defecatory frequency ( r = 0.35 , P = 0.005 ) and with stool output ( r = -0.41 , P = 0.001 ) but best with stool form ( r = -0.54 , P < 0.001 ) . When the volunteers took senna ( n = 44 ) , the WGTT decreased , whereas defecatory frequency , stool form score , and stool output increased ( all , P < 0.001 ) . With loperamide ( n = 43 ) all measurements changed in the opposite direction . Change in WGTT from base line correlated with change in defecatory frequency ( r = 0.41 , P < 0.001 ) and with change in stool output ( n = -0.54 , P < 0.001 ) but best with change in stool form ( r = -0.65 , P < 0.001 ) . CONCLUSIONS This study has shown that a stool form scale can be used to monitor change in intestinal function . Such scales have utility in both clinical practice and research BACKGROUND Irritable bowel syndrome has a high prevalence . Consensus diagnostic criteria ( ROME II ) based on symptoms have been established to aid diagnosis . Although coeliac disease can be misdiagnosed as irritable bowel syndrome , no prospect i ve study has been published in which patients with this disorder are investigated for coeliac disease . We aim ed to assess the association of coeliac disease with irritable bowel syndrome in patients fulfilling ROME II criteria . METHODS We undertook a case-control study at a university hospital . 300 consecutive new patients who fulfilled Rome II criteria for irritable bowel syndrome , and 300 healthy controls ( age and sex matched ) were investigated for coeliac disease by analysis of serum IgA antigliadin , IgG antigliadin , and endomysial antibodies ( EMA ) . Patients and controls with positive antibody results were offered duodenal biopsy to confirm the possibility of coeliac disease . FINDINGS 66 patients with irritable bowel syndrome had positive antibody results , of whom 14 had coeliac disease ( 11 EMA positive , three EMA negative ) . Nine patients with positive antibody results were lost to follow-up or refused biopsy ( only one EMA-positive patient refused biopsy ) , and 43 had normal duodenal mucosa . Two controls , both of whom were EMA positive , had coeliac disease . Compared with matched controls , irritable bowel syndrome was significantly associated with coeliac disease ( p=0.004 , odds ratio=7.0 [ 95 % CI 1.7 - 28.0 ] ) . INTERPRETATION Patients with irritable bowel syndrome referred to secondary care should be investigated routinely for coeliac disease . With only EMA , three of 14 cases would have been missed OBJECTIVES : Previous reports have linked irritable bowel syndrome ( IBS ) etiologically with various forms of mucosal inflammation , including infectious enterocolitides and inflammatory bowel disease . The mechanism is uncertain but may involve sensitization by inflammatory mediators . The enteropathy of celiac disease has theoretical advantages as a study model because it can be controlled with dietary gluten exclusion ; however , whether it also predisposes to functional bowel disorders is unclear . Therefore , we assessed the prevalence of IBS-type symptoms in adult celiac patients and correlated this with dietary compliance with gluten exclusion . METHODS : Adult patients ( n = 150 ; 106 women and 44 men ) with confirmed celiac disease were r and omly selected from a computerized data base of > 350 patients , and were asked to complete a bowel question naire and the Short Form 36 Health Survey ( SF-36 ) . The control group ( n = 162 ; 133 women and 29 men ) had no history of celiac disease and had similar mean age and sex profile . RESULTS : Of 150 celiac patients review ed , 30 of 150 ( 20 % ) fulfilled the Rome criteria compared with eight of 162 ( 5 % ) controls . Of the celiac patients 10 of 46 ( 22 % ) had partial or no compliance with a gluten-free diet , whereas 20 of 104 patients ( 19 % ) adhered to the diet ; this difference did not achieve statistical significance . Celiac patients with IBS-type symptoms had a markedly lower quality of life than those without , all eight domains being impaired to a clinical ly significant extent . Dietary gluten exclusion improved QOL in four of eight scales measured . CONCLUSIONS : The hypothesis that mucosal inflammation in celiac disease may have a sensitizing effect or may predispose to IBS-type symptoms is supported by these results . Failure to attain optimal subjective well-being is common in celiac patients , particularly in those with coexisting IBS . Compliance with a gluten-free diet confers some benefit Since it is not known whether the symptoms and bowel function of patients with the irritable bowel syndrome are truly abnormal we used diaries and frequent telephone interviews over a 31 day period to assess symptoms , defecation , and stool types in 26 unselected female hospital patients with the irritable bowel syndrome , 27 women who admitted to recurrent colonic pain but had not consulted a doctor ( non-complainers ) , and 27 healthy control subjects . Unexpectedly , abdominal pain and bloating occurred in most of the control subjects . Pain , however , was six times more frequent in the patients and was more often considered severe . Bloating occurred three times more often . Defecation was more frequent , more erratic in timing and stool form , and more likely to produce stools of extreme forms , indicating rapid fluctuations in intestinal transit time . Urgency was four times more prevalent in patients than control subjects . Straining to finish defecating was nine times more prevalent and was often accompanied by feelings of incomplete evacuation -- a combination which could lead to the misdiagnosis of constipation . The normal relation between stool form and the above symptoms was distorted , possibly due to rectal irritability . Non-complainers were intermediate between patients and control subjects in almost every parameter but were closer to control subjects than to patients . Patients with the irritable bowel syndrome have real cause for complaint and their bowel function is truly abnormal Objective : Irritable bowel syndrome ( IBS ) and panic disorder ( PD ) coexist with a high frequency . However , the nature of this relationship remains obscure . We have proposed that PD and IBS may share a common dysfunction of the central cholecystokinin ( CCK ) system . To test this hypothesis , we assessed whether the enhanced panicogenic response to CCK-tetrapeptide ( CCK-4 ) observed in PD is also present in IBS . Methods : Eight psychiatrically healthy IBS patients , 8 PD patients with no history of IBS , and 12 normal controls received a bolus injection of CCK-4 and placebo on two separate days in a double-blind , r and omized fashion . Results : Consistent with previous findings , panicogenic sensitivity to CCK-4 was enhanced in PD patients relative to controls . In contrast , IBS patients exhibited a response that was comparable to controls . Interestingly , CCK-4-induced nausea and abdominal distress were decreased in IBS patients relative to the other groups . No diagnostic difference was noted for cardiovascular response to CCK-4 . Conclusion : These data indicate that IBS patients with no lifetime psychiatric history do not share the CCK-2 receptor dysfunction implicated in the pathophysiology of PD and that this dysfunction may not be a common mechanism for both CNS and enteric nervous system disorders . Nevertheless , the results suggest that a dysfunction of the CCK system may be involved in the pathophysiology of some enteric symptoms associated with IBS . IBS = irritable bowel syndrome ; PD = panic disorder ; CCK = cholecystokinin ; NTS = nucleus tractus solitarius ; CBF = cerebral blood flow ; NC = normal controls ; PSS = Panic Symptom Scale ; CCK-4 = cholecystokinin-tetrapeptide ; VAS = visual analog scale |
1,166 | 29,608,096 | Conclusion : Despite the recommendations of the Consoli date d St and ards of Reporting Trials statement extension to cluster r and omised trials , treatment adherence is under-reported .
Among the trials providing adherence information , there was substantial variation in how adherence was defined , h and led and reported . | Background : Treatment non-adherence in r and omised trials refers to situations where some participants do not receive their allocated treatment as intended .
For cluster r and omised trials , where the unit of r and omisation is a group of participants , non-adherence may occur at the cluster or individual level .
When non-adherence occurs , r and omisation no longer guarantees that the relationship between treatment receipt and outcome is unconfounded , and the power to detect the treatment effects in intention-to-treat analysis may be reduced .
Thus , recording adherence and estimating the causal treatment effect adequately are of interest for clinical trials .
Objectives : To assess the extent of reporting of non-adherence issues in published cluster trials and to establish which methods are currently being used for addressing non-adherence , if any , and whether clustering is accounted for in these . | Please cite this paper as : MacIntyre et al. ( 2011 ) A cluster r and omized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers . Influenza and Other Respiratory Viruses DOI : 10.1111/j.1750‐2659.2010.00198.x . Background We compared the efficacy of medical masks , N95 respirators ( fit tested and non fit tested ) , in health care workers ( HCWs ) . Methods A cluster r and omized clinical trial ( RCT ) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter . Participants wore masks or respirators during the entire work shift for 4 weeks . Outcomes included clinical respiratory illness ( CRI ) , influenza‐like illness ( ILI ) , laboratory‐confirmed respiratory virus infection and influenza . A convenience no‐mask/respirator group of 481 health workers from nine hospitals was compared . Findings The rates of CRI ( 3·9 % versus 6·7 % ) , ILI ( 0·3 % versus 0·6 % ) , laboratory‐confirmed respiratory virus ( 1·4 % versus 2·6 % ) and influenza ( 0·3 % versus 1 % ) infection were consistently lower for the N95 group compared to medical masks . By intention‐to‐treat analysis , when P values were adjusted for clustering , non‐fit‐tested N95 respirators were significantly more protective than medical masks against CRI , but no other outcomes were significant . The rates of all outcomes were higher in the convenience no‐mask group compared to the intervention arms . There was no significant difference in outcomes between the N95 arms with and without fit testing . Rates of fit test failure were low . In a post hoc analysis adjusted for potential confounders , N95 masks and hospital level were significant , but medical masks , vaccination , h and washing and high‐risk procedures were not . Interpretation Rates of infection in the medical mask group were double that in the N95 group . A benefit of respirators is suggested but would need to be confirmed by a larger trial , as this study may have been underpowered . The finding on fit testing is specific to the type of respirator used in the study and can not be generalized to other respirators . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , ACTRN : ACTRN12609000257268 ( http://www.anzctr.org.au ) Background Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity Background In the UK public concern about the safety of the combined measles , mumps and rubella [ MMR ] vaccine continues to impact on MMR coverage . Whilst the sharp decline in uptake has begun to level out , first and second dose uptake rates remain short of that required for population immunity . Furthermore , international research consistently shows that some parents lack confidence in making a decision about MMR vaccination for their children . Together , this work suggests that effective interventions are required to support parents to make informed decisions about MMR.This trial assessed the impact of a parent-centred , multi-component intervention ( balanced information , group discussion , coaching exercise ) on informed parental decision-making for MMR . Methods This was a two arm , cluster r and omised trial . One hundred and forty two UK parents of children eligible for MMR vaccination were recruited from six primary healthcare centres and six childcare organisations . The intervention arm received an MMR information leaflet and participated in the intervention ( parent meeting ) . The control arm received the leaflet only . The primary outcome was decisional conflict . Secondary outcomes were actual and intended MMR choice , knowledge , attitude , concern and necessity beliefs about MMR and anxiety . Results Decisional conflict decreased for both arms to a level where an ' effective ' MMR decision could be made one-week ( effect estimate = -0.54 , p < 0.001 ) and three-months ( effect estimate = -0.60 , p < 0.001 ) post-intervention . There was no significant difference between arms ( effect estimate = 0.07 , p = 0.215 ) . Heightened decisional conflict was evident for parents making the MMR decision for their first child ( effect estimate = -0.25 , p = 0.003 ) , who were concerned ( effect estimate = 0.07 , p < 0.001 ) , had less positive attitudes ( effect estimate = -0.20 , p < 0.001 ) yet stronger intentions ( effect estimate = 0.09 , p = 0.006 ) . Significantly more parents in the intervention arm reported vaccinating their child ( 93 % versus 73 % , p = 0.04 ) . Conclusions Whilst both the leaflet and the parent meeting reduced parents ' decisional conflict , the parent meeting appeared to enable parents to act upon their decision leading to vaccination uptake INTRODUCTION Majority of studies on evaluation of emergency management courses have focused on outcomes such as knowledge and skills demonstrated in non- clinical or traditional testing manner . Such surrogate outcomes may not necessarily reflect vital changes in practice . The aim of this study was to determine if and to what extent , specific training in the management of life threatening emergencies result ed in an increased in compliance with established care guidelines of doctors working in the emergency departments of public sector hospitals in Pakistan . METHODS A cluster r and omised controlled trial was conducted in three districts hospitals in three cities ( Khairpur , Vehari and Peshawar ) of Pakistan . Thirty-six doctors , 18 in intervention ( trained in ESS-EMNCH training ) and 18 in control ( untrained ) , were enrolled and 248 life threatening emergency events , 124 in each group , were observed for the correct use of the Airway , Breathing , Circulation ( ABC ) structured approach . The outcome measure was structured approach defined a priori . Data was analysed by using STATA software . RESULTS At individual level , 79 ( 63.7 % ) life threatening episodes were managed according to the structured approach in the intervention group and 46 ( 37.1 % ) were managed according to the structured approach in controls ( OR 2.98 , 95%CI 1.78 - 4.99 , p-value=0.0001 ) . At cluster level , the mean percentage ( 95 % CI ) of the structured approach used by doctors in the intervention group [ 62.9 % ( 50.4 - 75.3 % ) ] , was significantly higher than those in the control group , [ 36.3 % ( 26.3 - 46.4 ) ] ( p-value=0.001 ) . CONCLUSIONS 5-day training of ESS-EMNCH significantly increased the compliance with established care guidelines of doctors during their management of life threatening emergency episodes in the public sector hospitals in Pakistan OBJECTIVE The number of extremely thin young women has increased and education at school on maintaining an optimal weight has become important . The aim of the present study was to assess the effectiveness of a group-based home-collaborative dietary education ( HCDE ) programme to maintain appropriate dietary intake compared to conventional school classroom education . DESIGN Two-arm cluster r and omized controlled trial . Twelve classes were r and omly assigned as clusters to either the HCDE group or the control group . Each participant in the HCDE group received twelve sessions of group counselling aim ed at increasing energy intake at breakfast by modifying dietary intake and adopting appropriate habits . The hypothesis underlying the study was that after 6 months of HCDE the total energy intake would be increased by 627 kJ from baseline ( primary endpoint ) . Secondary outcomes were differences in intake of various nutrients from baseline . Outcome measures after log transformation were examined by t tests and linear mixed models ( crude and baseline-adjusted ) . SETTING Young women among Japanese female adolescents in Tokyo . SUBJECTS Four hundred and seventy-four participants aged 13 - 15 years . RESULTS Students in twelve classes were used for analysis ( n 459 ) . Energy intake was decreased in many of the classes during the 6-month period , especially for those in the control group . After adjustment for the baseline value , significant increases in energy intake and protein , calcium , magnesium and iron intakes at breakfast were observed ( P<0.05 ) CONCLUSIONS Although energy intake was increased in the HCDE group compared to the control group , further study of the HCDE is warranted BACKGROUND Intensive care units ( ICUs ) are high-risk setting s for the transmission of methicillin-resistant Staphylococcus aureus ( MRSA ) and vancomycin-resistant enterococcus ( VRE ) . METHODS In a cluster-r and omized trial , we evaluated the effect of surveillance for MRSA and VRE colonization and of the exp and ed use of barrier pre caution s ( intervention ) as compared with existing practice ( control ) on the incidence of MRSA or VRE colonization or infection in adult ICUs . Surveillance cultures were obtained from patients in all participating ICUs ; the results were reported only to ICUs assigned to the intervention . In intervention ICUs , patients who were colonized or infected with MRSA or VRE were assigned to care with contact pre caution s ; all the other patients were assigned to care with universal gloving until their discharge or until surveillance cultures obtained at admission were reported to be negative . RESULTS During a 6-month intervention period , there were 5434 admissions to 10 intervention ICUs , and 3705 admissions to 8 control ICUs . Patients who were colonized or infected with MRSA or VRE were assigned to barrier pre caution s more frequently in intervention ICUs than in control ICUs ( a median of 92 % of ICU days with either contact pre caution s or universal gloving [ 51 % with contact pre caution s and 43 % with universal gloving ] in intervention ICUs vs. a median of 38 % of ICU days with contact pre caution s in control ICUs , P<0.001 ) . In intervention ICUs , health care providers used clean gloves , gowns , and h and hygiene less frequently than required for contacts with patients assigned to barrier pre caution s ; when contact pre caution s were specified , gloves were used for a median of 82 % of contacts , gowns for 77 % of contacts , and h and hygiene after 69 % of contacts , and when universal gloving was specified , gloves were used for a median of 72 % of contacts and h and hygiene after 62 % of contacts . The mean ( ±SE ) ICU-level incidence of events of colonization or infection with MRSA or VRE per 1000 patient-days at risk , adjusted for baseline incidence , did not differ significantly between the intervention and control ICUs ( 40.4±3.3 and 35.6±3.7 in the two groups , respectively ; P=0.35 ) . CONCLUSIONS The intervention was not effective in reducing the transmission of MRSA or VRE , although the use of barrier pre caution s by providers was less than what was required . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; STAR*ICU Clinical Trials.gov number , NCT00100386 . ) BACKGROUND We assessed patient outcomes 90 days after hospital admission for stroke following a multidisciplinary intervention targeting evidence -based management of fever , hyperglycaemia , and swallowing dysfunction in acute stroke units ( ASUs ) . METHODS In the Quality in Acute Stroke Care ( QASC ) study , a single-blind cluster r and omised controlled trial , we r and omised ASUs ( clusters ) in New South Wales , Australia , with immediate access to CT and on-site high dependency units , to intervention or control group . Patients were eligible if they spoke English , were aged 18 years or older , had had an ischaemic stroke or intracerebral haemorrhage , and presented within 48 h of onset of symptoms . Intervention ASUs received treatment protocol s to manage fever , hyperglycaemia , and swallowing dysfunction with multidisciplinary team building workshops to address implementation barriers . Control ASUs received only an abridged version of existing guidelines . We recruited pre-intervention and post-intervention patient cohorts to compare 90-day death or dependency ( modified Rankin scale [ mRS ] ≥2 ) , functional dependency ( Barthel index ) , and SF-36 physical and mental component summary scores . Research assistants , the statistician , and patients were masked to trial groups . All analyses were done by intention to treat . This trial is registered at the Australia New Zeal and Clinical Trial Registry ( ANZCTR ) , number ACTRN12608000563369 . FINDINGS 19 ASUs were r and omly assigned to intervention ( n=10 ) or control ( n=9 ) . Of 6564 assessed for eligibility , 1696 patients ' data were obtained ( 687 pre-intervention ; 1009 post-intervention ) . Results showed that , irrespective of stroke severity , intervention ASU patients were significantly less likely to be dead or dependent ( mRS ≥2 ) at 90 days than control ASU patients ( 236 [ 42 % ] of 558 patients in the intervention group vs 259 [ 58 % ] of 449 in the control group , p=0·002 ; number needed to treat 6·4 ; adjusted absolute difference 15·7 % [ 95 % CI 5·8 - 25·4 ] ) . They also had a better SF-36 mean physical component summary score ( 45·6 [ SD 10·2 ] in the intervention group vs 42·5 [ 10·5 ] in the control group , p=0·002 ; adjusted absolute difference 3·4 [ 95 % CI 1·2 - 5·5 ] ) but no improvement was recorded in mortality ( 21 [ 4 % ] of 558 in intervention group and 24 [ 5 % ] of 451 in the control group , p=0·36 ) , SF-36 mean mental component summary score ( 49·5 [ 10·9 ] in the intervention group vs 49·4 [ 10·6 ] in the control group , p=0·69 ) or functional dependency ( Barthel Index ≥60 : 487 [ 92 % ] of 532 patients vs 380 [ 90 % ] of 423 patients ; p=0·44 ) . INTERPRETATION Implementation of multidisciplinary supported evidence -based protocol s initiated by nurses for the management of fever , hyperglycaemia , and swallowing dysfunction delivers better patient outcomes after discharge from stroke units . Our findings show the possibility to augment stroke unit care . FUNDING National Health & Medical Research Council ID 353803 , St Vincent 's Clinic Foundation , the Curran Foundation , Australian Diabetes Society-Servier , the College of Nursing , and Australian Catholic University This study investigated the effectiveness of labeling foods with the Choices nutrition logo on influencing cafeteria menu selection and the behavioral determinants of menu choices in work site cafeterias in the Netherl and s. A cluster r and omized controlled trial was conducted . Intervention cafeterias ( n=13 ) , where the Choices logo was used to promote healthier eating for a 3-week period , were compared with control cafeterias ( n=12 ) , which offered the same menu without the logo . Sales data were collected daily for 9 weeks , from March to May 2009 . In addition , employees from one intervention and one control company completed an online question naire at baseline and after the intervention ( n=368 ) in which the behavioral determinants of food choice ( ie , attitude , self-efficacy , and intention ) and logo use were measured . Generalized estimating equation analyses , χ² tests , t tests and linear regression analyses were performed . No nutritionally meaningful intervention effects were found in the sales of s and wiches , soups , snacks , fruit , and salads . Also , no significant differences in behavioral determinants were found . " Intention to eat healthier " and " paying attention to product information " were positively associated with self-reported consumption of foods with the Choices logo at lunch . The intervention did not have a significant effect on employees ' lunchtime food choices . Labeling healthy choices might be useful for health-conscious employees in the volitional phase of behavior change . Further research should focus on the possible health benefits of menu reformulation in the catering sector OBJECTIVE : To determine the effectiveness of a quality improvement program to improve pediatricians ' adherence to existing , evidence -based , attention-deficit/hyperactivity disorder ( ADHD ) practice guidelines . METHODS : Forty-nine community-based pediatricians at 8 practice s participated in a cluster-r and omized trial . Practice s were matched according to the numbers of pediatricians and the proportions of patients receiving Medicaid . The medical charts for a r and om sample of patients with ADHD for each of the participating pediatricians were examined at baseline and 6 months . All practice s participated in 4 sessions of training , including didactic lectures and office flow modification workshops . Practice s were then given access to an ADHD Internet portal that allowed parents , teachers , and pediatricians to input information ( eg , rating scales ) about patients , after which information was scored , interpreted , and formatted in a report style that was helpful for assessment and treatment of patients with ADHD . Physicians evaluated their practice behaviors quarterly and addressed underperforming areas . RESULTS : Pediatricians in the intervention group , compared with those in the control group , demonstrated significantly higher rates of many American Academy of Pediatrics – recommended ADHD care practice s , including collection of parent ( Cohen 's d = 0.69 ) and teacher ( d = 0.68 ) rating scales for assessment of children with ADHD , use of Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria ( d = 0.85 ) , and use of teacher rating scales to monitor treatment responses ( d = 1.01 ) . CONCLUSION : A quality improvement intervention that can be widely disseminated by using Internet-based information technology significantly improved the quality of ADHD care in community-based pediatric setting BACKGROUND Most clinicians have no training about domestic violence , fail to identify patients experiencing abuse , and are uncertain about management after disclosure . We tested the effectiveness of a programme of training and support in primary health-care practice s to increase identification of women experiencing domestic violence and their referral to specialist advocacy services . METHODS In this cluster r and omised controlled trial , we selected general practice s in two urban primary care trusts , Hackney ( London ) and Bristol , UK . Practice s in which investigators from this trial were employed or those who did not use electronic records were excluded . Practice s were stratified by proportion of female doctors , postgraduate training status , number of patients registered , and percentage of practice population on low incomes . Within every primary care trust area , we r and omised practice s with a computer-minimisation programme with a r and om component to intervention or control groups . The intervention programme included practice -based training sessions , a prompt within the medical record to ask about abuse , and a referral pathway to a named domestic violence advocate , who also delivered the training and further consultancy . The primary outcome was recorded referral of patients to domestic violence advocacy services . The prespecified secondary outcome was recorded identification of domestic violence in the electronic medical records of the general practice . Poisson regression analyses accounting for clustering were done for all practice s receiving the intervention . Practice staff and research associates were not masked and patients were not aware they were part of a study . This study is registered at Current Controlled Trials , IS RCT N74012786 . FINDINGS We r and omised 51 ( 61 % ) of 84 eligible general practice s in Hackney and Bristol . Of these , 24 received a training and support programme , 24 did not receive the programme , and three dropped out before the trial started . 1 year after the second training session , the 24 intervention practice s recorded 223 referrals of patients to advocacy and the 24 control practice s recorded 12 referrals ( adjusted intervention rate ratio 22·1 [ 95 % CI 11·5 - 42·4 ] ) . Intervention practice s recorded 641 disclosures of domestic violence and control practice s recorded 236 ( adjusted intervention rate ratio 3·1 [ 95 % CI 2·2 - 4·3 ) . No adverse events were recorded . INTERPRETATION A training and support programme targeted at primary care clinicians and administrative staff improved referral to specialist domestic violence agencies and recorded identification of women experiencing domestic violence . Our findings reduce the uncertainty about the benefit of training and support interventions in primary care setting s for domestic violence and show that screening of women patients for domestic violence is not a necessary condition for improved identification and referral to advocacy services . FUNDING Health Foundation Background and Purpose — Thrombolysis with intravenous recombinant tissue plasminogen activator is an effective treatment for acute ischemic stroke , but the number of treatable patients is limited . The PRomoting ACute Thrombolysis in Ischemic StrokE ( PRACTISE ) trial evaluated the effectiveness of a multidimensional implementation strategy for thrombolysis with intravenous recombinant tissue plasminogen activator in acute ischemic stroke . Methods — The PRACTISE trial was a national multicenter cluster-r and omized controlled trial with r and omization after pairwise matching . Twelve hospitals , both urban and community , academic and nonacademic , in the Netherl and s participated . All patients admitted with stroke within 24 hours from onset of symptoms were registered . The intervention included 5 implementation meetings based on the Breakthrough Series model . The primary outcome was treatment with thrombolysis . Secondary outcomes were admission within 4 hours after onset of symptoms , death or disability at 3 months , and quality of life . Results — Overall 5515 patients were included in the study ' 308 patients ( 12.2 % ) in the control centers and 393 patients ( 13.1 % ) in the intervention centers were treated with thrombolysis ( adjusted OR , 1.25 ; 95 % CI , 0.93 to 1.68 ) . Among the 1657 patients with ischemic stroke admitted within 4 hours from onset , 391 ( 44.5 % ) of 880 in the intervention centers were treated with thrombolysis and 305 ( 39.3 % ) of 777 in the control centers ; the adjusted OR for treatment with thrombolysis was 1.58 ( 95 % CI , 1.11 to 2.27 ) . Conclusions — An intensive implementation strategy increases the proportion of patients with acute stroke treated with thrombolysis in real-life setting s. An apparently pivotal factor in the improvement of the treatment rate is better application of contraindications for thrombolysis AIMS A recent trial demonstrated that a brief guided self-help intervention reduces anxiety in palliative patients . This study investigated whether training palliative nurses to deliver a guided self-help intervention would improve their routine management of psychological distress . DESIGN A r and omized controlled cluster trial compared a team of nurses who attended training ( n=5 ) with a team allocated to a no-training control condition ( n=5 ) on self-reported behaviour and confidence in addressing psychological distress . Ratings of patient psychological distress at routine clinical assessment s were also examined pre- and post-training to assess the impact of training on patient distress . RESULTS As predicted , patients cared for by the trained team demonstrated a significantly greater reduction in distress post-training than patients cared for by the untrained team . However , there was no significant difference in self-reported behaviour and confidence . CONCLUSION These findings suggest that brief workshop-based training improves clinical outcomes on psychological distress and may be a means to increase the accessibility of effective psychological interventions in palliative care AIM Oral health is a reflection of general health and significantly influences the quality of life . Dental caries is one of the most common chronic diseases of childhood which may adversely affect physical , mental and social growth of children . Oral hygiene methods can effectively prevent oral and dental diseases , and oral hygiene education plays an important role in this regard . The aim of the present study was then to assess the effect of oral hygiene education on the oral and dental health of 6-year-olds . MATERIAL S AND METHODS A hundred and sixty 6-year-old children from 4 pre-school centers were divided into two groups , case and control , in this cluster r and omised controlled trail . The children in the case group received oral and dental education in one session . The parents of the case group were also instructed in one session . The children and parents of the control group did not receive any instructions . Plaque index ( PI ) : Turesky-Gilmore-Glickman ; gingival index ( GI ) : Loe & Silness ; at a ) baseline , b ) 1.5 and c ) 6 months after the first examination . Data were analysed by repeated measure ANOVA . RESULTS PI : A significant difference was found between the baseline examination and the first follow-up ( p < 0.01 ) , and between the baseline examination and the second follow-up ( p < 0.001 ) . GI : Although values in the case group were lower , no statistically significant difference was found between the two groups and within each group ( p > 0.05 ) . Regarding the number of brushing times , a statistically significant difference was found between the first and the second follow-ups of the study groups ( p > 0.05 ) . The brushing type and the application of other hygienic measures did not show any difference ( p > 0.05 ) . CONCLUSION Within the limitations of the present study it may be concluded that oral hygiene instruction to 6-year-old children and their parents improves their dental health Objectives We tested a dental health program in remote Aboriginal communities of Australia 's Northern Territory , hypothesizing that it would reduce dental caries in preschool children . Methods In this 2-year , prospect i ve , cluster-r and omized , concurrent controlled , open trial of the dental health program compared to no such program , 30 communities were allocated at r and om to intervention and control groups . All residents aged 18–47 months were invited to participate . Twice per year for 2 years in the 15 intervention communities , fluoride varnish was applied to children 's teeth , water consumption and daily tooth cleaning with toothpaste were advocated , dental health was promoted in community setting s , and primary health care workers were trained in preventive dental care . Data from dental examinations at baseline and after 2 years were used to compute net dental caries increment per child ( d3mfs ) . A multi-level statistical model compared d3mfs between intervention and control groups with adjustment for the clustered r and omization design ; four other models used additional variables for adjustment . Results At baseline , 666 children were examined ; 543 of them ( 82 % ) were re-examined 2 years later . The adjusted d3mfs increment was significantly lower in the intervention group compared to the control group by an average of 3.0 surfaces per child ( 95 % CI = 1.2 , 4.9 ) , a prevented fraction of 31 % . Adjustment for additional variables yielded caries reductions ranging from 2.3 to 3.5 surfaces per child and prevented fractions of 24–36 % . Conclusions These results corroborate findings from other studies where fluoride varnish was efficacious in preventing dental caries in young children INTRODUCTION The first-aid training necessary for obtaining a drivers license in Austria has a regulated and predefined curriculum but has been targeted for the implementation of a new course structure with less theoretical input , repetitive training in cardiopulmonary resuscitation ( CPR ) and structured presentations using innovative media . METHODS The st and ard and a new course design were compared with a prospect i ve , participant- and observer-blinded , cluster-r and omized controlled study . Six months after the initial training , we evaluated the confidence of the 66 participants in their skills , CPR effectiveness parameters and correctness of their actions . RESULTS The median self-confidence was significantly higher in the interventional group [ IG , visual analogue scale ( VAS:"0 " not-confident at all,"100 " highly confident):57 ] than in the control group ( CG , VAS:41 ) . The mean chest compression rate in the IG ( 98/min ) was closer to the recommended 100 bpm than in the CG ( 110/min ) . The time to the first chest compression ( IG:25s , CG:36s ) and time to first defibrillator shock ( IG:86s , CG:92s ) were significantly shorter in the IG . Furthermore , the IG participants were safer in their h and ling of the defibrillator and started with counter measures against developing shock more often . The management of an unconscious person and of heavy bleeding did not show a difference between the two groups even after shortening the lecture time . CONCLUSIONS Motivation and self-confidence as well as skill retention after six months were shown to be dependent on the teaching methods and the time for practical training . Courses may be reorganized and content rescheduled , even within predefined curricula , to improve course outcomes Background Regular laboratory test monitoring of patient parameters offers a route for improving the quality of chronic disease care . We evaluated the effects of brief educational messages attached to laboratory test reports on diabetes care . Methods A programme of cluster r and omised controlled trials was set in primary care practice s in one primary care trust in Engl and . Participants were the primary care practice s ' constituent healthcare professionals and patients with diabetes . Interventions comprised brief educational messages added to paper and electronic primary care practice laboratory test reports and introduced over two phases . Phase one messages , attached to Haemoglobin A1c ( HbA1c ) reports , targeted glycaemic and cholesterol control . Phase two messages , attached to albumin : creatinine ratio ( ACR ) reports , targeted blood pressure ( BP ) control , and foot inspection . Main outcome measures comprised practice mean HbA1c and cholesterol levels , diastolic and systolic BP , and proportions of patients having undergone foot inspections . Results Initially , 35 out of 37 eligible practice s participated . Outcome data were available for a total of 8,690 patients with diabetes from 32 practice s. The BP message produced a statistically significant reduction in diastolic BP ( -0.62 mmHg ; 95 % confidence interval -0.82 to -0.42 mmHg ) but not systolic BP ( -0.06 mmHg , -0.42 to 0.30 mmHg ) and increased the odds of achieving target BP control ( odds ratio 1.05 ; 1.00 , 1.10 ) . The foot inspection message increased the likelihood of a recorded foot inspection ( incidence rate ratio 1.26 ; 1.18 to 1.36 ) . The glycaemic control message had no effect on mean HbA1c ( increase 0.01 % ; -0.03 to 0.04 ) despite increasing the odds of a change in likelihood of HbA1c tests being ordered ( OR 1.06 ; 1.01 , 1.11 ) . The cholesterol message had no effect ( decrease 0.01 mmol/l , -0.04 to 0.05 ) . Conclusions Three out of four interventions improved intermediate outcomes or process of diabetes care . The diastolic BP reduction approximates to relative reductions in mortality of 3 % to 5 % in stroke and 3 % to 4 % in ischaemic heart disease over 10 years . The lack of effect for other outcomes may , in part , be explained by difficulties in bringing about further improvements beyond certain thresholds of clinical performance . Trial Registration Current Controlled Trials , IS RCT N2186314 OBJECTIVES To evaluate the effectiveness of a multifactorial intervention to reduce the use of physical restraints in residents of nursing homes . DESIGN Cluster-r and omized controlled trial . SETTING Forty-five nursing homes in Germany . PARTICIPANTS Three hundred thirty-three residents who were being restrained at the start of the intervention . INTERVENTION Persons responsible for the intervention in the nursing homes attended a 6-hour training course that included education about the reasons restraints are used , the adverse effects , and alternatives to their use . Technical aids , such as hip protectors and sensor mats , were provided . The training was design ed to give the change agents tools for problem-solving to prevent behavioral symptoms and injuries from falls without using physical restraints . MEASUREMENTS The main outcome was the complete cessation of physical restraint use on 3 consecutive days 3 months after the start of the intervention . Secondary outcomes were partial reductions in restraint use , percentage of fallers , number of psychoactive drugs , and occurrence of behavioral symptoms . RESULTS The probability of being unrestrained in the intervention group ( IG ) was more than twice that in the control group ( CG ) at the end of the study ( odds ratio=2.16 , 95 % confidence interval=1.05 - 4.46 ) . A partial reduction of restraint use was also about twice as often achieved in the IG as in the CG . No negative effect was observed regarding medication or behavioral symptoms . The percentage of fallers was higher in the IG . CONCLUSION The intervention reduced restraint use without a significant increase in falling , behavioral symptoms , or medication PURPOSE School-based substance abuse prevention programs are widespread but are rarely evaluated in Europe . We aim ed to evaluate the effect of a new school-based prevention program against substance use on the frequency of alcohol consumption and alcohol-related problem behaviors among European students . METHODS During the school year 2004 - 2005 , a total of 7,079 students aged 12 - 14 years from 143 schools in seven European countries participated in this cluster r and omized controlled trial . Schools were r and omly assigned to either control ( 65 schools , 3,532 students ) or to a 12-session st and ardized program based on the comprehensive social influence model ( 78 schools , 3,547 students ) . Alcohol use and frequency of alcohol-related problem behaviors were investigated through a self-completed anonymous question naire at baseline and 18 months thereafter . The association between intervention and changes in alcohol-related outcomes was expressed as odds ratio ( OR ) , estimated by multilevel regression model . RESULTS The preventive program was associated with a decreased risk of reporting alcohol-related problems ( OR = .78 , 95 % confidence intervals [ CI ] = .63-.98 ) , although this reduction was not statistically significant in the subgroup of 743 current drinkers at baseline . The risk for alcohol consumption was not modified by exposure to the program ( OR = .93 , 95 % CI = .79 - 1.09 ) . In the intervention group , nondrinkers and occasional drinkers at baseline progressed toward frequent drinking less often than in the control group . CONCLUSIONS School curricula based on the comprehensive social-influence model can delay progression to frequent drinking and reduce occurrence of alcohol-related behavioral problems in European students . These results , albeit moderate , have potentially useful implication s at the population level Objective To determine whether Therapeutic Assessment ( TA ) versus assessment as usual ( AAU ) improves engagement with follow-up in adolescents presenting with self-harm . Design R and omised controlled trial with 3 months naturalistic follow-up . Setting Child and adolescent mental health services in two London National Health Service Trusts . Participants 26 clinicians r and omised into TA and AAU groups recruited 70 newly referred adolescents with self-harm . Interventions TA , a manualised procedure including a basic psychosocial assessment and a 30 min therapeutic intervention ; AAU , st and ard psychosocial assessment . Main outcome measures Attendance at the first follow-up session ; number of the follow-up sessions attended and changes in Strengths and Difficulties Question naire and Children 's Global Assessment Scale scores . All measures were adjusted for clustering , social class , changes of therapist and previous contact with services . Results Using the data on all participants ( n=70 ) , those in the TA group were significantly more likely to attend the first follow-up appointment : 29 ( 83 % ) versus 17 ( 49 % ) , OR 5.12 , 95 % CI ( 1.49 to 17.55 ) and more likely to attend four or more treatment sessions : 14 ( 40 % ) versus 4 ( 11 % ) , OR 5.19 , 95 % CI ( 2.22 to 12.10 ) . Three months after the initial assessment there were no statistically significant differences between the groups on Strengths and Difficulties Question naire scores : 15.6 versus 16.0 , mean difference −0.37 , 95 % CI ( −3.28 to 2.53 ) or Children 's Global Assessment Scale scores : 64.6 versus 60.1 , mean difference 4.49 , 95 % CI ( −0.98 to 9.96 ) . Conclusions TA was associated with statistically significant improvement in engagement . TA could be usefully applied at the point of initial assessment for adolescents with self-harm . Trial registration IS RCT N 81605131 http://www.controlled-trials.com/IS RCT Background Increased physical activity levels benefit both an individuals ' health and productivity at work . The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention design ed to increase physical activity levels . Methods A total of 1260 participants from 44 UK worksites ( based within 5 organizations ) were recruited to a cluster r and omized controlled trial with worksites r and omly allocated to an intervention or control condition . Measurement of physical activity and other variables occurred at baseline , and at 0 months , 3 months and 9 months post-intervention . Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention . The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior , delivered in-house by nominated facilitators . Self-reported physical activity ( measured using the IPAQ short-form ) and health outcomes were assessed . Results and discussion Multilevel modelling found no significant effect of the intervention on MET minutes of activity ( from the IPAQ ) at any of the follow-up time points controlling for baseline activity . However , the intervention did significantly reduce systolic blood pressure ( B = -1.79 mm/Hg ) and resting heart rate ( B = -2.08 beats ) and significantly increased body mass index ( B = .18 units ) compared to control . The intervention was found not to be cost-effective , however the substantial variability round this estimate suggested that further research is warranted . Conclusions The current study found mixed support for this worksite physical activity intervention . The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale r and omized controlled trials in real-world setting s . Trial registration Current controlled trials IS RCT Background Health care workers comprise a high-risk workgroup with respect to deterioration and early retirement . There is high prevalence of obesity and many of the workers are overweight . Together , these factors play a significant role in the health-related problems within this sector . The present study evaluates the effects of the first 3-months of a cluster r and omized controlled lifestyle intervention among health care workers . The intervention addresses body weight , general health variables , physical capacity and musculoskeletal pain . Methods 98 female , overweight health care workers were cluster-r and omized to an intervention group or a reference group . The intervention consisted of an individually dietary plan with an energy deficit of 1200 kcal/day ( 15 min/hour ) , strengthening exercises ( 15 min/hour ) and cognitive behavioral training ( 30 min/hour ) during working hours 1 hour/week . Leisure time aerobic fitness was planned for 2 hour/week . The reference group was offered monthly oral presentations . Body weight , BMI , body fat percentage ( bioimpedance ) , waist circumference , blood pressure , musculoskeletal pain , maximal oxygen uptake ( maximal bicycle test ) , and isometric maximal muscle strength of 3 body regions were measured before and after the intervention period . Results In an intention-to-treat analysis from pre to post tests , the intervention group significantly reduced body weight with 3.6 kg ( p < 0.001 ) , BMI from 30.5 to 29.2 ( p < 0.001 ) , body fat percentage from 40.9 to 39.3 ( p < 0.001 ) , waist circumference from 99.7 to 95.5 cm ( p < 0.001 ) and blood pressure from 134/85 to 127/80 mmHg ( p < 0.001 ) , with significant difference between the intervention and control group ( p < 0.001 ) on all measures . No effect of intervention was found in musculoskeletal pain , maximal oxygen uptake and muscle strength , but on aerobic fitness . Conclusion The significantly reduced body weight , body fat , waist circumference and blood pressure as well as increased aerobic fitness in the intervention group show the great potential of workplace health promotion among this high-risk workgroup . Long-term effects of the intervention remain to be investigated . Trial registration Clinical Trials.gov : PURPOSE Physical activity in childhood has many health benefits ; however , the majority of children in many countries , including Mexico , are insufficiently active . The objective of this investigation was to test the effect of a school-based environmental intervention on the physical activity and physical fitness of students attending public primary schools in Mexico City . METHODS Twenty-seven schools were r and omly assigned to basic or plus intervention or control . The basic and plus groups were exposed to school environment and policy changes to enhance physical activity . Physical activity was evaluated in 699 r and omly selected fourth- and fifth- grade students by measuring school-day and all-day ( 24 h ) steps using pedometers worn for 5 d before and after the 6-month intervention . Physical fitness was assessed by measuring the 9-min run , flexibility , and sit-ups . We calculated the average change in school-day and all-day steps and fitness measures from baseline to follow-up . Using linear regression , we tested the effect of intervention on change controlling for baseline measures and covariates and accounting for the design effect of school . Using logistic regression , we tested the effect of intervention on reaching step cutoffs at baseline and follow-up . RESULTS The plus group significantly ( P < 0.05 ) increased school-day steps relative to control ( change = 687 vs -639 ) . Significantly ( P < 0.05 ) more participants in the basic ( 25.8 % ) and plus ( 36.4 % ) groups reached step cutoffs during school relative to control ( 12.0 % ) . The basic group significantly ( P < 0.05 ) increased all-day steps relative to control ( change = 581 vs -419 ) . The plus group significantly ( P = 0.05 ) increased sit-ups relative to control ( change = 0.3 vs -1.7 ) . CONCLUSIONS A school-based environmental intervention improved student physical activity during school in public schools in Mexico City OBJECTIVE To evaluate two counseling programs in general practice to help smokers with chronic obstructive pulmonary disease ( COPD ) to quit smoking . METHODS Cluster r and omized controlled trial including 68 general practice s ( 667 patients ) using a r and omly assigned intervention program with counseling and advice about nicotine replacement therapy ( and additional bupropion-SR in one of the programs ) or usual care . Usual care consisted of periodic regular check-ups and COPD information . The main outcome measure was biochemically verified point prevalence at 12 months . RESULTS The two intervention groups were treated as one in the analysis because they were equally effective . The intervention result ed in a significantly self-reported higher success rate ( 14.5 % ) compared to usual care ( 7.4 % ) ; odds ratio=2.1 , 95 % confidence interval=1.1 - 4.1 . Biochemically verified quit rates were 7.5 % ( intervention ) and 3.4 % ( usual care ) ; odds ratio=2.3 , 95 % confidence interval=0.9 - 6.0 . CONCLUSION The program doubled the cessation rates ( statistically nonsignificant ) . Too few participants used the additional bupropion-SR to prove its effectiveness . PRACTICE IMPLICATION S The protocol s can be used for COPD patients in general practice , but expectations should be modest . If quitting is unsuccessful , a stepped care approach should be considered Objectives Offering antenatal sickle cell and thalassaemia ( SCT ) screening early in pregnancy can maximize the range of post-screening choices available , however these benefits should not be obtained at the expense of informed choice . This study examined whether offering this screening in primary care at the time of pregnancy confirmation compromises women making informed choices . Design Partial factorial , cluster r and omized controlled trial . Setting 25 general practice s in two socially deprived UK areas . Participants 464 pregnant women offered antenatal SCT screening . Intervention Practice s were r and omly allocated to offer pregnant women screening : i ) in primary care at time of pregnancy confirmation , with parallel partner testing ( n = 191 ) , ii ) in primary care at time of pregnancy confirmation , with sequential partner testing ( n = 158 ) , or iii ) in secondary care by midwives , with sequential partner testing ( st and ard care , n = 115 ) . Main outcome Informed choice-a classification based on attitudes , knowledge and test uptake . Results 91 % of woman underwent screening . About a third ( 30.6 % ) made an informed choice to accept or decline screening : 34 % in primary care parallel group ; 23.4 % in primary care sequential and 34.8 % in secondary care sequential . Allowing for adjustments , rates of informed choice did not vary by intervention group : secondary care versus primary care with parallel partner testing OR 1.07 ( 95 % CI 0.56 to 2.02 ) ; secondary care versus primary care with sequential partner testing OR 0.67 ( 95 % CI 0.36 to 1.25 ) . Uninformed choices were generally attributable to poor knowledge ( 65 % ) . Conclusion Offering antenatal SCT screening in primary care did not reduce the likelihood that women made informed choices . Rates of informed choice were low and could be increased by improving knowledge Background The HEALTHY study was design ed to respond to the alarming trends in increasing rates of overweight , obesity , and type 2 diabetes mellitus in youth . The objective of this analysis was to examine the effects of the HEALTHY study on student self-reported dietary intakes ( energy , macronutrients and grams consumed of selected food groups ) . Methods HEALTHY was a cluster-r and omized study in 42 public middle schools . Students , n = 3908 , self-reported dietary intake using the Block Kids Question naire . General linear mixed models were used to analyze differences in dietary intake at the end of the study between intervention and control schools . Results The reported average daily fruit consumption was 10 % higher at the end of the study in the intervention schools than in the control schools ( 138 g or approximately 2 servings versus 122 g , respectively , p = 0.0016 ) . The reported water intake was approximately 2 fluid ounces higher in the intervention schools than in the control ( 483 g versus 429 g respectively ; p = 0.008 ) . There were no significant differences between intervention and control for mean intakes of energy , macronutrients , fiber , grains , vegetables , legumes , sweets , sweetened beverages , and higher- or lower-fat milk consumption . Conclusion The HEALTHY study , a five-semester middle school-based intervention program that integrated multiple components in nutrition , physical education , behavior change , and social marketing-based communications , result ed in significant changes to student 's reported fruit and water intake . Subsequent interventions need to go beyond the school environment to change diet behaviors that may affect weight status of children . Clinical Trials Registration BACKGROUND Dairy foods are nutrient rich but also a source of saturated fat in the diets of children . OBJECTIVE We assessed effects on dietary intakes and health outcomes of changing dairy foods consumed by children from regular- to reduced-fat varieties . DESIGN This study was a 24-wk cluster r and omized controlled trial in 93 families with 4 - 13-y-olds who were r and omly allocated to parental education regarding changing to reduced-fat dairy foods ( n = 76 children ) or reducing screen time ( n = 69 children ) . Study outcomes , which were measured at weeks 0 , 12 ( end of the intervention ) , and 24 , included saturated fat , energy , and nutrient intakes ; pentadecanoic acid and blood lipid concentrations ; body mass index z score ; and waist circumference . Multilevel analyses were used with adjustment for child- and family-level covariates . RESULTS There were no group differences in overall dairy intakes ( -45 g dairy ; 95 % CI : -141 , 51 g dairy ; P = 0.356 ) . Saturated fat intakes were 3.3 percentage points lower ( P < 0.0001 ) in the intervention group at week 24 than in the comparison group . Pentadecanoic acid concentrations were lower at week 12 ( 0.03 % ; P = 0.012 ) but not at week 24 . LDL-cholesterol concentrations were not different at week 12 , but LDL-cholesterol concentration was 0.15 mmol/L lower in the intervention group at week 24 than in the comparison group ( P = 0.037 ) . There were no significant group differences in total energy or adiposity measures . Regular-fat dairy foods decreased from 88 % to 14 % of dairy intake in the intervention group . Calcium , magnesium , and carbohydrate ( percentage of energy ) intakes were higher in the intervention group than in the comparison group ; retinol intakes were lower in the intervention group than in the comparison group ; and overall vitamin A intakes were similar between groups . CONCLUSION Advice to parents to change to reduced-fat products was effective in reducing children 's saturated fat intakes but did not alter energy intakes or measures of adiposity . This trial was registered in the Australia New Zeal and Clinical Trials Registry as ACTRN12609000453280 OBJECTIVES To evaluate the effectiveness of a coping training program for the Chinese Special-Service Military Personnel ( SSMP ) as civil emergency responders . METHODS A parallel control trial was carried out in four special-service units ( camps ) stationed in Chongqing , China from Feb. 14th to May 30th , 2009 . A total of 396 subjects were recruited and were r and omly divided into an intervention group ( n=201 ) and a control group ( n=195 ) by clustering . Over the trial , participants in the intervention group received an additional coping-training program with 14 weekly two-hour sessions while the control group continued their normal work . RESULTS Of all 396 participants , 343 attended all the sessions and completed the given measures . In comparison to their own scores in coping strategies at pre-intervention , significant and positive changes were observed in the intervention group ( n=176 ) at post-intervention . Except for the strategy of self-blaming , the coping strategies including problem-solving , help-seeking , avoidance , fantasy and rationalization were improved . The descending order of the absolute change values over the trial in 5 coping strategies was fantasy , help-seeking , avoidance , problem-solving and rationalization . In addition , most subscales of social support and self-consistency , as powerful predictors of coping strategies , changed significantly over the intervention , while these changes were not observed in the control group ( n=167 ) . CONCLUSIONS With the combined use of modular contents and procedural methods , our intervention not only led to fewer choices of immature coping strategies like fantasy , escape and rationalization , but also raised the use of mature coping strategies such as problem-solving and help-seeking . Accordingly , the intervention will be very helpful for regular coping training of Special-Service Units , something which can be verified and generalized for the whole SSMP in a future study OBJECTIVES To test whether a decision aid improves quality of decision-making about feeding options in advanced dementia . DESIGN Cluster r and omized controlled trial . SETTING Twenty-four nursing homes in North Carolina . PARTICIPANTS Residents with advanced dementia and feeding problems and their surrogates . INTERVENTION Intervention surrogates received an audio or print decision aid on feeding options in advanced dementia . Controls received usual care . MEASUREMENTS Primary outcome was the Decisional Conflict Scale ( range : 1 - 5 ) measured at 3 months ; other main outcomes were surrogate knowledge , frequency of communication with providers , and feeding treatment use . RESULTS Two hundred fifty-six residents and surrogate decision-makers were recruited . Residents ' average age was 85 ; 67 % were Caucasian , and 79 % were women . Surrogates ' average age was 59 ; 67 % were Caucasian , and 70 % were residents ' children . The intervention improved knowledge scores ( 16.8 vs 15.1 , P < .001 ) . After 3 months , intervention surrogates had lower Decisional Conflict Scale scores than controls ( 1.65 vs 1.90 , P < .001 ) and more often discussed feeding options with a healthcare provider ( 46 % vs 33 % , P = .04 ) . Residents in the intervention group were more likely to receive a dysphagia diet ( 89 % vs 76 % , P = .04 ) and showed a trend toward greater staff eating assistance ( 20 % vs 10 % , P = .08 ) . Tube feeding was rare in both groups even after 9 months ( 1 intervention vs 3 control , P = .34 ) . CONCLUSION A decision aid about feeding options in advanced dementia reduced decisional conflict for surrogates and increased their knowledge and communication about feeding options with providers Background Evidence of the clinical benefit of 3-in-1 point-of-care testing ( POCT ) for cardiac troponin T ( cTnT ) , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) and D-dimer in cardiovascular risk stratification at primary care level for diagnosing acute coronary syndromes ( ACS ) , heart failure ( HF ) and thromboembolic events ( TE ) is very limited . The aim of this study is to analyse the diagnostic accuracy of POCT in primary care . Methods Prospect i ve multicentre controlled trial cluster-r and omised to POCT-assisted diagnosis and conventional diagnosis ( controls ) . Men and women presenting in 68 primary care practice s in Zurich County ( Switzerl and ) with chest pain or symptoms of dyspnoea or TE were consecutively included after baseline consultation and working diagnosis . A follow-up visit including confirmed diagnosis was performed to determine the accuracy of the working diagnosis , and comparison of working diagnosis accuracy between the two groups . Results The 218 POCT patients and 151 conventional diagnosis controls were mostly similar in characteristics , symptoms and pre-existing diagnoses , but differed in working diagnosis frequencies . However , the follow-up visit showed no statistical intergroup difference in confirmed diagnosis frequencies . Working diagnoses overall were significantly more correct in the POCT group ( 75.7 % vs 59.6 % , p = 0.002 ) , as were the working diagnoses of ACS/HF/TE ( 69.8 % vs 45.2 % , p = 0.002 ) . All three biomarker tests showed good sensitivity and specificity . Conclusion POCT confers substantial benefit in primary care by correctly diagnosing significantly more patients .Trial registration DRKS : Objective : The aim of this study was to compare the effects of modified constraint-induced movement therapy ( mCIMT ; restraint of unaffected limb combined with unimanual intensive rehabilitation ) with those of a bimanual intensive rehabilitation treatment ( IRP ) in children with hemiplegic cerebral palsy after a 10-wk practice vs. st and ard treatment ( ST ) . Design : This study is a multicenter , cluster-r and omized controlled clinical trial of tested groups of children with hemiplegic cerebral palsy treated using mCIMT , IRP , or ST . For 10 wks , in mCIMT and IRP , the intensive practice lasted 3 hrs/day , 7 days/wk ; in ST , 1-hr sessions twice a week were provided . The primary outcomes are upper limb/h and function ( Quality of Upper Extremity Skills Test ) and activities of daily living ( Besta Scale ) , which are assessed before and after treatment . One hundred five patients were recruited , 39 to the mCIMT group , 33 to the IRP group , and 33 to the ST group . Results : IRP and mCIMT significantly improved paretic h and function both in the Quality of Upper Extremity Skills Test and in the Besta Scale , whereas ST did not . mCIMT improved grasp more than IRP did ( P < 0.01 ) , whereas bimanual spontaneous use in play increased more with IRP ( P = 0.0005 ) . Activities of daily living in 2- to 6-yr-olds improved more with IRP ( P < 0.0001 ) than with mCIMT ( P = 0.011 ) . Unaffected limb improved more from bimanual practice ( IRP ; P = 0.02 ) . Conclusions : More advantages result ed from intensive practice than in the st and ard one , in mCIMT for grasp and in IRP for bimanual spontaneous use and activities of daily living in younger children Objective To test the effectiveness of peer support for patients with type 2 diabetes . Design Cluster r and omised controlled . Setting 20 general practice s in the east of the Republic of Irel and . Participants 395 patients ( 192 in intervention group , 203 in control group ) and 29 peer supporters with type 2 diabetes . Intervention All practice s introduced a st and ardised diabetes care system . The peer support intervention ran over a two year period and contained four elements : the recruitment and training of peer supporters , nine group meetings led by peer supporters in participant ’s own general practice , and a retention plan for the peer supporters . Main outcome measures HbA1c ; cholesterol concentration ; systolic blood pressure ; and wellbeing score . Results There was no difference between intervention and control patients at baseline . All practice s and 85 % ( 337 ) of patients were followed up . At two year follow-up , there were no significant differences in HbA1c ( mean difference −0.08 % , 95 % confidence interval −0.35 % to 0.18 % ) , systolic blood pressure ( −3.9 mm Hg , −8.9 to 1.1 mm Hg ) , total cholesterol concentration ( −0.03 mmol/L , −0.28 to 0.22 mmol/L ) , or wellbeing scores ( −0.7 , −2.3 to 0.8 ) . While there was a trend towards decreases in the proportion of patients with poorly controlled risk factors at follow-up , particularly for systolic blood pressure ( 52 % ( 87/166 ) > 130 mm Hg in intervention v 61 % ( 103/169 ) > 130 mm Hg in control ) , these changes were not significant . The process evaluation indicated that the intervention was generally delivered as intended , though 18 % ( 35 ) of patients in the intervention group never attended any group meetings . Conclusions A group based peer support intervention is feasible in general practice setting s , but the intervention was not effective when targeted at all patients with type 2 diabetes . While there was a trend towards improvements of clinical outcomes , the results do not support the widespread adoption of peer support . Trial registration Current Controlled Trials IS RCT N42541690 Objective To investigate whether real-time audio and visual feedback during cardiopulmonary resuscitation outside hospital increases the proportion of subjects who achieved prehospital return of spontaneous circulation . Design A cluster-r and omised trial . Subjects 1586 people having cardiac arrest outside hospital in whom resuscitation was attempted by emergency medical services ( 771 procedures without feedback , 815 with feedback ) . Setting Emergency medical services from three sites within the Resuscitation Outcomes Consortium in the United States and Canada . Intervention Real-time audio and visual feedback on cardiopulmonary resuscitation ( CPR ) provided by the monitor-defibrillator . Main outcome measure Prehospital return of spontaneous circulation after CPR . Results Baseline patient and emergency medical service characteristics did not differ between groups . Emergency medical services muted the audible feedback in 14 % of cases during the period with feedback . Compared with CPR clusters lacking feedback , clusters assigned to feedback were associated with increased proportion of time in which chest compressions were provided ( 64 % v 66 % , cluster-adjusted difference 1.9 ( 95 % CI 0.4 to 3.4 ) ) , increased compression depth ( 38 v 40 mm , adjusted difference 1.6 ( 0.5 to 2.7 ) ) , and decreased proportion of compressions with incomplete release ( 15 % v 10 % , adjusted difference −3.4 ( −5.2 to −1.5 ) ) . However , frequency of prehospital return of spontaneous circulation did not differ according to feedback status ( 45 % v 44 % , adjusted difference 0.1 % ( −4.4 % to 4.6 % ) ) , nor did the presence of a pulse at hospital arrival ( 32 % v 32 % , adjusted difference −0.8 ( −4.9 to 3.4 ) ) , survival to discharge ( 12 % v 11 % , adjusted difference −1.5 ( −3.9 to 0.9 ) ) , or awake at hospital discharge ( 10 % v 10 % , adjusted difference −0.2 ( −2.5 to 2.1 ) ) . Conclusions Real-time visual and audible feedback during CPR altered performance to more closely conform with guidelines . However , these changes in CPR performance were not associated with improvements in return of spontaneous circulation or other clinical outcomes . Trial Registration Clinical Trials OBJECTIVE To investigate the impact of seasonal intermittent preventive treatment ( IPTc ) on malaria-related morbidity in children < 5 years of age who already had access to home-based management of malaria ( HMM ) for presumptive treatment of fevers . METHOD Thirty community-based drug distributors ( CDDs ) from all 13 communities of a rural subdistrict in Ghana were trained to provide prompt treatment for presumptive malaria using artesunate-amodiaquine ( AS+AQ ) to all children under 5 years of age . Six communities were r and omised to also receive bimonthly courses of seasonal IPTc with AS+AQ in May , July and September of 2007 . The primary outcome was the incidence rate of febrile episodes diagnosed presumptively as malaria by the CDDs in the communities in each intervention group . Cross-sectional surveys were conducted to determine the prevalence of parasitaemia and anaemia among the study children . RESULTS During the 6 months in which IPTc was delivered , incidence of fevers in communities given HMM+IPTc was lower than in communities given HMM alone , but this difference was not statistically significant ( protective efficacy : 37.0%(95 % CI : -9.7 to 63.8 ; P = 0.14 ) . However , incidence of presumptive malaria was significantly lower in IPTc communities when only children who received all three courses of IPTc were included in the analysis : protective efficacy 61.5 % ( 95 % CI:31.2 - 78.5 ; P = 0.018 ) . Protection with IPTc was not followed by rebound morbidity in the following year . At the end of the intervention period , prevalence of asymptomatic parasitaemia was lower in communities that had received IPTc , but there were no differences in anaemia or haemoglobin concentration . CONCLUSION In this study area , incidence of fevers was lower in communities given three courses of IPTc during the time of peak transmission than in communities that received only HMM . However , high levels of coverage for IPTc will be necessary for maximum impact OBJECTIVE To evaluate the time to communicate laboratory results to health centers ( HCs ) between the e-Chasqui web-based information system and the pre-existing paper-based system . METHODS Cluster r and omized controlled trial in 78 HCs in Peru . In the intervention group , 12 HCs had web access to results via e-Chasqui ( point-of-care HCs ) and forwarded results to 17 peripheral HCs . In the control group , 22 point-of-care HCs received paper results directly and forwarded them to 27 peripheral HCs . Baseline data were collected for 15 months . Post-r and omization data were collected for at least 2 years . Comparisons were made between intervention and control groups , stratified by point-of-care versus peripheral HCs . RESULTS For point-of-care HCs , the intervention group took less time to receive drug susceptibility tests ( DSTs ) ( median 9 vs 16 days , p<0.001 ) and culture results ( 4 vs 8 days , p<0.001 ) and had a lower proportion of ' late ' DSTs taking > 60 days to arrive ( p<0.001 ) than the control . For peripheral HCs , the intervention group had similar communication times for DST ( median 22 vs 19 days , p=0.30 ) and culture ( 10 vs 9 days , p=0.10 ) results , as well as proportion of ' late ' DSTs ( p=0.57 ) compared with the control . CONCLUSIONS Only point-of-care HCs with direct access to the e-Chasqui information system had reduced communication times and fewer results with delays of > 2 months . Peripheral HCs had no benefits from the system . This suggests that health establishments should have point-of-care access to reap the benefits of electronic laboratory reporting AIMS This study aim ed to assess the effectiveness of the Örebro prevention programme ( ÖPP ) , an alcohol misuse prevention programme that aims to reduce youth drinking by changing parental behaviour . DESIGN Cluster-r and omized trial , with schools assigned r and omly to the ÖPP or no intervention . SETTING Forty municipal schools in 13 counties in Sweden . PARTICIPANTS A total of 1752 students in the 7th grade and 1314 parents were assessed at baseline . Students ' follow-up rates in the 8th and 9th grade s were 92.1 % and 88.4 % , respectively . MEASUREMENTS Classroom question naires to students and postal question naires to parents were administered before r and omization and 12 and 30 months post-baseline . FINDINGS Two-level logistic regression models , under four different methods of addressing the problem of loss to follow-up , revealed a statistically significant programme effect for only one of three drinking outcomes under one loss-to-follow-up method , and that effect was observed only at the 12-month follow-up . CONCLUSIONS The Örebro prevention programme as currently delivered in Sweden does not appear to reduce or delay youth drunkenness Abstract Background Effective interventions to increase safety and wellbeing of mothers experiencing intimate partner violence ( IPV ) are scarce . As much attention is focussed on professional intervention , this study aim ed to determine the effectiveness of non-professional mentor support in reducing IPV and depression among pregnant and recent mothers experiencing , or at risk of IPV . Methods MOSAIC was a cluster r and omised trial in 106 primary care ( maternal and child health nurse and general practitioner ) clinics in Melbourne , Australia . 63/106 clinics referred 215 eligible culturally and linguistically diverse women between January 2006 and December 2007 . 167 in the intervention ( I ) arm , and 91 in the comparison ( C ) arm . 174 ( 80.9 % ) were recruited . 133 ( 76.4 % ) women ( 90 I and 43 C ) completed follow-up at 12 months . Intervention : 12 months of weekly home visiting from trained and supervised local mothers , ( English & Vietnamese speaking ) offering non-professional befriending , advocacy , parenting support and referrals . Main outcome measures : Primary outcomes ; IPV ( Composite Abuse Scale CAS ) and depression ( Edinburgh Postnatal Depression Scale EPDS ) ; secondary measures included wellbeing ( SF-36 ) , parenting stress ( PSI-SF ) and social support ( MOS-SF ) at baseline and follow-up . Analysis : Intention-to-treat using multivariable logistic regression and propensity scoring . Results There was evidence of a true difference in mean abuse scores at follow-up in the intervention compared with the comparison arm ( 15.9 vs 21.8 , AdjDiff -8.67 , CI -16.2 to -1.15 ) . There was weak evidence for other outcomes , but a trend was evident favouring the intervention : proportions of women with CAS scores ≥7 , 51/88 ( 58.4 % ) vs 27/42 ( 64.3 % ) AdjOR 0.47 , CI 0.21 to 1.05 ) ; depression ( EPDS score ≥13 ) ( 19/85 , 22 % ( I ) vs 14/43 , 33 % ( C ) ; AdjOR 0.42 , CI 0.17 to 1.06 ) ; physical wellbeing mean scores ( PCS-SF36 : AdjDiff 2.79 ; CI -0.40 to 5.99 ) ; mental wellbeing mean scores ( MCS-SF36 : AdjDiff 2.26 ; CI -1.48 to 6.00 ) . There was no observed effect on parenting stress . 82 % of women mentored would recommend mentors to friends in similar situations . Conclusion Non-professional mentor mother support appears promising for improving safety and enhancing physical and mental wellbeing among mothers experiencing intimate partner violence referred from primary care . Trial registration OBJECTIVE Low-cost ( e.g. , computer-tailored ) interventions with sustained effects are needed to increase and maintain physical activity in older adults . This study examined the long-term efficacy of 2 computer-tailored physical activity interventions for older adults and its psychosocial and environmental mediators . METHODS A clustered r and omized controlled trial ( N = 1,971 ) was conducted that included 3 research arms : ( a ) basic computer-tailored print intervention , targeting psychosocial mediators ; ( b ) environmentally computer-tailored print intervention , targeting psychosocial and environmental mediators ; and ( c ) no-intervention control group . Interventions were developed using the intervention mapping approach and consisted of 3 computer-tailored letters delivered over 4 months . Question naires assessed the study outcomes ( i.e. , total weekly days and total weekly minutes of physical activity ) at baseline and 12 months . Potential mediators ( i.e. , awareness , attitude , self-efficacy , intention , social influence , intrinsic motivation , self-regulation , and perceived environment ) were assessed at baseline and at 3 or 6 months . RESULTS Multilevel regression analyses revealed that both interventions significantly changed total weekly days of physical activity compared with the control group , but only the environmentally computer-tailored print intervention significantly changed weekly minutes of physical activity . Multiple mediation models showed that the effects of both interventions on weekly days of physical activity were mediated by changes in awareness and intention . CONCLUSIONS Computer-tailored interventions were effective in inducing long-term behavioral changes in physical activity behavior of older adults . Awareness and intention were found to be important mediators of changing daily physical activity and should be included in future computer-tailored intervention studies Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment . The aim was to assess the effect of implementing malaria rapid diagnostic tests ( m RDTs ) on prescription of anti-malarials in urban Tanzania . Methods The design was a prospect i ve collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in r and omly selected health facilities ( HF ) in Dar es Salaam , Tanzania . The participants were all clinicians and their patients in the above health facilities . The intervention consisted of training and introduction of m RDTs in all three hospitals and in six HF . Three HF without m RDTs were selected as matched controls . The use of routine m RDT and treatment upon result was advised for all patients complaining of fever , including children under five years of age . The main outcome measures were : ( 1 ) anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention ; ( 2 ) anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after m RDT implementation . Results Based on routine statistics , the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68 % ( 95%CI 57 - 80 ) in intervention and 32 % ( 9 - 54 ) in control HF . For quinine vials , the reduction was 63 % ( 54 - 72 ) in intervention and an increase of 2.49 times ( 1.62 - 3.35 ) in control HF . Before- and -after cross-sectional surveys showed a similar decrease from 75 % to 20 % in the proportion of patients receiving anti-malarial treatment ( Risk ratio 0.23 , 95%CI 0.20 - 0.26 ) . The cluster r and omized analysis showed a considerable difference of anti-malarial prescription between intervention HF ( 22 % ) and control HF ( 60 % ) ( Risk ratio 0.30 , 95%CI 0.14 - 0.70 ) . Adherence to test result was excellent since only 7 % of negative patients received an anti-malarial . However , antibiotic prescription increased from 49 % before to 72 % after intervention ( Risk ratio 1.47 , 95%CI 1.37 - 1.59 ) . Conclusions Programmatic implementation of m RDTs in a moderately endemic area reduced drastically over-treatment with anti-malarials . Properly trained clinicians with adequate support complied with the recommendation of not treating patients with negative results . Implementation of m RDT should be integrated h and -in-h and with training on the management of other causes of fever to prevent irrational use of antibiotics Parents commonly use rewards to encourage children to eat healthfully , but this practice remains controversial because rewards are suspected of undermining children ’s intrinsic motivation . A cluster-r and omized trial examined children ’s acceptance of a disliked vegetable over 12 daily taste exposures . These exposures were paired with a tangible reward , a social reward , or no reward , and the findings were compared with the results from a no-treatment control condition . Liking and intake of the vegetable were assessed in a free-choice consumption task at preintervention , postintervention , 1 month after intervention , and 3 months after intervention . Liking increased more in the three intervention conditions than in the control condition , and there were no significant differences between the intervention conditions . These effects were maintained at follow-up . Children in both reward conditions increased consumption , and these effects were maintained for 3 months ; however , the effects of exposure with no reward became nonsignificant by 3 months . These results indicate that external rewards do not necessarily produce negative effects and may be useful in promoting healthful eating BACKGROUND Blood culture contamination leads to inappropriate or unnecessary antibiotic use . However , practical guidelines are inconsistent about the routine use of sterile gloving in collection of blood for culture . OBJECTIVE To determine whether the routine use of sterile gloving before venipuncture reduces blood culture contamination rates . DESIGN Cluster r and omized , assessor-blinded , crossover trial ( Clinical Trials.gov registration number : NCT00973063 ) . SETTING Single-center trial involving medical wards and the intensive care unit . PARTICIPANTS 64 interns in charge of collection of blood for culture were r and omly assigned to routine-to-optional or optional-to-routine sterile gloving groups for 1854 adult patients who needed blood cultures . INTERVENTION During routine sterile gloving , the interns wore sterile gloves every time before venipuncture , but during optional sterile gloving , sterile gloves were worn only if needed . MEASUREMENTS Isolates from single positive blood cultures were classified as likely contaminant , possible contaminant , or true pathogen . Contamination rates were compared by using generalized mixed models . RESULTS A total of 10 520 blood cultures were analyzed : 5265 from the routine sterile gloving period and 5255 from the optional sterile gloving period . When possible contaminants were included , the contamination rate was 0.6 % in routine sterile gloving and 1.1 % in optional sterile gloving ( adjusted odds ratio , 0.57 [ 95 % CI , 0.37 to 0.87 ] ; P = 0.009 ) . When only likely contaminants were included , the contamination rate was 0.5 % in routine sterile gloving and 0.9 % in optional sterile gloving ( adjusted odds ratio , 0.51 [ CI , 0.31 to 0.83 ] ; P = 0.007 ) . LIMITATION Blood cultures from the emergency department , surgical wards , and pediatric wards were not assessed . CONCLUSION Routine sterile gloving before venipuncture may reduce blood culture contamination Anxiety disorders are prevalent in the school-aged population and are present across cultural groups . Scant research exists on culturally relevant prevention and intervention programs for mental health problems in the Aboriginal population s. An established cognitive behavioral program , FRIENDS for Life , was enriched to include content that was culturally relevant to Aboriginal students . Students ( N = 533 ) , including 192 students of Aboriginal background , participated in the cluster r and omized control study . Data were collected three times over 1 year . A series of multilevel models were conducted to examine the effect of the culturally enriched FRIENDS program on anxiety . These analyses revealed that the FRIENDS program did not effectively reduce anxiety for the total sample or for Aboriginal children specifically . However , all students , regardless of intervention condition , Aboriginal status , or gender , reported a consistent decrease in feelings of anxiety over the 6-month study period Background Diarrhoea is the second leading cause of childhood mortality , with an estimated 1.3 million deaths per year . Promotion of Solar Water Disinfection ( SODIS ) has been suggested as a strategy for reducing the global burden of diarrhoea by improving the microbiological quality of drinking water . Despite increasing support for the large-scale dissemination of SODIS , there are few reports describing the effectiveness of its implementation . It is , therefore , important to identify and underst and the mechanisms that lead to adoption and regular use of SODIS . Methods We investigated the behaviours associated with SODIS adoption among households assigned to receive SODIS promotion during a cluster-r and omized trial in rural Bolivia . Distinct groups of SODIS-users were identified on the basis of six compliance indicators using principal components and cluster analysis . The probability of adopting SODIS as a function of campaign exposure and household characteristics was evaluated using ordinal logistic regression models . Results St and ardised , community-level SODIS-implementation in a rural Bolivian setting was associated with a median SODIS use of 32 % ( IQR : 17 - 50 ) . Households that were more likely to use SODIS were those that participated more frequently in SODIS promotional events ( OR = 1.07 , 95%CI : 1.01 - 1.13 ) , included women ( OR = 1.18 , 95%CI : 1.07 - 1.30 ) , owned latrines ( OR = 3.38 , 95%CI : 1.07 - 10.70 ) , and had severely wasted children living in the home ( OR = 2.17 , 95%CI : 1.34 - 3.49 ) . Conclusions Most of the observed household characteristics showed limited potential to predict compliance with a comprehensive , year-long SODIS-promotion campaign ; this finding reflects the complexity of behaviour change in the context of household water treatment . However , our findings also suggest that the motivation to adopt new water treatment habits and to acquire new knowledge about drinking water treatment is associated with prior engagements in sanitary hygiene and with the experience of contemporary family health concerns . Household-level factors like the ownership of a latrine , a large proportion of females and the presence of a malnourished child living in a home are easily assessable indicators that SODIS-programme managers could use to identify early adopters in SODIS promotion campaigns . Trial Registration Clinical Trials.gov : CONTEXT Evidence -based practice s improve intensive care unit ( ICU ) outcomes , but eligible patients may not receive them . Community hospitals treat most critically ill patients but may have few re sources dedicated to quality improvement . OBJECTIVE To determine the effectiveness of a multicenter quality improvement program to increase delivery of 6 evidence -based ICU practice s. DESIGN , SETTING , AND PARTICIPANTS Pragmatic cluster-r and omized trial among 15 community hospital ICUs in Ontario , Canada . A total of 9269 admissions occurred during the trial ( November 2005 to October 2006 ) and 7141 admissions during a decay-monitoring period ( December 2006 to August 2007 ) . INTERVENTION We implemented a videoconference-based forum including audit and feedback , expert-led educational sessions , and dissemination of algorithms to sequentially improve delivery of 6 practice s. We r and omized ICUs into 2 groups . Each group received this intervention , targeting a new practice every 4 months , while acting as control for the other group , in which a different practice was targeted in the same period . MAIN MEASURE OUTCOMES : The primary outcome was the summary ratio of odds ratios ( ORs ) for improvement in adoption ( determined by daily data collection ) of all 6 practice s during the trial in intervention vs control ICUs . RESULTS Overall , adoption of the targeted practice s was greater in intervention ICUs than in controls ( summary ratio of ORs , 2.79 ; 95 % confidence interval [ CI ] , 1.00 - 7.74 ) . Improved delivery in intervention ICUs was greatest for semirecumbent positioning to prevent ventilator-associated pneumonia ( 90.0 % of patient-days in last month vs 50.0 % in first month ; OR , 6.35 ; 95 % CI , 1.85 - 21.79 ) and pre caution s to prevent catheter-related bloodstream infection ( 70.0 % of patients receiving central lines vs 10.6 % ; OR , 30.06 ; 95 % CI , 11.00 - 82.17 ) . Adoption of other practice s , many with high baseline adherence , changed little . CONCLUSION In a collaborative network of community ICUs , a multifaceted quality improvement intervention improved adoption of care practice s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00332982 In a cluster r and omized trial , Beth Kangwana and colleagues find that provision of subsidized packs of the malaria therapy artemether-lumefantrine to shops more than doubled the proportion of children with fever who received drugs promptly BACKGROUND In a departure from the previous strategy of immediate defibrillation , the 2005 resuscitation guidelines from the American Heart Association-International Liaison Committee on Resuscitation suggested that emergency medical service ( EMS ) personnel could provide 2 minutes of cardiopulmonary resuscitation ( CPR ) before the first analysis of cardiac rhythm . We compared the strategy of a brief period of CPR with early analysis of rhythm with the strategy of a longer period of CPR with delayed analysis of rhythm . METHODS We conducted a cluster-r and omized trial involving adults with out-of-hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the United States and Canada . Patients in the early- analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR and those in the later- analysis group were assigned to receive 180 seconds of CPR , before the initial electrocardiographic analysis . The primary outcome was survival to hospital discharge with satisfactory functional status ( a modified Rankin scale score of ≤3 , on a scale of 0 to 6 , with higher scores indicating greater disability ) . RESULTS We included 9933 patients , of whom 5290 were assigned to early analysis of cardiac rhythm and 4643 to later analysis . A total of 273 patients ( 5.9 % ) in the later- analysis group and 310 patients ( 5.9 % ) in the early- analysis group met the criteria for the primary outcome , with a cluster-adjusted difference of -0.2 percentage points ( 95 % confidence interval , -1.1 to 0.7 ; P=0.59 ) . Analyses of the data with adjustment for confounding factors , as well as subgroup analyses , also showed no survival benefit for either study group . CONCLUSIONS Among patients who had an out-of-hospital cardiac arrest , we found no difference in the outcomes with a brief period , as compared with a longer period , of EMS-administered CPR before the first analysis of cardiac rhythm . ( Funded by the National Heart , Lung , and Blood Institute and others ; ROC PRIMED Clinical Trials.gov number , NCT00394706 . ) Objective To evaluate the effectiveness of the community based Cardiovascular Health Awareness Program ( CHAP ) on morbidity from cardiovascular disease . Design Community cluster r and omised trial . Setting 39 mid-sized communities in Ontario , Canada , stratified by location and population size . Participants Community dwelling residents aged 65 years or over , family physicians , pharmacists , volunteers , community nurses , and local lead organisations . Intervention Communities were r and omised to receive CHAP ( n=20 ) or no intervention ( n=19 ) . In CHAP communities , residents aged 65 or over were invited to attend volunteer run cardiovascular risk assessment and education sessions held in community based pharmacies over a 10 week period ; automated blood pressure readings and self reported risk factor data were collected and shared with participants and their family physicians and pharmacists . Main outcome measure Composite of hospital admissions for acute myocardial infa rct ion , stroke , and congestive heart failure among all community residents aged 65 and over in the year before compared with the year after implementation of CHAP . Results All 20 intervention communities successfully implemented CHAP . A total of 1265 three hour long sessions were held in 129/145 ( 89 % ) pharmacies during the 10 week programme . 15 889 unique participants had a total of 27 358 cardiovascular assessment s with the assistance of 577 peer volunteers . After adjustment for hospital admission rates in the year before the intervention , CHAP was associated with a 9 % relative reduction in the composite end point ( rate ratio 0.91 , 95 % confidence interval 0.86 to 0.97 ; P=0.002 ) or 3.02 fewer annual hospital admissions for cardiovascular disease per 1000 people aged 65 and over . Statistically significant reductions favouring the intervention communities were seen in hospital admissions for acute myocardial infa rct ion ( rate ratio 0.87 , 0.79 to 0.97 ; P=0.008 ) and congestive heart failure ( 0.90 , 0.81 to 0.99 ; P=0.029 ) but not for stroke ( 0.99 , 0.88 to 1.12 ; P=0.89 ) . Conclusions A collaborative , multi-pronged , community based health promotion and prevention programme targeted at older adults can reduce cardiovascular morbidity at the population level . Trial registration Current controlled trials IS RCT N50550004 The aim of this study was to evaluate the effects of integrative neuromuscular training ( INT ) during physical education ( PE ) class on selected measures of health- and skill-related fitness in children . Forty children from two 2nd grade PE classes were cluster r and omized into either an INT group ( n = 21 ) or a control ( CON ) group ( n = 19 ) . INT was performed 2 × /wk during the first ~15 min of each PE class and consisted of body weight exercises . INT and CON participants were assessed for health- and skill-related fitness before and after 8 wks of PE with or without INT , respectively . A significant interaction of group by time was observed in INT participants with improvements noted in push-ups , curl-ups , long jump , single leg hop , and 0.5 mile ( 0.8 km ) run performance ( p < .05 ) . These data indicate that INT is an effective and time-efficient addition to PE as evidence d by improvements in health- and skill-related fitness measures in children BACKGROUND Newborn deaths account for 57 % of deaths in children younger than 5 years in Pakistan . Although a large programme of trained lady health workers ( LHWs ) exists , the effectiveness of this training on newborn outcomes has not been studied . We aim ed to evaluate the effectiveness of a community-based intervention package , principally delivered through LHWs working with traditional birth attendants and community health committees , for reduction of perinatal and neonatal mortality in a rural district of Pakistan . METHODS We undertook a cluster r and omised trial between February , 2006 , and March , 2008 , in Hala and Matiari subdistricts , Pakistan . Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters , which were allocated to intervention and control groups by restricted , stratified r and omisation . The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education , use of clean delivery kits , facility births , immediate newborn care , identification of danger signs , and promotion of careseeking ; control clusters received routine care . Independent data collectors undertook quarterly household surveillance to capture data for births , deaths , and household practice s related to maternal and newborn care . Data collectors were masked to cluster allocation ; those analysing data were not . The primary outcome was perinatal and all-cause neonatal mortality . Analysis was by intention to treat . This trial is registered , IS RCT N16247511 . FINDINGS 16 clusters were assigned to intervention ( 23,353 households , 12,391 total births ) and control groups ( 23,768 households , 11,443 total births ) . LHWs in the intervention clusters were able to undertake 4428 ( 63 % ) of 7084 planned group sessions , but were only able to visit 2943 neonates ( 24 % ) of a total 12,028 livebirths in their catchment villages . Stillbirths were reduced in intervention clusters ( 39·1 stillbirths per 1000 total births ) compared with control ( 48·7 per 1000 ; risk ratio [ RR ] 0·79 , 95 % CI 0·68 - 0·92 ; p=0·006 ) . The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups ( RR 0·85 , 0·76 - 0·96 ; p=0·02 ) . INTERPRETATION Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential . FUNDING WHO ; Saving Newborn Lives Program of Save the Children USA , funded by the Bill & Melinda Gates Foundation INTRODUCTION AND OBJECTIVES To assess the efficacy of a comprehensive program of secondary prevention of cardiovascular disease in general practice . METHODS A cluster r and omized clinical trial was carried out in a regular general practice setting . Male and female patients aged under 86 years with a diagnosis of ischemic heart disease , stroke or peripheral artery disease were recruited between January 2004 and May 2005 . Study participants were seen at 42 health centers throughout the whole of Spain . The primary endpoint was the combination of all-cause mortality and hospital cardiovascular readmission at 3-year follow-up . RESULTS In total , 1224 patients were recruited : 624 in the intervention group and 600 in the control group . The primary endpoint was observed in 29.9 % ( 95 % confidence interval [ CI ] , 25.5 - 34.8 % ) in the intervention group and 25.6 % ( 22.3 - 29.2 % ) in the control group ( P=.15 ) . At the end of follow-up , 8.5 % ( 6.3 - 11.3 % ) in the intervention group and 11 % ( 7.4 - 16 % ) in the control group were smokers ( P=.07 ) . The mean waist circumference of patients in the intervention and control groups was 100.44 cm ( 95 % CI , 98.97 - 101.91 cm ) and 102.58 cm ( 95 % CI , 100.96 - 104.21 cm ) , respectively ( P=.07 ) . Overall , 20.9 % ( 15.6 - 27.7 % ) of patients in the intervention group and 29.6 % ( 23.9 - 36.1 % ) in the control group suffered from anxiety ( P=.05 ) , and 29.6 % ( 22.4 - 37.9 % ) in the intervention group and 41.4 % ( 35.8 - 47.3 % ) in the control group had depression ( P=.02 ) . CONCLUSIONS A comprehensive program of secondary prevention of cardiovascular disease in general practice was not effective in reducing cardiovascular morbidity and mortality . However , some factors associated with a healthy lifestyle were improved and anxiety and depression were reduced A cluster r and omized controlled trial was initiated in the Triv and rum district ( Kerala , India ) on January 1 , 2006 , to evaluate whether three rounds of triennial clinical breast examination ( CBE ) can reduce the incidence rate of advanced disease incidence and breast cancer mortality . A total of 275 clusters that included 115,652 healthy women , aged 30 - 69 years , were r and omly allocated to intervention ( CBE ; 133 clusters ; 55,844 women ) or control ( no screening ; 142 clusters ; 59,808 women ) groups . Performance characteristics ( sensitivity , specificity , false-positive rate , and positive predictive value ) of CBE were evaluated . An intention-to-treat analysis was performed for comparison of incidence rates between the intervention and control groups . Preliminary results for incidence are based on follow-up until May 31 , 2009 , when the first round of screening was completed . Of the 50,366 women who underwent CBE , 30 breast cancers were detected among 2880 women with suspicious findings in CBE screening that warranted further investigations . Sensitivity , specificity , false-positive rate , and positive predictive value of CBE were 51.7 % ( 95 % confidence interval [ CI ] = 38.2 % to 65.0 % ) , 94.3 % ( 95 % CI = 94.1 % to 94.5 % ) , 5.7 % ( 95 % CI = 5.5 % to 5.9 % ) , and 1.0 % ( 95 % CI = 0.7 % to 1.5 % ) , respectively . The age-st and ardized incidence rates for early-stage ( stage IIA or lower ) breast cancer were 18.8 and 8.1 per 100,000 women and for advanced-stage ( stage IIB or higher ) breast cancer were 19.6 and 21.7 per 100,000 women , in the intervention and control groups , respectively Objectives : The Enriched Opportunities Programme ( EOP ) is a multi-level intervention focussing on improved quality of life for people with dementia . This study compared the experience of people living with dementia and other mental health problems in extra care housing schemes that utilised EOP with schemes that employed an active control intervention . Method : Ten extra care housing schemes were cluster r and omised to receive either the EOP intervention or an active control intervention for an 18-month period . Residents with dementia or other significant mental health problems ( 20–30 per scheme ) were assessed on a number of outcome measures at baseline , six months , one year and 18 months . The primary outcome measure was quality of life . Self-reported depression was an important secondary outcome . Results : The EOP-participating residents rated their quality of life more positively over time ( 4.0 ( SE 0.6 ) units ; 14 % p < 0.001 ) than the active control ( 1.3 ( SE 0.6 ) units ; 4 % p = 0.003 ) . There was also a significant group – time interaction for depressive symptoms ( p = 0.003 ) . The EOP-participating residents reported a reduction of 25 % at both six and 12 months and a 37 % reduction at 18 months ( all p 's < 0.001 ) . EOP residents were less likely than residents in the active control sites to move to a care home or to be admitted to a hospital inpatient bed . They were more likely to be seen by a range of community health professionals . Conclusion : The EOP had a positive impact on the quality of life of people with dementia in well-staffed extra care housing schemes Background Physical activity ( PA ) in children has declined in recent decades , highlighting the need for effective intervention programs for school-aged children . The main objective of this study was to assess to what extent PA during and after school hours changed among children who received a progressive two-year long intervention vs. that of children who only received general curriculum-based PA . Methods A cluster r and omized intervention study was conducted and six elementary schools r and omly assigned to serve as control- or intervention schools . All children attending second grade ( mean age = 7.4 years - born in 1999 ) were invited to participate in the fall of 2006 ( N = 320 , 82 % participated ) , again in 2007 ( midpoint ) and 2008 ( end of intervention ) . The intervention consisted of multi-component PA-intervention during school hours and was conducted by teachers at each intervention school . PA was assessed by means of accelerometers and subjectively at the intervention schools via teachers ' PA log-books . Results There was no difference in PA intensity ( minutes of moderate-to-vigorous physical activity - min of MVPA ) between the two study groups at baseline , but children in the intervention schools were more physically active at moderate-to-vigorous intensity compared to those in control schools after one year of intervention ( mean difference of MVPAlog-minutes : 0.61 , 95%CI : 0.02 , 1.20 , p = 0.04 ) . Moreover , the model for minutes of MVPA during school hours , showed a significant three-way interaction between time at mid-point , group and gender ( mean difference of MVPAlog-minutes : 1.06 , 95%CI : 0.15 , 1.97 , p = .02 ) , indicating a significantly greater increase among the boys in the intervention schools compared to girls . No difference in PA was detected between the study groups at the end of the study period after two years of intervention . Conclusions The results suggest that the objective of increasing PA at school was met after one year of intervention , and it was more pronounced among boys . The lack of increase at the end of the study period suggested that any increase in PA during school may highly depend on both motivation and training of general teachers . Boys may respond better to PA interventions such as the one described in this study BACKGROUND Proper use of clinical practice guidelines can decrease variation in care between setting s. However , actual use of fertility guidelines is suboptimal and in need of improvement . Hence , a cluster-r and omized controlled trial was design ed to study the effects of two strategies to implement national Dutch guidelines on comprehensive fertility care . METHODS Sixteen fertility clinics participated in the trial . A minimal , professional-oriented implementation strategy of audit and feedback was tested versus a maximal multi-faceted strategy that was both professional and patient oriented . The extent of adherence to guideline recommendations , reflected in quality indicator scores , was the primary outcome measure . To gain an insight into unwanted side effects , patient anxiety and depression scores were gathered as secondary outcomes . Data collection encompassed medical record search , patient and professional question naires . RESULTS A total of 1499 couples were included at baseline and 1396 at the after-measurement . No overall significant improvement in indicator scores was found for either strategy [ odds ratios ranging from 0.23 ( 95 % confidence interval ( CI ) : 0.06 - 0.95 ) to 6.66 ( 95 % CI : 0.33 - 132.8 ] . Secondary outcomes did not differ significantly for both groups , although selected anxiety scores appeared lower in the maximal intervention group . Process evaluation of the trial revealed positive patient experiences with the intervention material [ e.g. an increased underst and ing of their doctor 's treatment policy ( 61 % ) , an increased ability to ask questions about the treatment ( 61 % ) ] . Professionals ' appreciation of intervention elements varied , and execution of the multi-faceted strategy appeared incomplete . DISCUSSION Absence of an intervention effect may be due to the nature of the strategies , incomplete execution or flaws in study design . Process evaluation data raise the question of whether professionals should be the only stakeholder responsible for guideline implementation . This study therefore contributes to an increased underst and ing of fertility guideline implementation in general , and the role of patients in particular BACKGROUND Acute pharyngitis is one of the most frequent reasons for a GP consultation , and in most cases an antibiotic is prescribed . AIM To determine the impact of rapid antigen detection testing ( RADT ) to identify group A beta haemolytic streptococcus in acute pharyngitis on the utilisation of antibiotics and appropriateness of their use . DESIGN AND SETTING Cluster r and omised controlled trial in primary care centres in Catalonia , Spain . METHOD Patients with acute pharyngitis aged 14 years or older with at least one Centor criterion ( fever , tonsillar exu date , tender enlarged anterior cervical lymph nodes , or absence of cough ) were recruited . Participant physicians were r and omly assigned to one of two study arms : an intervention group ( assigned to RADT ) and a control group ( following usual care , without RADT ) . RESULTS Of the 557 adults enrolled , 543 could be evaluated for analysis ( 281 [ 51.7 % ] in the intervention group and 262 [ 48.3 % ] in the control group ) . GPs without access to RADT were more likely to prescribe antibiotics compared with those who performed rapid tests ( 64.1 % versus 43.8 % , P<0.001 ) . The more Centor criteria the patients presented , the greater the number of antibiotics prescribed , regardless of whether RADT was available ( P<0.001 ) . Antibiotics were prescribed in 30.7 % of the cases with negative RADT results . Inappropriate antibiotic prescription was observed in 226 cases ( 43 % ) , and was significantly greater in the control than in the intervention group ( 60 % versus 26.9 % ; P<0.001 ) . CONCLUSION Even though more than 30 % of negative RADT results result ed in antibiotic prescribing , the study findings support the use of RADT in the consultation . This strategy has an important impact on reducing antibiotic prescription among adults with acute pharyngitis Background Cleaners constitute a job group with poor health and low socioeconomic re sources . Therefore , there is a great need for scientifically documented health promoting initiatives for cleaners . However , both workplace initiatives and high quality intervention studies are lacking . The aim of this study was to evaluate the effects of a 3-month workplace trial with interventions to improve physical or cognitive behavioural re sources among cleaners . Methods A cluster r and omised controlled trial was conducted among 294 female cleaners from 9 workplaces . The participants were allocated to three groups : Physical coordination training ( PCT , n = 95 ) , Cognitive behavioural theory-based training ( CBTr , n = 99 ) and Reference group ( REF , n = 100 ) . Interventions were conducted during work hours for an average of 1 hour/week . Muscle strength was measured by maximal voluntary contractions in trunk/extension , and shoulder abduction/elevation . Postural balance was measured on a force platform . Kinesiophobia was measured with Tampa Scale for Kinesiophobia . Test and question naires were completed at baseline and at 3-month follow-up and analyses followed the intention-to-treat ( ITT ) principle with last observation carried forward in case of missing data at follow-up . Reports and analyses are given on true observations as well . Results ITT-analyses revealed that PCT improved strength of the trunk ( p < .05 ) and postural balance ( p < .05 ) compared to CBTr and REF . Based on true observations the strength and balance improvements corresponded to ~20 % and ~16 % , respectively . ITT-analyses showed that CBTr reduced kinesiophobia compared to PCT and REF ( p < .05 ) . Based on true observations , the improvement corresponded to a ~16 % improvement . Conclusion This workplace-based intervention study including PCT and CBTr among cleaners improved strength and postural balance from PCT , and kinesiophobia from CBTr . The improved strength , postural balance and kinesiophobia may improve the cleaners ' tolerance for high physical work dem and s. Future studies should investigate the potential in the combination of PCT and CBTr in a workplace intervention . Trial registration Current controlled trials IS RCT Summary We conducted a cluster r and omized trial evaluating the effect of a central ized coordinator who identifies and follows up with fracture patients and their primary care physicians about osteoporosis . Compared with controls , intervention patients were five times more likely to receive BMD testing and two times more likely to receive appropriate management . Introduction To determine if a central ized coordinator who follows up with fracture patients and their primary care physicians by telephone and mail ( intervention ) will increase the proportion of patients who receive appropriate post-fracture osteoporosis management , compared to simple fall prevention advice ( attention control ) . Methods A cluster r and omized controlled trial was conducted in small community hospitals in the province of Ontario , Canada . Hospitals that treated between 60 and 340 fracture patients per year were eligible . Patients 40 years and older presenting with a low trauma fracture were identified from Emergency Department records and enrolled in the trial . The primary outcome was ‘ appropriate ’ management , defined as a normal bone mineral density ( BMD ) test or taking osteoporosis medications . Results Thirty-six hospitals were r and omized to either intervention or control and 130 intervention and 137 control subjects completed the study . The mean age of participants was 65 ± 12 years and 69 % were female . The intervention increased the proportion of patients who received appropriate management within 6 months of fracture ; 45 % in the intervention group compared with 26 % in the control group ( absolute difference of 19 % ; adjusted OR , 2.3 ; 95 % CI , 1.3–4.1 ) . The proportion who had a BMD test scheduled or performed was much higher with 57 % of intervention patients compared with 21 % of controls ( absolute difference of 36 % ; adjusted OR , 4.8 ; 95 % CI , 3.0–7.0 ) . Conclusions A central ized osteoporosis coordinator is effective in improving the quality of osteoporosis care in smaller communities that do not have on-site coordinators or direct access to osteoporosis specialists OBJECTIVES To evaluate the efficacy of a healthcare education program for patients with hypertension . METHODS A multicenter , prospect i ve , cluster-r and omized trial was conducted . R and omization was by primary care center ; 18 of 36 urban primary care centers in Barcelona and its metropolitan area were r and omized to the intervention group ( IG ) and 18 to the control group ( CG ) . The study sample consisted of patients with hypertension ( n=996 ; 515 in the IG and 481 in the CG ) receiving outpatient treatment with antihypertensive drugs . The intervention consisted of personalized information by a trained nurse and written leaflets . Question naires on knowledge and awareness of hypertension and its medication , treatment adherence , healthy lifestyle habits , systolic and diastolic blood pressure , and body mass index were assessed at each visit , with a 12-month follow-up . An intention-to-treat analysis was applied . RESULTS Knowledge of hypertension increased by 27.8 % in the IG and by 18.5 % in the CG , while that of medication increased by 10.1 % in the IG and 5.5 % in the CG . Treatment adherence measured by the Morisky-Green test increased by 9.6 % ( 95 % CI : 5.5 - 13.6 ) in the IG and 8.8 % ( 95 % CI : 4.9 - 12.6 ) in the CG . There were no differences in adherence on the other tests used . No differences were observed between the IG and CG in clinical variables such as blood pressure or BMI at the end of the trial . CONCLUSIONS The educational intervention had no significant impact on patients ' adherence to the medication Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544 Summary Background Health workers ' malaria case-management practice s often differ from national guidelines . We assessed whether text-message reminders sent to health workers ' mobile phones could improve and maintain their adherence to treatment guidelines for outpatient paediatric malaria in Kenya . Methods From March 6 , 2009 , to May 31 , 2010 , we did a cluster-r and omised controlled trial at 107 rural health facilities in 11 districts in coastal and western Kenya . With a computer-generated sequence , health facilities were r and omly allocated to either the intervention group , in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months , or the control group , in which health workers did not receive any text messages . Health workers were not masked to the intervention , although patients were unaware of whether they were in an intervention or control facility . The primary outcome was correct management with artemether-lumefantrine , defined as a dichotomous composite indicator of treatment , dispensing , and counselling tasks concordant with Kenyan national guidelines . The primary analysis was by intention to treat . The trial is registered with Current Controlled Trials , IS RCT N72328636 . Findings 119 health workers received the intervention . Case-management practice s were assessed for 2269 children who needed treatment ( 1157 in the intervention group and 1112 in the control group ) . Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23·7 percentage-points ( 95 % CI 7·6–40·0 ; p=0·004 ) immediately after intervention and by 24·5 percentage-points ( 8·1–41·0 ; p=0·003 ) 6 months later . Interpretation In re source -limited setting s , malaria control programmes should consider use of text messaging to improve health workers ' case-management practice s. Funding The Wellcome Trust Background Although leisure-time physical activity is important for health , adherence to regular exercise is challenging for many adults . The workplace may provide an optimal setting to reach a large proportion of the adult population needing regular physical exercise . This study evaluates the effect of implementing strength training at the workplace on non-specific neck and shoulder pain among industrial workers . Methods Cluster-r and omized controlled trial involving 537 adults from occupations with high prevalence of neck and shoulder pain ( industrial production units ) . Participants were r and omized to 20 weeks of high-intensity strength training for the neck and shoulders three times a week ( n = 282 ) or a control group receiving advice to stay physically active ( n = 255 ) . The strength training program followed principles of progressive overload and periodization . The primary outcome was changes in self-reported neck and shoulder pain intensity ( scale 0 - 9 ) . Results 85 % of the participants followed the strength training program on a weekly basis . In the training group compared with the control group , neck pain intensity decreased significantly ( -0.6 , 95 % CI -1.0 to -0.1 ) and shoulder pain intensity tended to decrease ( -0.2 , 95 % CI -0.5 to 0.1 , P = 0.07 ) . For pain-cases at baseline ( pain intensity > = 3 ) the odds ratio - in the training group compared with the control group - for being a non-case at follow-up ( pain intensity < 3 ) was 2.0 ( 95 % CI 1.0 to 4.2 ) for the neck and 3.9 ( 95 % CI 1.7 to 9.4 ) for the shoulders . Conclusion High-intensity strength training relying on principles of progressive overload can be successfully implemented at industrial workplaces , and results in significant reductions of neck and shoulder pain . Trial registration NCT01071980 BACKGROUND Antibiotic overuse is of great public health concern . This study assessed whether intervention among physicians and their treated population could achieve a sustained reduction in antibiotic use , specifically in classes known to promote antibiotic resistance among children in a community setting . METHODS We performed a cluster r and omized controlled multifaceted trial among 52 primary care pediatricians and the 88,000 children registered in their practice s. The intervention was led by local leaders and engaged the participating physicians . It included physician focus group meetings , workshops , seminars , and practice campaigns . These activities focused on self-developed guidelines , improving parent and physician knowledge , diagnostic skills , and parent-physician communication skills that promoted awareness of antibiotic resistance . The main outcome measure was the change in annual antibiotic prescription rates ( APRs ) of children treated by the intervention group physicians as compared with rates among those treated by control group physicians . The study comprised a 2-year pre-intervention period , a 3-year intervention period , and a 1-year follow-up period . Mixed-effect models were used to assess risk ratios to account for the clustered study design . RESULTS A decrease in the total APR among children treated by the intervention physicians compared with those treated by the control physicians was observed in the first intervention year ( APR decrease among control physicians , 40 % ; APR decrease among intervention physicians , 22 % ; relative risk [ RR ] , .76 ; 95 % confidence interval [ CI ] , .75-.78 ) . This reduction crossed over all antibiotic classes but was most prominent for macrolides ( macrolide prescription rate among control physicians , 58 % ; macrolide prescription rate among intervention physicians , 27 % ; RR , .58 ; 95 % CI , .55-.62 ) . The effect was sustained during the 4 following years . CONCLUSIONS . Multifaceted intervention that engages the physicians in an educational process is effective in reducing APRs and can be sustained . CLINICAL TRIALS REGISTRATION NCT01187758 In a cluster-r and omized trial conducted in Gambian villages , Anna Roca and colleagues find that vaccination of children with pneumococcal conjugate vaccines reduced vaccine-type pneumococcal carriage even among nonvaccinated older children and adults OBJECTIVES : The impact of endoscopic retro grade cholangiopancreatography ( ERCP ) mechanical simulator ( EMS ) practice on trainee clinical performance is unknown . The hypothesis that trainees with EMS practice ( study group ( SG ) ) have improved clinical outcomes compared with those without such practice ( control group ( CG ) ) is tested . METHODS : This was a r and omized controlled trial involving six US academic centers . Sixteen trainees were r and omized after ERCP didactic teaching . SG ( n=8 ) participated in two sessions of EMS practice on selective cannulation ; CG ( n=8 ) did not undergo EMS practice . All participants ’ clinical performances were monitored in the subsequent 16 weeks . Intervention effects were assessed in multivariable regression models using generalizing estimating equations ( GEE ) to account for cluster r and omization of trainees . The primary outcome was successful biliary cannulation , and secondary outcomes were cannulation time and competency score . RESULTS : Cannulation success rate was 47.1 % for CG and 69.6 % for SG . SG had higher odds of successful cannulation ( adjusted odds ratio=3.01 , P=0.021 ) . SG trainees achieved faster cannulation time ( min ) ( 4.7±4.2 vs. 10.3±14.1 , P<0.001 ) . Trainee competency scores given by supervising physicians were comparable confirming adequate blinding of the trainers . Limitations included short observation period , small number of ERCPs performed by individual trainees , and variation in the number of ERCPs between trainees . CONCLUSIONS : In a prospect i ve multicenter r and omized controlled trial during early training , a significantly higher proportion of the biliary cannulations performed by trainees with EMS practice were successful and with faster cannulation time compared with those performed by trainees without such practice . The results provide objective evidence to support the continued evaluation of EMS practice to augment clinical training The successful transfer of clinical practice guidelines ( CPGs ) into patient care depends on the appropriateness of the implementation method . This study strived for a better underst and ing of which intervention strategy is effective in implementing the CPG on Parkinson ’s disease ( CPG-PD ) . In a cluster r and omized controlled trial , we compared the impact of two different implementation strategies of the CPG-PD on health outcomes of PD patients . The primary outcome of health-related quality of life was measured by PDQ-39 . The neurologists of the intervention group ( IG ) versus a control group ( CG ) received the CPG-PD with special instructions , a 4-h training and were offered personal feedback . Patients were followed over three assessment times : baseline , post-test ( 6 months ) and follow-up ( 9 months ) . Lack of time and remuneration result ed in low study participation ( 32 out of 619 contacted neurologists ) . Multilevel modelling revealed that primary ( PDQ-39 ) and secondary efficacy variables ( EQ-5D , CGI , HADS-D , ZUF-8 ) of 386 patients were not affected significantly by the intervention and failed to show any significant difference between the two groups . The EQ-5D VAS scale ( p = 0.0288 ) and the CGI-P severity scale ( p = 0.0072 ) showed a significant worsening over time . A significant decrease of hours of dyskinesias in the IG ( p = 0.007 ) was observed , whereas Parkinson symptoms did not change significantly between the groups . Lacking awareness of the CPG-PD seems to be no longer a barrier for its use , but it is still a major challenge to find effective implementation methods to optimise clinical outcome . Further studies are needed for a more comprehensive underst and ing of successful implementation strategies OBJECTIVES To test different adherent strategies aim ed at improving hip protector use among nursing care facility residents . DESIGN , SETTING AND PARTICIPANTS A cluster r and omized controlled trial with 234 residents older than 75 years from 9 units of 7 nursing care facilities in the Northern Sydney region , Australia . INTERVENTION Residents were cluster r and omized in 3 groups . The first group received hard shell hip protectors without cost ( no cost group ) . The second group received an educational session , a demonstration of the use of hip protectors , and free choice of type of hip protectors without cost ( combined group ) . The third group was the control group who received a brochure about hip protectors . MEASUREMENTS Primary outcome was adherence with the use of hip protectors at 3 and 6 months after recruitment . Secondary outcomes were falls , injuries , and fractures . RESULTS No participants in the control group purchased hip protectors at any stage . At 3 months , 33 % of participants in the no cost group and 27 % in the combined group wore a hip protector at the time of visit . This declined to 25 % and 24 % respectively at 6 months . No significant difference was seen in any of the 3 adherence outcomes between the 2 intervention groups . The number of falls or hospitalizations did not differ between groups , with 5 hip fractures reported during the intervention period . Residents were more likely to be adherent if they were female and had greater restriction in daily activities . CONCLUSION Providing free hip protectors to older people living in nursing care facilities was necessary to increase initial acceptance and adherence . Nevertheless , after 6 months the achieved level of adherence was not high enough to be associated with a reduction of hip fractures . The provision of educational sessions and demonstrations to nursing staff and participants had no added value in this trial Objective To compare the uptake of faecal immunochemical occult blood test ( FIT ) with guaiac faecal occult blood test ( gFOBT ) in a screening programme , with specific attention to the demographic and socioeconomic factors that might affect test uptake . Setting The Clalit Health Service screening programme , Israel . Methods Average-risk individuals aged 50–75 years were r and omized into a FIT arm or gFOBT arm using a programme based on the socioeconomic status ( SES ) of their primary care clinics . G-FOBT was performed with Hemoccult SENSA ™ ( 3 evacuations ) and FIT with the OC- MICRO ™ ( 3 evacuations , refrigerating m and ated ) . The GLIMMIX model was used . Results There were 5,464 and 10,668 eligible participants in the FIT and gFOBT arms respectively . Compliance in taking the kits was better ( but not statistically significantly better ) with gFOBT ( 37.8 % vs. 29.3 % ; odds ratio [ OR ] 1.43 [ 95 % CI 0.73–2.80 ] ; P = 0.227 ) . Kit return was higher in the FIT arm ( 65.0 % vs. 78.9 % ; OR 0.45 [ 95 % CI 0.24–0.83 ] , P = 0.021 ) . Overall test uptake was affected by age , gender , being immigrant and SES ( determined by whether or not the participant paid national insurance tax , and the SES of the primary care clinic ) . The overall uptake of gFOBT and FIT was comparable ( OR 0.996 [ 95 % CI 0.46–2.17 ] , P = 0.99 ) . Conclusions Overall compliance for test uptake was comparable between the two methods despite the more dem and ing procedure in the FIT arm . Sociodemographic parameters were the major determinants of compliance . An educational programme , with emphasis on the sociodemographic characteristics of the target population , should be instigated BACKGROUND School-based asthma education programs targeting disadvantaged youth and teens with asthma are lacking . OBJECTIVES To assess the impact of the Fight Asthma Now ( FAN ) educational program among 2 population s of predominantly low-income minority students : youth ( 3(rd)-6(th ) grade rs ) and teens ( 7(th)-8(th ) grade rs ) . METHODS Chicago-area elementary schools were invited to participate in this stratified 2-arm study . Eligible schools were assigned to participate either in the intervention or in the control arm . Within each participating school , eligible students were recruited and grouped ( stratified by grade and age ) to form teen or youth classes . Participants completed a pre- and post-intervention asthma knowledge question naire and observation for spacer technique competency . The treatment group received the FAN curriculum between the evaluations . RESULTS A sample of 26 low-income , predominantly minority-serving schools was recruited . Most participating schools were r and omized in a 3:1 ratio to form 25 youth classes ( 19 intervention and 6 control group ) and 16 teen classes ( 11 intervention and 5 control group ) , result ing in 275 vs 69 youth and 141 vs 51 teens in the intervention and control groups , respectively . Stratified analyses were performed , and clustering within the school and class was taken into consideration in analyses . Multilevel models adjusting for school , class , ethnicity , sex , and pretest score indicate that the FAN intervention significantly increased both knowledge and spacer competency test scores , among both the youth and teen participants ( P = .011 with respect to knowledge score among teen students , P < .0001 for all other cases ) . CONCLUSIONS This study suggests that FAN significantly increases asthma knowledge and spacer technique competency within this high-risk population BACKGROUND The effect of interdisciplinary primary care teams on the use of health services by patients with multiple chronic conditions is uncertain . This study aim ed to measure the effect of guided care teams on multimorbid older patients ' use of health services . METHODS Eligible patients from 3 health care systems in the Baltimore , Maryl and -Washington , DC , area were cluster-r and omized to receive guided care or usual care for 20 months between November 1 , 2006 , and June 30 , 2008 . Eight services of a guided care nurse working in partnership with patients ' primary care physicians were provided : comprehensive assessment , evidence -based care planning , monthly monitoring of symptoms and adherence , transitional care , coordination of health care professionals , support for self-management , support for family caregivers , and enhanced access to community services . Outcome measures were frequency of use of emergency departments , hospitals , skilled nursing facilities , home health agencies , primary care physician services , and specialty physician services . RESULTS The study included 850 older patients at high risk for using health care heavily in the future . The only statistically significant overall effect of guided care in the whole sample was a reduction in episodes of home health care ( odds ratio , 0.70 ; 95 % confidence interval , 0.53 - 0.93 ) . In a preplanned analysis , guided care also reduced skilled nursing facility admissions ( odds ratio , 0.53 ; 95 % confidence interval , 0.31 - 0.89 ) and days ( 0.48 ; 0.28 - 0.84 ) among Kaiser-Permanente patients . CONCLUSIONS Guided care reduces the use of home health care but has little effect on the use of other health services in the short run . Its positive effect on Kaiser-Permanente patients ' use of skilled nursing facilities and other health services is intriguing . Trial Registration clinical trials.gov Identifier : NCT00121940 INTRODUCTION A smoking prevention program was developed to prepare children in elementary school for secondary school . This study assessed the effects on smoking in secondary school . METHODS In 2002 , 121 schools in The Netherl and s were r and omly assigned to the intervention or control group . The intervention group received 3 lessons in 5th grade of elementary school and a second 3 lessons in 6th grade . The control group received " usual care " . Students completed 5 question naires : before and after the lessons in 5th and 6th grade and in the first class of secondary school . At baseline , 3173 students completed the question naire ; 57 % completed all question naires . RESULTS The program had limited effect at the end of elementary school . One year later in secondary school significant effects on behavioral determinants and smoking were found . The intervention group had a higher intention not to smoke ( β=0.13 , 95 % confidence interval=0.01 - 0.24 ) and started to smoke less often than the control group ( odds ratio=0.59 , 95 % confidence interval=0.35 - 0.99 ) : smoking increased from 2.5 % to 3.6 % in the intervention group and from 3.2 % to 6.5 % in the control group . Girls showed the largest differences in smoking between intervention and control condition . CONCLUSIONS A prevention program in elementary school seems to be effective in preventing smoking Objective To investigate whether PALSA PLUS , an on-site educational outreach programme of non-didactic , case based , iterative clinical education of staff , led by a trainer , can increase access to and comprehensiveness of care for patients with HIV/AIDS . Design Cluster r and omised trial . Setting Public primary care clinics offering HIV/AIDS care , antiretroviral treatment ( ART ) , tuberculosis care , and ambulatory primary care in Free State province , South Africa . Participants Fifteen clinics all implementing de central isation and task shifting were r and omised . The clinics cared for 400 000 general primary care patients and 10 136 patients in an HIV/AIDS/ART programme . There were 150 nurses . Intervention On-site outreach education in eight clinics ; no such education in seven ( control ) . Main outcome measures Provision of co-trimoxazole prophylaxis among patients referred to the HIV/AIDS/ART programme , and detection of cases of tuberculosis among those in the programme . Proportion of patients in the programme enrolled through general primary care consultations . Results Patients referred to the HIV/AIDS programme through general primary care at intervention clinics were more likely than those at control clinics to receive co-trimoxazole prophylaxis ( 41 % , ( 2253/5523 ) v 32 % ( 1340/4210 ) ; odds ratio 1.95 , 95 % confidence interval 1.11 to 3.40 ) , and tuberculosis was more likely to be diagnosed among patients with HIV/AIDS/ART ( 7 % ( 417/5793 ) v 6 % ( 245/4343 ) ; 1.25 , 1.01 to 1.55 ) . Enrolment in the HIV/AIDS and ART programme through HIV testing in general primary care was not significantly increased ( 53 % v 50 % ; 1.19 , 0.51 to 2.77 ) . Secondary outcomes were similar , except for weight gain , which was higher in the intervention group ( 2.3 kg v 1.9 kg , P<0.001 ) . Conclusion Though outreach education is an effective and feasible strategy for improving comprehensiveness of care and wellbeing of patients with HIV/AIDS , there is no evidence that it increases access to the ART programme . It is now being widely implemented in South Africa . Trial registration Current Controlled Trials IS RCT N 24820584 OBJECTIVE The aim of this r and omized controlled trial ( RCT ) was to investigate the effectiveness of the Stay@Work participatory ergonomics ( PE ) program to prevent low-back and neck pain . METHODS A total of 37 departments were r and omly allocated to either the intervention ( PE ) or control group ( no PE ) . During a six-hour meeting , working groups followed the PE steps and composed and prioritized ergonomic measures aim ed at preventing low-back and neck pain . Subsequently , working groups were requested to implement the ergonomic measures in the departments . The primary outcomes were low-back and neck pain prevalence and secondary outcomes were pain intensity and duration . Data were collected by question naires at baseline , and after 3- , 6- , 9- , and 12-months follow-up . Additionally , the course of low-back and neck pain ( transitions from no symptoms to symptoms and from symptoms to no symptoms ) was modeled . RESULTS The r and omization procedure result ed in 19 intervention departments ( N=1472 workers ) and 18 control departments ( N=1575 workers ) . After 12 months , the intervention was not more effective than the control group in reducing the prevalence of low-back and neck pain or reducing pain intensity and duration . PE did not increase the probability of preventing low-back pain [ odds ratio ( OR ) 1.23 , 95 % confidence interval ( 95 % CI ) 0.97 - 1.57 ) or neck pain ( OR 1.01 , 95 % CI 0.74 - 1.40 ) . However , PE increased the probability of recovering from low-back pain ( OR 1.41 , 95 % CI 1.01 - 1.96 ) , but not from neck pain ( OR 0.95 , 95 % CI 0.72 - 1.26 ) . CONCLUSION PE neither reduced low-back and neck pain prevalence nor pain intensity and duration nor was it effective in the prevention of low-back and neck pain or the recovery from neck pain . However , PE was more effective in the recovery from low-back pain OBJECTIVE Clinical asthma guidelines recommend spirometry for asthma diagnosis , but there is inconsistent evidence about benefits to patients in using it for ongoing management . Our aim was to determine whether training in the use of spirometry for management of asthma provided better health outcomes and improved the quality of care in the primary care setting . DESIGN Pragmatic , cluster r and omized controlled trial . SETTING General practice s in two states of Australia . PARTICIPANTS Forty practice s and 397 adults with asthma . INTERVENTION The staff of 26 intervention practice s received comprehensive spirometry training . Fourteen control practice s provided usual care . MAIN OUTCOME MEASURES Primary outcome measures were quality of life , self-reported asthma symptoms and lung function . Secondary measures related to the process of care ( e.g. performance of spirometry , preparation of a written asthma action plan ) and patient and general practitioner rating of the acceptability and usefulness of spirometry . RESULTS There were no statistically significant differences between the groups at 12 months for quality of life ( mean difference = -0.23 ; 95 % CI : -0.44 , -0.01 ) , days off work ( rate ratio = 1.52 ; 95 % CI : 0.91 , 2.54 ) , exacerbations ( rate ratio = 1.09 ; 95 % CI : 0.85 , 1.41 ) , asthma on waking ( rate ratio = 1.21 ; 95 % CI : 0.79 , 1.85 ) , nocturnal asthma ( rate ratio = 0.98 ; 95 % CI : 0.63 , 1.51 ) and post-bronchodilator FEV(1)/FVC ratio ( mean difference = -0.01 , 95 % CI : -0.03 , 0.02 ) . There was no improvement in the quality of care provided . CONCLUSIONS Training in spirometry did not result in any measurable improvement in the use of spirometry , quality of management of asthma or patient outcomes in primary care PURPOSE We wanted to determine whether an intervention based on patient activation and a physician decision support tool was more effective than usual care for improving adherence to National Cholesterol Education Program guidelines . METHODS A 1-year cluster r and omized controlled trial was performed using 30 primary care practice s ( 4,105 patients ) in southeastern New Engl and . The main outcome was the percentage of patients screened for hyperlipidemia and treated to their low-density lipoprotein ( LDL ) and non – high-density lipoprotein ( HDL ) cholesterol goals . RESULTS After 1 year of intervention , both r and omized practice groups improved screening ( 89 % screened ) , and 74 % of patients in both groups were at their LDL and non-HDL cholesterol goals ( P < .001 ) . Using intent-to-treat analysis , we found no statistically significant differences between practice groups in screening or percentage of patients who achieved LDL and non-HDL cholesterol goals . Post hoc analysis showed practice s who made high use of the patient activation kiosk were more likely to have patients screened ( odds ratio [ OR ] = 2.54 ; 95 % confidence interval [ CI ] , 1.97–3.27 ) compared with those who made infrequent or no use . Additionally , physicians who made high use of decision support tools were more likely to have their patients at their LDL cholesterol goals ( OR = 1.27 ; 95 % CI , 1.07–1.50 ) and non-HDL goals ( OR = 1.23 ; 95 % CI , 1.04–1.46 ) than low-use or no-use physicians . CONCLUSION This study showed null results with the intent-to-treat analysis regarding the benefits of a patient activation and a decision support tool in improving cholesterol management in primary care practice s. Post hoc analysis showed a potential benefit in practice s that used the e-health tools more frequently in screening and management of dyslipidemia . Further research on how to incorporate and increase adoption of user-friendly , patient-centered e-health tools to improve screening and management of chronic diseases and their risk factors is warranted BACKGROUND Postpartum home visiting by nurses can benefit higher-risk families . Yet , little is known about the effects of universal services which provide care for all families including those at lowest risk ( e.g. , provision by health visitors-United Kingdom specialist community public health nurses ) . OBJECTIVE It was to determine the effect of frequency of health visitors ' home visits on ' low-risk ' first-time families ' outcomes to 8 weeks postpartum and 7 months follow-up . DESIGN A cluster r and omised controlled trial . SETTING Within one health and social care managerial area in Northern Irel and . PARTICIPANTS First-time ' low risk ' mothers who had given birth during 2002 - 2004 and were visited by a health visitor who had agreed to take part in the study , were invited to participate . In total , n=39 health visitors were allocated to ' intervention ' and n=41 to ' control ' . Of n=295 ' low-risk ' first-time mothers who agreed to take part , n=136 with intervention health visitors were offered six home visits 2 - 8 weeks postpartum and n=159 within the control group were offered one planned visit . METHODS Self-completed measures of parenting , maternal wellbeing and service use were gathered pre-intervention , 8 weeks and 7 months postpartum . The main outcome was the Edinburgh Postnatal Depression Scale ( EPDS ) . At 8 weeks and 7 months postpartum , n=129 and n=115 intervention mothers , also n=151 and n=141 control mothers completed outcome measures . RESULTS An intention to treat analysis was performed using multilevel modelling analysis which statistically controlled for pre-home visit outcomes , clinic attendance and antenatal contact . The intervention had no impact on most outcomes , however , it was associated with an increased EPDS score ( after adjustment : 0.16 , 2.36 95 % CI ) at 8 weeks ( before accounting for outliers ) but not at 7 months ( -0.62 , 1.65 95 % CI ) . Intervention mothers had higher service satisfaction ( 7.7 , 21.28 , 95 % CI 8 weeks ; 4.69 , 22.71 , 7 months ) and were less likely to have used emergency medical services for their infants to 8 weeks ( OR : 0.15 , 0.85 , 95 % CI ) . CONCLUSION Weekly postpartum visits to ' low-risk ' mothers had variable effects , therefore , practitioners and research ers should consider further development and application of effective , evidence based home visiting content Objectives : To determine the impact of a peer-led education program , developed in Australia , on health-related outcomes in high school students with asthma in Jordan . Methods : In this cluster-r and omized controlled trial , 4 high schools in Irbid , Jordan , were r and omly assigned to receive the Adolescent Asthma Action program or st and ard practice . Bilingual health workers trained 24 peer leaders from Year 11 to deliver asthma education to younger peers from Year 10 ( n = 92 ) , who in turn presented brief asthma skits to students in Years 8 and 9 ( n = 148 ) and to other members of the school community in the intervention schools . Students with asthma ( N = 261 ) in Years 8 , 9 , and 10 completed baseline surveys in December 2006 and 3 months after the intervention . Results : Students from the intervention group reported clinical ly significant improvements in health-related quality of life ( mean difference : 1.35 [ 95 % confidence interval : 1.04–1.76 ] ) , self-efficacy to resist smoking ( mean difference : 4.63 [ 95 % confidence interval : 2.93–6.35 ] ) , and knowledge of asthma self- management ( mean difference : 1.62 [ 95 % confidence interval : 1.15–2.19 ] ) compared with the control group . Conclusions : This trial demonstrated that the Adolescent Asthma Action program can be readily adapted to suit different cultures and context s. Adolescents in Jordan were successful in teaching their peers about asthma self-management and motivating them to avoid smoking . The findings revealed that peer education can be a useful strategy for health promotion programs in Jordanian schools when students are given the opportunity and training The purpose of the present study was to evaluate an intervention to prevent weight gain among households ( HHs ) in the community . Ninety HHs were r and omized to intervention or control group for 1 year . Intervention consisted of six face-to-face group sessions , placement of a television ( TV ) locking device on all home TVs , and home-based intervention activities . Measures were collected in person at baseline and 1 year . Weight , height , eating behaviors , physical activity ( PA ) , and TV viewing were measured among HH members ages ≥ 12 years . Follow-up rate at 1 year was 96 % . No significant intervention effects were observed for change in HH BMI -z score . Intervention HHs significantly reduced TV viewing , snacks/sweets intake , and dollars per person spent eating out , and increased ( adults only ) PA and self-weighing frequency compared with control HHs . A 1 year obesity prevention intervention targeting entire HHs was effective in reducing TV viewing , snack/sweets intake and eating out purchases . Innovative methods are needed to strengthen the home food environment intervention component . Longer intervention duration s also need to be evaluated Objective : This study aim ed to determine the impact of a triage team on patient length of stay ( LOS ) overall and by patient acuity in a pediatric emergency department ( ED ) . Methods : We conducted a cluster r and omized controlled trial in which existing ED staffing was reallocated to include a triage team . The study was conducted in an urban children 's ED Monday through Friday , from 6:00 p.m. to 2:00 a.m. , for 4 weeks in February 2008 . Twenty study periods were r and omized according to the absence or presence of a triage team ( physician , nurse , and nurse assistant ) that initiated evaluations of nonurgent and urgent patients . We compared patient LOS between study periods with and without triage teams , using generalized estimating equations to allow for the clustering of effects by day . Results : Of the 1726 patients , 843 were seen during nontriage team times and 883 during triage team times . Overall , there was a 21-minute decrease in LOS during triage team times compared with nontriage team times , but this was not statistically significant . Stratifying by patient acuity level , LOS was significantly decreased during triage team times for nonurgent ( 25 minutes , P = 0.001 ) and urgent patients ( 50 minutes , P = 0.047 ) but prolonged for emergent patients ( 79 minutes , P = 0.019 ) and unchanged for critically ill patients . Conclusions : Overall , although we did not find a statistically significant decrease in the LOS with the use of a dedicated triage team , we did find statistically significant decreases in the stratified analysis for urgent , nonurgent patient , and discharged patients . An important reason statistical significance may not have been reached in this study may have been our hospital 's current staffing model , and therefore , the use of a triage team as additional staffing versus reallocation of existing staffing may depend on an institution 's current level of staffing and its ability to meet patient dem and Abstract Objective : To investigate whether a proactive multifactorial risk factor intervention strategy using single-pill amlodipine/atorvastatin ( 5/10 , 10/10 mg ) in addition to other antihypertensive and lipid-lowering therapy , as required , result ed in greater reduction in calculated Framingham 10-year coronary heart disease ( CHD ) risk compared with usual care ( UC ) after 52-weeks treatment . Research design and methods : Prospect i ve , multinational , open-label , cluster r and omized trial , with the investigator as the unit of r and omization . Eligible hypertensive patients were 35–79 years of age , with ≥3 additional cardiovascular risk factors , but no history of CHD and baseline total cholesterol ( TC ) ≤6.5 mmol/l . Clinical trial registration : Trial registration : Clinical Trials.gov identifier : NCT00407537 . Main outcome measure : The primary endpoint was calculated Framingham 10-year CHD risk at 52 weeks . Results : Of the 140 r and omized sites , 136 sites contributed 1461 patients . Mean baseline age and low-density lipoprotein cholesterol ( LDL-C ) were comparable between treatment arms . Mean baseline BP ( 150.3/89.7 vs. 144.3/86.5 mmHg ) and Framingham CHD risk ( 20.0 vs. 18.1 % ) were higher in the proactive intervention versus the UC arm ( p < 0.002 for both ) . At week 52 , mean CHD risk was 12.5 % in the proactive intervention arm and 16.3 % in the UC arm ( p < 0.001 ) . The difference , observed at weeks 16 and 52 , was primarily driven by significant differences in systolic BP and in TC between the two arms . Overall , adverse events ( AEs ) were reported in 48.8 % and 44.0 % of patients in the proactive intervention and the UC arm , respectively . Although there were differences in the incidence of AEs between the treatment arms , the AE profile in the proactive intervention arm was consistent with previous safety experience for this medication . Conclusions : A proactive multifactorial risk factor intervention strategy that simultaneously treated both BP and cholesterol regardless of individual risk factors per se , is more effective in reducing calculated Framingham 10-year CHD risk than UC in patients with hypertension and additional risk factors ABSTRACT BACKGROUND Four population -based studies of screening for CRC with fecal occult blood testing ( FOBT ) have shown that mortality can be significantly reduced . However , nearly half of all positive screening tests are not appropriately evaluated . OBJECTIVES We evaluated whether an electronic record intervention improved the follow-up of patients with a positive FOBT ( FOBT+ ) result . DESIGN We conducted a cluster r and omized trial involving four Veteran ’s Affairs ( VA ) medical centers pair-matched by colonoscopy volume and r and omized within the pair to receive the electronic intervention or usual care . PARTICIPANTS All patients with FOBT+ results at participating facilities during a matched pre- and post-intervention time period . INTERVENTIONS In the two intervention sites , an electronic consult that imported relevant clinical information was automatically su bmi tted to the gastroenterology ( GI ) clinic for all FOBT+ patients at the time the result was recorded in the laboratory . In both intervention and control sites ( usual care ) , PCPs continued to be notified of FOBT+ results in the usual manner MEASURES Pre- and post-intervention changes in the proportion of FOBT+ patients having : ( 1 ) a GI consult or ( 2 ) a GI consult plus complete diagnostic evaluation ( CDE ) of the colon within 30 , 90 and 180 days were compared across intervention and control sites . Log rank tests were used to determine statistical significance . RESULTS The 30- , 90- and 180-day GI consult rates improved 21–33 % ( p < 0.001 ) among intervention sites , but did not change in the usual care sites . Thirty- , 90- and 180-day CDE rates improved 9–31 % ( p < 0.03 ) in intervention sites , but did not significantly change in the usual care sites . Time to GI consult and CDE decreased significantly over time in the intervention sites ( p < 0.001 ) , but remained unchanged in the usual care sites . CONCLUSIONS The relatively simple electronic intervention evaluated can significantly improve the follow-up of FOBT+ results . Interventions such as this could improve patient care and may be applicable to other practice setting s , as well as other types of tests BACKGROUND Information technology offers the promise , as yet unfulfilled , of delivering efficient , evidence -based health care . OBJECTIVE To evaluate whether a primary care network-based informatics intervention can improve breast cancer screening rates . DESIGN Cluster-r and omized controlled trial of 12 primary care practice s conducted from March 20 , 2007 to March 19 , 2008 . PATIENTS Women 42–69 years old with no record of a mammogram in the prior 2 years . INTERVENTIONS In intervention practice s , a population -based informatics system was implemented that : connected overdue patients to appropriate care providers , presented providers with a Web-based list of their overdue patients in a non-visit-based setting , and enabled “ one-click ” mammography ordering or documented deferral reasons . Patients selected for mammography received automatically generated letters and follow-up phone calls . All practice s had electronic health record reminders about breast cancer screening available during clinical encounters . MAIN MEASURES The primary outcome was the proportion of overdue women undergoing mammography at 1-year follow-up . KEY RESULTS Baseline mammography rates in intervention and control practice s did not differ ( 79.5 % vs 79.3 % , p = 0.73 ) . Among 3,054 women in intervention practice s and 3,676 women in control practice s overdue for mammograms , intervention patients were somewhat younger , more likely to be non-Hispanic white , and have health insurance . Most intervention providers used the system ( 65 of 70 providers , 92.9 % ) . Action was taken for 2,652 ( 86.8 % ) intervention patients [ 2,274 ( 74.5 % ) contacted and 378 ( 12.4 % ) deferred ] . After 1 year , mammography rates were significantly higher in the intervention arm ( 31.4 % vs 23.3 % in control arm , p < 0.001 after adjustment for baseline differences ; 8.1 % absolute difference , 95 % CI 5.1–11.2 % ) . All demographic subgroups benefited from the intervention . Intervention patients completed screening sooner than control patients ( p < 0.001 ) . CONCLUSIONS A novel population -based informatics system functioning as part of a non-visit-based care model increased mammography screening rates in intervention practice s . TRIAL REGISTRATION Clinical Trials.gov ; BACKGROUND Cardiovascular risk reduction in ambulatory patients who survive myocardial infa rct ion ( MI ) is effective but underused . We sought to evaluate a provider-directed , Internet-delivered intervention to improve cardiovascular management for post-MI out patients . METHODS The Department of Veterans Affairs ( VA ) MI-Plus study was a cluster-r and omized trial involving 168 community-based primary care clinics and 847 providers in 26 states , the Virgin Isl and s , and Puerto Rico , from January 1 , 2002 , through December 31 , 2008 , with the clinic as the r and omization unit . We collected administrative data for 15,847 post-MI patients and medical record data for 10,452 of these . A multicomponent , Internet-delivered intervention included quarterly educational modules , practice guidelines , monthly literature summaries , and automated e-mail reminders delivered to providers for 27 months . Main outcome measures included percentage of patients who achieved each of 7 clinical indicators , a composite score of the 7 clinical indicators , and mean low-density lipoprotein cholesterol and hemoglobin A(1c ) levels . RESULTS Clinics had a median of 3 providers ( interquartile range , 2 - 6 ) , with a median of 50.0 % of providers ( 33.3%-66.7 % ) participating in the study . Patients in intervention clinics had greater improvements ( from 70.0 % to 85.5 % ) in the percentages prescribed β-blockers than patients in control clinics ( 71.9 % to 84.0 % ; adjusted improvement gain for intervention vs control , 2.6 % ; 95 % CI , 0.1%-4.1 % ) . We found nonsignificant differences in improvements favoring patients in intervention clinics for 5 of 6 remaining clinical indicators and levels of low-density lipoprotein cholesterol and hemoglobin A(1c ) . CONCLUSION A longitudinal , Internet-delivered intervention improved only 1 of 7 clinical indicators of cardiovascular management in ambulatory post-MI patients OBJECTIVE To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity ( LE ) injuries in female athletes in a mixed-ethnicity , predominantly low-income , urban population . DESIGN Cluster r and omized controlled trial . SETTING Chicago public high schools . PARTICIPANTS Of 258 coaches invited to participate , 95 ( 36.8 % ) enrolled ( 1558 athletes ) . Ninety coaches and 1492 athletes completed the study . INTERVENTIONS We r and omized schools to intervention and control groups . We trained intervention coaches to implement a 20-minute neuromuscular warm-up . Control coaches used their usual warm-up . MAIN OUTCOME MEASURES Coach compliance was tracked by self-report and direct observation . Coaches reported weekly athlete exposures ( AEs ) and LE injuries causing a missed practice or game . Research assistants interviewed injured athletes . Injury rates were compared between the control and intervention groups using χ(2 ) and Fisher exact tests . Significance was set at P < .05 . Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information ( n = 855 ; 57.3 % ) . RESULTS There were 28 023 intervention AEs and 22 925 control AEs . Intervention coaches used prescribed warm-up in 1425 of 1773 practice s ( 80.4 % ) . Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries ( 0.43 vs 1.22 , P < .01 ) , acute-onset noncontact LE injuries ( 0.71 vs 1.61 , P < .01 ) , noncontact ankle sprains ( 0.25 vs 0.74 , P = .01 ) , and LE injuries treated surgically ( 0 vs 0.17 , P = .04 ) . Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries ( 0.33 ; 95 % CI , 0.17 - 0.61 ) , noncontact ankle sprains ( 0.38 ; 95 % CI , 0.15 - 0.98 ) , noncontact knee sprains ( 0.30 ; 95 % CI , 0.10 - 0.86 ) , and noncontact anterior cruciate ligament injuries ( 0.20 ; 95 % CI , 0.04 - 0.95 ) . CONCLUSION Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity , predominantly low-income , urban population . TRIAL REGISTRATION CLINICAL TRIALS.ORG IDENTIFIER : NCT01092286 Background : The incidence of acute hamstring injuries is high in several sports , including the different forms of football . Purpose : The authors investigated the preventive effect of eccentric strengthening of the hamstring muscles using the Nordic hamstring exercise compared with no additional hamstring exercise on the rate of acute hamstring injuries in male soccer players . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Fifty Danish male professional and amateur soccer teams ( 942 players ) were allocated to an intervention group ( 461 players ) or a control group ( 481 players ) . Players in the intervention group conducted a 10-week progressive eccentric training program followed by a weekly seasonal program , whereas players in the control group followed their usual training program . The main outcome measures were numbers of overall , new , and recurrent acute hamstring injuries during 1 full soccer season . Results : Fifty-two acute hamstring injuries in the control group compared with 15 injuries in the intervention group were registered . Comparing intervention versus the control group , overall acute hamstring injury rates per 100 player seasons were 3.8 versus 13.1 ( adjusted rate ratio [ RR ] , 0.293 ; 95 % confidence interval [ CI ] , 0.150 - 0.572 ; P < .001 ) . New injury rates per 100 player seasons were 3.1 versus 8.1 ( RR , 0.410 ; 95 % CI , 0.180 - 0.933 ; P = .034 ) , whereas recurrent injury rates per 100 player seasons were 7.1 versus 45.8 ( RR , 0.137 ; 95 % CI , 0.037 - 0.509 ; P = .003 ) . Number needed to treat [ NNT ] to prevent 1 acute hamstring injury ( new or recurrent ) is 13 ( 95 % CI , 9 - 23 ) players . The NNT to prevent 1 new injury is 25 ( 95 % CI , 15 - 72 ) players , and NNT to prevent 1 recurrent injury is 3 ( 95 % CI , 2 - 6 ) players . Conclusion : In male professional and amateur soccer players , additional eccentric hamstring exercise decreased the rate of overall , new , and recurrent acute hamstring injuries Background : Sophisticated approaches are needed to improve the quality of care for elderly people living in residential care facilities . We determined the effects of multidisciplinary integrated care on the quality of care and quality of life for elderly people in residential care facilities . Methods : We performed a cluster r and omized controlled trial involving 10 residential care facilities in the Netherl and s that included 340 participating residents with physical or cognitive disabilities . Five of the facilities applied multidisciplinary integrated care , and five provided usual care . The intervention , inspired by the disease management model , consisted of a geriatric assessment of functional health every three months . The assessment included use of the Long-term Care Facility version of the Resident Assessment Instrument by trained nurse-assistants to guide the design of an individualized care plan ; discussion of outcomes and care priorities with the family physician , the resident and his or her family ; and monthly multidisciplinary meetings with the nurse-assistant , family physician , psychologist and geriatrician to discuss residents with complex needs . The primary outcome was the sum score of 32 risk-adjusted quality -of-care indicators . Results : Compared with the facilities that provided usual care , the intervention facilities had a significantly higher sum score of the 32 quality -of-care indicators ( mean difference − 6.7 , p = 0.009 ; a medium effect size of 0.72 ) . They also had significantly higher scores for 11 of the 32 indicators of good care in the areas of communication , delirium , behaviour , continence , pain and use of antipsychotic agents . Interpretation : Multidisciplinary integrated care result ed in improved quality of care for elderly people in residential care facilities compared with usual care . Trial registration : www.controlled-trials.com trial register no. IS RCT N11076857 Background : Helping novices transition toward expertise requires “ meaningful ” learning . Advance organizers are educational tools which help connect prior knowledge with new information , a critical step in making learning meaningful . Concept maps visually represent knowledge organization and can serve as advance organizers enabling deeper and more meaningful learning while enhancing knowledge integration . Aim : To compare respiratory failure underst and ing of resident physicians instructed , using an expert concept map advance organizer with learners receiving traditional didactic teaching . Methods : Residents were r and omized by month of service to receive either a control lecture or a session using an expert concept map as an advanced organizer . Participants completed three concept maps ; pre-education ( CM1 ) , immediately post-education ( CM2 ) , and 1 week later ( CM3 ) . Concept maps were scored using a st and ardized structural scoring method . Results : Forty-six pediatric residents ( 23 control and 23 experimental ) participated . To account for repeated measures within subjects , the generalized estimating equations method compared concept map improvement between groups . The experimental group improved significantly more than controls ( CM1–CM2–CM3 p = 0.001 ; CM1–CM2 p = 0.001 ; and CM1–CM3 p = 0.017 ) . Conclusions : Using an expert concept map as an advance organizer improves knowledge organization and integration while offering a tool to enhance deeper underst and ing of medical knowledge among resident physicians Background : Implementing an anterior cruciate ligament injury prevention program to athletes before the age at which the greatest injury risk occurs ( 15 - 17 years ) is important from a prevention st and point . However , it is unknown whether st and ard programs can modify lower extremity biomechanics in pediatric population s or if specialized training is required . Hypothesis/ Purpose : To compare the effects of traditional and age-specific pediatric anterior cruciate ligament injury prevention programs on lower extremity biomechanics during a cutting task in youth athletes . The authors hypothesized that the age-specific pediatric program would result in greater sagittal plane motion ( ie , hip and knee flexion ) and less motion in the transverse and frontal plane ( ie , knee valgus , knee and hip rotation ) as compared with the traditional program . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Sixty-five youth soccer athletes ( 38 boys , 27 girls ) volunteered to participate . The mean age of participants was 10 ± 1 years . Teams ( n , 7 ) were cluster r and omized to a pediatric injury prevention program , a traditional injury prevention program , or a control group . The pediatric program was modified from the traditional program to include more feedback , progressions , and variety . Teams performed their programs as part of their normal warm-up routine . Three-dimensional lower extremity biomechanics were assessed during a sidestep cutting task before and after completion of the 9-week intervention period . Results : The pediatric program reduced the amount of knee external rotation at initial ground contact during the cutting task , F ( 2,62 ) = 3.79 , P = .03 ( change : pediatric , 7.73 ° ± 10.71 ° ; control , –0.35 ° ± 7.76 ° ) , as compared with the control group after the intervention period . No other changes were observed . Conclusion : The injury prevention program design ed for a pediatric population modified only knee rotation during the cutting task , whereas the traditional program did not result in any changes in cutting biomechanics . These findings suggest limited effectiveness of both programs for athletes younger than 12 years of age in terms of biomechanics during a cutting task OBJECTIVES Effective real-time feedback is critical to medical education . This study tested the hypothesis that an educational intervention related to feedback would improve emergency medicine ( EM ) faculty and resident physician satisfaction with feedback . METHODS This was a cluster-r and omized , controlled study of 15 EM residency programs in 2007 - 2008 . An educational intervention was created that combined a feedback curriculum with a card system design ed to promote timely , effective feedback . Sites were r and omized either to receive the intervention or to continue their current feedback method . All participants completed a Web-based survey before and after the intervention period . The primary outcome was overall feedback satisfaction on a 10-point scale . Additional items addressed specific aspects of feedback . Responses were compared using a generalized estimating equations model , adjusting for confounders and baseline differences between groups . The study was design ed to achieve at least 80 % power to detect a one-point difference in overall satisfaction ( α = 0.05 ) . RESULTS Response rates for pre- and postintervention surveys were 65.9 and 47.3 % ( faculty ) and 64.7 and 56.9 % ( residents ) . Residents in the intervention group reported a mean overall increase in feedback satisfaction scores compared to those in the control group ( mean increase 0.96 points , st and ard error [ SE ] ± 0.44 , p = 0.03 ) and significantly higher satisfaction with the quality , amount , and timeliness of feedback . There were no significant differences in mean scores for overall and specific aspects of satisfaction between the faculty physician intervention and control groups . CONCLUSIONS An intervention design ed to improve real-time feedback in the ED result ed in higher resident satisfaction with feedback received , but did not affect faculty satisfaction with the feedback given BACKGROUND Bacterial vaginosis ( BV ) in pregnancy is linked to preterm birth , but its risk factors are not well understood . Micronutrient deficiencies may be associated with an increased risk of this condition . OBJECTIVE We assessed the effect of weekly vitamin A or β-carotene supplementation during pregnancy until 3 mo postpartum on BV risk in rural northeastern Bangladesh . DESIGN In this cluster-r and omized , placebo-controlled trial , 33 clusters ( n = 33 ) were r and omly assigned to 3 groups . Women ( n = 1812 ) were examined for BV by using self-administered swabs and the Nugent scoring method in early pregnancy , at 32 wk of gestation , and at 3 mo postpartum . RESULTS The prevalence of BV in early pregnancy , before supplementation , was 7.6 % ( 95 % CI : 6.3 % , 9.1 % ) overall . Neither the prevalence nor the incidence of BV in the third trimester differed by supplement group . However , the prevalence ( OR : 0.71 ; 95 % CI : 0.52 , 0.98 ) and incidence ( RR : 0.58 ; 95 % CI : 0.41 , 0.81 ) of BV at 3 mo postpartum was lower among women in the vitamin A group ( 9.1 % and 6.7 % , respectively ) than in the placebo group ( 12.4 % and 11.8 % , respectively ) , but not in the β-carotene group . Both vitamin A and β-carotene reduced the prevalence and incidence of BV at both time points ( ie , third trimester and 3 mo postpartum ) by 30 - 40 % compared with placebo ( all P < 0.05 ) . CONCLUSIONS Weekly vitamin A supplementation reduced the risk of maternal BV in this rural Bangladeshi population . Enhancement of vitamin A status before and during pregnancy may reduce the risk of BV in areas with vitamin A deficiency . This trial is registered at clinical trials.gov as NCT00198822 OBJECTIVE To evaluate the short- and long-term results of FATaintPHAT , a Web-based computer-tailored intervention aim ing to increase physical activity , decrease sedentary behavior , and promote healthy eating to contribute to the prevention of excessive weight gain among adolescents . DESIGN Cluster r and omized trial with an intervention group and a no-intervention control group . SETTING Twenty schools in the Netherl and s. PARTICIPANTS A total of 883 students ( aged 12 - 13 years ) . INTERVENTION The FATaintPHAT ( VETisnietVET in Dutch ) Web-based computer-tailored intervention . OUTCOME MEASURES Self-reported behaviors ( diet , physical activity , sedentary behavior ) and pedometer counts were measured at baseline and at 4-month and 2-year follow-up ; body mass index ( BMI ) , waist circumference , and fitness were measured at baseline and at 2-year follow-up . Descriptive and multilevel regression analyses were conducted among the total study population and among students not meeting behavioral recommendations at baseline ( students at risk ) . RESULTS The complete case analyses showed that FATaintPHAT had no effect on BMI and waist circumference . However , the intervention was associated with lower odds ( 0.54 ) of drinking more than 400 mL of sugar-sweetened beverages per day and with lower snack intake ( β = -0.81 snacks/d ) and higher vegetable intake ( β = 19.3 g/d ) but also with a lower step count ( β = -10 856 steps/wk ) at 4-month follow-up . In addition , among students at risk , FATaintPHAT had a positive effect on fruit consumption ( β = 0.39 g/d ) at 4-month follow-up and on step count ( β = 14 228 steps/wk ) at 2-year follow-up but an inverse effect on the odds of sports participation ( odds ratio , 0.45 ) at 4-month follow-up . No effects were found for sedentary behavior . CONCLUSION The FATaintPHAT intervention was associated with positive short-term effects on diet but with no effects or unfavorable effects on physical activity and sedentary behavior BACKGROUND : Early shared reading and literacy promotion benefits have stimulated international interest in the development of early-years literacy-promotion programs despite limited evidence of effectiveness at a broader population level . OBJECTIVE : To determine whether a population -based primary care literacy promotion intervention during the first 2 years of life improves early markers of subsequent literacy by 2 years of age . DESIGN AND METHODS : This cluster r and omized controlled trial took place in 5 relatively disadvantaged areas in Melbourne , Australia . Infants attending their maternal and child health centers were recruited at age 1–2 months . The intervention ( 4–8 , 12 , and 18 months ) comprised maternal and child health nurses modelling shared reading activities to parents , supported by parent information and free books . Outcomes ( at 2 years ) included expressive vocabulary ( MacArthur Bates Communicative Development Inventory ) , communication ( Communication and Symbolic Behavior Scales ) , and home literacy environment ( StimQ-Toddler ) . We analyzed the outcomes using r and om-effects ( linear regression ) models allowing for clustering . RESULTS : A total of 552 families ( 87.6 % ; 324 intervention and 228 control families ) of 630 recruited families ( 66.5 % response ) were retained to outcome . A total of 97.3 % of intervention parents received some ( 93.7 % to all ) of the intervention . At 2 years , the trial arms had similar vocabulary ( adjusted mean difference : −2.0 [ 95 % confidence interval : −6.2 to 2.2 ] ; P = .36 ) , communication ( adjusted mean difference : 0.2 [ 95 % confidence interval : −2.3 to 2.7 ] ; P = .87 ) , and home literacy ( adjusted mean difference : −0.4 [ 95 % confidence interval : −1.0 to 0.2 ] ; P = .21 ) . CONCLUSIONS : This universal literacy-promotion program was not beneficial in relatively disadvantaged communities by the age of 2 years and may be ineffective . Alternative interpretations may relate to program intensity , reach and /or sleeper effects . Definitive outcomes at 4 years are awaited Rates of chronic diseases are high among Black South Africans but few studies have tested cognitive-behavioural health-promotion interventions to reduce this problem . We tested the efficacy of such an intervention among adolescents in a cluster-r and omised controlled trial . We r and omly selected 9 of 17 matched pairs of schools and r and omised one school in each pair to the cognitive-behavioural health-promotion intervention design ed to encourage health-related behaviours and the other to a human immunodeficiency virus (HIV)/sexually transmitted disease ( STD ) risk-reduction intervention that served as the control . Interventions were based on social cognitive theory , the theory of planned behaviour and qualitative data from the target population . Data collectors , blind to participants ’ intervention , administered confidential assessment s at baseline and 3 , 6 and 12 months post-intervention . Primary outcomes were fruit and vegetable consumption and physical activity . Participants were 1057 grade 6 learners ( mean age = 12.4 years ) , with 96.7 % retained at 12-month follow-up . Generalised estimating equations revealed that averaged over the follow-ups , a greater percentage of health-promotion intervention participants than HIV/STD control participants met 5-a-Day fruit and vegetable and physical activity guidelines . The intervention also increased health-promotion knowledge , attitude and intention , but did not decrease substance use or substance-use attitude and intention . The findings suggest that theory based and context ually appropriate interventions may increase health behaviours among young adolescents in sub-Saharan Africa AIM To evaluate the effectiveness in primary care of a stepped smoking cessation intervention based on the transtheoretical model of change . DESIGN Cluster r and omized trial ; unit of r and omization : basic care unit ( family physician and nurse who care for the same group of patients ) ; and intention-to-treat analysis . SETTING All interested basic care units ( n = 176 ) that worked in 82 primary care centres belonging to the Spanish Preventive Services and Health Promotion Research Network in 13 regions of Spain . PARTICIPANTS A total of 2,827 smokers ( aged 14 - 85 years ) who consulted a primary care centre for any reason , provided written informed consent and had valid interviews . MEASUREMENTS The outcome variable was the 1-year continuous abstinence rate at the 2-year follow-up . The main variable was the study group ( intervention/control ) . Intervention involved 6-month implementation of recommendations from a Clinical Practice Guideline which included brief motivational interviews for smokers at the precontemplation-contemplation stage , brief intervention for smokers in preparation-action who do not want help , intensive intervention with pharmacotherapy for smokers in preparation-action who want help and reinforcing intervention in the maintenance stage . Control group involved usual care . Among others , characteristics of tobacco use and motivation to quit variables were also collected . FINDINGS The 1-year continuous abstinence rate at the 2-year follow-up was 8.1 % in the intervention group and 5.8 % in the control group ( P = 0.014 ) . In the multivariate logistic regression , the odds of quitting of the intervention versus control group was 1.50 ( 95 % confidence interval = 1.05 - 2.14 ) . CONCLUSIONS A stepped smoking cessation intervention based on the transtheoretical model significantly increased smoking abstinence at a 2-year follow-up among smokers visiting primary care centres UNLABELLED BACKGROUND L : Pressure ulcers are common , costly and impact negatively on individuals . Pressure is the prime cause , and immobility is the factor that exposes individuals to pressure . International guidelines advocate repositioning ; however , there is confusion surrounding the best method and frequency required . DESIGN A pragmatic , multi-centre , open label , prospect i ve , cluster-r and omised controlled trial was conducted to compare the incidence of pressure ulcers among older persons nursed using two different repositioning regimens . METHOD Ethical approval was received . Study sites ( n=12 ) were allocated to study arm using cluster r and omisation . The experimental group ( n=99 ) were repositioned three hourly at night , using the 30 ° tilt ; the control group ( n=114 ) received routine prevention ( six-hourly repositioning , using 90 ° lateral rotation ) . Data analysis was by intention to treat ; follow-up was for four weeks . RESULTS All participants ( n=213 ) were Irish and white , among them 77 % were women and 65 % aged 80 years or older . Three patients ( 3 % ) in the experimental group and 13 patients ( 11 % ) in the control group developed a pressure ulcer ( p=0·035 ; 95 % CI 0·031 - 0·038 ; ICC=0·001 ) . All pressure ulcers were grade 1 ( 44 % ) or grade 2 ( 56 % ) . Mobility and activity were the highest predictors of pressure ulcer development ( β=-0·246 , 95 % CI=-0·319 to -0·066 ; p=0·003 ) ; ( β=0·227 , 95 % CI=0·041 - 0·246 ; p = 0·006 ) . CONCLUSION Repositioning older persons at risk of pressure ulcers every three hours at night , using the 30 ° tilt , reduces the incidence of pressure ulcers compared with usual care . The study supports the recommendations of the 2009 international pressure ulcer prevention guidelines . RELEVANCE TO CLINICAL PRACTICE An effective method of pressure ulcer prevention has been identified ; in the light of the problem of pressures ulcers , current prevention strategies should be review ed . It is important to implement appropriate prevention strategies , of which repositioning is one A group-r and omized controlled trial was carried out to investigate the effects of a postural education program on daily life habits related to low back pain in children . The study sample included 137 children aged 10.7 years . 6 classes from 2 primary schools were r and omly allocated into an experimental group ( EG ) ( N=63 ) or a control group ( CG ) ( N=74 ) . The EG received a postural education program over 6 weeks consisting of 6 sessions , while the CG followed the usual school curriculum . A question naire was completed by the participants at pretest , post-test and 3 months after the intervention finished . The outcomes collected were : correct use of sofa , stooping correctly , take care to sit correctly at home/school and frequent posture change on chair at home/school . A sum score was computed from the 6 items . To examine the effect of the intervention , we used repeated measures analysis of co-variance ( ANCOVA ) ; with baseline , post-test and follow-up outcome values as dependent variables , study group as fixed factor , and sex and age as covariates . Single healthy items mostly improved after the intervention and remained improved after 3 month follow-up in EG , while no substantial changes were observed in the CG . Healthy habits score was significantly increased at post-test compared to baseline in the EG ( P<0.001 ) , and remained significantly increased after 3-months , compared to baseline ( P<0.001 ) . No significant changes were observed in the CG ( P>0.6 ) . The results suggest that children are able to learn healthy daily life habits which might contribute to future prevention of low back pain Bojang and colleagues report a r and omized trial showing that delivery of intermittent preventive treatment for malaria in children by village health workers is more effective than delivery by reproductive and child health trekking clinics BACKGROUND Exclusive breastfeeding ( EBF ) is reported to be a life-saving intervention in low-income setting s. The effect of breastfeeding counselling by peer counsellors was assessed in Africa . METHODS 24 communities in Burkina Faso , 24 in Ug and a , and 34 in South Africa were assigned in a 1:1 ratio , by use of a computer-generated r and omisation sequence , to the control or intervention clusters . In the intervention group , we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers . The data gathering team were masked to the intervention allocation . The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks . Country-specific prevalence ratios were adjusted for cluster effects and sites . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00397150 . FINDINGS 2579 mother-infant pairs were assigned to the intervention or control clusters in Burkina Faso ( n=392 and n=402 , respectively ) , Ug and a ( n=396 and n=369 , respectively ) , and South Africa ( n=535 and 485 , respectively ) . The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 ( 79 % ) of 392 and 139 ( 35 % ) of 402 , respectively , in Burkina Faso ( prevalence ratio 2·29 , 95 % CI 1·33 - 3·92 ) ; 323 ( 82 % ) of 396 and 161 ( 44 % ) of 369 , respectively , in Ug and a ( 1·89 , 1·70 - 2·11 ) ; and 56 ( 10 % ) of 535 and 30 ( 6 % ) of 485 , respectively , in South Africa ( 1·72 , 1·12 - 2·63 ) . The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 ( 77 % ) and 94 ( 23 % ) , respectively , in Burkina Faso ( 3·27 , 2·13 - 5·03 ) ; 305 ( 77 % ) and 125 ( 34 % ) , respectively , in Ug and a ( 2·30 , 2·00 - 2·65 ) ; and 41 ( 8 % ) and 19 ( 4 % ) , respectively , in South Africa ( 1·98 , 1·30 - 3·02 ) . At 24 weeks , the prevalences based on 24-h recall were 286 ( 73 % ) in the intervention cluster and 88 ( 22 % ) in the control cluster in Burkina Faso ( 3·33 , 1·74 - 6·38 ) ; 232 ( 59 % ) and 57 ( 15 % ) , respectively , in Ug and a ( 3·83 , 2·97 - 4·95 ) ; and 12 ( 2 % ) and two ( < 1 % ) , respectively , in South Africa ( 5·70 , 1·33 - 24·26 ) . The prevalences based on 7-day recall were 279 ( 71 % ) in the intervention cluster and 38 ( 9 % ) in the control cluster in Burkina Faso ( 7·53 , 4·42 - 12·82 ) ; 203 ( 51 % ) and 41 ( 11 % ) , respectively , in Ug and a ( 4·66 , 3·35 - 6·49 ) ; and ten ( 2 % ) and one ( < 1 % ) , respectively , in South Africa ( 9·83 , 1·40 - 69·14 ) . Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 ( 5 % ) and 36 ( 9 % ) , respectively , in Burkina Faso ( 0·57 , 0·27 - 1·22 ) ; 39 ( 10 % ) and 32 ( 9 % ) , respectively , in Ug and a ( 1·13 , 0·81 - 1·59 ) ; and 45 ( 8 % ) and 33 ( 7 % ) , respectively , in South Africa ( 1·16 , 0·78 - 1·75 ) . The prevalence at age 24 weeks in the intervention and control clusters was 26 ( 7 % ) and 32 ( 8 % ) , respectively , in Burkina Faso ( 0·83 , 0·45 - 1·54 ) ; 52 ( 13 % ) and 59 ( 16 % ) , respectively , in Ug and a ( 0·82 , 0·58 - 1·15 ) ; and 54 ( 10 % ) and 33 ( 7 % ) , respectively , in South Africa ( 1·31 , 0·89 - 1·93 ) . INTERPRETATION Low-intensity individual breastfeeding peer counselling is achievable and , although it does not affect the diarrhoea prevalence , can be used to effectively increase EBF prevalence in many sub-Saharan African setting s. FUNDING European Union Sixth Framework International Cooperation-Developing Countries , Research Council of Norway , Swedish International Development Cooperation Agency , Norwegian Programme for Development , Research and Education , South African National Research Foundation , and Rockefeller Brothers Foundation The authors tested the effectiveness and estimated the cost of several interventions aim ed at reducing drug interactions in primary care by design ing a 15-month cluster-controlled trial . The trial involved 265 family physicians and their patients who were r and omized into 4 groups : control , report ( received feedback reports ) , session ( group sessions ) , and face-to-face ( personal interviews ) . The outcome was the mean of relevant interactions detected on electronic medical records . Cost-effectiveness was defined as the incremental cost to reduce drug interactions by 1 % . The authors detected a baseline mean of 6.7 interactions per 100 patients , which was reduced to 5.3 interactions after follow-up . No improvement was seen in the report group when compared with the control group , whereas progressive improvement in the other groups was noted ( P < .001 ) . Incremental cost was higher in the face-to-face group ( 69.4 vs 50.7 ) ; cost-effectiveness results were slightly better in the session group ( 4.2 vs 4.5 ) OBJECTIVE We assessed the short-term effects of a community-based intervention for Hispanic men to encourage informed decision making ( IDM ) about prostate cancer screening with prostate specific antigen ( PSA ) . METHODS All senior social and housing centers in El Paso , TX were r and omized to intervention , a group-based Spanish language educational program facilitated by promotores ( 12 centers ; 161 men ) [ I 's ] , or to control , promotores-facilitated diabetes video and discussion ( 13 centers ; 160 men ) [ C 's ] . RESULTS Participants had low levels of schooling and baseline knowledge ; 44 % reported previous PSA testing . At post-test , the I 's made large knowledge gains , increased their underst and ing that experts disagree about testing , shifted toward more active decision making roles , were more likely to believe that it is important to weigh the advantages and disadvantages of screening and to anticipate potential screening outcomes in making a decision , and were less likely to consider the screening decision easy . The I 's did not change in their screening intention or the belief that choosing not to be screened could be a responsible choice . CONCLUSIONS A community-based intervention to support IDM for prostate cancer screening can increase knowledge and may promote more active involvement in decision making about prostate cancer screening . Such an approach can increase knowledge and may promote more active involvement in decision making about prostate cancer screening . PRACTICE IMPLICATION S It is feasible to develop and implement a community-based intervention program to promote IDM for prostate cancer screening RATIONALE Little is known about the consequences of intensivists ’ work schedules , or intensivist continuity of care . OBJECTIVES To assess the impact of weekend respite for intensivists , with consequent reduction in continuity of care , on them and their patients . METHODS In five medical intensive care units ( ICUs ) in four academic hospitals we performed a prospect i ve , cluster-r and omized , alternating trial of two intensivist staffing schedules . Daily coverage by a single intensivist in half-month rotations ( continuous schedule ) was compared with weekday coverage by a single intensivist , with weekend cross-coverage by colleagues ( interrupted schedule ) . We studied consecutive patients admitted to study units , and the intensivists working in four of the participating units . MEASUREMENTS AND MAIN RESULTS The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates . The primary intensivist outcome was physician burnout . Analysis was by multivariable regression . A total of 45 intensivists and 1,900 patients participated in the study . Continuity of care differed between schedules ( patients with multiple intensivists = 28 % under continuous schedule vs. 62 % under interrupted scheduling ; P < 0.0001 ) . LOS and mortality were nonsignificantly higher under continuous scheduling ( ΔICU LOS 0.36 d , P = 0.20 ; Δhospital LOS 0.34 d , P = 0.71 ; ICU mortality , odds ratio = 1.43 , P = 0.12 ; hospital mortality , odds ratio = 1.17,P = 0.41 ) . Intensivists experienced significantly higher burnout , work – home life imbalance , and job distress working under the continuous schedule . CONCLUSIONS Work schedules where intensivists received weekend breaks were better for the physicians and , despite lower continuity of intensivist care , did not worsen outcomes for medical ICU patients CONTEXT Human papillomavirus ( HPV ) vaccine programs may decrease the morbidity and mortality due to cervical cancer seen among women in low-re source countries . However , the 3-dose schedule over a 6-month period is a potential barrier to vaccine introduction in such setting s. OBJECTIVE To determine the immunogenicity and reactogenicity of different dosing schedules of quadrivalent HPV vaccine in adolescent girls in Vietnam . DESIGN , SETTING , AND PARTICIPANTS Open-label , cluster r and omized , noninferiority study ( conducted between October 2007 and January 2010 ) assessing 4 schedules of an HPV vaccine delivered in 21 schools to 903 adolescent girls ( aged 11 - 13 years at enrollment ) living in northwestern Vietnam . INTERVENTION Intramuscular injection of 3 doses of quadrivalent HPV vaccine delivered on a st and ard dosing schedule ( at 0 , 2 , and 6 months ) and 3 alternative dosing schedules ( at 0 , 3 , and 9 months ; at 0 , 6 , and 12 months ; or at 0 , 12 , and 24 months ) . MAIN OUTCOME MEASURES Serum anti-HPV geometric mean titers ( GMT ) measured 1 month after the third dose of the HPV vaccine was administered ; GMT was determined by type-specific competitive immunoassay . Noninferiority of each alternative vaccination dosing schedule was achieved if the lower bound of the multiplicity-adjusted confidence interval ( CI ) of the type-specific GMT ratio for HPV-16 and HPV-18 was greater than 0.5 ( primary outcome ) . Safety outcomes were immediate reactions , local reactions , fever within 7 days after each dose , and serious adverse events up to 30 days following the last dose . RESULTS In the intention-to-treat analysis , 809 girls who received at least 1 HPV vaccine dose had valid serum measurements 1 month after the third dose . After the third dose , the GMTs for those in the st and ard schedule group who received doses at 0 , 2 , and 6 months were 5808.0 ( 95 % CI , 4961.4 - 6799.0 ) for HPV-16 and 1729.9 ( 95 % CI , 1504.0 - 1989.7 ) for HPV-18 ; 5368.5 ( 95 % CI , 4632.4 - 6221.5 ) and 1502.3 ( 95 % CI , 1302.1 - 1733.2 ) , respectively , for those whose received doses at 0 , 3 , and 9 months ; 5716.4 ( 95 % CI , 4876.7 - 6700.6 ) and 1581.5 ( 95 % CI , 1363.4 - 1834.6 ) , respectively , for those who received doses at 0 , 6 , and 12 months ; and 3692.5 ( 95 % CI , 3145.3 - 4334.9 ) and 1335.7 ( 95 % CI , 1191.6 - 1497.3 ) , respectively , for those who received doses at 0 , 12 , and 24 months . Noninferiority criteria were met for the alternative schedule groups that received doses at 0 , 3 , and 9 months ( HPV-16 GMT ratio : 0.92 [ 95 % CI , 0.71 - 1.20 ] ; HPV-18 GMT ratio : 0.87 [ 95 % CI , 0.68 - 1.11 ] ) and at 0 , 6 , and 12 months ( HPV-16 GMT ratio : 0.98 [ 95 % CI , 0.75 - 1.29 ] ; HPV-18 GMT ratio : 0.91 [ 95 % CI , 0.71 - 1.17 ] ) . Prespecified noninferiority criteria were not met for the alternative schedule group that received doses at 0 , 12 , and 24 months ( HPV-16 GMT ratio : 0.64 [ 95 % CI , 0.48 - 0.84 ] ; HPV-18 GMT ratio : 0.77 [ 95 % CI , 0.62 - 0.96 ] ) . Pain at the injection site was the most common adverse event . CONCLUSIONS Among adolescent girls in Vietnam , administration of the HPV vaccine on st and ard and alternative schedules was immunogenic and well tolerated . The use of 2 alternative dosing schedules ( at 0 , 3 , and 9 months and at 0 , 6 , and 12 months ) compared with a st and ard schedule ( at 0 , 2 , and 6 months ) did not result in inferior antibody concentrations . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00524745 BACKGROUND Accumulating evidence suggests that collaborative models of care enhance communication among primary care providers , improving quality of care and outcomes for patients with chronic conditions . We sought to determine whether a multifaceted intervention that used a collaborative care model and was directed through primary care providers would improve symptoms of angina , self-perceived health , and concordance with practice guidelines for managing chronic stable angina . METHODS We conducted a prospect i ve trial , cluster r and omized by provider , involving patients with symptomatic ischemic heart disease recruited from primary care clinics at 4 academically affiliated Department of Veterans Affairs health care systems . Primary end points were changes over 12 months in symptoms on the Seattle Angina Question naire , self-perceived health , and concordance with practice guidelines . RESULTS In total , 183 primary care providers and 703 patients participated in the study . Providers accepted and implemented 91.6 % of 701 recommendations made by collaborative care teams . Almost half were related to medications , including adjustments to β-blockers , long-acting nitrates , and statins . The intervention did not significantly improve symptoms of angina or self-perceived health , although end points favored collaborative care for 10 of 13 prespecified measures . While concordance with practice guidelines improved 4.5 % more among patients receiving collaborative care than among those receiving usual care ( P < .01 ) , this was mainly because of increased use of diagnostic testing rather than increased use of recommended medications . CONCLUSION A collaborative care intervention was well accepted by primary care providers and modestly improved receipt of guideline -concordant care but not symptoms or self-perceived health in patients with stable angina OBJECTIVE To evaluate the effectiveness of the Systematic Care Program for Dementia ( SCPD ) on patient institutionalization and to determine the predictors of institutionalization . DESIGN Single-blind , multicenter , cluster-r and omized , controlled trial . SETTING Six community mental health services ( CMHSs ) across the Netherl and s. PARTICIPANTS A total of 295 patient-caregiver dyads referred to a CMHS with suspected patient dementia . INTERVENTION Training of health professionals in the SCPD and its subsequent use . The SCPD consists of a systematic assessment of caregiver problems and alerts health professionals in flexible , connecting , proactive interventions to them . The intensity of the SCPD depends on the judgment of the health professional , based on individual caregiver needs . PRIMARY OUTCOME Institutionalization in long-term care facilities at 12 months of follow-up . RESULTS No main intervention effect on institutionalization was found . However , a better sense of competence in the control group reduced the chance of institutionalization but not in the intervention group . The caregiver 's sense of competence and depressive symptoms and the patient 's behavioral problems and severity of dementia were the strongest predictors of institutionalization . The intensity of the program was low , even for dyads exposed to the SCPD . CONCLUSIONS Although no main effect was found , the results suggest that the SCPD might prevent a deterioration of the sense of competence in the intervention group . The intensity of a program is crucial and should be prescribed on the basis of evidence rather than left to the discretion of health professionals . Future controlled trials in daily clinical practice should use a process analysis to control for compliance OBJECTIVES : The goal of this study was to determine if a responsive stimulation and feeding intervention improved developmental and nutritional outcomes compared with a regular information-based parenting program . The hypothesis was that mothers in the intervention would exhibit better parenting skills and children would exhibit better developmental and nutritional outcomes than controls . METHODS : A cluster-r and omized field trial was conducted with 302 children aged 8 to 20 months and their mothers in rural Bangladesh who were r and omly assigned according to village to 1 of 3 groups . The control mothers received 12 informational sessions on health and nutrition . The intervention groups received an additional 6 sessions delivered by peer educators who included modeling and coached practice in self-feeding and verbal responsiveness with the child during play . A second intervention group received , along with the sessions , 6 months of a food powder fortified with minerals and vitamins . Developmental outcomes included the Home Observation for Measurement of the Environment ( HOME ) Inventory , mother-child responsive talk , and language development . Nutritional outcomes included weight , height , self-feeding , and mouthfuls eaten . We used analysis of covariance to compare the 3 groups at the posttest and at follow-up , covarying the pretest levels and confounders . RESULTS : At follow-up , responsive stimulation-feeding groups had better HOME inventory scores , responsive talking , language , mouthfuls eaten , and h and -washing . Micronutrient fortification result ed in more weight gain . CONCLUSIONS : A brief behavior-change program that focused on modeling and practice in stimulation and feeding was found to benefit children 's nutrition and language development . Micronutrients benefited children 's weight but not length CONTEXT Maternal vitamin A deficiency is a public health concern in the developing world . Its prevention may improve maternal and infant survival . OBJECTIVE To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized , double-masked , placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks ( 84 days ) postpartum in rural northern Bangladesh between 2001 and 2007 . Interventions Five hundred ninety-six community clusters ( study sectors ) were r and omized for pregnant women to receive weekly , from the first trimester through 12 weeks postpartum , 7000 μg of retinol equivalents as retinyl palmitate , 42 mg of all-trans beta carotene , or placebo . Married women ( n = 125,257 ) underwent 5-week surveillance for pregnancy , ascertained by a history of amenorrhea and confirmed by urine test . Blood sample s were obtained from participants in 32 sectors ( 5 % ) for biochemical studies . MAIN OUTCOME MEASURES All-cause mortality of women related to pregnancy , stillbirth , and infant mortality to 12 weeks ( 84 days ) following pregnancy outcome . RESULTS Groups were comparable across risk factors . For the mortality outcomes , neither of the supplement group outcomes was significantly different from the placebo group outcomes . The numbers of deaths and all-cause , pregnancy-related mortality rates ( per 100,000 pregnancies ) were 41 and 206 ( 95 % confidence interval [ CI ] , 140 - 273 ) in the placebo group , 47 and 237 ( 95 % CI , 166 - 309 ) in the vitamin A group , and 50 and 250 ( 95 % CI , 177 - 323 ) in the beta carotene group . Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 ( 95 % CI , 0.75 - 1.76 ) and 1.21 ( 95 % CI , 0.81 - 1.81 ) , respectively . In the placebo , vitamin A , and beta carotene groups the rates of stillbirth and infant mortality were 47.9 ( 95 % CI , 44.3 - 51.5 ) , 45.6 ( 95 % CI , 42.1 - 49.2 ) , and 51.8 ( 95 % CI , 48.0 - 55.6 ) per 1000 births and 68.1 ( 95 % CI , 63.7 - 72.5 ) , 65.0 ( 95 % CI , 60.7 - 69.4 ) , and 69.8 ( 95 % CI , 65.4 - 72.3 ) per 1000 live births , respectively . Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study ( 1.46 [ 95 % CI , 1.42 - 1.50 ] μmol/L vs 1.13 [ 95 % CI , 1.09 - 1.17 ] μmol/L and 1.18 [ 95 % CI , 1.14 - 1.22 ] μmol/L , respectively ; P < .001 ) and reduced , but did not eliminate , gestational night blindness ( 7.1 % for vitamin A vs 9.2 % for placebo and 8.9 % for beta carotene [ P < .001 for both ] ) . CONCLUSION Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh , compared with placebo , did not reduce all-cause maternal , fetal , or infant mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00198822 BACKGROUND The high morbidity and mortality in African Americans associated with behavior-linked chronic diseases are well documented . METHODS We tested the efficacy of an intervention to increase multiple health-related behaviors in African Americans . In a multisite cluster-r and omized controlled trial , groups of African American human immunodeficiency virus (HIV)-serodiscordant heterosexual couples in Atlanta ( Georgia ) , Los Angeles ( California ) , New York ( New York ) , and Philadelphia ( Pennsylvania ) were allocated to an individual-focused health promotion that addressed multiple health-related behaviors or to a couple-focused HIV/sexually transmitted disease ( STD ) risk reduction intervention . Primary outcomes were adherence to fruit and vegetable consumption and physical activity guidelines assessed preintervention , immediately postintervention , and 6 and 12 months postintervention . Secondary outcomes included fatty food consumption , prostate and breast cancer screening , and alcohol use . Generalized estimating equations tested the efficacy of the health promotion intervention over the postintervention assessment s. RESULTS Health promotion intervention participants were more likely to report consuming 5 or more servings of fruits and vegetables daily ( rate ratio [ RR ] , 1.38 ; 95 % confidence interval [ CI ] , 1.18 to 1.62 ) and adhering to physical activity guidelines ( 1.39 ; 1.22 to 1.59 ) compared with HIV/STD intervention participants . In the health promotion intervention compared with the HIV/STD intervention , participants consumed fatty foods less frequently ( mean difference , -0.18 ; 95 % CI , -0.30 to -0.07 ) , more men received prostate cancer screening ( RR , 1.51 ; 95 % CI , 1.21 to 1.88 ) , and more women received a mammogram ( RR , 1.26 ; 95 % CI , 1.06 to 1.50 ) . Alcohol use did not differ between the intervention groups . CONCLUSION This trial demonstrates the efficacy of interventions targeting multiple health-related behaviors in African American HIV-seropositive and HIV-seronegative men and women . Trial Registration clinical trials.gov Identifier : NCT00644163 Effectiveness comparison of different school-based nutrition education interventions to improve fruit and vegetable ( F&V ) consumption in schoolchildren not yet well research ed . We evaluated the effectiveness of two school-based interventions promoting fruit and vegetable intake among Italian schoolchildren . In this r and omized intervention trials , the first intervention was conducted by schoolteachers who attended a nutritionist-led training course ( group-1 ) , the second intervention conducted by schoolteachers who performed a self-training course ( group-2 ) . Thirty-two second to fifth- grade elementary classes enrolling 96 schoolteachers and 813 schoolchildren were r and omized , and assigned to the two different nutrition education interventions . 804 students completed the study . By the end of the study , the group-1 ( n = 409 ) followed by the teachers who attended a nutritionist-led course successfully increased the consumption of fruit and vegetables : in 183 ( 44.7 % ) and 157 ( 38.3 % ) schoolchildren respectively ; the group-2 ( n = 395 ) with teachers who performed a self-training course reported an increased consumption of fruit and vegetables in 81 ( 20.5 % ) and 76 ( 19.2 % ) , respectively . This study indicates that a school-based nutrition education conducted by teachers who attended a nutritionist-led training course has a significant impact on primary school-age children 's F&V intake OBJECTIVE To explore factors associated with the frequency of multidisciplinary Team Care Arrangements ( TCAs ) and the impact of TCAs on patient-assessed quality of care in Australian general practice . DESIGN AND SETTING Data were collected as part of a cluster r and omised controlled trial conducted in 60 general practice s in New South Wales , the Australian Capital Territory and Victoria between July 2006 and June 2008 . Multilevel logistic regression analysis evaluated factors associated with the frequency of TCAs recorded in the 12 months after baseline , and multilevel multivariable analysis examined the association between TCAs and patient-assessed quality of chronic illness care , adjusted for patient and practice characteristics . MAIN OUTCOME MEASURES Frequency of TCAs ; Patient Assessment of Chronic Illness Care ( PACIC ) scores . RESULTS Of 1752 patients with clinical audit data available at 12-month follow-up , 398 ( 22.7 % ) had a TCA put in place since baseline . Women , patients with two or more chronic conditions , and patients from metropolitan areas had an increased probability of having a TCA . There was an association between TCAs and practice s with solo general practitioners and those with greater levels of teamwork involving non-GP staff for the control group but not the intervention group . Patients who had a TCA self-assessed their quality of care ( measured by PACIC scores ) to be higher than those who did not . CONCLUSIONS Findings were consistent with the purpose of TCAs -- to provide multidisciplinary care for patients with longer-term complex conditions . Significant barriers to TCA use remain , especially in rural areas and for men , and these may be more challenging to overcome in larger practice BACKGROUND Barbershop-based hypertension ( HTN ) outreach programs for black men are becoming increasingly common , but whether they are an effective approach for improving HTN control remains uncertain . METHODS To evaluate whether a continuous high blood pressure ( BP ) monitoring and referral program conducted by barbers motivates male patrons with elevated BP to pursue physician follow-up , leading to improved HTN control , a cluster r and omized trial ( BARBER-1 ) of HTN control was conducted among black male patrons of 17 black-owned barbershops in Dallas County , Texas ( March 2006-December 2008 ) . Participants underwent 10-week baseline BP screening , and then study sites were r and omized to a comparison group that received st and ard BP pamphlets ( 8 shops , 77 hypertensive patrons per shop ) or an intervention group in which barbers continually offered BP checks with haircuts and promoted physician follow-up with sex-specific peer-based health messaging ( 9 shops , 75 hypertensive patrons per shop ) . After 10 months , follow-up data were obtained . The primary outcome measure was change in HTN control rate for each barbershop . RESULTS The HTN control rate increased more in intervention barbershops than in comparison barbershops ( absolute group difference , 8.8 % [ 95 % confidence interval ( CI ) , 0.8%-16.9 % ] ) ( P = .04 ) ; the intervention effect persisted after adjustment for covariates ( P = .03 ) . A marginal intervention effect was found for systolic BP change ( absolute group difference , -2.5 mm Hg [ 95 % CI , -5.3 to 0.3 mm Hg ] ) ( P = .08 ) . CONCLUSIONS The effect of BP screening on HTN control among black male barbershop patrons was improved when barbers were enabled to become health educators , monitor BP , and promote physician follow-up . Further research is warranted . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325533 OBJECTIVES To develop and test the Function-Focused Care in Assisted Living ( FFC-AL ) intervention so as to alter the decline that older adults in AL experience . DESIGN Cluster-r and omized controlled trial using repeated measures to test the effect of FFC-AL . SETTING Four AL facilities with at least 100 beds . PARTICIPANTS One hundred seventy-one residents and 96 direct care workers ( DCWs ) were recruited . Ninety-five of the DCWs were female ( 99 % ) , and 59 were black ( 62 % ) , with a mean age of 41.7 ± 13.8 . The residents were mostly female ( 80 % ) , white ( 93 % ) , and widowed ( 80 % ) , with a mean age of 87.7 ± 5.7 . INTERVENTION FFC-AL included four components implemented by a research -supported function focused-care nurse ( FFCN ) and a site-identified champion over a 12-month period . Control sites were exposed to FFC education only . MEASUREMENTS Outcomes for residents included psychosocial domains ( mood , resilience , self-efficacy , and outcome expectations for function and physical activity ) , function , gait and balance , and actigraphy . Outcomes for DCWs included knowledge , performance , and beliefs associated with FFC . RESULTS DCWs in treatment sites provided more FFC by 12 months than those in control sites . Residents in treatment sites demonstrated less decline in function , a greater percentage returned to ambulatory status , and there were positive trends demonstrating more time in moderate-level physical activity at 4 months and more overall counts of activity at 12 months than for residents in control sites . CONCLUSION Using a function-focused approach in AL may help prevent some of the functional decline commonly noted in these setting & NA ; The aim of this study was to test a 180‐minute group HIV risk – reduction counseling intervention trial with men undergoing traditional circumcision in South Africa to reduce behavioral disinhibition ( false security ) as a result of the procedure . A cluster r and omized controlled trial design was employed using a sample of 160 men , 80 in the experimental group and 80 in the control group . Comparisons between baseline and 3‐month follow‐up assessment s on key behavioral outcomes were completed . We found that behavioral intentions , risk‐reduction skills , and male role norms did not change in the experimental compared to the control condition . However , HIV‐related stigma beliefs were significantly reduced in both conditions over time . These findings show that one small‐group HIV risk – reduction intervention did not reduce sexual risk behaviors in recently traditionally circumcised men at high risk for behavioral disinhibition Background Research findings are not rapidly or fully implemented into policies and practice in care . Objectives To assess whether an ‘ active ’ strategy was more likely to lead to changes in policy and practice in preterm baby care than traditional information dissemination . Design Cluster r and omised trial . Participants 180 neonatal units ( 87 active , 93 control ) in Engl and ; clinicians from active arm units ; babies born < 27 weeks gestation . Control arm Dissemination of research report ; slides ; information about newborn care position statement . Active arm As above plus offer to become ‘ regional ‘ champion ’ ( attend two workshops , support clinicians to implement research evidence regionally ) , or attend one workshop , promote implementation of research evidence locally . Main outcome measures timing of surfactant administration ; admission temperature ; staffing of resuscitation team present at birth . Results 48/87 Lead clinicians in the active arm attended one or both workshops . There was no evidence of difference in post-intervention policies between trial arms . Practice outcomes based on babies in the active ( 169 ) and control arms ( 186 ) , in 45 and 49 neonatal units respectively , showed active arm babies were more likely to have been given surfactant on labour ward ( RR=1.30 ; 95 % CI 0.99 to1.70 ) ; p=0.06 ) ; to have a higher temperature on admission to neonatal intensive care unit ( mean difference=0.29oC ; 95 % CI 0.22 to 0.55 ; p=0.03 ) ; and to have had the baby 's trunk delivered into a plastic bag ( RR=1.27 ; 95 % CI 1.01 to 1.60 ; p=0.04 ) than the control group . The effect on having an ‘ ideal ’ resuscitation team at birth was in the same direction of benefit for the active arm ( RR=1.18 ; 95 % CI 0.97 to 1.43 ; p=0.09 ) . The costs of the intervention were modest . Conclusions This is the first trial to evaluate methods for transferring information from neonatal research into local policies and practice in Engl and . An active approach to research dissemination is both feasible and cost-effective . Trial registration Current controlled trials IS RCT OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year ( 6 intervention contacts ) of a planned 2-year study . DESIGN Cluster r and omized controlled trial . SETTING Ten pediatric practice s , 5 intervention and 5 usual care . PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index ( BMI ) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight ; 445 ( 93 % ) had 1-year outcomes . INTERVENTION Intervention practice s received primary care restructuring , and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake . OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year . RESULTS Compared with usual care , intervention participants had a smaller , nonsignificant change in BMI ( -0.21 ; 95 % confidence interval [ CI ] , -0.50 to 0.07 ; P = .15 ) , greater decreases in television viewing ( -0.36 h/d ; 95 % CI , -0.64 to -0.09 ; P = .01 ) , and slightly greater decreases in fast food ( -0.16 serving/wk ; 95 % CI , -0.33 to 0.01 ; P = .07 ) and sugar-sweetened beverage ( -0.22 serving/d ; 95 % CI , -0.52 to 0.08 ; P = .15 ) intake . In post hoc analyses , we observed significant effects on BMI among girls ( -0.38 ; 95 % CI , -0.73 to -0.03 ; P = .03 ) but not boys ( 0.04 ; 95 % CI , -0.55 to 0.63 ; P = .89 ) and among participants in households with annual incomes of $ 50 000 or less ( -0.93 ; 95 % CI , -1.60 to -0.25 ; P = .01 ) but not in higher-income households ( 0.02 ; 95 % CI , -0.30 to 0.33 ; P = .92 ) . CONCLUSION After 1 year , the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI OBJECTIVE Patients with COPD consistently express a desire to discuss end-of-life care with clinicians , but these discussion s rarely occur . We assessed whether an intervention using patient-specific feedback about preferences for discussing end-of-life care would improve the occurrence and quality of communication between patients with COPD and their clinicians . METHODS We performed a cluster-r and omized trial of clinicians and patients from the outpatient clinics at the Veterans Affairs Puget Sound Health Care System . Using self-reported question naires , we assessed patients ' preferences for communication , life-sustaining therapy , and experiences at the end of life . The intervention clinicians and patients received a one-page patient-specific feedback form , based on question naire responses , to stimulate conversations . The control group completed question naires but did not receive feedback . Patient-reported occurrence and quality of end-of-life communication ( QOC ) were assessed within 2 weeks of a targeted visit . Intention-to-treat regression analyses were performed with generalized estimating equations to account for clustering of patients within clinicians . RESULTS Ninety-two clinicians contributed 376 patients . Patients in the intervention arm reported nearly a threefold higher rate of discussion s about end-of-life care ( unadjusted , 30 % vs 11 % ; P < .001 ) . Baseline end-of-life communication was poor ( intervention group QOC score , 23.3 ; 95 % CI , 19.9 - 26.8 ; control QOC score , 19.2 ; 95 % CI , 15.9 - 22.4 ) . Patients in the intervention arm reported higher- quality end-of-life communication that was statistically significant , although the overall improvement was small ( Cohen effect size , 0.21 ) . CONCLUSIONS A one-page patient-specific feedback form about preferences for end-of-life care and communication improved the occurrence and quality of communication from patients ' perspectives . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT00106080 ; URL : www . clinical trials.gov Nasopharyngeal ( NP ) carriage of S. pneumoniae ( Spn ) is a risk factor for pneumococcal disease and its transmission . We assessed the impact of vitamin A ( VA ) supplementation shortly after birth in reducing Spn colonization in early infancy in rural Bangladesh . We recruited 500 infants participating in a cluster-r and omized trial that reported a 15 % reduction in mortality following receipt of an oral dose of VA ( 52.25 μmol ) compared to placebo . NP specimens were collected at the age of 3 mo to study the effect of VA on the prevalence of culture-confirmed Spn . Analyses were conducted by intention to treat . Spn carriage prevalence did not differ between VA and placebo recipients [ OR = 0.83 ( 95 % CI : 0.55 - 1.27 ) ; P = 0.390 ] . Spn carriage at the age of 3 mo was not lowered by VA given at birth . Results are similar to those from an Indian study in which impact on Spn carriage was assessed at the age of 4 mo [ OR = 0.73 ( 95 % CI : 0.48 - 1.10 ) ; P = 0.128 ] . The point estimate of the pooled effect size for the 2 studies is OR = 0.78 [ ( 95 % CI : 0.58 - 1.04 ) ; P = 0.095 ] , which may imply a modest impact on carriage . If so , then the evidence thus far would suggest that Spn carriage reduction is unlikely to be a primary ancillary benefit of newborn VA supplementation BACKGROUND Brief advice for smoking patients has not been sufficiently integrated in routine care . Computer-based interventions emerged as a time saving option that might help to exhaust the potential population impact of the general practice setting . METHOD 151 practice s were r and omly assigned to one of three intervention programs consisting in the delivery of : ( 1 ) brief advice by the practitioner ; ( 2 ) individually tailored computer-generated letters ; or ( 3 ) a combination of both interventions . We assessed three dimensions of population impact : ( 1 ) adoption , i.e. , the rate of practice s participating in the program ; ( 2 ) reach , measured as the number of interventions provided within 7 months ; ( 3 ) effectiveness , measured as smoking abstinence at 12-months follow-up . RESULTS Among the practice s , 70 % adopted the program with no significant differences across study groups . Treatment was provided to 3086 adult smokers . Negative binomial regression analysis revealed that the number of interventions provided was higher in practice s allocated to the tailored letter and combination intervention groups by 215 % ( p<.01 ) and 127 % ( p=.02 ) , respectively , compared to the brief advice intervention group . Among the patients who received the combination of both intervention , the odds of point abstinence from smoking was increased by 65 % ( p=.02 ) and 32 % ( p=.01 ) compared to the brief advice and tailored letters intervention respectively . Comparing the number of abstinent patients at follow-up revealed that the tailored letter and combination interventions were superior to the brief advice intervention . CONCLUSIONS Computer-based interventions alone or in addition to conventional practitioner-delivered advice can foster the participation of general medical practice s in tobacco control OBJECTIVE A r and omized cluster controlled trial tested the hypothesis that weekly feedback to clinicians would improve the effectiveness of home-based mental health treatment received by youths in community setting s. METHODS Youths , caregivers , and clinicians at 28 sites in ten states completed assessment s of the youths ' symptoms and functioning every other week . Clinicians at 13 sites were provided with weekly feedback about the assessment s , and clinicians at 15 sites received feedback every 90 days . Data were collected from June 1 , 2006 , through December 31 , 2008 . Intent-to-treat analyses were conducted with hierarchical linear modeling of data provided by youths , caregivers , and clinicians . RESULTS Assessment s by youths , caregivers , and clinicians indicated that youths ( N=173 ) treated at sites where clinicians could receive weekly feedback improved faster than youths ( N=167 ) treated at sites where clinicians did not receive weekly feedback . A dose-response analysis showed even stronger effects when clinicians viewed more feedback reports . CONCLUSIONS Routine measurement and feedback can be used to improve outcomes for youths who receive typical home-based services in the community OBJECTIVE To determine the effectiveness of a provider-based education and implementation intervention for improving diabetes control . DESIGN Cluster-r and omized trial with baseline and follow-up cross sections of diabetes patients in each participating physician 's practice . SETTING Eleven US Southeastern states , 2006 - 08 . PARTICIPANTS Two hundred and five rural primary care physicians . INTERVENTION Multi-component interactive intervention including Web-based continuing medical education , performance feedback and quality improvement tools . Primary Outcome Measures ' Acceptable control ' [ hemoglobin A1c ≤9 % , blood pressure ( BP ) < 140/90 mmHg , low-density lipoprotein cholesterol ( LDL ) < 130 mg/dl ] and ' optimal control ' ( A1c < 7 % , BP < 130/80 mmHg , LDL < 100 mg/dl ) . RESULTS Of 364 physicians attempting to register , 205 were r and omized to the intervention ( n= 102 ) or control arms ( n= 103 ) . Baseline and follow-up data were provided by 95 physicians ( 2127 patients ) . The proportion of patients with A1c ≤9 % was similar at baseline and follow-up in both the control [ adjusted odds ratio ( AOR ) : 0.94 ; 95 % confidence interval ( CI ) : 0.61 , 1.47 ] and intervention arms [ AOR : 1.16 ( 95 % CI : 0.80 , 1.69 ) ] ; BP < 140/90 mmHg and LDL < 130 mg/dl were also similar at both measurement points ( P= 0.66 , P= 0.46 ; respectively ) . We observed no significant effect on diabetes control attributable to the intervention for any of the primary outcome measures . Intervention physicians engaged with the Website over a median of 64.7 weeks [ interquartile range ( IQR ) : 45.4 - 81.8 ) for a median total of 37 min ( IQR : 16 - 66 ) . CONCLUSIONS A wide-reach , low-intensity , Web-based interactive multi-component intervention did not improve control of glucose , BP or lipids for patients with diabetes of physicians practicing in the rural Southeastern US BACKGROUND Patient care guidelines are usually implemented one at a time , yet patients are at risk for multiple , often preventable , adverse events simultaneously . OBJECTIVE This study aim ed to test the effect of the SAFE or SORRY ? programme on the incidence of three adverse events ( pressure ulcers , urinary tract infections and falls ) . This paper describes Part I of the study : the effect on the incidence of adverse events . DESIGN A cluster r and omised trial was conducted between September 2006 and November 2008 . After a three-month baseline period the intervention was implemented followed by a nine-month follow-up period . SETTING S Ten wards from four hospitals and ten wards from six nursing homes were stratified for institute and ward type and then r and omised to intervention or usual care group . PARTICIPANTS During baseline and follow-up , patients ( ≥18 years ) with an expected length of stay of at least five days , were asked to participate . METHODS The SAFE or SORRY ? programme consisted of the essential recommendations of guidelines for the three adverse events . A multifaceted implementation strategy was used for the implementation : education , patient involvement and feedback on process and outcome indicators . The usual care group continued care as usual . Data were collected on the incidence of adverse events and a Poisson regression model was used to estimate the rate ratio of the adverse events between the intervention and the usual care group at follow-up . RESULTS At follow-up , 2201 hospital patients with 3358 patient weeks and 392 nursing home patients with 5799 patient weeks were observed . Poisson regression analyses showed a rate ratio for the development of an adverse event in favour of the intervention group of 0.57 ( 95 % CI : 0.34 - 0.95 ) and 0.67 ( 95 % CI : 0.48 - 0.99 ) for hospital patients and nursing home patients respectively . CONCLUSION This study showed that implementing multiple guidelines simultaneously is possible , which is promising . Patients in the intervention groups developed 43 % and 33 % fewer adverse events compared to the usual care groups in hospitals and nursing homes respectively . Even so , more research is necessary to underline these results . TRIAL REGISTRATION clinical trials.gov , number NCT00365430 BACKGROUND Registries have shown that quality of care for acute coronary syndromes ( ACS ) often falls below the st and ards recommended in professional guidelines . Quality improvement ( QI ) is a strategy to improve st and ards of clinical care for patients , but the efficacy of QI for ACS has not been tested in r and omized trials . METHODS We undertook a prospect i ve , cluster-r and omized , multicenter , multinational study to evaluate the efficacy of a QI program for ACS . Participating centers collected data on consecutive admissions for non-ST-elevation ACS for 4 months before the QI intervention and 3 months after . Thirty-eight hospitals in France , Italy , Pol and , Spain , and the United Kingdom were r and omized to receive the QI program or not , 19 in each group . We measured 8 in-hospital quality indicators ( risk stratification , coronary angiography , anticoagulation , β-blockers , statins , angiotensin-converting enzyme inhibitors , and clopidogrel loading and maintenance ) before and after the intervention and compared composite changes between the QI and non-QI groups . RESULTS A total of 2604 patients were enrolled . The absolute overall change in use of quality indicators in the QI group was 8.5 % compared with 0.8 % in the non-QI group ( odds ratio for achieving a quality indicator in QI versus non-QI 1.66 , 95 % CI 1.43 - 1.94 ; P < .001 ) . The main changes were observed in the use of risk stratification and clopidogrel loading dose . CONCLUSIONS The QI strategy result ed in a significant improvement in the quality indicators measured . This type of QI intervention can lead to useful changes in health care practice for ACS in a wide range of setting BACKGROUND The prevalence of health care-associated infections ( HAIs ) in general medical wards at Siriraj Hospital in Bangkok , Thail and remains at 10 % even after infection control measures were launched . The present study aim ed to determine the effectiveness of comprehensive individualized bundling infection control measures in reducing HAIs and to identify the lowest possible rate of HAIs in general medical wards . METHODS This was a cluster r and omized controlled study conducted in 8 general medical wards ( 4 control wards and 4 intervention wards ) at Siriraj Hospital . The patients hospitalized in the control wards received regular health care , as well as regular measures for preventing HAIs . The patients hospitalized in the intervention wards received additional measures . Each patient in the intervention wards was visited by the infection control team once a day until he or she left the hospital . The infection control team identified risk factors for developing HAI in each patient , coordinated with the local health care team to eliminate or minimize such risk factors , and encouraged responsible personnel to comply with the appropriate infection control measures for each patient . RESULTS Between January and April 2009 , there were 954 patients ( 9,650 hospitalization-days ) in the intervention wards and 920 patients ( 9,777 hospitalization-days ) in the control wards . The patient characteristics were comparable in the 2 groups . The prevalence of HAI was significantly lower in the intervention wards compared with the control wards ( 5.6 % vs. 9.2 % ; P = .003 ) . Six episodes of HAI in patients in the intervention wards could have been avoided . CONCLUSION Comprehensive individualized bundling infection control measures were effective in reducing the prevalence of HAIs in general medical wards . The target overall prevalence of HAIs in general medical wards should not exceed 4.9 % In a cluster-r and omized trial , Riitta Luoto and colleagues find that counseling on diet and activity can reduce the birthweight of babies born to women at risk of developing gestational diabetes mellitus ( GDM ) , but fail to find an effect on GDM |
1,167 | 19,270,730 | Glutamine ( i.v . )
There was no effect of oral or i.v . | It is unclear whether supplemental glutamine is of benefit in haematopoietic stem cell transplantation ( HSCT ) . | BACKGROUND Total parenteral nutrition ( TPN ) supplemented with glutamine ( GLN ) has been reported to be effective for patients with bone marrow transplantation ( BMT ) . Our aim was to evaluate enteral and parenteral glutamine in patients undergoing BMT . METHODS For evaluation of GLN in BMT , 66 patients with 43 hematologic and 23 solid malignancies ( 21 breast carcinomas ) , were r and omized , double-blinded , to either oral GLN ( n = 35 ) or glycine-control ( GLY ) ( n = 31 ) , 10 g three times daily . When TPN became necessary , patients who received GLN orally were given TPN with GLN ( 0.57 g/kg ) . Those who received GLY received st and ard TPN , isocaloric and isonitrogenous . Patients with hematologic malignancies received high-dose chemotherapy , total body irradiation , and either allogeneic ( ALLO ) BMT ( n = 18 ) or autologous ( AUTO ) stem cell transplantation ( n = 25 ) . Patients with solid malignancies ( n = 23 ) received AUTO . RESULTS There were 14 in-hospital deaths without relationship to GLN administration . For respective comparisons of ALLO and AUTO transplants in the GLN and GLY hematologic groups and AUTO in the solid tumor groups , there were no significant differences in hospital stay , duration of stay after BMT , TPN days , neutrophil recovery > 500/mm3 , incidence of positive blood cultures , sepsis , mucositis , and diarrhea . Acute graft us host disease occurred in 1 of 10 hematologic patients receiving GLN and in 3 of 8 patients receiving GLY placebo ( p > .05 ) . Possible reduction in need for TPN and a suggestion of improved long-term survival were associated with GLN . CONCLUSIONS Oral and parenteral GLN seemed to be of limited benefit for patients having AUTO or ALLO BMT for hematologic or solid malignancies . Further study of long-term effects of GLN in BMT seems warranted Forty-four adult autologous transplant patients with hematological malignancies were r and omized to receive either prophylactic parenteral nutrition PN ( P group ) , or PN given ad hoc ( C group ) . In each group , they were further r and omized to receive st and ard PN ( B group ) , or PN with 0.5 g glutamine/kg as L-Ala-L-Gln ( A group ) . The overall survival ( OS ) , disease-free survival ( DFS ) and event-free survival ( EFS ) in groups C vs. P and A vs. B were compared during follow-up with median 38 months . The final outcome rates in C/P/A/B groups , respectively ( OS 65/81/63/85 % , EFS 45/53/33/65 % and DFS 56/50/35/77 % ) , were not significantly different , apart from A < B in DFS rate ( p=0.03 , Fisher 's exact test ) . Also in survival analysis ( logrank test ) , no significant difference between groups C and P was found but generally worse parameters were observed for A vs. B group : for DFS ( p=0.04 ) and EFS ( p=0.01 ) the difference was significant , and for OS ( p=0.09 ) it was borderline . In the three years ' follow-up , no clinical ly useful benefit of prophylactic PN in autologous transplant patients was proven . Also , glutamine supplementation was not helpful , and was even connected with apparently worse long-term outcome Objective : The purpose of this study was to determine the most appropriate dose of oral glutamine to use in a further clinical study in paediatric oncology patients . Design : This was a phase I , pharmokinetic study . Setting : The study was carried out at The Yorkshire Regional Centre for Paediatric Oncology and Haematology , St James 's University Hospital , Leeds , UK.Subjects : Thirteen patients undergoing treatment for paediatric malignancy participated in this study . All 13 completed the study . Interventions : The most appropriate dose was determined by patient acceptability and by plasma glutamine and ammonia levels measured at timed intervals after ingestion of a single glutamine dose . Results : Doses of 0.35 , 0.5 and 0.65 g/kg were well tolerated with no untoward plasma glutamine and ammonia levels . One patient was recruited to a higher dose of 0.75 g/kg , but the plasma glutamine and ammonia levels peaked at 2601 and 155 µmol/l , respectively . The ammonia level was greater than the acceptable upper limit . It was difficult to disperse the glutamine adequately at this dose , result ing in the suspension being found to be unpalatable and therefore no further patients were recruited at this dose . Conclusion : It was concluded that 0.65 g/kg is a safe dose of glutamine to use in a clinical study in paediatric oncology patients .Sponsorship : Scientific Hospital Supplies UK Ltd provided the L-glutamine and financial help for the biochemical analysis Painful oral mucositis is a common complication after bone marrow transplantation ( BMT ) . Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium . This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT . Glutamine or a placebo ( glycine ) were administered from admission until day + 28 in 193 BMT patients in a r and omized , double-blind , placebo-controlled study at a dose of 1.0 g amino acid/m2/dose swish and swallow four times a day . In autologous BMT patients ( n = 87 ) glutamine was associated with significantly less mouth pain by self report and by opiate use ( 5.0 ± 6.2 days of morphine for glutamine vs 10.3 ± 9.8 days for placebo ; P = 0.005 ) . Matched sibling BMT patients had no effect by self report and an increased duration of opiate use ( 23.2 ± 5.7 days for glutamine vs 16.3 ± 8.3 days for placebo ) ( P = 0.002 ) . However , day 28 survival of allogeneic patients was improved by glutamine . No significant differences in TPN use , rate of relapse or progression of malignancy , parenteral antibiotic use , acute or chronic GVHD , or days of hospitalization were observed in either autologous or allogeneic recipients . No toxicity of glutamine was observed . We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients , possibly due to interaction with methotrexate An oral glutamine load was administered to nine healthy subjects to determine the effect on plasma glutamine , bicarbonate , and circulating growth hormone concentrations . Two grams glutamine were dissolved in a cola drink and ingested over a 20-min period 45 min after a light breakfast . Forearm venous blood sample s were obtained at zero time and at 30-min intervals for 90 min and compared with time controls obtained 1 wk earlier . Eight of nine subjects responded to the oral glutamine load with an increase in plasma glutamine at 30 and 60 min before returning to the control value at 90 min . Ninety minutes after the glutamine administration load both plasma bicarbonate concentration and circulating plasma growth hormone concentration were elevated . These findings demonstrate that a surprisingly small oral glutamine load is capable of elevating alkaline reserves as well as plasma growth hormone UNLABELLED Bone marrow transplantation ( BMT ) is a therapy used for hematologic malignancies and solid tumors . Associated chemotherapy and radiotherapy to which these patients are su bmi tted induce secondary effects , with a high metabolic stress . Glutamine is considered a conditionally essential amino acid , and has been shown effective in severe catabolic states . The aim of the study was to assess the effect of parenteral nutrition ( PN ) therapy supplemented with glutamine on duration of nutritional support in a group of patients with BMT . We have also analyzed associated complications , the nutritional status , the clinical course at 6 months , differences as to type of transplantation , and oral ingestion capability . This is a phase IV , r and omized , double blind , and parallel clinical trial , done at a single center . The study was performed on 49 patients , 29 % male and 71 % female patients , with ages between 21 - 63 years , distributed in 3 diagnostic groups ( leukemia , lymphoma , and solid tumors ) , and admitted to the Hematology Department of our Hospital . Fifty percent of the patients in each group have received PN supplemented with glutamine ( 0.4 g/kg/day of L-alanine-L-glutamine ) , and the other 50 % have received st and ard PN . RESULTS we have not found significant differences nor at the beginning nor at the end of the study between both groups with regards to studied variables . CONCLUSIONS PN is and effective therapy for maintenance of the nutritional status in patients su bmi tted to a therapy with a , highly catabolic effect such as BMT . Although we have not been able to show the efficacy of glutamine supplementation in this study with the used dose , it does have been effective in other reports Glutamine ( Gln ) is an important nutrient substrate for lymphocytes and macrophages in vitro . This pilot study evaluated effects of Gln supplementation on circulating lymphocytes and lymphocyte subsets after allogeneic bone marrow transplantation ( BMT ) . Adult patients received either parenteral nutrition supplemented by L-Gln ( Gln-PN ) or st and ard Gln-free PN after BMT . Leukocyte and total lymphocyte counts were determined during hospitalization , and flow cytometry studies of peripheral mononuclear cells were performed 1 to 2 weeks after hospital discharge . The Gln-PN group demonstrated a higher percentage of blood lymphocytes during hospitalization . At flow cytometry , patients who received Gln-PN had an increased total lymphocyte count ( 332 + /- 50 versus 590 + /- 71 cells/microL , P = 0.010 ) ; greater numbers of total T lymphocytes ( 54 + /- 19 versus 229 + /- 70 cells/microL , P = 0.030 ) ; and higher CD4 + and CD8 + T-lymphocyte counts in peripheral blood compared with controls . Gln-PN may support lymphocyte recovery after BMT OBJECTIVE In a r and omized , double-blind , prospect i ve clinical trial , we evaluated the metabolic effects of glutamine-supplemented parenteral nutrition in patients with bone marrow transplants . We compared hospital charge and cost data for the two groups of patients in the trial . DESIGN Retrospective review . SETTING Bone Marrow Transplant Unit , Brigham and Women 's Hospital , Boston , Mass. SUBJECTS Forty-three patients admitted to the Bone Marrow Transplant Unit were assigned r and omly to receive either st and ard parenteral nutrition or an isocaloric , isonitrogenous parenteral nutrition solution containing glutamine starting on day 1 after bone marrow transplant . The two groups were well matched for diagnosis , antineoplastic treatment , and sex . MEASURES The primary clinical end points evaluated were nitrogen balance , length of hospitalization , incidence of infection , and results of microbial culture . After completion of the study , we compared the hospital charges for the categories of room and board , surgery , laboratory , pharmacy , radiology , ancillary , and miscellaneous between the two groups of patients . STATISTICAL ANALYSIS PERFORMED The two groups were compared using the unpaired t test or Mann-Whitney test for nonparametric measurements . A P value of < .05 was considered significant . RESULTS Nitrogen balance improved in the glutamine-supplemented group compared with control subjects ( -1.4 + /- 0.5 g/day vs 4.2 + /- 1.2 g/day , respectively ; P = .002 ) . Length of hospitalization was significantly shorter in the glutamine-supplemented group than in the control group ( 29 + /- 1 day vs 36 + /- 2 days , respectively ; P = .017 ) . The incidence of positive microbial cultures and clinical infection was also significantly lower with glutamine supplementation . Hospital charges were $ 21,095 per patient less in the glutamine-supplemented group compared with charges for patients who received st and ard therapy . Room and board charges were significantly different : $ 51,484 + /- 2,647 for the glutamine-supplemented group vs $ 61,591 + /- 3,588 in the control group ( P = .02 ) . CONCLUSION This intervention study using a new therapy demonstrated clinical and nutritional benefits to patients and cost savings to the hospital BACKGROUND / AIMS Long-term total parenteral nutrition is accompanied with mucosal atrophy and subsequent malabsorption syndrome . Current information attests the important role of glutamine in maintaining intestinal structure and function . The aim of this study was to investigate the effect of glutamine dipeptide supplementation on small intestinal absorption capacity during critical illness . METHODS Twelve intensive care unit patients were uniformly r and omized to receive isonitrogenous ( 0.26 g nitrogen.kg-1.day-1 ) and isoenergetic ( 155 kJ.kg-1.day-1 ) parenteral nutrition over 9 days . The control group received a conventional amino acid solution ( 1.5 g amino acids.kg-1.day-1 ) , and the test group received a complete amino acid solution containing the dipeptide L-alanyl-L-glutamine ( 20 g/L ) . On days 8 and 9 , a modified D-xylose test was performed . RESULTS Excretion of D-xylose during the 5-hour test period was 7.4 + /- 1.1 g ( test ) vs. 3.8 + /- 0.9 g ( control ) ( P < 0.05 ) . The 2-hour serum D-xylose concentration was 38.7 + /- 3.0 ( test ) vs. 27.8 + /- 2.9 mg/100 mL ( control ) ( P < 0.05 ) . Kinetic evaluation showed higher maximum D-xylose blood concentration and higher values for the area under the curve with the peptide . CONCLUSIONS The results strongly suggest that glutamine dipeptide-containing total parenteral nutrition prevents intestinal atrophy and increased permeability associated with glutamine-free parenteral nutrition We conducted a prospect i ve , r and omised , double-blinded , placebo-controlled pilot study of parenteral nutrition ( PN ) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant ( SCT ) recipients to determine its effect on mucosal barrier injury ( MBI ) . All patients had been prepared with idarubicin , cyclophosphamide and total body irradiation . PN ( by continuous infusion ) started on SCT day −6 for a median of 19 days . MBI measured by sugar permeability tests , daily mucositis score , daily gut score , and citrulline concentrations was not reduced by glutamine-dipeptide . However , the daily gut score was significantly lower for the glutamine group on SCT + 7 ( p=0.001 ) whilst citrulline was lower ( p=0.03 ) for the placebo group on SCT day + 21 . Albumin was significantly lower in the placebo group on SCT day + 21 ( 32±4 versus 37±3 , p=0.001 ) whilst CRP was higher ( 74±48 versus 34±38 , p=0.003 ) . Other transplant-related complications ( infections , acute graft-versus-host disease ) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality . These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications Nutritional effects have traditionally focused on outcomes , such as nitrogen balance , wound healing , or muscle strength . Little emphasis has been placed on how biochemical or physical improvements translate into functional changes as perceived by the patient . Because glutamine (GLN)-supplemented nutrition promotes protein synthesis and improves nitrogen balance , we assessed the mood of individuals participating in a r and omized controlled blinded trial receiving GLN solutions . Patients ( n = 23 ) undergoing marrow transplantation were r and omized by the research pharmacist to receive either st and ard total parenteral nutrition ( TPN ) ( control ) or GLN-containing TPN ( 40 g of glutamine total ) . The solutions were isocaloric and isonitrogenous and were administered until the patient was eating 50 % of estimated requirements . Before TPN and on admission to the hospital , the patient completed the Profile of Mood States question naire , a st and ardized test quantifying the degree of tension , depression , anger , vigor , fatigue , and confusion . The patient completed the question naire again at the end of TPN near discharge . The tests were scored and the change from baseline for each mood for both groups of patients was calculated at the completion of TPN . The scores for vigor in the control group ( delta scores ) decreased over the course of hospitalization as would be expected with a serious illness . The group receiving glutamine TPN , however , essentially showed little change in vigor from baseline and the delta score was significantly different from the control group ( delta vigor score -0.85 + /- 2.1 in the glutamine group vs. -5.90 + /- 1.7 in the control group ; p = .07 ) . ( ABSTRACT TRUNCATED AT 250 WORDS In a paper by Ziegler et al ( Ann Intern Med 116 : 821 - 828 , 1992 ) , total parenteral nutrition supplemented with L-glutamine ( TPN/GLN ) was reported beneficial in patients receiving bone marrow transplantation ( BMT ) for hematologic malignancies . By using a similar protocol , we studied 29 patients with both hematologic malignancies and solid tumors , and with both allogeneic and autologous BMTs . In a double-blind , r and omized approach , patients were given isocaloric , isonitrogenous TPN after BMT until they consumed 50 % of their required diet orally . Total body water and extracellular water were measured before and after TPN in 10 patients . Total body water increased in patients receiving st and ard TPN and decreased significantly in patients receiving TPN/GLN . Length of hospital stay after BMT was significantly ( 5.8 days ) less in patients receiving TPN/GLN . Incidence of positive bacterial cultures , clinical infections , and mortality did not differ significantly between the two groups . When the groups were subdivided into patients with hematologic malignancies and those with solid tumors , there were no significant differences in the above variables associated with TPN/GLN . In 17 of 30 additional hospitalized patients receiving st and ard TPN , substitution of TPN/GLN did not have discernible clinical or laboratory effects but appeared to be safe . Inclusion of patients with solid tumors and a higher mortality in our patients may have obscured beneficial effects of TPN/GLN observed by others Data from animal studies suggests that glutamine supplementation may reduce the incidence or severity of cytotoxic-induced mucositis . This study examined the effect of glutamine supplements on mucositis in patients receiving bone marrow transplants . 24 patients were r and omly assigned to receive an oral supplement of either glutamine or placebo ( 16 g/day ) from the time of transplantation until discharge from hospital . There was no significant difference in the incidence of oral mucositis , assessed either by the patient ( mucositis score : glutamine 17 vs. placebo 26.6 ) or an independent observer ( glutamine 31.1 vs. placebo 32.3 ) , or the number of days of diarrhoea ( glutamine 3.1 vs. placebo 3.3 days ) . Similarly there were no significant differences in haematological indices ( haemoglobin , WBC , platelets ) , the requirement for parenteral nutrition or hospital stay . Possible reasons for this negative result , which contrasts with those obtained in recent studies of patients receiving intravenous glutamine after bone marrow transplants , are discussed Hepatic veno-occlusive disease ( VOD ) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation ( BMT ) . The major pathological changes are seen in centrilobular ( zone 3 ) hepatocytes and adjacent endothelium . Glutathione ( GSH ) becomes depleted following chemotherapy and experimental evidence suggests reduced levels predispose to centrilobular hepatocyte and endothelial cell injury . Animal studies have shown that glutamine infusions can maintain GSH levels and protect against free radical injury . We have prospect ively studied the effect of glutamine supplementation during BMT . Thirty-four patients undergoing BMT were r and omised to receive either glycl-L-glutamine ( n = 18 ) or an isonitrogenous mixture of non-essential amino acids ( n = 16 ) . Glutamine was shown to significantly preserve protein C ( days + 4 and + 7 , P < 0.05 ) and albumin levels ( days 0 and + 4 , P < 0.02 ) . markers of thrombin and plasmin generation ( thrombin-antithrombin , prothrombin fragment f1 + 2 and plasmin-antiplasmin levels ) were not significantly changed between the two groups . these findings suggest that glutamine preserves hepatic function but does not alter thrombin or plasmin generation during bmt . previous studies have shown reductions in protein c , albumin , factor x and factor vii levels post bmt . falling protein c levels have been shown to be predictive of severe vod . these data suggest a role for glutamine in the protection of hepatic function following bmt We conducted a controlled , double-blind study of parenteral glutamine supplementation in an unselected group of consecutive autologous transplant patients . Patients received 30 g of alanyl-glutamine dipeptide ( Dipeptiven ; Fresenius-Kabi , Bad Homburg , Germany ) or glutamine-free amino acid solution i.v . from day + 1 to day + 14 or to discharge . All patients were assessed for clinical status , mucositis , blood counts , oral intake and immune reconstitution . Parenteral nutrition was administered according to predefined guidelines . Forty patients were r and omized ; 21 into the glutamine and 19 into the placebo arm . Glutamine patients had less days with diarrhoea ( 3.3 ± 4.0 vs4.3 ± 3.0 , P = 0.03 ) , but they had more severe oral mucositis ( mean 4 ± 4.7 vs 1.4 ± 2.3 days of mucositis score > 13 , P = 0.04 ) , spent more days on opioids ( mean 3.5 ± 4.2 vs 1.2 ± 2.2 days , P = 0.03 ) and left hospital later than placebo patients ( mean 13.5 ± 3.1 vs 11.7 ± 2.4 days after transplant , P = 0.06 ) . There were more relapses ( P = 0.02 ) and deaths ( P = 0.05 ) in the glutamine group . The cost of supportive care ( mean 2960 ± 1694 vs 1534 ± 513 Euro , P = 0.002 ) was also greater for glutamine patients , mainly due to the cost of glutamine dipeptide itself . The described mode and dosage of glutamine administration did not produce meaningful benefit in our autologous transplant patients and it was certainly not cost-effective Fifty-three patients with hematological malignancies who underwent Allo-SCT from HLA-identical siblings were r and omly assigned to receive glutamine-enriched parenteral nutrition — PN ( GlPN , n=27 ) or st and ard PN ( PN , n=26 ) , in isonitrogenous solutions . Deaths ( D+100 and D+180 ) , infections , acute GVHD , length of stay , time of neutropenia and intestinal permeability ( IP ) were studied . Ages , gender , diagnosis , disease status and treatment variables were equally distributed between groups . Survival on D+180 was increased in GlPN ( 74 % ) vs PN ( 46 % ) , P=0.03 ( log-rank ) , as on D+100 ( P=0.05 ) . Most deaths occurred before D+100 , especially in PN ( 10/26 , 39 % ) vs GlPN ( 4/27 , 15 % ) . GVHD was the most frequent cause of death ( 8/21 , 38 % ) , especially in PN ( n=6 , five before D+100 ) . Other outcomes were not affected . IP was affected on admission , was not affected by glutamine enrichment , but consistently worsened throughout the study . Results showed that GlPN was efficacious in increasing short-term survival after Allo-SCT . Benefits of glutamine seem to be independent of mucosal protection , as IP was not affected by its use . A trend to a lower incidence of GVHD deaths may suggest an immunomodulatory role of glutamine Summary : Severe mucositis is a common cause of morbidity in hematopoietic stem cell transplant ( HSCT ) recipients . Glutamine has been shown to reduce mucositis in children receiving chemotherapy . Patients were r and omized in a double-blind manner to receive glutamine or glycine at a dose of 2 g/m2/dose ( maximum dose 4 g ) twice daily until 28 days post transplant or discharge if sooner . Mucositis was grade d by use of a modified Walsh scale . A total of 120 children were evaluable : 57 children received glutamine and 63 received glycine . The mean mucositis score was 3.0±0.3 vs 3.9±0.4 ( P=0.07 ) in the glutamine and glycine groups , respectively . The glutamine group demonstrated a reduction in mean number of days of intravenous narcotics use ( 12.1±1.5 vs 19.3±2.8 in the glycine group , P=0.03 ) and total parenteral nutrition ( 17.3±1.7 vs 27.3±3.6 in glycine group , P=0.01 ) . There was no statistically significant difference in toxicity between the two groups . Glutamine appears to be safe and beneficial in reducing the severity of mucositis . Strong consideration should be given to include oral glutamine supplementation as a routine part of supportive care of SCT patients BACKGROUND Because all patients receiving bone marrow transplant ( BMT ) and peripheral blood progenitor cell transplant ( PBPCT ) experience gastrointestinal ( GI ) toxicity from the preparative regimen of chemotherapy , with or without radiation , oral glutamine was administered during the preparatory regimen and after transplant to maintain GI structure and function . METHODS To evaluate effects of oral glutamine on nutritional status and overall outcome , a prospect i ve , r and omized , double-blinded study was performed on 58 autologous and allogeneic BMT patients . Patients received 30 g of oral glutamine or placebo daily . RESULTS The trends of decreased median length of stay and the median number of days of total parenteral nutrition ( TPN ) were seen in the group supplemented with the > 0.285-g/kg ( the recommended dosage ) dose of glutamine ; however , there was no statistically significant difference in the nutritional status and overall patient outcome as assessed by days receiving TPN , number of days required until oral intake resumed , length of hospitalization , number of days and highest grade of mucositis , and quantity and number of days of diarrhea . CONCLUSIONS This study does not support the hypothesis that oral glutamine may offer benefit . Further investigation is required regarding clinical tools for determining effectiveness , administration for tolerance and compliance , dosage , and potential of oral glutamine usage Within the framework of a r and omized double blind study focused on the effect of glutamine on the clinical course of autologous transplantation of peripheral cells the authors assessed lymphocyte sub- population s ( CD3 , CD4 , CD8 , CD19 and CD57 + cells ) before transplantation and 14 , 28 and 42 days after transplantation . A total of 36 patients were investigated ( 18 glutamine , 18 placebo ) . In the whole group of patients the authors found restoration of CD4 and CD19 cells to pretransplantation values one day + 42 after transplantation , in CD8 and CD57 cells a statistically significant increase as compared with the pre-transplantation state occurred . In the glutamine group they observed on day + 28 a more rapid restoration of CD8 and a marginally better restoration of CD19 positive cells , while patients who were given placebo restored CD57 + cells more rapidly . All these differences were balanced on day + 42 , only CD19 + cells were at that time marginally higher in the placebo group . With the exception of CD19 + lymphocytes the authors observed weak correlations between the number of lymphocytes on day + 42 after transplantation and the number of transplanted CD34 + cells . It may thus be stated that the drop of lymphocyte sub- population s has a short-term character , the restoration correlates among others with the administered amount of haematopoietic cells . Significant importance of glutamine for the restoration of the lymphocyte sub- population was however not proved BACKGROUND AND OBJECTIVES Glutamine ( gln ) , a non-essential amino acid , has recently received increasing attention because it becomes essential during stress and catabolic states : glutamine seems to modulate immune function and to promote faster intestinal healing after chemotherapy . We design ed two consecutive r and omized clinical trials to evaluate the role of glutamine-enriched parenteral nutrition ( GEPN ) in patients with hematologic malignancies su bmi tted to high dose chemotherapy and autologous peripheral blood stem cell transplantation ( aPBSCT ) or immunoselected CD34 + aPBSCT . DESIGN AND METHODS In study 1 , the Gln group ( 12 patients ) received total parenteral nutrition ( TPN ) enriched with glutamine 20 g from day + 1 after aPBSCT , while the placebo group ( 15 patients ) received TPN lacking in glutamine ( placebo ) . In study 2 , the Gln group ( 10 patients ) received TPN enriched with glutamine 13.46 g from day + 1 , while the placebo group ( 11 patients ) received a placebo . RESULTS In the first study , a lymphocyte count > 0.5 109/L was achieved on day 16.5 in the Gln group and on day 29 in the placebo group ( p=0.005 ) ; in the second study , the lymphocyte count > 0.5 109/L was achieved on day 18 in the Gln group and on day 29 in the placebo group ( p=0.009 ) . Lymphocyte subset analysis showed an increase of CD3 + and CD4 + and normalization of the CD16+CD56 + subset . Furthermore patients receiving GEPN showed a decrease in the mucositis severity peak calculated by the DMS ( daily mucositis score : sum of the daily score of signs and symptoms ) ( p=0.047 ) . INTERPRETATION AND CONCLUSIONS GEPN is safe and effective and improves lymphocyte recovery after aPBSCT ; further studies are needed to assess the clinical benefits of such an approach in order to justify its economic impact |
1,168 | 25,765,726 | Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models .
Natriuretic peptides are strongly increased in cardioembolic strokes . | BACKGROUND AND PURPOSE Determining the underlying cause of stroke is important to optimize secondary prevention treatment .
Increased blood levels of natriuretic peptides ( B-type natriuretic peptide/N-terminal pro-BNP [ BNP/NT-proBNP ] ) have been repeatedly associated with cardioembolic stroke .
Here , we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants ' data meta- analysis . | OBJECTIVE To investigate the significance of N-terminal proBrain natriuretic peptide ( NT-proBNP ) in predicting the outcome of acute stroke in relation to other cardiovascular variables and stroke severity . DESIGN Prospect i ve study of previously independent acute ischemic and hemorrhagic stroke patients admitted to the acute stroke ward . METHODS Measurements of NT-proBNP in acute phase in addition to st and ard assessment of cardiovascular and neurological details . MAIN OUTCOME MEASURES Concentrations and significance of NT-proBNP in patients who were dead versus alive at 120 days after acute stroke and Cox regression analysis with stroke severity measured as Sc and inavian Stroke Scale ( SSS ) and other cardiovascular disease to predict mortality . RESULTS One hundred fourteen patients were recruited , median age 74 years . At 120 days , 13 patients had died . Deceased patients had a significantly higher concentration of NT-proBNP as compared to alive patients ( P < .001 ) . All patients who had died had NT-proBNP concentration above the median for the whole group . Cox regression analysis revealed that NT-proBNP was the most significant independent variable predicting mortality ( odds ratio [ OR ] 2.4 , 95 % confidence interval [ CI ] 1.35 to 4.41 , P = .003 ) followed by the SSS ( OR 0.95 , 95 % CI 0.90 to 0.98 , P = .005 ) . Higher NT-proBNP and lower SSS predicted mortality . There was a significant negative correlation of NT-proBNP with SSS score ( r = -0.24 , P = .02 ) . There were no significant difference in NT-proBNP concentrations between ischemic and hemorrhagic strokes ( P < .346 ) . At 6 weeks , the dependent patients had higher concentrations of NT-proBNP than independent patients . CONCLUSION NT-proBNP , an index of cardiac impairment , has an independent prognostic value in acute stroke patients over other cardiovascular variables and stroke severity . This may provide a channel for interventional therapy in acute stroke Background and Purpose — Because there is no biologic marker offering precise information about stroke etiology , many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done , precluding correct treatment . Methods — To examine the diagnostic value of a panel of biochemical markers to differentiate stroke etiologies , consecutive acute stroke patients were prospect ively evaluated . Brain computed tomography , ultrasonography , cardiac evaluations , and other tests were done to identify an etiologic diagnosis according to TOAST classification . Blood sample s were drawn on Emergency Department arrival ( < 24 hours ) to test selected biomarkers : C-reactive protein , D-dimer , soluble receptor for advanced glycation end products , matrix metalloproteinase-9 , S-100b , brain natriuretic peptide ( BNP ) , neurotrophin-3 , caspase-3 , chimerin , and secretagogin ( assayed by ELISA ) . Results — Of 707 ischemic stroke patients included , 36.6 % were cardioembolic , 21.4 % atherothrombotic , 18.1 % lacunar , and 23.9 % of undetermined origin . High levels of BNP , soluble receptor for advanced glycation end products , and D-dimer ( P<0.0001 ) were observed in patients with cardioembolic stroke . Independent predictors ( odds ratios with CIs are given ) of cardioembolic stroke were as follows : atrial fibrillation 15.3 ( 8.4–27.7 , P<0.001 ) ; other embolic cardiopathies 14.7 ( 4.7–46 , P<0.001 ) ; total anterior circulation infa rct ion 4 ( 2.3–6.8 , P<0.001 ) ; BNP > 76 pg/mL 2.3 ( 1.4–3.7 , P=0.001 ) ; and D-dimer > 0.96 & mgr;g/mL 2.2 ( 1.4–3.7 , P=0.001 ) . Even among patients with transient symptoms ( n=155 ) , a high BNP level identified cardioembolic etiology ( 6.7 , 2.4–18.9 ; P<0.001 ) . A model combining clinical and biochemical data had a sensitivity of 66.5 % and a specificity of 91.3 % for predicting cardioembolism . Conclusions — Using a combination of biomarkers may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase , thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention OBJECTIVE To determine the value of the use of plasma B-type natriuretic peptide ( BNP ) among acute ischemic stroke patients in a Chinese emergency department ( ED ) . MATERIAL S AND METHODS In our ED , the emergency physicians prospect ively assessed consecutive adult patients with acute phase of ischemic stroke and measured plasma BNP by Biosite Triage( ® )BNP POCT platform on admission , then followed up these patients . And the stroke neurologists evaluated patients ' functional outcome at hospital discharge , and also made discharge diagnosis and stroke etiologic subtypes according to TOAST criteria : large-artery atherosclerosis ( LAA ) , cardioembolism ( CE ) , small-artery occlusion ( SAO ) , stroke of other determined etiology ( SOE ) and stroke of other undetermined etiology ( SUE ) . RESULTS In this study , 142 of 238 acute ischemic stroke patients met the study criteria [ mean age 70.84 ± 11.48 years , 74 ( 52.11 % ) female ] . Of the 142 patients , 35.92 % were diagnosed with LAA at discharge , 25.35 % with CE , 27.46 % with SAO , 11.27 % with SOE or SUE . Age , previous cardiac disease , atrial fibrillation , the length of hospital stays , SSS score on admission ≤ 25 and mRS ≥ 3 or death at discharge were all significantly higher in the CE patients compared to other subtypes ( p<0.01 ) . And the mean BNP concentration was significantly higher in the CE group than in other three subtypes ( p<0.001 ) . The optimal cut-off concentration , sensitivity and specificity of the plasma BNP concentration suitable to distinguish CE from non-CE were 66.50 pg/ml , 75.0 % and 88.7 % , respectively . CONCLUSIONS Plasma BNP level is significantly higher in CE patients than in other TOAST subtypes , and by using Biosite Triage( ® )BNP POCT platform , emergency physicians should strongly consider CE subtype with the plasma BNP level of over 66.50 pg/ml . However , the single BNP biomarker panel can not be used to confidently rule out or identify stroke subtypes as a diagnosis and must be taken in context with clinical assessment and judgment before making management decisions in the ED Background and Purpose — A new clinical construct termed embolic stroke of undetermined source ( ESUS ) was recently introduced , but no such population has been described yet . Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospect i ve ischemic stroke registry using the proposed diagnostic criteria . Methods — The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients . ESUS was defined as a radiologically confirmed nonlacunar brain infa rct in the absence of ( a ) extracranial or intracranial atherosclerosis causing ≥50 % luminal stenosis in arteries supplying the ischemic area , ( b ) major-risk cardioembolic source , and ( c ) any other specific cause of stroke . Results — Among 2735 patients admitted between 1992 and 2011 , 275 ( 10.0 % ) were classified as ESUS . In the majority of ESUS ( 74.2 % ) , symptoms were maximal at onset . ESUS were of moderate severity ( median National Institute Health Stroke Scale score , 5 ) . The most prevalent risk factor was arterial hypertension ( 64.7 % ) , and 50.9 % of patients were dyslipidemic . Among potential causes of the ESUS , covert atrial fibrillation ( AF ) was the most prevalent : in 30 ( 10.9 % ) patients , AF was diagnosed during hospitalization for stroke recurrence , whereas in 50 ( 18.2 % ) patients AF was detected after repeated ECG monitoring during follow-up . Also , covert AF was strongly suggested in 38 patients ( 13.8 % ) but never recorded . Conclusions — About 10 % of patients with first-ever ischemic stroke met criteria for ESUS ; covert paroxysmal AF seems to be a frequent cause of ESUS Background and Purpose The etiology of ischemic stroke affects prognosis , outcome , and management . Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke . A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) . Methods A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies . “ Possible ” and “ probable ” diagnoses can be made based on the physician 's certainty of diagnosis . The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria . The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients , first based only on clinical features and then after review ing the results of diagnostic tests . Results The TOAST classification denotes five subtypes of ischemic stroke : 1 ) large-artery atherosclerosis , 2 ) cardioembolism , 3 ) small-vessel occlusion , 4 ) stroke of other determined etiology , and 5 ) stroke of undetermined etiology . Using this rating system , interphysician agreement was very high . The two physicians disagreed in only one patient . They were both able to reach a specific etiologic diagnosis in 11 patients , whereas the cause of stroke was not determined in nine . Conclusions The TOAST stroke subtype classification system is easy to use and has good interobserver agreement . This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke . Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke Background and Purpose : Our previous retrospective study demonstrated that a brain natriuretic peptide ( BNP ) level of > 140 pg/ml on admission was useful to distinguish cardioembolism ( CE ) from non-CE . The aim of the present study was to prospect ively investigate the utility of this predefined threshold . Method : Two hundred and twenty-one consecutive patients were prospect ively enrolled . On admission , the BNP levels of the patients were measured and classified according to low BNP ( ≤140.0 pg/ml ) or high BNP ( > 140.0 pg/ml ) levels . Final diagnosis of stroke subtype on discharge was made using the TOAST criteria . Measured parameters included the sensitivity , specificity , positive predictive value , and negative predictive value for CE in the high BNP group . Results : There were 81 patients in the high BNP group and 140 patients in the low BNP group . A total of 76 ( 34.4 % ) patients were diagnosed with CE , including 59 ( 72.8 % ) patients in the high BNP group and 17 ( 12.1 % ) patients in the low BNP group ( p < 0.001 ) . A BNP level > 140.0 pg/ml corresponded to a sensitivity of 77.6 % , specificity of 84.8 % , positive predictive value of 72.8 % , and negative predictive value of 87.9 % for a diagnosis of CE . Conclusion : A BNP level of > 140.0 pg/ml on admission in patients with acute ischemic stroke is a strong biochemical predictor for CE Objective : Antiplatelets are recommended for secondary prevention in patients with cryptogenic stroke ; however , some patients may present with a cardioembolic source that has not been detected , which may modify the treatment . Because high pro – brain natriuretic peptide ( BNP ) levels are associated with cardioembolic stroke , our objective was to determine whether pro-BNP levels in the acute phase of stroke predict the development of atrial fibrillation ( AF ) in patients with cryptogenic stroke . Methods : A prospect i ve study including patients with cryptogenic stroke was conducted . Demographic data , medical history , and stroke characteristics were assessed at admission . A blood sample was obtained within the first 24 hours from stroke onset to determine pro-BNP levels . Patients were followed by a neurologist at 3 and 6 months and later by a primary care physician for 2 years to evaluate the development of AF . Results : One thous and fifty patients with ischemic stroke were evaluated . Three hundred seventy-two patients ( 35 % ) had cryptogenic stroke . One hundred eight patients were excluded from the study , so 264 patients were valid for the analysis . AF was detected in 15 patients ( 5.6 % ) during the follow-up . Patients who developed AF were older , had hypertension more frequently , and showed higher levels of pro-BNP . In the logistic regression model , we found that pro-BNP ≥360 pg/mL was the only variable independently associated with the risk of developing AF ( odds ratio 5.70 , 95 % confidence interval 1.11–29.29 , p = 0.037 ) . Conclusions : Pro-BNP ≥360 pg/mL increases by 5-fold the possibility of detecting AF during follow-up in patients with cryptogenic stroke Background The study aim ed to evaluate the prognostic role and discriminative power of aortic stiffness and plasma brain natriuretic peptide levels in a cohort of patients hospitalized for acute ischemic stroke . Methods and Results Three hundred and ten consecutive patients aged 50 years and older with a first episode of acute ischemic stroke were prospect ively evaluated . All patients were admitted to the hospital within 24 h of the onset of stroke symptoms . The type of acute ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment classification . Blood sample s were taken for measurement of brain natriuretic peptide levels at admission . Aortic stiffness indices , aortic strain and distensibility , were calculated from the aortic diameters measured by transthoracic echocardiography . The patients were followed for one-year or until death , whichever came first . Death occurred in 51 ( 16·5 % ) patients . On multivariate logistic regression analysis , National Institutes of Health Stroke Scale score > 13 , diabetes , brain natriuretic peptide > 235 pg/mL , aortic distensibility , and aortic strain were associated with all-cause mortality . The optimal cutoff level of brain natriuretic peptide to distinguish the deceased group from the survival group was 235 pg/mL ( sensitivity 71·0 % and specificity 63·0 % ) and to distinguish cardioembolic stroke from noncardioembolic stroke was 155 pg/mL ( sensitivity 81 % and specificity 63 % ) . Conclusions Aortic stiffness and brain natriuretic peptide predict mortality in patients with first-ever acute ischemic stroke . Brain natriuretic peptide also differentiates cardioembolic stroke from noncardioembolic stroke Background — Cardiac biomarkers are strong predictors of adverse outcomes in several patient population s. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) and their association to cardiovascular events in atrial fibrillation ( AF ) patients in the R and omized Evaluation of Long-Term Anticoagulation Therapy ( RE-LY ) trial . Methods and Results — Biomarkers at r and omization were analyzed in 6189 patients . Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS2 and CHA2DS2-VASc risk scores . Patients were stratified based on troponin I concentrations : < 0.010 & mgr;g/L , n=2663 ; 0.010 to 0.019 & mgr;g/L , n=2006 ; 0.020 to 0.039 & mgr;g/L , n=1023 ; ≥0.040 & mgr;g/L , n=497 ; and on NT-proBNP concentration quartiles : < 387 ; 387 to 800 ; 801 to 1402 ; > 1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group ( hazard ratio [ HR ] , 1.99 [ 95 % CI , 1.17–3.39 ] ; P=0.0040 ) , and to NT-proBNP with 2.30%/year versus 0.92 % in the highest versus lowest NT-proBNP quartile groups , ( HR , 2.40 [ 95 % CI , 1.41–4.07 ] ; P=0.0014 ) . Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group ( HR , 4.38 [ 95 % CI , 3.05–6.29 ] ; P<0.0001 ) , and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups ( HR , 6.73 [ 3.95–11.49 ] ; P<0.0001 ) . Biomarkers increased the C-statistic from 0.68 to 0.72 , P<0.0001 , for a composite of thromboembolic events . Conclusions — Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality . Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00262600 BACKGROUND Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical . However , paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack ( TIA ) . METHODS We r and omly assigned 572 patients 55 years of age or older , without known atrial fibrillation , who had had a cryptogenic ischemic stroke or TIA within the previous 6 months ( cause undetermined after st and ard tests , including 24-hour electrocardiography [ ECG ] ) , to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder ( intervention group ) or a conventional 24-hour monitor ( control group ) . The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after r and omization . Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days . RESULTS Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients ( 16.1 % ) in the intervention group , as compared with 9 of 277 ( 3.2 % ) in the control group ( absolute difference , 12.9 percentage points ; 95 % confidence interval [ CI ] , 8.0 to 17.6 ; P<0.001 ; number needed to screen , 8) . Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients ( 9.9 % ) in the intervention group , as compared with 7 of 277 ( 2.5 % ) in the control group ( absolute difference , 7.4 percentage points ; 95 % CI , 3.4 to 11.3 ; P<0.001 ) . By 90 days , oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group ( 52 of 280 patients [ 18.6 % ] vs. 31 of 279 [ 11.1 % ] ; absolute difference , 7.5 percentage points ; 95 % CI , 1.6 to 13.3 ; P=0.01 ) . CONCLUSIONS Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older , paroxysmal atrial fibrillation was common . Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment , as compared with the st and ard practice of short- duration ECG monitoring . ( Funded by the Canadian Stroke Network and others ; EMBRACE Clinical Trials.gov number , NCT00846924 . ) BACKGROUND AND PURPOSE We investigated whether the plasma brain natriuretic peptide ( BNP ) level on admission can serve as a biological marker of in-hospital death in patients with acute ischemic stroke . METHODS We prospect ively enrolled 335 consecutive patients ( 125 females ; mean age , 72.3 years ) with acute ischemic stroke within 24 hours of onset and measured plasma BNP on admission . Patients were divided into two groups : the deceased group , who died during hospitalization ; and the survival group . The factors associated with in-hospital death were investigated by multivariate logistic regression analysis . RESULTS Death was observed in 20 ( 6.0 % ) patients . Frequencies of atrial fibrillation , cardioembolism , the use of diuretics before ischemic stroke , the use of digitalis before ischemic stroke , National Institutes of Health Stroke Scale ( NIHSS ) score on admission , glucose level , and D-dimer were significantly higher in the deceased group than in the survival group . On the other h and , albumin was significantly lower in the deceased group than in the survival group . The mean + /- SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group ( 731.5+/-1,070.9 vs. 213.1+/-384.5 pg/mL , p=0.001 ) . The optimal cut-off level , sensitivity , and specificity of BNP levels to distinguish the deceased group from the survival group were 240 pg/mL , 75.0 % and 73.0 % , respectively . Multivariate logistic regression analysis demonstrated that a NIHSS score of > 13 ( odds ratio [ OR ] , 4.87 ; 95 % confidence interval , 1.54 to 15.44 , p=0.007 ) and plasma BNP level of > 240 pg/mL ( OR , 4.67 ; 95 % confidence interval , 1.28 to 17.09 , p=0.020 ) were independent factors associated with in-hospital death . CONCLUSION The plasma BNP level on admission can predict in-hospital death in patients with acute ischemic stroke INTRODUCTION The National Institutes of Health Stroke Scale ( NIHSS ) and Sc and inavian Stroke Scale ( SSS ) are both vali date d measures of neurologic impairment and have been used in many acute stroke trials . Methods for interconverting SSS and NIHSS are needed . METHODS Conversion equations were developed using linear regression ( both unadjusted , and adjusted for age and sex ) using a r and om 50 % of the data at both baseline and 90 days . The remaining 50 % of data were used to test the accuracy of the models produced . RESULTS Data from 5 acute stroke trials ( 2004 patients ) were included . Fitted models at baseline were NIHSS = 25.68 - 0.43 * SSS ( R(2 ) = 0.57 , prediction error [ PE ] -0.2 , P = .20 ) , and SSS = 50.37 - 1.63 * NIHSS ( R(2 ) = 0.59 , PE 0.2 , P = .35 ) . The 90-day models were NIHSS = 22.99 - 0.39 * SSS ( R(2 ) = 0.82 , PE -0.3 , P = .001 ) , and SSS = 56.68 - 2.20 * NIHSS ( R(2 ) = 0.80 , PE -0.4 , P = .08 ) . Adjustment did not material ly improve the R(2 ) values . CONCLUSION Total scores for NIHSS and SSS may be interconverted with good precision ; the mathematic conversion equations may prove useful in clinical practice and in comparison of data from observational studies and r and omized trials Background and purpose N-terminal probrain natriuretic peptide , which is mainly produced by the heart , is increased in acute stroke . We aim ed to determine if N-terminal probrain natriuretic peptide could be a biomarker for ischemic stroke with a cardioembolic cause . Methods Consecutive sample of acute stroke patients admitted to a Stroke Unit . Ischemic stroke subtype was classified using the TOAST classification . Blood sample s were drawn within 72 h after stroke onset . Serum N-terminal probrain natriuretic peptide concentration was measured using an electrochemiluminescence immunoassay . Mean values of N-terminal probrain natriuretic peptide were compared between patients with hemorrhagic stroke vs. ischemic stroke , cardioembolic stroke vs. noncardioembolic stroke , cardioembolic stroke with atrial fibrillation vs. noncardioembolic stroke using t-test . Receiver operating characteristic curves were used to test the ability of N-terminal probrain natriuretic peptide values to identify cardioembolic stroke and cardioembolic stroke with atrial fibrillation . Results Ninety-two patients were included ( 66 with ischemic stroke ) with a mean age of 58·6 years . Twenty-eight ( 42·4 % ) ischemic strokes had a cardioembolic cause . Mean N-terminal probrain natriuretic peptide values for cardioembolic stroke were significantly higher ( P < 0·001 ) ( 491·6 ; 95 % confidence interval 283·7–852·0 pg/ml ) than for noncardioembolic ischemic stroke ( 124·7 ; 86·3–180·2 pg/ml ) . The area under the receiver operating characteristic curve for N-terminal probrain natriuretic peptide in cardioembolic stroke was 0·77 . The cut-off point with the highest sensitivity and specificity was set at 265·5 pg/ml ( 71·4 % and 73·7 % respectively ) . The area under the curve of N-terminal probrain natriuretic peptide for cardioembolic stroke related to atrial fibrillation was 0·92 , cut-off was set at 265·5 pg/ml ( sensitivity 94·4 % , specificity 72·9 % ) . Conclusion N-terminal probrain natriuretic peptide is a biomarker with a good accuracy to predict ischemic stroke of cardioembolic cause , namely associated with atrial fibrillation BACKGROUND Plasma brain natriuretic peptide ( BNP ) is used as a marker of congestive heart failure . Moreover , plasma BNP levels are increased in patients with acute ischemic stroke , in particular , cardioembolic stroke . We investigated whether the plasma BNP level can also be used as a biological marker to differentiate specific stroke subtype , in particular cardioembolic stroke from the other ischemic stroke subtypes . METHODS Consecutive patients ( total 200 ; 124 males , 76 females ; mean age , 71.4 years ) with acute ischemic stroke within 24 hours of onset were prospect ively enrolled . We measured plasma BNP on admission . Patients were divided into four groups according to the TOAST classification : large-vessel disease ( LVD ) , cardioembolism ( CE ) , small-vessel disease ( SVD ) , and other stroke . Correlation between plasma BNP level and stroke subtype was then examined . RESULTS Cardioembolism ( 41 % ) was the most frequent stroke subtype , followed by other stroke ( 34 % ) , SVD ( 16 % ) , and LVD ( 9 % ) . Age , female , atrial fibrillation , NIHSS score > or = 7 on admission and mRS score > or = 3 at discharge were significantly higher in CE than in the other stroke subtypes . The mean plasma BNP level of the CE group was significantly higher than that of the other 3 subtypes ( 409.6 pg/mL for CE , 94.0 pg/mL for LVD , 37.4 pg/mL for SVD , and 156.9 pg/mL for others , p<0.001 ) . The optimal cut-off concentration , sensitivity , and specificity of plasma BNP levels to distinguish CE from other stroke subtypes were 140.0 pg/mL , 80.5 % and 80.5 % , respectively . CONCLUSION Plasma BNP level is significantly higher in CE patients than in other stroke subtypes , and thus physicians should strongly consider CE when the plasma BNP level is over 140.0 pg/mL in patients with acute ischemic stroke BACKGROUND AND PURPOSE atrial fibrillation ( AF ) is the most powerful predictor of early death in patients with acute ischaemic stroke . We investigated whether the plasma brain natriuretic peptide ( BNP ) level on admission can serve as a biological marker of in-hospital death in acute ischaemic stroke and transient ischaemic attack ( TIA ) patients with AF . METHODS we prospect ively enrolled ischaemic stroke and TIA patients with AF within 24 h of onset and measured plasma BNP on admission . Patients were divided into two groups : the deceased group , who died during hospitalization , and the survival group . The factors associated with in-hospital death were investigated by multivariate logistic regression analysis . RESULTS a total of 221 patients with AF were enrolled . Death occurred in 24 ( 10.9 % ) patients . The mean ± SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group ( 714.1 ± 716.3 vs. 320.0 ± 380.7 pg/ml , P < 0.0001 ) . The optimal cutoff level , sensitivity , and specificity of BNP levels to distinguish the deceased group from the survival group were 320 pg/ml , 79.2 , and 69.0 % , respectively . Multivariate logistic regression analysis demonstrated that age per 10 years increase ( OR , 3.56 ; 95 % CI , 1.728 - 7.346 , P = 0.0006 ) , internal carotid artery occlusion ( OR , 10.20 ; 95 % CI , 2.525 - 41.177 , P = 0.0011 ) , NIHSS score of > 17 ( OR , 4.68 ; 95 % CI , 1.137 - 19.286 , P = 0.0325 ) , and plasma BNP level of > 320 pg/ml ( OR , 4.74 ; 95 % CI , 1.260 - 17.800 , P = 0.0213 ) were independent factors associated with in-hospital death . CONCLUSION the plasma BNP level on admission can predict in-hospital death in acute ischaemic stroke and TIA patients with AF Cryptogenic ( of unknown cause ) ischaemic strokes are now thought to comprise about 25 % of all ischaemic strokes . Advances in imaging techniques and improved underst and ing of stroke pathophysiology have prompted a re assessment of cryptogenic stroke . There is persuasive evidence that most cryptogenic strokes are thromboembolic . The thrombus is thought to originate from any of several well established potential embolic sources , including minor-risk or covert cardiac sources , veins via paradoxical embolism , and non-occlusive atherosclerotic plaques in the aortic arch , cervical , or cerebral arteries . Accordingly , we propose that embolic strokes of undetermined source are a therapeutically relevant entity , which are defined as a non-lacunar brain infa rct without proximal arterial stenosis or cardioembolic sources , with a clear indication for anticoagulation . Because emboli consist mainly of thrombus , anticoagulants are likely to reduce recurrent brain ischaemia more effectively than are antiplatelet drugs . R and omised trials testing direct-acting oral anticoagulants for secondary prevention of embolic strokes of undetermined source are warranted BACKGROUND Current guidelines recommend at least 24 hours of electrocardiographic ( ECG ) monitoring after an ischemic stroke to rule out atrial fibrillation . However , the most effective duration and type of monitoring have not been established , and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40 % of cases ( cryptogenic stroke ) . Detection of atrial fibrillation after cryptogenic stroke has therapeutic implication s. METHODS We conducted a r and omized , controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor ( ICM ) is more effective than conventional follow-up ( control ) for detecting atrial fibrillation in patients with cryptogenic stroke . Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring underwent r and omization within 90 days after the index event . The primary end point was the time to first detection of atrial fibrillation ( lasting > 30 seconds ) within 6 months . Among the secondary end points was the time to first detection of atrial fibrillation within 12 months . Data were analyzed according to the intention-to-treat principle . RESULTS By 6 months , atrial fibrillation had been detected in 8.9 % of patients in the ICM group ( 19 patients ) versus 1.4 % of patients in the control group ( 3 patients ) ( hazard ratio , 6.4 ; 95 % confidence interval [ CI ] , 1.9 to 21.7 ; P<0.001 ) . By 12 months , atrial fibrillation had been detected in 12.4 % of patients in the ICM group ( 29 patients ) versus 2.0 % of patients in the control group ( 4 patients ) ( hazard ratio , 7.3 ; 95 % CI , 2.6 to 20.8 ; P<0.001 ) . CONCLUSIONS ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke . ( Funded by Medtronic ; CRYSTAL AF Clinical Trials.gov number , NCT00924638 . ) Recent advances in cardiovascular research point to a critical role of inflammatory processes in the etiology of cardiovascular disease . This has led to the discovery of novel inflammatory biomarkers , which may be useful as additional screening tools for the identification of individuals at increased risk of coronary heart disease . One such novel inflammatory biomarker is lipoprotein-associated phospholipase A2 . This review discusses the recent development of a US Food and Drug Administration-approved blood test for lipoprotein-associated phospholipase A2 ( PLAC ™ test , diaDexus , Inc. ) and its efficacy as a predictive biomarker of risk for cardiovascular disease . More specifically , the article addresses the potential target group most likely to benefit from this new screening test and provides a prospect i ve scenario for its implementation |
1,169 | 18,266,784 | Despite method ological limitations , the evidence suggested that combining sexual risk reduction , condom promotion and improved access to STI treatment reduces HIV and STI acquisition in sex workers receiving the intervention .
Strong evidence that regular STI screening or periodic treatment of STIs confers additional protection against HIV was lacking .
It appears that structural interventions , policy change or empowerment of sex workers , reduce the prevalence of STIs and HIV .
There is some evidence for the efficacy of multi-component interventions , and /or structural interventions . | null | null |
1,170 | 26,347,089 | Based on these findings , strong evidence exists for promoting CHW programs to improve access to FP services . | This systematic review evaluates the strength of the evidence that community health workers ' ( CHW ) provision of family planning ( FP ) services in low- and middle-income countries is effective . | OBJECTIVE To determine whether community-based health workers in a rural region of Ethiopia can provide injectable contraceptives to women with similar levels of safety , effectiveness and acceptability as health extension workers ( HEWs ) . METHODS This was a prospect i ve non-r and omized community intervention trial design ed to test the provision of injectable contraceptives by community-based reproductive health agents ( CBRHAs ) . Effectiveness , safety , acceptability and continuation rates were the outcomes of interest . The outcomes observed when injectable contraceptives were administered by HEWs in health posts and when they were administered by CBRHAs were compared by means of χ(2 ) tests for association among categorical variables and t-tests for independent sample s to determine differences between group means . FINDINGS A total of 1062 women participated in the study . Compared with health post clients , the clients of CBRHAs were , on average , slightly older , less likely to be married and less educated , and they had significantly more living children . Women seeking services from CBRHAs were also significantly more likely to be using injectable contraceptives for the first time ; health post clients were more likely to have used them in the past . In addition , clients of CBRHAs were less likely to discontinue using injectable contraceptives over three injection cycles than health post clients . CONCLUSION Receiving injectable contraceptives from CBRHAs proved as safe and acceptable to this sample of Ethiopian women as receiving them in health posts from HEWs . These findings add to the growing body of evidence supporting the development , introduction and scale up of programmes to train community-based health workers such as CBRHAs to safely administer injectable contraceptives OBJECTIVE To compare the safety and quality of contraceptive injections by community-based health workers with those of clinic-based nurses in a rural African setting . METHODS A nonr and omized community trial tested provision of injectable Depo Provera ( DMPA ) by community reproductive health workers and compared it with routine DPMA provision at health units in Nakasongola District , Ug and a. The primary outcome measures were safety , acceptability and continuation rates . FINDINGS A total of 945 new DMPA users were recruited by community workers , clinic-based nurses and midwives . Research ers successfully followed 777 ( 82 % follow-up ) : 449 community worker clients and 328 clinic-based clients . Ninety-five percent of community-worker clients were " satisfied " or " highly satisfied " with services , and 85 % reported receiving information on side-effects . There were no serious injection site problems in either group . Similarly , there was no significant difference between continuation to second injection ( 88 % among clients of community-based workers , 85 % among clinic-going clients ) , nor were there significant differences in other measures of safety , acceptability and quality . CONCLUSION Community-based distribution ( CBD ) of injectable contraceptives is now routine in some countries in Asia and Latin America , but is practically unknown in Africa , where arguably the need for this practice is greatest . This research reinforces experience from other regions suggesting that well-trained community health workers can safely provide contraceptive injections CONTEXT Contraceptive use among young couples in India is low , and early childbearing and short birth intervals are common . The PRACHAR Project , an ongoing intervention in Bihar , seeks to increase contraceptive use for delaying and spacing births through communication interventions . METHODS R and om sample s of married women younger than 25 with no more than one child were surveyed in 2002 - 2003 , before PRACHAR was implemented ( N=1,995 ) , and in 2004 , 21 - 27 months after implementation ( N=2,080 ) . Contraceptive dem and and use , and related attitudes and knowledge , were assessed in the two surveys in both intervention areas and comparison areas . Logistic regression was used to assess the effect of the interventions on these indicators . RESULTS Contraceptive use was very low ( 2 - 6 % ) at baseline in both comparison and intervention areas . Dem and for contraception increased from 25 % at baseline to 40 % at follow-up in intervention areas , but remained virtually unchanged in comparison areas . At follow-up , contraceptive use had risen in both areas , but the adjusted odds of use in intervention areas were 3.8 times those in comparison areas . Women in intervention areas had elevated odds of knowing that fertility varies during the menstrual cycle , and of agreeing that early childbirth can be harmful and that contraceptive use is necessary and safe for delaying first births ( odds ratios , 1.6 - 3.0 ) . CONCLUSION Culturally appropriate , community-based communication programs that target youth and those who influence their decisions can create dem and for contraception among young couples and lead to increased contraceptive use A r and omized community trial of a family planning outreach program was conducted in Rakai District , Ug and a. Five communities received st and ard services ; six intervention communities received additional family planning information , counseling , and contraceptive methods from government service providers and community-based volunteer agents using social marketing and other strategies . Condom use was promoted in all of the communities . The community-based family planning outreach program was implemented in two phases--1999 - 2000 ( early ) and 2001(late)-- and its impact was evaluated by means of population surveys in 2002 - 03 . At follow-up , hormonal contraceptive prevalence was 23 percent in the intervention communities , compared with 20 percent in the control communities . The differential was greater in the early-intervention communities than the late-intervention communities . Pregnancy rates at follow-up were 15 percent in the control and 13 percent in the intervention communities . No differentials in condom use were found between study arms . Family planning outreach via social marketing can significantly increase hormonal contraceptive use and decrease pregnancy rates , but the impact of this outreach program was modest The impact of community-based family planning programs and access to credit on contraceptive use , fertility , and family size preferences has not been established conclusively in the literature . We provide additional evidence on the possible effect of such programs by describing the results of a r and omized field experiment whose main purpose was to increase the use of contraceptive methods in rural areas of Ethiopia . In the experiment , administrative areas were r and omly allocated to one of three intervention groups or to a fourth control group . In the first intervention group , both credit and family planning services were provided and the credit officers also provided information on family planning . Only credit or family planning services , but not both , were provided in the other two intervention groups , while areas in the control group received neither type of service . Using pre- and post-intervention surveys , we find that neither type of program , combined or in isolation , led to an increase in contraceptive use that is significantly greater than that observed in the control group . We conjecture that the lack of impact has much to do with the mismatch between women ’s preferred contraceptive method ( injectibles ) and the contraceptives provided by community-based agents ( pills and condoms ) Objective Despite the availability of free contraception from family planning clinics , the rate of unwanted pregnancy in Iran is still high . The effectiveness of other methods for contraceptive supply should , therefore , be evaluated . The aim of this study was to determine the effects of community-based distribution ( CBD ) on contraceptive usage in Iran . Methods This controlled field trial study involved 297 individuals ( 100 subjects in the CBD group and 197 subjects in the control group ) from four major remote areas of Hamedan , Iran . Stratified r and om sampling was used . Results Data analysis suggested that using CBD has four major effects : ( 1 ) it increases the level of contraceptive knowledge ( p<0.0001 ) , ( 2 ) it enhances correct contraceptive choice by couples ( p<0.0001 ) , ( 3 ) it improves contraceptive usage ( p<0.0001 ) and ( 4 ) it improves contraceptive continuation rates ( p<0.0001 ) . Conclusions CBD facilitates better knowledge , proper choice , and correct and continuous usage of contraception . This method should , therefore , be adopted for family planning services in remote areas of Iran |
1,171 | 22,513,943 | The currently available evidence from trials reporting clinical ly relevant outcomes is low quality and insufficient to draw conclusions on the effects of taping , whether used on its own or as part of a treatment programme . | BACKGROUND Patellofemoral pain syndrome refers to the clinical presentation of knee pain related to changes in the patellofemoral joint .
Patellofemoral pain syndrome usually has a gradual onset of pain with none of the features associated with other knee diseases or trauma .
It is often treated by physiotherapists , who use a variety of techniques including patellar taping .
This involves the application of adhesive sports medical tape applied directly to the skin over the patella on the front of the knee .
Patients often report an instantaneous improvement in pain and function after the tape is applied , but its longer term effects are uncertain .
OBJECTIVES The objective was to assess the effects , primarily on pain and function , of patellar taping for treating patellofemoral pain syndrome in adults . | A common rehabilitation strategy for patellofemoral pain syndrome ( PFPS ) , which lacks scientific evidence , includes pulling the patella medially with tape to reduce pain and increase the vastus medialis oblique ( VMO ) muscle activity . The purpose of this study was to examine the effect of various patellar taping procedures on force production , EMG activity of the VMO and vastus lateralis ( VL ) muscles , and perceived pain experienced by 30 women ( 27.3 + /- 1.53 ) , half diagnosed with PFPS . The perceived pain , force , and EMG of the VMO and VL , were recorded while subjects performed maximal isokinetic leg presses at 30 degrees /s for each of the following patellar taping conditions : no tape ( control ) , no glide ( placebo ) , medial and lateral glide ( experimental ) . The medial and placebo procedures significantly ( P < 0.01 ) reduced perceived pain ( 70 - 80 % ) in PFPS subjects . Although patellar taping did not influence leg press force ( P > 0.05 ) , it increased the VMO activity and decreased the VL activity in PFPS subjects but had the opposite effect in healthy subjects . The findings suggest that taping the patella medially can contribute positively to PFPS rehabilitation . Because the medial glide and placebo taping conditions had similar effects , it is proposed that the benefits of patellar taping are not due to a change in patellar position but rather due to enhanced support of the patellofemoral ligaments and /or pain modulation via cutaneous stimulation BACKGROUND AND PURPOSE Quadriceps strengthening , quadriceps stretching and patellar taping are commonly prescribed together for patellofemoral pain patients . This study aim ed to examine the effectiveness of each of these techniques in isolation for one week and in combination for one week . METHODS A prospect i ve double-blind r and omized control study was design ed involving 41 subjects with 60 knees diagnosed with patellofemoral pain . The knees were r and omized in onto one of four groups ( n = 15 ) : infrapatellar taping , quadriceps strengthening , quadriceps stretching and control . The taping was worn continually for the week ; the strengthening group followed a programme of non-weight-bearing terminal range quadriceps exercises , the stretching group performed rectus femoris stretches . The control group did not receive treatment . All subjects received advice . Seven pre- and post-treatment measures included isokinetic quadriceps strength , quadriceps length , pain measured during four activities and maximum eccentric , posturally controlled , pain-free knee flexion angle during a step-down . Results showed significant changes over time ( p < 0.01 ) in two out of seven measures for the taping group , in five out of seven for the strengthening group and five out of seven for the stretching group and none in the control group . When the three modalities were combined for one week , ( n = 60 ) all seven measures improved significantly ( p < 0.01 ) . CONCLUSION In isolation , quadriceps stretching and quadriceps strengthening result ed in more improvements than taping . Combining these treatments is recommended as the initial approach to treating patellofemoral pain but further individualized more functional , global treatment is essential OBJECTIVE To compare a commercially available electric muscle stimulation regimen with a novel form of stimulation for the rehabilitation of the quadriceps muscle , in patients with patellofemoral pain syndrome . DESIGN Double-blinded r and omized trial with a parallel control group and stratified r and omization . SETTING Home-based rehabilitation program assessed in research center . PARTICIPANTS Eighty patients ( 47 women , 33 men ) with patellofemoral pain syndrome . INTERVENTIONS One group ( EMPI ) received 1 uniform constant frequency component of 35Hz . The other ( EXPER ) group received an experimental form of stimulation that contained 5 simultaneously delivered frequency components of 125 , 83 , 50 , 2.5 , and 2Hz . Stimulation was applied to the quadriceps muscles of the affected leg for 1 hour daily for 6 weeks , a total of 42 treatments . MAIN OUTCOME MEASURES Lower-limb isometric and isokinetic torque , quadriceps fatigue , knee flexion , patellar pain , a step test , quadriceps cross-sectional area , and Kujala patellofemoral score for pain before and after treatment . RESULTS Seventy-four patients ( 43 women , 31 men ) completed the trial . Patients in both groups showed significant improvements in all outcomes ( P<.05 ) . No significant differences existed between the 2 stimulators in any outcome ( P>.05 ) except for quadriceps cross-sectional area ( P=.023 ) . CONCLUSIONS One form of stimulation was just as efficacious as the other in improving subjective and objective measures Objective To compare the clinical efficacy of foot orthoses in the management of patellofemoral pain syndrome with flat inserts or physiotherapy , and to investigate the effectiveness of foot orthoses plus physiotherapy . Design Prospect i ve , single blind , r and omised clinical trial . Setting Single centre trial within a community setting in Brisbane , Australia . Participants 179 participants ( 100 women ) aged 18 to 40 years , with a clinical diagnosis of patellofemoral pain syndrome of greater than six weeks ’ duration , who had no previous treatment with foot orthoses or physiotherapy in the preceding 12 months . Interventions Six weeks of physiotherapist intervention with off the shelf foot orthoses , flat inserts , multimodal physiotherapy ( patellofemoral joint mobilisation , patellar taping , quadriceps muscle retraining , and education ) , or foot orthoses plus physiotherapy . Main outcome measures Global improvement , severity of usual and worst pain over the preceding week , anterior knee pain scale , and functional index question naire measured at 6 , 12 , and 52 weeks . Results Foot orthoses produced improvement beyond that of flat inserts in the short term , notably at six weeks ( relative risk reduction 0.66 , 99 % confidence interval 0.05 to 1.17 ; NNT 4 ( 99 % confidence interval 2 to 51 ) . No significant differences were found between foot orthoses and physiotherapy , or between physiotherapy and physiotherapy plus orthoses . All groups showed clinical ly meaningful improvements in primary outcomes over 52 weeks . Conclusion While foot orthoses are superior to flat inserts according to participants ’ overall perception , they are similar to physiotherapy and do not improve outcomes when added to physiotherapy in the short term management of patellofemoral pain . Given the long term improvement observed in all treatment groups , general practitioners may seek to hasten recovery by prescribing prefabricated orthoses . Trial registration Australian Clinical Trials Registry ACTRN012605000463673 and Clinical Trials.gov NCT00118521 Background : McConnell recommended that patellar tape be kept on all day , until patients learn how to activate their vastus medialis obliquus ( VMO ) during an exercise program . This application may pose problems because prolonged taping may be inadvisable for some patients or even contraindicated owing to skin discomfort , irritation , or allergic reaction . Hypothesis : Wearing patellofemoral tape for a shorter duration during an exercise program would be just as beneficial as a prolonged taping application . Study Design : Prospect i ve cohort . Methods : Twelve patients and 16 healthy people participated . Patients underwent short-period patellar taping plus an exercise program for 3 months . Numeric pain rating , muscle strength of the knee extensors , and electromyogram activity of the vastus lateralis and VMO were evaluated . Results : There were significant differences in electromyogram activity ( P = .04 ) and knee extensor muscle strength ( P = .03 ) between involved and uninvolved sides before treatment . After treatment , pain scores decreased , and there were no significant differences between involved and uninvolved sides in electromyogram activity ( P = .68 ) and knee extensor strength ( P = .62 ) . Before treatment , mean VMO activation started significantly later than that of vastus lateralis , as compared with the matched healthy control group ( P = .01 ) . After treatment , these differences were nonsignificant ( P = .08 ) . Conclusion : Short-period patellar taping plus an exercise program improves VMO and vastus lateralis activation . Clinical Relevance : A shorter period of taping for the exercise program may be as beneficial as a prolonged taping application STUDY DESIGN A r and omized controlled trial . OBJECTIVES To investigate the effectiveness of daily patella taping and exercise on pain and function in individuals with patellofemoral pain syndrome . BACKGROUND Patella taping and muscle-strengthening programs are commonly used to treat patellofemoral pain syndrome . There is , however , little evidence for the effectiveness of these approaches . METHODS AND MEASURES Twenty-four men and 6 women aged 17 to 25 years ( mean + /- SD , 18.7 + /- 1.2 years ) participated in the study . Subjects were r and omly and exclusively assigned to 1 of 3 treatment groups : patella taping combined with a st and ardized exercise program , placebo patella taping and exercise program , or exercise program alone ( n = 10 in each group ) . Taping was applied and exercises performed on a daily basis for 4 weeks . Outcome measures were visual analog scales for pain and the functional index question naire , recorded at weekly intervals by a therapist who was blinded to group allocation . RESULTS Separate mixed-model ANOVAs , with repeated measures on time , indicated statistically significant improvements in pain and function over time for all groups ( P<.01 ) and also significant differences between groups for all measures ( P<.01 ) . Separate independent sample s t tests showed that the group receiving taping and exercises had better pain and function scores following treatment than the placebo taping- and -exercise group and the exercise-alone group . There were no significant differences between the placebo taping- and -exercise group and exercise-alone group at any time point . CONCLUSIONS These findings indicate that over a period of 4 weeks a combination of daily patella taping and exercises was successful in improving pain and function in individuals with patellofemoral pain syndrome . The combination of patella taping and exercise was superior to the use of exercise alone STUDY DESIGN A multicenter , single-masked study of patients with patellofemoral pain syndrome ( PFPS ) using a repeated- measures design . OBJECTIVE To compare 3 different methods of patellar taping for individuals with PFPS . BACKGROUND Patellar taping is commonly used as a treatment for PFPS . It is commonly thought that taping works by medially realigning the patella . However , comparisons have been rarely made with other methods of taping which attempt to realign the patella in different directions . METHODS AND MEASURES Seventy-one patients with PFPS ( 39 men , 32 women ; average age + /- SD , 34 + /- 10 years ) from 3 different treatment centers were tested . Each patient performed 4 single step-downs from a st and ard 8-inch ( 20.3-cm ) platform , initially with the patella untaped and then with the patella taped in a medial , neutral , and lateral direction . Pain was recorded on a st and ard 11-point numerical pain rating scale . The sequence of taping was r and omly allocated and patients were masked to the method used . The methods of taping were compared using repeated- measures generalized linear model analysis . RESULTS All methods of taping significantly decreased pain when compared to the untaped condition ( P<.0001 ) . Neutral- and lateral-glide techniques produced a significantly greater degree of pain relief ( P<.0001 ) than the medial-glide technique . CONCLUSION In this study , patellar taping produced an immediate decrease in pain in patients with PFPS , irrespective of how taping was applied . These data raise questions as to the mechanism of action of patellar taping . Furthermore , these results suggest that it is unlikely that taping works by altering patellar position Background Patellar taping is widely used clinical ly to treat patients with patellofemoral pain syndrome ( PFPS ) . Although patellar taping has been demonstrated to reduce patellofemoral pain in patients with PFPS , the kinematic source for this pain reduction has not been identified . Objective The purpose of this study was to quantify the changes in the 6-degrees-of-freedom patellofemoral kinematics due to taping in patients with PFPS . Design A within-subject design and a sample of convenience were used . Participants Fourteen volunteers ( 19 knees ) who were diagnosed with patellofemoral pain that was present for a year or longer were included . Each knee had to meet at least 1 of the following inclusion criteria : Q-angle of ≥15 degrees , a positive apprehension test , patellar lateral hypermobility ( ≥10 mm ) , or a positive “ J sign . ” Methods Each knee underwent 2 r and omly ordered testing conditions ( untaped and taped ) . A full fast-phase contrast ( PC ) magnetic resonance image set was acquired for each condition while the participants volitionally extended and flexed their knee . Three-dimensional displacements and rotations were calculated through integration of the fast-PC velocity data . Statistical comparisons between baseline patellofemoral kinematics and the change in kinematics due to taping were performed using a 2-tailed paired Student t test . Correlations between baseline patellofemoral kinematics and the change in kinematics due to taping also were quantified . Results Patellar taping result ed in a significant patellofemoral inferior shift . The strongest correlation existed between the change in lateral-medial displacement with taping and baseline ( r=−.60 ) . Conclusions The inferior shift in patellar displacement with taping partially explains the previously documented decrease in pain due to increases in contact area . The lack of alteration in 5 of the 6 kinematic variables with taping may have been due to the fact that post-taping kinematic alterations are sensitive to the baseline kinematic values INTRODUCTION In the previous study we have demonstrated that in healthy subjects significant changes in coronal and transverse plane mechanics can be produced by the application of a neutral patella taping technique and a patellar brace . Recently it has also been identified that patients with patellofemoral pain syndrome ( PFPS ) display alterations in gait in the coronal and transverse planes . OBJECTIVE This study investigated the effect of patellar bracing and taping on the three-dimensional mechanics of the knee of patellofemoral pain patients during a step descent task . METHOD Thirteen patients diagnosed with patellofemoral pain syndrome performed a slow step descent . This was conducted under three r and omized conditions : ( a ) no intervention , ( b ) neutral patella taping , ( c ) patellofemoral bracing . A 20 cm step was constructed to accommo date an AMTI force platform . Kinematic data were collected using a ten camera infra-red Oqus motion analysis system . Reflective markers were placed on the foot , shank and thigh using the Calibrated Anatomical System Technique ( CAST ) . RESULTS The coronal plane knee range of motion was significantly reduced with taping ( P=0.031 ) and bracing ( P=0.005 ) . The transverse plane showed a significant reduction in the knee range of motion with the brace compared to taping ( P=0.032 ) and no treatment ( P=0.046 ) . CONCLUSION Patients suffering from patellofemoral pain syndrome demonstrated improved coronal plane and torsional control of the knee during slow step descent following the application of bracing and taping . This study further reinforces the view that coronal and transverse plane mechanics should not be overlooked when study ing patellofemoral pain PURPOSE To investigate the effect of physical therapy treatment on the timing of electromyographic ( EMG ) activity of the vasti in individuals with patellofemoral pain syndrome ( PFPS ) . METHODS Sixty-five ( 42 female , 23 male ) participants aged 40 yr or less ( 29.2 + /- 7.8 yr ) diagnosed with PFPS . Participants were r and omly allocated into physical therapy treatment ( McConnell-based ) or placebo groups . Treatment programs were st and ardized and consisted of six-treatment sessions over 6 wk . Vastus medialis oblique ( VMO ) and vastus lateralis ( VL ) EMG activity was recorded with surface electrodes during a stair-stepping task and onsets of EMG activity were measured pre- and post-treatment . RESULTS Before treatment , the EMG onset of VL occurred before that of VMO in both participant groups . After physical therapy intervention , there was a reduction in symptoms , and this improvement was associated with a significant change in the time of onset of VMO EMG compared with that of VL in both phases of the stair-stepping task . After physical therapy treatment , the onset of VMO preceded VL in the eccentric phase and occurred at the same time in the concentric phase of the stair-stepping task . There was no change in time of EMG onset in the placebo group . CONCLUSION This study demonstrates that a " McConnell"-based physical therapy treatment regime for PFPS alters the motor control of VMO relative to VL in a functional task and this is associated with a positive clinical outcome The purpose of this prospect i ve r and omized intervention study was to evaluate the effect of two exercise protocol s on reflex response time of vastus medialis obliquus ( VMO ) , vastus lateralis ( VL ) , in patients with anterior knee pain . Sixty patients were r and omized into a 5-week treatment program , which consisted of only open kinetic chain tonification exercises ( group I ) ( n = 30 ) , or only closed kinetic chain tonification exercises ( group II ) ( n = 30 ) . Assessment of an aspect of neuromotor control was obtained by measuring the reflex response times of VMO and VL at the time of initial clinical examination , at the end of the exercise period ( five weeks ) , and three months after the completion of the exercise period . At these evaluation occasions , the intensity and the number of times that the patients experienced anterior knee pain during daily life was recorded on a Visual Analog Scale ( VAS ) . No alterations in reflex response times of VMO and VL were observed in either group . Changes of anterior knee pain over time were statistically significant in both groups . Only small and not statistically supported differences in anterior knee pain were found between the two groups . These results suggest that the reflex response times of the two vasti muscles can not be altered after a five week open or closed kinetic chain exercise program . In contrast , knee pain decreased significantly in both groups OBJECTIVE To determine the efficacy of the individual components of physiotherapy in subjects with anterior knee pain . METHODS An observer blind , prospect i ve , factorial design r and omised controlled trial . 81 young adults with anterior knee pain were r and omly allocated to one of four treatment groups : ( 1 ) exercise , taping , and education ; ( 2 ) exercise and education ; ( 3 ) taping and education ; and ( 4 ) education alone . Each group received six physiotherapist-led treatments over three months . Follow up took place at three months using the following outcome measures : patient satisfaction ( discharge/refer for further treatment ) ; a visual analogue pain score ; the WOMAC lower limb function score ; the Hospital Anxiety and Depression scale ( HAD ) ; and quadriceps strength . At 12 months the WOMAC and HAD were assessed by postal question naire . RESULTS All groups showed significant improvements in WOMAC , visual analogue , and HAD scores ; these improvements did not vary significantly between the four groups or between exercising/non-exercising and taped/non-taped patients at three and 12 months . However , patients who exercised were significantly more likely to be discharged at three months than non-exercising patients ( χ2 , p<0.001 ) . Taping was not significantly associated with discharge . Significantly greater improvements in WOMAC , visual analogue , and the anxiety score ( but not the depression score ) were seen in patients who were discharged than in those who were referred . CONCLUSIONS The proprioceptive muscle stretching and strengthening aspects of physiotherapy have a beneficial effect at three months sufficient to permit discharge from physiotherapy . These benefits are maintained at one year . Taping does not influence the outcome Background Although physical therapy forms the mainstay of nonoperative management for patellofemoral pain , its efficacy has not been established . Hypothesis Significantly more pain relief will be achieved from a 6-week regimen of physical therapy than from placebo treatment . Study Design Multicenter , r and omized , double-blinded , placebo-controlled trial . Methods Seventy-one subjects , 40 years of age or younger with patellofemoral pain of 1 month or longer , were r and omly allocated to a physical therapy or placebo group . A st and ardized treatment program consisted of six treatment sessions , once weekly . Physical therapy included quadriceps muscle retraining , patellofemoral joint mobilization , and patellar taping , and daily home exercises . The placebo treatment consisted of sham ultrasound , light application of a nontherapeutic gel , and placebo taping . Results Sixty-seven participants completed the trial . The physical therapy group ( N = 33 ) demonstrated significantly greater reduction in the scores for average pain , worst pain , and disability than did the placebo group ( N = 34 ) . Conclusions A six-treatment , 6-week physical therapy regimen is efficacious for alleviation of patellofemoral pain PURPOSE This study aim ed to examine whether a physical therapy intervention , design ed to reduce pain and improve the neuromotor control result ed in greater improvements in stance-phase knee flexion during stair ambulation in individuals with patellofemoral pain . The relationship between changes in stance-phase knee flexion and changes in pain , disability , and onset timing of individual vasti activity was also examined . METHODS Forty participants aged 40 yr or younger diagnosed with patellofemoral pain were r and omly allocated to a physical therapy ( N = 21 ) or placebo ( N = 19 ) treatment group . Stance-phase knee flexion was measured in two dimensions using a PEAK movement analysis system during stair ambulation . Individuals were divided into those with improvements in onset of vastus medialis obliquus ( VMO ) activity relative to that of the vastus lateralis ( VL ) of more or less than 10 ms . RESULTS Groups were similar at baseline . After the 6-wk intervention , individuals in the physical therapy group had significantly greater changes in knee flexion at heel strike ( mean difference 4 degrees , 95 % CI = 2 - 7 degrees ) and peak stance-phase knee flexion ( mean difference 9 degrees , 95 % CI = 5 - 12 degrees ) than those in the placebo group . No differences were noted during stair ascent . Individuals with greater change in the onset timing of the vasti had greater improvements in stance-phase knee flexion . Changes in usual pain in the week before testing and change in the vasti onset timing were independent predictors of change in stance-phase knee flexion during stair descent , together accounting for 27 - 40 % of the variability in knee motion . CONCLUSIONS Physical therapy intervention result ed in significantly greater changes in knee joint motion than a placebo treatment , and these changes in knee motion were partly related to changes in pain and changes in onset timing of the vasti Objective To examine the effect of the application of tape over the patella on the onset of electromyographic ( EMG ) activity of vastus medialis obliquus ( VMO ) relative to vastus lateralis ( VL ) in participants with and without patellofemoral pain syndrome ( PFPS ) . Design R and omised within subject . Setting sUniversity laboratory . Participants Ten participants with PFPS and 12 asymptomatic controls . Interventions Three experimental taping conditions : no tape , therapeutic tape , and placebo tape . Main Outcome Measures Electromyographic onset of VMO and VL assessed during the concentric and eccentric phases of a stair stepping task . Results When participants with PFPS completed the stair stepping task , the application of therapeutic patellar tape was found to alter the temporal characteristics of VMO and VL activation , whereas placebo tape had no effect . In contrast , there was no change in the EMG onset of VMO and VL with the application of placebo or therapeutic tape to the knee in the asymptomatic participants . Conclusions These data support the use of patellar taping as an adjunct to rehabilitation in people with PFPS Objective : To examine the immediate effects of patellar taping on pain and relative activity of vastus medialis obliquus to vastus lateralis in subjects with patellofemoral pain and patellofemoral joint malalignment . Design : Pre- and post-treatment design , with order of testing determined r and omly . Setting : Outpatient physiotherapy department . Subjects : Fifteen subjects with patellofemoral joint pain and malalignment . Interventions : With and without patellar taping with a st and ard force of application . Main outcome measures : Pain and surface EMG activity ratio of vastus medialis obliquus to vastus lateralis during single-legged semi-squat with 20 % of extra body weight loading . Results : There was a significant decrease in anterior knee pain ( p < 0.001 ) and vastus medialis obliquus to vastus lateralis activity ratio ( p = 0.05 ) during single-legged st and ing after patellar taping . Conclusions : Patellar taping can reduce pain in people with patellofemoral pain syndrome and patellofemoral malalignment but it decreases the relative activity of vastus medialis obliquus to vastus lateralis . Such a decrease in relative activity of vastus medialis obliquus after taping implies that it may not be suitable to combine patellar taping with vastus medialis obliquus facilitative exercise training The purpose of this prospect i ve study was to evaluate the efficacy of a patellar taping program in the conser vative management of patellofemoral pain . Twenty-five patients with patellofemoral pain were r and omized into two groups . One group underwent a st and ard physical therapy program for patellofemoral pain . The other group underwent the same physical therapy program , but use of a patellar taping technique was added to this program . Results of a subjective visual analog scale and changes in isokinetic strength and electromyo graphic activity of the quadriceps muscle were ana lyzed . Both the tape and no-tape groups experienced a statistically significant decrease in symptoms ( P < 0.05 ) , but no difference in improvement of patellofemo ral pain was noted between the groups . Likewise , both groups demonstrated significant improvement in quad riceps muscle isokinetic strength ( P < 0.05 ) and activ ity ( P < 0.001 ) , but no difference in improvement was noted between groups . The results of this study sug gest no beneficial effect of adding a patellar taping program to a st and ard physical therapy program in the conservative treatment of patellofemoral pain . Larger prospect i ve studies are warranted to support this opinion |
1,172 | 22,895,988 | Based on the available evidence , a conclusion can not be drawn as to the efficacy of tobacco prevention initiatives tailored for Indigenous youth .
Smoking prevalence in Indigenous youth is twice that of the non-Indigenous population , with tobacco experimentation commencing at an early age .
As such , a significant health disparity exists where Indigenous population s , a minority , are over-represented in the burden of smoking-related morbidity and mortality . | BACKGROUND Tobacco use in Indigenous population s ( people who have inhabited a country for thous and s of years ) is often double that in the non-Indigenous population .
Addiction to nicotine usually begins during early adolescence and young people who reach the age of 18 as non-smokers are unlikely to become smokers thereafter .
Indigenous youth in particular commence smoking at an early age , and a disproportionate burden of substance-related morbidity and mortality exists as a result .
OBJECTIVES To evaluate the effectiveness of intervention programmes to prevent tobacco use initiation or progression to regular smoking amongst young Indigenous population s and to summarise these approaches for future prevention programmes and research . | We present statistical considerations for the design of the Community Intervention Trial for Smoking Cessation ( COMMIT ) . One outcome measurement , the quit rate in r and omly selected cohorts of smokers , is compared with another outcome measurement , the decrease in smoking prevalence , in terms of statistical efficiency and interpretability . The COMMIT study uses both types of outcome measurements . The merits of pair-matching the communities are considered , and sample size calculations take into account heterogeneity among pair-matched communities . In addition to significance tests based on the permutational ( r and omization ) distribution , we also describe approaches for covariate adjustment . The COMMIT design includes 11 pair-matched communities , which should provide good power to detect a 10 % or greater difference in quit rates between the intervention and control communities in cohorts of heavy smokers and in cohorts of light or moderate smokers . The power is only moderate to detect intervention effects on the decreases in overall smoking prevalence or in the prevalence of heavy smoking PURPOSE Toward developing attractive and effective means to reduce cancer risks faced by Native American people , this study developed and tested interactive computer software to improve dietary choices and prevent tobacco use among Native American adolescents . METHODS Based on a legend of the Seneca Nation , a cancer prevention lesson was developed and programmed for software . A sample of 368 Native American adolescents were divided r and omly into intervention and control arms . Youths in both arms were pre-tested , youths in the intervention arm interacted with the software , and all youths were post-tested . Pre-test and post-test measures covered information and attitudes about cancer risks from dietary practice s and tobacco use . RESULTS Pre-test scores differed between the two arms on youths ' age and on one outcome variable . Relative to their counterparts in the control arm , youths in the intervention arm increased their post-test scores on 8 of 12 outcome measurement variables . Process data gathered during intervention delivery indicated that nearly all youths were involved with the interactive software and lesson . CONCLUSION Interactive computer software holds promise for delivering cancer risk reduction intervention aim ed at modifying dietary habits and preventing tobacco use among Native American youth BACKGROUND This article discusses the development , implementation , and preliminary testing of an intervention to reduce cancer risks through tobacco use prevention and dietary modification among Native American youth in the Northeastern United States . METHODS The intervention outcome study includes a research design and outcome measurement instruments . In collaboration with Native American communities , reservations , and organizations in the Northeastern United States , implementation of the design quantifies the separate and combined effects of a tobacco use prevention and a dietary modification intervention . RESULTS Native American youths in the tobacco prevention intervention and in the combined tobacco and dietary intervention increased their knowledge of tobacco facts and their awareness of the motives of tobacco advertising , and showed higher ratings for an ability to resist peer pressure and to refuse offers of tobacco use between pretest and posttest . Youths in the combined intervention were significantly less apt to report smoking of any kind . Youths in the tobacco use prevention-only condition reported significantly less smoking than their counterparts in the dietary modification-only condition and control condition on 4 of 8 measurement items . As for dietary variables , pretest to posttest measurement scores showed that , after receiving the curriculum , youths in the dietary modification intervention and in the combined intervention improved their knowledge of the health implication s of consuming dietary fat , fiber , fruits , and vegetables . Youths in the dietary modification and combined intervention also improved their scores of knowledge related to cancer risk-reducing nutritional practice s , cultural dietary habits , and healthy food choices available for Native American cultures . Youths in the dietary modification-only condition report significantly increasing their consumption of complex carbohydrates and significantly decreasing their fat intake between pretest and posttest occasions . CONCLUSIONS Data from this longitudinal study suggest the value of the FACETS curriculum for helping Native American youth reduce their risks for cancer associated with tobacco use and dietary preference and consumption patterns . In particular , results indicate the enhanced effects of the combined tobacco use prevention and dietary modification intervention for preventing tobacco use and for improving youths ' knowledge and attitudes with regard to tobacco use and diet . Further , the study demonstrates the value of collaborating with Native American organizations to design a cancer risk-reducing curriculum and to implement tests of that curriculum A smoking prevention project in six European countries ( European Smoking prevention Framework Approach ) was developed , featuring activities for adolescents , schools and parents , including out-of-school activities . Consensus meetings result ed in agreement between the countries on goals , objectives and theoretical methods . Countries ' specific objectives were also included . National diversities required country-specific methods to realize the goals and objectives . The community intervention trial was used as the research design . Since interventions took place at the community level , communities or regions were allocated at r and om to the experimental or control conditions . Complete r and omization was achieved in four countries . At baseline , smoking prevalence among 23 125 adolescents at the start of the project was 5.6 % for regular smoking and 4.0 % for daily smoking . Smoking prevalence rates were higher among girls than boys in all countries as far as weekly smoking was concerned . Process evaluations revealed that the project 's ambitions were high , but were limited by various constraints including time and delays in receiving funds . Future smoking prevention projects should aim to identify the effective components within the social influence approach as well as within broader approaches and on reaching sustained effects This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth . After completing pretest measurements , 1,396 third- through fifth- grade Native American students from 27 elementary schools in five states were divided r and omly by school into two intervention arms and one control arm . Following intervention delivery , youths in all arms completed posttest measurements and three annual follow-up measurements . Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention . One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth . Outcome assessment batteries measured youths ' reported use of smoked and smokeless tobacco , alcohol , and marijuana . Over the course of the 3.5-year study , increased rates of tobacco , alcohol , and marijuana use were reported by youths across the three arms of the study . Though cigarette use was unaffected by intervention , follow up rates of smokeless tobacco , alcohol , and marijuana use were lower for youths who received skills intervention than for youths in the control arm . Community intervention components appeared to exert no added beneficial influence on youths ' substance use , beyond the impact of skills intervention components alone . Finally , gender differences were apparent across substances , measurements , and study arms , with girls smoking more cigarettes and boys using more smokeless tobacco , alcohol , and marijuana |
1,173 | 30,037,679 | Conclusions : Population ‐based one‐time screening for AAA with ultrasound in asymptomatic men aged 65 years and older remains beneficial during the longer term after screening has ceased , with significant reductions in AAA mortality and AAA rupture rate , and hence avoids unnecessary AAA‐related deaths .
The sensitivity analyses also showed that the benefits of AAA screening were more pronounced in men at a mean age of < 70 years with a relatively lower prevalence of AAA than in men at a mean age of > 70 years with a relatively higher prevalence of AAA . | Background : An up‐to‐ date systematic review on the long‐term benefits of one‐time abdominal aortic aneurysm ( AAA ) screening in men with ultrasound is required as new evidence is available .
This report was produced for the Canadian Task Force on Preventive Health Care to provide evidence on screening for AAA with ultrasound .
The aim of this systematic review was to examine the short‐term ( 3‐5 years of follow‐up ) vs long‐term ( 13‐15 years of follow‐up ) effectiveness of one‐time screening for AAA in men . | The long‐term effects of abdominal aortic aneurysm ( AAA ) screening were investigated in extended follow‐up from the UK Multicentre Aneurysm Screening Study ( MASS ) r and omized trial Context Is it cost-effective to screen older adults for abdominal aortic aneurysm ( AAA ) ? Contribution This 7-year follow-up report of a large r and omized trial in the United Kingdom found that men age 65 to 74 years who were invited to have ultrasonography and surveillance for AAA had lower mortality rates than did those who were not invited ( hazard ratio , 0.53 [ CI , 0.42 to 0.68 ] ) . Cost-effectiveness for AAA-related deaths , based on costs applied to the events experienced by the men , was estimated at $ 19500 ( CI , $ 12400 to $ 39800 ) per life-year gained . Caution s Only men were studied . Actual costs of screening and surveillance may vary substantially in different setting s. The Editors A fast-growing body of literature is providing evidence in favor of screening men for abdominal aortic aneurysm ( AAA ) . Several large , r and omized trials published in the past few years ( 14 ) have consistently shown that screening reduces AAA-related mortality . A few observational studies of programs under way in localized areas have established the feasibility of systematic screening and have explored its practical implementation ( 57 ) . In addition to the mortality benefit , evidence indicating that screening is highly cost-effective is increasing ( 811 ) . In light of this evidence , national screening programs are now being considered in many countries ( 1214 ) . However , there is little evidence regarding long-term outcomes after AAA screening ; almost all of the evidence from r and omized trials is limited to the first 4 years after screening ( 14 ) . Moreover , long-term cost-effectiveness has been estimated only through health economic modeling ( 10 ) . We describe cost-effectiveness based on 7-year follow-up from the largest of the 4 trials of AAA screeningthe Multicentre Aneurysm Screening Study ( MASS ) ( 2 ) . The trial r and omly assigned approximately 67800 men age 65 to 74 years to receive an invitation to screening or to not receive an invitation . At 4-year follow-up , the trial reported a substantial relative reduction of 42 % ( 95 % CI , 22 % to 58 % ) in AAA-related mortality and an incremental cost-effectiveness ratio of $ 44900 ( CI , $ 24000 to $ 231000 ) per life-year gained ( 9 ) , which is at the borderline of the commonly accepted threshold for interventions . All values are reported in U.S. dollars ( U.K. 1 = U.S. $ 1.58 ) ( 15 ) . The costs of AAA screening are primarily incurred at the start of the program , but benefits continue to accrue in terms of life-years gained in patients in whom AAA rupture is avoided through elective surgery . It is therefore expected that cost-effectiveness of screening will improve over time . The mid-term results of MASS provide reliable , trial-based information regarding clinical outcomes and cost-effectiveness over a longer period . Methods The details of the MASS protocol were described previously ( 2 ) , but a brief summary is provided ( Figure 1 ) . Between 1997 and 1999 , a population -based sample of 70495 men age 65 to 74 years from 4 centers in the United Kingdom was identified by obtaining records for every man in this age range who was registered with a family physician ( registered persons account for approximately 98 % of the population ) . Persons who were ineligible for the trial ( incorrect details , known AAA , previous AAA surgery , or terminal illness ) were excluded before r and omization . The remaining 67770 men were r and omly assigned to receive an invitation to ultrasonography for AAA or to not receive an invitation to ultrasonography . At screening , men with an aortic diameter of 3.0 cm or greater were defined as having an AAA and were subsequently invited for recall scans to monitor growth of the aneurysm . Men with an aortic diameter of 3.0 to 4.4 cm were rescreened every year , and those with an aortic diameter of 4.5 to 5.4 cm were rescreened every 3 months . Participants were considered for elective surgery when the aortic diameter reached 5.5 cm , aortic expansion was 1.0 cm or more in 1 year , or they experienced symptoms attributable to the aneurysm . Men with an aortic diameter less than 3.0 cm on the initial scan were not rescreened . Blood pressure was also measured ; although family physicians were informed of these measurements , no further intervention was provided through the screening program . We obtained approval from local ethics committees at each center , and all patients who had screening provided signed informed consent . Figure 1 . Study flow diagram . Additional data on follow-up scans and AAA surgeries were collected from hospital records . Deaths up to 31 March 2005 were confirmed by the U.K. Office of National Statistics after matching of the unique National Health Service number for each person . Follow-up ranged from 5.9 to 8.2 years ( mean , 7.1 years ) . The primary outcome of interest , AAA-related mortality , is defined as all deaths within 30 days of any AAA surgery ( elective or emergency ) plus all deaths with International Classification of Diseases , Ninth Revision , codes 441.3 ( ruptured abdominal aortic aneurysm ) , 441.4 ( abdominal aortic aneurysm without mention of rupture ) , 441.5 ( ruptured aortic aneurysm at unspecified site ) , or 441.6 ( aortic aneurysm at unspecified site without mention of rupture ) . The use of codes 441.5 and 441.6 may result in inclusion of some thoracic aortic aneurysm deaths . Investigation of the accuracy of cause-of-death coding on the death certificates was done by an independent mortality working party that was blinded to group allocation . The results of this analysis showed that inaccuracies in coding did not have an important impact on study outcomes ( 2 ) . Statistical Analysis All analyses were done by using Stata , version 9 ( Stata Corp. , College Station , Texas ) . Deaths related to AAA ( primary analysis ) and all-cause mortality ( secondary analysis ) were compared between the 2 r and omized groups by using unadjusted Cox regression by intention-to-treat analysis . Adjustment for age at baseline did not influence the results . The proportional hazards assumption was tested by using Schoenfeld residuals . An unbiased r and omization-based estimate of the benefit of screening was also obtained ( 16 ) . This estimate is calculated by subtracting from the control group a subgroup that is equivalent in terms of survival to the nonadherent subgroup in the invited group . Thus , the remaining controls are comparable to the group of invited patients who attended screening . Life-years gained are estimated as the area between the KaplanMeier curves for both groups ( 17 ) . The cost-effectiveness of screening is estimated from a health service perspective for follow-up truncated at 7 years , with adjustment for censoring ( 18 ) . Details of the costing exercise in the trial at 20002001 prices were reported previously ( 9 ) . The unit costs obtained ( U.K. 1 = U.S. $ 1.58 for the year 2000 [ 15 ] ) are inflated to the 20042005 financial-year level by using annual hospital and community health services pay and price inflation indices ( 19 ) . Costs are applied to the following events on the basis of individual re source use : invitation to screening ( $ 2.46 ) , reinvitation after nonresponse ( $ 2.42 ) , initial scan ( $ 35.95 ) , recall scan ( $ 86.74 ; done in the hospital rather than in the community and including costs for periodic routine meetings with a consultant ) , consultation for elective surgery ( $ 583.79 ) , elective AAA surgery ( $ 13015.74 ) , and emergency AAA surgery ( $ 21054.32 ) . Costs relating to scans of incidentally detected AAAs in the control group are not included ( data not available ) , but costs relating from result ant AAA repair surgery are included . Sensitivity analyses were done by using 1 ) costs retained at the 20002001 financial-year level for comparison with previous publications , 2 ) quality -adjusted life-years based on age-related reductions , 3 ) U.S.-based unit cost estimates for scans and surgeries , 4 ) an increase of 50 % in the cost of a consultation ( a U.S.-based estimate was not available , but this analysis reflects possible additional assessment s ) , 5 ) 3 and 4 combined . Quality -of-life adjustments are made only on the basis of age , with an adjustment of 0.78 for life-years gained between the ages 65 and 74 years and an adjustment of 0.75 for life-years gained at ages older than 75 years ( 20 ) . The U.S.-specific estimates for scans ( initial and recall ) are based on Medicare reimbursement for AAA screening at $ 90.95 ( Current Procedural Terminology code G0389 ) ( 21 ) , and U.S.-specific costs for surgeries are based on previously published estimates ( 22 , 23 ) that were inflated to 2004 prices ( 24 ) : $ 18160 for elective procedures and $ 31106 for emergency procedures . Discounting is applied at the current recommended values of 3 % per annum for costs and effects ( 25 ) . Estimates of AAA-related costs and effects take into account the rate of nonAAA-related deaths across both groups over time . The Fieller method is used to calculate bounds for the CI for cost-effectiveness ( 26 , 27 ) . Role of the Funding Source This study was funded by the Medical Research Council . The funding source had no role in the design , implementation , or analysis of the study . Results Figure 1 shows the flow of participants through the trial . Numbers differ slightly from earlier publications because of identification of a few duplicate records in the data base . Of 67770 r and omly assigned men , 33883 were invited to be screened : 27204 ( 80 % ) attended and 1334 ( 4.9 % ) AAAs were identified . The mean age at r and omization was 69.2 years in both groups . Loss to follow-up because of death was 2.1 % overall ( 2.2 % in the control group and 2.1 % in the invited group ) . Loss to clinical follow-up ( nonattendance at recall scans ) was 19 % at 4 years and 24 % at 7 years . The Appendix Table shows surgeries and deaths within 30 days in each of the r and omly assigned groups . A few endovascular operations are included in these figures6 in the control group and 14 in the invited group . As expected , the total number of elective procedures is greater in the invited group than in the control group BACKGROUND At present , several regions and countries are considering screening for abdominal aortic aneurysm ( AAA ) . However , The Chichester Aneurysms Screening Trial has reported poor long term benefit of screening for AAA . We therefore supplement previously published data with a preliminary analysis of the ten-year mortality from AAA , based upon population -based data until 2002 ( 7 years ) and incomplete hospital-based information on deaths until 2005 ( 10 years ) . METHODS AND MATERIAL In 1994 we started a r and omised screening trial of 12,639 64 - 73 year-old males ; 6,306 were controls , and 6,333 were invited to an abdominal ultrasound scan at their district hospital . Information on all deaths until 15.3.2005 was obtained from the Office of Civil Registration . Information on AAA related deaths was obtained from the national registry of Causes of Deaths from 1.4.1994 to 31.12.2001 , and supplemented with AAA deaths known to the Danish National Patient Registry until 15.3.2005 . Operations were obtained from the Danish National Vascular Registry from 1.4.1994 to 15.3.2005 . Death certificates and medical records were review ed by two independent assessors . The analyses were based on " intention to treat " from the date of r and omisation . RESULTS The attendance rate was 76.6 % and 191 ( 4.0 % ) had an AAA . The median observation time was 9.58 years . In the invited group 13 subjects were acutely operated on compared to 40 in the control group ( Risk ratio : 0.32 ( 95 % C.I. 0.17 - 0.60 , P<0.001 ) ) , and 14 died due to AAA compared to 51 in the control group ( Hazard ratio : 0.27 ( 95 % C.I. : 0.15 - 0.49 , P<0.001 ) . CONCLUSION Over ten years , screening reduced mortality from AAA by 73 % , and the frequency of emergency operations by 68 % Screening for abdominal aortic aneurysm ( AAA ) is commonly restricted to men . Recent studies have indicated a possible increase in deaths due to ruptured AAA in women , and a higher rate of rupture in women than in men . The present report details results from a r and omized controlled trial that assessed the effects of screening women for AAA BACKGROUND Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms . The Multicentre Aneurysm Screening Study was design ed to assess whether or not such screening is beneficial . METHODS A population -based sample of men ( n=67800 ) aged 65 - 74 years was enrolled , and each individual r and omly allocated to either receive an invitation for an abdominal ultrasound scan ( invited group , n=33839 ) or not ( control group , n=33961 ) . Men in whom abdominal aortic aneurysms ( > or =3 cm in diameter ) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years . Surgery was considered on specific criteria ( diameter > or = 5.5 cm , expansion > or = 1 cm per year , symptoms ) . Mortality data were obtained from the Office of National Statistics , and an intention-to-treat analysis was based on cause of death . Quality of life was assessed with four st and ardised scales . The primary outcome measure was mortality related to abdominal aortic aneurysm . FINDINGS 27147 of 33839 ( 80 % ) men in the invited group accepted the invitation to screening , and 1333 aneurysms were detected . There were 65 aneurysm-related deaths ( absolute risk 0.19 % ) in the invited group , and 113 ( 0.33 % ) in the control group ( risk reduction 42 % , 95 % CI 22 - 58 ; p=0.0002 ) , with a 53 % reduction ( 95 % CI 30 - 64 ) in those who attended screening . 30-day mortality was 6 % ( 24 of 414 ) after elective surgery for an aneurysm , and 37 % ( 30 of 81 ) after emergency surgery . INTERPRETATION Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms BACKGROUND Cardiovascular diseases and chronic obstructive pulmonary disease ( COPD ) are both associated with abdominal aortic aneurysms ( AAA ) . The aim of this study was therefore to analyse whether screening for AAA could be restricted to men with such diseases ( high risk group ) . METHODS Before the date of r and omisation of a population screening trial of 12,639 64 - 73-year-old males , all discharge diagnoses from the National Patient Registry concerning AAA-related diseases were merged with the screening results on attendance , AAA prevalence , and AAA-related mortality and overall mortality . Differences in proportions were compared by Chi square tests and differences in mortality by Cox regression analyses . RESULTS The attendance rate was 78.8 % and 6.7 % had an AAA in the high risk group compared to 75.8 % attendance ( P<0.001 ) and 2.9 % ( P<0.001 ) in the remaining population . Cumulatively , screening of only high risk men with would have required 72.9 % ( 95 % C.I. : 72.3 - 74.5 % ) fewer screening invitations , would have discovered 46.1 % ( 95 % C.I. : 38.9 - 53.4 % ) of the AAA cases diagnosed and prevented 46.7 % ( 95 % C.I. : 28.3 - 65.7 % ) of the AAA-related deaths . However , screening decreased AAA-related mortality both among men with and without known COPD or cardiovascular diseases : mortality ratio : 0.22 ( 95 % C.I. : 0.08 - 0.65 ) , P=0.006 , and 0.24 ( 95 % C.I : 0.09 - 0.63 , P=0.004 , respectively . CONCLUSION High-risk population screening would prevent less than half of AAA-related deaths . Therefore , restricting screening to such high-risk groups does not seem justified , but cost effectiveness analyses are needed to reach a firm conclusion Long‐term benefits of screening for abdominal aortic aneurysm ( AAA ) are uncertain . These are the final results of a r and omized controlled screening trial for AAA in men , updating those reported previously . Benefit and compliance over a median 15‐year interval were examined The study was an up date at 10 years of a r and omized trial of the efficacy of screening for abdominal aortic aneurysm ( AAA ) . The extent of benefit , feasibility and compliance were examined , and reasons why this intervention may fail a proportion of those screened were identified OBJECTIVES to analyse the hospital costs and benefits of screening older males for abdominal aortic aneurysm ( AAA ) . MATERIAL S AND METHODS in 1994 a hospital-based screening trial of 12 658 65 - 73-year-old males was started . AAA > 5 cm were referred for surgery . The remaining AAA were offered annual scans . Those with aortic ectasia were rescreened at 5 yearly intervals . AAA-operations and hospital AAA-related deaths were research ed . The costs of screening , surveillance , and treatment were also registered . RESULTS the attendance rate was 76 % ; of whom 191 ( 4.0 % ) had AAA . Mean observation time was 5.13 years . Sixty in the screened and 41 in the control group were operated ( p=0.06 ) , of which 7 and 27 respectively were operated as an emergency ( p<0.001 ) , and 6 and 19 respectively died due to AAA ( p=0.009 ) . The costs per scan were 83.50 DKK , 81 400 DKK per emergency operation ( 71 485 DKK after screening ) , and 117 000 DKK per emergency operation . The cost per prevented hospital death was 67 855 DKK , equivalent to approximately life year saved approx . 7540 DKK ( GBP1=12 DKK ) . CONCLUSION screening appears to reduce hospital AAA mortality and to be cost-effective OBJECTIVE To describe the potential psychological consequences of screening for abdominal aortic aneurysms ( AAAs ) . METHODS The participants were prospect ively and r and omly sample d from a r and omised screening trial for AAA and asked to complete a vali date d generic and global anonymous quality of life ( QL ) question naire by self- assessment ( ScreenQL ) . Material case-control study : ScreenQL was completed once by 168 ( 48 % ) of 350 non-responders to screening , 271 ( 81 % ) of 335 attenders before screening , 286 ( 85 % ) of 335 attenders after screening , 127 ( 85 % ) of 149 with a small AAA diagnosed at screening , and 231 ( 66 % ) of 350 who were r and omised not to be offered screening for AAA ( controls ) . Prospect i ve study ( paired data ): 127 men having a small AAA diagnosed . Twenty-nine ( 81 % ) of 36 men operated after initial conservative treatment . RESULTS Initially , the QL score was 5 % lower among men with a small AAA compared to the controls ( p<0.05 ) , mainly because of poorer health perception . The QL score declined significantly further to 7 % below control values during the period of conservative treatment . This impairment was mainly due to a 21 % and 15 % reduction in scores relating to health perception and psychosomatic distress , respectively . However , all scores improved to control levels in patients operated on . The QL of attending men for screening was significantly lower than that of the controls and the attenders after the screening . No differences were noticed concerning the non-attenders . CONCLUSION The offer of screening causes transient psychological stress in subjects found not to have AAA . However , diagnosis of an AAA seems to impair QL permanently and progressively in conservatively treated cases . This impairment seems reversible by operation . Nevertheless , the impairment seems considerable , and must be considered in the management of AAA and in the final evaluation of screening for AAA OBJECTIVE To assess whether screening for abdominal aortic aneurysms in men reduces mortality . DESIGN Population based r and omised controlled trial of ultrasound screening , with intention to treat analysis of age st and ardised mortality . SETTING Community based screening programme in Western Australia . PARTICIPANTS 41,000 men aged 65 - 83 years r and omised to intervention and control groups . INTERVENTION Invitation to ultrasound screening . MAIN OUTCOME MEASURE Deaths from abdominal aortic aneurysm in the five years after the start of screening . RESULTS The corrected response to invitation to screening was 70 % . The crude prevalence was 7.2 % for aortic diameter > or = 30 mm and 0.5 % for diameter > or = 55 mm . Twice as many men in the intervention group than in the control group underwent elective surgery for abdominal aortic aneurysm ( 107 v 54 , P = 0.002 , chi2 test ) . Between scheduled screening and the end of follow up 18 men in the intervention group and 25 in the control group died from abdominal aortic aneurysm , yielding a mortality ratio of 0.61 ( 95 % confidence interval 0.33 to 1.11 ) . Any benefit was almost entirely in men aged between 65 and 75 years , where the ratio was reduced to 0.19 ( 0.04 to 0.89 ) . CONCLUSIONS At a whole population level screening for abdominal aortic aneurysms was not effective in men aged 65 - 83 years and did not reduce overall death rates . The success of screening depends on choice of target age group and the exclusion of ineligible men . It is also important to assess the current rate of elective surgery for abdominal aortic aneurysm as in some communities this may already approach a level that reduces the potential benefit of population based screening Importance Mortality from ruptured abdominal aortic aneurysms ( AAAs ) remains high . The benefit of screening older men for AAAs needs to be assessed in a range of health care setting s. Objective To assess the influence of screening for AAAs in men aged 64 to 83 years on mortality from AAAs . Design , Setting , and Participants This r and omized clinical trial performed from April 1 , 1996 , through March 31 , 1999 , with a mean of 12.8 years of follow-up ( range , 11.6 - 14.2 years ) included a population -based sample from a single metropolitan region in Western Australia identified via the electoral roll . Data analysis was performed from June 1 , 2015 , to June 1 , 2016 . Interventions R and omization to an invitation to undergo ultrasonography of the abdominal aorta or a control group without invitation . Main Outcomes and Measures Surgery for and mortality from AAA . Results A total of 49 801 men aged 64 to 83 years were identified for the study . Men living too far from screening centers ( n = 8671 ) or who died before invitation ( n = 2650 ) were excluded , result ing in 19 249 men in the invited group and 19 231 controls ( mean [ SD ] age , 72.5 [ 4.6 ] years ; 95 % white ) . Of 19 249 men invited for screening , 12 203 ( 63.4 % ) attended . There were more elective operations ( 536 vs 414 , P < .001 ) and fewer ruptured AAAs ( 72 vs 99 , P = .04 ) in the invited group compared with the control group . Overall , there were 90 deaths from AAAs in the invited group ( mortality rate , 47.86 per 100 000 person-years ; 95 % CI , 38.93 - 58.84 ) and 98 in the control group ( 52.53 per 100 000 person-years ; 95 % CI , 43.09 - 64.03 ) for a rate ratio of 0.91 ( 95 % CI , 0.68 - 1.21 ) . For men aged 65 to 74 years , the AAA mortality rate in the invited group was 34.52 per 100 000 person-years ( 95 % CI , 26.02 - 45.81 ) compared with 37.67 per 100 000 person-years ( 95 % CI , 28.71 - 49.44 ) in the control group for a rate ratio of 0.92 ( 95 % CI , 0.62 - 1.36 ) . The number needed to invite for screening to prevent 1 death from an AAA in 5 years was 4784 for men aged 64 to 83 years and 3290 for men aged 65 to 74 years . There were no meaningful differences in all-cause , cardiovascular , and other mortality risks . Conclusions and Relevance Use of the electoral roll to identify and invite men aged 64 to 83 years for screening for AAAs had no significant effect on the overall mortality from AAAs . Trial Registration is rct n.org Identifier : IS RCT N16171472 From family medical practice s 15775 men and women aged 65‐80 years were identified and r and omized into two groups : one group was invited for ultrasonographic screening for abdominal aortic aneurysm ( AAA ) , and the other acted as age‐ and sex‐matched controls . Of the 7887 invited for screening 5394 ( 68·4 per cent ) accepted . AAA was detected in 218 ( 4·0 per cent overall and 7·6 per cent of men ) . Aortic surgery was offered to the screened group if certain criteria were met and no patient died from rupture who was fit for operation and accepted elective treatment . The incidence of rupture was reduced by 55 per cent in men in the group invited for screening , compared with controls . The incidence of rupture in women was low in both groups |
1,174 | 30,074,022 | A diferencia de la terapia de reemplazo renal para pacientes con enfermedad renal crónica donde la fístula arteriovenosa es la primera opción , seguida del catéter tunelizado , en pacientes con lesión renal aguda el acceso vascular de elección es el catéter temporal .
En pacientes que cuentan con fístula arteriovenosa preexistente , su punción en pacientes con inestabilidad hemodinámica conlleva riesgos y no puede ser recomendada .
The length of the access should be evaluated according to the insertion site , while 20 cm catheters are usually suitable for right jugular puncture , the left jugular usually requires 25 cm for achieving the position inside the right atrium .
On the other h and , the femoral access increases its performance with lengths of 25 - 35 cm .
The low posterior jugular approach is considered a simple , safe technique that allows up to 5 cm further towards the right atrium .
The use of heparin 1000 U/ml for sealing the ports reduces the risk of bleeding compared to heparin 5000 U/ml . | El acceso vascular es el primer eslabón para la terapia de apoyo extracorpórea renal .
Por su parte , el acceso femoral incrementa su desempeño con longitudes de 25 a 35 cm .
La punción yugular posterior baja derecha es considerada una técnica de abordaje sencilla , segura y que permite una aproximación de hasta 5 cm más caudal hacia la aurícula derecha .
La interacción entre catéteres central es debe ser anticipada o evaluada ante el riesgo de aspiración de infusiones por el circuito extracorpóreo .
En el cuidado del catéter , la aplicación de heparina 1,000 U/ml reduce el riesgo de sangrado al sellar los puertos comparada con heparina 5,000 U/ml .
Vascular access is the first link for renal extracorporeal support therapy .
Unlike renal replacement therapy for patients with end-stage renal disease where the arteriovenous fistula is the first option , followed by the tunneled catheter , in patients with acute kidney injury a temporary catheter is the first choice .
The use of tunneled catheter as first option implies a complex , time-consuming procedure with higher cost that also limits its recommendation .
The change of catheters by metal guide has shown to be a safe method in the absence of infection .
Femoral access has been shown not to be inferior to right jugular access , while left jugular access reduces the life of the circuit and should be considered as a fourth option after right jugular , right femoral and left femoral sites . | BACKGROUND AND OBJECTIVES Several temporary venous catheterizations are sometimes required for acute renal replacement therapy ( RRT ) in the intensive care unit ( ICU ) . This study compares first and second catheterizations in the femoral and jugular veins in terms of patient safety . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A crossover study from the catheter-dialysis r and omized study ( Cathedia ) , which was conducted among 736 critically ill adults requiring RRT , was performed . Catheter insertion complications , catheter-tip colonization , catheter dysfunction and urea reduction ratio ( URR ) were analyzed considering the crossover and longitudinal design s. RESULTS This study analyzed 134 patients who underwent two different sites of catheterization , 57 and 77 of whom were initially r and omized in the femoral and jugular site , respectively . Using anatomic l and marks , time to insert a femoral catheter was shorter ( P=0.01 ) and more successful ( P=0.003 ) compared with catheterization in the jugular site . Time to catheter-tip colonization at removal was not significantly different between the two sites of insertion ( median , 14 days in both groups ; hazard ratio , 0.99 ; 95 % confidence interval , 0.61 - 1.59 ; P=0.96 ) , as well as time to dysfunction . URRs were analyzed from 395 dialysis sessions ( n=48 patients ) . No significant difference ( P=0.49 ) in mean URR was detected between sessions performed through femoral ( n=213 ; 50.9 % ) and jugular ( n=182 ; 49.5 % ) dialysis catheters . CONCLUSIONS These results vali date prior results of this study group and extend external validity to the second catheter used for RRT in the ICU . Femoral and internal jugular acute vascular access sites are both acceptable for RRT therapy in the ICU BACKGROUND Intravascular-catheter-related infections are frequent life-threatening events in health care , but incidence can be decreased by improvements in the quality of care . Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections . We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections . METHODS In this open-label , r and omised controlled trial with a two-by-two factorial design , we enrolled consecutive adults ( age ≥18 years ) admitted to one of 11 French intensive-care units and requiring at least one of central -venous , haemodialysis , or arterial catheters . Before catheter insertion , we r and omly assigned ( 1:1:1:1 ) patients via a secure web-based r and om-number generator ( permuted blocks of eight , stratified by centre ) to have all intravascular catheters prepared with 2 % chlorhexidine-70 % isopropyl alcohol ( chlorhexidine-alcohol ) or 5 % povidone iodine-69 % ethanol ( povidone iodine-alcohol ) , with or without scrubbing of the skin with detergent before antiseptic application . Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were . The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01629550 and is closed to new participants . FINDINGS Between Oct 26 , 2012 , and Feb 12 , 2014 , 2546 patients were eligible to participate in the study . We r and omly assigned 1181 patients ( 2547 catheters ) to chlorhexidine-alcohol ( 594 patients with scrubbing , 587 without ) and 1168 ( 2612 catheters ) to povidone iodine-alcohol ( 580 patients with scrubbing , 588 without ) . Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections ( 0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol ; hazard ratio 0·15 , 95 % CI 0·05 - 0·41 ; p=0·0002 ) . Scrubbing was not associated with a significant difference in catheter colonisation ( p=0·3877 ) . No systemic adverse events were reported , but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol ( 27 [ 3 % ] patients vs seven [ 1 % ] with povidone iodine-alcohol ; p=0·0017 ) and led to chlorhexidine discontinuation in two patients . INTERPRETATION For skin antisepsis , chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections . FUNDING University Hospital of Poitiers , CareFusion The low-flow method has been shown as a reliable evaluation of access recirculation . Few data is available on temporary central catheter blood recirculation ; results of 2 % and 4 % have been reported in subclavian , 10 % in 24 cm long femoral , and 18 % in 15 cm long femoral catheters , mostly in indwelling catheters for chronic hemodialysis . The purpose of this prospect i ve study was to evaluate blood recirculation in a larger number of recently inserted temporary intravenous catheters for acute hemodialysis , comparing subclavian and femoral sites . Fifty blood recirculation measurements were performed in 38 different temporary central venous dialysis catheters inserted in thirty-one critically ill patients from medical and surgical intensive care units presenting acute renal failure supported by intermittent hemodialysis . All the catheters used were well-functioning 11.5 French dual lumen Quinton of 13.5 or 19.5 cm length . Catheters presenting mechanical dysfunction , which did not allow a blood flow rate of 300 ml/min or for which lines had to be reversed were excluded from the analysis . Access blood recirculation was measured shortly after catheter insertion according to the low flow method applied after the first 30 minutes of hemodialysis at a blood flow rate of 300 ml/min . Mean blood recirculation for the 50 measurements was 10.3 + /- 9.2 % . It was significantly higher in the 26 femoral catheters than in the 24 subclavian catheters , reaching respective means of 16.1 + /- 9.1 % and 4.1 + /- 3.6 % ( p = 0.0001 ) . Blood recirculation rate was not different between 13.5 cm and 19.5 cm long subclavian catheters ( 3.0 + /- 2.6 % , n = 13 , versus 5.4 + /- 4.3 % , n = 11 , respectively ) , but was significantly higher in 13.5 cm long femoral catheters ( 22.8 + /- 9.1 % , n = 9 , versus 12.6 + /- 6.9 % , n = 17 ) ( p = 0.004 ) . Blood recirculation was measured on two separate occasions in 12 catheters r and omly selected ( 5 femoral and 7 subclavian catheters ) ; the obtained results were reproducible with a mean difference of only 2.1 + /- 1.8 % between the two measurements and a correlation of 0.96 . The mean time elapsed between catheter insertion and recirculation assessment was 2.2 + /- 3.1 days and was similar for femoral and subclavian catheters . No correlation was found between the percentage of recirculation and the arterial and venous resistances recorded during dialysis session or with the time from catheter insertion . Mean urea reduction ratio ( URR ) for the 50 dialysis sessions was 57.8 + /- 13.0 % . It was significantly higher for sessions performed with subclavian than with femoral catheters ( 62.5 + /- 10.9 % , n = 24 , versus 54.5 + /- 14.2 % , n = 26 ) ( p = 0.03 ) . In conclusion , the expected blood recirculation in well-functioning and recently inserted temporary dialysis catheters is under 5 % for subclavian , over 12 % in 19.5 cm femoral , and over 22 % in shorter 13.5 cm femoral catheters at a blood flow rate of 300 ml/min . The consequently reduced dialysis efficiency with femoral catheters is another factor to be considered in the choice of a site for temporary dialysis catheter insertion in acute renal failure patients , particularly when dialysis dose delivery is a priority , such as intoxication cases treated by extracorporeal therapy Background Intensive care unit ( ICU ) patients require dialysis catheters ( DCs ) for renal replacement therapy ( RRT ) . They carry a high risk of developing end-stage renal disease , and therefore their vascular access must be preserved . Guidewire exchange ( GWE ) is often used to avoid venipuncture insertion ( VPI ) at a new site . However , the impact of GWE on infection and dysfunction of DCs in the ICU is unknown . Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients . Methods Using data from the ELVIS r and omized controlled trial ( RCT ) ( 1496 ICU adults requiring DC for RRT or plasma exchange ) we performed a matched-cohort analysis . Cases were DCs inserted by GWE ( n = 178 ) . They were matched with DCs inserted by VPI . Matching criteria were participating centre , simplified acute physiology score ( SAPS ) II + /-10 , insertion site ( jugular or femoral ) , side for jugular site , and length of ICU stay before DC placement . We used a marginal Cox model to estimate the effect of DC insertion ( GWE vs. VPI ) on DC colonization and dysfunction . Results DC colonization rate was not different between GWE-DCs and VPI-DCs ( 10 ( 5.6 % ) for both groups ) but DC dysfunction was more frequent with GWE-DCs ( 67 ( 37.6 % ) vs. 28 ( 15.7 % ) ; hazard ratio ( HR ) , 3.67 ( 2.07–6.49 ) ; p < 0.01 ) . Results were similar if analysis was restricted to DCs changed for dysfunction . Conclusions GWE for DCs in ICU patients , compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction . Trial registration This study is registered with Clinical Trials.gov , number NCT00563342 . Registered 2 April 2009 Aims : The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy ( CRRT ) and to study the impact of femoral versus non-femoral access on CRRT dose . Methods : Statistical analysis and predictive modelling of data from the R and omized Evaluation of Normal vs. Augmented Level renal replacement therapy trial . Results : The femoral vein was the first access site in 937 ( 67 % ) of 1,399 patients . These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores ( p = 0.009 ) and lower pH ( p < 0.001 ) but similar mortality to patients with non-femoral access ( 44 vs. 45 % ; p = 0.63 ) . Lower body weight was independently associated with femoral access placement ( OR 0.97 , 95 % CI 0.96 - 0.98 ) . Femoral access was associated with a 1.03 % lower CRRT dose ( p = 0.05 ) , but a 4.20 % higher dose was achieved with 13.5 Fr catheters ( p = 0.03 ) . Conclusions : Femoral access was preferred in lighter and sicker patients . Catheter gauge had greater impact than catheter site in CRRT dose delivery . Video Journal Club “ Cappuccino with Claudio Ronco ” at http://www.karger.com/?doi=439581 From January 1986 to December 1990 we studied angiographically the subclavian-brachiocephalic vein of 100 patients dialysed by subclavian catheter for 50 ( first group ) and by internal jugular catheter for the 50 others ( second group ) . These two groups were not statistically different as regards age ( 61.6 + /- 11.3 years in the first and 61 + /- 11.1 in the second ) , sex ( 48 % and 56 % were women ) , duration of catheter insertion ( 31 + /- 21.8 and 31.7 + /- 16 days ) , and the number of dialysis sessions ( 13.5 + /- 9.1 and 13.6 + /- 7.1 ) . The type of catheters , the frequency of removal for poor flow ( 16 % in both groups ) or infections ( 6 % in both groups ) , and the local nursing were similar in the two groups . The only difference was the side of cannulation : the right side in 58 % of cases in group 1 and 78 % in group 2 . The angiographic study revealed a stenosis of the vein in 42 % of the subclavian group and in 10 % of the internal jugular group : a dramatic difference in favour of the internal jugular route , whose superiority over the subclavian route is asserted in respect of venous access of dialysed patients Internal jugular ( IJ ) catheter insertion for hemodialysis ( HD ) is an indispensable procedure in the management of patients with renal failure . The central approach is favored over posterior approach to insert IJ catheters . There are no studies comparing the outcomes between the two approaches . The aim of this study was to compare central approach with posterior approach for IJ HD catheter insertion and to analyze various outcomes like procedure-related complication rates , catheter insertion failure rates , interruptions during dialysis due to blood flow obstruction and catheter infection rates between the two methods among patients receiving HD . All patients requiring IJ HD catheter insertion during a 1-month period were r and omly assigned to undergo catheter insertion via either conventional central approach or posterior approach . Patients were followed-up till the removal of the catheter . Among 104 patients included in the study , 54 were assigned to the central approach group and 50 to the posterior approach group . The central approach group had higher rate of procedure-related complications ( 14.81 % vs. 6 % , P = 0.04 ) . Catheter insertion failure rates were marginally higher in posterior approach group ( 20 % vs. 12.96 % , P = 0.07 ) . One or more instance of interruption during HD due to obstruction in blood flow was more common in posterior approach ( 46 % vs. 9.25 % , P < 0.01 ) . Catheter infection rates were similar between the two groups ; 16.66 % ( n = 9 ) in central group vs. 14 % ( n = 7 ) in posterior group . Posterior approach is a reasonable alternative to conventional central approach in IJ cannulation for HD catheter . It is , however , associated with a significantly high rate of interruption in HD blood flow and catheter insertion failure rates . The posterior approach can be used in patients with local exit site infection or in failed attempts to cannulate IJ vein via the conventional central approach BACKGROUND Untunnelled straight jugular catheters ( USC ) are uncomfortable for patients and can not be well fixated . This could be a reason for the high incidence of catheter-related complications . METHODS We prospect ively analysed the outcome of a novel design ed untunnelled precurved catheter ( UPC ) with better fixation properties and compared it with the outcome of USC . The outcome was also related to data on tunnelled cuffed catheters ( TCC ) . RESULTS The outcome of USC was documented over a 32-month period . Thereafter , we switched to an UPC . The same catheter care protocol was used and not changed over time . A total of 104 USC and 65 UPC were inserted . Compared to USC , less UPC had to be removed for a complication ( 53 versus 15 % ; P < 0.001 ) and less periods of catheter-related bacteraemia were observed in UPC compared to USC [ 0 versus 5.6 per 1000 catheter days ( cd ) ; P < 0.01 ] . Removal for flow problems was similar . Compared to 64 TCC , inserted in the same period , UPC had more flow problems . Other outcomes and complication rates were similar . Complication rates for TCC inserted before and after the switch from USC to UPC were similar . CONCLUSIONS UPC have better patency rates and a lower risk for bacteraemia and exit-site infection compared to USC Tunneled catheters are widely used for the provision of hemodialysis . Long-term catheter survival is limited by tunneled catheter-related infections ( CRI ) . This study assesses the efficacy of catheter-restricted filling with gentamicin and citrate in preventing CRI in hemodialysis patients . A double-blind r and omized study was conducted to compare heparin ( 5000 U/ml ) with gentamicin/citrate ( 40 mg/ml and 3.13 % citrate ; ratio 2:1 ) as catheter-lock solutions . A total of 112 tunneled catheters in 83 patients were enrolled at the time of catheter insertion for commencement or maintenance of hemodialysis . The primary end point was CRI . Catheter malfunction , defined as blood flow rate of < 200 ml/min for three consecutive dialyses and /or the use of urokinase , was also assessed as a secondary end point . Infection rates per 100 catheter-days were 0.03 in the gentamicin group versus 0.42 in the heparin group ( P = 0.003 ) . Kaplan-Meier survival analyses showed mean infection-free catheter survival of 282 d ( 95 % CI , 272 to 293 d ) in the gentamicin group versus 181 d ( 95 % CI , 124 to 237 d ) in the heparin group ( log rank , 9.58 ; P = 0.002 ) . Cox regression analyses showed a relative risk for infection-free catheter survival of 0.10 ( 95 % CI , 0.01 to 0.92 ) in the gentamicin group when adjusted for gender , race , diabetes mellitus , catheter malfunction , and hemoglobin ( P = 0.042 ) . The incidence of catheter malfunction was not significantly different between groups . Predialysis gentamicin levels were significantly higher in patients r and omized to gentamicin ( gentamicin/citrate : median 2.8 mg/L [ range , 0.6 to 3.5 mg/L ] , n = 5 ; heparin : median < 0.2 mg/L [ range < 0.2 to 0.2 mg/L ] , n = 5 ; P = 0.008 ) . Tunneled hemodialysis catheter-restricted filling with gentamicin and citrate is a highly effective strategy for prevention of CRI . Although citrate as a catheter-lock solution provides adequate anticoagulation for the interdialytic period , gentamicin levels suggest significant risk for chronic aminoglycoside exposure and associated ototoxicity . Before this technique is adopted , these preliminary observations warrant replication in future studies that will examine the efficacy and safety of lower doses of gentamicin or alternative agents with a reduced potential for toxicity The use of real-time ultrasound ( US ) is advantageous in the insertion of central venous catheters ( CVCs ) in adults , especially in whom difficulties are anticipated for various reasons . The aim of the present study was to compare two different real-time 2-dimensional US-guided techniques [ short axis view/out-of-plane approach ( SAX OOP approach ) versus long axis view/in-plane approach ( LAX IP approach ) ] for internal jugular vein ( IJV ) cannulation . In this prospect i ve study , 90 critical care and hemodialysis patients were assigned for insertion of CVCs using either the real-time US-guided ( SAX OOP approach or LAX IP approach ) or l and mark technique ( control group ) . Failed catheter placement , risk of complications from placement , failure on first attempt at placement , number of attempts until successful catheterization , time to successful catheterization , incidence of central line-associated blood stream infection ( CLA-BSI ) and demographics of each patient were recorded . There were no significant differences in patient 's demographic characteristics , side of cannulation ( right or left ) or presence of risk factors for difficult venous cannulation between the three groups of patients . Cannulation of the IJV was achieved in all patients by using US ( SAX OOP and LAX IP approaches ) and in 27 of the patients ( 90 % ) by using the l and mark technique ( P = 0.045 ) . Average access time ( skin to vein ) and number of attempts were comparable between the SAX OOP and the LAX IP approaches while significantly reduced in both US groups of patients compared with the l and mark group ( P < 0.001 ) . In the l and mark group , puncture of the carotid artery occurred in 16.7 % of the patients , hematoma in 23.3 % of the patients , pneumothorax in 3.3 % of the patients and CLA-BSI in 20 % of the patients , which were all significantly increased compared with the US group ( P < 0.05 ) . The findings of this study suggest that the SAX OOP and LAX IP approaches were comparable for cannulation of IJV in critical care and hemodialysis patients . Furthermore , both US-guided techniques were superior to the l and mark technique for insertion of CVCs BACKGROUND The purpose of this study is to compare a new temporary triple-lumen catheter ( TLC ) for dialysis that has a third lumen devoted to fluid and medication administration or blood sampling with a marketed dual-lumen catheter ( DLC ) . METHODS Four hundred eighty-five patients referred for acute hemodialysis or apheresis were r and omly assigned to either a TLC or DLC in a multicenter , prospect i ve , r and omized trial . RESULTS Analysis of blood flow rates was completed on 464 patients ( 228 patients , DLC ; 236 patients , TLC ) with a total of 1,681 hemodialysis ( 808 treatments , DLC ; 873 treatments , TLC ) and 82 apheresis treatments ( 37 treatments , DLC ; 45 treatments , TLC ) . During hemodialysis , a median achieved flow rate ( AFR ) of 267 mL/min was realized for both groups ( P = 0.58 ) . During apheresis , a median AFR of 72.5 mL/min ( range , 50 to 150 mL/min ) was achieved in the DLC group , and 87 mL/min ( range , 60 to 150 mL/min ) , in the TLC group ( P = 0.14 ) . Three hundred ninety-three patients ( 193 patients , DLC ; 200 patients , TLC ) had blood and catheter tip cultures performed on removal , and catheter-related bloodstream infection ( CRBSI ) status was determined . Thirty-one patients ( 7.9 % ) had a CRBSI : 16 patients ( 8.3 % ) , DLC ; and 15 patients ( 7.5 % ) , TLC ( P= 0.77 ) . Incidence densities of CRBSI were 12.4/1,000 DLC-days and 10.2/1,000 TLC-days ( P = 0.59 ) . The CRBSI incidence of 18.2/1,000 catheter-days for femoral sites was significantly greater than the 7/1,000 catheter-days for jugular sites ( P = 0.02 ) and 6.6/1,000 catheter-days for combined jugular and subclavian sites ( P = 0.01 ) . In multivariate analysis , antibiotic use was the only factor related to CRBSI ( odds ratio , 0.30 ; 95 % confidence interval , 0.12 to 0.76 ) . There were no statistically significant differences in rates of other complications between the 2 catheters . CONCLUSION Results show that the new TLC is similar to the marketed DLC BACKGROUND Susceptibility to infection and thrombosis of intravascular catheters is increased by surface irregularities , which might be prevented by coating . METHODS BaSO4 release from conventional haemodialysis catheters ( CC ) and modified catheters ( MC ) which had been coated with a surface-modifying additive ( SMA ) was assessed in vivo and in vitro . For the in vivo part , patients were r and omized to receive a temporary CC or MC , with crossover after 1 week . After retrieval , catheters were examined using scanning electron microscopy to assess surface integrity , and an in vitro model of catheter exposure to the bloodstream was used to evaluate surface morphology and susceptibility to bacterial adhesion and proliferation . RESULTS BaSO(4 ) moieties covered 14.7 + /- 3.7 % of the surface of unused CC . After in vivo use in 16 patients , 62.7 + /- 32.9 x 10(3 ) holes/mm(2 ) were detected , indicating BaSO(4 ) detachment from 3.3 + /- 1.7 % of the catheter surface . No defects were observed in unused CC and in MC , whether used or unused . After incubation of four catheters ( two of each type ) with Staphylococcus epidermidis , the two de grade d CC showed an immediate and strong bacterial growth as indicated by an increase in medium impedance of 0.512%/10 min compared to -0.021%/10 min in MC ( P < 0.001 ) . CONCLUSIONS Short-term exposure of CC to the bloodstream causes BaSO(4 ) particle release , result ing in surface irregularities predisposing to bacterial proliferation . BaSO(4 ) release can be prevented by SMA coating BACKGROUND Uncuffed , nontunneled hemodialysis catheters remain the preferred means to gain immediate access to the circulation for hemodialysis . Bacteremia is the primary complication that limits their use . The risk of bacteremia by site of insertion and duration of use has not been well studied . METHODS Two hundred eighteen consecutive patients who required a temporary hemodialysis catheter were prospect ively followed . RESULTS Catheters were placed at 318 new insertion sites and remained in use for a total of 6235 days . The incidence of bacteremia was 5.4 % after three weeks of placement in internal jugular vein and 10.7 % after one week in femoral vein [ relative risk for bacteremia 3.1 ( 95 % CI , 1.8 to 5.2 ) ] . The incidence of bacteremia was 1.9 % one day after the onset of an exit site infection but increased to 13.4 % by the second day if the catheter was not removed . Guidewire exchange for malfunction and patient factors did not significantly affect the risk of bacteremia . CONCLUSIONS Internal jugular catheters may be left in place for up to three weeks without a high risk of bacteremia , but femoral catheters in bed-bound patients should be removed after one week . Catheter exchanges over a guidewire for catheter malfunction do not increase bacteremia rates . Temporary catheters should be removed immediately if an exit site infection occurs Background : The objective of this study was to assess the impact of heparin concentration retained in temporary double-lumen catheters on bleeding risk . Methods : Activated partial thromboplastin time ( aPTT ) was measured in patients hemodialyzed via double-lumen catheters . Heparin solutions of 5,000 U/ml ( group 1 , n = 95 ) and 1,000 U/ml ( group 2 , n = 89 ) were r and omly retained in catheters after placement and each hemodialysis ( HD ) session . Blood transfusion , bleeding episodes , and changes of hematocrit were recorded . Results : The aPTT at the beginning of HD or 10 min after heparin lock was significantly prolonged , which was more prominent in the 5,000 U/ml group , whereas the aPTT declined to baseline values at the end of HD or before the next dialysis session in both groups . Infection and occlusion rates were similar in both groups . More patients suffered from major bleeding and prominent decline of hematocrit in the 5,000 U/ml group . Conclusions : Low-dose heparin ( 1,000 U/ml ) retention in double-lumen catheters for temporary HD maintains comparable catheter patency and might reduce the bleeding risk Ultrasound dilution technology is emerging as the st and ard for measuring access recirculation and blood flow in hemodialysis patients . In temporary dialysis catheters , studies using the traditional two-needle urea method have suggested that short femoral catheters are associated with an unacceptably high degree of recirculation . This problem has never been assessed using ultrasound dilution technology . We performed a prospect i ve observational study of consecutive patients undergoing dialysis through a temporary catheter . Measurements were made on 49 catheters ; 10 catheters were excluded because poor flow necessitated reversal of the dialysis ports . Thirty-nine catheters in 33 patients were included in this analysis , of which 26 catheters were located in the femoral vein , and 13 catheters , in the internal jugular vein . Dialyzer blood flow was adjusted to give an ultrasonic flow rate of 250 mL/min ( actual mean blood flow , 234.3 mL/min ; 95 % confidence interval [ CI ] , 228 to 241 ) . Overall mean recirculation rate was 8.9 % ( 95 % CI , 4.8 to 13.0 ) . Multivariate analysis showed catheter location and length to be independent predictors of recirculation . Blood flow ( within the range tested ) , duration into dialysis , time since catheter insertion , cardiac rhythm , and catheter type had no significant effect on recirculation rates . Recirculation in femoral catheters ( 13.1 % ) was significantly greater than that in internal jugular catheters ( 0.4 % ; P : < 0.001 ) . Femoral catheters shorter than 20 cm had significantly greater recirculation ( 26.3 % ) than those longer than 20 cm ( 8.3 % ; P : = 0.007 ) . We conclude that temporary femoral catheters shorter than 20 cm are associated with increased recirculation rates . In addition , when dialysis dose delivery is a priority , locating the temporary catheter in the internal jugular vein is an advantage BACKGROUND The aim was to assess whether inserting a longer soft silicone short-term dialysis catheter targeting tip placement in the right atrium could improve dialyzer circuit life span compared with inserting a shorter dialysis catheter targeting tip placement in the superior vena cava . STUDY DESIGN R and omized unblinded controlled study . SETTING & PARTICIPANTS A tertiary multidisciplinary intensive care unit enrolling 100 critically ill patients requiring continuous renal replacement therapy ( CRRT ) . INTERVENTION Placement of longer ( 20 - 24 cm ) versus shorter dialysis catheters ( 15 - 20 cm ) within one of the major thoracic veins for initiation of CRRT . OUTCOMES The primary study outcome was duration of dialysis circuit life span . Secondary outcomes included delivered daily dialysis dose , incidence and cause of CRRT circuit failure , complications potentially related to the position of the short-term dialysis catheter , mortality , and patient length of stay . RESULTS Placing the longer dialysis catheters was associated with an increased average dialyzer life span of 6.5 hours ( 24 hours [ 25th-75th percentile , 11 - 32 ] vs 17.5 hours [ 25th-75th percentile , 8 - 23 ] ; P = 0.001 ) , improved delivered daily dialysis dose ( 91 % [ 25th-75th percentile , 85%-100 % ] vs 81 % [ 25th-75th percentile , 72%-97 % ] ; P < 0.001 ) , and reduced number of dialyzers clotted ( 2.3 vs 3.6 ; P = 0.04 ) or circuits taken down due to vascular access problem ( 0.19 vs 0.53 ; P = 0.04 ) per patient compared with placing shorter dialysis catheters . The incidence of atrial arrhythmias was similar between groups ( 28 % vs 21 % ; P = 0.6 ) and the only mechanical complication was the malposition of one dialysis catheter tip in the longer dialysis catheter group . LIMITATIONS Single-center study design . CONCLUSIONS The use of longer soft silicone short-term dialysis catheters targeting right atrial placement appeared to be safe and could improve dialyzer life span and daily dialysis dose of CRRT delivered compared with the use of shorter catheters targeting superior vena cava placement |
1,175 | 31,485,431 | Conclusions The meta- analysis results shows that PDT for patients with prostate cancer can be considered as effective based on single-arm clinical trials .
Meanwhile , this study reveals that there are not only low levels of side effect rates but also insignificant effect on both urinary and erectile function . | Purpose Photodynamic therapy ( PDT ) is an emerging focal treatment modality for prostate cancer .
However , the efficacy , safety , and functional outcomes of PDT are not clear .
We performed a meta- analysis of available single-arm studies and control trials which used PDT for prostate cancer . | PURPOSE Vascular targeted photodynamic therapy with WST11 ( TOOKAD ® Soluble ) is a form of tissue ablation that may be used therapeutically for localized prostate cancer . To study dosing parameters and associated treatment effects we performed a prospect i ve , multicenter , phase I/II trial of WST11 vascular targeted photodynamic therapy of prostate cancer . MATERIAL S AND METHODS A total of 30 men with unilateral , low volume , Gleason 3 + 3 prostate cancer were enrolled at 5 centers after local institutional review board approval . Light energy , fiber number and WST11 dose were escalated to identify optimal dosing parameters for vascular targeted photodynamic therapy hemi-ablation . Men were treated with photodynamic therapy and evaluated by posttreatment magnetic resonance imaging and biopsy . Prostate specific antigen , light dose index ( defined as fiber length/desired treatment volume ) , toxicity and quality of life parameters were recorded . RESULTS After dose escalation 21 men received optimized dosing of 4 mg/kg WST11 at 200 J energy . On posttreatment biopsy residual prostate cancer was found in the treated lobe in 10 men , the untreated lobe in 4 and both lobes in 1 . At a light dose index of 1 or greater with optimal dosing in 15 men 73.3 % had a negative biopsy in the treated lobe . Six men undergoing retreatment with the optimal dose and a light dose index of 1 or greater had a negative posttreatment biopsy . Minimal effects were observed on urinary and sexual function , and overall quality of life . CONCLUSIONS Hemi-ablation of the prostate with WST11 vascular targeted photodynamic therapy was well tolerated and result ed in a negative biopsy in the treated lobe in the majority of men . Dosing parameters and the light dose index appear related to tissue response as determined by magnetic resonance imaging and biopsy . These parameters may serve as the basis for further prospect i ve studies Purpose : We assessed the midterm oncologic outcomes of vascular targeted photodynamic therapy with padeliporfin for low risk prostate cancer treatment . Material s and Methods : We prospect ively assessed all patients treated with vascular targeted photodynamic therapy for low risk prostate cancer at our center . Patients were followed every 6 months . All patients underwent prostate biopsies 6 months after treatment or when there was biological or clinical progression . The primary end point was progression‐free survival . Secondary end points were absent clinical ly significant cancer in the treated lobes , radical therapy and the prostate specific antigen rate . Variables were compared with the chi‐square , Mann‐Whitney or Wilcoxon test . Progression‐free survival is reported with Kaplan‐Meier curves . Results : A total of 82 men were treated with vascular targeted photodynamic therapy . Median followup was 68 months ( range 6 to 89 ) . Median progression‐free survival was 86 months ( 95 % CI 82–90 ) . Median prostate specific antigen decreased significantly by 41 % 6 months after treatment and it remained stable during followup ( p < 0.001 ) . A total of 115 lobes were treated and absent clinical ly significant cancer was achieved in 94 ( 82 % ) . Of the 82 patients 20 ( 24 % ) underwent radical therapy , including radical prostatectomy in 18 and brachytherapy in 2 , at a median of 22 months ( range 6 to 86 ) . Study limitations include a single arm design , small population size and midterm followup . Conclusions : Padeliporfin vascular targeted photodynamic therapy for low risk prostate cancer achieved an 82 % rate of absent clinical ly significant cancer in treated lobes and 76 % of patients avoided radical therapy at a median followup of 68 months . However , longer followup is required to determine long‐term outcomes Low-risk prostate adenocarcinoma is classically managed either with active surveillance or radical therapy ( such as external radiotherapy or radical prostatectomy ) , but both have significant side effects . Vascular-targeted photodynamic therapy ( VTP ) is a focal therapy proposed as an alternative approach for localized , low-volume , and low-Gleason score ( ≤6 ) carcinomas . We report histological modifications observed in prostate biopsies of 56 patients , performed 6 months after VTP using the photosensitizer TOOKAD ® Soluble ( WST11 ) and low-energy laser administered in the tumor area transperineally by optic fibers . In 53 patients , we observed sharply demarcated hyaline fibrotic scars , with or without rare atrophic gl and s , sometimes reduced to corpora amylacea surrounded by giant multinuclear macrophages . Mild chronic inflammation , hemosiderin , and coagulative necrosis were also observed . When residual cancer was present in a treated lobe ( 17 patients ) , it was always located outside the scar , most often close to the prostate capsule , and it showed no therapy-related modification . Histopathological interpretation of post-WST11 VTP prostate biopsies was straightforward , in contrast with that of prostate biopsies after radio or hormonal therapy , which introduces lesions difficult to interpret . VTP result ed in complete ablation of cancer in the targeted area To report on the efficacy of TOOKAD ® ( WST 09 ; NegmaLerads , Magny‐Les‐Hameaux , France ) vascular‐targeted photodynamic therapy ( VTP ) as a method of whole‐prostate ablation in patients with recurrent localized prostate cancer after the failure of external beam radiotherapy ( EBRT ) BACKGROUND AND OBJECTIVES Interstitial photodynamic therapy ( PDT ) is an emerging modality for the treatment of solid organ disease . Our group at the University of Pennsylvania has performed extensive studies that demonstrate the feasibility of interstitial PDT for prostate cancer . Our pre clinical and clinical experience is herein detailed . STUDY DESIGN / MATERIAL S AND METHODS We have treated 16 canines in pre clinical studies , and 16 human subjects in a Phase I study , using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma . Dosimetry of light fluence , drug level and oxygen distribution for these patients were performed . RESULTS We demonstrate the safe and comprehensive treatment of the prostate using PDT . However , there is significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate . CONCLUSIONS PDT is an attractive option for the treatment of prostate adenocarcinoma . However , the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility . Our future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time , in order to deliver a consistent overall PDT dose distribution BACKGROUND AND OBJECTIVES Prostate cancer is increasing in incidence , but current treatments including surgery and radiotherapy have significant side effects . This pilot study was design ed to assess the potential of photodynamic therapy ( PDT ) using meso tetra hydroxy phenyl chlorin ( mTHPC ) for organ confined prostate cancer . STUDY DESIGN / PATIENTS AND METHODS Six men with organ confined prostate cancer were photosensitised with mTHPC ( 0.15 mg/kg ) . Between 2 and 5 days later , red light ( 652 nm ) was delivered to areas of biopsy proven cancer via fibres inserted through transperineal needles ( 50 - 100 J per site ) . RESULTS After 8 of 10 PDT sessions , the prostate specific antigen ( PSA ) fell by up to 67 % . Early MRI scans showed oedema and patchy necrosis , which resolved over 2 months . Biopsies of treated areas revealed necrosis and fibrosis at 1 - 2 months . CONCLUSIONS PDT for primary prostate cancer appears safe and can reduce PSA levels . As this was a phase I study , no attempt was made to treat the whole prostate ; this or targeted tumour ablation could be attempted in a phase II study with an increased number of fibres . This technique merits further investigation in early prostate cancer To determine the optimal drug and light dose for prostate ablation using WST11 ( TOOKAD ® Soluble ) for vascular‐targeted photodynamic ( VTP ) therapy in men with low‐risk prostate cancer It is desirable to quantify the distribution of the light fluence rate , the optical properties , the drug concentration , and the tissue oxygenation for photodynamic therapy ( PDT ) of prostate cancer . We have developed an integrated system to determine these quantities before and after PDT treatment using motorized probes . The optical properties ( absorption ( micro(a ) ) , transport scattering ( micro(s ' ) , and effective attenuation ( micro(eff ) ) coefficients ) of cancerous human prostate were measured in-vivo using interstitial isotropic detectors . Measurements were made at 732 nm before and after motexafin lutetium ( MLu ) mediated PDT at different locations along each catheter . The light fluence rate distribution was also measured along the catheters during PDT . Diffuse absorption spectroscopy measurement using a white light source allows extrapolation of the distribution of oxygen saturation StO2 , total blood volume ( [Hb]t ) , and MLu concentration . The distribution of drug concentration was also studied using fluorescence from a single optical fiber , and was found to be in good agreement with the values determined by absorption spectroscopy . This study shows significant inter- and intra-prostatic variations in the tissue optical properties and MLu drug distribution , suggesting that a real-time dosimetry measurement and feedback system for monitoring these values during treatment should be considered in future PDT studies Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments . One potential treatment , photodynamic therapy ( PDT ) , is a modality that uses laser light , drug photosensitizer , and oxygen to kill tumor cells through direct cellular cytotoxicity and /or through destruction of tumor vasculature . A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer . In this ongoing trial , the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT . Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate . Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated . Treatment plans were developed using transrectal ultrasound images . The PDT dose was escalated by increasing the Motexafin lutetium dose , increasing the 732 ran light dose , and decreasing the drug-light interval . Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24 , 6 , or 3 hr prior to 732 ran light delivery . The light dose , measured in real time with in situ spherical detectors was 25 - 100 J/cm2 . Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room . Optical property measurements were made before and after light therapy . Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake . Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity . Grade I genitourinary symptoms that are PDT related have been observed . One patient had Grade II urinary urgency that was urinary catheter related . No rectal or other gastrointestinal PDT-related tox-icities have been observed to date . Measurements of Motexafin lutetium demonstrated the presence of photosensitizer in prostate tissue from all patients . Optical property measurements demonstrated substantial heterogeneity in the optical properties of the human prostate gl and which supports the use of individualized treatment planning for prostate PDT PURPOSE Photodynamic therapy , using a photosensitizing drug activated by red light , can destroy localized areas of cancer with safe healing and without the cumulative toxicity associated with ionizing radiation . We used photodynamic therapy in a phase I-II study to treat patients with locally recurrent prostate cancer after radiotherapy . MATERIAL S AND METHODS Patients with an increasing prostate specific antigen ( PSA ) and biopsy proven local recurrence after radiotherapy were offered photodynamic therapy . Three days after intravenous administration of the photosensitizer meso-tetrahydroxyphenyl chlorin , light was applied using optical fibers inserted percutaneously through perineal needles positioned in the prostate with imaging guidance . Patients were followed with PSA measurements , prostate biopsies , computerized tomography or magnetic resonance imaging and question naires on urinary and sexual function . RESULTS Photodynamic therapy was given to 14 men using high light doses in 13 . Treatment was well tolerated . PSA decreased in 9 patients ( to undetectable levels in 2 ) and 5 had no viable tumor on posttreatment biopsies . After photodynamic therapy , contrast enhanced computerized tomography or magnetic resonance imaging showed necrosis involving up to 91 % of the prostate cross section . In 4 men stress incontinence developed ( troublesome in 2 and mild in 2 ) which is slowly improving . Sexual potency was impaired in 4 of the 7 men able to have intercourse before photodynamic therapy , which did not improve . There were no rectal complications directly related to photodynamic therapy , but in 1 patient a urethrorectal fistula developed following an ill-advised rectal biopsy 1 month after therapy . CONCLUSIONS Photodynamic therapy is a new option that could be suitable for organ confined prostate cancer recurrence after radiotherapy . With more precise light dosimetry , it may be possible to destroy essentially all gl and ular tissue within the prostate with few complications . These results suggest that photodynamic therapy merits further investigation BACKGROUND Vascular-targeted photodynamic therapy , a novel tissue-preserving treatment for low-risk prostate cancer , has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies . We compared this treatment with the st and ard of care , active surveillance , in men with low-risk prostate cancer in a phase 3 trial . METHODS This r and omised controlled trial was done in 47 European university centres and community hospitals . Men with low-risk , localised prostate cancer ( Gleason pattern 3 ) who had received no previous treatment were r and omly assigned ( 1:1 ) to vascular-targeted photodynamic therapy ( 4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s ) or active surveillance . R and omisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients . Best practice for active surveillance at the time of study design was followed ( ie , biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals ) . The co- primary endpoints were treatment failure ( histological progression of cancer from low to moderate or high risk or death during 24 months ' follow-up ) and absence of definite cancer ( absence of any histology result definitely positive for cancer at month 24 ) . Analysis was by intention to treat . Treatment was open-label , but investigators assessing primary efficacy outcomes were masked to treatment allocation . This trial is registered with Clinical Trials.gov , number NCT01310894 . FINDINGS Between March 8 , 2011 , and April 30 , 2013 , we r and omly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance . Median follow-up was 24 months ( IQR 24 - 25 ) . The proportion of participants who had disease progression at month 24 was 58 ( 28 % ) of 206 in the vascular-targeted photodynamic therapy group compared with 120 ( 58 % ) of 207 in the active surveillance group ( adjusted hazard ratio 0·34 , 95 % CI 0·24 - 0·46 ; p<0·0001 ) . 101 ( 49 % ) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 ( 14 % ) men in the active surveillance group ( adjusted risk ratio 3·67 , 95 % CI 2·53 - 5·33 ; p<0·0001 ) . Vascular-targeted photodynamic therapy was well tolerated . The most common grade 3 - 4 adverse events were prostatitis ( three [ 2 % ] in the vascular-targeted photodynamic therapy group vs one [ < 1 % ] in the active surveillance group ) , acute urinary retention ( three [ 2 % ] vs one [ < 1 % ] ) and erectile dysfunction ( two [ 1 % ] vs three [ 1 % ] ) . The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine ( 15 patients ; severe in three ) ; this event resolved within 2 months in all patients . The most common serious adverse event in the active surveillance group was myocardial infa rct ion ( three patients ) . INTERPRETATION Padeliporfin vascular-targeted photodynamic therapy is a safe , effective treatment for low-risk , localised prostate cancer . This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy . FUNDING Steba Biotech BACKGROUND Focal therapy ( FT ) for prostate cancer ( PCa ) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease . OBJECTIVE To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management . DESIGN , SETTING , AND PARTICIPANTS From 2009 to 2011 , a total of 1213 patients with clinical ly localized PCa were treated at our institution . Of these patients , 547 were considered to have indolent disease according to the D'Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies . A total of 106 patients underwent FT using high-intensity focused ultrasonography ( HIFU ) , brachytherapy , cryotherapy , or vascular-targeted photodynamic therapy ( VTP ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Complications were prospect ively recorded and grade d according to the Clavien-Dindo scale . Data were prospect ively collected and retrospectively analyzed . RESULTS AND LIMITATIONS This study included 106 patients , median age 66.5 yr ( interquartile range [ IQR ] ) : 61 - 73 ) , who had a prostate hemiablation ; 50 patients ( 47 % ) had cryotherapy , 23 patients ( 22 % ) had VTP , 21 patients ( 20 % ) received HIFU , and 12 patients ( 11 % ) had brachytherapy . The median prostate-specific antigen ( PSA ) level was 6.1 ng/ml ( IQR : 5 - 8.1 ) , all the patients had a biopsy Gleason score of 6 , and the median prostate weight was 43 g ( IQR : 33 - 55 ) . The median International Prostate Symptom Score was 6 ( IQR : 3 - 10 ) , and the median International Index of Erectile Function score was 20 ( IQR : 15 - 23 ) . After treatment , the median PSA at 3 , 6 , and 12 mo was 3.1 2.9 , and 2.7 ng/ml ( IQR : 2 - 5.1 , 1.1 - 4.7 , and 1 - 4.4 ) , respectively . Thirteen percent of the patients experienced treatment-related complications . There were 11 minor medical complications ( 10 grade 1 complications and 1 grade 2 complication ) , 2 grade 3 complications , and no grade 4 or higher complications . CONCLUSIONS FT for a highly selected population with PCa is feasible and had an acceptable morbidity with < 2 % major complications |
1,176 | 30,781,593 | Exercise training did not lead to consistent changes in body mass index ( BMI ) , blood pressure , triglycerides , high-density lipoprotein cholesterol ( HDL-C ) , or low-density lipoprotein cholesterol ( LDL-C ) .
In persons living with T1D , exercise training is associated with a beneficial cardiovascular profile , including improvements in lipid profile , glycemic control ( decreased daily insulin dosage and HbA1c ) , and aerobic fitness | Exercise is advocated in the management of type 1 diabetes ( T1D ) , but the effects of different forms of exercise training on cardiovascular risk factors in T1D still remain unclear .
The aim of this study was to conduct a systematic review and meta- analysis on exercise training for cardiovascular risk factors in T1D . | OBJECTIVE -Impaired endothelial function of resistance and conduit arteries can be detected in patients with type 1 diabetes . We studied whether a persistent improvement of endothelial function can be achieved by regular physical training . RESEARCH DESIGN AND METHODS -The study included 26 patients with type 1 diabetes of 20 + /- 10 years ' duration and no overt angiopathy ; 18 patients ( 42 + /- 10 years old ) participated in a bicycle exercise training program , and 8 patients with type 1 diabetes ( 33 + /- 11 years old ) served as control subjects . Vascular function of conduit arteries was assessed by flow-mediated and endothelium-independent dilation of the brachial artery and of resistance vessels by the response of ocular fundus pulsation amplitudes to intravenous N(G)-monomethyl-L-arginine ( L-NMMA ) at baseline , after 2 and 4 months of training , and 8 months after cessation of regular exercise . RESULTS -Training increased peak oxygen uptake ( VO(2max ) ) by 13 % after 2 months and by 27 % after 4 months ( P = 0.04 ) . Flow-mediated dilation ( FMD ) of the brachial artery increased from 6.5 + /- 1.1 to 9.8 + /- 1.1 % ( P = 0.04 ) by training . L-NMMA administration decreased fundus pulsation amplitude ( FPA ) by 9.1 + /- 0.9 % before training and by 13.4 + /- 1.5 % after 4 months of training ( P = 0.02 ) . VO(2max ) , FMD , and FPA were unchanged in the control group . Vascular effects from training were abrogated 8 months after cessation of exercise . CONCLUSIONS -Our study demonstrates that aerobic exercise training can improve endothelial function in different vascular beds in patients with long-st and ing type 1 diabetes , who are at considerable risk for diabetic angiopathy . However , the beneficial effect on vascular function is not maintained in the absence of exercise OBJECTIVES This study aim ed to identify clinical features associated with premature mortality in a large contemporary cohort of adults with type 1 diabetes . RESEARCH DESIGN AND METHODS The Finnish Diabetic Nephropathy ( FinnDiane ) study is a national multicenter prospect i ve follow-up study of 4,201 adults with type 1 diabetes from 21 university and central hospitals , 33 district hospitals , and 26 primary health care centers across Finl and . RESULTS During a median 7 years of follow-up , there were 291 deaths ( 7 % ) , 3.6-fold ( 95 % CI 3.2–4.0 ) more than that observed in the age- and sex-matched general population . Excess mortality was only observed in individuals with chronic kidney disease . Individuals with normoalbuminuria showed no excess mortality beyond the general population ( st and ardized mortality ratio [ SMR ] 0.8 , 95 % CI 0.5–1.1 ) , independent of the duration of diabetes . The presence of microalbuminuria , macroalbuminuria , and end-stage kidney disease was associated with 2.8 , 9.2 , and 18.3 times higher SMR , respectively . The increase in mortality across each stage of albuminuria was equivalent to the risk conferred by preexisting macrovascular disease . In addition , the glomerular filtration rate was independently associated with mortality , such that individuals with impaired kidney function , as well as those demonstrating hyperfiltration , had an increased risk of death . CONCLUSIONS An independent grade d association was observed between the presence and severity of kidney disease and mortality in a large contemporary cohort of individuals with type 1 diabetes . These findings highlight the clinical and public health importance of chronic kidney disease and its prevention in the management of type 1 diabetes Objective : To investigate the impact of intensive lifestyle education on dietary practice s , exercise and metabolic measurements in people with insulin-dependent diabetes mellitus ( IDDM ) . Design : Sixty-one volunteer subjects with IDDM were r and omised to intensive ( Group 1 ) or st and ard ( Group 2 ) education programmes for six months . During a second six month period of observation Group 1 subjects received routine surveillance for their condition and those in Group 2 were given intensive advice ( phase 2 ) . Current insulin regimens were modified to optimise glycaemic control before the start of the intervention phase . Nutrient intakes , weight , blood pressure , glycated haemoglobin ( HbA ) , plasma lipids , lipoproteins and maximal oxygen consumption ( VO max ) were measured at the time of recruitment and at three monthly intervals during the trial and phase 2 . Setting : Department of Human Nutrition at the University of Otago . Results : Glycated haemoglobin decreased significantly in both groups between recruitment and r and omisation , the improvement being sustained during the six months of the r and omised trial and for group 1 during the six months of post trial observation . A further decrease was seen in Group 2 during the second six month period when they were given intensive advice . Comparable changes were seen with total and low density lipoprotein ( LDL ) cholesterol in Group 1 during the trial , but significant decreases were only seen in Group 2 in association with intensive intervention ( phase 2 ) . These changes occurred in parallel with increases in intakes of carbohydrate and monounsaturated fatty acids , a reduction in intakes of total and saturated fat , and an improvement in maximum oxygen consumption . Conclusions : A lifestyle programme for people with IDDM results in modest changes in diet and exercise habits sufficient to improve measures of glycaemic control and lipoprotein mediated risk of coronary heart disease independent of changes in insulin regime . More innovative approaches to achieve lifestyle changes are required to meet current recommendations which in turn are likely to produce even greater beneficial changes than those observed here . Sponsorship : This study was supported by the Eli Lilly Research Grant ( Eli Lilly and Company ( New Zeal and ) Ltd ) , The Deans Research Grant ( Otago Medical School , New Zeal and ) and The New Zeal and Dietetic Association ( Abbott Award ) Physical inactivity is highly common in adults with type 1 diabetes ( T1D ) as specific barriers ( i.e. , hypoglycemia ) may prevent them from being active . The objective of this study was to examine the efficacy of the Physical Exercise Promotion program in type 1 diabetes ( PEP-1 ) program , a group program of physical activity ( PA ) promotion ( intervention ) compared with an information leaflet ( control ) , to improve total energy expenditure ( TEE ) in adults with T1D after 12 weeks . TEE was measured with a motion sensor over a 7-day period at inclusion , after the program ( 12 weeks ) and 1-year after inclusion . The 12 weekly sessions of the program included a 30-min information session ( glycemic control and PA ) and 60 min of PA . A total of 48 adults , aged 18 to 65 years with a reported PA practice < 150 min per week , were recruited ( 45.8 % men ; aged 44.6 ± 13.3 years ; 8.0 % ± 1.1 % glycated hemoglobin ( A1c ) ) and r and omized in this pilot trial . Ninety percent of participants completed the program and 88 % completed the 1-year follow-up . No change was observed for TEE and A1c in both groups . After the 12-week program , the mean peak oxygen uptake increased ( 14 % ; p = 0.003 ) in the intervention group ; however , at the 1-year follow-up , it was no longer different from baseline . In the control group , no difference was observed for the peak oxygen uptake . These results suggest that the PEP-1 pilot program could increase cardiorespiratory fitness . However , this benefit is not sustained over a long-term period . The PEP-1 program did not increase TEE in patients with T1D and other strategies remain necessary to counteract physical inactivity in this population Summary No objective evidence has been presented to support the beneficial effect of physical training on glycaemic control in Type 1 ( insulin-dependent ) diabetic patients trained two to three times a week for several months . In the present study we examined the possibility that a daily exercise programme would be more suitable for improving glycaemic control . Thirteen patients completed a 5-month study ; 6 were r and omized to exercise training ( 20 min daily bicycle exercise ) and 7 served as non-exercising controls . The training result ed in an 8 % increase in maximal oxygen uptake ( p < 0.05 ) . No change in glycaemic control occurred during the study period in either group . In addition , serum lipid and lipoprotein levels were followed . Total cholesterol decreased during the study period irrespective of training . No effect was noted on the levels of LDL , VLDL , HDL and HDL2 cholesterol . A significant training effect was obtained in the HDL3 subfraction ( −10%,p < 0.05 ) . Total triglycerides were unchanged , but a decrease in the level of LDL triglycerides was observed with training ( −12%,p < 0.01 ) . It is concluded that , in female Type 1 diabetic patients , daily physical training for several months does not improve glycaemic control and results only in minor changes in serum lipoprotein profiles BACKGROUND Intensive diabetes therapy aim ed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes . We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial ( DCCT ) affected the long-term incidence of cardiovascular disease . METHODS The DCCT r and omly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy , treating them for a mean of 6.5 years between 1983 and 1993 . Ninety-three percent were subsequently followed until February 1 , 2005 , during the observational Epidemiology of Diabetes Interventions and Complications study . Cardiovascular disease ( defined as nonfatal myocardial infa rct ion , stroke , death from cardiovascular disease , confirmed angina , or the need for coronary-artery revascularization ) was assessed with st and ardized measures and classified by an independent committee . RESULTS During the mean 17 years of follow-up , 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT , as compared with 98 events in 52 patients who had received conventional treatment . Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent ( 95 percent confidence interval , 9 to 63 percent ; P=0.02 ) and the risk of nonfatal myocardial infa rct ion , stroke , or death from cardiovascular disease by 57 percent ( 95 percent confidence interval , 12 to 79 percent ; P=0.02 ) . The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease . Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease , but differences between treatment groups remained significant ( P < or = 0.05 ) after adjusting for these factors . CONCLUSIONS Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention . We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1.97 to 3.67 ) ( P<0.001 for all comparisons ) . Similar associations were apparent for a range of nonvascular outcomes , including respiratory , digestive , and skin conditions ( P<0.01 for all comparisons ) . No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death . CONCLUSIONS Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes . It is possible that severe hypoglycemia contributes to adverse outcomes , but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events . ( Funded by Servier and the National Health and Medical Research Council of Australia ; Clinical Trials.gov number , NCT00145925 . ) OBJECTIVE To assess whether pedometers and text messaging increase physical activity in adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS A 12-week r and omized controlled trial was conducted . A total of 78 subjects participated in the trial ( mean ± SD age 14.4 ± 2.37 years , 36 [ 47 % ] male ) . Intervention participants wore an open pedometer and received regular motivational text messages . Control participants received usual care . Primary outcomes were daily step count ( 4-day closed pedometer ) and physical activity question naire . RESULTS Baseline median step count was 11,063 steps/day ( range 1,541–20,158 ) . At 12 weeks , mean daily step count reduced by 840 ( 95 % CI −1,947 to 266 ) in the control group and by 22 ( −1,407 to 1,364 ) in the intervention group ( P = 0.4 ) . Mean self-reported moderate or vigorous physical activity increased by 38.5 min/week in the control group and by 48.4 in the intervention group ( P = 0.9 ) . CONCLUSIONS A 12-week intervention using pedometers and text messaging as motivational tools in adolescents with type 1 diabetes did not increase physical activity Sixteen postmenarcheal Type 1 diabetic adolescent girls were r and omized into training ( involving aerobic and strength exercises ) and nontraining groups . Body composition ( skinfold thickness ) , aerobic fitness ( PWC170 ) , plasma lipids , serum apolipoproteins , lipoprotein(a ) , leptin , and adiponectin were assessed before and after the 6-month period . After the 6-month period , fat mass and leptin increased significantly in the nontraining group but not in the training group . Conversely , in the latter group , fat-free mass increased ( P < .01 ) . Moreover , PWC170 improved and apolipoproteinB : apolipoproteinA-1 ratio decreased with physical training ( P < .05 ) . Thus , physical training reduces cardiovascular risks and the increase of insulin resistance risk factors in diabetic adolescent girls PURPOSE Despite the potential importance of favorable changes in the lipid profile produced by aerobic exercise , training-induced lipid profile changes in atherosclerosis-prone type 1 diabetes mellitus ( DM ) have not heretofore been adequately addressed . METHODS We assessed the effect of a 12- to 16-wk aerobic exercise program on cardiorespiratory fitness and the lipid profile in young men with type 1 DM . Generally active men aged 20 - 40 yr with type 1 DM ( N = 56 ) were r and omized into training ( N = 28 ) and control ( untrained , N = 28 ) groups after baseline measurements . Training consisted of 30 - 60 min moderate-intensity running 3 - 5 times a week for 12 - 16 wk . RESULTS For the 42 men finishing the study , peak oxygen consumption ( VO2 peak ) increased significantly only in the trained group . Total and low-density lipoprotein ( LDL ) cholesterol and apolipoprotein ( apo ) B decreased and the high-density lipoprotein (HDL)/apo A-I ratio increased in the trained group . HDL and apo A-I increased in both groups . The exercise program brought about improvements in the HDL/LDL and apo A-I/apo B ratios and apo B and triglyceride levels when comparing the relative ( % ) changes in the trained versus control group . In the trained group , men with HDL/LDL ratios below the group median at baseline showed even more favorable changes in their lipid profile than those with higher initial HDL/LDL ratios . Body mass index , percent body fat and hemoglobin A1c did not change during the training period in either group . CONCLUSIONS Endurance training improved the lipid profile in already physically active type 1 diabetic men , independently of effects on body composition or glycemic control . The most favorable changes were in patients with low baseline HDL/LDL ratios , likely the group with the greatest benefit to be gained by such changes The goal of this study was to evaluate a program of resistance weight training on cardiovascular risk factors , blood glucose management , and overallstrength in diabetic subjects . A r and omized crossover design was performed on eight male type I ( insulin-dependent ) diabetic subjects ( mean ± SD age 31 ± 3.5 yr , height 176 ± 5.6 cm , body wt 80 ± 15 kg , duration of diabetes 12.3 ± 9.8 yr , and insulin dose 24 U NPH/day and 21 U regular/day ) . The program consisted of heavy-resistance weight training 3 days/wk for 10 wk , concentrating on the strengthening of major muscle groups through progressive resistance . Blood tests included total cholesterol , triglycerides , very-low-density lipoprotein and high-densitylipoprotein cholesterol , and HbA1c . These tests were repeated atthree time points during the program . Field-strength testing was performed before and after training . An improvement was seen in the squat ( 93.6 % increase , P < 0.0001 ) and bench press ( 58 % increase , P < 0.005 ) . HbA1c and triglyceride levels showed no change during the resting portion ofthe experiment but showed a significant change with the training program : HbA1c 6.9 ± 1 . 4 vs. 5.8 ± 0.9 % ( P = 0.05 ) and triglyceride 5.044 ± 1.06 vs. 4.628 ± 0.88 mM ( P = 0.01 ) . Self-monitored glucose ( taken pre- and postexercise ) showed a decrease from 7.85 ± 3.13 to 7.05 ± 2.91 mM ( P = 0.0001 ) . Very-low-density lipoprotein cholesterol and triglycerides did not change after training . Analysis of variance showed no significant differences over time from the three time points with regard to reductions in cardiovascular risk factors or HbA1c . Heavy-resistance strength training may be associated with a decrease inglycosylated hemoglobin and cholesterol in type I diabetic men after training , in addition to increasing overall strength This study sought to establish whether the glycemic control achieved in exercise-trained adolescents with type 1 diabetes mellitus ( DM ) is dependent on the quality of glycemic control prior to the initiation of exercise training . Adolescents with type 1 DM were r and omly assigned to groups with either lower or higher than 9 % glycosylated hemoglobin ( HbA1c ) , and su bmi tted to 12 weeks of supervised training followed by 12 weeks of unsupervised training ( n = 12 per group ) . Supervised training caused a 17 % rise in the patients ' aerobic capacity which during the ensuing period of unsupervised training decreased to pre-training levels , thus suggesting a poor compliance with unsupervised training . The average levels of HbA1c in poorly and well controlled diabetic patients were not affected by training , a finding indicating that irrespective of the quality of glycemia prior to exercise training , glycemic control in adolescents with type 1 DM does not improve in response to exercise training alone 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 INTRODUCTION Osteoporosis is a growing health problem in patients with type 1 diabetes mellitus ( T1DM ) . The aim of this study was to determine the effects of a 9-month weight-bearing physical activity program on bone mineral density ( BMD ) and bone biomarkers in T1DM compared with healthy children . METHODS This was a r and omized controlled trial including 27 diabetic and 32 healthy children ( mean age = 10.5 ± 2.5 yr ) . Both T1DM and healthy participants were r and omized to either an exercise or a control group ( i.e. , four groups ) . At baseline and 9 months , total body ( TB ) , lumbar spine ( LS2-LS4 ) , femoral neck , and greater trochanter areal BMD ( aBMD ) and serum bone biomarkers ( osteocalcin , type 1 collagen cross-linking ) were measured . The intervention consisted of two 90-min sessions per week of weight-bearing physical activity ( ball games , jumping , rope skipping , and gymnastics ) . RESULTS Baseline variables were similar among groups . At 9 months , changes in TB ( T1DM = 0.035 ± 0.022 g·cm(-2 ) , healthy = 0.031 ± 0.017 g·cm(-2 ) ) and LS2-LS4 ( T1DM = 0.046 ± 0.038 g·cm(-2 ) , healthy = 0.063 ± 0.034 g·cm(-2 ) ) aBMD were statistically significant in the intervention groups and of similar magnitude between T1DM and healthy subjects . The level of type 1 collagen cross-linking ( T1DM = -0.12 ± 0.32 ng·mL(-1 ) , healthy = -0.36 ± 0.11 ng·mL(-1 ) ) decreased in the intervention groups but was not associated with TB aBMD changes . CONCLUSIONS Regular weight-bearing physical activity ( 180 min·wk(-1 ) , including ball games , jumping activities , and gymnastics ) improves total and LS2-LS4 bone mineral accretion in children with T1DM , in a similar magnitude to healthy subjects . We conclude that children with T1DM should be encouraged to practice regular physical activity to enhance peak bone mass and prevent osteoporosis later in life AIM To verify the occurrence of post-exercise hypotension ( PEH ) in type 2 diabetics ( DM(2 ) ) and the effects of exercise intensity on post-exercise blood pressure ( BP ) . METHODS Eleven men and women with DM(2 ) ( 58.5+/-10.2 years ; 160+/-0.1 cm ; 80.6+/-13.5 kg ; 31.2+/-3.8kg/m(2 ) , 19+/-3.2mLkgmin(-1 ) of VO(2max ) , 155.0+/-39.2mgdL(-1 ) of fasting blood glucose and 126+/-10/75+/-7mmHg of resting BP ) performed an incremental test ( IT ) for cardiovascular evaluation and anaerobic threshold ( AT ) determination . Then , participants r and omly underwent 2 exercise sessions ( 90 % and 110 % AT ) and a control session ( CON ) . In all sessions , BP was measured at resting , during 20min of exercise/control and at each 15min through 120min of post-exercise recovery ( R15-R120 ) . RESULTS The mean results of systolic BP (SBP)/diastolic BP ( DBP ) over the 120min of recovery were 125+/-16/76+/-7mmHg , 122+/-13/75+/-6mmHg and 129+/-16/78+/-7mmHg , respectively for 90 % , 110 % and CON . Significant reductions of SBP occurred after 90 % ( R15-R45 ) and 110 % ( R15-R90 ) , while only after 110 % there were reductions of DBP ( R15 , R45 ) and MAP ( R15 , R45 , R75 , R90 , R105 ) . CONCLUSIONS Both exercise intensities evoked reductions in SBP while DBP and MAP were reduced only after 110 % . Despite the higher intensity exercise to be more effective in promoting BP reductions , we suggest caution while prescribing exercise for DM(2 ) Diabetes is defined by its association with hyperglycemia-specific microvascular complications ; however , it also imparts a two- to fourfold risk of cardiovascular disease ( CVD ) . Although microvascular complications can lead to significant morbidity and premature mortality , by far the greatest cause of death in people with diabetes is CVD . Results from r and omized controlled trials have demonstrated conclusively that the risk of microvascular complications can be reduced by intensive glycemic control in patients with type 1 ( 1,2 ) and type 2 diabetes ( 3–5 ) . In the Diabetes Control and Complications Trial ( DCCT ) , there was an ∼60 % reduction in development or progression of diabetic retinopathy , nephropathy , and neuropathy between the intensively treated group ( goal A1C < 6.05 % , mean achieved A1C ∼7 % ) and the st and ard group ( A1C ∼9 % ) over an average of 6.5 years . The relationship between glucose control ( as reflected by the mean on- study A1C value ) and risk of complications was log-linear and extended down to the normal A1C range ( < 6 % ) with no threshold noted . In the UK Prospect i ve Diabetes Study ( UKPDS ) , participants newly diagnosed with type 2 diabetes were followed for 10 years , and intensive control ( median A1C 7.0 % ) was found to reduce the overall microvascular complication rate by 25 % compared with conventional treatment ( median A1C 7.9 % ) . Here , too , secondary analyses showed a continuous relationship between the risk of microvascular complications and glycemia extending into the normal range of A1C , with no glycemic threshold . On the basis of these two large controlled trials , along with smaller studies and numerous epidemiologic reports , the consistent findings related to microvascular risk reduction with intensive glycemic control have led the American Diabetes Association ( ADA ) to recommend an A1C goal of < 7 % for most adults with diabetes ( 6 ) , recognizing that more or less stringent goals may be appropriate for certain patients . Whereas many epidemiologic studies and meta-analyses |
1,177 | 30,808,653 | RESULTS We found high- quality evidence to recommend MT plus best medical management ( BMM , including intravenous thrombolysis whenever indicated ) to improve functional outcome in patients with LVO-related acute ischemic stroke within 6 hours after symptom onset .
MT is the st and ard of care in patients with LVO-related acute stroke . | BACKGROUND Mechanical thrombectomy ( MT ) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion ( LVO ) .
OBJECTIVE To assist physicians in their clinical decisions with regard toMT . | Objective The Pragmatic Ischaemic Thrombectomy Evaluation ( PISTE ) trial was a multicentre , r and omised , controlled clinical trial comparing intravenous thrombolysis ( IVT ) alone with IVT and adjunctive intra-arterial mechanical thrombectomy ( MT ) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography ( CTA ) . Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset . Those r and omised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device , with target interval times for IVT start to arterial puncture of < 90 min . The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale ( mRS ) score of 0–2 at day 90 . Results Ten UK centres enrolled 65 patients between April 2013 and April 2015 . Median National Institutes of Health Stroke Scale score was 16 ( IQR 13–21 ) . Median stroke onset to IVT start was 120 min . In the intention-to-treat analysis , there was no significant difference in disability-free survival at day 90 with MT ( absolute difference 11 % , adjusted OR 2.12 , 95 % CI 0.65 to 6.94 , p=0.20 ) . Secondary analyses showed significantly greater likelihood of full neurological recovery ( mRS 0–1 ) at day 90 ( OR 7.6 , 95 % CI 1.6 to 37.2 , p=0.010 ) . In the per- protocol population ( n=58 ) , the primary and most secondary clinical outcomes significantly favoured MT ( absolute difference in mRS 0–2 of 22 % and adjusted OR 4.9 , 95 % CI 1.2 to 19.7 , p=0.021 ) . Conclusions The trial did not find a significant difference between treatment groups for the primary end point . However , the effect size was consistent with published data and across primary and secondary end points . Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe , improves excellent clinical outcomes and , in the per- protocol population , improves disability-free survival . Trial registration number NCT01745692 ; Results Background and Purpose — Imaging findings can predict outcomes in patients with acute stroke . Relationships between imaging findings and clinical and imaging outcomes in patients r and omized to intravenous tissue-type plasminogen activator – alone versus tissue-type plasminogen activator plus endovascular therapy ( Solitaire device ) in the Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke ( SWIFT PRIME ) study were assessed . Methods — We evaluated associations between imaging assessment s ( baseline mismatch profiles/ischemic core volumes and successful reperfusion ) with imaging outcomes ( 27-hour infa rct volume/growth ) and clinical outcomes ( modified Rankin Scale scores at 90 days ) . Imaging variables that predict favorable clinical outcomes were assessed in both univariate and multivariate models . Results — One hundred and ninety-five patients were included . Successful reperfusion and infa rct volume ( assessed at 27 hours ) were powerful independent predictors of favorable clinical outcomes ( modified Rankin Scale score of 0–2 at 90 days ) . Patients with the target mismatch profile at baseline had a higher rate of reperfusion , lesser infa rct growth , smaller infa rct volumes , and better clinical outcomes in the Solitaire plus tissue-type plasminogen activator ( intervention ) group than those in the tissue-type plasminogen activator – alone ( control ) group . Patients with larger mismatch volumes at baseline had a trend toward better treatment response in the intervention group than patients who had smaller ( < 50 mL ) mismatch volumes . Conclusions — Patients who achieved reperfusion had substantially more favorable clinical and imaging outcomes in both the intervention and the control groups . Infa rct volume at 27 hours strongly correlated with clinical outcome at 90 days in both treatment groups . SWIFT PRIME patients with the target mismatch profile had a highly favorable response to endovascular therapy on both clinical and imaging outcomes . Both reperfusion and infa rct volumes at 27 hours were powerful and independent predictors of 90-day clinical outcomes . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01657461 Introduction The minimal stroke severity justifying endovascular intervention remains elusive ; however , a significant proportion of patients presenting with large vessel occlusion ( LVO ) and mild symptoms subsequently decline and face poor outcomes . Objective To evaluate our experience with these patients by comparing best medical therapy with thrombectomy in an intention-to-treat analysis . Methods Analysis of prospect ively collected data of all consecutive patients with National Institutes of Health Stroke Scale ( NIHSS ) score ≤5 , LVO on CT angiography , and baseline modified Rankin Scale ( mRS ) score 0–2 from November 2014 to May 2016 . After careful discussion with patients /family , a decision to pursue medical or interventional therapy was made . Deterioration ( development of aphasia , neglect , and /or significant weakness ) triggered reconsideration of thrombectomy . The primary outcome measure was NIHSS shift ( discharge NIHSS score minus admission NIHSS score ) . Results Of the 32 patients qualifying for the study , 22 ( 69 % ) were primarily treated with medical therapy and 10 ( 31 % ) intervention . Baseline characteristics were comparable . Nine ( 41 % ) medically treated patients had subsequent deterioration requiring thrombectomy . Median time from arrival to deterioration was 5.2 hours ( 2.0–25.0 ) . Successful reperfusion ( modified Treatment in Cerebral Infa rct ion 2b−3 ) was achieved in all 19 thrombectomy patients . The NIHSS shift significantly favored thrombectomy ( −2.5 vs 0 ; p<0.01 ) . The median NIHSS score at discharge was low with both thrombectomy ( 1 ( 0–3 ) ) and medical therapy ( 2 ( 0.5–4.5 ) ) . 90-Day mRS 0–2 rates were 100 % and 77 % , respectively ( p=0.15 ) . Multivariable linear regression indicated that thrombectomy was independently associated with a beneficial NIHSS shift ( unst and ardized β −4.2 ( 95 % CI −8.2 to −0.1 ) ; p=0.04 ) . Conclusions Thrombectomy led to a shift towards a lower NIHSS in patients with LVO presenting with minimal stroke symptoms . Despite the overall perception that this condition is benign , nearly a quarter of patients primarily treated with medical therapy did not achieve independence at 90 days Background and objective Acute ischemic stroke is a potentially devastating condition and leading cause of morbidity and mortality , affecting an estimated 800 000 people per year in the USA . The natural history of untreated or unrevascularized large vessel occlusions in acute stroke patients results in mortality rates approaching 30 % , with only 25 % achieving good neurologic outcomes at 90 days . Recently , data have demonstrated that early endovascular recanalization of large vessel occlusions results in better outcomes than medical therapy alone . However , the majority of patients in these studies were treated with a stent retriever based approach . The purpose of COMPASS is to evaluate whether patients treated with a direct aspiration first pass ( ADAPT ) approach have non-inferior functional outcomes to those treated with a stent retriever as the firstline ( SRFL ) approach . Material s and methods All patients who meet the inclusion and exclusion criteria and consent to participate will be enrolled at participating centers . Treatment will be r and omly assigned by a central web based system in a 1:1 manner to treatment with either ADAPT or SRFL thrombectomy . Statistical methodology is prespecified with details available in the statistical analysis plan . Results The trial recently completed enrollment , and data collection /verification is ongoing . The final results will be made available on completion of enrollment and follow-up . Conclusions This paper details the design of the COMPASS trial , a r and omized , blinded adjudicator , concurrent , controlled trial of patients treated with either ADAPT or SRFL approaches in order to evaluate whether ADAPT results in non-inferior functional outcome . Trial registration number NCT02466893 , Results Background and Purpose — In acute ischemic stroke , fast and complete recanalization of the occluded vessel is associated with improved outcomes . We describe a novel measure for newer generation devices : the first pass effect ( FPE ) . FPE is defined as achieving a complete recanalization with a single thrombectomy device pass . Methods — The North American Solitaire Acute Stroke Registry data base was used to identify a FPE subgroup . Their baseline features and clinical outcomes were compared with non-FPE patients . Clinical outcome measures included 90-days modified Rankin Scale score , National Institutes of Health Stroke Scale score , mortality , and symptomatic intracranial hemorrhage . Multivariate analyses were performed to determine whether FPE independently result ed in improved outcomes and to identify predictors of FPE . Results — A total of 354 acute ischemic stroke patients underwent thrombectomy in the North American Solitaire Acute Stroke registry . FPE was achieved in 89 out of 354 ( 25.1 % ) . More middle cerebral artery occlusions ( 64 % versus 52.5 % ) and fewer internal carotid artery occlusions ( 10.1 % versus 27.7 % ) were present in the FPE group . Balloon guide catheters were used more frequently with FPE ( 64.0 % versus 34.7 % ) . Median time to revascularization was significantly faster in the FPE group ( median 34 versus 60 minutes ; P=0.0003 ) . FPE was an independent predictor of good clinical outcome ( modified Rankin Scale score ⩽2 was seen in 61.3 % in FPE versus 35.3 % in non-FPE cohort ; P=0.013 ; odds ratio , 1.7 ; 95 % confidence interval , 1.1–2.7 ) . The independent predictors of achieving FPE were use of balloon guide catheters and non-internal carotid artery terminus occlusion . Conclusions — The achievement of complete revascularization from a single Solitaire thrombectomy device pass ( FPE ) is associated with significantly higher rates of good clinical outcome . The FPE is more frequently associated with the use of balloon guide catheters and less likely to be achieved with internal carotid artery terminus occlusion Background and Purpose — The Los Angeles Motor Scale ( LAMS ) is a 3-item , 0- to 10-point motor stroke-deficit scale developed for prehospital use . We assessed the convergent , divergent , and predictive validity of the LAMS when performed by paramedics in the field at multiple sites in a large and diverse geographic region . Methods — We analyzed early assessment and outcome data prospect ively gathered in the FAST-MAG trial ( Field Administration of Stroke Therapy – Magnesium phase 3 ) among patients with acute cerebrovascular disease ( cerebral ischemia and intracranial hemorrhage ) within 2 hours of onset , transported by 315 ambulances to 60 receiving hospitals . Results — Among 1632 acute cerebrovascular disease patients ( age 70±13 years , male 57.5 % ) , time from onset to prehospital LAMS was median 30 minutes ( interquartile range 20–50 ) , onset to early postarrival ( EPA ) LAMS was 145 minutes ( interquartile range 119–180 ) , and onset to EPA National Institutes of Health Stroke Scale was 150 minutes ( interquartile range 120–180 ) . Between the prehospital and EPA assessment s , LAMS scores were stable in 40.5 % , improved in 37.6 % , and worsened in 21.9 % . In tests of convergent validity , against the EPA National Institutes of Health Stroke Scale , correlations were r=0.49 for the prehospital LAMS and r=0.89 for the EPA LAMS . Prehospital LAMS scores did diverge from the prehospital Glasgow Coma Scale , r=−0.22 . Predictive accuracy ( adjusted C statistics ) for nondisabled 3-month outcome was as follows : prehospital LAMS , 0.76 ( 95 % confidence interval 0.74–0.78 ) ; EPA LAMS , 0.85 ( 95 % confidence interval 0.83–0.87 ) ; and EPA National Institutes of Health Stroke Scale , 0.87 ( 95 % confidence interval 0.85–0.88 ) . Conclusions — In this multicenter , prospect i ve , prehospital study , the LAMS showed good to excellent convergent , divergent , and predictive validity , further establishing it as a vali date d instrument to characterize stroke severity in the field Importance Intravenous thrombolysis ( IVT ) followed by mechanical thrombectomy ( MT ) is recommended to treat acute ischemic stroke ( AIS ) with a large vessel occlusion ( LVO ) . Most hospitals do not have on-site MT facilities , and most patients need to be transferred secondarily after IVT ( drip and ship ) , which may have an effect on the neurologic outcome . Objective To compare the functional independence at 3 months between patients treated under the drip- and -ship paradigm and those treated on site ( mothership ) . Design , Setting , and Participants This study used a prospect ively gathered registry of patients with AIS to select patients admitted through the Saint-Antoine and Tenon ( drip and ship ) or the Fondation Rothschild ( mothership ) hospitals from January 1 , 2013 , through April 30 , 2016 . The study included patients older than 18 years treated with bridging therapy for AIS with LVO of the anterior circulation . Among the 159 patients who received MT at the mothership , 100 had been transferred after IVT from the drip- and -ship hospitals and 59 had received IVT on site . Main Outcomes and Measures The main outcome was 3-month functional independence ( modified Rankin scale score ⩽2 ) . Both groups were compared using a multivariate linear model , including variables that were significantly different in the 2 groups . Results During the study period , 497 patients were hospitalized at the drip- and -ship and mothership hospitals for an AIS eligible to reperfusion therapy ; 11 patients had a basilar artery occlusion and were excluded , leaving 100 patients in the drip- and -ship group ( mean age , 73 years ; age range , 60 - 81 years ; 57 men [ 57.0 % ] ) and 59 in the mothership group ( mean age , 70 years ; age range , 58 - 82 years ; 29 men [ 49.2 % ] ) . The proportion of patients with a favorable neurologic outcome at 3 months was similar in both groups ( drip and ship , 61 [ 61.0 % ] ; mothership , 30 [ 50.8 % ] ; P = .26 ) , even after adjusting the analysis for the baseline National Institutes of Health Stroke Scale score , diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score , and general anesthesia ( P = .82 ) . Patients had less severe conditions in the drip- and -ship group ( median baseline National Institutes of Health Stroke Scale score , 15 vs 17 [ P = .03 ] ; median diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score , 7.5 vs 7 [ P = .05 ] ) . Process times were longer in the drip- and -ship group ( onset-to-needle time , 150 vs 135 minutes ; onset-to-puncture time , 248 vs 189 minutes ; and onset-to-recanalization time , 297 vs 240 minutes ; P < .001 ) . Both groups were similar in terms of substantial recanalization ( Thrombolysis in Cerebral Ischemia scores 2B to 3 ; drip and ship , 84 [ 84.0 % ] ; mothership , 47 [ 79.7 % ] ; P = .49 ) and symptomatic hemorrhagic transformation ( drip and ship , 2 [ 2.0 % ] ; mothership , 2 [ 3.4 % ] ; P = .63 ) . Conclusions and Relevance This study found that patients treated under the drip- and -ship paradigm also benefit from bridging therapy , with no statistically significant difference compared with those treated directly in a comprehensive stroke center Background and Purpose — Thrombectomy , primarily with stent retrievers with or without adjunctive aspiration , provided clinical benefit across multiple prospect i ve r and omized trials . Whether this benefit is exclusive to stent retrievers is unclear . Methods — THERAPY ( The R and omized , Concurrent Controlled Trial to Assess the Penumbra System ’s Safety and Effectiveness in the Treatment of Acute Stroke ; NCT01429350 ) was an international , multicenter , prospect i ve , r and omized ( 1:1 ) , open label , blinded end point evaluation , concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase ( IAT ) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm . The primary efficacy end point was the percent of patients achieving independence at 90 days ( modified Rankin Scale score , 0–2 ; intention-to-treat analysis ) . The primary safety end point was the rate of severe adverse events ( SAEs ) by 90 days ( as treated analysis ) . Patients were r and omized 1:1 across 36 centers in 2 countries ( United States and Germany ) . Results — Enrollment was halted after 108 ( 55 IAT and 53 intravenous ) patients ( of 692 planned ) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone . Functional independence was achieved in 38 % IAT and 30 % intravenous intention-to-treat groups ( P=0.52 ) . Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 ( 95 % confidence interval , 0.86–3.59 ; P=0.12 ) in favor of IAT . Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT . No differences in symptomatic intracranial hemorrhage rates ( 9.3 % IAT versus 9.7 % intravenous , P=1.0 ) or 90-day mortality ( IAT : 12 % versus intravenous : 23.9 % , P=0.18 ) were observed . Conclusions — THERAPY did not achieve its primary end point in this underpowered sample . Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit . It is possible that an alternate method of thrombectomy , primary aspiration , will benefit selected patients harboring large vessel occlusions . Further study on this topic is indicated . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01429350 Background and Purpose — Since demonstration of the benefit of endovascular treatment ( EVT ) in acute ischemic stroke patients with proximal arterial occlusion , stroke care systems need to be reorganized to deliver EVT in a timely and equitable way . We analyzed differences in the access to EVT by geographical areas in Catalonia , a territory with a highly de central ized stroke model . Methods — We studied 965 patients treated with EVT from a prospect i ve multicenter population -based registry of stroke patients treated with reperfusion therapies in Catalonia , Spain ( SONIIA ) . Three different areas were defined : ( A ) health areas primarily covered by Comprehensive Stroke Centers , ( B ) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center , and ( C ) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center . We compared the number of EVT × 100 000 inhabitants/year and time from stroke onset to groin puncture between groups . Results — Baseline characteristics were similar between groups . Throughout the study period , there were significant differences in the population rates of EVT across geographical areas . EVT rates by 100 000 in 2015 were 10.5 in A area , 3.7 in B , and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B ( 312 minutes [ 245–435 ] ) and 120 minutes longer in group C ( 350 minutes [ 284–408 ] ) compared with group A ( 230 minutes [ 160–407 ] ; P<0.001 ) . Conclusions — Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers Background and Purpose — The National Institutes of Health Stroke Scale ( NIHSS ) correlates with presence of large anterior vessel occlusion ( LAVO ) . However , the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited . Therefore , we aim ed to evaluate the prognostic value of simple clinical selection strategies . Methods — Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry ( January 2012–May 2014 ) were analyzed retrospectively . Patients with complete breakdown of NIHSS scores and documented vessel status were included . We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO ( internal carotid artery , carotid-terminus or M1-segment of the middle cerebral artery ) . Results — Among 3505 patients , 23.6 % ( n=827 ) had LAVO . Pathological finding on the NIHSS item best gaze was strongly associated with LAVO ( adjusted odds ratio 4.5 , 95 % confidence interval 3.8–5.3 ) . All 3 face – arm – speech – time test ( FAST ) items identified LAVO with high sensitivity . Addition of the item best gaze to the original FAST score ( G-FAST ) or high scores on other simplified stroke scales increased specificity . The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile . If compared with an NIHSS threshold of ≥6 , the prehospital stroke scales performed similarly or even better without losing sensitivity . Conclusions — Simple modification of the face – arm – speech – time score or evaluating the NIHSS symptom profile may help to stratify patients ’ risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers . Prospect i ve validation in the prehospital setting is required Background and Purpose — Retrospective studies have found that patients receiving general anesthesia for endovascular treatment in acute ischemic stroke have worse neurological outcome compared with patients receiving conscious sedation . In this prospect i ve r and omized single-center study , we investigated the impact of anesthesia technique on neurological outcome in acute ischemic stroke patients . Methods — Ninety patients receiving endovascular treatment for acute ischemic stroke in 2013 to 2016 were included and r and omized to general anesthesia or conscious sedation . Difference in neurological outcome at 3 months , measured as modified Rankin Scale score , was analyzed ( primary outcome ) and early neurological improvement of National Institutes of Health Stroke Scale and cerebral infa rct ion volume . Age , sex , comorbidities , admission National Institutes of Health Stroke Scale score , intraprocedural blood pressure , blood glucose , Paco2 and Pco2 modified Thrombolysis in Cerebral Ischemia score , and relevant time intervals were recorded . Results — In the general anesthesia group 19 of 45 patients ( 42.2 % ) and in the conscious sedation group 18 of 45 patients ( 40.0 % ) achieved a modified Rankin Scale score ⩽2 ( P=1.00 ) at 3 months , with no differences in intraoperative blood pressure decline from baseline ( P=0.57 ) ; blood glucose ( P=0.94 ) ; PaCO2 ( P=0.68 ) ; time intervals ( P=0.78 ) ; degree of successful recanalization , 91.1 % versus 88.9 % ( P=1.00 ) ; National Institutes of Health Stroke Scale score at 24 hours 8 ( 3–5 ) versus 9 ( 2–15 ; P=0.60 ) ; infa rct ion volume , 20 ( 10–100 ) versus 20(10–54 ) mL ( P=0.53 ) ; and hospital mortality ( 13.3 % in both groups ; P=1.00 ) . Conclusions — In endovascular treatment for acute ischemic stroke , no difference was found between general anesthesia and conscious sedation in neurological outcome 3 months after stroke . Clinical Trial Registration — URL : https://www . clinical trials.gov . Unique identifier : NCT01872884 Background and Purpose — High blood pressure ( BP ) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke . Whether BP influences the benefit or safety of intra-arterial treatment ( IAT ) is not known . We aim ed to assess the relation of BP with functional outcome , occurrence of symptomatic intracranial hemorrhage and effect of IAT . Methods — This is a post hoc analysis of the MR CLEAN ( Multicenter R and omized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherl and s ) . BP was measured at baseline , before IAT or stroke unit admission . We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis . Effect of BP on the effect of IAT was tested with multiplicative interaction terms . Results — Systolic BP ( SBP ) had the best correlation with functional outcome . This correlation was U-shaped ; both low and high baseline SBP were associated with poor functional outcome . Higher SBP was associated with symptomatic intracranial hemorrhage ( adjusted odds ratio , 1.25 for every 10 mm Hg higher SBP [ 95 % confidence interval , 1.09–1.44 ] ) . Between SBP and IAT , there was no interaction for functional outcome , symptomatic intracranial hemorrhage , or other safety parameters ; the absolute benefit of IAT was evident for the whole SBP range . The same was found for diastolic BP . Conclusions — BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion . Our data provide no arguments to withhold or delay IAT based on BP . Clinical Trial Registration — URL : http://www.is rct n.com . Unique identifier : IS RCT N10888758 Background and Purpose — Proximal large vessel occlusion ( LVO ) is present in up to 30 % of minor strokes . The effectiveness of mechanical thrombectomy ( MT ) in the subgroup of minor stroke with LVO in the anterior circulation is still open to debate . Data about MT in this subgroup of patients are sparse , and their optimal management has not yet been defined . The purpose of this multicenter cohort study was to evaluate the effectiveness of MT in patients experiencing acute ischemic stroke ( AIS ) because of LVO in the anterior circulation , presenting with minor-to-mild stroke symptoms ( National Institutes of Health Stroke Scale score of < 8) . Methods — Multicenter cohort study involving 4 comprehensive stroke centers having 2 therapeutic approaches ( urgent thrombectomy associated with best medical treatment [ BMT ] versus BMT first and MT if worsening occurs ) about management of patients with minor and mild acute ischemic stroke harboring LVO in the anterior circulation . An intention-to-treat analysis was conducted . The primary end point was the rate of excellent outcome defined as the achievement of a modified Rankin Scale score of 0 to 1 at 3 months . Results — Three hundred one patients were included , 170 with urgent MT associated with BMT , and 131 with BMT alone as first-line treatment . Patients treated with MT were younger , more often received intravenous thrombolysis , and had shorter time to imaging . Twenty-four patients ( 18.0 % ) in the medical group had rescue MT because of neurological worsening . Overall , excellent outcome was achieved in 64.5 % of patients , with no difference between the 2 groups . Stratified analysis according to key subgroups did not find heterogeneity in the treatment effect size . Conclusions — Minor-to-mild stroke patients with LVO achieved excellent and favorable functional outcomes at 3 months in similar proportions between urgent MT versus delayed MT associated with BMT . There is thus an urgent need for r and omized trials to define the effectiveness of MT in this patient subgroup Background Current guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy . Currently , no studies exist to guide blood pressure management in patients with stroke treated specifically with mechanical thrombectomy . We aim ed to determine the association between blood pressure parameters within the first 24 hours after mechanical thrombectomy and patient outcomes . Methods and Results We retrospectively studied a consecutive sample of adult patients who underwent mechanical thrombectomy for acute ischemic stroke of the anterior cerebral circulation at 3 institutions from March 2015 to October 2016 . We collected the values of maximum , minimum , and average values of systolic blood pressure , diastolic blood pressure , and mean arterial pressures in the first 24 hours after mechanical thrombectomy . Primary and secondary outcomes were patients ’ functional status at 90 days measured on the modified Rankin scale and the incidence and severity of intracranial hemorrhages within 48 hours . Associations were explored using an ordered multivariable logistic regression analyses . A total of 228 patients were included ( mean age 65.8±14.3 ; 104 males , 45.6 % ) . Maximum systolic blood pressure independently correlated with a worse 90‐day modified Rankin scale and hemorrhagic complications within 48 hours ( adjusted odds ratio=1.02 [ 1.01–1.03 ] , P=0.004 ; 1.02 [ 1.01–1.04 ] , P=0.002 ; respectively ) in multivariable analyses , after adjusting for several possible confounders . Conclusions Higher peak values of systolic blood pressure independently correlated with worse 90‐day modified Rankin scale and a higher rate of hemorrhagic complications . Further prospect i ve studies are warranted to identify whether systolic blood pressure is a therapeutic target to improve outcomes Introduction While effectiveness of mechanical thrombectomy ( MTE ) in M1 segment occlusion is approved for patients with severe impairment , there is a lack of evidence for a potential benefit of MTE in patients with minor to moderate symptoms . The purpose of this study was to evaluate neurological outcome and occurrence of periprocedural complications after MTE in patients with low National Institutes of Health Stroke Scale ( NIHSS ) scores . Material s and methods A retrospective analysis of 1081 consecutive patients with anterior circulation ischemic stroke due to M1 occlusion detected by computed tomography angiography and treated with MTE at our hospital between February 2012 and November 2017 was performed . NIHSS , Barthel Index ( BI ) and modified Rankin Scale ( mRS ) scores between admission and discharge were compared with paired Mann – Whitney test , and recanalization rate and complications were assessed in patients with NIHSS ≤ 5 at admission . Results Thirty patients were included with a median NIHSS score of 4 . NIHSS score ( median : 4 vs. 1 ; p < 0.001 ) , BI ( median : 43 vs. 80 ; p < 0.001 ) and mRS ( 2 vs. 1 ; p < 0.001 ) showed significant improvement from admission to discharge after MTE . Recanalization rate was Thrombolysis in Cerebral Infa rct ion ( TICI ) 2b to 3 in 29 of 30 patients ( 96.7 % ) . One case of an intracerebral reperfusion hematoma ( ECASS : PH2 ) required surgical treatment . Conclusion MTE might lead to a significantly improved clinical outcome also for patients with low NIHSS score due to M1 segment occlusion . Periprocedural complications appeared infrequently . These results encourage further evaluation of the benefit-risk profile of MTE compared to st and ard treatment in patients with low NIHSS scores in future r and omized trials Background and Purpose — Clinical triage scales for prehospital recognition of large vessel occlusion ( LVO ) are limited by low specificity when applied by paramedics . We created the 3-step ambulance clinical triage for acute stroke treatment ( ACT-FAST ) as the first algorithmic LVO identification tool , design ed to improve specificity by recognizing only severe clinical syndromes and optimizing paramedic usability and reliability . Methods — The ACT-FAST algorithm consists of ( 1 ) unilateral arm drift to stretcher < 10 seconds , ( 2 ) severe language deficit ( if right arm is weak ) or gaze deviation/hemineglect assessed by simple shoulder tap test ( if left arm is weak ) , and ( 3 ) eligibility and stroke mimic screen . ACT-FAST examination steps were retrospectively vali date d , and then prospect ively vali date d by paramedics transporting culturally and linguistically diverse patients with suspected stroke in the emergency department , for the identification of internal carotid or proximal middle cerebral artery occlusion . The diagnostic performance of the full ACT-FAST algorithm was then vali date d for patients accepted for thrombectomy . Results — In retrospective ( n=565 ) and prospect i ve paramedic ( n=104 ) validation , ACT-FAST displayed higher overall accuracy and specificity , when compared with existing LVO triage scales . Agreement of ACT-FAST between paramedics and doctors was excellent ( & kgr;=0.91 ; 95 % confidence interval , 0.79–1.0 ) . The full ACT-FAST algorithm ( n=60 ) assessed by paramedics showed high overall accuracy ( 91.7 % ) , sensitivity ( 85.7 % ) , specificity ( 93.5 % ) , and positive predictive value ( 80 % ) for recognition of endovascular-eligible LVO . Conclusions — The 3-step ACT-FAST algorithm shows higher specificity and reliability than existing scales for clinical LVO recognition , despite requiring just 2 examination steps . The inclusion of an eligibility step allowed recognition of endovascular-eligible patients with high accuracy . Using a sequential algorithmic approach eliminates scoring confusion and reduces assessment time . Future studies will test whether field application of ACT-FAST by paramedics to bypass suspected patients with LVO directly to endovascular-capable centers can reduce delays to endovascular thrombectomy Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion . No r and omized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset . Aim The aim of the study is to demonstrate that , among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging , endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke . Design The study is a prospect i ve , r and omized , multicenter , phase III , adaptive , blinded endpoint , controlled trial . A maximum of 476 patients will be r and omized and treated between 6 and 16 h of symptom onset . Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion , and automated software ( RAPID ) determines if the Target Mismatch Profile is present . Patients who meet both clinical and imaging selection criteria are r and omized 1:1 to endovascular therapy plus medical management or medical management alone . The individual endovascular therapist chooses the specific device ( or devices ) employed . Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90 . The secondary endpoint is the proportion of patients with modified Rankin Scale 0–2 at day 90 ( indicating functional independence ) . Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon – Mann – Whitney test ( the generalized likelihood ratio test ) BACKGROUND Trials of endovascular therapy for ischemic stroke have produced variable results . We conducted this study to test whether more advanced imaging selection , recently developed devices , and earlier intervention improve outcomes . METHODS We r and omly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR ( Flow Restoration ) stent retriever or to continue receiving alteplase alone . All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic ( CT ) perfusion imaging . The co primary outcomes were reperfusion at 24 hours and early neurologic improvement ( ≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3 ) . Secondary outcomes included the functional score on the modified Rankin scale at 90 days . RESULTS The trial was stopped early because of efficacy after 70 patients had undergone r and omization ( 35 patients in each group ) . The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group ( median , 100 % vs. 37 % ; P<0.001 ) . Endovascular therapy , initiated at a median of 210 minutes after the onset of stroke , increased early neurologic improvement at 3 days ( 80 % vs. 37 % , P=0.002 ) and improved the functional outcome at 90 days , with more patients achieving functional independence ( score of 0 to 2 on the modified Rankin scale , 71 % vs. 40 % ; P=0.01 ) . There were no significant differences in rates of death or symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging , early thrombectomy with the Solitaire FR stent retriever , as compared with alteplase alone , improved reperfusion , early neurologic recovery , and functional outcome . ( Funded by the Australian National Health and Medical Research Council and others ; EXTEND-IA Clinical Trials.gov number , NCT01492725 , and Australian New Zeal and Clinical Trials Registry number , ACTRN12611000969965 . ) Importance Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from r and omized trials . Objective To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy . Design , Setting , and Participants SIESTA ( Sedation vs Intubation for Endovascular Stroke Treatment ) , a single-center , r and omized , parallel-group , open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany ( April 2014-February 2016 ) included 150 patients with acute ischemic stroke in the anterior circulation , higher National Institutes of Health Stroke Scale ( NIHSS ) score ( > 10 ) , and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery . Intervention Patients were r and omly assigned to an intubated general anesthesia group ( n = 73 ) or a nonintubated conscious sedation group ( n = 77 ) during stroke thrombectomy . Main Outcomes and Measures Primary outcome was early neurological improvement on the NIHSS after 24 hours ( 0 - 42 [ none to most severe neurological deficits ; a 4-point difference considered clinical ly relevant ] ) . Secondary outcomes were functional outcome by modified Rankin Scale ( mRS ) after 3 months ( 0 - 6 [ symptom free to dead ] ) , mortality , and peri-interventional parameters of feasibility and safety . Results Among 150 patients ( 60 women [ 40 % ] ; mean age , 71.5 years ; median NIHSS score , 17 ) , primary outcome was not significantly different between the general anesthesia group ( mean NIHSS score , 16.8 at admission vs 13.6 after 24 hours ; difference , -3.2 points [ 95 % CI , -5.6 to -0.8 ] ) vs the conscious sedation group ( mean NIHSS score , 17.2 at admission vs 13.6 after 24 hour ; difference , -3.6 points [ 95 % CI , -5.5 to -1.7 ] ) ; mean difference between groups , -0.4 ( 95 % CI , -3.4 to 2.7 ; P = .82 ) . Of 47 prespecified secondary outcomes analyzed , 41 showed no significant differences . In the general anesthesia vs the conscious sedation group , substantial patient movement was less frequent ( 0 % vs 9.1 % ; difference , 9.1 % ; P = .008 ) , but postinterventional complications were more frequent for hypothermia ( 32.9 % vs 9.1 % ; P < .001 ) , delayed extubation ( 49.3 % vs 6.5 % ; P < .001 ) , and pneumonia ( 13.7 % vs 3.9 % ; P = .03 ) . More patients were functionally independent ( unadjusted mRS score , 0 to 2 after 3 months [ 37.0 % in the general anesthesia group vs 18.2 % in the conscious sedation group P = .01 ] ) . There were no differences in mortality at 3 months ( 24.7 % in both groups ) . Conclusions and Relevance Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy , conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours . The study findings do not support an advantage for the use of conscious sedation . Trial Registration clinical trials.gov Identifier : NCT02126085 PURPOSE To describe the use of an imaging selection tool , multiphase computed tomographic ( CT ) angiography , in patients with acute ischemic stroke ( AIS ) and to demonstrate its interrater reliability and ability to help determine clinical outcome . MATERIAL S AND METHODS The local ethics board approved this study . Data are from the pilot phase of PRoveIT , a prospect i ve observational study analyzing utility of multimodal imaging in the triage of patients with AIS . Patients underwent baseline unenhanced CT , single-phase CT angiography of the head and neck , multiphase CT angiography , and perfusion CT . Multiphase CT angiography generates time-resolved images of pial arteries . Pial arterial filling was scored on a six-point ordinal scale , and interrater reliability was tested . Clinical outcomes included a 50 % or greater decrease in National Institutes of Health Stroke Scale ( NIHSS ) over 24 hours and 90-day modified Rankin Scale ( mRS ) score of 0 - 2 . The ability to predict clinical outcomes was compared between single-phase CT angiography , multiphase CT angiography , and perfusion CT by using receiver operating curve analysis , Akaike information criterion ( AIC ) , and Bayesian information criterion ( BIC ) . RESULTS A total of 147 patients were included . Interrater reliability for multiphase CT angiography is excellent ( n = 30 , κ = 0.81 , P < .001 ) . At receiver operating characteristic curve analysis , the ability to predict clinical outcome is modest ( C statistic = 0.56 , 95 % confidence interval [ CI ] : 0.52 , 0.63 for ≥50 % decrease in NIHSS over 24 hours ; C statistic = 0.6 , 95 % CI : 0.53 , 0.68 for 90-day mRS score of 0 - 2 ) but better than that of models using single-phase CT angiography and perfusion CT ( P < .05 overall ) . With AIC and BIC , models that use multiphase CT angiography are better than models that use single-phase CT angiography and perfusion CT for a decrease of 50 % or more in NIHSS over 24 hours ( AIC = 166 , BIC = 171.7 ; values were lowest for multiphase CT angiography ) and a 90-day mRS score of 0 - 2 ( AIC = 132.1 , BIC = 137.4 ; values were lowest for multiphase CT angiography ) . CONCLUSION Multiphase CT angiography is a reliable tool for imaging selection in patients with AIS Background and Purpose — Intravenous alteplase ( rtPA ) remains the only approved treatment for acute ischemic stroke , but its use remains limited . In a previous pilot dose-escalation study , intravenous tenecteplase showed promise as a potentially safer alternative . Therefore , a Phase IIB clinical trial was begun to ( 1 ) choose a best dose of tenecteplase to carry forward ; and ( 2 ) to provide evidence for either promise or futility of further testing of tenecteplase versus rtPA . If promise was established , then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to st and ard rtPA . Methods — The trial began as a small , multicenter , r and omized , double-blind , controlled clinical trial comparing 0.1 , 0.25 , and 0.4 mg/kg tenecteplase with st and ard 0.9 mg/kg rtPA in patients with acute stroke within 3 hours of onset . An adaptive sequential design used an early ( 24-hour ) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage to choose a “ best ” dose of tenecteplase to carry forward . Once a “ best ” dose was established , the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus st and ard rtPA could be compared by 3-month outcome using the modified Rankin Scale in an interim analysis . Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III . Results — The trial was prematurely terminated for slow enrollment after only 112 patients had been r and omized at 8 clinical centers between 2006 and 2008 . The 0.4-mg/kg dose was discarded as inferior after only 73 patients were r and omized , but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped . There were no statistically persuasive differences in 3-month outcomes between the remaining tenecteplase groups and rtPA . Symptomatic intracranial hemorrhage rates were highest in the discarded 0.4-mg/kg tenecteplase group and lowest ( 0 of 31 ) in the 0.1-mg/kg tenecteplase group . Neither promise nor futility could be established . Conclusion — This prematurely terminated trial has demonstrated the potential efficiency of a novel design in selecting a propitious dose for future study of a new thrombolytic agent for acute stroke . Given the truncation of the trial , no convincing conclusions can be made about the promise of future study of tenecteplase in acute stroke Objective : To test the transferability of the Helsinki stroke thrombolysis model that achieved a median 20-minute door-to-needle time ( DNT ) to an Australian health care setting . Methods : The existing “ code stroke ” model at the Royal Melbourne Hospital was evaluated and restructured to include key components of the Helsinki model : 1 ) ambulance prenotification with patient details alerting the stroke team to meet the patient on arrival ; 2 ) patients transferred directly from triage onto the CT table on the ambulance stretcher ; and 3 ) tissue plasminogen activator ( tPA ) delivered in CT immediately after imaging . We analyzed our prospect i ve , consecutive tPA registry for effects of these protocol changes on our DNT after implementation during business hours ( 8 am to 5 pm Monday – Friday ) from May 2012 . Results : There were 48 patients treated with tPA in the 8 months after the protocol change . Compared with 85 patients treated in 2011 , the median ( interquartile range ) DNT was reduced from 61 ( 43–75 ) minutes to 46 ( 24–79 ) minutes ( p = 0.040 ) . All of the effect came from the change in the in-hours DNT , down from 43 ( 33–59 ) to 25 ( 19–48 ) minutes ( p = 0.009 ) , whereas the out-of-hours delays remain unchanged , from 67 ( 55–82 ) to 62 ( 44–95 ) minutes ( p = 0.835 ) . Conclusion : We demonstrated rapid transferability of an optimized tPA protocol to a different health care setting . With the cooperation of ambulance , emergency , and stroke teams , we succeeded in the absence of a dedicated neurologic emergency department or electronic patient records , which are features of the Finnish system . The next challenge is providing the same service out-of-hours BACKGROUND Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase . Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results . We aim ed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis . METHODS This phase 3 , r and omised , open-label , blinded endpoint , superiority trial was done in 13 stroke units in Norway . We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms , or who were eligible for bridging therapy before thrombectomy . Patients were r and omly assigned ( 1:1 ) to receive intravenous tenecteplase 0·4 mg/kg ( to a maximum of 40 mg ) or alteplase 0·9 mg/kg ( to a maximum of 90 mg ) , via a block r and omisation schedule stratified by centre of inclusion . Patients were not informed of treatment allocation ; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not . The primary outcome was excellent functional outcome defined as modified Rankin Scale ( mRS ) score 0 - 1 at 3 months . The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data . This study is registered with Clinical Trials.gov , number NCT01949948 . FINDINGS Between Sept 1 , 2012 , and Sept 30 , 2016 , 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered . 1100 patients were r and omly assigned to the tenecteplase ( n=549 ) or alteplase ( n=551 ) groups . The median age of participants was 77 years ( IQR 64 - 79 ) and the median National Institutes of Health Stroke Scale score at baseline was 4 points ( IQR 2 - 8 ) . A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 ( 18 % ) patients in the tenecteplase group and 91 ( 17 % ) patients in the alteplase group . The primary outcome was achieved by 354 ( 64 % ) patients in the tenecteplase group and 345 ( 63 % ) patients in the alteplase group ( odds ratio 1·08 , 95 % CI 0·84 - 1·38 ; p=0·52 ) . By 3 months , 29 ( 5 % ) patients had died in the tenecteplase group compared with 26 ( 5 % ) in the alteplase group . The frequency of serious adverse events was similar between groups ( 145 [ 26 % ] in the tenecteplase group vs 141 [ 26 % ] in the alteplase group ; p=0·74 ) . INTERPRETATION Tenecteplase was not superior to alteplase and showed a similar safety profile . Most patients enrolled in this study had mild stroke . Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase . FUNDING Research Council of Norway BACKGROUND We aim ed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population -based stroke reperfusion registry . METHODS During a 2-year period at four centers in Catalonia , Spain , we r and omly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy ( including intravenous alteplase when eligible ) and endovascular therapy with the Solitaire stent retriever ( thrombectomy group ) or medical therapy alone ( control group ) . All patients had confirmed proximal anterior circulation occlusion and the absence of a large infa rct on neuroimaging . In all study patients , the use of alteplase either did not achieve revascularization or was contraindicated . The primary outcome was the severity of global disability at 90 days , as measured on the modified Rankin scale ( ranging from 0 [ no symptoms ] to 6 [ death ] ) . Although the maximum planned sample size was 690 , enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials . RESULTS Thrombectomy reduced the severity of disability over the range of the modified Rankin scale ( adjusted odds ratio for improvement of 1 point , 1.7 ; 95 % confidence interval [ CI ] , 1.05 to 2.8 ) and led to higher rates of functional independence ( a score of 0 to 2 ) at 90 days ( 43.7 % vs. 28.2 % ; adjusted odds ratio , 2.1 ; 95 % CI , 1.1 to 4.0 ) . At 90 days , the rates of symptomatic intracranial hemorrhage were 1.9 % in both the thrombectomy group and the control group ( P=1.00 ) , and rates of death were 18.4 % and 15.5 % , respectively ( P=0.60 ) . Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals . CONCLUSIONS Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset , stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence . ( Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others ; REVASCAT Clinical Trials.gov number , NCT01692379 . ) BACKGROUND Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation , less than 40 % regain functional independence when treated with intravenous tissue plasminogen activator ( t-PA ) alone . Thrombectomy with the use of a stent retriever , in addition to intravenous t-PA , increases reperfusion rates and may improve long-term functional outcome . METHODS We r and omly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone ( control group ) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset ( intervention group ) . Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions . The primary outcome was the severity of global disability at 90 days , as assessed by means of the modified Rankin scale ( with scores ranging from 0 [ no symptoms ] to 6 [ death ] ) . RESULTS The study was stopped early because of efficacy . At 39 centers , 196 patients underwent r and omization ( 98 patients in each group ) . In the intervention group , the median time from qualifying imaging to groin puncture was 57 minutes , and the rate of substantial reperfusion at the end of the procedure was 88 % . Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale ( P<0.001 ) . The rate of functional independence ( modified Rankin scale score , 0 to 2 ) was higher in the intervention group than in the control group ( 60 % vs. 35 % , P<0.001 ) . There were no significant between-group differences in 90-day mortality ( 9 % vs. 12 % , P=0.50 ) or symptomatic intracranial hemorrhage ( 0 % vs. 3 % , P=0.12 ) . CONCLUSIONS In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation , thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days . ( Funded by Covidien ; SWIFT PRIME Clinical Trials.gov number , NCT01657461 . ) BACKGROUND Until recently , the benefits of endovascular treatment in stroke were not proven . Care trials have been design ed to simultaneously offer yet-to-be vali date d interventions and verify treatment outcomes . Our aim was to implement a care trial for patients with acute ischemic stroke . METHODS The study was offered to all patients considered for endovascular management of acute ischemic stroke in one Canadian hospital . Inclusion criteria were broad : onset of symptoms≤5h or at any time in the presence of clinical -imaging mismatch and suspected or demonstrated proximal large vessel occlusion . Exclusion criteria were few : established infa rct ion or hemorrhagic transformation of the target symptomatic territory and poor 3-month prognosis . The primary outcome was mRS≤2 at 3 months . Patients were r and omly allocated to st and ard care or st and ard care plus endovascular treatment . Clinical Trials.gov : Identifier NCT02157532 . RESULTS Seventy-seven patients were recruited in 19 months ( March 2013-October 2014 ) at a single center . R and omized allocation was interrupted when other trials showed the benefits of endovascular therapy . At 3 months , 20 of 40 patients ( 50.0 % ; 95 % CI : 35%-65 % ) in the intervention group had reached the primary outcome , compared to 14 of 37 patients ( 37.8 % ; 95 % CI : 24%-54 % ) in the control group ( P=0.36 ) . Eleven patients in the intervention group died within 3 months compared to 9 patients in the st and ard care group . CONCLUSION A care trial was implemented to offer verifiable care to acute stroke patients . This approach offers a promising means to manage clinical dilemmas and guide uncertain practice BACKGROUND Treatment strategies for acute basilar artery occlusion ( BAO ) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories , and information on the efficacy of different treatments in unselected patients with BAO is scarce . We therefore assessed outcomes and differences in treatment response after BAO . METHODS The Basilar Artery International Cooperation Study ( BASICS ) is a prospect i ve , observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1 , 2002 , and October 1 , 2007 . Stroke severity at time of treatment was dichotomised as severe ( coma , locked-in state , or tetraplegia ) or mild to moderate ( any deficit that was less than severe ) . Outcome was assessed at 1 month . Poor outcome was defined as a modified Rankin scale score of 4 or 5 , or death . Patients were divided into three groups according to the treatment they received : antithrombotic treatment only ( AT ) , which comprised antiplatelet drugs or systemic anticoagulation ; primary intravenous thrombolysis ( IVT ) , including subsequent intra-arterial thrombolysis ; or intra-arterial therapy ( IAT ) , which comprised thrombolysis , mechanical thrombectomy , stenting , or a combination of these approaches . Risk ratios ( RR ) for treatment effects were adjusted for age , the severity of neurological deficits at the time of treatment , time to treatment , prodromal minor stroke , location of the occlusion , and diabetes . FINDINGS 619 patients were entered in the registry . 27 patients were excluded from the analyses because they did not receive AT , IVT , or IAT , and all had a poor outcome . Of the 592 patients who were analysed , 183 were treated with only AT , 121 with IVT , and 288 with IAT . Overall , 402 ( 68 % ) of the analysed patients had a poor outcome . No statistically significant superiority was found for any treatment strategy . Compared with outcome after AT , patients with a mild-to-moderate deficit ( n=245 ) had about the same risk of poor outcome after IVT ( adjusted RR 0.94 , 95 % CI 0.60 - 1.45 ) or after IAT ( adjusted RR 1.29 , 0.97 - 1.72 ) but had a worse outcome after IAT compared with IVT ( adjusted RR 1.49 , 1.00 - 2.23 ) . Compared with AT , patients with a severe deficit ( n=347 ) had a lower risk of poor outcome after IVT ( adjusted RR 0.88 , 0.76 - 1.01 ) or IAT ( adjusted RR 0.94 , 0.86 - 1.02 ) , whereas outcomes were similar after treatment with IAT or IVT ( adjusted RR 1.06 , 0.91 - 1.22 ) . INTERPRETATION Most patients in the BASICS registry received IAT . Our results do not support unequivocal superiority of IAT over IVT , and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a r and omised controlled trial . FUNDING Department of Neurology , University Medical Center Utrecht BACKGROUND In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion , intraarterial treatment is highly effective for emergency revascularization . However , proof of a beneficial effect on functional outcome is lacking . METHODS We r and omly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone . Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset . The primary outcome was the modified Rankin scale score at 90 days ; this categorical scale measures functional outcome , with scores ranging from 0 ( no symptoms ) to 6 ( death ) . The treatment effect was estimated with ordinal logistic regression as a common odds ratio , adjusted for prespecified prognostic factors . The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores , as compared with usual care alone ( shift analysis ) . RESULTS We enrolled 500 patients at 16 medical centers in The Netherl and s ( 233 assigned to intraarterial treatment and 267 to usual care alone ) . The mean age was 65 years ( range , 23 to 96 ) , and 445 patients ( 89.0 % ) were treated with intravenous alteplase before r and omization . Retrievable stents were used in 190 of the 233 patients ( 81.5 % ) assigned to intraarterial treatment . The adjusted common odds ratio was 1.67 ( 95 % confidence interval [ CI ] , 1.21 to 2.30 ) . There was an absolute difference of 13.5 percentage points ( 95 % CI , 5.9 to 21.2 ) in the rate of functional independence ( modified Rankin score , 0 to 2 ) in favor of the intervention ( 32.6 % vs. 19.1 % ) . There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation , intraarterial treatment administered within 6 hours after stroke onset was effective and safe . ( Funded by the Dutch Heart Foundation and others ; MR CLEAN Netherl and s Trial Registry number , NTR1804 , and Current Controlled Trials number , IS RCT N10888758 . ) 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 : Endovascular treatment with mechanical thrombectomy ( MT ) is beneficial for patients with acute stroke suffering a large-vessel occlusion , although treatment efficacy is highly time-dependent . We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation . Methods : STRATIS ( Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke ) was a prospect i ve , multicenter , observational , single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years , including 1000 patients with severe stroke and treated within 8 hours . Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation . The primary clinical outcome was functional independence ( modified Rankin Score 0–2 ) at 90 days . We assessed ( 1 ) real-world time metrics of stroke care delivery , ( 2 ) outcome differences between direct and transfer patients undergoing MT , and ( 3 ) the potential impact of local hospital bypass . Results : A total of 984 patients were analyzed . Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P<0.001 ) . Clinical outcomes were better in the direct group , with 60.0 % ( 299/498 ) achieving functional independence compared with 52.2 % ( 213/408 ) in the transfer group ( odds ratio , 1.38 ; 95 % confidence interval , 1.06–1.79 ; P=0.02 ) . Likewise , excellent outcome ( modified Rankin Score 0–1 ) was achieved in 47.4 % ( 236/498 ) of direct patients versus 38.0 % ( 155/408 ) of transfer patients ( odds ratio , 1.47 ; 95 % confidence interval , 1.13–1.92 ; P=0.005 ) . Mortality did not differ between the 2 groups ( 15.1 % for direct , 13.7 % for transfer ; P=0.55 ) . Intravenous tissue plasminogen activator did not impact outcomes . Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes , but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers . If bypass is limited to a 20-mile radius from onset , then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier . Conclusions : In this large , real-world study , interhospital transfer was associated with significant treatment delays and lower chance of good outcome . Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT02239640 Background and Purpose — The utility of computed tomographic perfusion (CTP)–based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in r and omized trials and requires further study in a cohort that was not selected based on CTP . Our objective was to study the relationship between CTP-derived parameters and outcome and treatment effect in patients with acute ischemic stroke because of a proximal intracranial arterial occlusion . Methods — We included 175 patients who underwent CTP in the Multicenter R and omized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherl and s ( MR CLEAN ) . Association of CTP-derived parameters ( ischemic-core volume , penumbra volume , and percentage ischemic core ) with outcome was estimated with multivariable ordinal logistic regression as an adjusted odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale . Interaction between CTP-derived parameters and treatment effect was determined using multivariable ordinal logistic regression . Interaction with treatment effect was also tested for mismatch ( core < 70 mL ; penumbra core > 1.2 ; penumbra core > 10 mL ) . Results — The adjusted odds ratio for improved functional outcome for ischemic core , percentage ischemic core , and penumbra were 0.79 per 10 mL ( 95 % confidence interval : 0.71–0.89 ; P<0.001 ) , 0.82 per 10 % ( 95 % confidence interval : 0.66–0.90 ; P=0.002 ) , and 0.97 per 10 mL ( 96 % confidence interval : 0.92–1.01 ; P=0.15 ) , respectively . No significant interaction between any of the CTP-derived parameters and treatment effect was observed . We observed no significant interaction between mismatch and treatment effect . Conclusions — CTP seems useful for predicting functional outcome , but can not reliably identify patients who will not benefit from intra-arterial therapy Background : In population -based studies , patients presenting with minor or mild stroke symptoms represent about two-thirds of stroke patients , and almost one-third of these patients are unable to ambulate independently at the time of discharge . Although mechanical thrombectomy ( MT ) has become the st and ard of care for acute ischaemic stroke with proximal large vessel occlusion ( LVO ) in the anterior circulation , the management of patients harbouring proximal occlusion and minor-to-mild stroke symptoms has not yet been determined by recent trials . The purpose of this study was to evaluate the impact of reperfusion on clinical outcome in low National Institutes of Health Stroke Scale ( NIHSS ) patients treated with MT . Methods : We analysed 138 consecutive patients with acute LVO of the anterior circulation ( middle cerebral artery M1 or M2 segment , internal carotid artery or t and em occlusion ) with NIHSS < 8 , having undergone MT in 3 different centres . Reperfusion was grade d using the modified thrombolysis in cerebral infa rct ion ( TICI ) score and 3 grade s were defined , ranging from failed or poor reperfusion ( TICI 0 , 1 , 2A ) to complete reperfusion ( TICI 3 ) . The primary clinical endpoint was an excellent outcome defined as a modified Rankin score ( mRs ) 0 - 1 at 3-months . The impact of reperfusion grade was assessed in univariate and multivariate analyses . The secondary endpoints included favourable functional outcome ( 90-day mRS 0 - 2 ) , death and safety concerns . Results : Successful reperfusion was achieved in 81.2 % of patients ( TICI 2B , n = 47 ; TICI 3 , n = 65 ) . Excellent outcome ( mRs 0 - 1 ) was achieved in 69 patients ( 65.0 % ) and favourable outcome ( mRs ≤2 ) in 108 ( 78.3 % ) . Death occurred in 7 ( 5.1 % ) . Excellent outcome increased with reperfusion grade s , with a rate of 34.6 % in patients with failed/poor reperfusion , 61.7 % in patients with TICI 2B reperfusion , and 78.5 % in patients with TICI 3 reperfusion ( p < 0.001 ) . In multivariate analysis adjusted for patient characteristics associated with excellent outcome , the reperfusion grade remained significantly associated with an increase in excellent outcome ; the OR ( 95 % CI ) was 3.09 ( 1.06 - 9.03 ) for TICI 2B and 6.66 ( 2.27 - 19.48 ) for TICI 3 , using the failed/poor reperfusion grade as reference . Similar results were found regarding favourable outcome ( 90-day mRs 0 - 2 ) or overall mRS distribution ( shift analysis ) . Conclusion : Successful reperfusion is strongly associated with better functional outcome among patients with proximal LVO in the anterior circulation and minor-to-mild stroke symptoms . R and omized controlled studies are m and atory to assess the benefit of MT compared with optimal medical management in this subset of patients Background and Purpose — We aim ed to develop and vali date a simple prehospital stroke scale to predict the presence of large vessel occlusion ( LVO ) in patients with acute stroke . Methods — The Rapid Arterial oCclusion Evaluation ( RACE ) scale was design ed based on the National Institutes of Health Stroke Scale ( NIHSS ) items with a higher predictive value of LVO on a retrospective cohort of 654 patients with acute ischemic stroke : facial palsy ( scored 0–2 ) , arm motor function ( 0–2 ) , leg motor function ( 0–2 ) , gaze ( 0–1 ) , and aphasia or agnosia ( 0–2 ) . Thereafter , the RACE scale was vali date d prospect ively in the field by trained medical emergency technicians in 357 consecutive patients transferred by Emergency Medical Services to our Comprehensive Stroke Center . Neurologists evaluated stroke severity at admission and LVO was diagnosed by transcranial duplex , computed tomography , or MR angiography . Receiver operating curve , sensitivity , specificity , and global accuracy of the RACE scale were analyzed to evaluate its predictive value for LVO . Results — In the prospect i ve cohort , the RACE scale showed a strong correlation with NIHSS ( r=0.76 ; P<0.001 ) . LVO was detected in 76 of 357 patients ( 21 % ) . Receiver operating curves showed a similar capacity to predict LVO of the RACE scale compared with the NIHSS ( area under the curve 0.82 and 0.85 , respectively ) . A RACE scale ≥5 had sensitivity 0.85 , specificity 0.68 , positive predictive value 0.42 , and negative predictive value 0.94 for detecting LVO . Conclusions — The RACE scale is a simple tool that can accurately assess stroke severity and identify patients with acute stroke with large artery occlusion at prehospital setting by medical emergency technicians OBJECTIVE To develop an abbreviated and practical neurologic scale that could assist emergency medical services or triage personnel in identifying patients with stroke . METHODS A prospect i ve , observational , cohort study was performed at university-based EDs . Participants were 74 patients treated in a thrombolytic stroke trial and 225 consecutive non-stroke patients evaluated during 4 r and om 12-hour shifts in the ED . Scores on the NIH Stroke Scale were obtained for all patients by physicians . Items of this scale were modified and recoded to a binomial ( normal or abnormal ) scale . Serial univariate analyses using chi 2 were performed to rank items . Recursive partitioning was then performed to develop the decision rule for predicting the presence of stroke . RESULTS Three items identified 100 % of patients with stroke : facial palsy , motor arm , and dysarthria . An Abbreviated NIH Stroke Scale based on these items had a sensitivity of 100 % and a specificity of 92 % . A proposed Out-of-hospital NIH Stroke Scale consisting of facial palsy , motor arm , and a combination of dysarthria and best language items ( abnormal speech ) had a sensitivity of 100 % and a specificity of 88 % . CONCLUSION Using the derivation data set , a proposed Out-of-hospital NIH Stroke Scale had a high sensitivity and specificity for identifying patients with stroke when performed by physicians in this group of 299 ED patients . Prospect i ve studies of other health care professionals using the scale in the out-of-hospital arena are needed BACKGROUND Intravenous alteplase is the only approved treatment for acute ischemic stroke . Tenecteplase , a genetically engineered mutant tissue plasminogen activator , is an alternative thrombolytic agent . METHODS In this phase 2B trial , we r and omly assigned 75 patients to receive alteplase ( 0.9 mg per kilogram of body weight ) or tenecteplase ( 0.1 mg per kilogram or 0.25 mg per kilogram ) less than 6 hours after the onset of ischemic stroke . To favor the selection of patients most likely to benefit from thrombolytic therapy , the eligibility criteria were a perfusion lesion at least 20 % greater than the infa rct core on computed tomographic ( CT ) perfusion imaging at baseline and an associated vessel occlusion on CT angiography . The co primary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale ( NIHSS , a 42-point scale on which higher scores indicate more severe neurologic deficits ) . RESULTS The three treatment groups each comprised 25 patients . The mean ( ±SD ) NIHSS score at baseline for all patients was 14.4±2.6 , and the time to treatment was 2.9±0.8 hours . Together , the two tenecteplase groups had greater reperfusion ( P=0.004 ) and clinical improvement ( P<0.001 ) at 24 hours than the alteplase group . There were no significant between-group differences in intracranial bleeding or other serious adverse events . The higher dose of tenecteplase ( 0.25 mg per kilogram ) was superior to the lower dose and to alteplase for all efficacy outcomes , including absence of serious disability at 90 days ( in 72 % of patients , vs. 40 % with alteplase ; P=0.02 ) . CONCLUSIONS Tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging . ( Funded by the Australian National Health and Medical Research Council ; Australia New Zeal and Clinical Trials Registry number , ACTRN12608000466347 . ) BACKGROUND Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke . Tenecteplase , which is more fibrin‐specific and has longer activity than alteplase , is given as a bolus and may increase the incidence of vascular reperfusion . METHODS We r and omly assigned patients with ischemic stroke who had occlusion of the internal carotid , basilar , or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase ( at a dose of 0.25 mg per kilogram of body weight ; maximum dose , 25 mg ) or alteplase ( at a dose of 0.9 mg per kilogram ; maximum dose , 90 mg ) within 4.5 hours after symptom onset . The primary outcome was reperfusion of greater than 50 % of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment . Noninferiority of tenecteplase was tested , followed by superiority . Secondary outcomes included the modified Rankin scale score ( on a scale from 0 [ no neurologic deficit ] to 6 [ death ] ) at 90 days . Safety outcomes were death and symptomatic intracerebral hemorrhage . RESULTS Of 202 patients enrolled , 101 were assigned to receive tenecteplase and 101 to receive alteplase . The primary outcome occurred in 22 % of the patients treated with tenecteplase versus 10 % of those treated with alteplase ( incidence difference , 12 percentage points ; 95 % confidence interval [ CI ] , 2 to 21 ; incidence ratio , 2.2 ; 95 % CI , 1.1 to 4.4 ; P=0.002 for noninferiority ; P=0.03 for superiority ) . Tenecteplase result ed in a better 90‐day functional outcome than alteplase ( median modified Rankin scale score , 2 vs. 3 ; common odds ratio , 1.7 ; 95 % CI , 1.0 to 2.8 ; P=0.04 ) . Symptomatic intracerebral hemorrhage occurred in 1 % of the patients in each group . CONCLUSIONS Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset . ( Funded by the National Health and Medical Research Council of Australia and others ; EXTEND‐IA TNK Clinical Trials.gov number , NCT02388061 . BACKGROUND AND PURPOSE : In past years , thrombectomy has become a widely used procedure in interventional neuroradiology for the treatment of acute intracranial occlusions . However , in 10–20 % of patients , there are additional occlusions or stenotic lesions of the ipsilateral cervical internal carotid artery . The purpose of this study was to evaluate the feasibility of emergency carotid artery stent placement in combination with intracranial thrombectomy and the clinical outcome of the treated patients . MATERIAL S AND METHODS : We analyzed clinical and angiographic data of patients who underwent emergency cervical ICA stent placement and intracranial thrombectomy with stent-retriever devices in our institution between November 2009 and July 2012 . Recanalization was assessed according to the Thrombolysis in Cerebral-Infa rct ion score . Clinical outcome was evaluated at discharge ( NIHSS ) and after 3 months ( mRS ) . RESULTS : Overall , 24 patients were treated . The mean age was 67.2 years ; mean occlusion time , 230.2 minutes . On admission , the median NIHSS score was 18 . In all patients , the Thrombolysis in Cerebral Infa rct ion score was zero before the procedure . Stent implantation was feasible in all cases . In 15 patients ( 62.5 % ) , a Thrombolysis in Cerebral Infa rct ion score ≥ 2b could be achieved . Six patients ( 25 % ) improved ≥10 NIHSS points between admission and discharge . After 90 days , the median mRS score was 3.0 . Seven patients ( 29.2 % ) had a good clinical outcome ( mRS 0–2 ) , and 4 patients ( 16.6 % ) died , 1 due to fatal intracranial hemorrhage . Overall , symptomatic intracranial hemorrhage occurred in 4 patients ( 16.6 % ) . CONCLUSIONS : Emergency ICA stent implantation was technically feasible in all patients , and the intracranial recanalization Thrombolysis in Cerebral Infa rct ion score of ≥2b was reached in a high number of patients . Clinical outcome and mortality seem to be acceptable for a cohort with severe stroke . However , a high rate of symptomatic intracranial hemorrhage occurred in our study BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear . METHODS In this study , we r and omly assigned patients within 8 hours after the onset of large-vessel , anterior-circulation strokes to undergo mechanical embolectomy ( Merci Retriever or Penumbra System ) or receive st and ard care . All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain . R and omization was stratified according to whether the patient had a favorable penumbral pattern ( substantial salvageable tissue and small infa rct core ) or a nonpenumbral pattern ( large core or small or absent penumbra ) . We assessed outcomes using the 90-day modified Rankin scale , ranging from 0 ( no symptoms ) to 6 ( dead ) . RESULTS Among 118 eligible patients , the mean age was 65.5 years , the mean time to enrollment was 5.5 hours , and 58 % had a favorable penumbral pattern . Revascularization in the embolectomy group was achieved in 67 % of the patients . Ninety-day mortality was 21 % , and the rate of symptomatic intracranial hemorrhage was 4 % ; neither rate differed across groups . Among all patients , mean scores on the modified Rankin scale did not differ between embolectomy and st and ard care ( 3.9 vs. 3.9 , P=0.99 ) . Embolectomy was not superior to st and ard care in patients with either a favorable penumbral pattern ( mean score , 3.9 vs. 3.4 ; P=0.23 ) or a nonpenumbral pattern ( mean score , 4.0 vs. 4.4 ; P=0.32 ) . In the primary analysis of scores on the 90-day modified Rankin scale , there was no interaction between the pretreatment imaging pattern and treatment assignment ( P=0.14 ) . CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke , nor was embolectomy shown to be superior to st and ard care . ( Funded by the National Institute of Neurological Disorders and Stroke ; MR RESCUE Clinical Trials.gov number , NCT00389467 . ) Background Despite recent advances in acute stroke treatment , basilar artery occlusion ( BAO ) is associated with a death or disability rate of close to 70 % . R and omised trials have shown the safety and efficacy of intravenous thrombolysis ( IVT ) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke , but these results do not directly apply to patients with an acute BAO because only few , if any , of these patients were included in r and omised acute stroke trials . Recently the results of the Basilar Artery International Cooperation Study ( BASICS ) , a prospect i ve registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment ( IAT ) is superior to IVT . Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely . Design BASICS is a r and omised controlled , multicentre , open label , phase III intervention trial with blinded outcome assessment , investigating the efficacy and safety of additional IAT after IVT in patients with BAO . The trial targets to include 750 patients , aged 18 to 85 years , with CT angiography or MR angiography confirmed BAO treated with IVT . Patients will be r and omised between additional IAT followed by optimal medical care versus optimal medical care alone . IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3 . Discussion The BASICS registry was observational and has all the limitations of a non-r and omised study . As the IAT approach becomes increasingly available and frequently utilised an adequately powered r and omised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed ( clinical trials.gov : NCT01717755 ) Background The recent success of several mechanical thrombectomy trials has result ed in a significant change in management for patients presenting with stroke . However , it is still unclear how to manage patients that present with stroke and low National Institutes of Health Stroke Scale ( NIHSS ) ≤5 . We sought to review our experience of mechanical thrombectomy in patients with low NIHSS and confirmed M1 occlusion . Methods We retrospectively analysed our prospect ively maintained data base of all patients undergoing mechanical thrombectomy between January 2008 and August 2016 . We identified 41 patients with confirmed M1 occlusion and low NIHSS ( ≤5 ) on admission to our hospital . We collected demographic , radiological , procedural and outcome data . Results The mean age of patients was 72±14 , with 20 male patients . Associated medical conditions were common with hypertension seen in ∼80 % . Just over 50 % presented with NIHSS 4 or 5 . The average ASPECTS score on admission was 8.8 ( range 6–10 ) , and the average clot length 10 mm . Angiographically Thrombolysis in Cerebral Infa rct ion ( TICI ) ≥2b was obtained in 87.8 % of patients . 7 patients had haemorrhage on follow-up , 2 of which were symptomatic . Of 40 patients with 90-day follow-up , 75 % had modified Rankin Scale ( mRS ) score 0–2 . There were 3 deaths at 90 days . Conclusions Mechanical thrombectomy in patients with low NIHSS and proximal large vessel occlusion is technically possible and carries a high degree of success with good safety profile . Patients with low NIHSS and confirmed occlusion should be considered for mechanical thrombectomy Ischemic stroke is a leading cause of death and disability worldwide . Much of the long-term disability occurs in patients with Emergent Large Vessel Occlusion ( ELVO ) . In fact , in these patients , occlusion of a major intracerebral artery results in a large area of brain injury often result ing in death or severe disability.1 Until recently , intravenous tissue plasminogen activator ( t-PA ) was the only proven treatment for ELVO . However , the l and scape of stroke treatment has changed with the publication of five r and omized multicenter controlled clincal trials . These trials provide Class 1 , Level A evidence that endovascular thrombectomy ( ET ) is the st and ard of care for patients with ELVO . In particular , thrombectomy results in significantly better clinical outcomes compared to best medical therapy in patients with acute occlusion of the intracranial internal carotid artery ( ICA ) and /or M1 segment of the middle cerebral artery (MCA).2–6 These results have led to guideline recommendations advocating for endovascular treatment in addition to t-PA for patients with ELVO . In addition , ET is now offered as first line therapy for patients that are not eligible for intravenous thrombolysis.7–9 However , achieving the best possible clinical outcomes with endovascular stroke treatment m and ates structured training and education of those physicians who are providing endovascular stroke treatment . On this regard , a recent meta- analysis of these five clinical trials showed that the vast majority of thrombectomies were performed by experienced neurointerventionalists . These include interventional neuroradiologists , endovascular neurosurgeons , and interventional neurologists who routinely perform neuroendovascular procedures .10 None of the studies allowed physicians without previous experience in mechanical thrombectomy to enroll patients . The centers participating in these trials offered endovascular stroke therapy 24 hours a day ( with the exception of those in the EXTEND-IA trial ) with expertise in vascular neurology and neurocritical care in a comprehensive stroke center . On-site expertise in vascular neurology and Background Under current guidelines , intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours . We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infa rct ion on magnetic resonance imaging ( MRI ) would benefit from thrombolysis with the use of intravenous alteplase . Methods In a multicenter trial , we r and omly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo . All the patients had an ischemic lesion that was visible on MRI diffusion‐weighted imaging but no parenchymal hyperintensity on fluid‐attenuated inversion recovery ( FLAIR ) , which indicated that the stroke had occurred approximately within the previous 4.5 hours . We excluded patients for whom thrombectomy was planned . The primary end point was favorable outcome , as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability ( which ranges from 0 [ no symptoms ] to 6 [ death ] ) at 90 days . A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo ( shift analysis ) . Results The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients . Of these patients , 254 were r and omly assigned to receive alteplase and 249 to receive placebo . A favorable outcome at 90 days was reported in 131 of 246 patients ( 53.3 % ) in the alteplase group and in 102 of 244 patients ( 41.8 % ) in the placebo group ( adjusted odds ratio , 1.61 ; 95 % confidence interval [ CI ] , 1.09 to 2.36 ; P=0.02 ) . The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group ( adjusted common odds ratio , 1.62 ; 95 % CI , 1.17 to 2.23 ; P=0.003 ) . There were 10 deaths ( 4.1 % ) in the alteplase group and 3 ( 1.2 % ) in the placebo group ( odds ratio , 3.38 ; 95 % CI , 0.92 to 12.52 ; P=0.07 ) . The rate of symptomatic intracranial hemorrhage was 2.0 % in the alteplase group and 0.4 % in the placebo group ( odds ratio , 4.95 ; 95 % CI , 0.57 to 42.87 ; P=0.15 ) . Conclusions In patients with acute stroke with an unknown time of onset , intravenous alteplase guided by a mismatch between diffusion‐weighted imaging and FLAIR in the region of ischemia result ed in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days . ( Funded by the European Union Seventh Framework Program ; WAKE‐UP Clinical Trials.gov number , NCT01525290 ; and EudraCT number , 2011‐005906‐32 . Objective : There are limited data evaluating the effect of post mechanical thrombectomy ( MT ) blood pressure ( BP ) levels on early outcomes of patients with large vessel occlusions ( LVO ) . We sought to investigate the association of BP course following MT with early outcomes in LVO . Methods : Consecutive patients with LVO treated with MT during a 3-year period were evaluated . Hourly systolic BP ( SBP ) and diastolic BP ( DBP ) values were recorded for 24 hours following MT and maximum SBP and DBP levels were identified . LVO patients with complete reperfusion following MT were stratified in 3 groups based on post-MT achieved BP goals : < 140/90 mm Hg ( intensive ) , < 160/90 mm Hg ( moderate ) , and < 220/110 mm Hg or < 180/105 mm Hg when pretreated with IV thrombolysis ( permissive hypertension ) . Three-month functional independence was defined as modified Rankin Scale score of 0–2 . Results : A total of 217 acute ischemic stroke patients with LVO were prospect ively evaluated . A 10 mm Hg increment in maximum SBP documented during the first 24 hours post MT was independently ( p = 0.001 ) associated with a lower likelihood of 3-month functional independence ( odds ratio [ OR ] 0.70 ; 95 % confidence interval [ CI ] 0.56–0.87 ) and a higher odds of 3-month mortality ( OR 1.49 ; 95 % CI 1.18–1.88 ) after adjusting for potential confounders . In addition , achieving a BP goal of < 160/90 mm Hg during the first 24 hours following MT was independently associated with a lower likelihood of 3-month mortality ( OR 0.08 ; 95 % CI 0.01–0.54 ; p = 0.010 ) in comparison to permissive hypertension . Conclusions : High maximum SBP levels following MT are independently associated with increased likelihood of 3-month mortality and functional dependence in LVO patients . Moderate BP control is also related to lower odds of 3-month mortality in comparison to permissive hypertension Objective Permissive hypertension may benefit patients with non-recanalized large vessel occlusion ( nrLVO ) post mechanical thrombectomy ( MT ) by maintaining brain perfusion . Data evaluating the impact of post-MT blood pressure ( BP ) levels on outcomes in nrLVO patients are scarce . We investigated the association of the post-MT BP course with safety and efficacy outcomes in nrLVO . Methods Hourly systolic BP ( SBP ) and diastolic BP ( DBP ) values were prospect ively recorded for 24 hours following MT in consecutive nrLVO patients . Maximum , minimum , and mean BP levels were documented . Three-month functional independence ( FI ) was defined as modified Rankin Scale ( mRS ) scores of 0–2 . Results A total of 88 nrLVO patients were evaluated post MT . Patients with FI had lower maximum SBP ( 160±19 mmHg vs 179±23 mmHg ; P=0.001 ) and higher minimum SBP levels ( 119±12 mmHg vs 108±25 mmHg ; P=0.008 ) . Maximum SBP ( 183±20 mmHg vs 169±23 mmHg ; P=0.008 ) and DBP levels ( 105±20 mmHg vs 89±18 mmHg ; P=0.001 ) were higher in patients who died at 3 months while minimum SBP values were lower ( 102±28 mmHg vs 115±16 mmHg ; P=0.007 ) . On multivariable analyses , both maximum SBP ( OR per 10 mmHg increase : 0.55 , 95 % CI 0.39 to 0.79 ; P=0.001 ) and minimum SBP ( OR per 10 mmHg increase : 1.64 , 95 % CI 1.04 to 2.60 ; P=0.033 ) levels were independently associated with the odds of FI . Maximum DBP ( OR per 10 mmHg increase : 1.61 ; 95 % CI 1.10 to 2.36 ; P=0.014 ) and minimum SBP ( OR per 10 mmHg increase : 0.65 , 95 % CI 0.47 to 0.90 ; P=0.009 ) values were independent predictors of 3-month mortality . Conclusions Our study demonstrates that wide BP excursions from the mean during the first 24 hours post MT are associated with worse outcomes in patients with nrLVO BACKGROUND AND PURPOSE : The adverse effects of general anesthesia in stroke thrombectomy have been attributed to intraprocedural hypotension , yet optimal hemodynamic targets remain elusive . Identifying hemodynamic thresholds from patients without exposure to general anesthesia may help separate the effect of hypotension from the effect of anesthesia in thrombectomy outcomes . Therefore , we investigated which hemodynamic parameters and targets best correlate with outcome in patients treated under sedation with monitored anesthesia care . MATERIAL S AND METHODS : We performed a retrospective analysis of a prospect ively collected data base of patients with anterior circulation stroke who were successfully reperfused ( modified TICI ≥ 2b ) under monitored anesthesia care sedation from 2010 to 2015 . Receiver operating characteristic curves were generated for the lowest mean arterial pressure before reperfusion , both as absolute values and relative changes from baseline . Cutoffs were tested in binary logistic regression models of poor outcome ( 90-day mRS > 2 ) . RESULTS : Two-hundred fifty-six of 714 patients met the inclusion criteria . In a multivariable model , a ≥10 % mean arterial pressure decrease from baseline had an OR for poor outcome of 4.38 ( 95 % CI , 1.53–12.56 ; P < .01 ) . Other models revealed that any mean pressure of < 85 mm Hg before reperfusion had an OR for poor outcome of 2.22 ( 95 % CI , 1.09–4.55 ; P = .03 ) and that every 10-mm Hg drop in mean arterial pressure below 100 mm Hg had an OR of 1.28 ( 95 % CI , 1.01–1.62 ; P = .04 ) . CONCLUSIONS : A ≥10 % mean arterial pressure drop from baseline is a strong risk factor for poor outcome in a homogeneous population of patients with stroke undergoing thrombectomy under sedation . This threshold could guide hemodynamic management of patients during sedation and general anesthesia BACKGROUND Intravenous thrombolysis with alteplase alone can not reperfuse most large-artery strokes . We aim ed to determine whether mechanical thrombectomy in addition to intravenous thrombolysis improves clinical outcome in patients with acute ischaemic stroke . METHODS THRACE is a r and omised controlled trial done in 26 centres in France . Patients aged 18 - 80 years with acute ischaemic stroke and proximal cerebral artery occlusion were r and omly assigned to receive either intravenous thrombolysis alone ( IVT group ) or intravenous thrombolysis plus mechanical thrombectomy ( IVTMT group ) . Intravenous thrombolysis ( alteplase 0·9 mg/kg [ maximum 90 mg ] , with an initial bolus of 10 % of the total dose followed by infusion of the remaining dose over 60 min ) had to be started within 4 h and thrombectomy within 5 h of symptom onset . Occlusions had to be confirmed by CT or magnetic resonance angiography . R and omisation was done central ly with a computer-generated sequential minimisation method and was stratified by centre . The primary outcome was the proportion of patients achieving functional independence at 3 months , defined by a score of 0 - 2 on the modified Rankin scale , assessed in the modified intention-to-treat population ( ie , patients lost to follow-up and those with missing data were excluded ) . Safety outcomes were analysed in the per- protocol population ( ie , all patients who did not follow the protocol of their r and omisation group precisely were excluded from the analysis ) . THRACE is registered with Clinical Trials.gov , NCT01062698 . FINDINGS Between June 1 , 2010 , and Feb 22 , 2015 , 414 patients were r and omly assigned to the IVT group ( n=208 ) or the IVTMT group ( n=204 ) . Four patients ( two in each group ) lost to follow-up and six ( four in the IVT group and two in the IVTMT group ) with missing data were excluded . 85 ( 42 % ) of 202 patients in the IVT group and 106 ( 53 % ) of 200 patients in the IVTMT group achieved functional independence at 3 months ( odds ratio 1·55 , 95 % CI 1·05 - 2·30 ; p=0·028 ) . The two groups had no significant differences in mortality at 3 months ( 24 [ 12 % ] deaths of 202 patients vs 27 [ 13 % ] of 206 ; p=0·70 ) or symptomatic intracranial haemorrhage at 24 h ( four [ 2 % ] of 185 vs three [ 2 % ] of 192 ; p=0·71 ) . Common adverse events related to thrombectomy were vasospasm ( 33 [ 23 % ] patients ) and embolisation in a new territory ( nine [ 6 % ] ) . INTERPRETATION Mechanical thrombectomy combined with st and ard intravenous thrombolysis improves functional independence in patients with acute cerebral ischaemia , with no evidence of increased mortality . Bridging therapy should be considered for patients with large-vessel occlusions of the anterior circulation . FUNDING French Ministry for Health Objectives : Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset . We analyzed the effect of interventions aim ed to reduce treatment delays in our single-center observational series . Methods : All consecutive ischemic stroke patients treated with IV alteplase ( tissue plasminogen activator [ tPA ] ) were prospect ively registered in the Helsinki Stroke Thrombolysis Registry . A series of interventions to reduce treatment delays were implemented over the years 1998 to 2011 . In-hospital delays were analyzed as annual median door-to-needle time ( DNT ) in minutes , with interquartile range . Results : A total of 1,860 patients were treated between June 1995 and June 2011 , which included 174 patients with basilar artery occlusion ( BAO ) treated mostly beyond 4.5 hours from symptom onset . In the non-BAO patients , the DNT was reduced annually , from median 105 minutes ( 65–120 ) in 1998 , to 60 minutes ( 48–80 ) in 2003 , further on to 20 minutes ( 14–32 ) in 2011 . In 2011 , we treated with tPA 31 % of ischemic stroke patients admitted to our hospital . Of these , 94 % were treated within 60 minutes from arrival . Performing angiography or perfusion imaging doubled the in-hospital delays . Patients with in-hospital stroke or arriving very soon from symptom onset had longer delays because there was no time to prepare for their arrival . Conclusions : With multiple concurrent strategies it is possible to cut the median in-hospital delay to 20 minutes . The key is to do as little as possible after the patient has arrived at the emergency room and as much as possible before that , while the patient is being transported Background and Purpose — We derived and vali date d the Cincinnati Prehospital Stroke Severity Scale ( CPSSS ) to identify patients with severe strokes and large vessel occlusion ( LVO ) . Methods — CPSSS was developed with regression tree analysis , objectivity , anticipated ease in administration by emergency medical services personnel and the presence of cortical signs . We derived and vali date d the tool using the 2 National Institute of Neurological Disorders and Stroke ( NINDS ) tissue-type plasminogen activator Stroke Study trials and Interventional Management of Stroke III ( IMS III ) Trial cohorts , respectively , to predict severe stroke ( National Institutes of Health Stroke Scale [ NIHSS ] ≥15 ) and LVO . St and ard test characteristics were determined and receiver operator curves were generated and summarized by the area under the curve . Results — CPSSS score ranges from 0 to 4 ; composed and scored by individual NIHSS items : 2 points for presence of conjugate gaze ( NIHSS ≥1 ) ; 1 point for presence of arm weakness ( NIHSS ≥2 ) ; and 1 point for presence abnormal level of consciousness comm and s and questions ( NIHSS level of consciousness ≥1 each ) . In the derivation set , CPSSS had an area under the curve of 0.89 ; score ≥2 was 89 % sensitive and 73 % specific in identifying NIHSS ≥15 . Validation results were similar with an area under the curve of 0.83 ; score ≥2 was 92 % sensitive , 51 % specific , a positive likelihood ratio of 3.3 , and a negative likelihood ratio of 0.15 in predicting severe stroke . For 222 of 303 IMS III subjects with LVO , CPSSS had an area under the curve of 0.67 ; a score ≥2 was 83 % sensitive , 40 % specific , positive likelihood ratio of 1.4 , and negative likelihood ratio of 0.4 in predicting LVO . Conclusions — CPSSS can identify stroke patients with NIHSS ≥15 and LVO . Prospect i ve prehospital validation is warranted Background : After thrombectomy has shown to be effective in acute stroke patients with large vessel occlusion , the potential benefit of secondary referral for such an intervention needs to be vali date d. Aims : We aim ed to compare consecutive stoke patients directly admitted and treated with thrombectomy at a neurointerventional centre with patients secondarily referred for such a procedure from hospitals with a stroke unit . Methods : Periprocedure times and mortality in 300 patients primarily treated in eight neurointerventional centres were compared with 343 patients referred from nine other hospitals in a prospect i ve multicentre study of a German neurovascular network . Data on functional outcome at 3 months was available in 430 ( 76.4 % ) patients . Results : In-hospital mortality ( 14.8 % versus 11.7 % , p = 0.26 ) and 3 months mortality ( 21.9 % versus 24.1 % , p = 0.53 ) were not statistically different in both patient groups despite a significant shorter symptom to groin puncture time in directly admitted patients , which was mainly caused by a longer interfacility transfer time . We found a nonsignificant trend for better functional outcome at 3 months in directly admitted patients ( modified Rankin Scale 0–2 , 44.0 % versus 35.7 % , p = 0.08 ) . Conclusions : Our results show that a drip- and -ship thrombectomy concept can be effectively organized in a metropolitan stroke network . Every effort should be made to speed up the emergency interfacility transfer to a neurointerventional centre in stroke patients eligible for thrombectomy after initial brain imaging BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator ( t-PA ) for patients with moderate-to-severe acute ischemic stroke , but whether a combined approach is more effective than intravenous t-PA alone is uncertain . METHODS We r and omly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone , in a 2:1 ratio . The primary outcome measure was a modified Rankin scale score of 2 or less ( indicating functional independence ) at 90 days ( scores range from 0 to 6 , with higher scores indicating greater disability ) . RESULTS The study was stopped early because of futility after 656 participants had undergone r and omization ( 434 patients to endovascular therapy and 222 to intravenous t-PA alone ) . The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment ( 40.8 % with endovascular therapy and 38.7 % with intravenous t-PA ; absolute adjusted difference , 1.5 percentage points ; 95 % confidence interval [ CI ] , -6.1 to 9.1 , with adjustment for the National Institutes of Health Stroke Scale [ NIHSS ] score [ 8 - 19 , indicating moderately severe stroke , or ≥20 , indicating severe stroke ] ) , nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher ( 6.8 percentage points ; 95 % CI , -4.4 to 18.1 ) and those with a score of 19 or lower ( -1.0 percentage point ; 95 % CI , -10.8 to 8.8 ) . Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days ( 19.1 % and 21.6 % , respectively ; P=0.52 ) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA ( 6.2 % and 5.9 % , respectively ; P=0.83 ) . CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA , as compared with intravenous t-PA alone . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT00359424 . ) Purpose To prospect ively evaluate the prognostic impact of multimodal computed tomography-based imaging in ischemic stroke patients potentially eligible for reperfusion therapy . Methods Anterior circulation stroke patients underwent non-contrast CT ( NCCT ) , CT-angiography , and CT-perfusion within 12 h from symptom-onset . Patients could be treated with intravenous-tissue plasminogen activator ( IV-tPA ) , endovascular or combined reperfusion therapies . Cerebral imaging profiles ( IP ) were NCCT-Alberta Stroke Program Early CT Score ( ASPECTS ) > 7 ( IP1 ) ; NCCT-ASPECTS > 5 and proximal occlusion on CT-angiography ( IP2 ) ; CT-perfusion mismatch between cerebral blood volume (CBV)-ASPECTS , and cerebral blood flow (CBF)-ASPECTS ≥ 2 ( IP3 ) . Favorable outcome was defined as modified Rankin Scale ≤ 2 at 3 months . Results Of 102 included patients , 62 ( 61 % ) received any reperfusion therapy . In IP2 and IP3 , favorable outcome was more frequent in patients with reperfusion therapy than in those without ; however , this did not reach statistical significance ( IP2 : 39 % vs 15 % , p = 0.26 ; IP3 : 50 % vs 17 % ; p = 0.31 ) . No difference was seen in IP1 ( 58 % vs 58 % , p = 1.0 ) . In IP2 , patients with IV-tPA alone achieved better functional outcome ( 50 % vs 11 % , p = 0.03 ) and lower mortality ( 0 % vs 28 % , p = 0.045 ) than those without . Conclusions Our results suggest a benefit with imaging profile selection based upon the combination of a small-to-moderate-sized infa rct ion and a visible intracranial occlusion in patients receiving IV-tPA . Reperfusion therapy may be futile in patients without proven vessel occlusion This is a retrospective analysis of 484 patients in a prospect ively collected stroke data base . The inclusion criteria were anterior circulation ischemic stroke treated with mechanical thrombectomy at a single institution between September 2010 and October 2015 with an NIHSS score of ≤8 . The purpose was to assess the clinical and interventional data in patients treated with mechanical thrombectomy in case of ischemic stroke with mild-to-moderate symptoms ( n = 33 ) . Recanalization ( TICI 2b–3 ) was achieved in 26 ( 78.7 % ) patients . Two cases of symptomatic intracranial hemorrhage occurred . Favorable ( mRS 0–2 ) and moderate ( mRS 0–3 ) clinical 90-day outcome was achieved in 63.6 % and 90.9 % of patients , respectively . The authors conclude that the clinical outcome of patients undergoing mechanical thrombectomy for acute ischemic mild stroke due to large-vessel occlusion is predominately favorable , even in a prolonged time window . BACKGROUND AND PURPOSE : Mechanical thrombectomy , in addition to intravenous thrombolysis , has become st and ard in acute ischemic stroke treatment in patients with large-vessel occlusion in the anterior circulation . However , previous r and omized controlled stroke trials were not focused on patients with mild-to-moderate symptoms . Thus , there are limited data for patient selection , prediction of clinical outcome , and occurrence of complications in this patient population . The purpose of this analysis was to assess clinical and interventional data in patients treated with mechanical thrombectomy in case of ischemic stroke with mild-to-moderate symptoms . MATERIAL S AND METHODS : We performed a retrospective analysis of a prospect ively collected stroke data base . Inclusion criteria were anterior circulation ischemic stroke treated with mechanical thrombectomy at our institution between September 2010 and October 2015 with an NIHSS score of ≤8 . RESULTS : Of 484 patients , we identified 33 ( 6.8 % ) with the following characteristics : median NIHSS = 5 ( interquartile range , 4–7 ) , median onset-to-groin puncture time = 320 minutes ( interquartile range , 237–528 minutes ) . Recanalization ( TICI = 2b–3 ) was achieved in 26 ( 78.7 % ) patients . Two cases of symptomatic intracranial hemorrhage were observed . Favorable ( mRS 0–2 ) and moderate ( mRS 0–3 ) clinical outcome at 90 days was achieved in 21 ( 63.6 % ) and 30 ( 90.9 % ) patients , respectively . CONCLUSIONS : The clinical outcome of patients undergoing mechanical thrombectomy for acute ischemic stroke with mild stroke due to large-vessel occlusion appears to be predominately favorable , even in a prolonged time window . However , although infrequent , angiographic complications could impair clinical outcome . Future r and omized controlled trials should assess the benefit compared with the best medical treatment IMPORTANCE Time to thrombolysis is crucial for outcome in acute ischemic stroke . OBJECTIVE To determine if starting thrombolysis in a specialized ambulance reduces delays . DESIGN , SETTING , AND PARTICIPANTS In the Prehospital Acute Neurological Treatment and Optimization of Medical care in Stroke Study ( PHANTOM-S ) , conducted in Berlin , Germany , we r and omly assigned weeks with and without availability of the Stroke Emergency Mobile ( STEMO ) from May 1 , 2011 , to January 31 , 2013 . Berlin has an established stroke care infrastructure with 14 stroke units . We included 6182 adult patients ( STEMO weeks : 44.3 % male , mean [ SD ] age , 73.9 [ 15.0 ] y ; control weeks : 45.2 % male , mean [ SD ] age , 74.3 [ 14.9 ] y ) for whom a stroke dispatch was activated . INTERVENTIONS The intervention comprised an ambulance ( STEMO ) equipped with a CT scanner , point-of-care laboratory , and telemedicine connection ; a stroke identification algorithm at dispatcher level ; and a prehospital stroke team . Thrombolysis was started before transport to hospital if ischemic stroke was confirmed and contraindications excluded . MAIN OUTCOMES AND MEASURES Primary outcome was alarm-to-thrombolysis time . Secondary outcomes included thrombolysis rate , secondary intracerebral hemorrhage after thrombolysis , and 7-day mortality . RESULTS Time reduction was assessed in all patients with a stroke dispatch from the entire catchment area in STEMO weeks ( 3213 patients ) vs control weeks ( 2969 patients ) and in patients in whom STEMO was available and deployed ( 1804 patients ) vs control weeks ( 2969 patients ) . Compared with thrombolysis during control weeks , there was a reduction of 15 minutes ( 95 % CI , 11 - 19 ) in alarm-to-treatment times in the catchment area during STEMO weeks ( 76.3 min ; 95 % CI , 73.2 - 79.3 vs 61.4 min ; 95 % CI , 58.7 - 64.0 ; P < .001 ) . Among patients for whom STEMO was deployed , mean alarm-to-treatment time ( 51.8 min ; 95 % CI , 49.0 - 54.6 ) was shorter by 25 minutes ( 95 % CI , 20 - 29 ; P < .001 ) than during control weeks . Thrombolysis rates in ischemic stroke were 29 % ( 310/1070 ) during STEMO weeks and 33 % ( 200/614 ) after STEMO deployment vs 21 % ( 220/1041 ) during control weeks ( differences , 8 % ; 95 % CI , 4%-12 % ; P < .001 , and 12 % , 95 % CI , 7%-16 % ; P < .001 , respectively ) . STEMO deployment incurred no increased risk for intracerebral hemorrhage ( STEMO deployment : 7/200 ; conventional care : 22/323 ; adjusted odds ratio [ OR ] , 0.42 , 95 % CI , 0.18 - 1.03 ; P = .06 ) or 7-day mortality ( 9/199 vs 15/323 ; adjusted OR , 0.76 ; 95 % CI , 0.31 - 1.82 ; P = .53 ) . CONCLUSIONS AND RELEVANCE Compared with usual care , the use of ambulance-based thrombolysis result ed in decreased time to treatment without an increase in adverse events . Further studies are needed to assess the effects on clinical outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01382862 Within the context of a prospect i ve r and omized trial ( SWIFT PRIME ) , we assessed whether early imaging of stroke patients , primarily with computed tomography ( CT ) perfusion , can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue . We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infa rct volume in patients with the target mismatch profile BACKGROUND It is unclear what factors providers take into account to determine the target blood pressure ( BP ) after mechanical thrombectomy ( MT ) in patients who had acute ischemic stroke . We aim ed to underst and practice patterns of post-MT BP management across institutions in the United States . METHODS We surveyed StrokeNet institutions providing MT and post-MT care with an online question naire , design ed to underst and institutional post-MT BP management practice s. RESULTS Of 131 potential institutions , 58 completed the survey . The majority of institutions target systolic BP ( SBP , n = 53 , 91 % ) during the first 24 hours post-MT ( n = 32 , 55 % ) using nicardipine as a first-line agent ( n = 43 , 74 % ) . At most institutions , BP management is determined by a team of physicians in a collaborative fashion ( n = 30 , 52 % ) and individualized on a case-by-case basis ( n = 39 , 67 % ) after taking the reperfusion status into account ( n = 42 , 72 % ) . In patients with successful reperfusion , 36 % ( n = 21 ) of the institutions target SBP in the range of 120 - 139 mm Hg , 21 % ( n = 12 ) target 140 - 159 mm Hg , and 28 % ( n = 16 ) would accept any value less than or equal to 180 mm Hg . In patients with unsuccessful reperfusion , 43 % ( n = 25 ) would accept any SBP value less than or equal to 180 mm Hg and 10 % ( n = 6 ) would target SBP less than or equal to 220 mm Hg . CONCLUSIONS We found that majority of the institutions do not have a st and ardized protocol for post-MT BP management . There was interinstitutional heterogeneity in the preferred target of SBP post-MT and most institutions target values of SBP lower than 180 mm Hg in post-MT patients . Prospect i ve data and r and omized control trial are needed to identify the optimal target BP Rapid reperfusion of the entire territory distal to vascular occlusions is the aim of stroke interventions . Recent studies defined successful reperfusion as establishing some perfusion with distal branch filling of < 50 % of territory visualized ( Thrombolysis In Cerebral Infa rct ion “ TICI ” 2a ) or more . We investigate the importance of the quality of final reperfusion and whether a revision of the successful reperfusion definition is warranted . We retrospectively evaluated a prospect i ve data base of anterior circulation strokes treated using stentrievers to assess the quality of final reperfusion using two scores : the traditional TICI score and a modified TICI score . The modified TICI score includes an additional category ( TICI 2c ) : near complete perfusion except for slow flow or distal emboli in a few distal cortical vessels . We compared different cut-off definitions of reperfusion ( TICI 2a–3 vs. TICI-2b–3 vs. TICI 2c–3 ) using the area under the curve to identify their correlation with a favorable 90-day outcome ( mRS≤2 ) . In our cohort of 110 patients , 90 % achieved TICI 2a-3 reperfusion with 80 % achieving TICI 2b-3 and 55.5 % achieving TICI 2c-3 . The proportion of patients with a favorable 90-day outcome was higher in the TICI 2c ( 62.5 % ) compared to TICI 2b ( 44.4 % ) or TICI 2a ( 45.5 % ) but similar to the TICI 3 group ( 75.9 % ) . A TICI 2c-3 reperfusion had a better predictive value than TICI 2b-3 for 90-day mRS 0–1 . Defining successful reperfusion as TICI 2c/3 has merits . In this cohort , there was evidence toward faster recovery and better outcomes in patients with the TICI 2c vs. the traditional TICI 2b grade Importance Endovascular therapy ( EVT ) is the st and ard of care for select patients who had a stroke caused by a large vessel occlusion in the anterior circulation , but there is uncertainty regarding the optimal anesthetic approach during EVT . Observational studies suggest that general anesthesia ( GA ) is associated with worse outcomes compared with conscious sedation ( CS ) . Objective To examine the effect of type of anesthesia during EVT on infa rct growth and clinical outcome . Design , Setting , and Participants The General or Local Anesthesia in Intra Arterial Therapy ( GOLIATH ) trial was a single-center prospect i ve , r and omized , open-label , blinded end-point evaluation that enrolled patients from March 12 , 2015 , to February 2 , 2017 . Although the trial screened 1501 patients , it included 128 consecutive patients with acute ischemic stroke caused by large vessel occlusions in the anterior circulation within 6 hours of onset ; 1372 patients who did not fulfill inclusion criteria and 1 who did not provide consent were excluded . Primary analysis was unadjusted and according to the intention-to-treat principle . Interventions Patients were r and omized to either the GA group or the CS group ( 1:1 allocation ) before EVT . Main Outcomes and Measures The primary end point was infa rct growth between magnetic resonance imaging scans performed before EVT and 48 to 72 hours after EVT . The hypothesis formulated before data collection was that patients who were under CS would have less infa rct growth . Results Of 128 patients included in the trial , 65 were r and omized to GA , and 63 were r and omized to CS . For the entire cohort , the mean ( SD ) age was 71.4 ( 11.4 ) years , and 62 ( 48.4 % ) were women . Baseline demographic and clinical variables were balanced between the GA and CS treatment arms . The median National Institutes of Health Stroke Scale score was 18 ( interquartile range [ IQR ] , 14 - 21 ) . Four patients ( 6.3 % ) in the CS group were converted to the GA group . Successful reperfusion was significantly higher in the GA arm than in the CS arm ( 76.9 % vs 60.3 % ; P = .04 ) . The difference in the volume of infa rct growth among patients treated under GA or CS did not reach statistical significance ( median [ IQR ] growth , 8.2 [ 2.2 - 38.6 ] mL vs 19.4 [ 2.4 - 79.0 ] mL ; P = .10 ) . There were better clinical outcomes in the GA group , with an odds ratio for a shift to a lower modified Rankin Scale score of 1.91 ( 95 % CI , 1.03 - 3.56 ) . Conclusions and Relevance For patients who underwent thrombectomy for acute ischemic stroke caused by large vessel occlusions in the anterior circulation , GA did not result in worse tissue or clinical outcomes compared with CS . Trial Registration clinical trials.gov Identifier : Importance More than half of patients with acute ischemic stroke have minor neurologic deficits ( National Institutes of Health Stroke Scale [ NIHSS ] score of 0 - 5 ) at presentation . Although prior major trials of alteplase included patients with low NIHSS scores , few without clearly disabling deficits were enrolled . Objective To evaluate the efficacy and safety of alteplase in patients with NIHSS scores of 0 to 5 whose deficits are not clearly disabling . Design , Setting , and Participants The PRISMS trial was design ed as a 948-patient , phase 3b , double-blind , double-placebo , multicenter r and omized clinical trial of alteplase compared with aspirin for emergent stroke at 75 stroke hospital networks in the United States . Patients with acute ischemic stroke whose deficits were scored as 0 to 5 on the NIHSS and judged not clearly disabling and in whom study treatment could be initiated within 3 hours of onset were eligible and enrolled from May 30 , 2014 , to December 20 , 2016 , with final follow-up on March 22 , 2017 . Interventions Participants were r and omized to receive intravenous alteplase at the st and ard dose ( 0.9 mg/kg ) with oral placebo ( n = 156 ) or oral aspirin , 325 mg , with intravenous placebo ( n = 157 ) . Main Outcomes and Measures The primary outcome was the difference in favorable functional outcome , defined as a modified Rankin Scale score of 0 or 1 at 90 days via Cochran-Mantel-Haenszel test stratified by pretreatment NIHSS score , age , and time from onset to treatment . Because of early termination of the trial , prior to unblinding or interim analyses , the plan was revised to examine the risk difference of the primary outcome by a linear model adjusted for the same factors . The primary safety end point was symptomatic intracranial hemorrhage ( sICH ) within 36 hours of intravenous study treatment . Results Among 313 patients enrolled at 53 stroke networks ( mean age , 62 [ SD , 13 ] years ; 144 [ 46 % ] women ; median NIHSS score , 2 [ interquartile range { IQR } , 1 - 3 ] ; median time to treatment , 2.7 hours [ IQR , 2.1 - 2.9 ] ) , 281 ( 89.8 % ) completed the trial . At 90 days , 122 patients ( 78.2 % ) in the alteplase group vs 128 ( 81.5 % ) in the aspirin group achieved a favorable outcome ( adjusted risk difference , −1.1 % ; 95 % CI , −9.4 % to 7.3 % ) . Five alteplase-treated patients ( 3.2 % ) vs 0 aspirin-treated patients had sICH ( risk difference , 3.3 % ; 95 % CI , 0.8%-7.4 % ) . Conclusions and Relevance Among patients with minor nondisabling acute ischemic stroke , treatment with alteplase vs aspirin did not increase the likelihood of favorable functional outcome at 90 days . However , the very early study termination precludes any definitive conclusions , and additional research may be warranted . Trial Registration Clinical Trials.gov Identifier : Background Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms . Methods We conducted a multicenter , r and omized , open‐label trial , with blinded outcome assessment , of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infa rct ed . Patients with proximal middle‐cerebral‐artery or internal‐carotid‐artery occlusion , an initial infa rct size of less than 70 ml , and a ratio of the volume of ischemic tissue on perfusion imaging to infa rct volume of 1.8 or more were r and omly assigned to endovascular therapy ( thrombectomy ) plus st and ard medical therapy ( endovascular‐therapy group ) or st and ard medical therapy alone ( medical‐therapy group ) . The primary outcome was the ordinal score on the modified Rankin scale ( range , 0 to 6 , with higher scores indicating greater disability ) at day 90 . Results The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone r and omization ( 92 to the endovascular‐therapy group and 90 to the medical‐therapy group ) . Endovascular therapy plus medical therapy , as compared with medical therapy alone , was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days ( odds ratio , 2.77 ; P<0.001 ) and a higher percentage of patients who were functionally independent , defined as a score on the modified Rankin scale of 0 to 2 ( 45 % vs. 17 % , P<0.001 ) . The 90‐day mortality rate was 14 % in the endovascular‐therapy group and 26 % in the medical‐therapy group ( P=0.05 ) , and there was no significant between‐group difference in the frequency of symptomatic intracranial hemorrhage ( 7 % and 4 % , respectively ; P=0.75 ) or of serious adverse events ( 43 % and 53 % , respectively ; P=0.18 ) . Conclusions Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus st and ard medical therapy result ed in better functional outcomes than st and ard medical therapy alone among patients with proximal middle‐cerebral‐artery or internal‐carotid‐artery occlusion and a region of tissue that was ischemic but not yet infa rct ed . ( Funded by the National Institute of Neurological Disorders and Stroke ; DEFUSE 3 Clinical Trials.gov number , NCT02586415 . Abstract Background and Purpose : A simple , easily adoptable scale with good performance characteristics is needed for EMS providers to appropriately triage suspected stroke patients to comprehensive stroke centers ( CSC ) . Many existing tools are complex , require substantial training , or have not been prospect ively vali date d in the prehospital setting . We describe the feasibility and effectiveness of prehospital implementation of our previously retrospectively derived and vali date d Cincinnati Stroke Triage Assessment Tool ( C-STAT ) to identify subjects with severe stroke ( NIHSS ≥15 ) among all prehospital patients with clinical suspicion of stroke/TIA . Secondarily , we evaluated the tool 's ability to identify subjects with NIHSS ≥10 , large vessel occlusion ( LVO ) , or needing services available only at a CSC . Methods : Without formalized training , Cincinnati Fire Department providers performed st and ard stroke screening ( “ face , arm , speech , time ; ” FAST ) and C-STAT as part of their assessment of suspected stroke/TIA patients . Outcomes for patients brought to the region 's only CSC or assessed by the regional stroke team were determined through structured chart review by a stroke team nurse . C-STAT test characteristics for each outcome were calculated with 95 % confidence intervals . Results : Complete prehospital and outcome data were available for 58 FAST-positive subjects among 158 subjects with prehospital suspicion for stroke/TIA . Subjects were excluded if FAST was negative ( n = 22 ) , FAST or C-STAT was incompletely documented ( n = 24 ) , if the patient was taken to a non-CSC and did not receive a stroke team consult ( n = 48 ) , or if outcome data were missing ( n = 6 ) . C-STAT sensitivity and specificity for each outcome were : NIHSS ≥ 15 , 77 % ( 95 % CI 46–95 ) and 84 % ( 95 % CI 69–93 ) ; NIHSS ≥10 , 64 % ( 95 % CI 41–83 ) and 91 % ( 95 % CI 76–98 ) ; LVO , 71 % ( 95 % CI 29–96 ) and 70 % ( 95 % CI 55–83 ) ; overall CSC need 57 % ( 95 % CI 34–78 ) and 79 % ( 95 % CI 61–91 ) . Conclusion : In this pilot prospect i ve evaluation performed in the prehospital setting by EMS providers without formalized training , C-STAT is comparable to other published tools in test characteristics and may inform appropriate CSC triage beyond LVO ascertainment alone BACKGROUND In most countries , alteplase given within 4·5 h of onset is the only approved medical treatment for acute ischaemic stroke . The newer thrombolytic drug tenecteplase has been investigated in one r and omised trial up to 3 h after stroke and in another trial up to 6 h after stroke in patients selected by advanced neuroimaging . In the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis ( ATTEST ) , we aim ed to assess the efficacy and safety of tenecteplase versus alteplase within 4·5 h of stroke onset in a population not selected on the basis of advanced neuroimaging , and to use imaging biomarkers to inform the design of a definitive phase 3 clinical trial . METHODS In this single-centre , phase 2 , prospect i ve , r and omised , open-label , blinded end-point evaluation study , adults with supratentorial ischaemic stroke eligible for intravenous thrombolysis within 4·5 h of onset were recruited from The Institute of Neurological Sciences , Glasgow , Scotl and . Patients were r and omly assigned ( 1:1 ) to receive tenecteplase 0·25 mg/kg ( maximum 25 mg ) or alteplase 0·9 mg/kg ( maximum 90 mg ) . Treatment allocation used a mixed r and omisation and minimisation algorithm including age and National Institutes of Health Stroke Scale score , generated by an independent statistician . Patients were not informed of treatment allocation ; treating clinicians were aware of allocation but those assessing the primary outcome were not . Imaging comprised baseline CT , CT perfusion , and CT angiography ; and CT plus CT angiography at 24 - 48 h. The primary endpoint was percentage of penumbra salvaged ( CT perfusion-defined penumbra volume at baseline minus CT infa rct volume at 24 - 48 h ) . Analysis was per protocol . This study is registered with Clinical Trials.gov , number NCT01472926 . FINDINGS Between Jan 1 , 2012 , and Sept 7 , 2013 , 355 patients were screened , of whom 157 were eligible for intravenous thrombolysis , and 104 patients were enrolled . 52 were assigned to the alteplase group and 52 to tenecteplase . Of 71 patients ( 35 assigned tenecteplase and 36 assigned alteplase ) contributing to the primary endpoint , no significant differences were noted for percentage of penumbral salvaged ( 68 % [ SD 28 ] for the tenecteplase group vs 68 % [ 23 ] for the alteplase group ; mean difference 1·3 % [ 95 % CI -9·6 to 12·1 ] ; p=0·81 ) . Neither incidence of symptomatic intracerebral haemorrhage ( by SITS-MOST definition , 1/52 [ 2 % ] tenecteplase vs 2/51 [ 4 % ] alteplase , p=0·55 ; by ECASS II definition , 3/52 [ 6 % ] vs 4/51 [ 8 % ] , p=0·59 ) nor total intracerebral haemorrhage events ( 8/52 [ 15 % ] vs 14/51 [ 29 % ] , p=0·091 ) differed significantly . The incidence of serious adverse events did not differ between groups ( 32 in the tenecteplase group , three considered probably or definitely related to drug treatment ; 16 in the alteplase group , five were considered drug-related ) . INTERPRETATION Neurological and radiological outcomes did not differ between the tenecteplase and alteplase groups . Evaluation of tenecteplase in larger trials of patients with acute stroke seems warranted . FUNDING The Stroke Association Five recently published r and omized controlled trials ( RCTs ) and respective meta-analyses provide strong evidence that endovascular thrombectomy ( EVT ) combined with best medical treatment , including intravenous ( IV ) tissue plasminogen activator ( tPA ) ( IV thrombolysis , IVT ) for eligible patients , improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of proximal occlusions in the carotid circulation ( large vessel occlusion , LVO ) . Four out of the five studies were stopped early after a first RCT showed the superiority of EVT combined with medical management over medical management alone . Such premature trial termination will on average lead to overestimation of the treatment effect . Nonetheless , since all five RCTs showed consistent benefit of EVT over optimal medical management alone , and a dose – effect relation ( reperfusion rates vs. clinical outcome ) , the benefit of EVT is considered established . After the publication of the ‘ ‘ Consensus statement by ESO-Karolinska Stroke Up date ’’ as timely response to the new evidence , the purpose of EROICAS is to provide recommendations based on a structured collaborative process conducted by six relevant European professional societies Background and Purpose — Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings , subsequent infa rct growth , and clinical outcome in patients undergoing endovascular therapy for ischemic stroke . Methods — Sixty patients with a thrombolysis in cerebral infa rct ion ( TICI ) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated . A blinded reader assigned a collateral score using a previous 5-point scale , from 0 ( no collateral flow ) to 4 ( complete/rapid collaterals to the entire ischemic territory ) . The analysis was dichotomized to poor flow ( 0–2 ) versus good flow ( 3–4 ) . Collateral score was correlated with baseline National Institutes of Health Stroke Scale , diffusion-weighted imaging volume , perfusion-weighted imaging volume ( Tmax ≥6 seconds ) , TICI reperfusion , infa rct growth , and modified Rankin Scale score at day 90 . Results — Collateral score correlated with baseline National Institutes of Health Stroke Scale ( P=0.002 ) and median volume of tissue at Tmax ≥6 seconds ( P=0.009 ) . Twenty-nine percent of patients with poor collateral flow had TICI 2B–3 reperfusion versus 65.5 % with good flow ( P=0.009 ) . Patients with poor collaterals who reperfused ( TICI 2B–3 ) were more likely to have a good functional outcome ( modified Rankin Scale score 0–2 at 90 days ) compared with patients who did not reperfuse ( odds ratio , 12 ; 95 % confidence interval , 1.6–98 ) . There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals ( P=1.0 ) . Patients with poor reperfusion ( TICI 0–2a ) showed a trend toward greater infa rct growth if they had poor collaterals versus good collaterals ( P=0.06 ) . Conclusions — Collaterals correlate with baseline National Institutes of Health Stroke Scale , perfusion-weighted imaging volume , and good reperfusion . However , target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate , irrespective of the collateral score . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01349946 |
1,178 | 30,925,881 | In network meta- analysis , all regimen comparisons did not produce statistically significant differences in survival .
Based on treatment ranking of OS and the benefit-risk ratio , S-1-cisplatin ( SP ) was likely to be the most preferable regimen for its best efficacy and low risk of causing SAEs .
Gemcitabine-cisplatin ( GP ) and PC + Cetuximab ( PC-Cet ) appeared to be the worst and second-worst regimens for their poor efficacy and poor tolerability .
Conclusions Based on efficacy and tolerability , SP is likely to be the most preferable regimen used concurrently with thoracic radiation for locally advanced NSCLC , followed by UP and PP . | Background It remains unknown which is the most preferable regimen used concurrently with thoracic radiation for locally advanced non-small cell lung cancer ( NSCLC ) .
We performed a network meta- analysis to address this important issue . | Purpose Concurrent chemoradiotherapy ( CCRT ) is recommended for the management of patients with unresectable non-small cell lung cancer ( NSCLC ) . This prospect i ve study aim ed to compare the efficacy of concurrently delivered cisplatin doublets with paclitaxel , or docetaxel , or gemcitabine . Methods The main eligibility criteria consisted of previously untreated stage IIIB NSCLC . The subjects were r and omized into three arms : paclitaxel 45 mg/m2/week ( TP ) , docetaxel 20 mg/m2/week ( DP ) , and gemcitabine 350 mg/m2/week ( GP ) in addition to cisplatin 20 mg/m2/week . Three-dimensional conformal radiotherapy was given once daily , weekly 5 fractions and the total prescription dose was 60–66 Gy . The primary endpoint was response rate , and the secondary endpoints were survival and toxicity . Results A total of 101 patients were recruited into this trial of whom 93 ( TP : 33 , DP : 29 , GP : 31 ) patients were treated with CCRT from March 2005 to July 2007 . Similar response rates were observed across arms : TP : 63.6 % , DP : 72.4 % , GP : 61.3 % ( p = 0.679 ) . There was no statistically significant difference of median survival ( TP : 27.3 , DP : 27.6 , GP : 16.5 months , p = 0.771 ) . In subgroup analysis , a survival benefit of consolidation chemotherapy was not seen , but leucopenia ( 63.2 % ) and neutropenia ( 68.4 % ) more than grade 3 were significantly high in DP arm . The grade ≥3 radiation esophagitis was more frequent in the GP arm ( 22.6 % , p = 0.163 ) . Conclusions Among the three arms , no statistically significant difference in response rate , survival , and toxicity was observed . However , clinical ly significant radiation toxicity was more frequent in the GP arm PURPOSE The phase III PROCL AIM study evaluated overall survival ( OS ) of concurrent pemetrexed-cisplatin and thoracic radiation therapy ( TRT ) followed by consolidation pemetrexed , versus etoposide-cisplatin and TRT followed by nonpemetrexed doublet consolidation therapy . PATIENTS AND METHODS Patients with stage IIIA/B unresectable nonsquamous non-small-cell lung cancer r and omly received ( 1:1 ) pemetrexed 500 mg/m(2 ) and cisplatin 75 mg/m(2 ) intravenously every 3 weeks for three cycles plus concurrent TRT ( 60 to 66 Gy ) followed by pemetrexed consolidation every 3 weeks for four cycles ( arm A ) , or st and ard therapy with etoposide 50 mg/m(2 ) and cisplatin 50 mg/m(2 ) intravenously , every 4 weeks for two cycles plus concurrent TRT ( 60 to 66 Gy ) followed by two cycles of consolidation platinum-based doublet chemotherapy ( arm B ) . The primary objective was OS . The study was design ed as a superiority trial with 80 % power to detect an OS hazard ratio of 0.74 with a type 1 error of .05 . RESULTS Enrollment was stopped early because of futility . Five hundred ninety-eight patients were r and omly assigned ( 301 to arm A , 297 to arm B ) and 555 patients ( 283 in arm A , 272 in arm B ) were treated . Arm A was not superior to arm B in terms of OS ( hazard ratio , 0.98 ; 95 % CI , 0.79 to 1.20 ; median , 26.8 v 25.0 months ; P = .831 ) . Arm A had a significantly lower incidence of any drug-related grade 3 to 4 adverse events ( 64.0 % v 76.8 % ; P = .001 ) , including neutropenia ( 24.4 % v 44.5 % ; P < .001 ) , during the overall treatment period . CONCLUSION Pemetrexed-cisplatin combined with TRT followed by consolidation pemetrexed was not superior to st and ard chemoradiotherapy for stage III unresectable nonsquamous non-small-cell lung cancer Purpose The purpose of this phase I/II study was to evaluate the feasibility and efficacy of S-1 plus cisplatin at the recommended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer ( LA-NSCLC ) . Methods Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m2 on day 8 plus oral S-1 at a dosage of 40 mg/m2 twice per day for two different treatment schedules for up to 4 cycles . Patients also concurrently received 60 Gy of thoracic radiation in 30 fractions . The primary endpoint of the phase II study was the proportion of patients who survived for more than 2 years . Results Between August 2005 and October 2010 , a total of 45 patients were enrolled in this phase I/II study ; their long-term survival was then followed for a median period of 5.8 years . Nineteen of the 39 patients in the phase II study survived for more than 2 years and met the primary endpoint of the study . The median overall survival period was 24.9 months [ 95 % confidence interval ( CI ) 17.4–74.5 months ] , and the 2- and 5-year overall survival rates were 51.0 and 43.0 % , respectively . The response rate was 85 % , and the median progression-free survival period was 13.8 months ( 95 % CI 9.5–27.1 months ) . Hematological toxicity was mild . Grade 3 febrile neutropenia and pneumonitis was observed in 5 and 5 % , respectively . Conclusion Our study indicated that S-1 plus cisplatin with concurrent thoracic radiotherapy yielded encouraging survival outcomes and an acceptable safety profile for LA-NSCLC Background The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer ( NSCLC ) remains unclear . A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin ( EP ) or carboplatin/paclitaxel ( PC ) in patients with stage III NSCLC . Patients and methods Patients were r and omly received 60–66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1–5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles ( EP arm ) , or paclitaxel 45 mg/m2 and carboplatin ( AUC 2 ) on day 1 weekly ( PC arm ) . The primary end point was overall survival ( OS ) . The study was design ed with 80 % power to detect a 17 % superiority in 3-year OS with a type I error rate of 0.05 . Results A total of 200 patients were r and omized and 191 patients were treated ( 95 in the EP arm and 96 in the PC arm ) . With a median follow-up time of 73 months , the 3-year OS was significantly higher in the EP arm than that of the PC arm . The estimated difference was 15.0 % ( 95 % CI 2.0%–28.0 % ) and P value of 0.024 . Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm ( log-rank test P = 0.095 , HR 0.76 , 95%CI 0.55–1.05 ) . The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm ( 33.3 % versus 18.9 % , P = 0.036 ) , while the incidence of Grade ≥3 esophagitis was higher in the EP arm ( 20.0 % versus 6.3 % , P = 0.009 ) . Conclusion EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC . Trial registration ID NCT01494558 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 Our aim was to evaluate the efficacy and safety of cisplatin with pemtrexed or vinorelbine and concurrent late course accelerated hyperfractionated radiotherapy ( LCAHRT ) . Patients with unresectable stage III non-small-cell lung cancer ( NSCLC ) were r and omly assigned to two regimens . The experimental ( PP ) arm included cisplatin , pemtrexed and concurrent LCAHRT based on bilateral lung V20 = 33 % . The control ( NP ) arm used cisplatin , vinorelbine with the same radiotherapy protocol . The primary endpoint was overall survival . Median survival times were 26.0 months ( 95 % CI 23.2 to 28.7 months ) and 28.5 months ( 95 % CI 17.1 to 39.9 months ) for the NP and PP arms , respectively ( P = 0.26 ) . Median progression-free survival was 12.5 months and 17.5 months in the NP and PP arms ( P = 0.07 ) . In both arms of the study , there were no differences in overall survival between patients with squamous and nonsquamous NSCLC . The incidences of grade 3 or 4 toxicity were higher in NP than PP arm . With concurrent LCAHRT , pemetrexed/cisplatin was equally as efficacious as vinorelbine/cisplatin , but showed a more favorable toxicity profile OBJECTIVE To evaluate the activity and safety of concurrent thoracic radiotherapy ( TRT ) plus weekly paclitaxel/carboplatin ( PC ) regimen compared with widely used cisplatin/etoposide ( PE ) regimen in patients with unresectable stage III non-small cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omly assigned to receive the following treatments : PE arm , cisplatin ( 50mg/m(2 ) ) on days 1 , 8 , 29 , and 36 and etoposide ( 50 mg/m(2 ) ) on days 1 - 5 and 29 - 33 plus 60 Gy of TRT ; PC arm , weekly concurrent carboplatin ( AUC = 2 ) and paclitaxel ( 45 mg/m(2 ) ) plus 60 Gy of TRT . RESULTS A total of 65 patients were r and omized ( PE arm , n = 33 ; PC arm , n = 32 ) . The 3-year overall survival ( OS ) was significantly better in the PE arm than in the PC arm ( 33.1 % vs. 13 % , P = .04 ) . The incidence of Grade 3/4 neutropenia was 78.1 % in the PE arm and 51.5 % in the PC arm ( P = .05 ) . The rate of Grade 2 or greater radiation pneumonitis was 25 % in the PE arm and 48.5 % in the PC arm ( P = .09 ) . CONCLUSIONS Compared to PE regimen , weekly PC regimen can not be recommended since it failed to achieve an improvement in either OS or PFS INTRODUCTION The optimal chemotherapy with thoracic radiotherapy ( TRT ) for locally advanced non-small-cell lung cancer ( NSCLC ) remains to be established . This r and omized phase II study of concurrent chemoradiotherapy was conducted to compare uracil/tegafur ( UFT ) and cisplatin with vinorelbine and cisplatin for stage III NSCLC . PATIENTS AND METHODS Patients with unresectable stage III NSCLC were r and omized to receive UP ( 400 mg/m(2 ) UFT on days 1 - 14 and 29 - 42 and 80 mg/m(2 ) cisplatin on days 8 and 36 ) or NP ( 20 mg/m(2 ) vinorelbine on days 1 , 8 , 29 , and 36 and 80 mg/m(2 ) cisplatin on days 1 and 29 ) . TRT began on day 1 ( total 60 Gy in 30 fractions ) . RESULTS Of 70 enrolled patients , 66 were evaluable for efficacy and safety . The overall response rates were 80 % ( 95 % CI : 67 - 93 % ) and 71 % ( 95 % CI : 55 - 87 % ) for the UP arm and the NP arm . With a median follow-up of 20.2 months , the progression-free survival and median survival time were 8.8 and 26.9 months in the UP arm , and 6.8 and 21.7 months in the NP arm . The 2-/3-year survival rates were 51.0/34.3 % and 46.9/33.4 % for the UP arm and the NP arm , respectively . Grade 3/4 neutropenia occurred in 20 % and 58 % of patients in the UP and NP arms , respectively . CONCLUSION Combined with concurrent TRT , the UP arm achieved better efficacy and safety compared with the NP arm , suggesting it to be a promising c and i date as a st and ard regimen for locally advanced NSCLC . Further evaluation of the UP arm is warranted PURPOSE To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer ( NSCLC ) . METHODS AND MATERIAL S S-1 ( 50mg/m(2 ) ) was administered orally twice daily for 14 days , with cisplatin ( 40 mg/m(2 ) ) on days 1 and 8 of each cycle every 3 weeks , for 2 - 4 cycles . Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy . The primary endpoint was the response rate , and secondary endpoints included progression-free survival , overall survival and safety . RESULTS Forty-one patients were enrolled in this study . The objective response rate was 87.8 % ( 98 % CI : 77.8 - 97.8 % ) . The median progression-free survival was 467 days ( 15.4 months ) , and the median survival time was 904 days ( 29.7 months ) . The overall survival rates at 1- and 2-years were 85.7 % and 52.9 % , respectively . Hematological toxicities included grade 3/4 neutropenia ( 17 % ) and grade 3/4 leukopenia ( 27 % ) . No grade 3 febrile neutropenia was detected , and grade 3/4 non-hematological toxicities were also mild . A grade 3 gastrointestinal hemorrhage was observed in one patient . CONCLUSIONS The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC PURPOSE This phase III trial of concurrent thoracic radiotherapy ( TRT ) was conducted to compare third-generation chemotherapy with second-generation chemotherapy in patients with unresectable stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Eligible patients received the following treatments : A ( control ) , four cycles of mitomycin ( 8 mg/m(2 ) on day 1)/vindesine ( 3 mg/m(2 ) on days 1 , 8)/cisplatin ( 80 mg/m(2 ) on day 1 ) plus TRT 60 Gy ( treatment break for 1 week ) ; B , weekly irinotecan ( 20 mg/m(2))/carboplatin ( area under the plasma concentration-time curve [ AUC ] 2 ) for 6 weeks plus TRT 60 Gy , followed by two courses of irinotecan ( 50 mg/m(2 ) on days 1 , 8)/carboplatin ( AUC 5 on day 1 ) ; C , weekly paclitaxel ( 40 mg/m(2))/carboplatin ( AUC 2 ) for 6 weeks plus TRT 60 Gy , followed by two courses of paclitaxel ( 200 mg/m(2 ) on day 1)/carboplatin ( AUC 5 on day 1 ) . RESULTS The median survival time and 5-year survival rates were 20.5 , 19.8 , and 22.0 months and 17.5 % , 17.8 % , and 19.8 % in arms A , B , and C , respectively . Although no significant differences in overall survival were apparent among the treatment arms , noninferiority of the experimental arms was not achieved . The incidences of grade 3 to 4 neutropenia , febrile neutropenia , and gastrointestinal disorder were significantly higher in arm A than in arm B or C ( P < .001 ) . Chemotherapy interruptions were more common in arm B than in arm A or C. CONCLUSION Arm C was equally efficacious and exhibited a more favorable toxicity profile among three arms . Arm C should be considered a st and ard regimen in the management of locally advanced unresectable NSCLC BACKGROUND We aim ed to compare overall survival after st and ard-dose versus high-dose conformal radiotherapy with concurrent chemotherapy and the addition of cetuximab to concurrent chemoradiation for patients with inoperable stage III non-small-cell lung cancer . METHODS In this open-label r and omised , two-by-two factorial phase 3 study in 185 institutions in the USA and Canada , we enrolled patients ( aged ≥ 18 years ) with unresectable stage III non-small-cell lung cancer , a Zubrod performance status of 0 - 1 , adequate pulmonary function , and no evidence of supraclavicular or contralateral hilar adenopathy . We r and omly assigned ( 1:1:1:1 ) patients to receive either 60 Gy ( st and ard dose ) , 74 Gy ( high dose ) , 60 Gy plus cetuximab , or 74 Gy plus cetuximab . All patients also received concurrent chemotherapy with 45 mg/m(2 ) paclitaxel and carboplatin once a week ( AUC 2 ) ; 2 weeks after chemoradiation , two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel ( 200 mg/m(2 ) ) and carboplatin ( AUC 6 ) . R and omisation was done with permuted block r and omisation methods , stratified by radiotherapy technique , Zubrod performance status , use of PET during staging , and histology ; treatment group assignments were not masked . Radiation dose was prescribed to the planning target volume and was given in 2 Gy daily fractions with either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy . The use of four-dimensional CT and image-guided radiation therapy were encouraged but not necessary . For patients assigned to receive cetuximab , 400 mg/m(2 ) cetuximab was given on day 1 followed by weekly doses of 250 mg/m(2 ) , and was continued through consolidation therapy . The primary endpoint was overall survival . All analyses were done by modified intention-to-treat . The study is registered with Clinical Trials.gov , number NCT00533949 . FINDINGS Between Nov 27 , 2007 , and Nov 22 , 2011 , 166 patients were r and omly assigned to receive st and ard-dose chemoradiotherapy , 121 to high-dose chemoradiotherapy , 147 to st and ard-dose chemoradiotherapy and cetuximab , and 110 to high-dose chemoradiotherapy and cetuximab . Median follow-up for the radiotherapy comparison was 22.9 months ( IQR 27.5 - 33.3 ) . Median overall survival was 28.7 months ( 95 % CI 24.1 - 36.9 ) for patients who received st and ard-dose radiotherapy and 20.3 months ( 17.7 - 25.0 ) for those who received high-dose radiotherapy ( hazard ratio [ HR ] 1.38 , 95 % CI 1.09 - 1.76 ; p=0.004 ) . Median follow-up for the cetuximab comparison was 21.3 months ( IQR 23.5 - 29.8 ) . Median overall survival in patients who received cetuximab was 25.0 months ( 95 % CI 20.2 - 30.5 ) compared with 24.0 months ( 19.8 - 28.6 ) in those who did not ( HR 1.07 , 95 % CI 0.84 - 1.35 ; p=0.29 ) . Both the radiation-dose and cetuximab results crossed protocol -specified futility boundaries . We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups . By contrast , the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects ( 205 [ 86 % ] of 237 vs 160 [ 70 % ] of 228 patients ; p<0.0001 ) . There were more treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups ( radiotherapy comparison : eight vs three patients ; cetuximab comparison : ten vs five patients ) . There were no differences in severe pulmonary events between treatment groups . Severe oesophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received st and ard-dose treatment ( 43 [ 21 % ] of 207 patients vs 16 [ 7 % ] of 217 patients ; p<0.0001 ) . INTERPRETATION 74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not better than 60 Gy plus concurrent chemotherapy for patients with stage III non-small-cell lung cancer , and might be potentially harmful . Addition of cetuximab to concurrent chemoradiation and consolidation treatment provided no benefit in overall survival for these patients . FUNDING National Cancer Institute and Bristol-Myers Squibb BACKGROUND The combination of chemotherapy with thoracic radiotherapy ( TRT ) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer . However , it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy . METHODS A total of 610 patients were r and omly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial . The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 63 Gy TRT delivered as once-daily fractions beginning on day 50 . Arm 2 used the same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily fractions beginning on day 1 [ corrected ] . Arm 3 used cisplatin at 50 mg/m2 on days 1 , 8 , 29 , and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1 , 2 , 5 , and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1 . The primary endpoint was overall survival , and secondary endpoints included tumor response and time to tumor progression . Kaplan-Meier analyses were used to assess survival , and toxic effects were examined using the Wilcoxon rank sum test . All statistical tests were two-sided . RESULTS Median survival times were 14.6 , 17.0 , and 15.6 months for arms 1 - 3 , respectively . Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment ( 5-year survival : sequential , arm 1 , 10 % [ 20 patients ] , 95 % confidence interval [ CI ] = 7 % to 15 % ; concurrent , arm 2 , 16 % [ 31 patients ] , 95 % CI = 11 % to 22 % , P = .046 ; concurrent , arm 3 , 13 % [ 22 patients ] , 95 % CI = 9 % to 18 % ) . With a median follow-up time of 11 years , the rates of acute grade 3 - 5 nonhematologic toxic effects were higher with concurrent than sequential therapy , but late toxic effects were similar . CONCLUSION Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 ( n = 862 ) every 3 weeks for up to six cycles . RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine ( median survival , 10.3 v 10.3 months , respectively ; HR = 0.94 ; 95 % CI , 0.84 to 1.05 ) . Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma ( n = 847 ; 12.6 v 10.9 months , respectively ) and large-cell carcinoma histology ( n = 153 ; 10.4 v 6.7 months , respectively ) . In contrast , in patients with squamous cell histology , there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed ( n = 473 ; 10.8 v 9.4 months , respectively ) . For cisplatin/pemetrexed , rates of grade 3 or 4 neutropenia , anemia , and thrombocytopenia ( P < or= .001 ) ; febrile neutropenia ( P = .002 ) ; and alopecia ( P < .001 ) were significantly lower , whereas grade 3 or 4 nausea ( P = .004 ) was more common . CONCLUSION In advanced NSCLC , cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine . This is the first prospect i ve phase III study in NSCLC to show survival differences based on histologic type PURPOSE Cancer and Leukemia Group B conducted a r and omized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy ( TRT ) . PATIENTS AND METHODS Patients with unresectable stage III non-small-cell lung cancer ( NSCLC ) were r and omly assigned to carboplatin ( area under the curve , 5 ) and pemetrexed ( 500 mg/m(2 ) ) every 21 days for four cycles and TRT ( 70 Gy ; arm A ) or the same treatment with cetuximab administered concurrent only with TRT ( arm B ) . Patients in both arms received up to four cycles of pemetrexed as consolidation therapy . The primary end point was the 18-month overall survival ( OS ) rate ; if the 18-month OS rate was ≥ 55 % , the regimen(s ) would be considered for further study . RESULTS Of the 101 eligible patients enrolled ( 48 in arm A and 53 in arm B ) , 60 % were male ; the median age was 66 years ( range , 32 to 81 years ) ; 44 % and 35 % had adenocarcinoma and squamous carcinoma , respectively ; and more patients enrolled onto arm A compared with arm B had a performance status of 0 ( 58 % v 34 % , respectively ; P = .04 ) . The 18-month OS rate was 58 % ( 95 % CI , 46 % to 74 % ) in arm A and 54 % ( 95 % CI , 42 % to 70 % ) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed ( P = .667 ) . The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy . CONCLUSION The combination of pemetrexed , carboplatin , and TRT met the prespecified criteria for further evaluation . This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC Background Cisplatin-based chemoradiotherapy is the st and ard treatment for unresectable , locally advanced non-small-cell lung cancer ( NSCLC ) . This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy . Methods Eligible patients with unresectable stage III NSCLC were r and omised to either the SP arm ( S-1 and cisplatin ) or VP arm ( vinorelbine and cisplatin ) , with early concurrent thoracic radiotherapy of 60 Gy , comprising 2 Gy per daily fraction . The primary endpoint was the overall survival rate at 2 years ( 2-year overall survival ( OS ) ) ( Study ID : UMIN000002420 ) . Results From September 2009 to September 2012 , 112 patients were enroled . Of the 108 eligible patients , the 2-year OS was 75.6 % ( 80 % confidence interval ( CI ) , 67–82 % ) in the SP arm and 68.5 % ( 80 % CI : 60–76 % ) in the VP arm . The hazard ratio ( HR ) for death between the two arms was 0.85 ( 0.48–1.49 ) . The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 ( 0.58–1.44 ) . There were four treatment-related deaths in the SP arm and five in the VP arm . Conclusions The null hypotheses for 2-year OS were rejected in both arms . The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study Purpose : To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin ( SP ) with concurrent thoracic radiotherapy ( RT ) followed by the consolidation SP for locally advanced non-small cell lung cancer . Patients and Methods : Patients with stage III non-small cell lung cancer , 20 to 74 years of age , and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible . The concurrent phase consisted of full dose S-1 ( orally at 40 mg/m2/dose twice daily , on days 1–14 ) and cisplatin ( 60 mg/m2 on day 1 ) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 ( 60 Gy/30 fractions over 6 weeks ) . After SP-RT , patients received an additional two cycles of SP as the consolidation phase . Results : Fifty-five patients were registered between November 2006 and December 2007 . Of the 50 patients for efficacy analysis , the median age was 64 years ; male/female 40/10 ; Eastern Cooperative Oncology Group performance status 0/1 , 21/29 ; clinical stage IIIA/IIIB 18/32 ; and adenocarcinoma/others 20/30 . There were 42 clinical responses including one complete response with an objective response rate of 84 % ( 95 % confidence interval [ CI ] , 71–93 % ) . The 1- and 2-year overall survival rates were 88 % ( 95 % CI , 75–94 % ) and 70 % ( 95 % CI , 55–81 % ) , respectively . The median progression-free survival was 20 months . Of the 54 patients for safety analysis , common toxicities in the concurrent phase included grade 3/4 neutropenia ( 26 % ) , thrombocytopenia ( 9 % ) , and grade 3 esophagitis ( 9 % ) and febrile neutropenia ( 9 % ) . In one patient , grade 3 pneumonitis was observed in the consolidation phase . There were two treatment-related deaths caused by infection in the concurrent phase . Conclusions : SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity PURPOSE To demonstrate the efficacy of docetaxel and cisplatin ( DP ) chemotherapy with concurrent thoracic radiotherapy ( TRT ) for patients with locally advanced non-small-cell lung cancer ( LA-NSCLC ) . PATIENTS AND METHODS Patients age 75 years or younger with LA-NSCLC , stratified by performance status , stage , and institution , were r and omly assigned to two arms consisting of DP ( docetaxel 40 mg/m(2 ) and cisplatin 40 mg/m(2 ) on days 1 , 8 , 29 , and 36 ) or mitomycin , vindesine , and cisplatin ( MVP ) chemotherapy with concurrent TRT . RESULTS Between July 2000 and July 2005 , 200 patients were allocated into either the DP or MVP arm . The survival time at 2 years , a primary end point , was favorable to the DP arm ( P = .059 by a stratified log-rank test as a planned analysis and P = .044 by an early-period , weighted log-rank as an unplanned analysis ) . There was a trend toward improved response rate , 2-year survival rate , median progression-free time , and median survival in the DP arm ( 78.8 % , 60.3%,13.4 months , and 26.8 months , respectively ) compared with the MVP arm ( 70.3 % , 48.1 % , 10.5 months , and 23.7 months , respectively ) , which was not statistically significant ( P > .05 ) . Grade 3 febrile neutropenia occurred more often in the MVP arm than in the DP arm ( 39 % v 22 % , respectively ; P = .012 ) , and grade 3 to 4 radiation esophagitis was likely to be more common in the DP arm than in the MVP arm ( 14 % v 6 % , P = .056 ) . CONCLUSION DP chemotherapy combined with concurrent TRT is an alternative to MVP chemotherapy for patients with LA-NSCLC |
1,179 | 25,515,689 | A ' low ' grade means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate .
No evidence emerged that short-term EC use is associated with health risk | BACKGROUND Electronic cigarettes ( ECs ) are electronic devices that heat a liquid - usually comprising propylene glycol and glycerol , with or without nicotine and flavours , stored in disposable or refillable cartridges or a reservoir - into an aerosol for inhalation .
Since ECs appeared on the market in 2006 there has been a steady growth in sales .
Smokers report using ECs to reduce risks of smoking , but some healthcare organisations have been reluctant to encourage smokers to switch to ECs , citing lack of evidence of efficacy and safety .
Smokers , healthcare providers and regulators are interested to know if these devices can reduce the harms associated with smoking .
In particular , healthcare providers have an urgent need to know what advice they should give to smokers enquiring about ECs .
OBJECTIVES To examine the efficacy of ECs in helping people who smoke to achieve long-term abstinence ; to examine the efficacy of ECs in helping people reduce cigarette consumption by at least 50 % of baseline levels ; and to assess the occurrence of adverse events associated with EC use . | Background Cigarette smoking is a tough addiction to break . Therefore , improved approaches to smoking cessation are necessary . The electronic-cigarette ( e-Cigarette ) , a battery-powered electronic nicotine delivery device ( ENDD ) resembling a cigarette , may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated . Methods In this prospect i ve proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers ( unwilling to quit ) experimenting the ' Categoria ' e-Cigarette with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend a total of five study visits : at baseline , week-4 , week-8 , week-12 and week-24 . Product use , number of cigarettes smoked , and exhaled carbon monoxide ( eCO ) levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events and product preferences were also review ed . Results Sustained 50 % reduction in the number of cig/day at week-24 was shown in 13/40(32.5 % ) participants ; their median of 25 cigs/day decreasing to 6 cigs/day ( p < 0.001 ) . Sustained 80 % reduction was shown in 5/40(12.5 % ) participants ; their median of 30 cigs/day decreasing to 3 cigs/day ( p = 0.043 ) . Sustained smoking abstinence at week-24 was observed in 9/40(22.5 % ) participants , with 6/9 still using the e-Cigarette by the end of the study . Combined sustained 50 % reduction and smoking abstinence was shown in 22/40 ( 55 % ) participants , with an overall 88 % fall in cigs/day . Mouth ( 20.6 % ) and throat ( 32.4 % ) irritation , and dry cough ( 32.4 % ) were common , but diminished substantially by week-24 . Overall , 2 to 3 cartridges/day were used throughout the study . Participants ' perception and acceptance of the product was good . Conclusion The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit ( http:// Clinical Trials.gov number NCT01195597 ) Electronic cigarettes ( e-Cigarette ) are battery-operated devices design ed to vaporise nicotine that may aid smokers to quit or reduce their cigarette consumption . Research on e-Cigarettes is urgently needed to ensure that the decisions of regulators , healthcare providers and consumers are evidence based . Here we assessed long-term effectiveness and tolerability of e-Cigarette used in a ‘ naturalistic ’ setting . This prospect i ve observational study evaluated smoking reduction/abstinence in smokers not intending to quit using an e-Cigarette ( ‘ Categoria ’ ; Arbi Group , Italy ) . After an intervention phase of 6 months , during which e-Cigarette use was provided on a regular basis , cigarettes per day ( cig/day ) and exhaled carbon monoxide ( eCO ) levels were followed up in an observation phase at 18 and 24 months . Efficacy measures included : ( a ) ≥50 % reduction in the number of cig/day from baseline , defined as self-reported reduction in the number of cig/day ( ≥50 % ) compared to baseline ; ( b ) ≥80 % reduction in the number of cig/day from baseline , defined as self-reported reduction in the number of cig/day ( ≥80 % ) compared to baseline ; ( c ) abstinence from smoking , defined as complete self-reported abstinence from tobacco smoking ( together with an eCO concentration of ≤10 ppm ) . Smoking reduction and abstinence rates were computed , and adverse events review ed . Of the 40 subjects , 17 were lost to follow-up at 24 months . A > 50 % reduction in the number of cig/day at 24 months was shown in 11/40 ( 27.5 % ) participants with a median of 24 cig/day use at baseline decreasing significantly to 4 cig/day ( p = 0.003 ) . Smoking abstinence was reported in 5/40 ( 12.5 % ) participants while combined > 50 % reduction and smoking abstinence was observed in 16/40 ( 40 % ) participants at 24 months . Five subjects stopped e-Cigarette use ( and stayed quit ) , three relapsed back to tobacco smoking and four up grade d to more performing products by 24 months . Only some mouth irritation , throat irritation , and dry cough were reported . Withdrawal symptoms were uncommon . Long-term e-Cigarette use can substantially decrease cigarette consumption in smokers not willing to quit and is well tolerated . ( http:// Clinical Trials.govnumberNCT01195597 ) Background Electronic cigarettes ( e-cigarettes or electronic nicotine delivery systems [ ENDS ] ) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and /or glycerol mist to the airway of users when drawing on the mouthpiece . Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device . People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids . However , to date there have been no adequately powered r and omised trials investigating their cessation efficacy or safety . This paper outlines the protocol for this study . Methods / design Design : Parallel group , 3-arm , r and omised controlled trial . Participants : People aged ≥18 years resident in Auckl and , New Zeal and ( NZ ) who want to quit smoking . Intervention : Stratified blocked r and omisation to allocate participants to either Elusion ™ e-cigarettes with nicotine cartridges ( 16 mg ) or with placebo cartridges ( i.e. no nicotine ) , or to nicotine patch ( 21 mg ) alone . Participants r and omised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day , while participants r and omised to patches will be told to use them daily for the same period . All participants will be offered behavioural support to quit from the NZ Quitline . Primary outcome : Biochemically verified ( exhaled carbon monoxide ) continuous abstinence at six months after quit day . Sample size : 657 people ( 292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarettes group ) will provide 80 % power at p = 0.05 to detect an absolute difference of 10 % in abstinence between the nicotine e-cigarette and nicotine patch groups , and 15 % between the nicotine and placebo e-cigarette groups . Discussion This trial will inform international debate and policy on the regulation and availability of e-cigarettes . If shown to be efficacious and safe , these devices could help many smokers as an alternative smoking cessation aid to st and ard nicotine products . Trial registration Australian NZ Clinical Trials Registry ( ACTRN12610000866000 ) Background While electronic cigarettes are forbidden in several countries , their sales are exploding in many others . Although e-cigarettes have been proposed as long-term substitutes for traditional smoking or as a tool for smoking cessation , very scarce data are available on their efficacy and safety . We describe the protocol of a 5-year multicentric prospect i ve study aim ed to evaluate short- and long-term adherence to e-cigarette smoking and the efficacy of e-cigarettes in reducing and /or quitting traditional cigarette smoking . The study will also compare the health effects of electronic vs traditional vs mixed cigarette smoking . Methods / design From June to December 2013 , we will enroll adult smokers of : ( EC ) e-cigarettes ( self-reported inhaling ≥ 50 puffs per week since ≥ 6 months ) ; ( TC ) traditional cigarettes ( ≥ 1 per day since ≥ 6 m ) ; ( Mixed ) both electronic and traditional cigarettes ( ≥1 per day since ≥ 6 m ) . Eligible subjects will be requested participation through newspaper advertisements and direct contact at the shops . Each subject will have to compile a structured question naire at enrolment and after 6 , 12 , 24 , 36 and 60 months . The level of carbon monoxide in expired after breath will be evaluated in all subjects declaring no traditional cigarette smoking in any follow-up phase , using portable carbon monoxide analyzers . The primary outcomes are traditional smoking cessation rates and number of smoked cigarettes . Secondary outcomes include adherence to e-cigarettes , self-reported adverse events , quality of life , and time to hospital admission for one among cardiovascular diseases , chronic obstructive pulmonary diseases , cancer of the lung , esophagus , larynx , oral cavity , bladder , pancreas , kidney , stomach , cervix , and myeloid leukemia . Admissions will be checked using official discharge data of the Abruzzo Region . A minimum of 500 subjects in each group will be enrolled , for a total of 1500 participants . Cox proportional hazards analysis will be used to calculate adjusted relative hazards of smoking cessation by each variable . Discussion Data on long-term efficacy and safety of e-cigarettes will be of utmost importance to form the basis for guidelines and regulatory decisions on e-cigarettes . Trial registration The protocol has been registered ( NCT01785537 ) and approved by the Ethics Committee of the University of Chieti ( Record n. 6 ; 25 - 03 - 2013 ) Background and Aims Electronic cigarettes ( e-cigarettes ) are rapidly increasing in popularity . Two r and omized controlled trials have suggested that e-cigarettes can aid smoking cessation , but there are many factors that could influence their real-world effectiveness . This study aim ed to assess , using an established methodology , the effectiveness of e-cigarettes when used to aid smoking cessation compared with nicotine replacement therapy ( NRT ) bought over-the-counter and with unaided quitting in the general population . Design and Setting A large cross-sectional survey of a representative sample of the English population . Participants The study included 5863 adults who had smoked within the previous 12 months and made at least one quit attempt during that period with either an e-cigarette only ( n = 464 ) , NRT bought over-the-counter only ( n = 1922 ) or no aid in their most recent quit attempt ( n = 3477 ) . Measurements The primary outcome was self-reported abstinence up to the time of the survey , adjusted for key potential confounders including nicotine dependence . Findings E-cigarette users were more likely to report abstinence than either those who used NRT bought over-the-counter [ odds ratio ( OR ) = 2.23 , 95 % confidence interval ( CI ) = 1.70–2.93 , 20.0 versus 10.1 % ] or no aid ( OR = 1.38 , 95 % CI = 1.08–1.76 , 20.0 versus 15.4 % ) . The adjusted odds of non-smoking in users of e-cigarettes were 1.63 ( 95 % CI = 1.17–2.27 ) times higher compared with users of NRT bought over-the-counter and 1.61 ( 95 % CI = 1.19–2.18 ) times higher compared with those using no aid . Conclusions Among smokers who have attempted to stop without professional support , those who use e-cigarettes are more likely to report continued abstinence than those who used a licensed NRT product bought over-the-counter or no aid to cessation . This difference persists after adjusting for a range of smoker characteristics such as nicotine dependence Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly Background Electronic cigarettes ( e-cigarettes ) are becoming increasingly popular with smokers worldwide . Users report buying them to help quit smoking , to reduce cigarette consumption , to relieve tobacco withdrawal symptoms , and to continue having a ‘ smoking ’ experience , but with reduced health risks . Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators , healthcare providers and consumers are based on science . Methods ECLAT is a prospect i ve 12-month r and omized , controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model ( ‘ Categoria ’ ; Arbi Group Srl , Italy ) compared to its non-nicotine choice . GroupA ( n = 100 ) received 7.2 mg nicotine cartridges for 12 weeks ; GroupB ( n = 100 ) , a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges ; GroupC ( n = 100 ) received no-nicotine cartridges for 12 weeks . The study consisted of nine visits during which cig/day use and exhaled carbon monoxide ( eCO ) levels were measured . Smoking reduction and abstinence rates were calculated . Adverse events and product preferences were also review ed . Results Declines in cig/day use and eCO levels were observed at each study visits in all three study groups ( p<0.001 vs baseline ) , with no consistent differences among study groups . Smoking reduction was documented in 22.3 % and 10.3 % at week-12 and week-52 respectively . Complete abstinence from tobacco smoking was documented in 10.7 % and 8.7 % at week-12 and week-52 respectively . A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study . Participants ’ perception and acceptance of the product under investigation was satisfactory . Conclusion In smokers not intending to quit , the use of e-cigarettes , with or without nicotine , decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects . Trial Registration Clinical Trials.gov NCT01164072 The objective of this study was to compare the short-term respiratory effects due to the inhalation of electronic and conventional tobacco cigarette-generated mainstream aerosols through the measurement of the exhaled nitric oxide ( eNO ) . To this purpose , twenty-five smokers were asked to smoke a conventional cigarette and to vape an electronic cigarette ( with and without nicotine ) , and an electronic cigarette without liquid ( control session ) . Electronic and tobacco cigarette mainstream aerosols were characterized in terms of total particle number concentrations and size distributions . On the basis of the measured total particle number concentrations and size distributions , the average particle doses deposited in alveolar and tracheobronchial regions of the lungs for a single 2-s puff were also estimated considering a subject performing resting ( sitting ) activity . Total particle number concentrations in the mainstream result ed equal to 3.5±0.4 × 10(9 ) , 5.1±0.1 × 10(9 ) , and 3.1±0.6 × 10(9 ) part . cm(-3 ) for electronic cigarettes without nicotine , with nicotine , and for conventional cigarettes , respectively . The corresponding alveolar doses for a resting subject were estimated equal to 3.8 × 10(10 ) , 5.2 × 10(10 ) and 2.3 × 10(10 ) particles . The mean eNO variations measured after each smoking/vaping session were equal to 3.2ppb , 2.7ppb and 2.8ppb for electronic cigarettes without nicotine , with nicotine , and for conventional cigarettes , respectively ; whereas , negligible eNO changes were measured in the control session . Statistical tests performed on eNO data showed statistically significant differences between smoking/vaping sessions and the control session , thus confirming a similar effect on human airways whatever the cigarette smoked/vaped , the nicotine content , and the particle dose received AIM To determine the combined effect of very low nicotine content ( VLNC ) cigarettes and usual Quitline care [ nicotine replacement therapy ( NRT ) and behavioural support ] on smoking abstinence , in smokers motivated to quit . DESIGN Single-blind , parallel r and omized trial . SETTING New Zeal and . PARTICIPANTS Smokers who called the Quitline for quitting support were r and omized to either VLNC cigarettes to use whenever they had an urge to smoke for up to 6 weeks after their quit date , in combination with usual Quitline care ( 8 weeks of NRT patches and /or gum or lozenges , plus behavioural support ) or to usual Quitline care alone . MEASUREMENTS The primary outcome was 7-day point-prevalence smoking abstinence 6 months after quit day . Secondary outcomes included continuous abstinence , cigarette consumption , withdrawal , self-efficacy , alcohol use , serious adverse events and views on the use of the VLNC cigarettes at 3 and 6 weeks and 3 and 6 months . FINDINGS A total of 1410 participants were r and omized ( 705 in each arm ) , with a 24 % loss to follow-up at 6 months . Participants in the intervention group were more likely to have quit smoking at 6 months compared to the usual care group [ 7-day point-prevalence abstinence 33 versus 28 % , relative risk ( RR ) = 1.18 , 95 % confidence interval ( CI ) : 1.01 , 1.39 , P = 0.037 ; continuous abstinence 23 versus 15 % , RR = 1.50 , 95 % CI : 1.20 , 1.87 , P = 0.0003 ] . The median time to relapse in the intervention group was 2 months compared to 2 weeks in the usual care group ( P < 0.0001 ) . CONCLUSIONS Addition of very low nicotine content cigarettes to st and ard Quitline smoking cessation support may help some smokers to become abstinent Abstract Context : Electronic cigarettes ( e-cigarettes ) are becoming increasingly popular yet their effects on health remain unknown . Objective : To conduct the first comprehensive and st and ardized assessment of the acute impact of active and passive e-cigarette smoking on serum cotinine and lung function , as compared to active and passive tobacco cigarette smoking . Material s and methods : Fifteen smokers ( ≥15 cigarettes/day ; seven females ; eight males ) and 15 never-smokers ( seven females ; eight males ) completed this repeated- measures controlled study . Smokers underwent a control session , an active tobacco cigarette ( their favorite br and ) smoking session and an active e-cigarette smoking session . Never-smokers underwent a control session , a passive tobacco cigarette smoking session and a passive e-cigarette smoking session . Serum cotinine , lung function , exhaled carbon monoxide and nitric oxide were assessed . The level of significance was set at p ≤ 0.001 to adjust for multiple comparisons . Results : e-Cigarettes and tobacco cigarettes generated similar ( p > 0.001 ) effects on serum cotinine levels after active ( 60.6 ± 34.3 versus 61.3 ± 36.6 ng/ml ) and passive ( 2.4 ± 0.9 versus 2.6 ± 0.6 ng/ml ) smoking . Neither a brief session of active e-cigarette smoking ( indicative : 3 % reduction in FEV1/FVC ) nor a 1 h passive e-cigarette smoking ( indicative : 2.3 % reduction in FEV1/FVC ) significantly affected the lung function ( p > 0.001 ) . In contrast , active ( indicative : 7.2 % reduction in FEV1/FVC ; p < 0.001 ) but not passive ( indicative : 3.4 % reduction in FEV1/FVC ; p = 0.005 ) tobacco cigarette smoking undermined lung function . Conclusion : Regarding short-term usage , the studied e-cigarettes generate smaller changes in lung function but similar nicotinergic impact to tobacco cigarettes . Future research should target the health effects of long-term e-cigarette usage , including the effects of nicotine dosage BACKGROUND Electronic cigarettes ( e-cigarettes ) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts . We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit . METHODS We did this pragmatic r and omised-controlled superiority trial in Auckl and , New Zeal and , between Sept 6 , 2011 , and July 5 , 2013 . Adult ( ≥18 years ) smokers wanting to quit were r and omised ( with computerised block r and omisation , block size nine , stratified by ethnicity [ Māori ; Pacific ; or non-Māori , non-Pacific ] , sex [ men or women ] , and level of nicotine dependence [ > 5 or ≤5 Fagerström test for nicotine dependence ] ) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes , nicotine patches ( 21 mg patch , one daily ) , or placebo e-cigarettes ( no nicotine ) , from 1 week before until 12 weeks after quit day , with low intensity behavioural support via voluntary telephone counselling . The primary outcome was biochemically verified continuous abstinence at 6 months ( exhaled breath carbon monoxide measurement < 10 ppm ) . Primary analysis was by intention to treat . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12610000866000 . FINDINGS 657 people were r and omised ( 289 to nicotine e-cigarettes , 295 to patches , and 73 to placebo e-cigarettes ) and were included in the intention-to-treat analysis . At 6 months , verified abstinence was 7·3 % ( 21 of 289 ) with nicotine e-cigarettes , 5·8 % ( 17 of 295 ) with patches , and 4·1 % ( three of 73 ) with placebo e-cigarettes ( risk difference for nicotine e-cigarette vs patches 1·51 [ 95 % CI -2·49 to 5·51 ] ; for nicotine e-cigarettes vs placebo e-cigarettes 3·16 [ 95 % CI -2·29 to 8·61 ] ) . Achievement of abstinence was substantially lower than we anticipated for the power calculation , thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes . We identified no significant differences in adverse events , with 137 events in the nicotine e-cigarettes group , 119 events in the patches group , and 36 events in the placebo e-cigarettes group . We noted no evidence of an association between adverse events and study product . INTERPRETATION E-cigarettes , with or without nicotine , were modestly effective at helping smokers to quit , with similar achievement of abstinence as with nicotine patches , and few adverse events . Uncertainty exists about the place of e-cigarettes in tobacco control , and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels . FUNDING Health Research Council of New Zeal and INTRODUCTION This study examined changes in smokers ' readiness and confidence to quit smoking , smoking behavior , nicotine withdrawal symptoms , and tobacco product preference following electronic cigarette ( EC ) experimentation and 1 week of ad libitum use . METHODS Current cigarette smokers , with no prior use of ECs and uninterested in quitting , completed 3 study phases : baseline assessment ( N = 20 ) , experimentation ( N = 19 ) , and ad libitum use ( N = 16 ) . Baseline assessment consisted of completion of assessment measures and exhaled carbon monoxide measurements . Experimentation phases consisted of four , 75-min sessions in which participants completed assessment measures and sample d 3 EC br and s and their own br and of cigarette ( OBC ) . Ad libitum use included participants selecting and being provided their preferred EC br and from the experimentation phase to be used " as you want " for 1 week . Outcome measures included readiness and confidence to quit smoking , nicotine withdrawal symptoms , product preference/satisfaction , and smoking behavior items . RESULTS Readiness and confidence to quit increased significantly during the experimentation period and continued to increase during ad libitum use . There were no significant differences in reported effectiveness in reducing smoking urges and cravings between OBC and EC though OBC were rated as more enjoyable and satisfying . During ad libitum use , regular cigarette smoking decreased by approximately 44 % from baseline levels with overall tobacco use ( EC + OBC ) remaining the same . CONCLUSIONS Among a small convenience sample of unmotivated cigarette smokers , EC experimentation and 1 week of ad libitum use increased readiness and confidence to quit regular cigarettes and reduced regular cigarette smoking Rationale It is well established that nicotine improves , and deprivation impairs , cognitive performance and mood in smokers . Prospect i ve memory ( PM ) , remembering to execute a delayed intention at a given time point , is under-explored in smokers . Whilst a h and ful of studies have shown improved PM with nicotine , the effects of nicotine delivered via the electronic cigarette ( e-cigarette ) have not been investigated . Objective This study explores whether , by comparison with placebo , nicotine delivered via the e-cigarette can improve PM , tobacco withdrawal symptoms and desire to smoke in abstinent smokers . Methods Twenty smokers , abstinent for 8–10 h , each completed two experimental sessions under nicotine ( 18 mg ) and placebo ( 0 mg ) e-cigarette conditions . Participants completed a single-item desire-to-smoke scale and the Mood and Physical Symptoms Scale . PM was measured using the Cambridge Prospect i ve Memory Test . Results Compared with placebo , the nicotine e-cigarette reduced the desire to smoke and tobacco withdrawal symptoms , and improved time-based but not event-based PM . There was a moderate , marginally significant negative correlation between PM performance during abstinence and nicotine dependence . Conclusions This is the first study to show that nicotine derived via e-cigarette can improve PM in abstinent smokers , suggesting efficient nicotine delivery . The finding that the effect of nicotine was restricted to time-based rather than event-based PM is consistent with the view that nicotine acts to improve performance on strategic ( effortful ) rather than automatic processing . These findings add to the growing body of evidence that the e-cigarette can replace some of the effects of nicotine derived from tobacco smoking , thus highlighting its potential for smoking cessation Background It is well established in studies across several countries that tobacco smoking is more prevalent among schizophrenic patients than the general population . Electronic cigarettes are becoming increasingly popular with smokers worldwide . To date there are no large r and omized trials of electronic cigarettes in schizophrenic smokers . A well- design ed trial is needed to compare efficacy and safety of these products in this special population . Methods / Design Intervention : We have design ed a r and omized controlled trial investigating the efficacy and safety of electronic cigarette . The trial will take the form of a prospect i ve 12-month r and omized clinical study to evaluate smoking reduction , smoking abstinence and adverse events in schizophrenic smokers not intending to quit . We will also monitor quality of life , neurocognitive functioning and measure participants ’ perception and satisfaction of the product . Outcome measures : A ≥50 % reduction in the number of cigarettes/day from baseline , will be calculated at each study visit ( “ reducers ” ) . Abstinence from smoking will be calculated at each study visit ( “ quitters ” ) . Smokers who leave the study protocol before its completion and will carry out the Early Termination Visit or who will not satisfy the criteria of “ reducers ” and “ quitters ” will be defined “ non responders”.Statistical analysis : The differences of continuous variables between the three groups will be evaluated with the Kruskal-Wallis Test , followed by the Dunn multiple comparison test . The differences between the three groups for normally distributed data will be evaluated with ANOVA test one way , followed by the Newman-Keuls multiple comparison test . The normality of the distribution will be evaluated with the Kolmogorov-Smirnov test . Any correlations between the variables under evaluation will be assessed by Spearman r correlation . To compare qualitative data will be used the Chi-square test . Discussion The main strengths of the SCARIS study are the following : it ’s the first large RCT on schizophrenic patient , involving in and outpatient , evaluating the effect of a three-arm study design , and a long term of follow-up (52-weeks).The goal is to propose an effective intervention to reduce the risk of tobacco smoking , as a complementary tool to treat tobacco addiction in schizophrenia . Trial registration Clinical Trials.gov , NCT01979796 BACKGROUND Smoking acutely relieves negative affect ( NA ) due to smoking abstinence but may not relieve NA from other sources , such as stressors . METHODS Dependent smokers ( n = 104 ) r and omly assigned to one of three smoking conditions ( nicotine or denicotinized cigarettes , or no smoking ) completed four negative mood induction procedures ( one per session ) : 1 ) overnight smoking abstinence , 2 ) challenging computer task , 3 ) public speech preparation , and 4 ) watching negative mood slides . A fifth session involved a neutral mood control . The two smoking groups took four puffs on their assigned cigarette and then smoked those same cigarettes ad libitum during continued mood induction . All subjects rated their level of NA and positive affect on several measures ( Mood Form , Positive and Negative Affect Scale , Stress-Arousal Checklist , and State-Trait Anxiety Inventory-state ) . They also rated craving and withdrawal . RESULTS Negative affect relief from smoking depended on the NA source ( i.e. , mood induction procedure ) and the affect measure . Smoking robustly relieved NA due to abstinence on all four measures but only modestly relieved NA due to the other sources and typically on only some measures . Smoking 's effects on positive affect and withdrawal were similar to effects on NA , but relief of craving depended less on NA source . Smoking reinforcement only partly matched the pattern of NA relief . Few responses differed between the nicotine and denicotinized smoking groups . CONCLUSIONS Acute NA relief from smoking depends on the situation and the affect measure used but may not depend on nicotine intake . These results challenge the common assumption that smoking , and nicotine in particular , broadly alleviates NA Previous studies have suggested that sensory cues associated with cigarette smoking can suppress certain smoking withdrawal symptoms , including craving for cigarettes . In this study we investigated the subjective effects of a cigarette substitute delivering a vapor of black pepper essential oil . Forty-eight cigarette smokers participated in a 3-h session conducted after overnight deprivation from smoking . Subjects were r and omly assigned to one of three conditions : one group of smokers puffed on a device that delivered a vapor from essential oil of black pepper ; a second group puffed on the device with a mint/menthol cartridge , and a third group used a device containing an empty cartridge . Subjects puffed and inhaled ad libitum from the device throughout the session during which no smoking was allowed . Reported craving for cigarettes was significantly reduced in the pepper condition relative to each of the two control conditions . In addition , negative affect and somatic symptoms of anxiety were alleviated in the pepper condition relative to the unflavored placebo . The intensity of sensations in the chest was also significantly higher for the pepper condition . These results support the view that respiratory tract sensations are important in alleviating smoking withdrawal symptoms . Cigarette substitutes delivering pepper constituents may prove useful in smoking cessation treatment Rationale Electronic cigarettes are becoming increasingly popular among smokers worldwide . Commonly reported reasons for use include the following : to quit smoking , to avoid relapse , to reduce urge to smoke , or as a perceived lower-risk alternative to smoking . Few studies , however , have explored whether electronic cigarettes ( e-cigarettes ) deliver measurable levels of nicotine to the blood . Objective This study aims to explore in experienced users the effect of using an 18-mg/ml nicotine first-generation e-cigarette on blood nicotine , tobacco withdrawal symptoms , and urge to smoke . Methods Fourteen regular e-cigarette users ( three females ) , who are abstinent from smoking and e-cigarette use for 12 h , each completed a 2.5 h testing session . Blood was sample d , and question naires were completed ( tobacco-related withdrawal symptoms , urge to smoke , positive and negative subjective effects ) at four stages : baseline , 10 puffs , 60 min of ad lib use and a 60-min rest period . Results Complete sets of blood were obtained from seven participants . Plasma nicotine concentration rose significantly from a mean of 0.74 ng/ml at baseline to 6.77 ng/ml 10 min after 10 puffs , reaching a mean maximum of 13.91 ng/ml by the end of the ad lib puffing period . Tobacco-related withdrawal symptoms and urge to smoke were significantly reduced ; direct positive effects were strongly endorsed , and there was very low reporting of adverse effects . Conclusions These findings demonstrate reliable blood nicotine delivery after the acute use of this br and /model of e-cigarette in a sample of regular users . Future studies might usefully quantify nicotine delivery in relation to inhalation technique and the relationship with successful smoking cessation/harm reduction Background Electronic cigarettes have been developed and marketed in recent years as smoking substitutes . However , no studies have evaluated their effects on the cardiovascular system . The purpose of this study was to examine the immediate effects of electronic cigarette use on left ventricular ( LV ) function , compared to the well-documented acute adverse effects of smoking . Methods Echocardiographic examinations were performed in 36 healthy heavy smokers ( SM , age 36 ± 5 years ) before and after smoking 1 cigarette and in 40 electronic cigarette users ( ECIG , age 35 ± 5 years ) before and after using the device with “ medium-strength ” nicotine concentration ( 11 mg/ml ) for 7 minutes . Mitral flow diastolic velocities ( E , A ) , their ratio ( E/A ) , deceleration time ( DT ) , isovolumetric relaxation time ( IVRT ) and corrected-to-heart rate IVRT ( IVRTc ) were measured . Mitral annulus systolic ( Sm ) , and diastolic ( Em , Am ) velocities were estimated . Myocardial performance index was calculated from Doppler flow ( MPI ) and tissue Doppler ( MPIt ) . Longitudinal deformation measurements of global strain ( GS ) , systolic ( SRs ) and diastolic ( SRe , SRa ) strain rate were also performed . Results Baseline measurements were similar in both groups . In SM , IVRT and IVRTc were prolonged , Em and SRe were decreased , and both MPI and MPIt were elevated after smoking . In ECIG , no differences were observed after device use . Comparing after-use measurements , ECIG had higher Em ( P = 0.032 ) and SRe ( P = 0.022 ) , and lower IVRTc ( P = 0.011 ) , MPI ( P = 0.001 ) and MPIt ( P = 0.019 ) . The observed differences were significant even after adjusting for changes in heart rate and blood pressure . Conclusions Although acute smoking causes a delay in myocardial relaxation , electronic cigarette use has no immediate effects . Electronic cigarettes ’ role in tobacco harm reduction should be studied intensively in order to determine whether switching to electronic cigarette use may have long-term beneficial effects on smokers ’ health . Trial registration Current Controlled Trials IS RCT Electronic cigarettes ( e-cigarettes ) are battery operated devices that deliver nicotine via inhaled vapour . Few studies have evaluated acute effects on craving and mood , and none have explored effects on cognition . This study aim ed to explore the effects of the White Super e-cigarette on desire to smoke , nicotine withdrawal symptoms , attention and working memory . Eighty-six smokers were r and omly allocated to either : 18 mg nicotine e-cigarette ( nicotine ) , 0 mg e-cigarette ( placebo ) , or just hold the e-cigarette ( just hold ) conditions . Participants rated their desire to smoke and withdrawal symptoms at baseline ( T1 ) , and five ( T2 ) and twenty ( T3 ) minutes after using the e-cigarette ad libitum for 5 min . A subset of participants completed the Letter Cancellation and Brown-Peterson Working Memory Tasks . After 20 min , compared with the just hold group , desire to smoke and some aspects of nicotine withdrawal were significantly reduced in the nicotine and placebo group ; the nicotine e-cigarette was superior to placebo in males but not in females . The nicotine e-cigarette also improved working memory performance compared with placebo at the longer interference intervals . There was no effect of nicotine on Letter Cancellation performance . To conclude , the White Super e-cigarette alleviated desire to smoke and withdrawal symptoms 20 min after use although the nicotine content was more important for males . This study also demonstrated for the first time that the nicotine e-cigarette can enhance working memory performance . Further evaluation of the cognitive effects of the e-cigarette and its efficacy as a cessation tool is merited Background : Cigarette smoking is a tough addiction to break . This dependence is the most common dual diagnosis for individuals with schizophrenia . Currently three effective drugs are approved for smoking cessation : nicotine replacement therapy ( NRT ) , varenicline and bupropion . However , some serious side effects of varenicline have been reported , including depression , suicidal thoughts , and suicide . The use of bupropion also has side effects . It should not be used by people who have epilepsy or any condition that lowers the seizure threshold , nor by people who take a specific class of drugs called monoamine oxidase inhibitors . Hence , there are pharmacodynamic reason to believe they could precipitate or exacerbate psychosis . For its capacity to deliver nicotine and provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures , electronic-cigarettes may reduce nicotine withdrawal symptoms without serious side effects . Our recent work with ECs in healthy smokers not intending to quit consistently show surprisingly high success rates . We hypothesised that these positive findings could be replicated in difficult patients with schizophrenia This tool may help smokers with schizophrenia remain abstinent during their quitting attempts or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated for this special population . Methods : In this study we monitored possible modifications in smoking habits of 14 smokers ( not intending to quit ) with schizophrenia experimenting with the “ Categoria ” e-Cigarette with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend six study visits : at baseline , week-4 , week-8 , week-12 week-24 and week 52 . Product use , number of cigarettes smoked , carbon monoxide in exhaled breath ( eCO ) and positive and negative symptoms of schizophrenia levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events were also review ed . Results : Sustained 50 % reduction in the number of cig/day at week-52 was shown in 7/14 ( 50 % ) participants ; their median of 30 cig/day decreasing significantly to 15 cig/day ( p = 0.018 ) . Sustained smoking abstinence at week-52 was observed in 2/14 ( 14.3 % ) participants . Combined sustained 50 % reduction and smoking abstinence was shown in 9/14 ( 64.3 % ) participants . Nausea was observed in 2/14 ( 14.4 % ) of participants , throat irritation in 2/14 ( 14.4 % ) of participants , headache in 2/14 ( 14.4 % ) of participants , and dry cough in 4/14 ( 28.6 % ) of participants . However , these adverse events diminished substantially by week-24 . Overall , one to two cartridges/day were used throughout the study . Positive and negative symptoms of schizophrenia are not increased after smoking reduction/cessation in patients using e-cigarettes . Conclusions : We have shown for the first time that the use of e-cigarette substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke not intending to quit . This was achieved without negative impacts on the symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales BACKGROUND There are several nicotine replacement products on the market , and physicians are likely to be asked with increasing frequency about which of these products their patients should use . OBJECTIVE To provide a basis for rational advice by comparing nicotine polacrilex ( gum ) , a transdermal patch , nasal spray , and an inhaler . DESIGN R and omized trial with assessment s at the quit date and 1 , 4 , and 12 weeks later . SETTING Hospital smokers ' clinic . PATIENTS Male and female community volunteers ( N = 504 ) smoking 10 or more cigarettes per day and seeking help to stop smoking . INTERVENTIONS Patients were given brief advice , and purchased their nicotine replacement treatment at approximately half the regular retail price . MAIN OUTCOME MEASURES Nicotine replacement treatment use , ratings of withdrawal symptoms , ratings of product characteristics and helpfulness , and biochemically vali date d continuous lapse-free abstinence . RESULTS The products did not differ in their effects on withdrawal discomfort , urges to smoke , or rates of abstinence . The continuous vali date d 12-week abstinence rates were 20 % , 21 % , 24 % , and 24 % in the gum , patch , spray , and inhaler groups , respectively . Compliance with recommended nicotine replacement treatment use was high for the patch , low for gum , and very low for the spray and the inhaler . The spray was underused because of adverse effects more often than the other products . In the subjects using the spray , the level of use among abstainers at week 1 predicted outcome at week 12 . The inhaler was rated as more embarrassing to use than the other products , but provided at least as much nicotine as the gum . CONCLUSION When asked about nicotine replacement treatment products available , physicians should note that , despite low compliance with the recommended dose of the spray and inhaler and differences in product ratings , overall , there are no notable differences between the products in their effects on withdrawal discomfort , perceived helpfulness , or general efficacy Sensory aspects of cigarette smoke are important for providing smoking satisfaction . In previous studies , we have found that substitution of the sensory cues of smoking with a citric acid aerosol significantly reduces craving for cigarettes and enhances smoking reduction and cessation with people trying to quit smoking cigarettes . In the current study , we conducted two clinical smoking cessation trials using an ascorbic acid aerosol as a sensory substitute . The cigarette substitute consisted of a cigarette-sized tube which delivered a fine aerosol of ascorbic acid ( approx . 1 mg/puff , up to a maximum of 300 mg/day ) . Study 1 examined the overall effectiveness of the ascorbic acid smoking substitute device . One group of subjects which used the device and received clinical counseling was compared with another group which received only clinical counseling . The group using the device showed significantly greater abstinence rates at 3 weeks post-cessation . After the subjects stopped using the device , no difference in abstinence was detected . Study 2 was conducted to focus specifically on the role of tracheobronchial sensations in relieving craving for cigarettes . Two closely matched ascorbic acid delivery systems were compared . One device delivered fine particles of ascorbic acid that were targeted to reach the trachea , while the other delivered coarser particles of ascorbic acid that were not expected to reach the trachea or lower airways . An initial enhancement in smoking reduction was found for subjects using the fine particle device relative to those using the coarse particle device . However , by the end of treatment ( 5 weeks ) both groups showed similar degrees of smoking reduction . For those who were abstinent from smoking at the end of treatment , craving for cigarettes and negative mood were both significantly lower for those using the fine particle device . Also , hunger for food was significantly lower in the fine particle device group . These results suggest that ascorbic acid delivered from a cigarette substitute may be effective in reducing smoking and promoting smoking abstinence Although electronic cigarettes ( e-cigarettes ) are aggressively promoted as smoking cessation aids,1 studies of their effectiveness for cessation have been unconvincing.2 , 3 One r and omized trial comparing e-cigarettes with and without nicotine , and nicotine patch found no differences in 6-month quit rates.2 Population -based , longitudinal studies have also not shown associations between e-cigarette use and quitting.4 , 5 A longitudinal , international study found that , although 85 % of smokers who used e-cigarettes reported using them to quit , e-cigarette users did not quit more frequently than non-users (p=.516).4 Among US quitline callers , e-cigarette users were less likely to have quit at 7 months than non-users.5 We employed a longitudinal analysis of a national sample of current US smokers to determine whether e-cigarette use predicted successful quitting , or reduced cigarette consumption STUDY OBJECTIVE This study was conducted to determine if the combination of airway sensory replacement and nicotine replacement improves 10-week smoking abstinence rates over nicotine replacement alone . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING Outpatient research clinic . PARTICIPANTS One hundred healthy volunteers who smoked at least one pack of cigarettes per day and desired to quit smoking . INTERVENTIONS Subjects received either citric acid ( n = 41 ) or lactose placebo ( n = 59 ) inhalers to cope with smoking urges for 10 weeks . All subjects received self-help material s and nicotine patches for 6 weeks . Return visits were at weeks 1 , 4 , 6 , and 10 . Abstinence was defined as zero cigarettes smoked since the quit date verified by exhaled carbon monoxide < or = 8 ppm at all return visits . Inhaler effects were measured by a st and ardized question naire . MEASUREMENTS AND RESULTS The primary outcome of continuous abstinence at the end of the 10-week treatment period was 19.5 % ( 95 % confidence interval [ CI ] = 7.4 to 31.6 % ) for the citric acid group vs 6.8 % ( 95 % CI = 0.4 to 13.2 % ) for the lactose group ( p = 0.05 ) . Relief from craving and short-term abstinence increased as airway sensations from the inhaler also increased . Abstinence at 10 weeks for subjects receiving strong airway sensations from the inhalers was 33.3 % ( 95 % CI = 14.5 to 52.1 % ) . At 6 months , there was no difference in abstinence between the treatment groups ( 0 % vs 5.1 % , p = 0.20 ) . CONCLUSIONS When combined with the nicotine patch , the citric acid inhaler improved 10-week smoking abstinence over lactose inhaler . The combination of airway sensory replacement and nicotine replacement may prove beneficial for smoking cessation Sensorimotor smoking stimuli are important determinants of cigarette use . The present study aim ed to determine whether denicotinized cigarettes lose their reinforcing and /or subjective effects over a 9-day outpatient period when they are smoked with or without concurrent transdermal nicotine . After a preferred br and baseline , 68 participants were r and omized into one of four conditions based on the dose ( mg ) of transdermal nicotine and the type of cigarettes ( dose/cigarette ) : 0/nicotine , 0/denicotinized , 7/denicotinized , and 21/denicotinized . Under placebo patch conditions , participants smoked a similar number of nicotine and denicotinized cigarettes and no group differences emerged over repeated testing . The total volume of smoke inhaled was lower in the denicotinized group , although this decrease dissipated over time . Denicotinized cigarettes were rated as having low positive and high negative subjective effects . Compared to placebo , transdermal nicotine decreased the number of denicotinized cigarette smoked , produced a lasting decrease in the total volume of denicotinized cigarette smoke inhaled , but had little effect on the subjective effects of denicotinized cigarettes . Transdermal nicotine attenuated withdrawal during initial smoking abstinence ; however , once participants were allowed to smoke withdrawal symptoms were relatively low regardless of patch condition . The persistent use of denicotinized cigarettes may result from the presence of nicotine withdrawal and /or the degree to which smoking becomes somewhat independent of the outcome of the behavior ( i.e. , habit learning ) . Additional studies would be useful to determine what factors drive continued use of denicotinized cigarettes , whether their use subsides as withdrawal dissipates , and whether they address motives for smoking distinct from current pharmacotherapy AIMS To provide an initial abuse liability assessment of an electronic cigarette ( EC ) in current tobacco cigarette smokers . DESIGN The first of four within-subject sessions was an EC sampling session that involved six , 10-puff bouts ( 30 seconds inter-puff interval ) , each bout separated by 30 minutes . In the remaining three sessions participants made choices between 10 EC puffs and varying amounts of money , 10 EC puffs and a varying number of own br and cigarette ( OB ) puffs , or 10 OB puffs and varying amounts of money using the multiple-choice procedure ( MCP ) . The MCP was completed six times at 30-minute intervals , and one choice was reinforced r and omly at each trial . SETTING Clinical laboratory . PARTICIPANTS Twenty current tobacco cigarette smokers . MEASUREMENTS Sampling session outcome measures included plasma nicotine , cardiovascular response and subjective effects . Choice session outcome was the cross-over value on the MCP . FINDINGS EC use result ed in significant nicotine delivery , tobacco abstinence symptom suppression and increased product acceptability ratings . On the MCP , participants chose to receive 10 EC puffs over an average of $ 1.06 or three OB puffs and chose 10 OB puffs over an average of $ 1.50 ( P < 0.003 ) . CONCLUSIONS Electronic cigarettes can deliver clinical ly significant amounts of nicotine and reduce cigarette abstinence symptoms and appear to have lower potential for abuse relative to traditional tobacco cigarettes , at least under certain laboratory conditions This study examined the subjective and cardiovascular effects of two of the components of cigarette smoking when given separately : nicotine and airway sensations . Using a within-subjects design , six healthy volunteer smokers , age 18 - 45 years , who smoked at least 20 cigarettes per day were given six conditions in a r and omized , counterbalanced order . The effects of IV nicotine , IV saline , and denicotinized cigarettes were compared to a st and ard 1-mg cigarette . The st and ard cigarette produced more of a calming effect and more irritability reduction than either the nicotine or airway sensations alone . The denicotinized cigarette was similar to the st and ard cigarette condition , except the cigarette condition was associated with higher feelings of " exhilaration . " Many of the positive subjective effects from a denicotinized cigarette were comparable to that of a st and ard cigarette . These data support the hypothesis that replacement of the sensory cues of smoking with " airway sensory replacement " may be useful for smoking cessation Objectives To measure the short-term effects of an electronic nicotine delivery device ( “ e cigarette ” , ENDD ) on desire to smoke , withdrawal symptoms , acceptability , pharmacokinetic properties and adverse effects . Design Single blind r and omised repeated measures cross-over trial of the Ruyan V8 ENDD . Setting University research centre in Auckl and , New Zeal and . Participants 40 adult dependent smokers of 10 or more cigarettes per day . Interventions Participants were r and omised to use ENDDs containing 16 mg nicotine or 0 mg capsules , Nicorette nicotine inhalator or their usual cigarette on each of four study days 3 days apart , with overnight smoking abstinence before use of each product . Main outcome measures The primary outcome was change in desire to smoke , measured as “ area under the curve ” on an 11-point visual analogue scale before and at intervals over 1 h of use . Secondary outcomes included withdrawal symptoms , acceptability and adverse events . In nine participants , serum nicotine levels were also measured . Results Over 60 min , participants using 16 mg ENDD recorded 0.82 units less desire to smoke than the placebo ENDD ( p=0.006 ) . No difference in desire to smoke was found between 16 mg ENDD and inhalator . ENDDs were more pleasant to use than inhalator ( p=0.016 ) and produced less irritation of mouth and throat ( p<0.001 ) . On average , the ENDD increased serum nicotine to a peak of 1.3 mg/ml in 19.6 min , the inhalator to 2.1 ng/ml in 32 min and cigarettes to 13.4 ng/ml in 14.3 min . Conclusions The 16 mg Ruyan V8 ENDD alleviated desire to smoke after overnight abstinence , was well tolerated and had a pharmacokinetic profile more like the Nicorette inhalator than a tobacco cigarette . Evaluation of the ENDD for longer-term safety , potential for long-term use and efficacy as a cessation aid is needed . Trial registration No.12607000587404 , Australia and New Zeal and Clinical Trials Despite the recent popularity of e-cigarettes , to date only limited data is available on their safety for both users and secondh and smokers . The present study reports a comprehensive inner and outer exposure assessment of e-cigarette emissions in terms of particulate matter ( PM ) , particle number concentrations ( PNC ) , volatile organic compounds ( VOC ) , polycyclic aromatic hydrocarbons ( PAH ) , carbonyls , and metals . In six vaping sessions nine volunteers consumed e-cigarettes with and without nicotine in a thoroughly ventilated room for two hours . We analyzed the levels of e-cigarette pollutants in indoor air and monitored effects on FeNO release and urinary metabolite profile of the subjects . For comparison , the components of the e-cigarette solutions ( liquids ) were additionally analyzed . During the vaping sessions substantial amounts of 1,2-propanediol , glycerine and nicotine were found in the gas-phase , as well as high concentrations of PM2.5 ( mean 197 μg/m(3 ) ) . The concentration of putative carcinogenic PAH in indoor air increased by 20 % to 147 ng/m(3 ) , and aluminum showed a 2.4-fold increase . PNC ranged from 48,620 to 88,386 particles/cm(3 ) ( median ) , with peaks at diameters 24 - 36 nm . FeNO increased in 7 of 9 individuals . The nicotine content of the liquids varied and was 1.2-fold higher than cl aim ed by the manufacturer . Our data confirm that e-cigarettes are not emission-free and their pollutants could be of health concern for users and secondh and smokers . In particular , ultrafine particles formed from supersaturated 1,2-propanediol vapor can be deposited in the lung , and aerosolized nicotine seems capable of increasing the release of the inflammatory signaling molecule NO upon inhalation . In view of consumer safety , e-cigarettes and nicotine liquids should be officially regulated and labeled with appropriate warnings of potential health effects , particularly of toxicity risk in children AIMS Sensorimotor stimuli associated with tobacco smoking influence smoking behavior ; however , current research has focused almost exclusively on the effects of brief , laboratory-based exposure to smoking-related stimuli . The purpose of this experiment was to characterize the effects of smoking stimuli delivered in the absence of nicotine over an extended ( 11-day ) exposure . DESIGN , SETTING AND PARTICIPANTS Thirty adult regular smokers participated in an in-patient study . After assessing preferred br and smoking , participants were assigned r and omly to one of three groups corresponding to subsequent smoking conditions : nicotine-containing cigarettes , de-nicotinized cigarettes or no smoking . MEASUREMENTS Measures of smoking reinforcement , subjective effects , physiological effects , withdrawal/craving and puff topography were taken repeatedly during both periods of free access and controlled assessment s during abstinence . FINDINGS Daily de-nicotinized cigarette use declined immediately by 1.7 cigarettes/day compared to the preferred br and baseline and declined by another 3.5 cigarettes over time ; participants smoking de-nicotinized cigarettes also demonstrated a 31 % decline in the number of puffs earned on a progressive ratio , a measure of the motivation to smoke , during the study . Subjective ratings of smoking were largely negative throughout the study in the de-nicotinized group , while the nicotine-containing condition reported increasingly positive subjective effects with repeated exposure . Acute craving suppression following smoking remained evident throughout the study regardless of nicotine content . CONCLUSIONS These effects highlight the importance of non-nicotine sensorimotor stimuli as determinants of the maintenance of smoking behavior and suggests that extinction of conditioned reinforcement in the absence of nicotine progresses slowly INTRODUCTION Electronic cigarettes ( ECs ) are marketed as nicotine delivery devices . Two studies with EC-naïve participants suggest that ECs deliver little or no nicotine . In those studies , st and ard-sized ECs were used , though experienced EC users often use larger devices that house higher voltage and /or longer lasting batteries . Whether user experience and device characteristics influence EC nicotine delivery is uncertain . The purpose of the present study was to examine the effects of ECs in experienced users who were using their preferred devices . METHODS Eight EC users ( 3 women ) who had been using ECs for at least 3 months , completed one 5-hr session using devices they provided and the flavor/strength nicotine cartridges they selected . Sessions consisted of 4 phases : baseline , 10 puffs ( 30-s interpuff interval ) from the device , 1-hr ad lib puffing period , and a 2-hr rest period ( no puffing ) . Outcome measures in each phase included plasma nicotine concentration , heart rate , and subjective ratings of nicotine/product effects and abstinence symptoms . RESULTS Relative to baseline , plasma nicotine and heart rate increased significantly within 5 min of the first puff and remained elevated throughout the ad lib puffing period . Increases in ratings of direct effects of nicotine and product were observed as well as decreases in abstinence symptoms . CONCLUSIONS User experience and /or device characteristics likely influence EC nicotine delivery and other effects . Systematic manipulation of these and other variables could eluci date conditions that produce intended effects BACKGROUND Previous cross-sectional studies found that positive beliefs about electronic nicotine delivery systems ( commonly known as electronic cigarettes or e-cigarettes ) were associated with use of these products . However , the prospect i ve association between these beliefs and subsequent use of e-cigarettes is unclear . PURPOSE To identify the beliefs predicting subsequent use of e-cigarettes . METHODS A total of 1379 young adults ( mean age=24.1 years ) from the Minnesota Adolescent Community Cohort who reported never using e-cigarettes at baseline ( collected Oct 2010-Mar 2011 ) and completed follow-up data collection ( during Oct 2011-Mar 2012 ) were included in this analysis . Participants ' beliefs about e-cigarettes ( potential as quit aids , harmfulness and addictiveness relative to cigarettes ) were asked at baseline ( yes/no ) . At follow-up , participants were asked if they had ever used e-cigarettes . Logistic regression models were used to assess the associations between beliefs about e-cigarettes and subsequent experimentation . Analysis was conducted in 2012 . RESULTS At follow-up , 7.4 % of the sample reported ever using e-cigarettes ( 21.6 % among baseline current smokers , 11.9 % among baseline former smokers , and 2.9 % among baseline nonsmokers ) . Participants who believed e-cigarettes can help people quit smoking and perceived e-cigarettes to be less harmful than cigarettes at baseline were more likely to report experimenting with e-cigarettes at follow-up ( p<0.05 ) . These associations did not differ by smoking status . CONCLUSIONS Given that young adults are still developing their tobacco use behaviors , informing them about the lack of evidence to support e-cigarettes as quit aids and the unknown health risk of e-cigarettes may deter young adults from trying these products The effects of the acute administration of nicotine [ through nicotine inhalers ( NI ) and placebo inhalers ( PI ) ] , nicotine-containing tobacco ( NT ) , and denicotinized tobacco ( DT ) , on smokers ' subjective responses and motivation to smoke were examined in 22 smokers ( 12 male , 10 female ; 11 low dependent , 11 high dependent ) . During four r and omized blinded sessions , participants self-administered NI , PI , NT , or DT , and assessed their effects using Visual Analogue Scales and the Brief Question naire of Smoking Urges . They could then self-administer their preferred br and of cigarettes using a progressive ratio task . NT and DT were each associated with increased satisfaction and relaxation as well as decreased craving relative to the inhalers and NT increased ratings of stimulation relative to each of the other products . Both NT and DT delayed the onset of preferred tobacco self-administration relative to NI and PI but only NT reduced the total amount self-administered . Sex differences were evident in the effects of DT on withdrawal-related cravings with women experiencing greater DT-induced craving relief than men . Findings suggest that DT is effective in acutely reducing many smoking abstinence symptoms , especially in women , but a combination of nicotine and non-nicotine tobacco ingredients may be necessary to suppress smoking behavior |
1,180 | 31,870,322 | The results suggested that targeting the DPP-4-GLP-1 pathway can improve exercise tolerance in heart failure patients [ MD 24.88 ( 95 % CI 5.45 , 44.31 ) , P = 0.01 ] without decreasing QoL [ SMD -0.51 ( 95 % CI -1.13 , 0.10 ) , P = 0.10 ] ; additionally , targeting the DPP-4-GLP-1 pathway did not show signs of increasing the incidence of serious AEs or mortality .
Conclusion Our results suggest that DPP-4 inhibitors or GLP-1 RAs improve exercise tolerance in heart failure patients .
Although the use of these drugs for heart failure has not been approved by any organization , they may be a better choice for type 2 diabetes mellitus patients with heart failure . | Background The most significant manifestation of heart failure is exercise intolerance .
This systematic review and meta- analysis was performed to investigate whether dipeptidyl peptidase-4 ( DPP-4 ) inhibitors or glucagon-like peptide 1 receptor agonists ( GLP-1 RAs ) , widely used anti-diabetic drugs , could improve exercise tolerance in heart failure patients with or without type 2 diabetes mellitus . | Background — Diabetes mellitus and heart failure frequently coexist . However , few diabetes mellitus trials have prospect ively evaluated and adjudicated heart failure as an end point . Methods and Results — A total of 16 492 patients with type 2 diabetes mellitus and a history of , or at risk of , cardiovascular events were r and omized to saxagliptin or placebo ( mean follow-up , 2.1 years ) . The primary end point was the composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . Hospitalization for heart failure was a predefined component of the secondary end point . Baseline N-terminal pro B-type natriuretic peptide was measured in 12 301 patients . More patients treated with saxagliptin ( 289 , 3.5 % ) were hospitalized for heart failure compared with placebo ( 228 , 2.8 % ; hazard ratio , 1.27 ; 95 % confidence intercal , 1.07–1.51 ; P=0.007 ) . Corresponding rates at 12 months were 1.9 % versus 1.3 % ( hazard ratio , 1.46 ; 95 % confidence interval , 1.15–1.88 ; P=0.002 ) , with no significant difference thereafter ( time-varying interaction , P=0.017 ) . Subjects at greatest risk of hospitalization for heart failure had previous heart failure , an estimated glomerular filtration rate ⩽60 mL/min , or elevated baseline levels of N-terminal pro B-type natriuretic peptide . There was no evidence of heterogeneity between N-terminal pro B-type natriuretic peptide and saxagliptin ( P for interaction=0.46 ) , although the absolute risk excess for heart failure with saxagliptin was greatest in the highest N-terminal pro B-type natriuretic peptide quartile ( 2.1 % ) . Even in patients at high risk of hospitalization for heart failure , the risk of the primary and secondary end points were similar between treatment groups . Conclusions — In the context of balanced primary and secondary end points , saxagliptin treatment was associated with an increased risk or hospitalization for heart failure . This increase in risk was highest among patients with elevated levels of natriuretic peptides , previous heart failure , or chronic kidney disease . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01107886 Abstract Background Diabetes is associated closely with an increased risk of cardiovascular events , including diastolic dysfunction and heart failure that leads to a shortening of life expectancy . It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function . However , the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern . We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub- analysis of the PROLOGUE study . Methods Patients in the PROLOGUE study were assigned r and omly to either add-on sitagliptin treatment or conventional antidiabetic treatment . Of the 463 patients in the overall study , 115 patients ( 55 in the sitagliptin group and 60 in the conventional group ) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity ( E ) to peak early diastolic mitral annular velocity ( e′ ) at baseline and after 12 and 24 months were included in this study . The primary endpoint of this post hoc sub- analysis was a comparison of the changes in the ratio of E to e′ ( E/e′ ) between the two groups from baseline to 24 months . Results The baseline-adjusted change in E/e′ during 24 months was significantly lower in the sitagliptin group than in the conventional group ( −0.18 ± 0.55 vs. 1.91 ± 0.53 , p = 0.008 ) , irrespective of a higher E/e′ value at baseline in the sitagliptin group . In analysis of covariance , sitagliptin treatment was significantly associated with change in E/e′ over 24 months ( β = −9.959 , p = 0.001 ) , independent of other clinical variables at baseline such as blood pressure , HbA1c , and medications for diabetes . Changes in other clinical variables including blood pressure and glycemic parameters , and echocardiographic parameters , such as cardiac structure and systolic function , were comparable between the two groups . There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period . Conclusions Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction ( E/e′ ) independent of other clinical variables such as blood pressure and glycemic control . Trial registration UMIN000004490 ( University Hospital Medical Information Network Clinical Trials ) . https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005356 ; registered November 1 , BACKGROUND An association between dipeptidyl peptidase-IV ( DPP-IV ) inhibitors with worse prognosis in HF has been suggested . We aim ed to assess the serum DPP-IV levels in chronic stable HF patients and determine their association with prognosis . METHODS AND RESULTS Chronic stable HF patients with optimized prognostic-modifying therapy were prospect ively recruited . EXCLUSION CRITERIA 1 ) ejection fraction>50 % , 2 ) hospitalizations or therapeutic adjustments in the previous 2months ; 3 ) patients on renal replacement therapy , and 4 ) use of DPP-IV inhibitors . A fasting venous blood sample was collected and DPP-IV was measured . Patients were followed-up for 3years and the endpoint studied was all-cause death . Patients ' characteristics were compared according to DPP-IV quartiles . A Cox regression analysis was performed and multivariate models were built . The 3rd DPP-IV quartile was the reference category . We studied 264 patients . Mean age : 69 (±13)years , 70.5 % were male and 33.7 % diabetic . Median ( IQR ) serum DPP-IV levels were 455.6 (350.0 - 625.5)ng/mL. DPP-IV had an inverse relationship with age . Patients in 3rd DPP-IV quartile were in lower NYHA classes and had the lowest 3years all-cause mortality . Patients in the 1st DPP-IV quartile had a multivariate adjusted HR of 3-year mortality of 2.62 ( 95%CI : 1.15 - 5.95 ) when compared with reference category and the HR for the 4th quartile was of 3.79 ( 95%CI : 1.68 - 8.54 ) . CONCLUSIONS There is a U-shaped association of serum DPP-IV with mortality in chronic systolic HF patients . Patients in the 3rd DPP-IV quartile have the best multivariate adjusted 3-year survival . DPP-IV inhibition might be harmful in patients with low DPP-IV BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) IMPORTANCE Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction ( LVEF ) . Glucagon-like peptide 1 ( GLP-1 ) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure , irrespective of type 2 diabetes status . OBJECTIVE To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure . DESIGN , SETTING , AND PARTICIPANTS Phase 2 , double-blind , placebo-controlled r and omized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized . Patients were enrolled between August 2013 and March 2015 at 24 US sites . INTERVENTIONS The GLP-1 agonist liraglutide ( n = 154 ) or placebo ( n = 146 ) via a daily subcutaneous injection ; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days . MAIN OUTCOMES AND MEASURES The primary end point was a global rank score in which all patients , regardless of treatment assignment , were ranked across 3 hierarchical tiers : time to death , time to rehospitalization for heart failure , and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days . Higher values indicate better health ( stability ) . Exploratory secondary outcomes included primary end point components , cardiac structure and function , 6-minute walk distance , quality of life , and combined events . RESULTS Among the 300 patients who were r and omized ( median age , 61 years [ interquartile range { IQR } , 52 - 68 years ] ; 64 [ 21 % ] women ; 178 [ 59 % ] with type 2 diabetes ; median LVEF of 25 % [ IQR , 19%-33 % ] ; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [ IQR , 1054 - 4235 pg/mL ] ) , 271 completed the study . Compared with placebo , liraglutide had no significant effect on the primary end point ( mean rank of 146 for the liraglutide group vs 156 for the placebo group , P = .31 ) . There were no significant between-group differences in the number of deaths ( 19 [ 12 % ] in the liraglutide group vs 16 [ 11 % ] in the placebo group ; hazard ratio , 1.10 [ 95 % CI , 0.57 - 2.14 ] ; P = .78 ) or rehospitalizations for heart failure ( 63 [ 41 % ] vs 50 [ 34 % ] , respectively ; hazard ratio , 1.30 [ 95 % CI , 0.89 - 1.88 ] ; P = .17 ) or for the exploratory secondary end points . Prespecified subgroup analyses in patients with diabetes did not reveal any significant between-group differences . The number of investigator-reported hyperglycemic events was 16 ( 10 % ) in the liraglutide group vs 27 ( 18 % ) in the placebo group and hypoglycemic events were infrequent ( 2 [ 1 % ] vs 4 [ 3 % ] , respectively ) . CONCLUSIONS AND RELEVANCE Among patients recently hospitalized with heart failure and reduced LVEF , the use of liraglutide did not lead to greater posthospitalization clinical stability . These findings do not support the use of liraglutide in this clinical situation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01800968 Background —Liraglutide , a glucagon-like peptide-1 analog , was reported to reduce reperfusion injury in mice . We planned to evaluate the effects of liraglutide on reperfusion injury in patients with acute ST-segment – elevation myocardial infa rct ion treated with primary percutaneous coronary intervention . Methods and Results —A total of 96 patients with ST-segment – elevation myocardial infa rct ion undergoing emergency primary percutaneous coronary intervention were r and omized to receive either subcutaneous liraglutide or placebo . Study treatment was commenced 30 minutes before intervention ( 1.8 mg ) and maintained for 7 days after the procedure ( 0.6 mg for 2 days , 1.2 mg for 2 days , followed by 1.8 mg for 3 days ) . The salvage index was calculated from myocardial area at risk , measured during the index admission ( 35±12 hours ) , and final infa rct size measured at 91±5 days after primary percutaneous coronary intervention by cardiac magnetic resonance . At 3 months , the primary end point , a higher salvage index was found in the liraglutide group than in the placebo group in 77 patients evaluated with cardiac magnetic resonance ( 0.66±0.14 versus 0.55±0.15 ; P=0.001 ) . The final infa rct size was lower in the liraglutide group than that in the placebo group ( 15±12 versus 21±15 g ; P=0.05 ) . Serum high-sensitivity C-reactive protein level was lower in the liraglutide group ( P<0.001 ) . During a 6-month follow-up period , no difference was observed in the incidence of major adverse cardiovascular event . Safety and tolerability were similar among the 2 groups . Conclusions —Our study provides evidence that liraglutide improves myocardial salvage and infa rct size after ST-segment – elevation myocardial infa rct ion , possibly by reducing reperfusion injury , making it a promising treatment for evaluation in larger trials . Clinical Trial Registration —URL : https://www . clinical trials.gov . Unique identifier : NCT02001363 Assessment of the ventilatory threshold ( VT ) has been proposed to assess exercise tolerance more objective ly , particularly in clinical trials , but reproducibility , interobserver variability and feasibility of the graphical methods for determination of VT have not been properly studied in patients with chronic heart failure ( CHF ) . Fifty-one patients with mild to moderate CHF ( mean peak oxygen uptake ( VO2 ) : 20.5 ml.min-1.kg-1 ) were assessed during two consecutive bicycle exercise tests within 8 days . Two grade d exercise protocol s were compared with stages of 30 W every 3 min ( 22 patients ) or 10 W/min ( 29 patients ) . VT was determined separately by five trained physicians using five different graphical methods . The ' crossing method ' ( first crossing of the VCO2 and VO2 curves ) yielded the highest rate of determination ( 88 % ) but tended to overestimate the mean VT . The VE method ( disproportionate increase of ventilation relative to VO2 ) produced the best interobserver agreement ( coefficient of variation = 78 % ) . Peak VO2 was very highly reproducible in both exercise protocol s ( relative difference 2-test 1/test 1 = -0.32 % for the 30 W 3 min protocol ; + 2.18 % for the 10 W.min-1 protocol ) . The reproducibility of VT was slightly lower regardless of the graphical method used to determine it ( relative differences varied from -3.3 % to + 7.3 % ) . Therefore , peak VO2 appears more suitable than VT for assessment of exercise tolerance in CHF The influence of glucagon-like peptide-1 has been studied in several studies in patients with acute myocardial infa rct ion , but not in patients with non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) . We planned to evaluate the effects of liraglutide on left ventricular function in patients with NSTEMI . A total of 90 patients were r and omized 1:1 to receive either liraglutide ( 0.6 mg for 2 days , 1.2 mg for 2 days , followed by 1.8 mg for 3 days ) or placebo for 7 days . Eighty-three patients completed the trial . Transthoracic echocardiography was used to assess left ventricular function . At 3 months , the primary endpoint , the difference in the change in left ventricular ejection fraction between the two groups was + 4.7 % ( liraglutide vs. placebo 95 % CI + 0.7 to + 9.2 % P = 0.009 ) under intention-to-treat analysis . The difference in decrease in serum glycosylated hemoglobin levels was −0.2 % ( liraglutide vs. placebo 95 % CI −0.1 to −0.3 % ; P < 0.001 ) . Inflammation and oxidative stress improved significantly in the liraglutide group compared to the placebo group . Liraglutide could improve left ventricular function in patients with NSTEMI , making it a potential adjuvant therapy for NSTEMI Purpose To compare the effect of liraglutide , sitagliptin and insulin glargine added to st and ard therapy on left ventricular function in post-ischemic type-2 diabetes mellitus patients . Methods We evaluated 32 type-2 diabetes mellitus Caucasians with history of post-ischemic chronic heart failure NYHA class II/III and /or left ventricular ejection fraction ≤45 % . Participants underwent laboratory determinations , electrocardiogram , echocardiogram , Minnesota Living with Heart Failure question naire and 6 min walking test at baseline and following 52 weeks treatment . Patients were treated with st and ard therapy for chronic heart failure and were r and omized to receive liraglutide , sitagliptin and glargine in addition to metformin and /or sulfonylurea . Results Liraglutide treatment induced an improvement in left ventricular ejection fraction from 41.5 ± 2.2 to 46.3 ± 3 % ; P = 0.001 ) . On the contrary , treatment with sitagliptin and glargine induced no changes in left ventricular ejection fraction ( 41.8 ± 2.6 vs. 42.5 ± 2.5 % and 42 ± 1.5 vs. 42 ± 1.6 % , respectively ; P = NS ) . Indexed end-systolic LV volume was reduced only in liraglutide-treated patients ( 51 ± 9 vs. 43 ± 8 ml/m2 ; P < 0.05 ) . Liraglutide treatment induced also a significant increase in the antero grade stroke volume ( 39 ± 9 vs. 49 ± 11 ml ; P < 0.05 ) , whereas no differences were observed in the other two groups . Cardiac output and cardiac index showed a significant increase only in liraglutide-treated patients ( 4.4 ± 0.5 vs. 5.0 ± 0.6 L/min ; P < 0.05 and 1.23 ± 0.26 vs. 1.62 ± 0.29 L/m2 ; P = 0.005 , respectively).Liraglutide treatment was also associated with an improvement of functional capacity and an improvement of quality of life . Conclusions These data provide evidence that treatment with liraglutide is associated with improvement of cardiac function and functional capacity in failing post-ischemic type-2 diabetes mellitus patients Aims To determine the effect of the glucagon‐like peptide‐1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes . Methods and results LIVE was an investigator‐initiated , r and omised , double‐blinded , placebo‐controlled multicentre trial . Patients ( n = 241 ) with reduced left ventricular ejection fraction ( LVEF ≤45 % ) were recruited ( February 2012 to August 2015 ) . Patients were clinical ly stable and on optimal heart failure treatment . Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks . The LVEF was similar at baseline in the liraglutide and the placebo group ( 33.7 ± 7.6 % vs. 35.4 ± 9.4 % ) . Change in LVEF did not differ between the liraglutide and the placebo group ; mean difference ( 95 % confidence interval ) was −0.8 % ( −2.1 , 0.5 ; P = 0.24 ) . Heart rate increased with liraglutide [ mean difference : 7 b.p.m . ( 5 , 9 ) , P < 0.0001 ] . Serious cardiac events were seen in 12 ( 10 % ) patients treated with liraglutide compared with 3 ( 3 % ) patients in the placebo group ( P = 0.04 ) . Conclusion Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes . Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events , and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function . More data on the safety of liraglutide in different subgroups of heart failure patients are needed AIMS To compare the management of patients with diabetes and heart failure with reduced ejection fraction ( HFrEF ) in the United States and Asia to underst and variations in treatment patterns across different healthcare systems . MATERIAL S AND METHODS Our cohort included patients with diabetes and HFrEF ( ejection fraction < 40 % ) from a US-based registry of adults with diabetes ( 2013 - 2016 , electronic health records ) and a multi-national Asian registry of adults with heart failure ( 2010 - 2016 , prospect i ve registry ) . Asian countries were categorized as high income ( HI ) or low income ( LI ) , according to the United Nations classification . Rates of use of guideline -directed medical therapies ( determined through review of active medication lists ) were compared across regions . RESULTS Patients with diabetes and HFrEF in the United States ( n = 28 877 ) were older , had higher body mass indices , and were more likely to have coronary disease than those in Asia ( n = 2235 ) . Compared with US patients , the use of guideline -directed medical therapy for HFrEF was lower in patients in LI Asian countries ( angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers : patients in the United States , 77 % vs. patients in HI Asian countries , 76 % vs patients in LI Asian countries , 69 % ; β-blockers : patients in the United States , 91 % vs. patients in HI Asian countries , 87 % vs. patients in LI Asian countries , 69 % ; P < 0.001 for both ) . Insulin was used more commonly in the United States ( 44 % vs. 24 % vs. 25 % , respectively ; P < 0.001 ) , whereas sulphonylureas were more often prescribed in Asian countries ( 42 % vs. 52 % vs. 54 % ; respectively , P < 0.001 ) . Thiazolidinediones were prescribed in 6 % of US patients compared with < 1 % of patients in Asia . The use of newer diabetes medications was < 5 % in all . CONCLUSION In both the United States and Asia , opportunities for improvement in the use of evidence -based therapies exist for patients with both diabetes and HFrEF . Effective tools to guide medication choices for these complex , high-risk patients could have substantial impact on quality and outcomes Background There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium . In this study , we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits . Methods A total of 30 rabbits were r and omized into control group ( CON , n = 10 ) , alloxan-induced diabetic group ( DM , n = 10 ) and alogliptin-treated ( 12.5 mg/kd/day for 12 weeks ) diabetic group ( DM-A , n = 10 ) . Echocardiographic and hemodynamic studies were performed in vivo . Mitochondrial morphology , respiratory function , membrane potential and reactive oxygen species ( ROS ) generation rate of left ventricular tissue were assessed . The serum concentrations of glucagon-like peptide-1 , insulin , inflammatory and oxidative stress markers were measured . Protein expression of TGF-β1 , NF-κB p65 and mitochondrial biogenesis related proteins were determined by Western blotting . Results DM rabbits exhibited left ventricular hypertrophy , left atrial dilation , increased E/e′ ratio and normal left ventricular ejection fraction . Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure ( − dp/dtmax ) were observed . Alogliptin alleviated ventricular hypertrophy , interstitial fibrosis and diastolic dysfunction in diabetic rabbits . These changes were associated with decreased mitochondrial ROS production rate , prevented mitochondrial membrane depolarization and improved mitochondrial swelling . It also improved mitochondrial biogenesis by PGC-1α/NRF1/Tfam signaling pathway . Conclusions The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling , explicable by improved mitochondrial function and increased mitochondrial biogenesis Aim To compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events ( MACE ) and all‐cause mortality among patients receiving basal insulin ( either insulin degludec [ degludec ] or insulin glargine 100 units/mL [ glargine U100 ] ) in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events ( DEVOTE ) . Material s and Methods Patients with type 2 diabetes and high cardiovascular risk were r and omized 1:1 to degludec or glargine U100 . Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time‐varying liraglutide use at any time during the trial , without interaction . Sensitivity analyses were adjusted for baseline covariates including , but not limited to , age , sex , smoking and prior cardiovascular disease . Results At baseline , 436/7637 ( 5.7 % ) patients were treated with liraglutide ; after baseline , 187/7637 ( 2.4 % ) started and 210/7637 ( 2.7 % ) stopped liraglutide . Mean liraglutide exposure from r and omization was 530.2 days . Liraglutide use versus no liraglutide use was associated with significantly lower hazard rates for MACE [ 0.62 ( 0.41 ; 0.92)95%CI ] and all‐cause mortality [ 0.50 ( 0.29 ; 0.88)95%CI ] . There was no significant difference in the rate of severe hypoglycaemia with versus without liraglutide use . Multiple sensitivity analyses yielded similar results . Conclusions Use of liraglutide was associated with significantly lower risk of MACE and death in patients with type 2 diabetes and high cardiovascular risk using basal insulin BACKGROUND To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes , regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies . We assessed cardiovascular outcomes with alogliptin , a new inhibitor of dipeptidyl peptidase 4 ( DPP-4 ) , as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome . METHODS We r and omly assigned patients with type 2 diabetes and either an acute myocardial infa rct ion or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy . The study design was a double-blind , noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS A total of 5380 patients underwent r and omization and were followed for up to 40 months ( median , 18 months ) . A primary end-point event occurred in 305 patients assigned to alogliptin ( 11.3 % ) and in 316 patients assigned to placebo ( 11.8 % ) ( hazard ratio , 0.96 ; upper boundary of the one-sided repeated confidence interval , 1.16 ; P<0.001 for noninferiority ) . Glycated hemoglobin levels were significantly lower with alogliptin than with placebo ( mean difference , -0.36 percentage points ; P<0.001 ) . Incidences of hypoglycemia , cancer , pancreatitis , and initiation of dialysis were similar with alogliptin and placebo . CONCLUSIONS Among patients with type 2 diabetes who had had a recent acute coronary syndrome , the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo . ( Funded by Takeda Development Center Americas ; EXAMINE Clinical Trials.gov number , NCT00968708 . ) Context Postmarketing placebo-controlled trials and observational studies have provided conflicting results about the risk for hospitalized heart failure ( hHF ) among patients using dipeptidyl peptidase-4 ( DPP-4 ) inhibitors . Contribution This large cohort study compared new users of 2 DPP-4 inhibitors ( saxagliptin or sitagliptin ) and new users of second-generation sulfonylureas , pioglitazone , or long-acting insulin products . The investigators did not find an increased risk for hHF among DPP-4 inhibitor users . Caution The average follow-up was less than 1 year . Implication This observational study provides additional evidence on the risk for hHF among users of DPP-4 inhibitors compared with other antihyperglycemic drugs used in routine clinical practice . Dipeptidyl peptidase-4 ( DPP-4 ) inhibitors are a class of oral antihyperglycemic medications that work by slowing the inactivation of the incretin hormones by the DPP-4 enzyme ( 1 ) . The result ing increase and prolongation of incretin levels reduces both fasting and postpr and ial glucose concentrations in a glucose-dependent manner . The cardiovascular safety of DPP-4 inhibitors has recently become a subject of considerable debate due to the conflicting findings from several large postmarketing trials ( 24 ) . The SAVOR-TIMI 53 ( Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes MellitusThrombolysis in Myocardial Infa rct ion 53 ) trial unexpectedly showed a higher incidence of hospitalized heart failure ( hHF ) in the saxagliptin group than the placebo group ( 2 ) . In contrast , 2 other postmarketing trialsthe EXAMINE ( Examination of Cardiovascular Outcomes with Alogliptin versus St and ard of Care ) trial ( 3 ) and TECOS ( Trial Evaluating Cardiovascular Outcomes with Sitagliptin ) (4)did not find a statistically significant difference in the risk for hHF among patients receiving alogliptin or sitagliptin versus placebo . Based on these clinical trials , it remains unclear whether the increased hHF risk observed with saxagliptin but not sitagliptin is due to properties of the drugs , different patient characteristics between the trials , or r and om error related to multiple hypothesis testing . Patients with diabetes have a higher hHF risk than those without ( 5 , 6 ) , so any antihyperglycemic agent that modifies the risk warrants further examination . Thus , we assessed the associations of hHF with the 2 most commonly used DPP-4 inhibitors , saxagliptin and sitagliptin , in a large population -based cohort of patients with type 2 diabetes mellitus ( T2DM ) treated with antihyperglycemic agents in routine clinical setting s. Supplement . Original Version ( PDF ) Methods Study Design This study was part of a larger , ongoing active surveillance project design ed to complement SAVOR-TIMI 53 . The primary goal of the project was to compare the risk for acute myocardial infa rct ion ( AMI ) between saxagliptin and selected antihyperglycemic agents among patients with T2DM . A detailed protocol has been published previously ( 7 , 8) . The AMI surveillance project uses a sequential design with up date d analyses as new data accrue . Within this larger project , we conducted the hHF analysis as a 1-time assessment , which allowed us to provide timely information about the safety of DPP-4 inhibitors while maintaining the scientific rigor of the analysis . Both the AMI and hHF analyses used a new-user cohort design ( Figure 1 ) ( 9 ) to compare saxagliptin with sitagliptin and each with pioglitazone , second-generation sulfonylureas , and long-acting insulin products . These comparators were chosen because they were common alternatives to saxagliptin in clinical practice at the time of the protocol development ( 10 ) . Therefore , this study included 7 head-to-head comparisons : saxagliptin versus sitagliptin , saxagliptin versus pioglitazone , saxagliptin versus sulfonylureas , saxagliptin versus insulin , sitagliptin versus pioglitazone , sitagliptin versus sulfonylureas , and sitagliptin versus insulin . Figure 1 . Study design for each of the 7 pairwise comparisons . AMI= acute myocardial infa rct ion ; HF= heart failure . Data Source This study was conducted within Mini-Sentinel , a pilot program created to assist the U.S. Food and Drug Administration ( FDA ) in developing a national active safety surveillance system of FDA -regulated medical products ( 11 , 12 ) . Mini-Sentinel uses a distributed data system that allows data to be stored locally under the control of the participating data partners ( 13 ) . At the time of this assessment ( August 2014 ) , the Mini-Sentinel Distributed Data base comprised quality -checked data covering 178 million persons and 358 million person-years of longitudinal observation time between 2000 and 2014 from 18 administrative cl aims and clinical data partners ( a complete list of data partners is provided in the Acknowledgment ) . Mini-Sentinel is a public health surveillance activity that is not under the purview of institutional review boards ( 14 , 15 ) . Study Cohort For each pairwise comparison ( for example , saxagliptin vs. sulfonylureas ) , we identified new users of the DPP-4 inhibitor of interest or the comparator drug among patients aged 18 years or older with T2DM beginning on 1 August 2009 ( for saxagliptin ) or 1 October 2006 ( for sitagliptin ) . We defined T2DM as having at least 1 dispensing for an antihyperglycemic agent ( except short-acting insulin ) or at least 1 diabetes diagnosis during the year before new use of saxagliptin or the comparator drug . Patients identified as new users of long-acting insulin products must also have at least 1 prior or concomitant dispensing for an antihyperglycemic agent that was not a short-acting insulin product . We defined new use of the DPP-4 inhibitor or the comparator drug as no prior dispensing of either drug during 365 days of continuous health plan enrollment , and we defined the dispensing date of the first eligible prescription of either drug as the index date . Use of other study drugs did not disqualify patients but was adjusted for in the analysis . For example , past use of pioglitazone disqualified saxagliptin users from the comparisons of saxagliptin versus pioglitazone but not from the comparisons of saxagliptin versus sulfonylureas . We excluded patients who had a principal discharge diagnosis of AMI ( International Classification of Diseases , Ninth Revision , Clinical Modification [ ICD-9-CM ] codes 410.x0 and 410.x1 ) or HF ( ICD-9-CM codes 402.x1 , 404.x1 , 404.x3 , and 428.xx ) in the 60 days before the index date because of their high risk for recurrence and the high potential for unmeasured confounding . As a reference , SAVOR-TIMI 53 also excluded patients who had an acute vascular ( cardiac or stroke ) event within 2 months before r and omization . In the comparisons with pioglitazone , we further excluded patients with an outpatient or inpatient diagnosis of HF during the 365-day baseline period because the condition is a contraindication to the use of pioglitazone . We divided all remaining patients into those with and those without a history of cardiovascular disease ( CVD ) ( see Appendix Table 1 for specific diagnoses and procedures ) during the baseline period . Appendix Table 1 . Diagnoses and Procedures Indicative of a History of Cardiovascular Disease Outcome Hospitalized HF was identified by ICD-9-CM codes 402.x1 , 404.x1 , 404.x3 , and 428.xx recorded as the principal discharge diagnosis . The algorithm has a positive predictive value greater than 90 % based on prior validation studies ( 16 ) . Follow-up Each pairwise comparison followed eligible new users of the DPP-4 inhibitor or comparator drug of interest from the index date until the earliest occurrence of an hHF event , discontinuation of the initiated therapy ( for example , new users of saxagliptin discontinuing its use ) , initiation of therapy with the other drug in the pair ( for example , new users of saxagliptin adding or switching to a sulfonylurea in the comparisons of saxagliptin vs. sulfonylureas ) , health plan disenrollment , death , or the end of the study period ( which varied by data partner from 30 June 2012 to 31 December 2013 ) . Discontinuation of use occurred when the days ' supply seemed to have been exhausted for a period of 10 days or one third of the days ' supply of the most recent dispensing , whichever was greater . Adjustment for Confounders We used 2 complementary approachesdisease risk score ( DRS ) stratification ( 17 ) and 1:1 exposure propensity score ( PS ) matching (18)to adjust for prespecified confounders , including patient demographic characteristics , medical history , medication use , risk factors for hHF and other cardiovascular events , other antihyperglycemic treatments , and health services utilization measures ( Table 1 and Appendix Table 2 ) . The protocol provides algorithms used to identify these covariates ( 7 ) . Table 1 . Selected Baseline Patient Characteristics , by Study Drug : Saxagliptin Analysis Appendix Table 2 . Baseline Patient Characteristics , by Study Drug : Saxagliptin Analysis DRS Stratification The DRS-stratified analysis was a 2-step process ( Appendix Figure ) ( 17 ) . We first used a larger , earlier T2DM population from the same data partners to estimate the relative hazard for hHF events associated with the baseline covariates using a multivariable Cox regression model . For the saxagliptin analysis , we created a cohort of patients with T2DM in 2007 to 2008 within each data partner and followed them through the end of 2009 for occurrence of hHF events . We required 12 months of baseline data to measure all potential confounders needed to estimate the DRS . The corresponding periods were 2004 to 2005 and 2006 for the sitagliptin analysis . Next , we assigned to each new user in our pairwise comparisons a DRS equal to , where was the new user 's covariate profile and was the vector of the log of the hazard ratio ( HR ) estimates for the covariates from the Cox model fitted to the larger T2DM population . The result ing DRS was the new user 's estimated hazard of hHF at baseline , conditional on |
1,181 | 32,282,223 | Most of the studies displayed positive effects of the curcumin supplementation for athletes and physical exercise practitioners , and no side effects were reported .
Participants supplemented with curcumin displayed reduced inflammation and oxidative stress , decreased pain and muscle damage , superior recovery and muscle performance , better psychological and physiological responses ( thermal and cardiovascular ) during training and improved gastrointestinal function .
Curcumin supplementation appears to be safe and beneficial for sport and physical exercise in human beings . | Curcumin is the main phenolic compound in turmeric .
It has been investigated recently due to its numerous medicinal properties and health benefits .
However , few studies assessed the effects of curcumin supplementation on physical activity practice .
Therefore , the purpose of this review is to assess the available evidence s with human beings about the potential effects of curcumin supplementation on sport and physical exercise . | Background : Chronic intensive exercise is associated with a greater induction of oxidative stress and with an excess of endogenous advanced glycation end-products ( AGEs ) . Curcumin can reduce the accumulation of AGEs in vitro and in animal models . We examined whether supplementation with curcumin and Boswellia serrata ( BSE ) gum resin for 3 months could affect plasma levels of markers of oxidative stress , inflammation , and glycation in healthy master cyclists . Methods . Forty-seven healthy male athletes were r and omly assigned to Group 1 , consisting of 22 subjects given a Mediterranean diet ( MD ) alone ( MD group ) , and Group 2 consisted of 25 subjects given a MD plus curcumin and BSE ( curcumin/BSE group ) . Interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNFα ) , high-sensitivity c-reactive protein ( hs-CRP ) , total AGE , soluble receptor for AGE ( sRAGE ) , malondialdehyde ( MDA ) , plasma phospholipid fatty acid ( PPFA ) composition , and non-esterified fatty acids ( NEFA ) were tested at baseline and after 12 weeks . Results : sRAGE , NEFA , and MDA decreased significantly in both groups , while only the curcumin/BSE group showed a significant decline in total AGE . Only the changes in total AGE and MDA differed significantly between the curcumin/BSE and MD groups . Conclusions . Our data suggest a positive effect of supplementation with curcumin and BSE on glycoxidation and lipid peroxidation in chronically exercising master athletes LI73014F2 is a novel composition prepared from extracts of Terminalia chebula fruit , Curcuma longa rhizome , and Boswellia serrata gum resin with synergistic benefit in 5-Lipoxygenase ( 5-LOX ) inhibition . This herbal composition with strong anti-5-LOX activity exhibited significant pain relief as indicated through improvements in weight-bearing capacity in a monosodium iodoacetate-induced osteoarthritis ( OA ) model of Sprague-Dawley rats . A 90-day r and omized , placebo-controlled double-blind study evaluates the clinical efficacy and tolerability of LI73014F2 in the management of symptoms of OA of the knee ( Clinical Trial Registration No. CTRI/2014/01/004338 ) . Subjects , ( n = 105 ) , were r and omized into three groups : placebo ( n = 35 ) , 200 mg/day of LI73014F2 ( n = 35 ) , and 400 mg/day of LI73014F2 ( n = 35 ) . All study participants were evaluated for pain and physical function by using st and ard tools , that is , Visual Analog Scale , Lequesne 's Functional Index , and Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) at the baseline ( day 0 ) and on day 14 ± 3 , 30 ± 3 , 60 ± 3 , and at the end of the study ( day 90 ± 3 ) . In addition , routine examinations on biochemical parameters in serum , urine , and hematological parameters were conducted on each visit to assess the safety of the study material . At the end of the trial period , LI73014F2 conferred significant pain relief , improved physical function , and quality of life in OA patients . In conclusion , pre clinical and clinical data together strongly suggest that the herbal formulation LI73014F2 is a safe and effective intervention for management of joint discomfort , demonstrating efficacy as early as 14 days Introduction Oral curcumin decreases inflammatory cytokines and increases muscle regeneration in mice . Purpose To determine effects of curcumin on muscle damage , inflammation and delayed onset muscle soreness ( DOMS ) in humans . MethodS eventeen men completed a double-blind r and omized-controlled crossover trial to estimate the effects of oral curcumin supplementation ( 2.5 g twice daily ) versus placebo on single-leg jump performance and DOMS following unaccustomed heavy eccentric exercise . Curcumin or placebo was taken 2 d before to 3 d after eccentric single-leg press exercise , separated by 14-d washout . Measurements were made at baseline , and 0 , 24 and 48-h post-exercise comprising : ( a ) limb pain ( 1–10 cm visual analogue scale ; VAS ) , ( b ) muscle swelling , ( c ) single-leg jump height , and ( d ) serum markers of muscle damage and inflammation . St and ardized magnitude-based inference was used to define outcomes . Results At 24 and 48-h post-exercise , curcumin caused moderate-large reductions in pain during single-leg squat ( VAS scale −1.4 to −1.7 ; 90 % CL : ±1.0 ) , gluteal stretch ( −1.0 to −1.9 ; ±0.9 ) , squat jump ( −1.5 to −1.1 ; ± 1.2 ) and small reductions in creatine kinase activity ( −22–29 % ; ±21–22 % ) . Associated with the pain reduction was a small increase in single-leg jump performance ( 15 % ; 90 % CL ± 12 % ) . Curcumin increased interleukin-6 concentrations at 0-h ( 31 % ; ±29 % ) and 48-h ( 32 % ; ±29 % ) relative to baseline , but decreased IL-6 at 24-h relative to post-exercise ( −20 % ; ±18 % ) . Conclusions Oral curcumin likely reduces pain associated with DOMS with some evidence for enhanced recovery of muscle performance . Further study is required on mechanisms and translational effects on sport or vocational performance Background Curcumin is the major yellow pigment extracted from turmeric , a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential . However , few systematic studies of curcumin 's pharmacology and toxicology in humans have been performed . Methods A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of st and ardized powder extract , uniformly milled curcumin ( C3Complex ™ , Sabinsa Corporation ) . Healthy volunteers were administered escalating doses from 500 to 12,000 mg . Results Seven of twenty-four subjects ( 30 % ) experienced only minimal toxicity that did not appear to be dose-related . No curcumin was detected in the serum of subjects administered 500 , 1,000 , 2,000 , 4,000 , 6,000 or 8,000 mg . Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg . Conclusion The tolerance of curcumin in high single oral doses appears to be excellent . Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention , these findings warrant further investigation for its utility as a long-term chemopreventive agent Background Exercise-Induced Muscle Damage ( EIMD ) and delayed onset muscle soreness ( DOMS ) impact subsequent training sessions and activities of daily living ( ADL ) even in active individuals . In sedentary or diseased individuals , EIMD and DOMS may be even more pronounced and present even in the absence of structured exercise . Methods The purpose of this study was to determine the effects of oral curcumin supplementation ( Longvida ® 400 mg/days ) on muscle & ADL soreness , creatine kinase ( CK ) , and inflammatory cytokines ( TNF-α , IL-6 , IL-8 , IL-10 ) following EMID ( eccentric-only dual-leg press exercise ) . Subjects ( N = 28 ) were r and omly assigned to either curcumin ( 400 mg/day ) or placebo ( rice flour ) and supplemented 2 days before to 4 days after EMID . Blood sample s were collected prior to ( PRE ) , and 1 , 2 , 3 , and 4 days after EIMD to measure CK and inflammatory cytokines . Data were analyzed by ANOVA with P < 0.05 . Results Curcumin supplementation result ed in significantly smaller increases in CK ( − 48 % ) , TNF-α ( − 25 % ) , and IL-8 ( − 21 % ) following EIMD compared to placebo . We observed no significant differences in IL-6 , IL-10 , or quadriceps muscle soreness between conditions for this sample size . Conclusions Collectively , the findings demonstrated that consumption of curcumin reduced biological inflammation , but not quadriceps muscle soreness , during recovery after EIMD . The observed improvements in biological inflammation may translate to faster recovery and improved functional capacity during subsequent exercise sessions . General significance These findings support the use of oral curcumin supplementation to reduce the symptoms of EIMD . The next logical step is to evaluate further the efficacy of an inflammatory clinical disease model We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults . Thirty-nine healthy men and postmenopausal women ( 45 - 74 yrs ) were r and omized to 12 weeks of curcumin ( 2000 mg/day Longvida ® ; n=20 ) or placebo ( n=19 ) supplementation . Forearm blood flow response to acetylcholine infusions ( FBFACh ; resistance artery endothelial function ) increased 37 % following curcumin supplementation ( 107±13 vs. 84±11 AUC at baseline , P=0.03 ) , but not placebo ( P=0.2 ) . Curcumin treatment augmented the acute reduction in FBFACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine ( L-NMMA ; P=0.03 ) , and reduced the acute increase in FBFACh to the antioxidant vitamin C ( P=0.02 ) , whereas placebo had no effect ( both P>0.6 ) . Similarly , brachial artery flow-mediated dilation ( conduit artery endothelial function ) increased 36 % in the curcumin group ( 5.7±0.4 vs. 4.4±0.4 % at baseline , P=0.001 ) , with no change in placebo ( P=0.1 ) . Neither curcumin nor placebo influenced large elastic artery stiffness ( aortic pulse wave velocity or carotid artery compliance ) or circulating biomarkers of oxidative stress and inflammation ( all P>0.1 ) . In healthy middle-aged and older adults , 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress , while also improving conduit artery endothelial function The aim of this study was to analyze the effects of oral consumption of curcumin and piperine in combination on the recovery kinetics after exercise-induced muscle damage . Forty-eight hours before and following exercise-induced muscle damage , ten elite rugby players consumed curcumin and piperine ( experimental condition ) or placebo . A r and omized cross-over design was performed . Concentric and isometric peak torque for the knee extensors , one leg 6 seconds sprint performance on a non-motorized treadmill , counter movement jump performance , blood creatine kinase concentration and muscle soreness were assessed immediately after exercise , then at 24h , 48h and 72h post-exercise . There were moderate to large effects of the exercise on the concentric peak torque for the knee extensors ( Effect size ( ES ) = -1.12 ; Confidence interval at 90 % ( CI90 % ) : -2.17 to -0.06 ) , the one leg 6 seconds sprint performance ( ES=-1.65 ; CI90 % = -2.51to -0.80 ) and the counter movement jump performance ( ES = -0.56 ; CI90 % = -0.81 to -0.32 ) in the 48h following the exercise . There was also a large effect of the exercise on the creatine kinase level 72h after the exercise in the control group ( ES = 3.61 ; CI90 % : 0.24 to 6.98 ) . This decrease in muscle function and this elevation in creatine kinase indicate that the exercise implemented was efficient to induce muscle damage . Twenty four hours post-exercise , the reduction ( from baseline ) in sprint mean power output was moderately lower in the experimental condition ( -1.77 ± 7.25 % ; 1277 ± 153W ) in comparison with the placebo condition ( -13.6 ± 13.0 % ; 1130 ± 241W ) ( Effect Size = -1.12 ; Confidence Interval 90%=-1.86 to -0.86 ) . However , no other effect was found between the two conditions . Curcumin and piperine supplementation before and after exercise can attenuate some , but not all , aspects of muscle damage BACKGROUND In response to physiologic stressors , skeletal muscle has the potential to elicit wide variety of adaptive responses , such as biogenesis of mitochondria and clearance of damaged mitochondria to promote healthy muscle . The polyphenol curcumin , derived from the rhizome Curcuma longa L. , is a natural antioxidant that exhibits various pharmacological activities and therapeutic properties . However , the effect of curcumin on the regulation of mitochondrial biogenesis in skeletal muscle remains unknown . The present study aim ed to examine the effects of combination of endurance training ( eTR ) and curcumin treatment on the expression of AMPK , SIRT1 , PGC-1α , and OXPHOS subunits , mitochondrial DNA copy number , and CS activity in rat skeletal muscle . Furthermore , the present study also examined the effect of exercise and curcumin treatment on the levels of cAMP and downstream targets of PKA including phosphorylated CREB and LKB-1 . METHODS Ten-week-old male Wistar rats were r and omly divided into non-eTR and eTR groups . Low doses ( 50 mg/kg-BW/day ) or high doses ( 100 mg/kg-BW/day ) of curcumin dissolved in dimethyl sulfoxide ( DMSO ) were injected intraperitoneally in all animals for 28 days to investigate the effect of curcumin alone and the combined effect of curcumin with eTR . Western blotting ( WB ) and immunoprecipitation ( IP ) were performed to detect the presence of proteins . RESULTS Our results demonstrated that combination of curcumin treatment and eTR increased the expression of COX-IV , OXPHOS subunits , mitochondrial DNA copy number and CS activity in the gastrocnemius ( Gas ) and soleus ( Sol ) muscles . In addition , this combination increased AMPK phosphorylation , NAD(+)/NADH ratio , SIRT1 expression , and PGC-1α deacetylation . Furthermore , curcumin treatment as well as exercise also increased levels of cAMP and downstream target of PKA including phosphorylation CREB and LKB-1 which are involved in the regulation of mitochondrial biogenesis . CONCLUSION Taken together , these results suggest that the combination of curcumin treatment and eTR has the potential to accelerate mitochondrial biogenesis in skeletal muscle by increasing cAMP levels Abstract Firefighters and military personnel are exposed to a variety of stressors . The combination of mental and physical stress ( i.e. , dual stress challenges [ DSCs ] ) results in significant oxidative stress ( OS ) , which may contribute to cardiometabolic dysfunction . Curcumin ( CUR ) is an exogenous antioxidant that may attenuate such OS . Fourteen trained men participated in a r and omized , cross-over design to investigate the impact of CUR on markers of OS result ing from DSC . CUR or placebo was ingested three days prior to , and the morning of , testing . The DSC involved 20 min of mental stress challenges during 35 min of cycling at 60 % V̇O2 peak . Blood was sample d before , as well as immediately , 30 min , and 60 min after , exercise and analyzed for glutathione ( GSH ) , superoxide dismutase ( SOD ) , hydrogen peroxide ( H2O2 ) , and advanced oxidation protein products ( AOPP ) . There was no treatment effect for any variable . However , the DSC result ed in significant reductions in SOD , H2O2 , and AOPP at 30 and 60 min after exercise . Previous studies have shown that DSC results in significant OS compared to exercise alone . However , these data suggest the DSC was associated with reductions in postexercise markers of OS . Antioxidant therapy is likely not needed in trained men exposed to DSC Curcumin is known to have potent anti-inflammatory effects . We have reported that acute curcumin ingestion attenuates eccentric exercise-induced muscle damage . This study aim ed to examine the effect of curcumin ingestion timing ( before or after exercise ) on the changes in muscle damage markers after eccentric exercise . In this r and omized , single-blind , parallel design study , 24 healthy young men performed 30 maximal isokinetic ( 120º/s ) eccentric contractions of the elbow flexors using an isokinetic dynamometer . Subjects were r and omly assigned to ingest 180 mg/d of oral curcumin either 7 d before ( PRE ) or 4 d after exercise ( POST ) or 180 mg/d of oral placebo 4 d after exercise ( CON ) . The maximal voluntary contraction ( MVC ) torque of the elbow flexors , elbow joint range of motion ( ROM ) , muscle soreness , and serum creatine kinase ( CK ) activity were measured before , immediately after , and 1 - 4 d after exercise . Changes in these variables were compared over time . In the POST group , ROM were higher at 3 - 4 d and muscle soreness was lower at 3 d after exercise compared with the CON group ( p<0.05 ) . However , in the PRE group , there were no significant differences compared with the CON group in changes in ROM and muscle soreness . Meanwhile , there were no significant differences among the groups in terms of changes in MVC torque and serum CK activity . Our results suggest that curcumin ingestion after exercise had a more beneficial effect in attenuating muscle soreness The purpose of this study was to investigate the effects of curcumin supplementation on exercise-induced oxidative stress in humans . 10 male participants , ages 26.8±2.0 years ( mean±SE ) , completed 3 trials in a r and om order : ( 1 ) placebo ( control ) , ( 2 ) single ( only before exercise ) and ( 3 ) double ( before and immediately after exercise ) curcumin supplementation trials . Each participant received oral administration of 90 mg of curcumin or the placebo 2h before exercise and immediately after exercise . Each participant walked or ran at 65 % of V˙2max on a treadmill for 60min . Blood sample s were collected pre-exercise , immediately after exercise and 2h after exercise . The concentrations of serum derivatives of reactive oxygen metabolites measured immediately after exercise were significantly higher than pre-exercise values in the placebo trial ( 308.8±12.9 U. CARR , P<0.05 ) , but not in the single ( 259.9±17.1 U. CARR ) or double ( 273.6±19.7 U. CARR ) curcumin supplementation trials . Serum biological antioxidant potential concentrations measured immediately after exercise were significantly elevated in the single and double curcumin supplementation trials compared with pre-exercise values ( P<0.05 ) . These findings indicate that curcumin supplementation can attenuate exercise-induced oxidative stress by increasing blood antioxidant capacity |
1,182 | 22,835,137 | Lactulose reduced adenoma recurrence , while resistant starch had no effect on adenoma or CRC development .
Crypt mitotic location , gene expression , and DNA methylation were somewhat improved after resistant starch consumption .
No changes in cell proliferation and apoptosis , crypt morphology , or aberrant crypt foci were found . | Prebiotics may prevent colorectal cancer ( CRC ) development in humans by modifying the composition or activity of the colorectal microflora .
Epidemiologic and animal studies have shown a reduction in CRC or CRC biomarkers after the administration of prebiotics .
Studies using indirect chemical biomarkers of CRC in humans , however , gave mixed results .
Recently , human studies measuring direct physical indices of CRC risk after prebiotic consumption have been published .
The purpose of this review is to summarize those studies to provide recommendations for the use of prebiotics in CRC risk reduction . | BACKGROUND Diet is an important factor in colorectal carcinogenesis ; thus , dietary supplements may have a role in colorectal cancer prevention . OBJECTIVE The objective was to establish the relative luminal , epithelial , and epigenetic consequences of prebiotic , probiotic , and synbiotic dietary supplementation in humans . DESIGN This was a r and omized , double-blind , placebo-controlled , 4-wk crossover trial of resistant starch and Bifidobacterium lactis , either alone or as a combined synbiotic preparation , in 20 human volunteers . Rectal biopsy , feces , and serum sample s were collected . The rectal mucosal endpoints were DNA methylation at 16 CpG isl and loci and LINE-1 , epithelial proliferation ( Ki67 immunohistochemistry ) , and crypt cellularity . The fecal endpoints were short-chain fatty acid concentrations , pH , ammonia , and microbiological profiles ( by denaturing gradient gel electrophoresis and sequencing ) . Serum endpoints were a panel of cytokines and high-sensitivity C-reactive protein . RESULTS Seventeen subjects completed the entire study . The synbiotic intervention fostered a significantly different fecal stream bacterial community than did either the prebiotic ( P = 0.032 ) or the probiotic ( P = 0.001 ) intervention alone , in part because of a greater proportion of patients harboring fecal Lachnospiraceae spp . These changes developed in the absence of any significant differences in fecal chemistry . There were no differences in epithelial kinetics . CONCLUSIONS This synbiotic supplementation with B. lactis and resistant starch , in the doses used , induced unique changes in fecal microflora but did not significantly alter any other fecal , serum , or epithelial variables . This trial was registered in the Australian New Zeal and Clinical Trials Registry at www.anzctr.org.au as ACTRN012606000115538 Objective : This study investigated the effects of oral supplementation of resistant starch ( RS ) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer ( CRC ) , and its potential role in colon cancer prevention . Methods : 65 patients with CRC were r and omised to treatment with RS or ordinary starch ( OS ) and were given starch treatment for up to 4 weeks . Pretreatment and post-treatment biopsies were obtained from the tumour and colonic mucosa , and the effects of the starch treatment on cell proliferation and expression of the cell cycle regulatory genes CDK4 ( cyclin-dependent kinase 4 ) and GADD45A ( growth arrest and DNA damage-inducible , alpha ) were investigated . Results : The proportion of mitotic cells in the top half of the colonic crypt was significantly lower following RS treatment ( 3.1 ( 1.5 ) , mean ( SEM ) ) as compared with OS treatment ( 13.7 ( 3.2 ) ) ( p = 0.028 ) . However , there was no effect of RS treatment on crypt dimensions and tumour cell proliferation index . There was significant upregulation in expression of CDK4 ( p<0.01 ) and downregulation in expression of GADD45A ( p<0.001 ) in the tumour tissue when compared with macroscopically normal mucosa . Following RS treatment , CDK4 expression in tumours ( 0.88 ( 0.15 ) ) was twofold higher than that in the OS group ( 0.37 ( 0.16 ) ) ( p = 0.02 ) . The expression of GADD45A , which was downregulated in the presence of cancer , was significantly upregulated ( p = 0.048 ) following RS treatment ( 1.41 ( 0.26 ) ) as compared with OS treatment ( 0.56 ( 0.3 ) ) . However , there were no significant differences in the expression of these genes in the normal mucosa following starch treatment . Conclusions : Cell proliferation in the upper part of colonic crypts is a premalignant marker and its reduction by RS supplementation is consistent with an antineoplastic action of this food component . Differential expression of the key cell cycle regulatory genes may contribute to the molecular mechanisms underlying these antineoplastic effects of RS . Trial registration number : IS RCT N93586244 BACKGROUND Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon , but human data supporting this suggestion are weak . OBJECTIVE The objective was to verify whether the prebiotic concept ( selective interaction with colonic flora of nondigested carbohydrates ) as induced by a synbiotic preparation-oligofructose-enriched inulin ( SYN1 ) + Lactobacillus rhamnosus GG ( LGG ) and Bifidobacterium lactis Bb12 (BB12)-is able to reduce the risk of colon cancer in humans . DESIGN The 12-wk r and omized , double-blind , placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients . Fecal and blood sample s were obtained before , during , and after the intervention , and colorectal biopsy sample s were obtained before and after the intervention . The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined . RESULTS Synbiotic intervention result ed in significant changes in fecal flora : Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased . The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients . Genotoxicity assays of colonic biopsy sample s indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period . Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon gamma in the cancer patients . CONCLUSIONS Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention Background To systematic ally develop dietary strategies based on resistant starch ( RS ) that modulate the human gut microbiome , detailed in vivo studies that evaluate the effects of different forms of RS on the community structure and population dynamics of the gut microbiota are necessary . The aim of the present study was to gain a community wide perspective of the effects of RS types 2 ( RS2 ) and 4 ( RS4 ) on the fecal microbiota in human individuals . Methods and Findings Ten human subjects consumed crackers for three weeks each containing either RS2 , RS4 , or native starch in a double-blind , crossover design . Multiplex sequencing of 16S rRNA tags revealed that both types of RS induced several significant compositional alterations in the fecal microbial population s , with differential effects on community structure . RS4 but not RS2 induced phylum-level changes , significantly increasing Actinobacteria and Bacteroidetes while decreasing Firmicutes . At the species level , the changes evoked by RS4 were increases in Bifidobacterium adolescentis and Parabacteroides distasonis , while RS2 significantly raised the proportions of Ruminococcus bromii and Eubacterium rectale when compared to RS4 . The population shifts caused by RS4 were numerically substantial for several taxa , leading for example , to a ten-fold increase in bifidobacteria in three of the subjects , enriching them to 18–30 % of the fecal microbial community . The responses to RS and their magnitudes varied between individuals , and they were reversible and tightly associated with the consumption of RS . Conclusion Our results demonstrate that RS2 and RS4 show functional differences in their effect on human fecal microbiota composition , indicating that the chemical structure of RS determines its accessibility by groups of colonic bacteria . The findings imply that specific bacterial population s could be selectively targeted by well design ed functional carbohydrates , but the inter-subject variations in the response to RS indicates that such strategies might benefit from more personalized approaches The potential ' nutritional advantages ' of probiotics and prebiotics consist of preventive , and sometimes curative , effects against certain diseases . The evidence supporting such advantages , which requires r and omised controlled trials and consistency of results from study to study , is rapidly increasing . This article summarizes the effects against diseases of intestinal origin . There is a high level of evidence for positive effects of some prebiotics to alleviate constipation and treat hepatic encephalopathy . Interesting aspects , but with a lower level of evidence at the present time , include prevention of colon cancer , intestinal infection , and recurrence of inflammatory bowel disease . There is a high level of evidence for positive effects of some probiotics in the alleviation of lactose intolerance , antibiotic-associated intestinal disorders and gastroenteritis . Evidence is rapidly growing regarding the prevention of recurrence of inflammatory bowel diseases . Positive trials have suggested preventive effects against intestinal colonization with specific gut pathogens including Clostridium difficile and Helicobacter pylori Certain nondigestible oligosaccharides can be selectively utilized by probiotics and reduce the risk of colon cancer . However , the inhibitory effects of xylooligosaccharides ( XOS ) on colon cancer are not well documented . This study evaluated the effects of xylooligosaccharides and fructooligosaccharides ( FOS ) on the alteration of cecal microbiota , cecal pH , cecal weight , and serum lipid levels , and also their inhibitory effect on precancerous colon lesions in male Sprague-Dawley rats . The rats were r and omly assigned to 4 groups : control , treatment with 1,2-dimethylhydrazine ( DMH ) [ 15 mg/(kg body wt.wk ) for 2 wk ] , treatment with DMH + 60 g XOS/kg diet , and treatment with DMH + 60 g FOS/kg diet . Rats were fed the experimental diets for 35 d , beginning 1 wk after the second dose of DMH . Both XOS and FOS markedly decreased the cecal pH and serum triglyceride concentration , and increased the total cecal weight and bifidobacteria population . XOS had a greater effect on the bacterial population than did FOS . Moreover , both XOS and FOS markedly reduced the number of aberrant crypt foci in the colon of DMH-treated rats . These results suggest that XOS and FOS dietary supplementation may be beneficial to gastrointestinal health , and indicate that XOS is more effective than FOS BACKGROUND Nondigestible oligosaccharides have been cl aim ed to benefit the health of the colon by selectively stimulating the growth of bifidobacteria and by decreasing the toxicity of the colon contents . OBJECTIVE We compared the effect of 2 doses of transgalactooligosaccharides and a placebo on the composition and activity of the intestinal microflora in 18 women and 22 men . DESIGN Strictly controlled experimental diets were supplied to 3 intervention groups in a parallel design . The study was divided into 2 consecutive 3-wk periods during which each participant consumed a run-in diet followed by an intervention diet that differed only in the amount of transgalactooligosaccharides : 0 ( placebo ) , 7.5 , and 15 g/d . Breath sample s and fecal sample s were collected at the end of both the run-in and intervention periods . RESULTS Apparent fermentability of transgalactooligosaccharides was 100 % . The highest dose of transgalactooligosaccharides significantly increased the concentration of breath hydrogen by 130 % ( P < 0.01 ) and the nitrogen density of the feces by 8.5 % ( P < 0.05 ) . The number of bifidobacteria increased after both placebo and transgalactooligosaccharides ingestion , but the differences between these increases were not significantly different . Transgalactooligosaccharides did not significantly affect bowel habits ; stool composition ; the concentration of short-chain fatty acids or bile acids in fecal water ; the concentration of ammonia , indoles , or skatoles in feces ; fecal pH ; or the composition of the intestinal microflora . CONCLUSION We conclude that transgalactooligosaccharides are completely fermented in the human colon , but do not beneficially change the composition of the intestinal microflora , the amount of protein fermentation products in feces , or the profile of bile acids in fecal water BACKGROUND Nondigestible carbohydrates ( NDCHs ) are fermented in the colon , where they can selectively promote the growth of bifidobacteria . OBJECTIVE Our aim was to determine the bifidogenic potential of different NDCHs used in human diets . DESIGN Two hundred healthy volunteers participated in this double-blind study . During phase 1 ( screening ) , 64 volunteers were r and omly assigned to 8 groups of 8 subjects each ; for 7 d , they ingested 10 g/d of 1 of the 7 NDCHs tested or of the placebo . During phase 2 ( dose-response study ) , 136 volunteers were r and omly assigned to 4 groups of 32 subjects who received 2.5 , 5.0 , 7.5 , or 10 g/d , respectively ( 8 subjects/dose ) , of one of the NDCHs that were proven to be bifidogenic during phase 1 and a fifth group of 8 subjects ( control subjects ) who received the placebo . Stools were recovered before and after NDCH consumption . RESULTS In phase 1 , 4 NDCHs were found to be bifidogenic : short-chain fructooligosaccharides ( P=0.008 ) , soybean oligosaccharides ( P=0.006 ) , galactooligosaccharides ( P < 0.0001 ) , and type III resistant starch ( P=0.02 ) ; lactulose , long-chain inulin , and isomaltooligosaccharides were not bifidogenic . In phase 2 , the effects of 7-d treatment on bifidobacteria concentrations were found to differ significantly among the 4 NDCHs ( P=0.009 for time x treatment interaction ) . However , no significant differences were found among doses , and there was no significant dose x time interaction . A low baseline bifidobacteria count was significantly associated with the bifidogenic response to treatment ( P < 0.001 ) . CONCLUSION This study showed the different bifidogenic properties among the substrates and underlined the importance of taking into account the baseline bifidobacteria counts when evaluating the effect of the treatment To investigate whether resistant starch ( RS ) affects putative risk factors for colon cancer , 24 healthy men consumed a daily RS supplement for 4 wk in addition to their habitual diet in a single-blind , r and omized , balanced multiple crossover trial . During the first week , all subjects consumed the control supplement containing glucose . Subsequently , each subject consumed , in r and om order , a supplement with RS2 ( uncooked high-amylose cornstarch ) , RS3 ( extruded and retro grade d high-amylose cornstarch ) , and glucose , each for 1 wk . The RS2 and RS3 supplements provided 32 g RS/d . Lithium was added to the supplements to measure compliance . Feces , 24-h urine , and breath sample s , as well as a 24-h food-consumption recall were obtained weekly from each subject . Compliance as measured by urinary lithium recovery was satisfactory . The mean composition of the background diet did not differ between the various supplementation periods . Breath-hydrogen excretion , stool weight , and fecal starch excretion were significantly higher during RS than during glucose supplementation , but did not differ during RS2 and RS3 supplementation . There were no significant differences in fecal dry weight , pH , or short-chain fatty acid concentrations , nor in the pH , bile acid concentrations , cytotoxicity , or osmolality of fecal water . It is concluded that in healthy men , supplementing the habitual diet for 1 wk with 32 g RS2 or RS3/d compared with glucose had no effect on putative risk factors for colon cancer , except for increasing stool weight and colonic fermentative activity . There were no significant differences between the effects of RS2 and RS3 on the indexes studied Recent evidence suggests that resistant starch ( RS ) is the single most important substrate for bacterial carbohydrate fermentation in the human colon . During two 4-wk periods . 12 healthy volunteers consumed a controlled basal diet enriched with either amylomaize starch ( 55.2 + /- 3.5 g RS/d ; high-RS diet ) or available cornstarch ( 7.7 + /- 0.3 g RS/d ; low-RS diet ) . Approximately 90 % of the RS consumed disappeared during intestinal passage ; increased fermentation was verified by elevated breath-hydrogen excretion . During the high-RS diet , fecal wet and dry weight increased 49 % and 56 % , respectively ( P < or = 0.005 ) , whereas stool water content did not change significantly . Fecal concentrations and daily excretion of short-chain fatty acids were not different in the two study periods . During the high-RS diet , bacterial beta-glucosidase activity decreased by 26 % ( P < or = 0.05 ) . Fecal concentrations of total and secondary bile acids were significantly lower during the high-RS than during the low-RS period [ a decrease of 30 % ( P < or = 0.05 ) and 32 % ( P < or = 0.01 ) , respectively , in total and secondary bile acids ] whereas concentrations of primary bile acids were unaffected by RS consumption . During the high-RS diet , fecal concentrations of total neutral sterols decreased by 30 % ( P < or = 0.005 ) and fecal concentrations of 4-cholesten-3-one decreased by 36 % ( P < or = 0.05 ) . These data suggest that RS has potentially important effects on bacterial metabolism in the human colon that may be relevant for cancer prevention A controlled study with eight healthy free-living subjects was carried out , in which energy intake was adjusted to the individual energy requirements . On administration of inulin , blood lipids , the faecal microflora , short-chain fatty acids and accompanying gastrointestinal symptoms were characterized in order to investigate the long-term effect of inulin . During the run-in phase ( 8 d ) , subjects received a typical Western diet providing 45 % energy as fat and 40 % energy as carbohydrate . Subsequently , the subjects consumed a fat-reduced diet which provided 30 % energy as fat and 55 % energy as carbohydrate for a period of 64 d using inulin as a fat replacer . The amounts of inulin consumed by the subjects ( up to 34 g/d ) were based on individual energy requirements with the aim to keep the diet isoenergetic with that used in the run-in period . To assess the effects of inulin administration , a control study ( run-in and intervention ) was carried out in which subjects consumed the same diet but devoid of inulin during the whole course of the study . To investigate the effect of inulin on faecal flora composition total bacteria and bifidobacteria in the faeces were enumerated by in situ hybridization with 16S rRNA targeted oligonucleotide probes . Inulin significantly increased bifidobacteria from 9.8 to 11.0 log10/g dry faeces and caused a moderate increase in gastrointestinal symptoms such as flatulence and bloatedness , whereas blood lipids and short-chain fatty acids remained essentially unaffected Background and aims : The mucosa associated flora of the large intestine is important in determining mucosal function although what controls its composition is unknown . This study has determined the effect of the prebiotic carbohydrates oligofructose and inulin on the mucosal flora . Methods : An in vitro chemostat model of both planktonic and surface associated bacteria was used followed by an intervention study in 29 subjects undergoing colonoscopy . Subjects : Fourteen subjects , recruited from colonoscopy waiting lists , supplemented their diet for two weeks with a mix of 7.5 g of oligofructose and 7.5 g inulin . Fifteen subjects were recruited at the time of colonoscopy and given no supplement . Multiple endoscopic biopsies were taken from the caecum , transverse and descending colon , and rectum . The mucosal flora was characterised by culture and to species level by cellular fatty acid profiles . Cell proliferation was assessed by immunohistochemical staining for minichromosome maintenance protein 2 , Ki67 , and proliferating cell nuclear antigen . Results : In vitro prebiotics increased surface counts of bifidobacteria from 6.6 to 7.3 log10 colony forming units ( CFU ) per slide ( p<0.0006 ) with no significant changes in planktonic bacteria . In the feeding study , prebiotics increased mucosal bifidobacteria ( log CFU/g mucosa ( SEM ) ) in both the proximal ( control 5.3 ( 0.4 ) v prebiotic 6.3 ( 0.3 ) ) ( p = 0.059 ) and distal ( control 5.2 ( 0.3 ) v prebiotic 6.4 ( 0.3 ) ) colon ( p = 0.01 ) . Lactobacilli were also increased ( 3.0 ( 0.1 ) v 3.7 ( 0.2 ) ( p = 0.02 ) in the proximal and 3.1 ( 0.1 ) v 3.6 ( 0.2 ) ( p = 0.04 ) in the distal colon , respectively ) . There were significantly more eubacteria in fed subjects but no changes in total anaerobes clostridia , bacteroides , or coliforms , nor in proliferation indices . Conclusion : Prebiotic carbohydrates can change the composition of the mucosa associated flora significantly Resistant starch decreases the concentration of secondary bile acids in the feces and the proliferation rate of colonic mucosal cells in healthy volunteers . This may reduce the risk of colon cancer . We investigated 23 patients with recently removed colonic adenoma(s ) in a controlled parallel trial . They consumed 45 g of maltodextrin per day as placebo for four weeks and were r and omly assigned to either 45 g of native amylomaize starch , containing 28 g of resistant starch type II or 45 g of maltodextrin for another four weeks . No effect on colorectal cell proliferation , fecal wet and dry weights , pH , and short-chain fatty acid excretion was seen . The bile acid concentration in fecal water decreased by 15 % ( P = 0.048 ) and the percentage secondary bile acids decreased by 14 % ( P = 0.002 ) on resistant starch relative to placebo . Whether this has a substantial role in colon cancer prevention in these patients remains to be established Objective : Faecal bifidobacteria and lactobacilli , perceived as exerting health-promoting properties , may be increased by ingestion of high-dose lactulose in humans . The effects of low and well-tolerated doses of lactulose are not well known . The aim of the study was to assess the effects of prolonged low-dose lactulose administration on faecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis . Subjects and methods : In all , 16 healthy volunteers were included in this controlled , r and omised , double-blind , parallel group trial . Participants ingested lactulose or placebo ( sucrose ) at a dose of 5 g b.i.d . for 6 weeks . Stools were regularly collected at baseline ( d0 ) , and after 3 ( d21 ) and 6 ( d42 ) weeks of sugar ingestion . Tolerance was evaluated using a daily chart . Results : Faecal bifidobacterial counts were higher in lactulose than in sucrose group ( P=0.03 ) . Lactulose ingestion led to a significant increase in faecal bifidobacteria counts from d0 to d21 and d42 ( ( m±s.e.m . ) 8.25±0.53 , 8.96±0.40 and 9.54±0.28 log colony-forming units/g wet wt ( CFU/g ) , respectively ( P=0.048 ) ) . Placebo ingestion did not lead to any faecal bifidobacterial count change . Total anaerobes , Lactobacillus and pH were not significantly changed throughout the study in the two groups . Neither faecal bile acids nor neutral sterols were modified by lactulose . Excess flatus was more common in the lactulose group ( P=0.03 ) , but was very mild . Bloating and borborygmi did not differ between both the groups . Conclusions : A measure of 10 g lactulose/day increases faecal bifidobacterial counts , and lactulose fulfils the criteria requested to be considered as a prebiotic Sulindac , atorvastatin , or prebiotic dietary fiber may reduce colorectal cancer ( CRC ) risk . However , clinical trial data are currently limited . We conducted a r and omized , phase II chemoprevention trial involving subjects 40 years or older , with previously resected colon cancer or multiple/advanced colorectal adenomas . Magnification chromoendoscopy ( MCE ) was performed to identify and characterize rectal aberrant crypt foci ( ACF ) ; eligibility criteria required five or more rectal ACFs at baseline . Intervention assignments were as follows : ( a ) atorvastatin 20 mg qd ; ( b ) sulindac 150 mg bid ; ( c ) oligofructose-enriched inulin ( as ORAFTI ® Synergy1 ) 6 gm bid ; or ( d ) control ( maltodextrin ) 6 gm bid , for 6 months . Percent change in rectal ACF number ( % ΔACF ) within arm was the primary endpoint . Secondary endpoints included changes in proliferation ( Ki67 ) and apoptosis ( caspase-3 ) , as measured from normal mucosa biopsy sample s. Among 85 eligible r and omized subjects , 76 ( 86 % ) completed the trial per protocol . The median ( range ) of rectal ACF was 9 ( 5–34 ) and 8 ( 0–37 ) at baseline and postintervention , respectively . The median ( SD ) for % ΔACF was 5.6 ( −69 % to 143 % ) , −18.6 ( −83 % to 160 % ) , −3.6 ( −88 % to 83 % ) , and −10.0 ( −100 % to 117 % ) in the atorvastatin , sulindac , ORAFTI ® Synergy1 and control arms , respectively . Neither within-arm ( P = 0.12–0.59 ) nor between-arm ( P = 0.30–0.92 ) comparisons of % ΔACF were statistically significant . The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis ( P > 0.05 for each comparison ) . Data from this multicenter , phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin , sulindac , or ORAFTI ® Synergy1 , although statistical power was limited by the relatively small sample size . Cancer Prev Res ; 4(2 ) ; 259–69 . © 2011 AACR Colonic adenomas represent the natural precursor lesions of most colorectal cancers . The treatment of choice is endoscopic polypectomy . However , after endoscopic removal , polyps recur in a large fraction of cases . Thus , we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps . After polypectomy , 255 individuals were r and omized into three groups . Group 1 was given vitamin A ( 30,000 IU/ day ) , vitamin C ( 1 g/day ) , and vitamin E ( 70 mg/day ) ; Group 2 was given lactulose ( 20 g/day ) ; Group 3 received no treatment . Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma . The remaining 209 individuals were included in the analysis according to the “ intention to treat ” criterion , though 34 did not adhere to the scheduled treatment or were lost during the follow-up . Subjects were followed at regular intervals for an average of 18 months . Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist . In the 209 evaluable subjects , the percentages of recurrence of adenomas were 5.7 percent , 14.7 percent , and 35.9 percent in the vitamins , lactulose , and untreated groups , respectively . The fraction of subjects remaining free of adenomas , estimated by Kaplan-Meier survival curves , was significantly different among the three groups ( log-rank chisquared = 17.138;P < 0.001 ) . Using Cox 's regression analysis , treatment was the only variable that significantly contributed to the model ( regression coefficient=0.905;P<0.001 ) . In conclusion , either antioxidant vitamins or , to a lesser extent , lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents , at least in high-risk individuals Patients with a history of sporadic adenomas have increased epithelial cell proliferative activity , an intermediate risk marker for colorectal cancer . Reduction of proliferation by dietary intervention may reflect a decreased colorectal cancer risk . To evaluate whether calcium or resistant starch could reduce proliferative activity throughout the colon , we performed a r and omized controlled trial in 111 sporadic adenoma patients . Patients received two placebos , 1 g of calcium + placebo , or 30 g of amylomaize ( 19 g of resistant starch ) + placebo . After 2 mo , biopsies were collected from the cecum , transverse and sigmoid colon , and rectum during colonoscopy . Epithelial cell proliferation was determined by dividing the number of 5-bromo-2-deoxyuridine-labeled nuclei by the total number of nuclei × 100 ( labeling index , LI ) . LI of luminal , mid , and basal compartments was determined . Twenty-five patients dropped out . In the remaining 86 patients ( 28 treated with placebo , 30 with calcium + placebo , and 28 with resistant starch + placebo ) , no difference was observed in total LI , the LI of the three compartments , or the crypt length in the four areas of the colorectum . Colonic epithelial cell proliferative activity throughout the colon of sporadic adenoma patients is not affected by supplementation with 1 g of calcium or 19 g of resistant starch Objective : To study the effect of the intake of 15 g nondigestible oligosaccharides per day on various parameters of large-bowel function , as well as on blood lipid concentrations and glucose absorption in man . Design : Latin square , r and omized , double-blind , diet-controlled . Setting : Metabolic research unit . Subjects : Twelve apparently healthy men ( mean age 23 years ) , recruited from the Institute ’s pool of volunteers , no drop-outs . Interventions : Four treatment periods of 3 weeks : inulin , fructo-oligosaccharides ( FOS ) , galacto-oligosaccharides ( GOS ) and control ; analyses of stool weight , intestinal transit , faecal pH , short-chain fatty acids , bile acids , faecal enzymes , blood lipids and glucose absorption . Results : As compared to the control treatment : higher concentration of faecal acetate ( inulin and GOS , P<0.05 ) and valerate ( inulin , P<0.05 ) , significantly lower concentration of faecal deoxycholic acid ( inulin and FOS , P<0.05 and P<0.02 , respectively ) and β-glucuronidase activity ( inulin and GOS , P<0.05 and P<0.02 respectively ) . Other changes of faecal parameters and those of blood lipids and glucose absorption were statistically not significant . Conclusions : Results indicate that nondigestible oligosaccharides are ( partly ) fermented in the human colon , but in healthy young men the effects are limited . Also the consumption of 15 g nondigestible oligosaccharides does not seem to alter blood lipid concentrations and glucose absorption in our young healthy adults . Sponsorship : European Union and ORAFTI s.a . , Tienen , Belgium BACKGROUND Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia ; however , the effects of aspirin in the Lynch syndrome ( hereditary nonpolyposis colon cancer ) are not known . Resistant starch has been associated with an antineoplastic effect on the colon . METHODS In a r and omized , placebo-controlled trial , we used a two-by-two design to investigate the effects of aspirin , at a dose of 600 mg per day , and resistant starch ( Novelose ) , at a dose of 30 g per day , in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome . RESULTS Among 1071 persons in 43 centers , 62 were ineligible to participate in the study , 72 did not enter the study , and 191 withdrew from the study . These three categories were equally distributed across the study groups . Over a mean period of 29 months ( range , 7 to 74 ) , colonic adenoma or carcinoma developed in 141 participants . Of 693 participants r and omly assigned to receive aspirin or placebo , neoplasia developed in 66 participants receiving aspirin ( 18.9 % ) , as compared with 65 receiving placebo ( 19.0 % ) ( relative risk , 1.0 ; 95 % confidence interval [ CI ] , 0.7 to 1.4 ) . There were no significant differences between the two groups with respect to the development of advanced neoplasia ( 7.4 % and 9.9 % , respectively ; P=0.33 ) . Among the 727 participants receiving resistant starch or placebo , neoplasia developed in 67 participants receiving starch ( 18.7 % ) , as compared with 68 receiving placebo ( 18.4 % ) ( relative risk , 1.0 ; 95 % CI , 0.7 to 1.4 ) . Advanced adenomas and colorectal cancers were evenly distributed in the two groups . The prevalence of serious adverse events was low , and the events were evenly distributed . CONCLUSIONS The use of aspirin , resistant starch , or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome . ( Current Controlled Trials number , IS RCT N59521990 . |
1,183 | 24,146,822 | Adverse effects were reported in all of the ten included studies , and well tolerated in all patients with DPN .
Despite of the apparently positive findings and low risk of bias , it is premature to conclude the efficacy of CHMs for the treatment of DPN because of the high clinical heterogeneity and small sample sizes of the included studies .
However , CHM therapy was safe for DPN . | BACKGROUND Diabetic peripheral neuropathy ( DPN ) is very common in people with diabetes .
Chinese herbal medicine ( CHM ) therapy has been developed for DPN empirically over the years .
The aim of this systematic review and meta- analysis was to assess the efficacy and safety of CHMs for patients suffering from DPN . | In a double-blind , r and omized , controlled study , the effectiveness of treatment with a combination of Benfotiamine ( an Allithiamine , a lipid-soluble derivative of vitamin B1 with high bioavailability ) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy . The results showed a significant improvement ( p = 0.006 ) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold . Long-term observation of 9 patients with verum over a period of 9 months support the results . Therapy-specific adverse effects were not seen . The results of this double-blind investigation , of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials BACKGROUND Diabetes is the most important cause of peripheral neuropathy ( DPN ) . No definitive treatment for DPN has been established , and very few data on the role of exercise training on DPN have been reported . AIM OF THE STUDY We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients . PARTICIPANTS AND METHODS Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled , r and omized , and subdivided in two groups : 31 diabetic participants [ 15 f , 16 m ; 49+/-15.5 years old ; body mass index ( BMI ) = 27.9+/-4.7 ] , who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50 % to 85 % of the heart rate reserve ( exercise group : EXE ) , and a control group of 47 diabetic participants ( CON ; 24 f , 23 m ; 52.9+/-13.4 years old ; BMI = 30.9+/-8.4 ) . Vibration perception threshold ( VPT ) , nerve distal latency ( DL ) , nerve conduction velocity ( NCV ) , and nerve action potential amplitude ( NAPA ) in the lower limbs were measured . RESULTS We found significant differences on Delta ( delta ) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P<.001 , for both ) . The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group ( 17 % vs. 0.0 % , P<.05 , and 29.8 % vs. 6.45 % , P<.05 , respectively ) . In addition , the percentage of diabetic patients who developed increased VPT ( 25 V ) during the study was significantly higher in the CON than the EXE group ( 21.3 % vs. 12.9 % , P<.05 ) . Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P<.05 ) ; no significant change in Malleolus VPT between the two groups occurred . CONCLUSIONS This study suggests , for the first time , that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED We studied the clinical and neurophysiological effects of methylcobalamin on patients with diabetic neuropathy . In a double-blind study , the active group showed statistical improvement in the somatic and autonomic symptoms with regression of signs of diabetic neuropathy . Motor and sensory nerve conduction studies showed no statistical improvement after 4 months . The drug was easily tolerated by the patients and no side effects were encountered The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Forty five insulin dependent diabetics were r and omised to treatment with continuous subcutaneous insulin infusion ( CSII ) , multiple insulin injections ( five or six daily ) , or conventional twice daily insulin injections . Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment ( p less than 0.01 ) . Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment ( p less than 0.001 ) , but blood glucose concentrations below 2.5 mmol/l ( 45 mg/100 ml ) were more common . After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment , in whom the number had increased significantly ( p less than 0.01 ) . Motor nerve conduction velocity deteriorated in the patients given conventional treatment ; in those given CSII it was unchanged during the first year but had improved after two years ( p less than 0.01 ) . Glomerular hyperfiltration was reduced with CSII , but no change occurred in urine albumin excretion rates . Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications OBJECTIVE To evaluate the effects of Shenmai Huoxue Decoction ( SMHXD ) on early diabetic peripheral neuropathy ( DPN ) in rats . METHODS The rats were r and omly divided into 3 groups : normal group , diabetic model group and SMHXD-treated diabetic group . The diabetic rats were induced by streptozotocin ( STZ ) intraperitoneally . After the treatment , sensory nerve conduction velocity ( SNCV ) of caudal nerve was detected with evoked electromyography , and the activity of aldose reductase ( AR ) in erythrocytes and the concentration of endothelin ( ET ) in plasma were measured . RESULTS It was showed that the SNCV reduced significantly and the activity of AR in erythrocytes and the concentration of ET in plasma were increased significantly in diabetic group as compared with those in the normal group . The SNCV was increased , and the activity of AR in erythrocytes and the concentration of ET in plasma were improved significantly in SMHXD-treated diabetic group after the treatment . CONCLUSION The results indicate that SMHXD can alleviate the lesion of DPN in the early stage of diabetic rats BACKGROUND Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus ( IDDM ) . We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications . METHODS A total of 1441 patients with IDDM--726 with no retinopathy at base line ( the primary -prevention cohort ) and 715 with mild retinopathy ( the secondary -intervention cohort ) were r and omly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections . The patients were followed for a mean of 6.5 years , and the appearance and progression of retinopathy and other complications were assessed regularly . RESULTS In the primary -prevention cohort , intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent ( 95 percent confidence interval , 62 to 85 percent ) , as compared with conventional therapy . In the secondary -intervention cohort , intensive therapy slowed the progression of retinopathy by 54 percent ( 95 percent confidence interval , 39 to 66 percent ) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent ( 95 percent confidence interval , 14 to 67 percent ) . In the two cohorts combined , intensive therapy reduced the occurrence of microalbuminuria ( urinary albumin excretion of > or = 40 mg per 24 hours ) by 39 percent ( 95 percent confidence interval , 21 to 52 percent ) , that of albuminuria ( urinary albumin excretion of > or = 300 mg per 24 hours ) by 54 percent ( 95 percent confidence interval 19 to 74 percent ) , and that of clinical neuropathy by 60 percent ( 95 percent confidence interval , 38 to 74 percent ) . The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia . CONCLUSIONS Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy , nephropathy , and neuropathy in patients with IDDM OBJECTIVE To investigate the effect of xiaokeling concentration fluid on insulin-like growth factor-1 ( IGF-1 ) mRNA expression in sciatic nerve of Streptozotocin-induced diabetic rats . METHODS Thirty diabetic rats were r and omly divided into model group , mecobalamin tablets group , and xiaokeling concentration fluid group . The IGF-1 mRNA level in sciatic nerve of each group was determined after 8 weeks by relative quantity RT-PCR . RESULTS The IGF-1 mRNA level in sciatic nerve of diabetic rats between xiaokeling concentration fluid group , mecobalamin tablets group and normal group showed no significant difference ( P = 0.213 , P = 0.822 , P = 0.304 ) , while was significantly higher than that of the model group ( P < 0.05 ) . IGF-1 mRNA level was negatively correlated with the level of blood sugar ( P < 0.05 ) . CONCLUSION IGF-1 mRNA level decreased in sciatic nerve of diabetic rats . Xiaokeling concentration fluid can increase the IGF-1 mRNA level in sciatic nerve of diabetic rats . Xiaokeling concentration fluid is involved in the regulation of IGF-1 expression , and probably prevents diabetic peripheral neuropathy from deteriorating UNLABELLED Although exercise can significantly reduce the prevalence and severity of diabetic complications , no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy ( DPN ) . The purpose of this pilot study was to examine feasibility and effectiveness of a supervised , moderately intense aerobic and resistance exercise program in people with DPN . We hypothesized that the exercise intervention can improve neuropathic symptoms , nerve function , and cutaneous innervation . METHODS A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program . Seventeen subjects with diagnosed DPN ( 8 males/9 females ; age 58.4±5.98 ; duration of diabetes 12.4±12.2 years ) completed the study . Outcome measures included pain measures ( visual analog scale ) , Michigan Neuropathy Screening Instrument ( MNSI ) question naire of neuropathic symptoms , nerve function measures , and intraepidermal nerve fiber ( IENF ) density and branching in distal and proximal lower extremity skin biopsies . RESULTS Significant reductions in pain ( -18.1±35.5 mm on a 100 mm scale , P=.05 ) , neuropathic symptoms ( -1.24±1.8 on MNSI , P=.01 ) , and increased intraepidermal nerve fiber branching ( + 0.11±0.15 branch nodes/fiber , P=.008 ) from a proximal skin biopsy were noted following the intervention . CONCLUSIONS This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy . These findings are particularly promising given the short duration of the intervention , but need to be vali date d by comparison with a control group in future studies R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly |
1,184 | 16,378,566 | Although telephone consultation appears to have the potential to reduce GP workload , questions remain about its effect on service use . | BACKGROUND In recent years there has been a growth in the use of the telephone consultation for healthcare problems .
This has developed , in part , as a response to increased dem and for GP and accident and emergency department care .
AIM To assess the effects of telephone consultation and triage on safety , service use , and patient satisfaction . | We recently published the results of a r and omised controlled trial of a nurse telephone consultation service in primary care out of hours.1 The new service , operating at evenings and weekends , significantly reduced general practitioners ’ workload and was at least as safe as the existing out of hours service . Contacts diminish sharply after about 10 pm,2 and , anecdotally , a higher proportion of night calls necessitate consultation with a general practitioner . We report here a parallel trial aim ed at establishing whether nurse telephone consultation was equally effective in managing workload at night Objective : To investigate the potential impact for ambulance services of telephone assessment and triage for callers who present with non-serious problems ( Category C calls ) as classified by ambulance service call takers . Design : Pragmatic controlled trial . Calls identified using priority dispatch protocol s as non-serious were allocated to intervention and control groups according to time of call . Ambulance dispatch occurred according to existing procedures . During intervention sessions , nurses or paramedics within the control room used a computerised decision support system to provide telephone assessment , triage and , if appropriate , offer advice to permit estimation of the potential impact on ambulance dispatch . Setting : Ambulance services in London and the West Midl and s. Subjects : Patients for whom emergency calls were made to the ambulance services between April 1998 and May 1999 during four hour sessions sample d across all days of the week between 0700 and 2300 . Main outcome measures : Triage decision , ambulance cancellation , attendance at an emergency department . Results : In total , there were 635 intervention calls and 611 controls . Of those in the intervention group , 330 ( 52.0 % ) were triaged as not requiring an emergency ambulance , and 119 ( 36.6 % ) of these did not attend an emergency department . This compares with 55 ( 18.1 % ) of those triaged by a nurse or paramedic as requiring an ambulance ( odds ratio 2.62 ; 95 % CI 1.78 to 3.85 ) . Patients triaged as not requiring an emergency ambulance were less likely to be admitted to an inpatient bed ( odds ratio 0.55 ; 95 % CI 0.33 to 0.93 ) , but even so 30 ( 9.2 % ) were admitted . Nurses were more likely than paramedics to triage calls into the groups classified as not requiring an ambulance . After controlling for age , case mix , time of day , day of week , season , and ambulance service , the results of a logistic regression analysis revealed that this difference was significant with an odds ratio for nurses : paramedics of 1.28 ( 95 % CI 1.12 to 1.47 ) . Conclusions : The findings indicate that telephone assessment of Category C calls identifies patients who are less likely to require emergency department care and that this could have a significant impact on emergency ambulance dispatch rates . Nurses were more likely than paramedics to assess calls as requiring an alternative response to emergency ambulance despatch , but the extent to which this relates to aspects of training and professional perspective is unclear . However , consideration should be given to the acceptability , reliability , and cost consequences of this intervention before it can be recommended for full evaluation OBJECTIVE To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls . DESIGN Block r and omised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks . One of each matched pair was r and omised to receive the intervention . SETTING One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire . SUBJECTS All patients contacting the out of hours service or about whom contact was made during specified times over the trial year . INTERVENTION A nurse telephone consultation service integrated within a general practice cooperative . The out of hours period was 615 pm to 1115 pm from Monday to Friday , 1100 am to 1115 pm on Saturday , and 800 am to 1115 pm on Sunday . Experienced and specially trained nurses received , assessed , and managed calls from patients or their carers . Management options included telephone advice ; referral to the general practitioner on duty ( for telephone advice , an appointment at a primary care centre , or a home visit ) ; referral to the emergency service or advice to attend accident and emergency . Calls were managed with the help of decision support software . MAIN OUTCOME MEASURES Deaths within seven days of a contact with the out of hours service ; emergency hospital admissions within 24 hours and within three days of contact ; attendance at accident and emergency within three days of a contact ; number and management of calls in each arm of the trial . RESULTS 14 492 calls were received during the specified times in the trial year ( 7308 in the control arm and 7184 in the intervention arm ) concerning 10 134 patients ( 10.4 % of the registered population ) . There were no substantial differences in the age and sex of patients in the intervention and control groups , though male patients were underrepresented overall . Reasons for calling the service were consistent with previous studies . Nurses managed 49.8 % of calls during intervention periods without referral to a general practitioner . A 69 % reduction in telephone advice from a general practitioner , together with a 38 % reduction in patient attendance at primary care centres and a 23 % reduction in home visits was observed during intervention periods . Statistical equivalence was observed in the number of deaths within seven days , in the number of emergency hospital admissions , and in the number of attendances at accident and emergency departments . Conclusions Nurse telephone consultation produced substantial changes in call management , reducing overall workload of general practitioners by 50 % while allowing callers faster access to health information and advice . It was not associated with an increase in the number of adverse events . This model of out of hours primary care is safe and effective The authors examined the effect of after-hours telephone access to physicians and physician access to computerized medical records on hospitalizations and emergency room ( ER ) visits in an inner-city , adult , general medicine clinic . Patients were r and omly assigned to a control ( C ) and two study groups ( S1 and S2 ) . Patients in study groups S1 and S2 had after-hours telephone access to physicians . Computerized medical records were accessible to physicians only for callers in study group S2 . During the initial 18 months of study , only 7.6 % of eligible patients called the after-hours service , a rate of 6 calls/1,000 patients / month ( 200 calls/1,849 patients /18 months ) . Repeated promotion of the service was subsequently undertaken , and 19.4 % of the patients used the service during the final 12 months of study , a rate of 24.1 calls/1,000 patients /month ( 467 calls/1,616 patients /12 months ) . There were no significant differences in hospitalizations or ER visits among the control and two study groups A r and omized clinical trial of pediatric protocol s administered by health assistants demonstrated an alternate method of h and ling telephone complaints in a large emergency room . The new system advised a higher medical examination rate than the current system in the emergency room probably bacause the current system has deficits with respect to collecting necessary information and making explicit decisions . This higher rate of recommended visits demonstrated in the emergency room was not confirmed in the two pediatric primary -care setting s in which the protocol system was also tested . In addition to this use , the telephone protocol s may also be useful in training medical and nursing students , in h and ling telephone complaints similar to a poison control center , in triaging problems in a rural or emergency medical service , and in providing a record of the telephone call BACKGROUND After-hours telephone calls are a stressful and frustrating aspect of pediatric practice . At the request of private practice pediatricians in Denver , a metropolitan area-wide system was created to manage after-hours pediatric telephone calls and after-hours patient care . This system , the After-Hours Program ( AHP ) , uses specially trained pediatric nurses with st and ardized protocol s to provide after-hours telephone triage and advice for the patients of 92 Denver pediatricians , representing 56 practice s. OBJECTIVES This report describes the AHP , presents data from 4 years ' experience with the program , and describes results of our evaluation of the following aspects of the program : subscribing physician satisfaction , parent satisfaction , the accuracy and appropriateness of telephone triage , and program costs . METHODS After-Hours Program records ( including quality assurance data ) for all 4 years of operation were retrospectively review ed , tabulated , and analyzed . The results of two subscribing physician surveys and one parent caller satisfaction survey are presented . A retrospective review of after-hours patient care encounter forms assessed the necessity for after-hours visits triaged by the AHP . An analysis of the total cost of this program to 10 r and omly selected subscribing physicians was conducted using current AHP data and a survey of the 10 physicians . RESULTS In 4 years , 107,938 calls have been successfully managed without an adverse clinical outcome . Minor errors in using protocol s occurred in one call out of 1450 after-hours calls . After-hours phoen calls necessitated an after-hours patient visit 20 % of the time and generated one after-hours hospital admission out of every 88 calls . Just over half of the patients were managed with home care advice only , and 28 % were given home care advice after-hours and seen the next day in the primary physician 's office . Of all patients directed by the telephone triage nurses to be seen after hours , 78 % were determined to have a condition necessitating after-hours care . Data are presented regarding call volumes by time of day , day of week , patient age , and patient 's initial complaint . The 6 most common complaints accounted for more than one half of the calls , and 38 complaints accounted for more than 95 % of all after-hours calls . Utilization by subscribing physicians is described . Satisfaction among subscribing pediatricians was 100 % , and among parents was 96 % to 99 % on a variety of issues . The total cost to participating Denver pediatricians ( which includes revenues " given up " as a result of not seeing patients after hours ) ranged from 1 % to 12 % of their annual net income , depending on a variety of factors . CONCLUSIONS Large-scale after-hours telephone coverage systems can be effective and well-received by patients , parents , and primary physicians . Data presented in this report can assist in planning the training of personnel who provide after-hours telephone advice and triage . Controversies associated with this type of program are discussed . Suggestions are made regarding the direction of future programs and research The purpose of this research was to determine whether a specialized telephone service could cut down on unscheduled visits to ambulatory care and improve satisfaction with care . Patients who were to receive care ( N=561 ) were assigned r and omly to a specialized telephone service or a control group . They were measured with regard to satisfaction with care before being assigned and 6 months later . The number of scheduled and unscheduled visits also were monitored for a 1-year follow-up period . The telephone service , which provided a triage system for referrals as well as a source of central contact for scheduling or for complaints , helped to improve satisfaction and reduce the number of unscheduled visits within 6 months . Such a service also may have application in other problem areas in the delivery of quality ambulatory care STUDY OBJECTIVES We sought to compare triage design ations derived from in-person and telephone interviews and systematic ally examine the effect of visual cues , vital signs , and complaint-based protocol s on the triage process . METHODS We conducted a 2-phase , prospect i ve , observational study employing a r and omized , crossover design in a university teaching hospital emergency department . In both phases , every eligible patient underwent sequential in-person and telephone triage interviews conducted by certified ED triage nurses . After taking a history , each nurse chose 1 of 5 hypothetical triage design ations and , after being told the patient 's vital signs , again selected a design ation . Phase 1 design ations were based solely on nurses ' clinical expertise . In phase 2 , both nurses used complaint-based protocol s. RESULTS Agreement between telephone and in-person design ations was poor ( percent agreement , 43.1 % to 48.8 % ; kappa,.19 to.26 ; taub,.34 to.45 for the 4 primary comparisons ) . Knowledge of vital signs and use of protocol s did not improve agreement or increase identification of patients requiring admission to hospital . CONCLUSION These data establish that telephone and in-person triage are not equivalent and suggest that visual cues may play an important role in the triage process . It is unclear whether telephone triage is an adequate method of assigning patients to an appropriate level of care |
1,185 | 29,101,767 | Most studies assessed promotions of fresh fruits and vegetables ( n = 20 ) ; however , these foods may be hard to source , have high perishability , and raise concerns about safety and h and ling .
Pricing interventions generally increased stocking , sales , purchasing , and consumption of promoted foods and beverages . | INTRODUCTION Food pricing policies to promote healthy diets , such as taxes , price manipulations , and food subsidies , have been tested in different setting s. However , little consensus exists about the effect of these policies on the availability of healthy and unhealthy foods , on what foods consumers buy , or on the impact of food purchases on consumer health outcomes .
We conducted a systematic review of studies of the effect of food-pricing interventions on retail sales and on consumer purchasing and consumption of healthy foods and beverages . | Objective Small food store interventions show promise to increase healthy food access in under-re source d areas . However , none have tested the impact of price discounts on healthy food supply and dem and . We tested the impact of store-directed price discounts and communications strategies , separately and combined , on the stocking , sales and prices of healthier foods and on storeowner psychosocial factors . Design Factorial design r and omized controlled trial . Setting Twenty-four corner stores in low-income neighbourhoods of Baltimore City , MD , USA . Subjects Stores were r and omized to pricing intervention , communications intervention , combined pricing and communications intervention , or control . Stores that received the pricing intervention were given a 10–30 % price discount by wholesalers on selected healthier food items during the 6-month trial . Communications stores received visual and interactive material s to promote healthy items , including signage , taste tests and refrigerators . Results All interventions showed significantly increased stock of promoted foods υ . control . There was a significant treatment effect for daily unit sales of healthy snacks ( β = 6·4 , 95 % CI 0·9 , 11·9 ) and prices of healthy staple foods ( β = −0·49 , 95 % CI −0·90 , −0·03 ) for the combined group υ . control , but not for other intervention groups . There were no significant intervention effects on storeowner psychosocial factors . Conclusions All interventions led to increased stock of healthier foods . The combined intervention was effective in increasing sales of healthier snacks , even though discounts on snacks were not passed to the consumer . Experimental research in small stores is needed to underst and the mechanisms by which store-directed price promotions can increase healthy food supply and dem and Objectives This study examined associations between high school students ' lunch patterns and vending machine purchases and the school food environment and policies . Methods A r and omly selected sample of 1088 high school students from 20 schools completed surveys about their lunch practice s and vending machine purchases . School food policies were assessed by principal and food director surveys . The number of vending machines and their hours of operation were assessed by trained research staff . Results Students at schools with open campus policies during lunchtime were significantly more likely to eat lunch at a fast food restaurant than students at schools with closed campus policies ( 0.7 days/week vs. 0.2 days/week , p < .001 ) . Student snack food purchases at school were significantly associated with the number of snack machines at schools ( p < .001 ) and policies about the types of food that can be sold . In schools with policies , students reported making snack food purchases an average of 0.5 ± 1.1 days/week as compared to an average of 0.9 ± 1.3 days/week in schools without policies ( p < .001 ) . In schools in which soft drink machines were turned off during lunch time , students purchased soft drinks from vending machines 1.4 ± 1.6 days/week as compared to 1.9 ± 1.8 days/week in schools in which soft drink machines were turned on during lunch ( p = .040 ) . ConclusionS chool food policies that decrease access to foods high in fats and sugars are associated with less frequent purchase of these items in school among high school students . Schools should examine their food-related policies and decrease access to foods that are low in nutrients and high in fats and sugars OBJECTIVES Financial constraint is the underpinning determinant of household food insecurity ; however , there has been little research examining the impact that increasing the ‘ money available ’ to food-insecure households could have on food purchasing . The main objective of the present study was to examine the effect of additional money ( in the form of supermarket vouchers ) on food expenditure in food-insecure households with children . DESIGN A parallel r and omized controlled trial with a 4-week baseline phase followed by a 4-week intervention phase . Households were r and omized to either receive vouchers ( coupons ) for 4 weeks or a control group that did not receive any vouchers . SETTING Dunedin , New Zeal and . SUBJECTS Low-income households with children ≥ 18 years ) reporting food insecurity ( n 214 ) . RESULTS The mean monetary value of the vouchers received by households was $ NZ 17?00 per week . The voucher group spent ≥ NZ 15.20 ( 95 % CI 1.46 , 28.94 ) more per week on food during the intervention phase compared with the control group ( P50.030 ) . There were no differences in expenditure between the voucher and the control group for the food groups ‘ fruit and vegetables ’ ( mean difference : ≥ NZ 0?46 ; 95 % CI 21.97 , 2.89 ; P50.709 ) , ‘ meat and poultry ’ ( mean difference : ≥ NZ 0.29 ; 95 % CI 23.07 , 3.64 ; P50.866 ) and ‘ dairy ’ ( mean difference : ≥ NZ 0.82 ; 95 % CI 20.75 , 2.42 ; P50.302 ) . CONCLUSIONS Providing money via supermarket vouchers to food-insecure result ed in an increase in overall expenditure on food Importance Strategies to improve the nutritional status of those participating in the Supplemental Nutrition Assistance Program ( SNAP ) are of interest to policymakers . Objective To evaluate whether the proposed policy of incentivizing the purchase of fruits and vegetables and prohibiting the purchase of less nutritious foods in a food benefit program improves the nutritional quality of participants ' diets . Design , Setting , and Participants Lower income participants ( n = 279 ) not currently enrolled in SNAP were r and omized to 1 of 4 experimental financial food benefit conditions : ( 1 ) incentive ( 30 % financial incentive for fruits and vegetables purchased using food benefits ) ; ( 2 ) restriction ( not allowed to buy sugar sweetened beverages , sweet baked goods , or c and ies with food benefits ) ; ( 3 ) incentive plus restriction ( 30 % financial incentive on fruits and vegetables and restriction of purchase of sugar sweetened beverages , sweet baked goods , or c and y with food benefits ) ; or ( 4 ) control ( no incentive or restrictions on foods purchased with food benefits ) . Participants in all conditions were given a study -specific debit card where funds were added every 4 weeks for a 12-week period . Outcome measures were collected at baseline and in the final 4 weeks of the experimental period . Main Outcomes and Measures Primary outcomes ( from 24-hour dietary recalls ) included intake of energy , discretionary calories , and overall diet quality . Results A number of favorable changes were observed in the incentive plus restriction condition that were significantly different from changes in the control condition . These included ( 1 ) reduced intake of energy ( -96 kcal/d , st and ard error [ SE ] , 59.9 ) ; ( 2 ) reduced intake of discretionary calories ( -64 kcal/d , SE 26.3 ) ; ( 3 ) reduced intake of sugar sweetened beverages , sweet baked goods , and c and ies ( -0.6 servings/d , SE 0.2 ) ; ( 4 ) increased intake of solid fruit ( 0.2 servings/d , SE 0.1 ) ; and ( 5 ) improved Healthy Eating Index score ( 4.1 points , SE 1.4 ) . Fewer improvements were observed in the incentive only and restriction only arms . Conclusions and Relevance A food benefit program that pairs incentives for purchasing more fruits and vegetables with restrictions on the purchase of less nutritious foods may reduce energy intake and improve the nutritional quality of the diet of participants compared with a program that does not include incentives or restrictions . Clinical Trial Registration clinical trials.gov Identifier : NCT02643576 Background Amateur sporting clubs represent an attractive setting for health promotion . This study assesses the impact of a multi-component intervention on the availability , promotion and purchase of fruit and vegetable and non sugar -sweetened drink products from community sporting club canteens . We also assessed the impact the intervention on sporting club revenue from the sale of food and beverages . Method A repeat cross-sectional , parallel group , cluster r and omized controlled trial was undertaken with amateur community football clubs in New South Wales , Australia . The intervention was conducted over 2.5 winter sporting seasons and sought to improve the availability and promotion of fruit and vegetables and non sugar-sweetened drinks in sporting club canteens . Trial outcomes were assessed via telephone surveys of sporting club representatives and members . Results Eighty five sporting clubs and 1143 club members participated in the study . Relative to the control group , at follow-up , clubs allocated to the intervention were significantly more likely to have fruit and vegetable products available at the club canteen ( OR = 5.13 ; 95 % CI 1.70 - 15.38 ) , were more likely to promote fruit and vegetable selection using reduced pricing and meal deals ( OR = 34.48 ; 95 % CI 4.18 - 250.00 ) and members of intervention clubs were more likely to report purchase of fruit and vegetable ( OR = 2.58 95 % CI ; 1.08 - 6.18 ) and non sugar -sweetened drink ( OR = 1.56 ; 95 % CI 1.09 - 2.25 ) products . There was no significant difference between groups in the annual club revenue from food and non-alcoholic beverage sales . Conclusion The findings demonstrate that the intervention can improve the nutrition environment of sporting clubs and the purchasing behaviour of members . Trial registration Australian New Zeal and Clinical Trials Registry : ACTRN12609000224224 Background U.S. adults are at unprecedented risk of becoming overweight or obese , and most scientists believe the primary cause is an obesogenic environment . Worksites provide an opportunity to shape the environments of adults to reduce obesity risk . The goal of this group-r and omized trial was to implement a four-component environmental intervention at the worksite level to positively influence weight gain among employees over a two-year period . Environmental components focused on food availability and price , physical activity promotion , scale access , and media enhancements . Methods Six worksites in a U.S. metropolitan area were recruited and r and omized in pairs at the worksite level to either a two-year intervention or a no-contact control . Evaluations at baseline and two years included : 1 ) measured height and weight ; 2 ) online surveys of individual dietary intake and physical activity behaviors ; and 3 ) detailed worksite environment assessment . Results Mean participant age was 42.9 years ( range 18 - 75 ) , 62.6 % were women , 68.5 % were married or cohabiting , 88.6 % were white , 2.1 % Hispanic . Mean baseline BMI was 28.5 kg/m2 ( range 16.9 - 61.2 kg/m2 ) . A majority of intervention components were successfully implemented . However , there were no differences between sites in the key outcome of weight change over the two-year study period ( p = .36 ) . Conclusions Body mass was not significantly affected by environmental changes implemented for the trial . Results raise questions about whether environmental change at worksites is sufficient for population weight gain prevention . Trial Registration Clinical Trials.gov : Peer education has become a popular strategy for health promotion interventions with adolescents , but it has not been used widely in school-based nutrition education . This paper describes and reports on the feasibility of the peer leader component of a school-based nutrition intervention for young adolescents design ed to increase fruit and vegetable intakes and lower fat foods . About 1,000 seventh- grade students in eight schools received the nutrition intervention . Of these , 272 were trained as peer leaders to assist the teacher in implementing the activities . Results from a multicomponent process evaluation based on peer leader and classroom student feedback , direct classroom observation , and teacher ratings and interviews are presented . Results show that peer-led nutrition education approaches in schools are feasible and have high acceptability among peer leaders , classroom students , and teachers OBJECTIVE To examine the effectiveness of two methods of increasing fruit and fruit juice intake in pregnancy : midwives ' advice and vouchers exchangeable for juice . DESIGN Pregnant women were r and omly allocated to three groups : a control group , who received usual care ; an advice group , given advice and leaflets promoting fruit and fruit juice consumption ; and a voucher group , given vouchers exchangeable for fruit juice from a milk delivery firm . Dietary question naires were administered at ~16 , 20 and 32 weeks of pregnancy . Serum beta-carotene was measured at 16 and 32 weeks . SETTING An antenatal clinic in a deprived area . SUBJECTS Pregnant women aged 17 years and over . RESULTS The study comprised 190 women . Frequency of fruit consumption declined during pregnancy in all groups , but that of fruit juice increased substantially in the voucher group . Serum beta-carotene concentration increased in the voucher group , from 106.2 to 141.8 micromol l(-1 ) in women with measurements on both occasions ( P = 0.003 ) , decreased from 120.0 to 99.8 micromol l(-1 ) in the control group ( P = 0.005 ) , and was unchanged in the advice group . CONCLUSIONS Pregnant women drink more fruit juice if they receive vouchers exchangeable for juice supplied by the milk delivery service . Midwives ' advice to eat more fruit has no great effect . Providing vouchers for fruit juice is a simple method of increasing its intake in a deprived population and may be useful for other sections of the community OBJECTIVE To pilot the design and methodology for a large r and omised controlled trial ( RCT ) of two interventions to promote healthier food purchasing : culturally appropriate nutrition education and price discounts . DESIGN A 12-week , single-blind , pilot RCT . Effects on food purchases were measured using individualised electronic shopping data ( ' Shop ' N Go ' system ) . Partial data were also collected on food expenditure at other ( non-supermarket ) retail outlets . SETTING A supermarket in Wellington , New Zeal and . PARTICIPANTS Eligible customers were those who were the main household shoppers , shopped mainly at the participating store , and were registered to use the Shop ' N Go system . Ninety-seven supermarket customers ( 72 % women ; age 40 + /- 9.6 years , mean + /- st and ard deviation ) were r and omised to one of four intervention groups : price discounts , nutrition education , a combination of price discounts and nutrition education , or control ( no intervention ) . RESULTS There was a 98 % follow-up rate of participants , with 85 % of all reported supermarket purchases being captured via the electronic data collection system . The pilot did , however , demonstrate difficulty recruiting Maori , Pacific and low-income shoppers using the electronic register and mail-out . CONCLUSIONS This pilot study showed that electronic sales data capture is a viable way to measure effects of study interventions on food purchases in supermarkets , and points to the feasibility of conducting a large-scale RCT to evaluate the effectiveness of price discounts and nutrition education . Recruitment strategies will , however , need to be modified for the main trial in order to ensure inclusion of all ethnic and socio-economic groups OBJECTIVES ( 1 ) To describe promotional activities , particularly student-led , targeting lower-fat à la carte foods that were conducted in secondary schools ; and ( 2 ) to describe the relationships between the number and duration of total promotional activities for lower-fat à la carte foods and cafeteria sales of such foods over two years . DESIGN Promotional activities were implemented in schools that were r and omised to the intervention condition of a larger , two-year , school-based , r and omised , controlled nutrition intervention trial . SETTING Ten Minnesota secondary schools . SUBJECTS Students and school faculty , school food-service and research staff ( measured at the school level ) . RESULTS Over two years , 181 promotions were implemented ( n=49 in Year 1 and n=132 in Year 2 ) . In Year 1 , the number of promotions conducted in schools was significantly associated with percentage lower-fat food sales . In Year 2 , the duration of promotions was significantly associated with percentage lower-fat food sales . CONCLUSIONS Collaborative efforts among students , school food-service staff and research staff can be successful in implementing a large number of nutrition-related , school-wide promotional activities . These efforts can increase the sales of lower-fat foods in à la carte areas of school cafeterias Background Low-income black residents of Baltimore City have disproportionately higher rates of obesity and chronic disease than other Maryl and residents . Increasing the availability and affordability of healthy food are key strategies to improve the food environment and can lead to healthier diets . This paper describes B’More Healthy : Retail Rewards ( BHRR ) , an intervention that tests the effectiveness of performance-based pricing discounts and health communications , separately and combined , on healthy food purchasing and consumption among low-income small store customers . Methods / design BHRR is 2x2 factorial design r and omized controlled trial . Fifteen regular customers recruited from each of 24 participating corner stores in Baltimore City were enrolled . Food stores were r and omized to 1 ) pricing intervention , 2 ) communications intervention , 3 ) combined intervention , or 4 ) control . Pricing stores were given a 10 - 30 % price discount on selected healthier food items , such as fresh fruits , frozen vegetables , and baked chips , at the point of purchase from two food wholesale stores during the 6-month trial . Storeowners agreed to pass on the discount to the consumer to increase dem and for healthy food . Communications stores received visual and interactive material s to promote healthy items , including signage , taste tests , and refrigerators . Primary outcome measures include consumer food purchasing and associated psychosocial variables . Secondary outcome measures include consumer food consumption , store sales , and associated storeowner psychosocial factors . Process evaluation was monitored throughout the trial at wholesaler , small store , and consumer levels . Discussion This is the first study to test the impact of performance-based pricing and communications incentives in small food stores , an innovative strategy to encourage local wholesalers and storeowners to share responsibility in creating a healthier food supply by stocking , promoting , and reducing costs of healthier foods in their stores . Local food wholesalers were involved in a top-down , participatory approach to develop and implement an effective and sustainable program . This study will provide evidence on the effectiveness of price incentives and health communications , separately and combined , among a low-income urban U.S. population .Trial registration Clinical Trials.gov : NCT02279849 ( 2/18/2014 ) Background In the context of rising food prices , there is a need for evidence on the most effective approaches for promoting healthy eating . Individually-targeted behavioural interventions for increasing food-related skills show promise , but are unlikely to be effective in the absence of structural supports . Fiscal policies have been advocated as a means of promoting healthy eating and reducing obesity and nutrition-related disease , but there is little empirical evidence of their effectiveness . This paper describes the Supermarket Healthy Eating for LiFe ( SHELf ) study , a r and omised controlled trial to investigate effectiveness and cost-effectiveness of a tailored skill-building intervention and a price reduction intervention , separately and in combination , against a control condition for promoting purchase and consumption of healthy foods and beverages in women from high and low socioeconomic groups . Methods / design SHELf comprises a r and omised controlled trial design , with participants r and omised to receive either ( 1 ) a skill-building intervention ; ( 2 ) price reductions on fruits , vegetables and low-joule soft drink beverages and water ; ( 3 ) a combination of skill-building and price reductions ; or ( 4 ) a control condition . Five hundred women from high and low socioeconomic areas will be recruited through a store loyalty card program and local media . R and omisation will occur on receipt of informed consent and baseline question naire . An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups . Discussion This study will build on a pivotal partnership with a major national supermarket chain and the Heart Foundation to investigate the effectiveness of intervention strategies aim ed at increasing women 's purchasing and consumption of fruits and vegetables and decreased purchasing and consumption of sugar-sweetened beverages . It will be among the first internationally to examine the effects of two promising approaches - skill-building and price reductions - on diet amongst women . Trial Registration Current Controlled Trials IS RCT OBJECTIVE This study evaluated the Michigan Farmers ' Market Nutrition Program in one Michigan county to determine its effect on fruit and vegetable consumption behavior . SUBJECTS/ SETTING Subjects were selected from WIC and Community Action Agency population s : 564 low income women completed the pretest ; 455 completed the posttest . Attrition rate was 19.3 % . INTERVENTION Subjects were assigned to one of 4 interventions : education about the use , storage and nutritional value of fruits and vegetables , distribution of farmers ' market coupons , both education and coupons , or no intervention . DESIGN Education-only and coupon and education groups were r and omly assigned ; clinic appointment timing determined assignment to no-intervention and coupon-only groups . MAIN OUTCOME MEASURES A self-administered question naire before and after intervention measured attitudes about fruit and vegetable consumption and intake of fruits and vegetables . WIC records documented redemption of coupons . STATISTICAL ANALYSES Data analysis included 2-way multivariate analysis of covariance , univariate analysis of covariance , logistic regression , and covariance structure modeling . RESULTS Both the education interventions and the coupon interventions had positive effects . Coupons had a direct effect on increasing fruit and vegetable consumption behavior but no effect on attitudes . Education had a direct effect on attitudes and seemed to exert an effect on consumption behavior through attitudes . The maximum impact of the intervention was achieved through a combination of education and coupons . APPLICATIONS This study demonstrated that a low-income population may be more likely to increase its fruit and vegetable consumption behavior when incentives such as coupons improve affordability OBJECTIVES We evaluated an environmental intervention intended to increase sales of lower-fat foods in secondary school cafeterias . METHODS Twenty secondary schools were r and omly assigned to either an environmental intervention or a control group for a 2-year period . The intervention increased the availability of lower-fat foods and implemented student-based promotions . RESULTS A steeper rate of increase in sales of lower-fat foods in year 1 ( 10 % intervention vs -2.8 % control , P = .002 ) and a higher percentage of sales of lower-fat foods in year 2 ( 33.6 % intervention vs 22.1 % control , P = .04 ) were observed . There were no significant changes in student self-reported food choices . CONCLUSIONS School-based environmental interventions to increase availability and promotion of lower-fat foods can increase purchase of these foods among adolescents The objective of this study was to evaluate an intervention that combined mindful eating and online pre-ordering to promote healthier lunch purchases at work . The study took place at an urban hospital with 26 employees who were overweight or obese . The design included a contemporaneous comparison with delayed-treatment control and a three-phase prospect i ve study . A minimum 4-week baseline period preceded a 4-week full-intervention , in which participants received mindful eating training , pre-ordered their lunches , and received price discounts toward lunch purchases . In a 4-week reduced intervention phase , participants pre-ordered lunches without price discounts . Participant lunch purchases were tracked electronically at the point of purchase . The primary outcome measures were the amounts of kilocalories and fat grams in purchased lunches . In contemporaneous comparisons , the treatment group purchased lunches with an average of 144.6 fewer kilocalories ( p = 0.01 ) and 8.9 fewer grams of fat ( p = 0.005 ) compared to controls . In multivariable longitudinal analyses , participants decreased the average number of calories in their meals by 114.6 kcal per lunch and the average grams of fat by 5.4 per lunch during the partial-intervention compared to the baseline ( p < 0.001 ) . At the end of the study , a moderate increase was observed in participants ' overall mindful eating behaviors as compared to the beginning of the study ( p < 0.001 ) . The majority of participants ( 92 % ) said they would use the pre-ordering system if offered in the future . Combined mindful eating training and online pre-ordering appears a feasible and useful worksite intervention to improve food choices by employees OBJECTIVE Population -level strategies to improve healthy food choices are needed for obesity prevention . We conducted a r and omized controlled trial of 2672 employees at the Massachusetts General Hospital who were regular customers of the hospital cafeteria with all items labeled green ( healthy ) , yellow ( less healthy ) , or red ( unhealthy ) to determine if social norm ( peer-comparison ) feedback with or without financial incentives increased employees ' healthy food choices . METHODS Participants were r and omized in 2012 to three arms : 1 ) monthly letter with social norm feedback about healthy food purchases , comparing employee to " all " and to " healthiest " customers ( feedback-only ) ; 2 ) monthly letter with social norm feedback plus small financial incentive for increasing green purchases ( feedback-incentive ) ; or 3 ) no contact ( control ) . The main outcome was change in proportion of green-labeled purchases at the end of 3-month intervention . Post-hoc analyses examined linear trends . RESULTS At baseline , the proportion of green-labeled purchases ( 50 % ) did not differ between arms . At the end of the 3-month intervention , the percentage increase in green-labeled purchases was larger in the feedback-incentive arm compared to control ( 2.2 % vs. 0.1 % , P=0.03 ) , but the two intervention arms were not different . The rate of increase in green-labeled purchases was higher in both feedback-only ( P=0.04 ) and feedback-incentive arms ( P=0.004 ) compared to control . At the end of a 3-month wash-out , there were no differences between control and intervention arms . CONCLUSIONS Social norms plus small financial incentives increased employees ' healthy food choices over the short-term . Future research will be needed to assess the impact of this relatively low-cost intervention on employees ' food choices and weight over the long-term . TRIAL REGISTRATION Clinical Trials.gov : NCT01604499 Background / Objectives : Lower-income subgroups consume fewer servings of fruit and vegetables ( FVs ) compared with their more advantaged counterparts . To overcome financial barriers , FV voucher delivery has been proposed . Subjects/ Methods : In a 12-month trial , 302 low-income adults 18–60 years old ( defined by evaluation of deprivation and inequalities in health examination centers , a specific deprivation score ) were r and omized into two groups : dietary advice alone ( ‘ advice ’ ) , or dietary advice plus FV vouchers ( ‘ FV vouchers ’ ) ( 10–40 euros/month ) exchangeable for fresh fruits and vegetables . Self-reported data were collected on FV consumption and socioeconomic status at baseline , 3 , 9 and 12 months . Anthropometric and blood pressure measurements were conducted at these periods , as well as blood sample s obtained for determination of vitamins . Descriptive analyses , multiple linear regression and logistic regression were performed to evaluate the impact of FV . Results : Between baseline and 3-month follow-up , mean FV consumption increased significantly in both the ‘ advice ’ ( 0.62±1.29 times/day , P=0.0004 ) and ‘ FV vouchers ’ groups ( 0.74±1.90 , P=0.002 ) , with no difference between groups . Subjects in the FV vouchers group had significantly decreased risk of low FV consumption ( < 1 time/day ) compared with those in the advice group ( P=0.008 ) . No change was noted in vitamin levels ( vitamin C and β-carotene ) . The high number of lost-to-follow-up cases did not permit analysis at 9 or 12 months . Conclusion : In the low-income population , FV voucher delivery decreased the proportion of low FV consumers at 3 months . Longer-term studies are needed to assess their impact on nutritional status Background Reducing health inequalities requires interventions that work as well , if not better , among disadvantaged population s. The aim of this study was to determine if the effects of price discounts and tailored nutrition education on supermarket food purchases ( percentage energy from saturated fat and healthy foods purchased ) vary by ethnicity , household income and education . Method A 2 × 2 factorial trial of 1104 New Zeal and shoppers r and omised to receive a 12.5 % discount on healthier foods and /or tailored nutrition education ( or no intervention ) for 6 months . Results There was no overall association of price discounts or nutrition education with percentage energy from saturated fat , or nutrition education with healthy food purchasing . There was an association of price discounts with healthy food purchasing ( 0.79 kg/week increase ; 95 % CI 0.43 to 1.16 ) that varied by ethnicity ( p=0.04 ) : European/other 1.02 kg/week ( n=755 ; 95 % CI 0.60 to 1.43 ) ; Pacific 1.20 kg/week ( n=101 ; 95 % CI 0.06 to 2.34 ) ; Māori −0.15 kg/week ( n=248 ; 95 % CI −1.10 to 0.80 ) . This association of price discounts with healthy food purchasing did not vary by household income or education . Conclusions While a statistically significant variation by ethnicity in the effect of price discounts on food purchasing was found , the authors caution against a causal interpretation due to likely biases ( eg , attrition ) that differentially affected Māori and Pacific people . The study highlights the challenges in generating valid evidence by social groups for public health interventions . The null findings for tailored nutritional education across all social groups suggest that structural interventions ( such as price ) may be more effective Objectives . We assessed the impact of a rewards-based incentive program on fruit and vegetable purchases by low-income families . Methods . We conducted a 4-phase prospect i ve cohort study with r and omized intervention and wait-listed control groups in Philadelphia , Pennsylvania , in December 2010 through October 2011 . The intervention provided a rebate of 50 % of the dollar amount spent on fresh or frozen fruit and vegetables , reduced to 25 % during a tapering phase , then eliminated . Primary outcome measures were number of servings of fruit and of vegetables purchased per week . Results . Households assigned to the intervention purchased an average of 8 ( 95 % confidence interval [ CI ] = 1.5 , 16.9 ) more servings of vegetables and 2.5 ( 95 % CI = 0.3 , 9.5 ) more servings of fruit per week than did control households . In longitudinal price-adjusted analyses , when the incentive was reduced and then discontinued , the amounts purchased were similar to baseline . Conclusions . Investigation of the financial costs and potential benefits of incentive programs to supermarkets , government agencies , and other stakeholders is needed to identify sustainable interventions Determinants of fruit and vegetable consumption , including affordability and attitudes , have been poorly investigated , especially in European deprived population s. Our objective was to analyze various determinants of low consumption of fruits and vegetables in disadvantaged participants . Our participants were r and omized into 2 groups , 1 which received nutritional advice alone and 1 that also received vouchers that were exchangeable for fruits and vegetables during a 12-mo period . Socioeconomic characteristics , food insufficiency , affordability , and motivation for eating fruits and vegetables were assessed . A short FFQ was administered . Determinants of consumption of < 1 fruit or vegetable/d were analyzed using multivariate logistic regression . A total of 295 participants were included ( mean age 44.8 y ; 133 men , 162 women ) . At baseline , mean daily consumption of fruits and vegetables was 2.13 + /- 1.57 times/d . Nearly 30 % of the sample did not eat fruits and vegetables every day . Determinants of low fruit and vegetable consumption were : age younger than 55 y , education level lower than tertiary , and absence of financial means for buying fruits and vegetables daily . Other determinants were affordability ( whether fruits and vegetables are affordable , lack of money in preventing healthy diet ) and attitudes ( whether one 's own diet is healthy , whether or not fruits and vegetables improve health , whether eating fruits and vegetables is a pleasure ) . Thus , determinants of inadequate consumption of fruits and vegetables in this deprived French population are numerous . The impact of financial difficulties is crucial , as is the perception of affordability of fruits and vegetables High prices remain a formidable barrier for many people , especially those of low socioeconomic status , to adopt a healthier diet . The Food , Conservation , and Energy Act of 2008 m and ated the U.S. Department of Agriculture ( USDA ) to conduct a pilot study to assess the impact of making fruits and vegetables more affordable for households in the Supplemental Nutrition Assistance Program ( SNAP ) . Based on the USDA final report of the Healthy Incentives Pilot ( HIP ) , a large-scale r and omized trial in 2011 - 2012 that provided 30 % rebate on targeted fruits and vegetables to 7500 study participants enrolled in the SNAP , we constructed a decision model to evaluate the cost-effectiveness of an expansion of the HIP to all SNAP households nationwide . The estimated life-time per capita costs of the HIP to the Federal government is $ 1323 in 2012 U.S. dollars , and the average gains in quality -adjusted life expectancy to a SNAP participant is 0.082 quality -adjusted life year ( QALY ) , result ing in an incremental cost-effectiveness ratio ( ICER ) of $ 16,172 per QALY gained . Sensitivity analysis using Monte Carlo simulations indicates a 94.4 % and 99.6 % probability that the estimated ICER would be lower than the cost-effective threshold of $ 50,000 and $ 100,000 per QALY gained , respectively . Moreover , the estimated ICER of the HIP expansion tends to be competitive in comparison to other interventions that aim ed at promoting fruit/vegetable intake among adult population . Findings from this study suggest that a nationwide expansion of the HIP is likely to nudge SNAP households towards purchasing and consuming more targeted fruits and vegetables . However , diet behavior modification is proportional to price change . When people 's actual eating behaviors and what dietary guidelines recommend differ by several folds , even a 30 % rebate closes just a small fraction of that gap and has limited beneficial impact on participants ' weight management , disease prevention , and health-related quality of life Providing financial incentives can be a useful behavioral economics strategy for increasing fruit and vegetable intake among consumers . It remains to be determined whether financial incentives can promote intake of other low energy-dense foods and if consumers who are already using promotional tools for their grocery purchases may be especially responsive to receiving incentives . This r and omized controlled trial tested the effects of offering financial incentives for the purchase of healthy groceries on 3-month changes in dietary intake , weight outcomes , and the home food environment among older adults . A secondary aim was to compare frequent coupon users ( FCU ) and non-coupon users ( NCU ) on weight status , home food environment , and grocery shopping behavior . FCU ( n = 28 ) and NCU ( n = 26 ) were r and omly assigned to either an incentive or a control group . Participants in the incentive group received $ 1 for every healthy food or beverage they purchased . All participants completed 3-day food records and a home food inventory and had their height , weight , and waist circumference measured at baseline and after 3 months . Participants who were responsive to the intervention and received financial incentives significantly increased their daily vegetable intake ( P = 0.04 ) . Participants in both groups showed significant improvements in their home food environment ( P = 0.0003 ) . No significant changes were observed in daily energy intake or weight-related outcomes across groups ( P < 0.12 ) . FCU and NCU did not differ significantly in any anthropometric variables or the level at which their home food environment may be considered ' obesogenic ' ( P > 0.73 ) . Increased consumption of vegetables did not replace intake of more energy-dense foods . Incentivizing consumers to make healthy food choices while simultaneously reducing less healthy food choices may be important This article describes perceptions of adolescents involved in peer-led school-based nutrition promotions encouraging lower-fat food purchases and assesses the differences by level of student involvement . Surveys were administered at schools . Data were collected from 397 high school students from 10 Minnesota schools r and omized to the intervention condition of the Trying Alternative Cafeteria Options in Schools study . Students were categorized as highly involved ( n=54 ) or less involved ( n=343 ) based on their level of involvement in promotional activity implementation . Chi 2 tests were conducted to measure the differences between highly-involved and less-involved students in perceptions and attitudes about lower-fat foods . Highly-involved students were significantly more likely than less-involved students to report more healthful eating behaviors and positive attitudes toward lower-fat foods . Student involvement in nutrition interventions should be integrated into programs aim ed at increasing healthful food choices among adolescents Background Little is known about the association between self-weighing frequency and weight gain prevention , particularly in worksite population s. Purpose The degree to which self-weighing frequency predicted 2-year body weight change in working adults was examined . Method The association between self-weighing frequency ( monthly or less , weekly , daily , or more ) and 24-month weight change was analyzed in a prospect i ve cohort analysis ( n = 1,222 ) as part of the larger HealthWorks trial . Results There was a significant interaction between follow-up self-weighing frequency and baseline body mass index . The difference in weight change ranged from −4.4 ± 0.8 kg weight loss among obese daily self-weighers to 2.1 ± 0.4 kg weight gain for participants at a healthy weight who reported monthly self-weighing . Conclusion More frequent self-weighing seemed to be most beneficial for obese individuals . These findings may aid in the refinement of self-weighing frequency recommendations used in the context of weight management interventions Objective : Little is known about the relationship between weight change and workplace absenteeism . The purpose of this study was to examine the degree to which weight change predicted 2-year absenteeism . Methods : A longitudinal analysis of 1,228 employees enrolled in a worksite-r and omized controlled trial was performed . Participants were all working adults in the Minneapolis , MN , area ( USA ) . Results : The final model indicated a significant interaction between weight change and baseline BMI . The difference in absenteeism ranged from ( mean ± SE ) 3.2 ± 1.2 days among healthy weight employees who maintained their weight to 6.6 ± 1.1 days among obese employees who gained weight ( and slightly higher among healthy weight employees who lost weight ) . The adjusted model also indicated that participants who were male , not depressed , nonsmokers , and had lower baseline absenteeism had significantly less workplace absenteeism relative to participants who were female , depressed , smokers , and had higher baseline absenteeism . Conclusion : Absenteeism was generally low in this sample , but healthy weight employees who maintained their body weight over 2 years had the fewest number of sick days . More research is needed in this area , but future workforce attendance interventions may be improved by focusing on the primary prevention of weight gain in healthy weight employees OBJECTIVES This study described the food environment in 20 Minnesota secondary schools . METHODS Data were collected on school food policies and the availability and nutritional content of foods in school à la carte ( ALC ) areas and vending machines ( VMs ) . RESULTS Approximately 36 % and 35 % of foods in ALC areas and in VMs , respectively , met the lower-fat criterion ( < or = 5.5 fat grams/serving ) . The chips/crackers category constituted the largest share of ALC foods ( 11.5 % ) . The median number of VMs per school was 12 ( 4 soft drink , 2 snack , 5 other ) . Few school food policies were reported . CONCLUSIONS The availability of healthful foods and beverages in schools as well as school food policies that foster healthful food choices among students needs greater attention OBJECTIVE Pricing strategies are a promising approach for promoting healthier dietary choices . However , robust evidence of the cost-effectiveness of pricing manipulations on dietary behaviour is limited . We aim ed to assess the cost-effectiveness of a 20 % price reduction on fruits and vegetables and a combined skills-based behaviour change and price reduction intervention . DESIGN AND METHODS Cost-effectiveness analysis from a societal perspective was undertaken for the r and omized controlled trial Supermarket Healthy Eating for Life ( SHELf ) . Female shoppers in Melbourne , Australia were r and omized to : ( 1 ) skill-building ( n = 160 ) ; ( 2 ) price reductions ( n = 161 ) ; ( 3 ) combined skill-building and price reduction ( n = 161 ) ; or ( 4 ) control group ( n = 161 ) . The intervention was implemented for three months followed by a six month follow-up . Costs were measured in 2012 Australian dollars . Fruit and vegetable purchasing and consumption were measured in grams/week . RESULTS At three months , compared to control participants , price reduction participants increased vegetable purchases by 233 g/week ( 95 % CI 4 to 462 , p = 0.046 ) and fruit purchases by 364 g/week ( 95 % CI 95 to 633 , p = 0.008 ) . Participants in the combined group purchased 280 g/week more fruits ( 95 % CI 27 to 533 , p = 0.03 ) than participants in the control group . Increases were not maintained six-month post intervention . No effect was noticed in the skill-building group . Compared to the control group , the price reduction intervention cost an additional A$ 2.3 per increased serving of vegetables purchased per week or an additional A$ 3 per increased serving of fruit purchased per week . The combined intervention cost an additional A$ 12 per increased serving of fruit purchased per week compared to the control group . CONCLUSIONS A 20 % discount on fruits and vegetables was effective in promoting overall fruit and vegetable purchases during the period the discount was active and may be cost-effective . The price discount program gave better value for money than the combined price reduction and skill-building intervention . The SHELf trial is registered with Current Controlled Trials Registration IS RCT N39432901 OBJECTIVE To report the design and baseline results of a rewards-based incentive to promote purchase of fruit and vegetables by lower-income households . DESIGN A four-phase r and omized trial with wait-listed controls . In a pilot study , despite inadequate study coupon use , purchases of fresh fruit ( but not vegetables ) increased , but with little maintenance . In the present study , credits on the study store gift card replace paper coupons and a tapering phase is added . The primary outcome is the number of servings of fresh and frozen fruit and vegetables purchased per week . SETTING A large full-service supermarket located in a predominantly minority community in Philadelphia , Pennsylvania , USA . SUBJECTS Fifty-eight households , with at least one child living in the home . RESULTS During the baseline period , households purchased an average of 3·7 servings of fresh vegetables and an average of less than 1 serving of frozen vegetables per week . Households purchased an average of 1·9 servings of fresh fruit per week , with little to no frozen fruit purchases . Overall , the range of fresh and frozen produce purchased during this pre-intervention period was limited . CONCLUSIONS At baseline , produce purchases were small and of limited variety . The study will contribute to underst and ing the impact of financial incentives on increasing the purchases of healthier foods by lower-income population Background : The Supermarket Healthy Options Project ( SHOP ) is a large , r and omised , controlled trial design ed to evaluate the effect of tailored nutrition education and price discounts on supermarket food purchases . A key objective was to recruit approximately equal numbers of Māori , Pacific and non-Māori , non-Pacific shoppers . This paper describes the recruitment strategies used and evaluates their impact on recruitment of Māori , Pacific and non-Māori , non-Pacific trial participants . Methods : Trial recruitment strategies included mailed invitations to an electronic register of supermarket customers ; in-store targeted recruitment ; and community-based recruitment . Results : Of the 1103 total trial r and omisations for whom ethnicity was known , 247 ( 22 % ) were Māori , 101 ( 9 % ) Pacific and 755 ( 68 % ) were non-Māori , non-Pacific shoppers . Mailed invitations produced the greatest proportion of r and omisations ( 73 % vs 7 % in-store , and 20 % from community recruitment ) . However , in-store and community recruitment were essential to boost Māori and Pacific sample s. The cost of mailout ( NZ$40 ( £ 14 ) per r and omised participant ) was considerably less than the cost of community and in-store recruitment ( NZ$301 ( £ 105 ) per r and omised participant ) . Conclusions : The findings demonstrate considerable challenges and cost in recruiting indigenous and minority ethnic participants into intervention trials . Research ers and funding organisations should allocate more re sources to recruitment of indigenous and minority population s than to recruitment of majority population s. Community recruitment and networks appear to be better ways to recruit these population s than passive strategies like mailouts Purpose The purpose of this study was to test the impact of distributing coupons redeemable at farmers markets plus an educational intervention on fruit and vegetable ( F&V ) purchase and consumption in overweight patients with type 2 diabetes ( T2DM ) . Methods Seventy-eight participants with T2DM being followed at Jacobi Medical Center , a large public hospital in the Bronx , New York , were r and omized to receive the st and ard of care or a 1-hour session focused on benefits of F&V consumption and $ 6 in coupons . Question naires assessed demographics , F&V intake , and farmers market purchasing at baseline and 12 weeks . Clinical parameters were obtained through chart review at baseline and at 12 weeks . Results Participants were predominantly Latino , females , and low income . At 12 weeks , there was a statistically significant increase in the number of participants in the intervention arm who reported purchasing from a farmers market . In addition , there was a minimal increase in fresh fruit intake in the intervention arm at 12 weeks . Conclusion Focused education combined with a small economic incentive result ed in an increase in purchasing behavior and fresh fruit intake per day . A more intense behavioral intervention combined with increased access may result in a significant impact on obesity and diabetes , particularly among low-income and racially diverse communities School environments that provide consistent and reliable nutrition information promote the development of healthful eating in children . High-energy , nutrient-poor beverages offered for sale to children during the school day compete with healthful choices . The primary objective of this prospect i ve , quasiexperimental study was to encourage children to choose more healthful beverages during the school day without adversely affecting the profits realized from vending sales . Fifteen of 18 schools completed voluntary changes to beverage sales practice s during the school day between August 2005 and May 2006 . Twelve of 15 schools reported increased profits from the previous year ( 2004 - 2005 ) while offering more healthful beverage choices at discounted prices . Units of carbonated soft drinks sold declined when sports drinks , 100 % fruit juice , and water were made available in their place . Passive marketing in the form of vending machine fronts , attractive pricing with a nominal 10 % to 25 % discount , and changing the types and proportions of beverages offered encouraged children to make more healthful choices . Local school administrators were receptive to making changes to beverage sales when local needs were incorporated into the study design . Profit information from this study informed state legislators and the Mississippi State Board of Education in the development and adoption of statewide snack and beverage vending guidelines . Registered dietitians serve as advocates to foster these collaborative efforts , inform key decision makers , and work in their local communities to develop and promote healthful practice s in K-12 school setting OBJECTIVE To determine the effect of increasing fruit visibility , adding information and lowering price on fruit purchasing at a university cafeteria in Lima , Peru . DESIGN Quasi-experimental pilot study of a three-phase stepped intervention . In Phase 1 , fruit was displayed > 3 m from the point of purchase with no additional information . Phase 2 consisted in displaying the fruit near the point of purchase with added health and price information . Phase 3 added a 33 % price reduction . The duration of each phase was 3 weeks and phases were separated by 2-week breaks . Primary outcomes were total pieces of fruit and number of meals sold daily . SETTING A university cafeteria in Lima , Peru . SUBJECTS Approximately 150 people , students and non-student adults , who purchased food daily . Twelve students participated in post-intervention interviews . RESULTS Fruit purchasing doubled from Phase 1 to Phase 3 ( P<0·01 ) and remained significant after adjusting for the number of meals sold daily ( P<0·05 ) . There was no evidence of a difference in fruit sold between the other phases . Females purchased 100 % of the fruit in Phase 1 , 82 % in Phase 2 and 67 % in Phase 3 ( P<0·01 ) . Males increased their purchasing significantly between Phase 1 and 3 ( P<0·01 ) . Non-student adults purchased more fruit with each phase ( P<0·05 ) whereas students did not . Qualitatively , the most common reason for not purchasing fruit was a marked preference to buy unhealthy snack foods . CONCLUSIONS Promoting fruit consumption by product placement close to the point of purchase , adding health information and price reduction had a positive effect on fruit purchasing in a university cafeteria , especially in males and non-student adults Background Supermarket Healthy Eating for Life ( SHELf ) was a r and omized controlled trial that operationalized a socioecological approach to population -level dietary behaviour change in a real-world supermarket setting . SHELf tested the impact of individual ( skill-building ) , environmental ( 20 % price reductions ) , and combined ( skill-building + 20 % price reductions ) interventions on women ’s purchasing and consumption of fruits , vegetables , low-calorie carbonated beverages and water . This process evaluation investigated the reach , effectiveness , implementation , and maintenance of the SHELf interventions . Methods RE- AIM provided a conceptual framework to examine the processes underlying the impact of the interventions using data from participant surveys and objective sales data collected at baseline , post-intervention ( 3 months ) and 6-months post-intervention . Fisher ’s exact , χ2 and t-tests assessed differences in quantitative survey responses among groups . Adjusted linear regression examined the impact of self-reported intervention dose on food purchasing and consumption outcomes . Thematic analysis identified key themes within qualitative survey responses . Results Reach of the SHELf interventions to disadvantaged groups , and beyond study participants themselves , was moderate . Just over one-third of intervention participants indicated that the interventions were effective in changing the way they bought , cooked or consumed food ( p < 0.001 compared to control ) , with no differences among intervention groups . Improvements in purchasing and consumption outcomes were greatest among those who received a higher intervention dose . Most notably , participants who said they accessed price reductions on fruits and vegetables purchased ( 519 g/week ) and consumed ( 0.5 servings/day ) more vegetables . The majority of participants said they accessed ( 82 % ) and appreciated discounts on fruits and vegetables , while there was limited use ( 40 % ) and appreciation of discounts on low-calorie carbonated beverages and water . Overall reported satisfaction with , use , and impact of the skill-building re sources was moderate . Maintenance of newly acquired behaviours was limited , with less than half of participants making changes or using study -provided re sources during the 6-month post-intervention period . Conclusions SHELf ’s reach and perceived effectiveness were moderate . The interventions were more effective among those reporting greater engagement with them ( an implementation-related construct ) . Maintenance of newly acquired behaviours proved challenging . Trial registration Current controlled trials IS RCT N39432901 BACKGROUND Traditional methods to improve population diets have largely relied on individual responsibility , but there is growing interest in structural interventions such as pricing policies . OBJECTIVE The aim was to evaluate the effect of price discounts and tailored nutrition education on supermarket food and nutrient purchases . DESIGN A 2 x 2 factorial r and omized controlled trial was conducted in 8 New Zeal and supermarkets . A total of 1104 shoppers were r and omly assigned to 1 of the following 4 interventions that were delivered over 6 mo : price discounts ( 12.5 % ) on healthier foods , tailored nutrition education , discounts plus education , or control ( no intervention ) . The primary outcome was change in saturated fat purchased at 6 mo . Secondary outcomes were changes in other nutrients and foods purchased at 6 and 12 mo . Outcomes were assessed by using electronic scanner sales data . RESULTS At 6 mo , the difference in saturated fat purchased for price discounts on healthier foods compared with that purchased for no discount on healthier foods was -0.02 % ( 95 % CI : -0.40 % , 0.36 % ; P = 0.91 ) . The corresponding difference for tailored nutrition education compared with that for no education was -0.09 % ( 95 % CI : -0.47 % , 0.30 % ; P = 0.66 ) . However , those subjects who were r and omly assigned to receive price discounts bought significantly more predefined healthier foods at 6 mo ( 11 % more ; mean difference : 0.79 kg/wk ; 95 % CI : 0.43 , 1.16 ; P < 0.001 ) and 12 mo ( 5 % more ; mean difference : 0.38 kg/wk ; 95 % CI : 0.01 , 0.76 ; P = 0.045 ) . Education had no effect on food purchases . CONCLUSIONS Neither price discounts nor tailored nutrition education had a significant effect on nutrients purchased . However , the significant and sustained effect of discounts on food purchases suggests that pricing strategies hold promise as a means to improve population diets |
1,186 | 27,496,650 | Both disease control ( PR plus stable disease status ) and l and mark progression-free survival were correlated with OS , with the longer interval l and mark PFS being the best predictor of survival in patients with NSCLC treated with anti-PD-1/PD-L1 antibodies | INTRODUCTION Alternative predictive end points for overall survival ( OS ) , such as tumor response and progression-free survival ( PFS ) , are useful in the early detection of drug efficacy ; however , they have not been fully investigated in patients with advanced NSCLC treated with anti-programmed death protein 1 (PD-1)/programmed death lig and 1 ( PD-L1 ) antibodies . | BACKGROUND We assessed the efficacy and safety of programmed cell death 1 ( PD-1 ) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study . We also sought to define and vali date an expression level of the PD-1 lig and 1 ( PD-L1 ) that is associated with the likelihood of clinical benefit . METHODS We assigned 495 patients receiving pembrolizumab ( at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks ) to either a training group ( 182 patients ) or a validation group ( 313 patients ) . We assessed PD-L1 expression in tumor sample s using immunohistochemical analysis , with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 ( proportion score ) . Response was assessed every 9 weeks by central review . RESULTS Common side effects that were attributed to pembrolizumab were fatigue , pruritus , and decreased appetite , with no clear difference according to dose or schedule . Among all the patients , the objective response rate was 19.4 % , and the median duration of response was 12.5 months . The median duration of progression-free survival was 3.7 months , and the median duration of overall survival was 12.0 months . PD-L1 expression in at least 50 % of tumor cells was selected as the cutoff from the training group . Among patients with a proportion score of at least 50 % in the validation group , the response rate was 45.2 % . Among all the patients with a proportion score of at least 50 % , median progression-free survival was 6.3 months ; median overall survival was not reached . CONCLUSIONS Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer . PD-L1 expression in at least 50 % of tumor cells correlated with improved efficacy of pembrolizumab . ( Funded by Merck ; KEYNOTE-001 Clinical Trials.gov number , NCT01295827 . ) BACKGROUND Previous , uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer . METHODS In this phase 3 , open-label study , we r and omly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib ( 250 mg per day ) ( 609 patients ) or carboplatin ( at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute ) plus paclitaxel ( 200 mg per square meter of body-surface area ) ( 608 patients ) . The primary end point was progression-free survival . RESULTS The 12-month rates of progression-free survival were 24.9 % with gefitinib and 6.7 % with carboplatin-paclitaxel . The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority , as compared with carboplatin-paclitaxel , with respect to progression-free survival in the intention-to-treat population ( hazard ratio for progression or death , 0.74 ; 95 % confidence interval [ CI ] , 0.65 to 0.85 ; P<0.001 ) . In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene ( EGFR ) mutation , progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel ( hazard ratio for progression or death , 0.48 ; 95 % CI , 0.36 to 0.64 ; P<0.001 ) , whereas in the subgroup of 176 patients who were negative for the mutation , progression-free survival was significantly longer among those who received carboplatin-paclitaxel ( hazard ratio for progression or death with gefitinib , 2.85 ; 95 % CI , 2.05 to 3.98 ; P<0.001 ) . The most common adverse events were rash or acne ( in 66.2 % of patients ) and diarrhea ( 46.6 % ) in the gefitinib group and neurotoxic effects ( 69.9 % ) , neutropenia ( 67.1 % ) , and alopecia ( 58.4 % ) in the carboplatin-paclitaxel group . CONCLUSIONS Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia . The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib . ( Clinical Trials.gov number , NCT00322452 . BACKGROUND This trial was design ed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer ( NSCLC ) and to identify patient population s most likely to benefit from the combination . PATIENTS AND METHODS Patients with one prior systemic therapy for advanced disease were eligible . Docetaxel ( 75 mg/m(2 ) on day 1 ) was administered alone or with ganetespib ( 150 mg/m(2 ) on days 1 and 15 ) every 3 weeks . The primary end points were progression-free survival ( PFS ) in two subgroups of the adenocarcinoma population : patients with elevated lactate dehydrogenase ( eLDH ) and mutated KRAS ( mKRAS ) . RESULTS Of 385 patients enrolled , 381 were treated . Early in the trial , increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients ( n = 71 ) ; therefore , only patients with adenocarcinoma histology were subsequently enrolled . Neutropenia was the most common grade ≥3 adverse event : 41 % in the combination arm versus 42 % in docetaxel alone . There was no improvement in PFS for the combination arm in the eLDH ( N = 114 , adjusted hazard ratio ( HR ) = 0.77 , P = 0.1134 ) or mKRAS ( N = 89 , adjusted HR = 1.11 , P = 0.3384 ) subgroups . In the intent-to-treat adenocarcinoma population , there was a trend in favor of the combination , with PFS ( N = 253 , adjusted HR = 0.82 , P = 0.0784 ) and overall survival ( OS ) ( adjusted HR = 0.84 , P = 0.1139 ) . Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease > 6 months before study entry ( N = 177 ) : PFS ( adjusted HR = 0.74 , P = 0.0417 ) ; OS ( adjusted HR = 0.69 , P = 0.0191 ) . CONCLUSION Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile . While the study 's primary end points were not met , significant prolongation of PFS and OS was observed in patients > 6 months from diagnosis of advanced disease , a subgroup chosen as the target population for the phase III study 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<0·0001 ) . We noted 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<0.001 ) . At 1 year , the 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<0.001 ) . The 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 . ) BACKGROUND Concomitant administration of erlotinib with st and ard chemotherapy does not appear to improve survival among patients with non-small-cell lung cancer ( NSCLC ) , but preliminary studies suggest that sequential administration might be effective . OBJECTIVE To assess the efficacy and tolerability of second-line sequential administration of erlotinib and docetaxel in advanced NSCLC . METHODS In an open-label phase II trial , patients with advanced NSCLC , EGFR wild-type or unknown , PS 0 - 2 , in whom initial cisplatin-based chemotherapy had failed were r and omized to sequential erlotinib 150 mg/d ( day 2 - 16)+docetaxel ( 75 mg/m(2 ) d1 ) ( arm ED ) or docetaxel ( 75 mg/m(2 ) d1 ) alone ( arm D ) ( 21-day cycle ) . The primary endpoint was the progression-free survival rate at 15 weeks ( PFS 15 ) . Secondary endpoints included PFS , overall survival ( OS ) , the overall response rate ( ORR ) and tolerability . Based on a Simon optimal two-stage design , the ED strategy was rejected if the primary endpoint was below 33/66 patients at the end of the two Simon stages . RESULTS 147 patients were r and omized ( median age : 60±8 years , PS 0/1/2 : 44/83/20 patients ; males : 78 % ) . The ED strategy was rejected , with only 18 of 73 patients achieving PFS15 in arm ED at the end of stage 2 and 17 of 74 patients in arm D. In arms ED and D , respectively , median PFS was 2.2 and 2.5 months and median OS was 6.5 and 8.3 months . CONCLUSION Sequential erlotinib and docetaxel was not more effective than docetaxel alone as second-line treatment for advanced NSCLC with wild-type or unknown EGFR status 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 < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was 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 ( < 1 % ) patient in 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 Summary Introduction This multicenter , open-label , phase II study was carried out to compare the efficacy and safety of cilengitide ( EMD 121974 ) , a selective inhibitor of the cell-surface integrins αVβ3 and αVβ5 , with that of docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) . Methods Patients ( n = 140 ) with advanced NSCLC who had failed first-line chemotherapy were r and omized to cilengitide 240 , 400 , or 600 mg/m2 twice weekly , or docetaxel 75 mg/m2 once every 3 weeks for eight cycles . Non-progressing patients could continue cilengitide for up to 1 year . The primary endpoint was progression-free survival ( PFS ) . No statistical tests were performed since the study was exploratory in nature and the number of patients enrolled was relatively small . Results Median PFS was 54 , 63 , 63 , and 67 days for cilengitide 240 , 400 , and 600 mg/m2 , and docetaxel 75 mg/m2 , respectively . One-year survival rates were 13 % , 13 % , 29 % , and 27 % , respectively . The response rate ( partial response only ) with docetaxel was 15 % . No responses were reported in any cilengitide arm . The most frequent grade 3/4 treatment-related adverse events in the docetaxel group were leukopenia and neutropenia ( experienced by 13 % of patients ) . Hematologic toxicity of this severity did not occur in cilengitide-treated patients . Conclusion With the highest dose of cilengitide ( 600 mg/m2 ) , median PFS and 1-year survival were similar to those in patients treated with docetaxel 75 mg/m2 and there were fewer grade 3/4 treatment-related adverse events The aim of this open‐label , multicenter , r and omized phase II trial was to evaluate the efficacy and safety of zoledronic acid in combination with docetaxel in previously treated patients with non‐small‐cell lung cancer ( NSCLC ) and bone metastases . In this study , patients r and omly received docetaxel ( 60 mg/m2 ) with ( group DZ ) or without ( group D ) zoledronic acid every 21 days . There were 50 patients in each group , and the primary endpoint was progression‐free survival . In an efficacy analysis of 94 patients ( DZ , 48 ; D , 46 ) , the median progression‐free survival was 2.7 months ( 95 % confidence interval [ CI ] , 1.5–3.5 months ) for the DZ group and 2.6 months ( 95 % CI , 1.5–3.4 months ) for the D group ( stratified log‐rank test , P = 0.89 ) . The median overall survival was 10.4 months ( 95 % CI , 7.0–15.8 months ) for the DZ group and 9.7 months ( 95 % CI , 6.1–12.5 months ) for the D group ( stratified log‐rank test , P = 0.62 ) . There were no clinical ly relevant differences in the frequencies of grade 3 or 4 adverse events between the two groups . No treatment‐related deaths occurred in the DZ group . Zoledronic acid combined with docetaxel was well tolerated but did not meet the primary endpoint of demonstrating a longer progression‐free survival in advanced NSCLC patients with bone metastases compared with docetaxel alone . This trial was registered with the University Hospital Medical Information Network ( UMIN000001098 ) 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<0.001 ) , result ing in early termination of the study . The 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<0.001 ) , as well as a higher response rate ( 73.7 % vs. 30.7 % , P<0.001 ) . The 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 . OBJECTIVE Prospect i ve trials specifically design ed for elderly patients with advanced non-small-cell lung cancer demonstrating the benefit of platinum-based therapies are still lacking . This trial was design ed to clarify whether the addition of cisplatin to monotherapy could improve survival for elderly patients . METHODS Elderly patients ( age ≥70 years , ECOG performance Status 0 - 1 ) with advanced non-small-cell lung cancer were r and omized to receive docetaxel 20 mg/m(2 ) plus cisplatin 25 mg/m(2 ) on Day 1 , 8 and 15 ( docetaxel plus cisplatin ) or docetaxel 25 mg/m(2 ) on the same schedule ( docetaxel ) . Both regimens were repeated every 4 weeks until disease progression . RESULTS One hundred and twenty-six patients were enrolled . Sixty-three were r and omly assigned docetaxel plus cisplatin and 63 docetaxel monotherapy . Median age was 76 years ( range 70 - 88 ) . The second planned interim analysis was performed on 112 assessable patients ( docetaxel/docetaxel plus cisplatin : 56/56 ) . Although the formal criterion for stopping the trial was not met , the Data and Safety Monitoring Committee recommended study termination on ethical grounds based on the interaction ( two-sided P = 0.077 , hazard ratios for ≤74/≥75 : 0.23/0.72 ) between age and subgroup and treatment arm , which suggested that docetaxel may not represent an adequate control arm regimen for the age subgroup of 70 - 74 years . CONCLUSIONS The interpretation of study results is limited due to early stopping . Further study is needed to confirm survival benefit of platinum-based chemotherapy for elderly non-small-cell lung cancer [ UMIN-CTR ( www.umin.ac.jp/ctr/ ) ID : C000000146 ] Purpose To provide evidence -based recommendations to up date the American Society of Clinical Oncology guideline on systemic therapy for stage IV non – small-cell lung cancer ( NSCLC ) . Methods An Up date Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of r and omized controlled trials from January 2007 to February 2014 . Results This guideline up date reflects changes in evidence since the previous guideline . Recommendations There is no cure for patients with stage IV NSCLC . For patients with performance status ( PS ) 0 to 1 ( and appropriate patient cases with PS 2 ) and without an EGFR-sensitizing mutation or ALK gene rearrangement , combination cytotoxic chemotherapy is recommended , guided by histology , with early concurrent palliative care . Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 ( bevacizumab may be added to carboplatin plus paclitaxel if no contraindications ) ; combination or single-agent chemotherapy or palliative care alone for those with PS 2 ; afatinib , erlotinib , or gefitinib for those with sensitizing EGFR mutations ; crizotinib for those with ALK or ROS1 gene rearrangement ; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma . Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens , alternative chemotherapy , or a chemotherapy break . In the second-line setting , recommendations include docetaxel , erlotinib , gefitinib , or pemetrexed for patients with nonsquamous cell carcinoma ; docetaxel , erlotinib , or gefitinib for those with squamous cell carcinoma ; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib . In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended . There are insufficient data to recommend routine third-line cytotoxic therapy . Decisions regarding systemic therapy should not be made based on age alone . Additional information can be found at http://www.asco.org/ guidelines /nsclc and http://www.asco.org/ guidelines wiki . J Clin Oncol 33:3488 - 3515 . © 2015 by American Society of Clinical 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<0.00825 ( one-sided ) for the analysis of overall survival and a threshold of p<0.001 for 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<0.0001 ) . 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<0.0001 ) . Likewise , for this patient population , 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<0.0001 ) . 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 & Chemoresistance is mediated , in part , by the inhibition of apoptosis in tumor cells . Survivin is an antiapoptotic protein that blocks chemotherapy-induced apoptosis . To investigate whether blocking survivin expression enhances docetaxel-induced apoptosis in patients with non – small-cell lung cancer ( NSCLC ) , we compared the antitumor activity of the survivin inhibitor LY2181308 plus docetaxel with docetaxel alone . We used change in tumor size ( CTS ) as a primary endpoint to assess its use in early decision-making for this and future studies of novel agents in NSCLC . Patients ( N = 162 ) eligible for second-line NSCLC treatment ( stage IIIB/IV ) with an Eastern Cooperative Oncology Group performance status of 0 to 1 were r and omized 2:1 to receive LY2181308 ( 750 mg intravenously , weekly ) and docetaxel ( 75 mg/m2 intravenously , day 1 ) or docetaxel alone every 21 days . CTS from baseline to the end of cycle 2 was compared between the two treatment arms . The mean ( SD ) tumor size ratio for LY2181308/docetaxel and docetaxel was 1.05 ( 0.21 ) and 1.00 ( 0.15 ) ( p = 0.200 ) , respectively , suggesting no significant improvement in antitumor activity between the arms . Because there was also no significant difference between the two arms for progression-free survival ( PFS ) ( 2.83 months with LY2181308/docetaxel and 3.35 months with docetaxel [ p = 0.191 ] ) , both arms were combined . Using the combined arms , CTS correlated with PFS ( PFS = 4.63 months in patients with decreased CTS compared with 2.66 months in patients with increased CTS ) , supporting its use in early decision-making in phase II studies BACKGROUND No targeted therapies are available for KRAS-mutant non-small-cell lung cancer ( NSCLC ) . Selumetinib is an inhibitor of MEK1/MEK2 , downstream of KRAS , with pre clinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers . We did a prospect i ve , r and omised , phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRAS-mutant NSCLC . METHODS Eligible patients were older than 18 years of age ; had histologically or cytologically confirmed stage IIIB-IV KRAS-mutant NSCLC ; had failed first-line therapy for advanced NSCLC ; had WHO performance status of 0 - 1 ; had not received previous therapy with either a MEK inhibitor or docetaxel ; and had adequate bone marrow , renal , and liver function . Patients were r and omly assigned ( in a 1:1 ratio ) to either oral selumetinib ( 75 mg twice daily in a 21 day cycle ) or placebo ; all patients received intravenous docetaxel ( 75 mg/m(2 ) on day 1 of a 21 day cycle ) . R and omisation was done with an interactive voice response system and investigators , patients , data analysts , and the trial sponsor were masked to treatment assignment . The primary endpoint was overall survival , analysed for all patients with confirmed KRAS mutations . This study is registered with Clinical Trials.gov , number NCT00890825 . FINDINGS Between April 20 , 2009 , and June 30 , 2010 , we r and omly assigned 44 patients to receive selumetinib and docetaxel ( selumetinib group ) and 43 to receive placebo and docetaxel ( placebo group ) . Of these , one patient in the selumetinib group and three in the placebo group were excluded from efficacy analyses because their tumours were not confirmed to be KRAS-mutation positive . Median overall survival was 9·4 months ( 6·8 - 13·6 ) in the selumetinib group and 5·2 months ( 95 % CI 3·8-non-calculable ) in the placebo group ( hazard ratio [ HR ] for death 0·80 , 80 % CI 0·56 - 1·14 ; one-sided p=0·21 ) . Median progression-free survival was 5·3 months ( 4·6 - 6·4 ) in the selumetinib group and 2·1 months ( 95 % CI 1·4 - 3·7 ) in the placebo group ( HR for progression 0·58 , 80 % CI 0·42 - 0·79 ; one-sided p=0·014 ) . 16 ( 37 % ) patients in the selumetinib group and none in the placebo group had an objective response ( p<0·0001 ) . Adverse events of grade 3 or higher occurred in 36 ( 82 % ) patients in the selumetinib group and 28 ( 67 % ) patients in the placebo group . The most common grade 3 - 4 adverse events were neutropenia ( 29 [ 67 % ] of 43 patients in the selumetinib group vs 23 [ 55 % ] of 42 patients in the placebo group ) , febrile neutropenia ( eight [ 18 % ] of 44 patients in the selumetinib group vs none in the placebo group ) , dyspnoea ( one [ 2 % ] of 44 patients in the selumetinib group vs five [ 12 % ] of 42 in the placebo group ) , and asthenia ( four [ 9 % ] of 44 patients in the selumetinib group vs none in the placebo group ) . INTERPRETATION Selumetinib plus docetaxel has promising efficacy , albeit with a higher number of adverse events than with docetaxel alone , in previously treated advanced KRAS-mutant NSCLC . These findings warrant further clinical investigation of selumetinib plus docetaxel in KRAS-mutant NSCLC . FUNDING AstraZeneca The validation of surrogate endpoints has been studied by Prentice ( 1989 , Statistics in Medicine 8 , 431 - 440 ) and Freedman , Graubard , and Schatzkin ( 1992 , Statistics in Medicine 11 , 167 - 178 ) . We extended their proposals in the cases where the surrogate and the final endpoints are both binary or normally distributed . Letting T and S be r and om variables that denote the true and surrogate endpoint , respectively , and Z be an indicator variable for treatment , Prentice 's criteria are fulfilled if Z has a significant effect on T and on S , if S has a significant effect on T , and if Z has no effect on T given S. Freedman relaxed the latter criterion by estimating PE , the proportion of the effect of Z on T that is explained by S , and by requiring that the lower confidence limit of PE be larger than some proportion , say 0.5 or 0.75 . This condition can only be verified if the treatment has a massively significant effect on the true endpoint , a rare situation . We argue that two other quantities must be considered in the validation of a surrogate endpoint : RE , the effect of Z on T relative to that of Z on S , and gamma Z , the association between S and T after adjustment for Z. A surrogate is said to be perfect at the individual level when there is a perfect association between the surrogate and the final endpoint after adjustment for treatment . A surrogate is said to be perfect at the population level if RE is 1 . A perfect surrogate fulfills both conditions , in which case S and T are identical up to a deterministic transformation . Fieller 's theorem is used for the estimation of PE , RE , and their respective confidence intervals . Logistic regression models and the global odds ratio model studied by Dale ( 1986 , Biometrics , 42 , 909 - 917 ) are used for binary endpoints . Linear models are employed for continuous endpoints . In order to be of practical value , the validation of surrogate endpoints is shown to require large numbers of observations BACKGROUND The phase 3 LUME-Lung 1 study assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for non-small-cell lung cancer ( NSCLC ) . METHODS Patients from 211 centres in 27 countries with stage IIIB/IV recurrent NSCLC progressing after first-line chemotherapy , stratified by ECOG performance status , previous bevacizumab treatment , histology , and presence of brain metastases , were allocated ( by computer-generated sequence through an interactive third-party system , in 1:1 ratio ) , to receive docetaxel 75 mg/m(2 ) by intravenous infusion on day 1 plus either nintedanib 200 mg orally twice daily or matching placebo on days 2 - 21 , every 3 weeks until unacceptable adverse events or disease progression . Investigators and patients were masked to assignment . The primary endpoint was progression-free survival ( PFS ) by independent central review , analysed by intention to treat after 714 events in all patients . The key secondary endpoint was overall survival , analysed by intention to treat after 1121 events had occurred , in a prespecified stepwise order : first in patients with adenocarcinoma who progressed within 9 months after start of first-line therapy , then in all patients with adenocarcinoma , then in all patients . This trial is registered with Clinical Trials.gov , number NCT00805194 . FINDINGS Between Dec 23 , 2008 , and Feb 9 , 2011 , 655 patients were r and omly assigned to receive docetaxel plus nintedanib and 659 to receive docetaxel plus placebo . The primary analysis was done after a median follow-up of 7·1 months ( IQR 3·8 - 11·0 ) . PFS was significantly improved in the docetaxel plus nintedanib group compared with the docetaxel plus placebo group ( median 3·4 months [ 95 % CI 2·9 - 3·9 ] vs 2·7 months [ 2·6 - 2·8 ] ; hazard ratio [ HR ] 0·79 [ 95 % CI 0·68 - 0·92 ] , p=0·0019 ) . After a median follow-up of 31·7 months ( IQR 27·8 - 36·1 ) , overall survival was significantly improved for patients with adenocarcinoma histology who progressed within 9 months after start of first-line treatment in the docetaxel plus nintedanib group ( 206 patients ) compared with those in the docetaxel plus placebo group ( 199 patients ; median 10·9 months [ 95 % CI 8·5 - 12·6 ] vs 7·9 months [ 6·7 - 9·1 ] ; HR 0·75 [ 95 % CI 0·60 - 0·92 ] , p=0·0073 ) . Similar results were noted for all patients with adenocarcinoma histology ( 322 patients in the docetaxel plus nintedanib group and 336 in the docetaxel plus placebo group ; median overall survival 12·6 months [ 95 % CI 10·6 - 15·1 ] vs 10·3 months [ 95 % CI 8·6 - 12·2 ] ; HR 0·83 [ 95 % CI 0·70 - 0·99 ] , p=0·0359 ) , but not in the total study population ( median 10·1 months [ 95 % CI 8·8 - 11·2 ] vs 9·1 months [ 8·4 - 10·4 ] ; HR 0·94 , 95 % CI 0·83 - 1·05 , p=0·2720 ) . Grade 3 or worse adverse events that were more common in the docetaxel plus nintedanib group than in the docetaxel plus placebo group were diarrhoea ( 43 [ 6·6 % ] of 652 vs 17 [ 2·6 % ] of 655 ) , reversible increases in alanine aminotransferase ( 51 [ 7·8 % ] vs six [ 0·9 % ] ) , and reversible increases in aspartate aminotransferase ( 22 [ 3·4 % ] vs three [ 0·5 % ] ) . 35 patients in the docetaxel plus nintedanib group and 25 in the docetaxel plus placebo group died of adverse events possibly unrelated to disease progression ; the most common of these events were sepsis ( five with docetaxel plus nintedanib vs one with docetaxel plus placebo ) , pneumonia ( two vs seven ) , respiratory failure ( four vs none ) , and pulmonary embolism ( none vs three ) . INTERPRETATION Nintedanib in combination with docetaxel is an effective second-line option for patients with advanced NSCLC previously treated with one line of platinum-based therapy , especially for patients with adenocarcinoma . FUNDING Boehringer Ingelheim BACKGROUND Pemetrexed and docetaxel are established therapies in second line non-small cell lung cancer ( NSCLC ) . Comparative data , concerning the two agents in the design ated setting s , however , are lacking in Chinese patients who account for the largest lung cancer population in the world . METHODS AND PATIENTS We design ed and performed a multi-center , r and omized , exploratory clinical trial of pemetrexed compared with docetaxel in second line chemotherapy in Chinese NSCLC patients . Eligible patients with histological or cytological diagnosis of stage IIIB or IV NSCLC , who were not suitable for curative therapy and had failed from prior first line chemotherapy regimen for at least 4 weeks , were r and omized to receive either pemetrexed 500 mg/m(2 ) intravenously day 1 with vitamin B12 , folic acid , and dexamethasone , or docetaxel 75 mg/m(2 ) intravenously day 1 with dexamethasone . Both regimens were implemented once every 21 days for 2 cycles . This study was design ed to be a non-inferiority trial that compared tumor response for overall response rate ( ORR ) between the two drugs as primary endpoint . The secondary endpoints included disease control rate ( DCR ) , Karnofsky performance status ( KPS ) scores and toxicities . RESULTS 260 patients were enrolled and r and omly assigned to receive chemotherapy of either pemetrexed ( 132 patients ) or docetaxel ( 128 patients ) . 106 patients in pemetrexed arm and 102 patients in docetaxel arm were evaluable for efficacy . The efficacy of pemetrexed was equivalent to that of docetaxel in the second-line treatment for Chinese NSCLC ( ORR : pemetrexed vs. docetaxel = 9.4 % vs. 4.9 , p = 0.285 , DCR : pemetrexed vs. docetaxel = 67.2 % vs. 69.6 % , p = 0.685 ) . And pemetrexed seemed to slightly promote patients ' average KPS score when comparing with docetaxel , although the difference was without statistical significance ( changes of average KPS scores : pemetrexed vs. docetaxel = 0.28 ± 5.93 vs. -1.67 ± 8.57 , p = 0.149 ) . Patients receiving pemetrexed experienced significantly lower incidences of grade 3/4 neutropenia ( 7.0 % vs. 27.6 % , p < 0.001 ) and leucocytopenia ( 4.7 % vs. 22.8 % , p < 0.001 ) than those who received docetaxel . Also , there were lower incidences of alopecia , stomatitis , and neural abnormality for patients receiving pemetrexed than those receiving docetaxel . Incidence of serum glutamic oxaloacetic transaminase elevation , however , was higher in pemetrexed arm than in docetaxel arm ( 32.3 % vs. 14.9 % , p = 0.013 ) . In addition , age ≥ 60 patients benefit from pemetrexed with equivalent efficacies yet much lower toxicities compared to docetaxel ( DCR : pemetrexed vs. docetaxel = 66.67 % vs. 81.58 % , p = 0.146 ; grade 3/4 hematologic toxicities : pemetrexed vs. docetaxel = 17.25 % vs. 39.6 % , p = 0.016 ) . CONCLUSION Treatment with pemetrexed result ed in equivalent efficacy outcomes and better safety profiles compared with docetaxel in second-line therapy for advanced NSCLC in Chinese lung cancer population . And age ≥ 60 patients may benefit from second-line single pemetrexed Docetaxel alone has been confirmed to be beneficial to patients with advanced previously treated non-small cell lung cancer ( NSCLC ) . However , the duration and survival time is short . The study of two-agent combination regimens has important clinical significance . We conducted this r and omized controlled phase II trial to comparatively evaluate the efficacy and side effects of capecitabine combined with docetaxel in previously treated patients with NSCLC . Patients with previously treated NSCLC who failed first-line chemotherapy were r and omized into two groups ; one received capecitabine combined with docetaxel ( XT group ) and the other received docetaxel alone ( T group ) . Patients in the XT group received chemotherapy as follows : capecitabine 625 mg/m(2 ) , p.o . bid , days 5 - 18 ; and docetaxel 30 mg/m(2 ) , days 1 and 8 , while patients in the T group received docetaxel 35 mg/m(2 ) on days 1 and 8 . The primary endpoint was time to progression ( TTP ) , and secondary endpoints were overall survival ( OS ) , response rate ( RR ) and disease control rate ( DCR ) . Forty-eight patients were recruited ( 23 in the XT group and 25 in the T group ) . TTP , median survival time ( MST ) and 1-year OS rate in the XT group and the T group were 7 months , 12 months , 47.6 % and 3 months , 12 months , 39.6 % , respectively . The TTP in the XT group was significantly longer compared to that in the T group ( χ(2)=4.763 , p=0.029 ) . The RR and DCR in the XT group and T group were 13.0 % ( 3/23 ) , 78.3 % ( 18/23 ) and 12.0 % ( 3/25 ) , 76 % ( 19/25 ) , respectively . The difference was not significant ( p>0.05 ) . The major side effects observed in the two groups were neutropenia , fatigue and nausea , and toxicities were mild to modest . No severe cases of h and -foot syndrome were observed in the XT group . In conclusion , compared with docetaxel alone , capecitabine combined with docetaxel for patients with previously treated NSCLC achieved a significantly longer TTP and this regimen was well tolerated . The relatively high median TTP , 1-year OS rate and DCR encourage further evaluation of this regimen in a r and omized phase III trial 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 Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes . We assessed the activity of nivolumab , a fully human IgG4 PD-1 immune checkpoint inhibitor antibody , for patients with advanced , refractory , squamous non-small-cell lung cancer . METHODS We did this phase 2 , single-arm trial at 27 sites ( academic , hospital , and private cancer centres ) in France , Germany , Italy , and USA . Patients who had received two or more previous treatments received intravenous nivolumab ( 3 mg/kg ) every 2 weeks until progression or unacceptable toxic effects . The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee . We included all treated patients in the analyses . This study is registered with Clinical Trials.gov , number NCT01721759 . FINDINGS Between Nov 16 , 2012 , and July 22 , 2013 , we enrolled and treated 117 patients . 17 ( 14·5 % , 95 % CI 8·7 - 22·2 ) of 117 patients had an objective response as assessed by an independent radiology review committee . Median time to response was 3·3 months ( IQR 2·2 - 4·8 ) , and median duration of response was not reached ( 95 % CI 8·31-not applicable ) ; 13 ( 77 % ) of 17 of responses were ongoing at the time of analysis . 30 ( 26 % ) of 117 patients had stable disease ( median duration 6·0 months , 95 % CI 4·7 - 10·9 ) . 20 ( 17 % ) of 117 patients reported grade 3 - 4 treatment-related adverse events , including : fatigue ( five [ 4 % ] of 117 patients ) , pneumonitis ( four [ 3 % ] ) , and diarrhoea ( three [ 3 % ] ) . There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease . INTERPRETATION Nivolumab has clinical ly meaningful activity and a manageable safety profile in previously treated patients with advanced , refractory , squamous non-small cell lung cancer . These data support the assessment of nivolumab in r and omised , controlled , phase 3 studies of first-line and second-line treatment . FUNDING Bristol-Myers Squibb BACKGROUND KRAS mutations are detected in 25 % of non-small-cell lung cancer ( NSCLC ) and no targeted therapies are approved for this subset population . Trametinib , a selective allosteric inhibitor of MEK1/MEK2 , demonstrated pre clinical and clinical activity in KRAS-mutant NSCLC . We report a phase II trial comparing trametinib with docetaxel in patients with advanced KRAS-mutant NSCLC . PATIENTS AND METHODS Eligible patients with histologically confirmed KRAS-mutant NSCLC previously treated with one prior platinum-based chemotherapy were r and omly assigned in a ratio of 2 : 1 to trametinib ( 2 mg orally once daily ) or docetaxel ( 75 mg/m(2 ) i.v . every 3 weeks ) . Crossover to the other arm after disease progression was allowed . Primary end point was progression-free survival ( PFS ) . The study was prematurely terminated after the interim analysis of 92 PFS events , which showed the comparison of trametinib versus docetaxel for PFS crossed the futility boundary . RESULTS One hundred and twenty-nine patients with KRAS-mutant NSCLC were r and omized ; of which , 86 patients received trametinib and 43 received docetaxel . Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm ( hazard ratio [ HR ] 1.14 ; 95 % CI 0.75 - 1.75 ; P = 0.5197 ) . Median overall survival , while the data are immature , was 8 months in the trametinib arm and was not reached in the docetaxel arm ( HR 0.97 ; 95 % CI 0.52 - 1.83 ; P = 0.934 ) . There were 10 ( 12 % ) partial responses ( PRs ) in the trametinib arm and 5 ( 12 % ) PRs in the docetaxel arm ( P = 1.0000 ) . The most frequent adverse events ( AEs ) in ≥20 % of trametinib patients were rash , diarrhea , nausea , vomiting , and fatigue . The most frequent grade 3 treatment-related AEs in the trametinib arm were hypertension , rash , diarrhea , and asthenia . CONCLUSION Trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive NSCLC . CLINICAL TRIALSGOV REGISTRATION NUMBER NCT01362296 PURPOSE Programmed death 1 is an immune checkpoint that suppresses antitumor immunity . Nivolumab , a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody , was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts . We report overall survival ( OS ) , response durability , and long-term safety in patients with non-small-cell lung cancer ( NSCLC ) receiving nivolumab in this trial . PATIENTS AND METHODS Patients ( N = 129 ) with heavily pretreated advanced NSCLC received nivolumab 1 , 3 , or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks . Tumor burden was assessed by RECIST ( version 1.0 ) after each cycle . RESULTS Median OS across doses was 9.9 months ; 1- , 2- , and 3-year OS rates were 42 % , 24 % , and 18 % , respectively , across doses and 56 % , 42 % , and 27 % , respectively , at the 3-mg/kg dose ( n = 37 ) chosen for further clinical development . Among 22 patients ( 17 % ) with objective responses , estimated median response duration was 17.0 months . An additional six patients ( 5 % ) had unconventional immune-pattern responses . Response rates were similar in squamous and nonsquamous NSCLC . Eighteen responding patients discontinued nivolumab for reasons other than progressive disease ; nine ( 50 % ) of those had responses lasting > 9 months after their last dose . Grade 3 to 4 treatment-related adverse events occurred in 14 % of patients . Three treatment-related deaths ( 2 % of patients ) occurred , each associated with pneumonitis . CONCLUSION Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC . R and omized clinical trials with nivolumab in advanced NSCLC are ongoing BACKGROUND St and ard first-line chemotherapy for elderly non-small cell lung cancer ( NSCLC ) patients has been monotherapy with vinorelbine or gemcitabine . Docetaxel has also been considered as an alternative option for the elderly population in Japan . We have previously demonstrated the high efficacy of carboplatin plus weekly paclitaxel for elderly NSCLC patients . Consequently , we conducted a r and omized phase II study to select the proper regimen for a future phase III trial . METHODS Eligible patients were aged 70 years or older with newly diagnosed advanced NSCLC . Patients were r and omly assigned either to a combination of carboplatin ( area under the curve : 6 mg/mL per minute ) with weekly paclitaxel ( 70 mg/m² ) ( CP regimen ) or to single-agent docetaxel ( 60 mg/m² ) . The primary endpoint of this study was objective response rate . Secondary endpoints were progression-free survival , overall survival , and toxicity profile . RESULTS Among 83 eligible patients ( 41 to CP , 42 to docetaxel ) , the objective response rates were 54 % ( 95 % confidence interval : 39%-69 % ) and 24 % ( 95 % confidence interval : 11%-37 % ) and median progression-free survival was 6.6 months and 3.5 months in the CP arm and the docetaxel arm , respectively . Severe neutropenia , febrile neutropenia , and nausea were significantly frequent in the docetaxel arm , whereas toxicities in the CP arm were generally moderate . One treatment-related death was observed in the docetaxel arm . CONCLUSION The CP regimen achieved higher activity with less toxicity than single-agent docetaxel . Considering the results of this phase II trial and the IFCT-0501 trial , we have selected the CP regimen for a future phase III trial in elderly patients with advanced NSCLC |
1,187 | 23,595,919 | CONCLUSIONS Simulation-based education was associated with small-moderate patient benefits in comparison with no intervention and non-simulation instruction , although the latter did not reach statistical significance . | ABSTRACT OBJECTIVES Evaluating the patient impact of health professions education is a societal priority with many challenges .
Research ers would benefit from a summary of topics studied and potential method ological problems .
We sought to summarize key information on patient outcomes identified in a comprehensive systematic review of simulation-based instruction . | Objective : To evaluate the viability and effectiveness of a simulation-based pediatric mock code program on patient outcomes , as well as residents ' confidence in performing resuscitations . A resident 's leadership ability is integral to accurate and efficient clinical response in the successful management of cardiopulmonary arrest ( CPA ) . Direct experience is a contributing factor to a resident 's code team leadership ability ; however , opportunities to gain experience are limited by relative infrequency of pediatric arrests and code occurrences when residents are on service . Design : Longitudinal , mixed- methods research design . Setting : Children 's hospital at an tertiary care academic medical center . Patients : Pediatric . Interventions : Clinicians responsible for pediatric resuscitations responded to mock codes r and omly called at increasing rates over a 48-month period , just as they would an actual CPA event . Events were recorded and used for immediate debriefing facilitated by clinical faculty to provide residents feedback about their performance . Measurements : Self- assessment data were collected from all team members . Hospital records for pediatric CPA survival rates were examined for the study duration . Results : Survival rates increased to approximately 50 % ( p = .000 ) , correlating with the increased number of mock codes ( r = .87 ) . These results are significantly above the average national pediatric CPA survival rates and held steady for 3 consecutive years , demonstrating the stability of the program 's outcomes . Conclusions : This study suggests that a simulation-based mock code program may significantly benefit pediatric patient CPA outcomes —applied clinical outcomes —not simply learner perceived value , increased confidence , or simulation-based outcomes . The use of mock codes as an integral part of residency programs could provide residents with the resuscitation training they require to become proficient in their practice . Future programs that incorporate transport scenarios , ambulatory care , and other outpatient setting s could further benefit pediatric patients in prehospital context Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement AIM Advanced simulation tools are increasingly being incorporated into cardiopulmonary resuscitation ( CPR ) training . These educational methods have been shown to improve trainee performance in simulated setting s , but translation into clinical practice remains unknown for many aspects of CPR quality . This study attempts to measure the impact of simulation-based training for resuscitation team leaders on some measures of CPR quality during actual in-hospital resuscitation attempts . METHODS In this prospect i ve , r and omized interventional cluster trial , internal medicine resident physicians ( post-graduate year 2 ) were r and omized using a r and om number generator to participate in a 4-h , immersive simulation course in cardiopulmonary resuscitation leadership using a high-fidelity simulator with video debriefing prior to serving as resuscitation team leaders at an academic medical center . Objective metrics of actual resuscitation performance were obtained from a CPR-sensing monitor/defibrillator . RESULTS Thirty-two residents were r and omized to receive simulation training or no additional training between April and July 2007 and data were collected following 98 actual resuscitations between July 2007 and June 2008 . CPR quality from resuscitations led by 14 simulation-trained and 16 control group residents was similar in terms of mean compression depth ( 48 vs 49 mm ; p = 0.53 ) ; compression rate ( 107 vs 104 min⁻¹ ; p = 0.30 ) ; ventilation rate ( 12 vs 12 min⁻¹ ; p = 0.45 ) and no-flow fraction ( 0.08 vs 0.07 ; p = 0.34 ) . CONCLUSIONS Although we failed to detect any significant differences in objective measures of CPR quality , we have demonstrated that CPR-sensing technology has the potential for use in assessing the impact of a simulation curriculum on some aspects of actual resuscitation performance . A larger study , performed in a setting with lower baseline performance , would be required to assess the specific simulation curriculum This study examines effectiveness of a donated Laerdal Virtual I.V. simulator when compared with traditional methods of teaching intravenous ( IV ) cannulation to third year medical students in the Philippines . Forty novice Filipino medical students viewed an instructional video on how to start intravenous lines and were then r and omly divided into two groups of twenty . The " Traditional " group observed an IV insertion on an actual patient performed by an experienced practitioner , and then subsequently performed an IV on an actual patient which was videotaped . The " Simulation " group practice d the Virtual I.V. simulator until they successfully completed level three using the " doctor " setting . These students then performed an IV on an actual patient which was videotaped . The videotapes for both groups were review ed by two pre-trained ( Inter-rater reliability of > or = 0.84 ) observers who were blinded to the group using a previously vali date d checklist for IV insertion . Students trained on the Virtual I.V. showed significantly greater success in successfully starting an IV on an actual patient ( 40 % VS . 15 % , p<0.05 ) , decreased constrictive b and time ( p<.05 ) , increased raw score on the check list ( p<.03 ) , and decreased overall time to start an IV ( p<.05 ) . The technology was well received but wider application in the non western world is limited by lack of in country company support and the relative expense Background With increasing pressure to use operating room time efficiently , opportunities for residents to learn fiberoptic orotracheal intubation in the operating room have declined . The purpose of this study was to determine whether fiberoptic orotracheal intubation skills learned outside the operating room on a simple model could be transferred into the clinical setting . Methods First-year anesthesiology residents and first- and second-year internal medicine residents were recruited . Subjects were r and omized to a didactic-teaching-only group ( n = 12 ) or a model-training group ( n = 12 ) . The didactic-teaching group received a detailed lecture from an expert bronchoscopist . The model-training group was guided , by experts , through tasks performed on a simple model design ed to refine fiberoptic manipulation skills . After the training session , subjects performed a fiberoptic orotracheal intubation on healthy , consenting , anesthetized , paralyzed female patients undergoing elective surgery with predicted “ easy ” laryngoscopic intubations . Two blinded anesthesiologists evaluated each subject . Results After the training session , the model group significantly outperformed the didactic group in the operating room when evaluated with a global rating scale ( P < 0.01 ) and checklist ( P < 0.05 ) . Model-trained subjects completed the fiberoptic orotracheal intubation significantly faster than didactic-trained subjects ( P < 0.01 ) . Model-trained subjects were also more successful at achieving tracheal intubation than the didactic group ( P < 0.005 ) . Conclusion Fiberoptic orotracheal intubation skills training on a simple model is more effective than conventional didactic instruction for transfer to the clinical setting . Incorporating an extraoperative model into the training of fiberoptic orotracheal intubation may greatly reduce the time and pressures that accompany teaching this skill in the operating room BACKGROUND We studied the reasons why patients undergoing thoracenteses performed in our outpatient pulmonary clinic had a higher frequency of iatrogenic pneumothorax compared to that in the concurrent radiology practice in our institution , which utilizes ultrasound guidance . We review ed our practice model and implemented a unique experiential training paradigm in a zero-risk simulation environment to improve efficacy , timeliness , service orientation , and safety . METHODS We retrospectively determined the rate of clinical ly significant pneumothoraces in our practice ( phase I , July 1 , 2001 , to June 30 , 2002 ) . The training system re design included the following : ( 1 ) a design ated group of pulmonologist instructors dedicated to treating pleural disease and reducing the number of iatrogenic complications ; ( 2 ) the use of ultrasound image guidance for all thoracenteses ; and ( 3 ) structured proficiency and competency st and ards for proceduralists . Postintervention ( phase II ) data were prospect ively collected ( January 2005 to December 2006 ) and compared with our baseline data . RESULTS The baseline rate of pneumothorax was 8.6 % ( 5 of 58 patients ) in our pulmonary practice . Following intervention ( phase II ) , the rate of pneumothorax declined to 1.1 % ( p = 0.0034 ) . During phase II , the number of thoracenteses performed increased ( 186 vs 58 per year , respectively ; p < 0.05 ) . The iatrogenic pneumothorax rate was stable in the 2 years following intervention ( 2005 , 0.7 % [ 1 of 137 pneumothoraces ] ; 2006 , 1.3 % [ 3 of 226 pneumothoraces ] ; p > 0.9 ) . Postintervention complications included procedure-related pain ( n = 19 ) , cough ( n = 4 ) , and hypotension ( n = 10 ) . CONCLUSIONS An improvement program that included simulation , ultrasound guidance , competency testing , and performance feedback reduced iatrogenic risk to patients . We recommend application of this process to procedural practice Purpose To determine whether simulation training of ultrasound (US)-guided central venous catheter ( CVC ) insertion skills on a partial task trainer improves cannulation and insertion success rates in clinical practice . Method This prospect i ve , r and omized , controlled , single-blind study of first- and second-year residents occurred at a tertiary care teaching hospital from January 2007 to September 2008 . The intervention group ( n = 90 ) received a didactic and h and s-on , competency-based simulation training course in US-guided CVC insertion , whereas the control group ( n = 95 ) received training through a traditional , bedside apprenticeship model . Success at first cannulation and successful CVC insertion served as the primary outcomes . Secondary outcomes included reduction in technical errors and decreased mechanical complications . Results Blinded independent raters observed 495 CVC insertions by 115 residents over a 21-month period . Successful first cannulation occurred in 51 % of the intervention group versus 37 % of the control group ( P = .03 ) . CVC insertion success occurred for 78 % of the intervention group versus 67 % of the control group ( P = .02 ) . Simulation training was independently and significantly associated with success at first cannulation ( odds ratio : 1.7 ; 95 % confidence interval : 1.1–2.8 ) and with successful CVC insertion ( odds ratio : 1.7 ; 95 % confidence interval : 1.1–2.8)—both independent of US use , patient comorbidities , or resident specialty . No significant differences related to technical errors or mechanical complications existed between the two groups . Conclusions Simulation training was associated with improved in-hospital performance of CVC insertion . Procedural simulation was associated with improved residents ' skills and was more effective than traditional training BACKGROUND AND STUDY AIM As for any manual procedure , the learning curves for medical interventions can have undesirable phases , occurring mostly in the early experience of applying a technique . There have been impressive advances in endoscopic procedures during recent years , and there is an emerging trend that the number of procedures is increasing in parallel with these . In addition , the introduction of screening programs for colorectal cancer will also increase the numbers of procedures needed . Recent developments in medical simulation seem promising with regard to the possibility of " training out " undesirable parts of the learning curve outside the operating room . The aim of this study was to investigate whether the use of the AccuTouch flexible endoscopy simulator improves the early part of the learning curve in colonoscopy training . METHOD 12 endoscopy trainees , 10 surgeons and two medical gastroenterologists , all with experience in gastroscopy but with no specific colonoscopy experience , were r and omly assigned to either simulator training or to a control group . They all received the same theoretical study package and the training group practice d with the AccuTouch colonoscopy simulator until a predefined expert level of performance was reached . All trainees performed their first ten individual colonoscopies described in detail in a separate protocol . RESULTS Trainees in the simulator-trained group performed significantly better ( P=0.0011 ) and managed to reach the cecum in 52 % of their cases ( vs. 19 % in the control group ) , and were 4.53 times more likely to succeed compared with the controls . Additionally , there was a significantly shorter procedure time and less patient discomfort in the h and s of the simulator-trained group . CONCLUSION Skills acquired using the AccuTouch simulator transfer well into the clinical colonoscopy environment . The results of this trial clearly support the plan to integrate simulator training into endoscopic education curricula BACKGROUND The GI Mentor is a virtual reality simulator that uses force feedback technology to create a realistic training experience . OBJECTIVE To define the benefit of training on the GI Mentor on competency acquisition in colonoscopy . DESIGN R and omized , controlled , blinded , multicenter trial . SETTING Academic medical centers with accredited gastroenterology training programs . PATIENTS First-year GI fellows . INTERVENTIONS Subjects were r and omized to receive 10 hours of unsupervised training on the GI Mentor or no simulator experience during the first 8 weeks of fellowship . After this period , both groups began performing real colonoscopies . The first 200 colonoscopies performed by each fellow were grade d by proctors to measure technical and cognitive success , and patient comfort level during the procedure . MAIN OUTCOME MEASUREMENTS A mixed-effects model comparison between the 2 groups of objective and subjective competency scores and patient discomfort in the performance of real colonoscopies over time . RESULTS Forty-five fellows were r and omized from 16 hospitals over 2 years . Fellows in the simulator group had significantly higher objective competency rates during the first 100 cases . A mixed-effects model demonstrated a higher objective competence overall in the simulator group ( P < .0001 ) , with the difference between groups being significantly greater during the first 80 cases performed . The median number of cases needed to reach 90 % competency was 160 in both groups . The patient comfort level was similar . CONCLUSIONS Fellows who underwent GI Mentor training performed significantly better during the early phase of real colonoscopy training Intravenous cannulation is a nursing procedure carried out in some clinical units that may induce trauma and discomfort . Nurses should be well prepared before practising the procedure with clients . Conventionally , a plastic arm was used for practice but , with innovative developments in technology , a computer program called the CathSim Intravenous Training System ( CathSim ITS ) is available for this purpose . This study was conducted to compare the effectiveness of learning using a plastic arm with the CathSim ITS . Twenty-eight nurses were divided into two groups and r and omly assigned to the two different methods : plastic arm ( control group ) or CathSim ITS ( experimental group ) . Both groups were provided with 1 hour of theory input and 2 hours of nursing laboratory work . When the nurses felt ready to practise on clients , their performances were assessed by research ers with an intravenous cannulation qualification using a vali date d checklist . Prior to the assessment , trait and state anxiety levels were measured using the State-Trait Anxiety Inventory ( Hong Kong Chinese adaptation ) to check whether anxiety would affect the performance . Following the assessment , a semi-structured interview was conducted to reveal my knowledge acquired through using the selected method . Both the control and CathSim ITS groups demonstrated a high success rate , scoring 100 % and 92.86 % , respectively , with their first client . The semi-structured interviews revealed that the CathSim ITS group appreciated several features of their assigned method . However , there is room for further development If you teach a medical student , can they learn ? The answer may seem self-evident . After all , undergraduates do n’t make it into medical school without demonstrating a remarkable capacity to learn and perform well on tests . So asking if medical students ( or other health professionals and students ) are capable of learning should be a superfluous question . Yet education research ers seem compelled to repeatedly ask this question . And surprisingly ( or not ) , they repeatedly come up with the same answer . Figure 1 shows the results of over 750 studies , summarized from 4 separate metaanalyses ( Cook et al. 2010a , 2008b , 2011a , McGaghie et al. 2011 ) , comparing various forms of training with no intervention . For example , a meta- analysis of Internet-based education found 126 studies comparing training with no intervention ( either a single-group pretest – posttest study , or a no-intervention comparison group ; Cook et al. 2008b ) . Only 2 studies failed to favor the training group for outcomes of knowledge , and the average effect size was 1.0—which according to Cohen ( 1988 ) would be considered a large effect . Results were similarly large for outcomes of skills and behaviors . Another meta- analysis found similar results for computer-based virtual patients ( Cook et al. 2010a ) . Most recently , two meta-analyses of simulation-based education confirmed similarly strong benefits , with effect sizes ranging 0.8–2.0 ( Cook et al. 2011a ; McGaghie et al. 2011 ) . Moreover , these results held true across various learner subgroups ( medical students , postgraduate physician trainees , physicians , nurses and nursing students , and others ) , study design s ( there were over 150 r and omized trials ) , and multiple other subgroup analyses . Only when actual impact on patients was considered was a lower effect size noted , and then it was still a moderately-large 0.50 . Even after adjusting for possible publication BACKGROUND The teaching of surgical skills is based mostly on the traditional " see one , do one , teach one " resident-to-resident method . Surgical skills laboratories provide a new environment for teaching skills but their effectiveness has not been adequately tested . Cognitive task analysis is an innovative method to teach skills , used successfully in nonmedical fields . The objective of this study is to evaluate the effectiveness of a 3-hour surgical skills laboratory course on central venous catheterization ( CVC ) , taught by the principles of cognitive task analysis to surgical interns . METHODS Upon arrival to the Department of Surgery , 26 new interns were r and omized to either receive a surgical skills laboratory course on CVC ( " course " group , n = 12 ) or not ( " traditional " group , n = 14 ) . The course consisted mostly of h and s-on training on inanimate CVC models . All interns took a 15-item multiple-choice question test on CVC at the beginning of the study . Within two and a half months all interns performed CVC on critically ill patients . The outcome measures were cognitive knowledge and technical-skill competence on CVC . These outcomes were assessed by a 14-item checklist evaluating the interns while performing CVC on a patient and by the 15-item multiple-choice- question test , which was repeated at that time . RESULTS There were no differences between the two groups in the background characteristics of the interns or the patients having CVC . The scores at the initial multiple-choice test were similar ( course : 7.33 + /- 1.07 , traditional : 8 + /- 2.15 , P = 0.944 ) . However , the course interns scored significantly higher in the repeat test compared with the traditional interns ( 11 + /- 1.86 versus 8.64 + /- 1.82 , P = 0.03 ) . Also , the course interns achieved a higher score on the 14-item checklist ( 12.6 + /- 1.1 versus 7.5 + /- 2.2 , P < 0.001 ) . They required fewer attempts to find the vein ( 3.3 + /- 2.2 versus 6.4 + /- 4.2 , P = 0.046 ) and showed a trend toward less time to complete the procedure ( 15.4 + /- 9.5 versus 20.6 + /- 9.1 minutes , P = 0.149 ) . CONCLUSIONS A surgical skills laboratory course on CVC , taught by the principles of cognitive task analysis and using inanimate models , improves the knowledge and technical skills of new surgical interns on this task BACKGROUND Changes in medical practice have constrained the time available for education and the availability of patients for training . Computer-based simulators have been devised that can be used to achieve manual skills without patient contact . This study prospect ively compared , in a clinical setting , the efficacy of a computer-based simulator for training in upper endoscopy . METHODS Twenty-two fellows with no experience in endoscopy were r and omly assigned to two groups : one group underwent 10 hours of pre clinical training with a computer-based simulator , and the other did not . Each trainee performed upper endoscopy in 19 or 20 patients . Performance parameters evaluated included the following : esophageal intubation , procedure duration and completeness , and request for assistance . The performance of the trainees also was evaluated by the endoscopy instructor . RESULTS A total of 420 upper endoscopies were performed ; the computer pretrained group performed 212 and the non-pretrained group , 208 . The pretrained group performed more complete procedures ( 87.8 % vs. 70.0 % ; p < 0.0001 ) , required less assistance ( 41.3 % vs. 97.9 % ; p < 0.0001 ) , and the instructor assessed performance as " positive " more often for this group ( 86.8 % vs. 56.7 % ; p < 0.0001 ) . The length of procedures was comparable for the two groups . CONCLUSIONS The computer-based simulator is effective in providing novice trainees with the skills needed for identification of anatomical l and marks and basic endoscopic maneuvers , and in reducing the need for assistance by instructors Research ers lack the rich evidence base and benchmark patient outcomes needed to evaluate the effectiveness of medical education practice and guide policy . The authors offer a framework for medical education research that focuses on physician-influenced patient outcomes that are potentially sensitive to medical education . Adapting the concept of ambulatory care sensitive conditions , which provided traction to health services research by defining benchmark patient outcomes to measure health system performance , the authors introduce the concept and propose the adoption of educationally sensitive patient outcomes and suggest two measures : patient activation and clinical microsystem activation . They assert that the ultimate goal of medical education is to ensure that measurement of future physicians ' competence and skills is based not only on biomedical knowledge and critical clinical skills but also on the ability to translate these competencies into effective patient- and systems-level outcomes . The authors consider method ological approaches and challenges to measuring such outcomes and argue for large , multiinstitutional , prospect i ve cohort studies and the development of a national Data base for Research in Education in Academic Medicine to provide the needed infrastructure . They advocate taking the next steps to establish an educational evidence base to guide the academic medical centers of the 21st century in aligning medical education practice with health care delivery that meets the needs of individuals and population The statistical methodology of health research experiments published in Lancet , the New Engl and Journal of Medicine , and Medical Care between 1975 and 1980 for the presence or absence of an error of experimental design and analysis was examined . The error is the result of inappropriately using patient-related observations as the unit of analysis to form conclusions about provider behavior or outcomes determined jointly by patients and providers . The error was present in 20 of 28 ( 71 % ) health care experiments addressing an issue of health provider professional performance . Its usual effect is to increase erroneously the power of an experiment to detect differences between experimental and control groups . It is likely that this type of error could be avoided by the explicit and prospect i ve definition of hypotheses and the population s to which they are intended to pertain Introduction : Simulation is a safe alternative to practicing procedural skills on patients . However , few published studies have examined the long-term effect of simulation technology on bedside procedures such as central venous catheter ( CVC ) insertion . Methods : To determine whether simulation-based teaching improves procedural comfort , performance , and clinical events in CVC insertion , over traditional methods of procedural teaching , and to assess the long-term effect of this training , we conducted a prospect i ve , r and omized controlled trial with 53 postgraduate year-1 and postgraduate year-2 medical residents at a tertiary-care teaching hospital . At the start of the study , we assessed all residents ’ procedural comfort and previous training and experience with CVCs . We then measured their baseline performance in placing CVCs on simulators , using a vali date d assessment tool ( pretest ) . For the intervention group , we reassessed performance immediately after simulation training ( posttest ) . All subjects then placed actual CVCs as clinical ly indicated while on their medical intensive care unit rotations , under the supervision of critical care faculty . We measured clinical events associated with these CVCs . After their medical intensive care unit rotations , we reassessed CVC insertion skills on simulators and procedural comfort of all subjects ( delayed posttest ) . Results : Intervention subjects demonstrated a significant improvement in skills immediately after simulation training . At delayed posttesting , performance diminished somewhat in the intervention subjects and was not significantly different from control subjects ; however , a significant increase over pretest scores persisted in both groups . Conclusions : A CVC insertion simulation course improves procedural skills . These skills decline over time , and simulation conferred no long-term additional benefit over traditional methods of procedural teaching BACKGROUND New Residency Review Committee requirements in general surgery require 50 colonoscopies . Simulators have been widely suggested to help prepare residents for live clinical experience . We assessed a computer-based colonoscopy simulator for effective transfer of skills to live patients . METHODS A r and omized controlled trial included general surgery and internal medicine residents with limited endoscopic experience . Following a pretest , the treatment group ( n = 12 ) practice d on the simulator , while controls ( n = 12 ) received no additional training . Both groups then performed a colonoscopy on a live patient . Technical ability was evaluated by expert endoscopists using previously vali date d assessment instruments . RESULTS In the live patient setting , the treatment group scored significantly higher global ratings than controls ( t(22 ) = 1.84 , P = .04 ) . Only 2 of the 8 computer-based performance metrics correlated significantly with previously vali date d global ratings of performance . CONCLUSIONS Residents trained on a colonoscopy simulator prior to their first patient-based colonoscopy performed significantly better in the clinical setting than controls , demonstrating skill transfer to live patients . The simulator 's performance metrics showed limited concurrent validity , suggesting the need for further refinement This study prospect ively compared the rates of skill acquisition in ileocolonoscopy in 2 consecutive groups of trainees in paediatric gastroenterology , with 1 cohort exposed to virtual endoscopy . All paediatric gastroenterology trainees rotating through our department during a 7-year period between 1997 and 2004 were formally assessed while performing ileocolonoscopies using a trainer case-by-case method . Fourteen consecutive trainees with no previous experience of ileocolonoscopy were assessed . Comparison of rates of skill acquisition and lesion recognition using multiple linear regressions revealed a significant acceleration of achievement of endoscopic goals ( P < 0.0001 ) in the group with prior exposure to virtual endoscopy OBJECTIVES : Computer-based colonoscopy simulation ( CBCS ) is being utilized in endoscopy training without supporting evidence that it improves patient-based colonoscopy performance . The goal of this pilot study was to determine if CBCS training improves gastroenterology ( GI ) fellows ' patient-based colonoscopy skills . METHODS : Competency at colonoscopy among 4 novice GI fellows who completed a 6-h CBCS curriculum was compared with 4 novice fellows who were not CBCS-trained . Measurements of competency were rendered by supervising faculty by recording “ insertion time,”“depth of unassisted insertion,”“independent procedure completion,”“ability to identify endoscopic l and marks,”“inserts in a safe manner,”“adequately visualizes mucosa on withdrawal , ” and “ responds appropriately to patient discomfort ” with each colonoscopy . RESULTS : Simulator-trained fellows outperformed traditionally trained fellows during their initial 15 colonoscopies in all performance aspects except “ insertion time ” ( pp < 0.05 ) . Simulator-trained fellows inserted the endoscope significantly further and reached the cecum independently nearly twice as often during this early training period . Three parameters ( “ depth of insertion,”“independent completion , ” and “ ability to identify l and marks ” ) demonstrated a continued advantage out to 30 colonoscopies . Beyond 30 procedures , there was no difference in the performance of the two groups . CONCLUSION : In this pilot study , a 6-h CBCS curriculum provides an early training advantage by enhancing competency at the early stages of patient-based colonoscopy . These advantages are negligible after approximately 30 patient-based procedures . CBCS-enhanced training may allow faculty to be more efficient with their colonoscopy practice BACKGROUND AND STUDY AIMS Clinical investigation using endoscopy simulators is now possible due to recent advances in virtual reality technology . A prospect i ve r and omized trial was conducted to compare the exclusive use of a virtual reality endoscopy simulator with bedside teaching for training in sigmoidoscopy . MATERIAL S AND METHODS Internal medicine residents were r and omly assigned to training exclusively using a virtual reality simulator ( group 1 ) or via bedside teaching ( group 2 ) . Residents were then observed performing five sigmoidoscopic procedures in asymptomatic patients referred for colorectal cancer screening . Endoscopic examinations were evaluated for procedure duration , completion , ability to perform retroflexion , and level of patient comfort/discomfort . Each examination was scored from 1 ( inability to insert the endoscope beyond the rectum ) to 5 ( able to complete the entire examination independently in less than 20 min ) . RESULTS Sixty-six sigmoidoscopic examinations were completed by nine residents in group 1 ( simulator-trained group ) and seven residents in group 2 ( traditional teaching group ) . Participants in group 1 had more difficulty with initial endoscope insertion and negotiation of the rectosigmoid junction ( mean score + /- SEM 2.9 + /- 0.2 ) than those in group 2 ( 3.8 + /- 0.2 ) ( P < 0.001 ) . The splenic flexure was reached independently in 10 of 34 examinations ( 29 % ) in group 1 , compared with 23 of 32 examinations ( 72 % ) in group 2 ( P = 0.001 ) . Retroflexion was successfully performed by 19 of 34 ( 56 % ) in group 1 compared to 27 of 32 ( 84 % ) in group 2 ( P = 0.02 ) . The average procedure time , patient satisfaction , and discomfort associated with the procedure did not differ statistically between the two groups . CONCLUSIONS The use of a state-of-the-art virtual reality-based endoscopy simulator is inferior to traditional bedside teaching techniques when used exclusively for training medical residents to perform sigmoidoscopy STUDY OBJECTIVES To determine the effect of manikin-only training on field success of endotracheal intubation by paramedics . DESIGN Prospect i ve evaluation of individual field endotracheal intubation success rates for paramedics after they participated in a manikin-only or a manikin-plus-cadaver training program . TYPES OF PARTICIPANTS Paramedics responding to emergency calls involving adult medical or trauma victims . INTERVENTIONS All participants were trained using a controlled manikin training program ; then , half were r and omly selected for additional instruction using fresh human cadavers . MEASUREMENTS AND MAIN RESULTS Individuals trained using only the manikin program had mean + /- SD individual success rates of 82 + /- 32 % , and individuals who received additional cadaver training had mean individual success rates of 83 + /- 31 % . Overall success rates for the two groups were 86 % for the manikin-only group and 85 % for the manikin-plus-cadaver-trained group . The sample size was not adequate to allow rejection of the null hypothesis . CONCLUSION Paramedics trained in endotracheal intubation using a systematic manikin-only teaching program can attain acceptable individual success rates in the actual field setting BACKGROUND This study was design ed to evaluate whether resident performance of placing central lines improved after simulation training on newly available partial-task simulators . METHODS This study was design ed as a prospect i ve , r and omized controlled trial of st and ard training versus simulated training using Central Line Man ( SimuLab , Seattle , WA , USA ) . After receiving a lecture on central line placement , all junior residents on the trauma rotation were r and omized on a monthly alternating schedule . Equivalency of groups was determined with a self-reported survey . All lines placed by the participants were monitored , and data were collected on performance and complications . RESULTS The 2 groups ( n = 34 ; 21 st and ard and 13 simulated ) were equivalent at baseline . The simulated training group had a significantly higher level of comfort and ability than the st and ard training group . The simulated group outperformed the st and ard group on 12 of the 15 specific variables monitored , although this did not reach statistical significance . There were significantly more complications in the st and ard group . CONCLUSIONS Simulation for central line placement using a partial-task simulator does positively impact resident performance BACKGROUND Virtual reality ( VR ) training has been shown previously to improve intraoperative performance during part of a laparoscopic cholecystectomy . The aim of this study was to assess the effect of proficiency-based VR training on the outcome of the first 10 entire cholecystectomies performed by novices . METHODS Thirteen laparoscopically inexperienced residents were r and omized to either ( 1 ) VR training until a predefined expert level of performance was reached , or ( 2 ) the control group . Videotapes of each resident 's first 10 procedures were review ed independently in a blinded fashion and scored for predefined errors . RESULTS The VR-trained group consistently made significantly fewer errors ( P = .0037 ) . On the other h and , residents in the control group made , on average , 3 times as many errors and used 58 % longer surgical time . CONCLUSIONS The results of this study show that training on the VR simulator to a level of proficiency significantly improves intraoperative performance during a resident 's first 10 laparoscopic cholecystectomies BACKGROUND : Pediatric housestaff are required to learn basic procedural skills and demonstrate competence during training . To our knowledge , an evidence d-based procedural skills curriculum does not exist . OBJECTIVE : To create , implement , and evaluate a modular procedural skills curriculum for pediatric residents . METHODS : A r and omized , controlled trial was performed . Thirty-eight interns in the Boston Combined Residency Program who began their training in 2005 were enrolled and r and omly assigned . Modules were created to teach residents bag-mask ventilation , venipuncture , peripheral intravenous catheter ( PIV ) insertion , and lumbar puncture skills . The curriculum was administered to participants in the intervention group during intern orientation . Interns in the control group learned procedural skills by usual methods . Subjects were evaluated by using a structured objective assessment on simulators immediately after the intervention and 7 months later . Success in performing live-patient procedures was self-reported by subjects . The primary outcome was successful performance of the procedure on the initial assessment . Secondary outcomes included checklist and knowledge examination scores , live-patient success , and qualitative assessment of the curriculum . RESULTS : Participants in the intervention group performed PIV placement more successfully than controls ( 79 % vs 35 % ) and scored significantly higher on the checklist for PIV placement ( 81 % vs 61 % ) and lumbar puncture ( 77 % vs 68 % ) at the initial assessment . There were no differences between groups at month 7 , and both groups demonstrated declining skills . There were no statistically significant differences in success on live-patient procedures . Those in the intervention group scored significantly higher on knowledge examinations . CONCLUSIONS : Participants in the intervention group were more successful performing certain simulated procedures than controls when tested immediately after receiving the curriculum but demonstrated declining skills thereafter . Future efforts must emphasize retraining , and residents must have sufficient opportunities to practice skills learned in a formal curriculum BACKGROUND The Erlangen Active Simulator for Interventional Endoscopy ( EASIE ) was introduced in 1997 for interventional endoscopy training . compactEASIE developed in 1998 is a modified , light-weight version of the original model . Objective evidence of the benefits of training with these models is limited . A r and omized controlled study , therefore , was conducted to compare the effects of intensive 7-month , h and s-on training in hemostatic techniques by using the compactEASIE model ( in addition to clinical endoscopic training ) vs. pure clinical training in endoscopic hemostatic methods . METHODS Thirty-seven fellows in gastroenterology in New York City area training programs were enrolled . Baseline skills were assessed on the simulator for the following techniques : manual skills , injection and electrocoagulation , hemoclip application , and variceal ligation . Twenty-eight fellows were then r and omized into two comparable groups . Those r and omized to Group A received purely clinical training in endoscopic hemostatic techniques at their hospitals . Those in Group B , in addition , were trained by experienced tutors in 3 full-day hemostasis workshops over 7 months . Both groups underwent a final evaluation on the compactEASIE simulator conducted by their tutors and additional evaluators who were blinded to the method of training . Initial and final evaluation scores were compared for each group and between groups . Outcomes of actual clinical hemostatic procedures performed during the study period also were analyzed . RESULTS Ten of 14 fellows r and omized to Group A ( st and ard training ) and 13 of 14 in Group B ( intensive training ) returned for the final evaluation . For Group B , scores for all techniques were significantly improved . In Group A , a significant improvement was noted for variceal ligation alone . CONCLUSIONS compactEASIE simulator training ( 3 sessions over 7 months ) , together with clinical endoscopic training result ed in objective improvement in the performance by fellows of all 4 endoscopic hemostatic techniques , whereas significant improvement was noted for variceal ligation alone for fellows who had st and ard clinical training . In clinical practice , fellows who had intensive simulator/ clinical training had a significantly higher success rate and a nonsignificant reduction in the frequency of occurrence of complications BACKGROUND Skills in gastrointestinal endoscopy mainly depend on experience and practice . Patients upon whom trainees perform their first endoscopic examinations are likely to suffer more discomfort and prolonged procedures . Training on endoscopy simulators may reduce the time required to reach competency in patient endoscopy . PATIENTS AND METHODS Residents in internal medicine without experience of endoscopy were r and omized to a group who trained on a simulator before conventional training ( group S ) or one that received conventional training only ( group C ) before starting upper gastrointestinal endoscopy in patients . After endoscopy , discomfort and pain were evaluated by patients , who were blind to the beginners ' training status . Results in terms of time , technique ( intubation , pyloric passage , J-maneuver ) , and diagnosis of pathological entities were evaluated by experts . RESULTS From 2003 to 2007 , 28 residents were enrolled . Comparing group S with group C in their first ten endoscopic examinations in patients , time taken to reach the duodenum ( 239 seconds ( range 50 - 620 ) vs. 310 seconds ( 110 - 720 ; P < 0.0001 ) and technical accuracy ( P < 0.02 ) were significantly better in group S. Diagnostic accuracy did not differ between the groups . Fourteen residents ( 7 simulator-trained , 7 not simulator-trained ) continued endoscopy training . After 60 endoscopic examinations , investigation time was still shorter in group S. Technical and diagnostic accuracy improved during on-patient training in both groups ; here differences between groups were no longer observable . There were no significant differences in discomfort and pain scores between the groups after 10 and after 60 endoscopies . Discomfort and pain were higher than for endoscopy performed by experts . CONCLUSION This r and omized controlled trial shows that virtual simulator training significantly affects technical accuracy in the early and mid-term stages of endoscopic training . It helps reduce the time needed to reach technical competency , but clinical ly the effect is limited . Simulator training could be useful in an endoscopy training curriculum but can not replace on-patient training This study compared a graduated training programme with that of a traditional teaching method to facilitate the learning of the technique of fibreoptic nasotracheal intubation . Thirty-two anaesthesia trainees were r and omly assigned to two groups . The graduated programme involved : practice on a bronchoscopy teaching model ; exposure of the epiglottis and vocal cords in patients recovering from general anaesthesia ; performance of fibreoptic nasotracheal intubation in awake se date d patients . The traditional programme involved : demonstration ( on a patient ) of one fibreoptic nasotracheal intubation by the instructor ; performance of fibreoptic nasotracheal intubation ( by the trainee ) in awake se date d patients . Nasotracheal intubation was accomplished significantly more often by the trainees in the graduated programme ( 86 out of 96 ( 89.6 % ) v. 64 out of 96 ( 66.5 % ) ( P less than 0.01 ) . The results demonstrate that trainees who undergo a graduated training programme using simulators are initially more successful at awake fibreoptic nasotracheal intubation than those who have learned in the traditional manner , and that the conditions of the investigation were acceptable to the trainees and patients OBJECTIVE To compare the outcomes of the first 50 cordocenteses at mid-gestation performed by operators who either or not received training on an in vitro model earlier . MATERIAL S AND METHODS Our unit keeps a prospect i ve data base on procedure details and outcomes of cordocenteses . We compared 50 consecutive procedures , from the first one onwards , performed by 5 specialists early in their maternal fetal medicine ( MFM ) practice , either systematic ally trained ( study group ) or not ( control group ) on an in vitro cordocentesis training model ( n = 500 procedures ) . This training was introduced at the time point MFM became a formal subspeciality in Thail and . Multiple pregnancies and fetuses with chromosomal or structural abnormalities were excluded . The main outcome measures included mean duration of the procedure , the success and fetal loss rate . RESULTS The average duration in the control group was significantly longer than that in the study group ( 13.2 vs 6.4 min , p < 0.001 ) . Conversely , the success rate was significantly lower ( 94.8 vs 98.8 % , p = 0.011 ) . There were no differences in fetal loss rate . CONCLUSION Systematic training on a cordocentesis model reduces the time required to successfully obtain a fetal cord blood sample Background : Previous studies have indicated that fiberoptic orotracheal intubation ( FOI ) skills can be learned outside the operating room . The purpose of this study was to determine which of two educational interventions allows learners to gain greater capacity for performing the procedure . Methods : Respiratory therapists were r and omly assigned to a low-fidelity or high-fidelity training model group . The low-fidelity group was guided by experts , on a nonanatomic model design ed to refine fiberoptic manipulation skills . The high-fidelity group practice d their skills on a computerized virtual reality bronchoscopy simulator . After training , subjects performed two consecutive FOIs on healthy , anesthetized patients with predicted “ easy ” intubations . Each subject 's FOI was evaluated by blinded examiners , using a vali date d global rating scale and checklist . Success and time were also measured . Results : Data were analyzed using a two-way mixed design analysis of variance . There was no significant difference between the low-fidelity ( n = 14 ) and high-fidelity ( n = 14 ) model groups when compared with the global rating scale , checklist , time , and success at achieving tracheal intubation ( all P = not significant ) . Second attempts in both groups were significantly better than first attempts ( P < 0.001 ) , and there was no interaction between “ fidelity of training model ” and “ first versus second attempt ” scores . Conclusions : There was no added benefit from training on a costly virtual reality model with respect to transfer of FOI skills to intraoperative patient care . Second attempts in both groups were significantly better than first attempts . Low-fidelity models for FOI training outside the operating room are an alternative for programs with budgetary constraints BACKGROUND The Olympus colonoscopy simulator provides a high-fidelity training platform design ed to develop knowledge and skills in colonoscopy . It has the potential to shorten the learning process to competency . OBJECTIVE To investigate the efficacy of the simulator in training novices in colonoscopy by comparing training outcomes from simulator training with those of st and ard patient-based training . DESIGN Multinational , multicenter , single-blind , r and omized , controlled trial . SETTING Four academic endoscopy centers in the United Kingdom , Italy , and The Netherl and s. PARTICIPANTS AND INTERVENTION This study included 36 novice colonoscopists who were r and omized to 16 hours of simulator training ( subjects ) or patient-based training ( controls ) . Participants completed 3 simulator cases before and after training . Three live cases were assessed after training by blinded experts . MAIN OUTCOME MEASUREMENTS Automatically recorded performance metrics for the simulator cases and blinded expert assessment of live cases using Direct Observation of Procedural Skills and Global Score sheets . RESULTS Simulator training significantly improved performance on simulated cases compared with patient-based training . Subjects had higher completion rates ( P=.001 ) and shorter completion times ( P < .001 ) and demonstrated superior technical skill ( reduced simulated pain scores , correct use of abdominal pressure , and loop management ) . On live colonoscopy , there were no significant differences between the 2 groups . LIMITATIONS Assessment tools for live colonoscopies may lack sensitivity to discriminate between the skills of relative novices . CONCLUSION Performance of novices trained on the colonoscopy simulator matched the performance of those with st and ard patient-based colonoscopy training , and novices in the simulator group demonstrated superior technical skills on simulated cases . The simulator should be considered as a tool for developing knowledge and skills prior to clinical practice Increasing attention has been given recently to the method ological issues associated with r and omization of clusters rather than individuals in lifestyle intervention trials . These issues are explored through an empirical study of the ' effective sample size ' imposed by r and omization of three experimental units frequently considered in epidemiological research : the spouse pair , the general practice , and the large geographic area ( county ) . The measurement of within-cluster dependence for a dichotomous outcome variable is also discussed , and a relationship shown between Fleiss 's kappa and Cornfield 's inflation factor BACKGROUND Catheter-related bloodstream infection ( CRBSI ) is a preventable cause of a potentially lethal ICU infection . The optimal method to teach health-care providers correct sterile techniques during central vein catheterization ( CVC ) remains unclear . METHODS We r and omly assigned second- and third-year internal medicine residents trained by a traditional apprenticeship model to simulation-based plus video training or video training alone from December 2007 to January 2008 , with a follow-up period to examine CRBSI ending in July 2009 . During the follow-up period , a simulation-based training program in sterile techniques during CVC was implemented in the medical ICU ( MICU ) . A surgical ICU ( SICU ) where no residents received study interventions was used for comparison . The primary outcome measures were median residents ' scores in sterile techniques and rates of CRBSI per 1,000 catheter-days . RESULTS Of the 47 enrolled residents , 24 were r and omly assigned to the simulation-based plus video training group and 23 to the video training group . Median baseline scores in both groups were equally poor : 12.5 to 13 ( 52%-54 % ) out of maximum score of 24 ( P = .95 ; median difference , 0 ; 95 % CI , 0.2 - 2.0 ) . After training , median score was significantly higher for the simulation-based plus video training group : 22 ( 92 % ) vs 18 ( 75 % ) for the video training group ( P < .001 ; median difference , 4 ; 95 % CI , 3 - 6 ) . During the follow-up period , there was a significantly lower rate of CRBSI in the MICU ( 1.0 per 1,000 catheter-days ) compared with the SICU ( 3.4 per 1,000 catheter-days ) ( P = .03 ) . The incidence rate ratio derived from the Poisson regression ( 0.30 ; 95 % CI , 0.10 - 0.91 ) indicated there was a 70 % reduction in the incidence of CRBSI in the postintervention MICU compared with the preintervention MICU and the postintervention SICU . CONCLUSIONS Simulation-based training in sterile techniques during CVC is superior to traditional training or video training alone and is associated with decreased rate of CRBSI . Simulation-based training in CVC should be routinely used to reduce iatrogenic risk . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT00612131 ; URL : clinical trials.gov A cluster r and omised study is one where a group of subjects are r and omised to the same treatment together — for example , when women in some districts are offered breast cancer screening and compared with women in other districts , or when the patients of general practitioners who have been given special training are compared with the patients of those who have not.1 Several techniques exist for analysing the data from such studies , but the essence of them is that the experimental unit ( district or general practitioner ) is the unit of analysis .2 A simple approach is to construct a summary statistic for each cluster and then analyse these summary values . The idea is similar to the analysis of repeated measurements on the same subject , where we construct a single summary Objectives To compare the effectiveness of training with an airway model simulator versus digital video disc (DVD)-based instruction in placement of double-lumen endotracheal ( DLT ) tubes by anaesthesiologists with limited thoracic experience . Design Single academic centre parallel r and omised controlled trial with computer-generated r and om allocation . Participants Sixty patients undergoing elective thoracic or oesophageal surgeries requiring one-lung ventilation . Twenty-seven non-thoracic anaesthesiologists were r and omised to place a DLT . Intervention DLT placement instruction by an interactive airway simulator or computer-based DVD training . The main outcome measure was successful DLT placement . Results Twenty-seven anaesthesiologists were r and omised to one of the two intervention groups . Sixty consecutive patients were assigned to a r and omised anaesthesiologist ( n = 30 in each group ) . Participants failed to correctly place or position the DLT tubes in 14 of 60 patients ( failure rate of 23 % ) . There was no difference in the probability of satisfactory placement or time for positioning of the DLT between the training groups ; 80.5 % ( 95 % confidence interval 58.2–96.2 % ) of tubes were successfully placed following intubation model simulator training versus 73.6 % ( 95 % confidence interval 49.8–88.5 % ) in the DVD group ( P = 0.378 ) . Conclusion Both teaching methods had similar outcomes for placement of DLTs by anaesthesiologists with limited thoracic anaesthesia experience . Both groups performed better than individuals in our prior study . Therefore , these methods should be considered when training anaesthesiologists to successfully place DLTs |
1,188 | 23,685,095 | Moderate-to-strong evidence was presented for meniscal lesion or meniscectomy , presence of bone marrow lesions ( BMLs ) , time from injury , and persisting altered biomechanics , possibly affecting cartilage change after ACL reconstruction .
First-year morphological change was more aggravated in ACL reconstruction compared to non-surgical treatment . | OBJECTIVE To summarize the current evidence of magnetic resonance imaging (MRI)-measured cartilage adaptations following anterior cruciate ligament ( ACL ) reconstruction and of the potential factors that might influence these changes , including the effect of treatment on the course of cartilage change ( i.e. , surgical vs non-surgical treatment ) . | Objective . To investigate over a 1-year period in dogs that underwent extracapsular stabilization surgery ( ECS ) following anterior cruciate ligament ( ACL ) transection : whether reconstructive surgery could prevent osteoarthritis ( OA ) progression and whether treatment with the bisphosphonate tiludronic acid ( TA ) could improve the chronic evolution of OA structural changes . Methods . ACL transection was performed on dogs on Day 0 and ECS on Day 28 . Dogs were r and omly divided into 2 groups : 15 received placebo and 16 were treated with TA ( 2 mg/kg subcutaneous injection ) on Days 14 , 28 , 56 , and 84 . Magnetic resonance images were acquired on Days −10 , 26 , 91 , 210 , and 357 , and cartilage volume was quantified . At sacrifice ( Day 364 ) , cartilage from femoral condyles and tibial plateaus was macroscopically and histologically evaluated . Expression levels of MMP-1 , -3 , -13 , ADAMTS-4 , -5 , BMP-2 , FGF-2 , IGF-1 , TGF-ß1 , collagen type II , and aggrecan were determined using real-time RT-PCR . Results . The loss of cartilage volume observed after ACL transection stabilized following ECS . Thereafter , a gradual gain occurred , with the cartilage volume loss on the tibial plateaus reduced at Day 91 ( p < 0.02 ) and Day 210 ( p < 0.001 ) in the TA-treated dogs . At sacrifice , TA-treated dogs presented a reduction in the severity of macroscopic ( p = 0.03 for plateaus ) and histologic ( p = 0.07 for plateaus ) cartilage lesions , had a better preserved collagen network , and showed decreased MMP-13 ( p = 0.04 ) , MMP-1 and MMP-3 levels . Conclusion . Our findings indicate that in dogs with ACL transection , ECS greatly prevents development of cartilage volume loss . Treatment with TA provided an additional benefit of reducing the development of OA lesions OBJECTIVES To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament ( ACL ) of volumes of joint fluid ( JF ) , bone marrow lesions ( BMLs ) , and cartilage volume ( VC ) , and cartilage thickness ( ThCcAB ) and cartilage surface area ( AC ) . To identify factors associated with these changes . METHODS Fifty-eight subjects ( mean age 26 years , 16 women ) with an ACL rupture to a previously un-injured knee were followed prospect ively using a 1.5 T MR imager at baseline ( within 5 weeks from injury ) , 3 months , 6 months , and 1 year . Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only . Morphometric data were acquired from computer-assisted segmentation of MR images . Morphometric cartilage change was reported as mean change divided by the st and ard deviation of change ( st and ard response mean , SRM ) . RESULTS JF and BML volumes gradually decreased over the first year , although BML persisted in 62 % of the knees after 1 year . One year after the ACL injury , a reduction of VC , AC and ThCcAB ( SRM -0.440 or greater ) was found in the trochlea femur ( TrF ) , while an increase of VC and ThCcAB was found in the central medial femur ( cMF ) ( SRM greater than 0.477 ) . ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months ( P<0.001 ) , BML volume at 6 months ( P=0.031 ) , VC and ThCcAB in cMF ( P<0.002 ) and decreased cartilage area in TrF ( P=0.010 ) at 12 months . CONCLUSION Following an acute ACL tear , cMF and TrF showed the greatest consistent changes of cartilage morphometry . An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF , compared to knees treated without reconstruction . This may suggest a delayed structural restitution in ACL reconstructed knees Background Bone marrow lesions ( BMLs ) , common osteoarthritis-related magnetic resonance imaging findings , are associated with osteoarthritis progression and pain . However , there are no articles describing the use of 3-dimensional quantitative assessment s to explore the longitudinal relationship between BMLs and hyaline cartilage loss . The purpose of this study was to assess the cross-sectional and longitudinal descriptive characteristics of BMLs with a simple measurement of approximate BML volume , and describe the cross-sectional and longitudinal relationships between BML size and the extent of hyaline cartilage damage . Methods 107 participants with baseline and 24-month follow-up magnetic resonance images from a clinical trial were included with symptomatic knee osteoarthritis . An ' index ' compartment was identified for each knee defined as the tibiofemoral compartment with greater disease severity . Subsequently , each knee was evaluated in four regions : index femur , index tibia , non-index femur , and non-index tibia . Approximate BML volume , the product of three linear measurements , was calculated for each BML within a region . Cartilage parameters in the index tibia and femur were measured based on manual segmentation . Results BML volume changes by region were : index femur ( median [ 95 % confidence interval of the median ] ) 0.1 cm3 ( -0.5 to 0.9 cm3 ) , index tibia 0.5 cm3 ( -0.3 to 1.7 cm3 ) , non-index femur 0.4 cm3 ( -0.2 to 1.6 cm3 ) , and non-index tibia 0.2 cm3 ( -0.1 to 1.2 cm3 ) . Among 44 knees with full thickness cartilage loss , baseline tibia BML volume correlated with baseline tibia full thickness cartilage lesion area ( r = 0.63 , p < 0.002 ) and baseline femur BML volume with longitudinal change in femoral full thickness cartilage lesion area ( r = 0.48 p < 0.002 ) . Conclusions Many regions had no or small longitudinal changes in approximate BML volume but some knees experienced large changes . Baseline BML size was associated to longitudinal changes in area of full thickness cartilage loss One of the primary goals of physiotherapy after anterior cruciate ligament ( ACL ) reconstruction is to restore of the patient 's normal gait patterns . However , to date , only a limited number of studies have examined gait during physiotherapeutic procedures following ACL reconstruction . Thus , the objective of the present study was to evaluate gait kinematics and symmetry in male patients after ACL reconstruction during the first two stages of their physiotherapy programme . Ninety-seven males , including 53 patients after primary ACL reconstruction in one limb and 44 healthy controls , participated in the study . The patients were examined using a movement analysis system during their physiotherapeutic programme ( from the 2nd to the 12th week following reconstruction ) . Some selected parameters of gait kinematics , a dynamic range of movement in the knee joint and gait asymmetry coefficients were evaluated . During the 12th week of physiotherapy , a mean gait velocity increased by more than 0.97 m/s compared to that obtained during the 2nd week of physiotherapy . A statistically significant increase in the relative length of stance phase was observed in the involved extremity , from 36.1 % to 62.7 % ( P = 0.01 ) ; the range of movement significantly improved from 25.8 degrees during the 2nd week to 63.7 degrees during the 12th week of physiotherapy . At the same time , the stance time asymmetry coefficient decreased from 68.5 % to -0.4 % . We observed a significant improvement in most of the gait parameters from the 2nd to the 12th week of physiotherapy after reconstruction and also in comparison to the results obtained for the control group BACKGROUND The optimal management of a torn anterior cruciate ligament ( ACL ) of the knee is unknown . METHODS We conducted a r and omized , controlled trial involving 121 young , active adults with acute ACL injury in which we compared two strategies : structured rehabilitation plus early ACL reconstruction and structured rehabilitation with the option of later ACL reconstruction if needed . The primary outcome was the change from baseline to 2 years in the average score on four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS)--pain , symptoms , function in sports and recreation , and knee-related quality of life ( KOOS(4 ) ; range of scores , 0 [ worst ] to 100 [ best ] ) . Secondary outcomes included results on all five KOOS subscales , the Medical Outcomes Study 36-Item Short-Form Health Survey , and the score on the Tegner Activity Scale . RESULTS Of 62 subjects assigned to rehabilitation plus early ACL reconstruction , 1 did not undergo surgery . Of 59 assigned to rehabilitation plus optional delayed ACL reconstruction , 23 underwent delayed ACL reconstruction ; the other 36 underwent rehabilitation alone . The absolute change in the mean KOOS(4 ) score from baseline to 2 years was 39.2 points for those assigned to rehabilitation plus early ACL reconstruction and 39.4 for those assigned to rehabilitation plus optional delayed reconstruction ( absolute between-group difference , 0.2 points ; 95 % confidence interval , -6.5 to 6.8 ; P=0.96 after adjustment for the baseline score ) . There were no significant differences between the two treatment groups with respect to secondary outcomes . Adverse events were common in both groups . The results were similar when the data were analyzed according to the treatment actually received . CONCLUSIONS In young , active adults with acute ACL tears , a strategy of rehabilitation plus early ACL reconstruction was not superior to a strategy of rehabilitation plus optional delayed ACL reconstruction . The latter strategy substantially reduced the frequency of surgical reconstructions . ( Funded by the Swedish Research Council and the Medical Faculty of Lund University and others ; Current Controlled Trials number , IS RCT N84752559 . OBJECTIVE Prevalence and clinical relevance of patellofemoral ( PF ) osteoarthritis ( OA ) after anterior cruciate ligament ( ACL ) injury . METHOD Prospect ively we studied 94 out of 100 consecutive patients 15 years after acute ACL injury . ACL reconstructions were only performed late if recurrent " give way " persisted or a secondary meniscal injury suitable for repair occurred . The subjects , mean age 42 years , had knee radiographs including skyline PF view taken , which were grade d according to the atlas of the Osteoarthritis Research Society International . Knee-related symptoms and function were assessed by question naires . RESULTS PF OA was present in 12/75 knees ( 16 % ) . Of 94 patients 22 ( 23 % ) have had their ACL reconstructed during follow-up . Meniscal injury and ACL reconstruction had occurred more often in knees with PF OA than in knees without PF OA ( P=0.004 and P=0.002 , respectively ) . Seven of 15 ACL reconstructed knees showed radiographic PF OA at follow-up . Knees with PF OA had more extension and flexion deficit than knees without PF OA . Subjects with PF OA maintained a higher activity level from injury to follow-up , but did not differ significantly from those without PF OA regarding patient-relevant symptoms and knee function . However , there was a trend for worse outcome in subjects with PF OA . CONCLUSION We found a relatively low prevalence of mild PF OA after ACL injury treated non-operatively , and it had limited impact on knee symptoms and patient-relevant knee function . At follow-up PF OA was associated with higher activity level , meniscal injury , extension and flexion deficit , and ACL reconstruction OBJECTIVE To evaluate the effects of a modified shoe that incorporates both lateral wedging and a variable-stiffness sole on knee joint loading in 3 population s : individuals with symptomatic and radiographic knee osteoarthritis ( OA ) , asymptomatic overweight individuals , and asymptomatic healthy weight individuals . METHODS Ninety participants ( 30 per group ) underwent a 3-dimensional gait analysis across 3 test conditions : modified shoes , st and ard control shoes , and barefoot . For each condition , the first peak knee adduction moment ( KAM ) and knee flexion moment ( KFM ) ( both expressed as Nm/[body weight × height]% ) as well as the KAM impulse ( expressed as Nm.s/[body weight × height]% ) were determined . RESULTS The modified shoes significantly reduced the peak KAM as compared to the control shoes in both the OA ( P = 0.002 ) and the overweight ( P = 0.03 ) groups . In the OA group , there was no significant difference in peak KAM when walking in the modified shoe as compared to walking barefoot . In the overweight and the healthy weight groups , the peak KAM when walking in the modified shoe was significantly higher than that when walking barefoot ( P < 0.001 ) . Irrespective of group , the KAM impulse was significantly reduced when walking in the modified shoe as compared to the control shoe ( P < 0.001 ) and was significantly higher during both shoe conditions as compared to walking barefoot ( P < 0.001 ) . There was no change in the KFM between walking conditions for any group . CONCLUSION The findings illustrate that a shoe incorporating both a lateral wedge and a variable-stiffness sole can significantly reduce medial knee joint load . Further research examining the effects of these shoes on pain , function , and structural changes in the joint is warranted 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 A clinical , radiographic , and scintigraphic comparative study was performed on 57 consecutive successful patellar tendon anterior cruciate ligament reconstructions for chronic laxity . Patients were divided into 3 matched groups according to the medial meniscal treatment . Group A included 18 patients with medial meniscal repairs ; Group B , 19 patients with partial medial meniscectomies ; and Group C , 20 patients with normal menisci ( controls ) . The average followup was 55 months . At clinical examination , patients in Group B had more activity-related pain than those in Group C ( p = 0.04 ) . The anteroposterior weight-bearing views in extension showed more degenerative changes in the medial compartment in Group B than in the other 2 groups ( Group A versus B , p = 0.01 ; Group C versus B , p < 0.001 ) . Scintigraphy showed an increased uptake in the operated knee as compared with the normal side ( 11 % ) , but no differences among the 3 study groups . The patients with partial meniscectomies had more pain and degenerative radiographically evident changes than the control group . Medial meniscal repair offers a better chance than partial meniscectomy to preserve the articular cartilage of the medial compartment . Bone homeostasis , as detected by bone scanning , remains slightly altered in successful reconstructions as compared with the opposite normal side OBJECTIVE In this observational longitudinal study we estimate knee joint cartilage glycosaminoglycan ( GAG ) content , in patients with an acute anterior cruciate ligament ( ACL ) injury , with or without a concomitant meniscus injury . METHODS 29 knees ( 19 men/10 women ) were prospect ively examined by repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage ( dGEMRIC ) , approximately 3 weeks and 2.3±1.3 ( range 4.5 ) years after the injury . We estimated the GAG content ( T1Gd ) in the central weight-bearing parts of the medial and lateral femoral cartilage and compared results with a reference cohort ( n=24 ) with normal knees and no history of injury examined by dGEMRIC at one occasion previously . RESULTS The healthy reference group had longer T1Gd values compared with the ACL-injured patients at follow-up both medially : 428±38 vs 363±61ms ( P<0.0001 ) and laterally : 445±41 vs 396±48ms ( P=0.0002 ) . At follow-up T1Gd was lower in meniscectomized patients compared to those without a meniscectomy , both medially ( -84ms , P=0.002 ) and laterally ( -38ms , P=0.05 ) . In the injured group , the medial femoral cartilage showed similar T1Gd at the two dGEMRIC investigations : 357±50 vs 363±61ms ( P=0.57 ) , whereas the lateral femoral cartilage T1Gd increased : 374±48 vs 396±48ms ( P=0.04 ) . CONCLUSIONS The general decrease in cartilage T1Gd in ACL-injured patients compared with references provide evidence for structural matrix GAG changes that seem more pronounced if a concomitant meniscal injury is present . The fact that post-traumatic OA commonly develops in ACL-injured patients , in particularly those with meniscectomy , suggests that shorter T1Gd may be an early biomarker for OA OBJECTIVES To examine the effects of 2 gait retraining protocol s on the gait patterns of patients with bone-patellar tendon-bone anterior cruciate ligament ( ACL ) reconstruction . DESIGN R and omized control , repeated- measures design . SETTING Private orthopedic center and research facility . PARTICIPANTS Sixteen patients with bone-patellar tendon-bone ACL reconstruction , r and omly subdivided into 2 groups ( group 1 , n=8 ; group 2 , n=8 ) , and a healthy control group of 8 subjects . INTERVENTION The 16 subjects with ACL reconstruction were r and omly assigned to 2 different gait retraining protocol s over a 6-week training interval : ( 1 ) . a protocol using a predicted stride frequency calculated from the resonant frequency of a force-driven harmonic oscillator ( FDHO ) model or ( 2 ) . a protocol using the preferred stride frequency ( PSF ) . MAIN OUTCOME MEASURES Gait analyses examining the lower-extremity kinematic , kinetic , and energetic gait patterns of each group . RESULTS Gait retraining with the FDHO model showed improvements in lower-extremity positions , hip and knee extensor angular impulse , and work parameters . Gait retraining with the PSF demonstrated no statistical improvements . The FDHO training protocol facilitated a greater midstance knee range of motion ( ROM ) and greater rates of improvement for midstance ROM , hip extensor angular impulse , and concentric hip extensor work . CONCLUSIONS Gait retraining with the resonant frequency of an FDHO model facilitated a greater recovery of gait function compared with training with the PSF OBJECTIVE To evaluate the effects of moderate exercise on glycosaminoglycan ( GAG ) content in knee cartilage in subjects at high risk of knee osteoarthritis ( OA ) . METHODS Forty-five subjects ( 16 women , mean age 46 years , mean body mass index 26.6 kg/m(2 ) ) who underwent partial medial meniscus resection 3 - 5 years previously were r and omized to undergo a regimen of supervised exercise 3 times weekly for 4 months or to a nonintervention control group . Cartilage GAG content , an important aspect of the biomechanical properties of cartilage , was estimated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage ( dGEMRIC ) , with results expressed as the change in the T1 relaxation time in the presence of Gd-DTPA ( T1[Gd ] ) . RESULTS Thirty of 45 patients were examined by dGEMRIC at baseline and followup . The exercise group ( n = 16 ) showed an improvement in the T1(Gd ) compared with the control group ( n = 14 ) ( 15 msec versus -15 msec ; P = 0.036 ) . To study the dose response , change in the T1(Gd ) was assessed for correlation with self-reported change in physical activity level , and a strong correlation was found in the exercise group ( n = 16 , r(S ) = 0.70 , 95 % confidence interval [ 95 % CI ] 0.31 - 0.89 ) and in the pooled group of all subjects ( n = 30 , r(S ) = 0.74 , 95 % CI 0.52 - 0.87 ) . CONCLUSION This in vivo cartilage monitoring study in patients at risk of knee OA who begin exercising indicates that adult human articular cartilage has a potential to adapt to loading change . Moderate exercise may be a good treatment not only to improve joint symptoms and function , but also to improve the knee cartilage GAG content in patients at high risk of developing OA PURPOSE To determine the frequency of degenerative knee morphologic abnormalities in asymptomatic individuals by using 3-T magnetic resonance ( MR ) imaging and to investigate the characteristics and evolution of cartilage T2 values in relation to morphologic abnormalities with a longitudinal study . MATERIAL S AND METHODS The study was approved by the institutional review board and was compliant with HIPAA . Ninety-five asymptomatic subjects aged 45 - 78 years who were free of risk factors for osteoarthritis ( OA ) were selected from the Osteoarthritis Initiative normal control cohort and examined with radiography and 3-T MR imaging . Data obtained at both baseline and 2-year follow-up were analyzed . OA-related knee abnormalities were analyzed by using the whole-organ MR imaging score ( WORMS ) . Cartilage T2 maps were generated by using sagittal two-dimensional multiecho spin-echo images of the right knee . Statistical significance was determined with the Student t test , the paired t test , a mixed r and om effects model , one-way analysis of variance , and a multiple linear regression model . RESULTS Knee abnormalities were identified with a high frequency ( 90 % at baseline and 92 % at 2-year follow-up ) . The prevalence of hyaline cartilage lesions was particularly high ( 86 % at baseline and 84 % at follow-up ) . A significant longitudinal increase in T2 was detected in the tibiofemoral cartilage but not the patellofemoral cartilage ( P = .0072 ) . The longitudinal change in T2 was significantly associated with worsening of the cartilage WORMS ( P = .038 ) . CONCLUSION Asymptomatic subjects have a high frequency of OA-related morphologic abnormalities . A significant increase in tibiofemoral cartilage T2 was detected over the 2-year period . A greater increase in T2 was associated with increased progression of cartilage morphologic abnormalities |
1,189 | 27,791,223 | Strong recommendations in favor of multicomponent interventions to prevent delirium , in surgical or medicals wards , were formulated .
In the latter case the evidence applied to older patients at intermediate - high risk of developing delirium .
Weak recommendations , to prevent delirium , were formulated for multicomponent interventions provided by family members ( medical ward ) , staff education ( medical ward ) , ear plugs ( intensive care unit ) , reorientation protocol ( intensive care unit ) , and the use of a software to perform drug review .
Weak recommendations were provided for the use of multicomponent interventions to prevent delirium in medical wards in patients not selected according to the risk of delirium .
Strong recommendations not to use bright light therapy to prevent delirium in intensive care unit setting s were articulated .
Moreover , weak recommendations were provided for the use of multicomponent interventions to treat delirium of older patients ( medical wards ) .
Conclusions Overall , the panel developed 12 recommendations for the delivery of non-pharmacological interventions to older patients at risk of developing or , with delirium | DescriptionThe ONTOP project aims to undertake a literature search of systematic review s concerning evidence -based non-pharmacological interventions of prevalent medical conditions affecting older people , including delirium .
Objectives To develop explicit and transparent recommendations for nonpharmacological interventions in older subjects at risk of developing delirium , as well as in older subjects with delirium , based on the Grading of Recommendations , Assessment , Development and Evaluation ( GRADE ) approach to rating the quality of evidence and the strength of recommendations . | Introduction This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium . Two research questions were formulated . First , does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU ? Second , does the use of earplugs during the night improve the quality of sleep in the ICU ? Methods A r and omized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night . The research ers were blinded during data collection . Assignment was performed by an independent nurse research er using a computer program . Eligible patients had an expected length of stay in the ICU of more than 24 hours , were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10 . Delirium was assessed using the vali date d NEECHAM scale , sleep perception was reported by the patient in response to five questions . Results The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients . A vast improvement was shown by a Hazard Ratio of 0.47 ( 95 % confidence interval ( CI ) 0.27 to 0.82 ) . Also , patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs . After the first night in the ICU , patients sleeping with earplugs reported a better sleep perception . Conclusions Earplugs may be a useful instrument in the prevention of confusion or delirium . The beneficial effects seem to be strongest within 48 hours after admission . The relation between sleep , sound and delirium , however , needs further research .Trial registration Current Controlled Trials IS RCT OBJECTIVE To develop and vali date a new st and ardized confusion assessment method ( CAM ) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk setting s. DESIGN Prospect i ve validation study . SETTING Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University ( site 1 ) and in general medicine wards at the University of Chicago ( site 2 ) . PATIENTS The study included 56 subjects , ranging in age from 65 to 98 years . At site 1 , 10 patients with and 20 without delirium participated ; at site 2 , 16 patients with and 10 without delirium participated . MEASUREMENTS AND MAIN RESULTS An expert panel developed the CAM through a consensus building process . The CAM instrument , which can be completed in less than 5 minutes , consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders ( DSM-III-R ) . An a priori hypothesis was established for the diagnostic value of four criteria : acute onset and fluctuating course , inattention , disorganized thinking , and altered level of consciousness . The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion . At both sites , the diagnoses made by the CAM were concurrently vali date d against the diagnoses made by psychiatrists . At sites 1 and 2 values for sensitivity were 100 % and 94 % , respectively ; values for specificity were 95 % and 90 % ; values for positive predictive accuracy were 91 % and 94 % ; and values for negative predictive accuracy were 100 % and 90 % . The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium . The CAM was shown to have convergent agreement with four other mental status tests , including the Mini-Mental State Examination . The interobserver reliability of the CAM was high ( kappa = 0.81 - 1.0 ) . CONCLUSIONS The CAM is sensitive , specific , reliable , and easy to use for identification of delirium Background : Major depression is a frequent and serious disorder in older medical in patients . Because the condition goes undetected and untreated in most of these patients , we conducted a r and omized clinical trial to evaluate the effectiveness of a strategy of systematic detection and multidisciplinary treatment of depression in this population . Methods : Consecutive patients aged 65 years or more admitted to general medical services in a primary care hospital between October 1999 and November 2002 were screened for depression with the Diagnostic Interview Schedule ( DIS ) within 48 hours after admission . Patients found to have major depression were r and omly allocated to receive the intervention or usual care . The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient 's family physician . Research assistants , blind to group allocation , collected data from the patients at enrolment and at 3 and 6 months later using the Hamilton Depression Rating Scale ( HAMD ) , the Medical Outcomes 36-item Short Form ( SF-36 ) , the DIS , the Mini-Mental State Examination ( MMSE ) , the Older Americans Re sources and Services ( OARS ) question naire to assess basic and instrumental activities of daily living ( OARS-ADL and OARS-IADL ) and the Rating Scale for Side Effects . Data on the severity of illness , length of hospital stay , health services and medication use , mortality and process of care were also collected . The primary outcome measures were the HAMD and SF-36 . Results : Of 1500 eligible patients who were screened , 157 were found to have major depression and consented to participate ( 78 in the intervention group and 79 in the usual care group ) . At r and omization , there were no clinical ly or statistically significant differences between the 2 groups . Sixty-four patients completed follow-up to 6 months , 57 withdrew , and 36 died . At 6 months , there were no clinical ly or statistically significant differences the 2 groups in HAMD or SF-36 scores or any of the secondary outcome measures . Interpretation : We were unable to demonstrate that systematic detection and multidisciplinary care of depression was more beneficial than usual care for elderly medical in patients BACKGROUND delirium is a frequent adverse consequence of hospitalisation for older patients , but there has been little research into its prevention . A recent study of Hospital in the Home ( admission substitution ) noted less delirium in the home-treated group . SETTING a tertiary referral teaching hospital in Sydney , Australia . METHODS we r and omised 104 consecutive patients referred for geriatric rehabilitation to be treated in one of two ways , either in Hospital in the Home ( early discharge ) or in hospital , in a rehabilitation ward . We compared the occurrence of delirium measured by the confusion assessment method . Secondary outcome measures were length of stay , hospital bed days , cost of acute care and rehabilitation , functional independence measure ( FIM ) , Mini-Mental State Examination ( MMSE ) and geriatric depression score ( GDS ) assessed on discharge and at 1- and 6-month follow-up and patient satisfaction . RESULTS the home group had lower odds of developing delirium during rehabilitation [ odds ratio ( OR ) = 0.17 ; 95 % confidence interval 0.03 - 0.65 ] , shorter duration of rehabilitation ( 15.97 versus 23.09 days ; P = 0.0164 ) and used less hospital bed days ( 20.31 versus 40.09 , P < or = 0.0001 ) . The cost was lower for the acute plus rehabilitation phases ( 7,680 pounds versus 10,598 pounds ; P = 0.0109 ) and the rehabilitation phase alone ( 2,523 pounds versus 6,100 pounds ; P < or = 0.0001 ) . There was no difference in FIM , MMSE or GDS scores . the home group was more satisfied ( P = 0.0057 ) . CONCLUSIONS home rehabilitation for frail elderly after acute hospitalisation is a viable option for selected patients and is associated with a lower risk of delirium , greater patient satisfaction , lower cost and more efficient hospital bed use The purpose of this r and omized controlled study was to determine the effects of music listening on acute confusion that is common in older adults after hip or knee surgery . A control group demonstrated greater decreases in cognition on the first postoperative day compared to a music-listening group ( F = 8.448 , p = .009 ) . In the 3-day postoperative period , the cognitive status of the control group improved ; on the third postoperative day , there was no significant difference between the two groups ( F = 3.52 , p = .075 ) . The music-listening group had higher scores on the NEECHAM Acute Confusion Scale across the 3-day postoperative period ( F = 7.28 , p = .014 ) OBJECTIVES Delirium ( or acute confusional state ) affects 35 % to 65 % of patients after hip-fracture repair , and has been independently associated with poor functional recovery . We performed a r and omized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture . DESIGN Prospect i ve , r and omized , blinded . SETTING Inpatient academic tertiary medical center . PARTICIPANTS 126 consenting patients 65 and older ( mean age 79 + /- 8 years , 79 % women ) admitted emergently for surgical repair of hip fracture . MEASUREMENTS Detailed assessment through interviews with patients and design ated proxies and review of medical records was performed at enrollment to ascertain prefracture status . Subjects were then r and omized to proactive geriatrics consultation , which began preoperatively or within 24 hours of surgery , or " usual care . " A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol . To ascertain study outcomes , all subjects underwent daily , blinded interviews for the duration of their hospitalization , including the Mini-Mental State Examination ( MMSE ) , the Delirium Symptom Interview ( DSI ) , and the Memorial Delirium Assessment Scale ( MDAS ) . Delirium was diagnosed using the Confusion Assessment Method ( CAM ) algorithm . RESULTS The 62 patients r and omized to geriatrics consultation were not significantly different ( P>.1 ) from the 64 usual-care patients in terms of age , gender , prefracture dementia , comorbidity , type of hip fracture , or type of surgical repair . Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively . A mean of 10 recommendations were made throughout the duration of the hospitalization , with 77 % adherence by the orthopedics team . Delirium occurred in 20 /62 ( 32 % ) intervention patients , versus 32 / 64 ( 50 % ) usual-care patients ( P = .04 ) , representing a relative risk of 0.64 ( 95 % confidence interval ( CI ) = 0.37 - 0.98 ) for the consultation group . One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group . There was an even greater reduction in cases of severe delirium , occurring in 7/ 60 ( 12 % ) of intervention patients and 18 / 62 ( 29 % ) of usual-care patients , with a relative risk of 0.40 ( 95 % CI = 0.18 - 0.89 ) . Despite this reduction in delirium , length of stay did not significantly differ between intervention and usual-care groups ( median + /- interquartile range = 5 + /- 2 days in both groups ) , likely because protocol s and pathways predetermined length of stay . In subgroup analyses , geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living ( ADL ) functional impairment . CONCLUSIONS Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair . Geriatrics consultation reduced delirium by over one-third , and reduced severe delirium by over one-half . Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients BACKGROUND delirium is a clinical syndrome associated with multiple short and long-term complications and therefore prevention is an essential part of its management . This study was design ed to assess the efficacy of multicomponent intervention in delirium prevention . METHODS a total of 287 hospitalised patients at intermediate or high risk of developing delirium were r and omised to receive a non-pharmacological intervention delivered by family members ( 144 patients ) or st and ard management ( 143 patients ) . The primary efficacy outcome was the occurrence of delirium at any time during the course of hospitalisation . Three vali date d observers performed the event adjudication by using the confusion assessment method screening instrument . RESULTS there were no significant differences in the baseline characteristics between the two groups . The primary outcome occurred in 5.6 % of the patients in the intervention group and in 13.3 % of the patients in the control group ( relative risk : 0.41 ; confidence interval : 0.19 - 0.92 ; P = 0.027 ) . CONCLUSION the results of this study show that there is a benefit in the non-pharmacological prevention of delirium using family members , when compared with st and ard management of patients at risk of developing this condition BACKGROUND Delirium is a common syndrome with poor prognosis affecting elderly in patients . Treatment is mainly based on common sense with wide variations in practice . We investigated whether intensified , multicomponent geriatric treatment could improve the prognosis of delirious patients . METHODS We performed a r and omized , controlled trial of 174 patients with delirium in six general medicine units from an acute hospital in Helsinki , Finl and . The intervention group received individually tailored geriatric treatment . The primary endpoint was the sum of those deceased individuals and the patients permanently institutionalized . Secondary endpoints included the number of days in hospitals and other institutions , delirium intensity , and cognition . RESULTS The mean age of patients was 83 years , and 31 % had previous dementia . The intervention group ( N = 87 ) received significantly more acetylcholinesterase inhibitors ( 58.6 % vs 9.2 % ) , atypical antipsychotics ( 69.8 % vs 30.2 % ) , specialist consultations ( 49.4 % vs 28.7 % ) , hip protectors ( 88.5 % vs 3.4 % ) , physiotherapy ( 87.4 % vs 47.1 % ) , and fewer conventional neuroleptics ( 8.0 % vs 23.0 % ) than did the control group ( N = 87 ) . During the 1-year follow-up , 60.9 % of the intervention group and 64.4 % of controls were either deceased or permanently institutionalized ( p = .638 ) . The intervention group spent a mean of 126 days in institutions , and the control group 140 days ( p = .688 ) . Delirium was , however , alleviated more rapidly during hospitalization , and cognition improved significantly at 6 months in the intervention group . CONCLUSIONS Faster alleviation of delirium and improved cognition justify good , comprehensive geriatric care for these patients although treatment produced no significant improvements in hard endpoints of prognosis BACKGROUND older people undergoing elective surgery have significant post-operative problems prolonging hospitalisation . OBJECTIVE to design , embed , and evaluate an evidence -based comprehensive geriatric assessment ( CGA ) service for at-risk older patients undergoing elective surgery . SETTING urban teaching hospital . SUBJECTS elective surgical patients aged 65 + . INTERVENTION multidisciplinary preoperative CGA service with post-operative follow-through ( proactive care of older people undergoing surgery [ ' POPS ' ] ) . METHODS observational cohort study and multilevel surveys ( development and modelling phase ) . Prospect i ve ' before and after ' comparison ( exploratory evaluation ) . RESULTS findings from the development phase showed high levels of preoperative co-morbidity , no multidisciplinary preoperative input , and multiple potentially preventable post-operative problems delaying discharge in older elective surgery patients . Comparison of 2 cohorts of elective orthopaedic patients ( pre-POPS vs POPS , N = 54 ) showed the POPS group had fewer post-operative medical complications including pneumonia ( 20 % vs 4 % [ p = 0.008 ] ) and delirium ( 19 % vs 6 % [ p = 0.036 ] ) , and significant improvements in areas reflecting multidisciplinary practice including pressure sores ( 19 % vs 4 % [ p = 0.028 ] ) , poor pain control ( 30 % vs 2 % [ p<0.001 ] ) , delayed mobilisation ( 28 % vs 9 % [ p = 0.012 ] ) and inappropriate catheter use ( 20 % vs 7 % [ p = 0.046 ] ) . Length of stay was reduced by 4.5 days . There were fewer delayed discharges relating to medical complications ( 37 % vs 13 % ) or waits for OT assessment or equipment ( 20 % vs 4 % ) . CONCLUSION a proactive evidence -based CGA service for at-risk older elective surgical patients was developed according to MRC framework for complex interventions . Pre/post comparison in elective orthopaedic patients showed improved ( within method ological limitations ) post-operative outcomes indicative of better clinical effectiveness and efficiency , and contributed to the service obtaining mainstream funding . Informed by the present study , a r and omised controlled trial is ongoing Objectives To develop and vali date a simple clinical prediction rule , based on variables easily measurable at admission , to identify patients at high risk of developing delirium during their hospital stay on an internal medicine ward . Design Prospect i ve study of two cohorts of patients admitted between 1 May and 30 June 2008 ( derivation cohort ) , and between 1 May and 30 June 2009 ( validation cohort ) . Setting A tertiary hospital in Donostia-Gipuzkoa ( Spain ) . Participants In total 397 patients participated in the study . The mean age and incidence of delirium were 75.9 years and 13 % , respectively , in the derivation cohort , and 75.8 years and 25 % in the validation cohort . Main outcome measures The predictive variables analysed and finally included in the rule were : being aged 85 years old or older , being dependent in five or more activities of daily living , and taking two or more psychotropic drugs ( antipsychotics , benzodiazepines , antidepressants , anticonvulsant and /or antidementia drugs ) . The variable of interest was delirium as defined by the short Confusion Assessment Method , which assesses four characteristics : acute onset and fluctuating course , inattention , disorganised thinking and altered level of consciousness . Results We developed a rule in which the individual risk of delirium is obtained by adding one point for each criterion met ( age≥85 , high level of dependence , and being on psychotropic medication ) . The result is considered positive if the score is ≥1 . The rule accuracy was : sensitivity=93.4 % ( 95 % CI 85.5 % to 97.2 % ) , specificity=60.6 % ( 95 % CI 54.1 % to 66.8 % ) , positive predictive value=44.4 % ( 95 % CI 36.9 % to 52.1 % ) and negative predictive value=96.5 % ( 95 % CI : 92 % to 98.5 % ) . The area under the receiver operator characteristic ( ROC ) curve was 0.85 for the validation cohort . Conclusions The presence or absence of any of the three predictive factors ( age≥85 , high level of dependence and psychotropic medication ) allowed us to classify patients on internal medicine wards according to the risk of developing delirium . The simplicity of the variables in our clinical prediction rule means that the data collection required is feasible in busy medicine units The purpose of this study was to examine the effects of music listening in older adults following hip or knee surgery . Acute confusion and pain after surgery can increase length of stay and reduce function . Study results demonstrate a reduction in acute confusion and pain and improved ambulation and higher satisfaction scores in older adults who listened to music Background and aims : Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs . We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures . Methods : One hundred and ninety-nine patients , aged 70 years and over ( mean age±SD , 82±6 , 74 % women ) , were r and omly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward . The intervention consisted of staff education focusing on the assessment , prevention and treatment of delirium and associated complications . The staff worked as a team , applying comprehensive geriatric assessment , management and rehabilitation . Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale , and delirium was diagnosed according to DSM-IV criteria . Results : The number of days of postoperative delirium among intervention patients was fewer ( 5.0±7.1 days vs 10.2±13.3 days , p=0.009 ) compared with controls . A lower proportion of intervention patients were delirious postoperatively than controls ( 56/102 , 54.9 % vs 73/97 , 75.3 % , p=0.003 ) . Eighteen percent in the intervention ward and 52 % of controls were delirious after the seventh postoperative day ( p<0.001 ) . Intervention patients suffered from fewer complications , such as decubitus ulcers , urinary tract infections , nutritional complications , sleeping problems and falls , than controls . Total postoperative hospitalization was shorter in the intervention ward ( 28.0±17.9 days vs 38.0±40.6 days , p=0.028 ) . Conclusions : Patients with postoperative delirium can be successfully treated , result ing in fewer days of delirium , fewer other complications , and shorter length of hospitalization This study was undertaken to determine the effect of music on elders undergoing elective hip and knee surgery who experience acute confusion and delirium postoperatively . Postoperative confusion and delirium in elders often cause complications that negatively effect recovery . Music listening was introduced as an intervention to an experimental group . Nurses documented episodes of acute confusion and delirium experienced by elders postsurgically . Scores from a readiness-to-ambulate profile to determine if patients were cognitively ready for postoperative therapy were evaluated . There was a significant decrease in the number of episodes of postoperative confusion among those in the experimental group compared with those in the non-listening control group . In addition , the experimental group had significantly higher scores on the readiness-to-ambulate profile than the control group . These findings indicate that music listening is an effective nursing intervention that can be used to decrease acute postoperative confusion and delirium in elders undergoing elective hip and knee surgery OBJECTIVES To investigate whether an education program and a reorganization of nursing and medical care improved the outcome for older delirious patients . DESIGN Prospect i ve intervention study . SETTING Department of General Internal Medicine , Sundsvall Hospital , Sweden . PARTICIPANTS Four hundred patients , aged 70 and older , consecutively admitted to an intervention or a control ward . INTERVENTION The intervention consisted of staff education focusing on the assessment , prevention , and treatment of delirium and on caregiver-patient interaction . Reorganization from a task-allocation care system to a patient-allocation system with individualized care . MEASUREMENTS The patients were assessed using the Organic Brain Syndrome Scale and the Mini-Mental State Examination on Days 1 , 3 , and 7 after admission . Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS Delirium was equally common on the day of admission at the two wards , but fewer patients remained delirious on Day 7 on the intervention ward ( n=19/63 , 30.2 % vs 37/62 , 59.7 % , P=.001 ) . The mean length of hospital stay+/-st and ard deviation was significantly lower on the intervention ward then on the control ward ( 9.4+/-8.2 vs 13.4+/-12.3 days , P<.001 ) especially for the delirious patients ( 10.8+/-8.3 vs 20.5+/-17.2 days , P<.001 ) . Two delirious patients in the intervention ward and nine in the control ward died during hospitalization ( P=.03 ) . CONCLUSION This study shows that a multifactorial intervention program reduces the duration of delirium , length of hospital stay , and mortality in delirious patients Objective 1 ) To confirm that vitamin D deficiency , defined as serum 25-hydroxyvitamin D ( 25OHD ) concentration < 25nmol/L , was associated with long length-of-stay ( LOS ) among older in patients admitted to geriatric acute care unit ; and 2 ) to examine which combination of risk factors of longer LOS including vitamin D deficiency best predicted longer LOS . Study design and setting Based on a prospect i ve cohort study with a 25-day follow-up on average , 531 consecutive older in patients ( mean age 85.0±7.2 years , 59.1 % women ) admitted to the geriatric acute care unit of Angers University Hospital , France , were included . Results Linear regression models showed that male gender ( P<0.025 ) , delirium ( P<0.015 ) and vitamin D deficiency ( P<0.001 ) were independently associated with a longer LOS . The highest risk of a longer LOS was shown while combining vitamin D deficiency with male gender ( Odds ratio (OR)=3.70 with P<0.001 ) . The risk increased significantly while delirium was associated with these two baseline characteristics ( OR=4.76 with P=0.001 ) . Kaplan-Meier distributions of discharge differed significantly between participants who had or not the combination of the 3 criteria ( P<0.007 ) . Conclusions Vitamin D deficiency , delirium and male gender were significant risk factors for a longer LOS in the studied sample of older in patients BACKGROUND The effects of residence in an acute geriatrics-based ward ( AGW ) with emphasis on early rehabilitation and discharge planning for older patients with acute medical illnesses were assessed . Outcome and use of re sources were compared with those of patients treated in general medical wards ( MWs ) . A per- protocol rather than intention-to-treat analysis was performed . METHODS A r and omized trial with 3-months follow-up . A total of 190 patients aged 70 years and older were r and omized to an acute geriatrics-based ward , and 223 patients were r and omized to general medical wards . RESULTS The two groups were comparable at inclusion . However , after care in the AGW , 71 % of patients could be discharged directly home compared with 64 % of those treated in MWs ( relative risk 1.17 ; 95 % CI , 0.93 - 1.49 ) . The length of stay was shorter in the AGW ( mean 5.9 vs 7.3 days ; P = .002 ) . The proportion of patients in geriatric or other hospital wards or in nursing homes did not differ , but the proportion of AGW patients in sheltered living tended to be lower ( P = .085 ) . At the follow-up , case fatality , ADL function , psychological well-being , need for daily personal assistance , drug consumption , need for readmission to hospital , and total health care costs after discharge did not differ between the two groups . Poor global outcome was observed in 37 % of AGW and 34 % of MW patients . CONCLUSIONS A geriatric approach with greater emphasis on early rehabilitation and discharge planning in the AGW shortened the length of hospital stay and may have reduced the need for long-term institutional living . This occurred despite patients in an acute geriatric ward not having better medical or functional outcome than older acute patients treated in general medical wards BACKGROUND A wide variability in the approach towards delirium prevention and treatment in the critically ill results from the dearth of prospect i ve r and omised studies . METHODS We launched a two-stage prospect i ve observational study to assess delirium epidemiology , risk factors and impact on patient outcome , by enrolling all patients admitted to our Intensive Care Unit ( ICU ) over a year . The first step - from January to June 2008 was the observational phase , whereas the second one from July to December 2008 was interventional . All the patients admitted to our ICU were recruited but those with pre-existing cognitive disorders , dementia , psychosis and disability after stroke were excluded from the data analysis . Delirium assessment was performed according with Confusion Assessment Method for the ICU twice per day after sedation interruption . During phase 2 , patients underwent both a re-orientation strategy and environmental , acoustic and visual stimulation . RESULTS We admitted a total of respectively 170 ( I-ph ) and 144 patients ( II-ph ) . The delirium occurrence was significantly lower in ( II-ph ) 22 % vs. 35 % in ( I-ph ) ( P=0.020 ) . A Cox 's Proportional Hazard model found the applied reorientation strategy as the strongest protective predictors of delirium : ( HR 0.504 , 95 % C.I. 0.313 - 0.890 , P=0.034 ) , whereas age ( HR 1.034 , 95 % CI : 1.013 - 1.056 , P=0.001 ) and sedation with midazolam plus opiate ( HR 2.145 , 95 % CI : 2.247 - 4.032 , P=0.018 ) were negative predictors . CONCLUSION A timely reorientation strategy seems to be correlated with significantly lower occurrence of delirium 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 OBJECTIVES To determine the extent to which the use of a clinical informatics tool that implements prospect i ve monitoring plans reduces the incidence of potential delirium , falls , hospitalizations potentially due to adverse drug events , and mortality . DESIGN R and omized cluster trial . SETTING Twenty-five nursing homes serviced by two long-term care pharmacies . PARTICIPANTS Residents living in nursing homes during 2003 ( 1,711 in 12 intervention ; 1,491 in 13 usual care ) and 2004 ( 1,769 in 12 intervention ; 1,552 in 13 usual care ) . INTERVENTION The pharmacy automatically generated Geriatric Risk Assessment MedGuide ( GRAM ) reports and automated monitoring plans for falls and delirium within 24 hours of admission or as part of the normal time frame of federally m and ated drug regimen review . MEASUREMENTS Incidence of potential delirium , falls , hospitalizations potentially due to adverse drug events , and mortality . RESULTS GRAM triggered monitoring plans for 491 residents . Newly admitted residents in the intervention homes experienced a lower rate of potential delirium onset than those in usual care homes ( adjusted hazard ratio (HR)=0.42 , 95 % confidence interval (CI)=0.35 - 0.52 ) , overall hospitalization ( adjusted HR=0.89 , 95 % CI=0.72 - 1.09 ) , and mortality ( adjusted HR=0.88 , 95 % CI=0.66 - 1.16 ) . In longer stay residents , the effects of the intervention were attenuated , and all estimates included unity . CONCLUSION Using health information technology in long-term care pharmacies to identify residents who might benefit from the implementation of prospect i ve medication monitoring care plans when complex medication regimens carry potential risks for falls and delirium may reduce adverse effects associated with appropriate medication use OBJECTIVES To develop and test the effect of a nurse-led interdisciplinary intervention program for delirium on the incidence and course ( severity and duration ) of delirium , cognitive functioning , functional rehabilitation , mortality , and length of stay in older hip-fracture patients . DESIGN Longitudinal prospect i ve before/after design ( sequential design ) . SETTING The emergency room and two traumatological units of an academic medical center located in an urban area in Belgium . PARTICIPANTS 60 patients in an intervention cohort ( 81.7 % females , median age = 82 , interquartile range ( IQR ) = 13 ) and another 60 patients in a usual care/nonintervention cohort ( 80 % females , median age = 80 , IQR = 12 ) . INTERVENTION ( 1 ) Education of nursing staff , ( 2 ) systematic cognitive screening , ( 3 ) consultative services by a delirium re source nurse , a geriatric nurse specialist , or a psychogeriatrician , and ( 4 ) use of a scheduled pain protocol . MEASUREMENTS All patients were monitored for signs of delirium , as measured by the Confusion Assessment Method ( CAM ) . Severity of delirium was assessed using a variant of the CAM . Cognitive and functional status were measured by the Mini-Mental State Examination ( MMSE ) ( including subscales of memory , linguistic ability , concentration , and psychomotor executive skills ) and the Katz Index of activities of daily living ( ADLs ) , respectively . RESULTS Although there was no significant effect on the incidence of delirium ( 23.3 % in the control vs 20.0 % in the intervention cohort ; P = .82 ) , duration of delirium was shorter ( P = .03 ) and severity of delirium was less ( P = .0049 ) in the intervention cohort . Further , clinical ly higher cognitive functioning was observed for the delirious patients in the intervention cohort compared with the nonintervention cohort . Additionally , a trend toward decreased length of stay postoperatively was noted for the delirious patients in the intervention cohort . Despite these positive intervention effects , no effect on ADL rehabilitation was found . Results for risk of mortality were inconclusive . CONCLUSIONS This study demonstrated the beneficial effects of an intervention program focusing on early recognition and treatment of delirium in older hip-fracture patients and confirms the reversibility of the syndrome in view of the delirium 's duration and severity Bright light therapy is a method of maintaining or restoring the natural circadian rhythm by assisting daytime awakening using bright lights . Postoperative delirium is one of the potential complications encountered by patients receiving postoperative care in the intensive care unit ( ICU ) , but there have been no studies on the use of light for the prevention of postoperative delirium . The objective of this study was to examine whether the circadian rhythms of patients after surgery for oesophageal cancer can be adjusted and whether the postoperative delirium crisis rate can be reduced by bright light therapy . The subjects were 11 patients operated on for oesophageal cancer in Osaka University Hospital . After informed consent was obtained , they were divided into a study group and a control group by a r and om sampling method . After removal of the endotracheal tube , the study group was exposed to light . The light intensity was about 5000lx immediately before the eyes , and the distance from the light source was about 100 cm . The control group was placed in a natural lighting environment after extubation . In both groups , the rhythms of physical activities and autonomic activities were monitored after surgery , and delirium was evaluated . A significant difference was observed in the delirium score between the study group and control group on the morning of day 3 of bright light therapy by the Mann-Whitney U-test ( P=0.014 ) . The study group could begin ambulation about 2 days earlier than the control group . Bright light therapy may reduce the rate of postoperative delirium and make early ambulation possible . However , our study involved a very small sample size . We want to increase the sample in the future after having review ed clinical application methods OBJECTIVES To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients . DESIGN Controlled study comparing an intervention in a geriatric unit ( GI ) with usual care in two internal medicine services ( UC ) . SETTING University hospital in Madrid , Spain . PARTICIPANTS Five hundred forty-two consecutive patients ( 170 GI , 372 UC ) , aged 70 and older , with any of the risk criteria for delirium ( cognitive impairment , visual impairment , acute disease severity , dehydration ) . INTERVENTION Educational measures and specific actions in seven risk areas ( orientation , sensory impairment , sleep , mobilization , hydration , nutrition , drug use ) . Daily monitoring of adherence . MEASUREMENTS Baseline characteristics , risk factors for delirium , and quality care indicators were analyzed . The primary endpoint was incidence of delirium assessed daily . The secondary endpoint was functional decline , defined as loss of independence in any of the activities of daily living . The intervention effect was evaluated using logistic regression analysis . RESULTS Delirium affected 11.7 % of the GI group and 18.5 % of the UC group ( P=.04 ) . After adjustment for confounders , the intervention was associated with lower incidence of delirium ( odds ratio=0.4 , 95 % confidence interval=0.24 - 0.77 ; P=.005 ) . In the patients who experienced delirium , severity , length , and recurrence of episodes were similar in both groups . Adherence to the intervention protocol s was 75.7 % . The intervention reduced the rate of functional decline ( 45.5 % in GI vs 56.3 % in UC , P=.03 ) and improved other quality indicators ( e.g. , mobilization and physical restraints reduction ) . CONCLUSION A multicomponent , nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients , improves quality of care , and can be implemented without additional re sources in a public healthcare system OBJECTIVE To assess a systematic intervention in cases of delirium in elderly in patients . DESIGN R and omized , controlled trial . SETTING University-affiliated , primary acute care hospital . PATIENTS Patients aged 75 years or over admitted to the medical department . They were screened within 24 hours after admission , and 88 patients with delirium ( according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders , third revised edition ) were detected and enrolled in the trial . The patients were r and omly allocated to the treatment group ( 42 ) or the control group ( 46 ) ; all were followed up until the end of the study . INTERVENTION Patients were assessed on enrolment and 1 , 2 , 4 and 8 weeks later . Those in the treatment group received a consultation by a geriatric internist or psychiatrist and follow-up by a liaison nurse . Those in the control group received regular medical care . OUTCOME MEASURES Short Portable Mental Status Question naire ( SPMSQ ) , Crichton Geriatric Behavioural Rating Scale ( CGBRS ) , use of restraints , length of hospital stay , discharge to a setting providing more care than was needed before admission and mortality rate . RESULTS Two weeks after admission , patients in the treatment group showed an improvement in their mean SPMSQ scores , from 8.2 ( st and ard deviation [ SD ] 1.9 ) to 7.9 ( SD 2.5 ) , whereas the control group showed a deterioration , from 8.4 ( SD 1.7 ) to 9.1 ( SD 1.1 ) ; this difference had disappeared by the end of the 8-week period ( p < 0.05 ) . Mean CGBRS scores were higher in the treatment group ( 32.0 [ SD 8.6 ] ) than the control group ( 28.5 [ SD 9.4 ] ) on enrolment and had improved more markedly by the end of the 8-week period ( to 23.9 [ SD 7.8 ] v. 25.0 [ SD 7.0 ] , p = 0.06 ) . There was no statistically significant difference between the groups in use of restraints , length of hospital stay , discharge to a setting providing more care than was needed before admission or mortality rate . CONCLUSION The beneficial effects of systematic detection and intervention in cases of delirium in elderly in patients were small Objectives To identify risk factors for long-term mortality in patients aged 90 years and over who are admitted to hospital through the emergency department . Design Prospect i ve cohort study ( SAFES cohort ; Sujet Âgé Fragile — Évaluation Suivi ) . Setting 8 university teaching hospitals and one regional , non-academic hospital in France . Participants Among 1306 patients in the SAFES cohort , 291 patients aged 90 or over were included . Measurements At inclusion , we recorded socio-demographic data ( age , sex , level of education , living alone or in an institution , number of children , presence of helper/caregiver ) , and data from geriatric evaluation ( dependence status , risk of depression , dementia , delirium , nutritional status , walking disorders , risk of falls , comorbidities , risk of pressure sores ) . Vital status at 36 months was obtained from the treating physician , the general practitioner , administrative registers , or during follow-up consultations . Results Among 291 patients included , 190 ( 65.3 % ) had died at 36 months . Risk factors for mortality at 36 months identified by multivariate analysis were risk of malnutrition ( HR 1.6 , 95%CI 1.1–2.3 , p=0.004 ) and delirium ( HR 1.6 , 95%CI 1.1–2.3 , p=0.01 ) . Conclusion Risk of malnutrition and presence of delirium are risk factors for mortality at 36 months in subjects aged 90 years and over hospitalized through the emergency department |
1,190 | 30,196,312 | There was moderate evidence for effectiveness on weight and physical activity outcomes , but insufficient evidence for healthy eating outcomes .
Conclusion Current evidence demonstrates that group-based workplace interventions can be effective for supporting shift workers to lose weight and increase physical activity , while further research is needed to change healthy eating and sedentary behaviors . | Objective Shift work is a risk factor for many chronic diseases and has been associated with unhealthy lifestyle behaviors .
Workplaces have great potential for promoting and supporting behavior change .
We conducted a systematic review of group-based lifestyle workplace interventions for shift workers to ( i ) identify adaptations and intervention components that accommo date shift working and ( ii ) assess their impact on weight , physical activity , sedentary behavior and healthy eating . | 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 OBJECTIVE Numerous studies has shown that regular physical exercise can reduce musculoskeletal pain , but the optimal setting to achieve high adherence and effectiveness remains unknown . This study investigated the effect of workplace versus home-based physical exercise on musculoskeletal pain among healthcare workers . METHODS The r and omized controlled trial ( RCT ) comprised 200 female healthcare workers from 18 departments at 3 hospitals . Participants were r and omly allocated at the cluster level to ten weeks of : ( i ) workplace physical exercise ( WORK ) performed during working hours for 5 × 10 minutes per week and up to 5 group-based coaching sessions on motivation for regular physical exercise , or ( ii ) home-based physical exercise ( HOME ) performed during leisure time for 5 × 10 minutes per week . Both groups received ergonomic counseling on patient h and ling and use of lifting aides . Average pain intensity ( 0 - 10 scale ) in the low back and neck/shoulder was the primary outcome . RESULTS Per week , 2.2 ( SD 1.1 ) and 1.0 ( SD 1.2 ) training sessions were performed in WORK and HOME groups , respectively . Pain intensity , back muscle strength and use of analgesics improved more following WORK than HOME ( P<0.05 ) . Between-group differences at follow-up ( WORK versus HOME ) was -0.7 points for pain intensity [ 95 % confidence interval ( 95 % CI ) -1.0- -0.3 ] , 5.5 Nm for back muscle strength ( 95 % CI 2.0 - 9.0 ) , and -0.4 days per week for use of analgesics ( 95 % CI -0.7- -0.2 ) . The effect size for between-group differences in pain intensity was small ( Cohen 's d=0.31 ) . CONCLUSIONS Workplace physical exercise is more effective than home-based exercise in reducing musculoskeletal pain , increasing muscle strength and reducing the use of analgesics among healthcare workers Purpose To evaluate whether information and reassurance about low back pain ( LBP ) given to employees at the workplace could reduce sick leave . Methods A Cluster r and omized controlled trial with 135 work units of about 3,500 public sector employees in two Norwegian municipalities , r and omized into two intervention groups ; Education and peer support ( EPS ) ( n = 45 units ) , education and “ peer support and access to an outpatient clinic ” ( EPSOC ) ( n = 48 units ) , and a control group ( n = 42 units ) . Both interventions consisted of educational meetings based on a “ non-injury model ” and a “ peer adviser ” appointed by colleagues . Employees in the EPSOC group had access to an outpatient clinic for medical examination and further education . The control group received no intervention . The main outcome was sick leave based on municipal records . Secondary outcomes were self-reported pain , pain related fear of movement , coping , and beliefs about LBP from survey data of 1,746 employees ( response rate about 50 % ) . Results EPS reduced sick leave by 7 % and EPSOC reduced sick leave by 4 % during the intervention year , while sick leave in the control group was increased by 7 % during the same period . Overall , Rate Ratios ( RR ) were statistically significant for EPSOC ( RR = .84 ( C.I = 0.71–.99 ) but not EPS ( RR = .92 ( C.I = 0.78–1.09 ) ) in a mixed Poisson regression analysis . Faulty beliefs about LBP were reduced in both intervention groups . Conclusions Educational meetings , combined with peer support and access to an outpatient clinic , were effective in reducing sick leave in public sector employees The aim of the present study was to compare the effect of increased aerobic capacity versus muscle strength rehabilitation of female hospital staff with long-lasting musculoskeletal back pain . Seventy-nine women agreed to participate in the intervention study . After a medical examination , 65 individuals were assigned to one of three balanced groups : Endurance training ( aerobic capacity promoting training : ET : n = 22 ) , strength promotion exercise ( SP : n = 24 ) or a control group ( CON : n = 19 ) . The active groups met twice a week for 60 minutes of exercise over 15 weeks . Aerobic capacity ( VO2max ) and musculoskeletal pain were measured immediately before ( T1 ) and after the intervention period ( T2 ) . Aerobic capacity significantly increased in the ET group , whereas no change was observed in the SP group , and a significant reduction was found in the CON group from T1 to T2 . Musculoskeletal pain was significantly reduced in both intervention groups , whereas minor changes were observed in the control group . Results from a 7-month follow-up ( T3 ) survey confirmed the beneficial effects of interventions on musculoskeletal pain . In conclusion , improved aerobic capacity appeared not to be a necessary mechanism in musculoskeletal back pain reduction Purpose . To report findings from Treatwell 5-a-Day process tracking . Design . Worksites were r and omly assigned to a minimal intervention control , worksite-only condition , or worksite-plus-family condition . Setting . Twenty-two small community health centers in Massachusetts . Subjects . Employees of the community health centers . Intervention . Both intervention conditions included the formation of employee advisory boards ; activities such as nutrition discussion s and taste tests targeting individual behavior change ; and point-of-purchase labeling as an environmental strategy . Worksite-plus-family sites incorporated activities such as family contests , campaigns , and picnics . Measures . Documentation of the number and type of activities for extent of implementation ; number of participants in activities for reach ; program awareness and participation from the follow-up employee survey ( n = 1306 , representing 76 % [ range , 56%–100 % ] of the sample ) ; change in fruit and vegetable consumption from a comparison between the follow-up and baseline surveys ( n = 1359 , representing 87 % [ range , 75%–100 % ] of the sample ) . Results . A higher number of activities per employee was significantly correlated with greater program awareness ( . 68 ; p = . 006 ) and greater change in fruit and vegetable consumption ( .55 ; p = .04 ) . Greater participation in activities was significantly correlated with greater awareness ( .67 ; p = .007 ) , higher participation ( .61 ; p = .02 ) , and increase in fruit and vegetable consumption . ( .55 ; p = .04 ) . Conclusions . These results provide quantitative indicators of a dose-response relationship between the number of intervention activities per employee and higher percentage of employee participation and observed increases in fruit and vegetable consumption OBJECTIVE Shift work is associated with adverse health outcomes , and an unhealthy diet may be a contributing factor . We compared diet quantity and quality between day and shift workers , and studied exposure-response relationships regarding frequency of night shifts and years of shift work . METHODS Cross-sectional general population data from the European Prospect i ve Investigation into Cancer and Nutrition-Netherl and s ( EPIC-NL ) cohort was used . Dietary intake was assessed in 1993 - 1997 among adults aged 20 - 70 years using a food frequency question naire . We calculated energy intake , the Mediterranean Diet Score ( MDS ) and WHO-based Healthy Diet Indicator ( HDI ) . In 2011 - 2014 , we retrospectively identified 683 shift workers and 7173 day workers in 1993 - 1997 . Using multivariable-adjusted linear regression analysis , we estimated regression coefficients ( β ) and 95 % confidence intervals ( 95 % CI ) of the differences in dietary intake between day and shift workers . RESULTS Shift workers had a higher energy intake than day workers ( β:56 kcal/d , 95 % CI 10 - 101 ) , and a higher consumption of grains , dairy products , meat and fish ( P<0.05 ) . The difference in energy intake was largest for shift workers with ≥5 night shifts/month . They consumed 103 kcal/d ( 95 % CI 29 - 176 ) more than day workers . No associations were found with MDS and HDI . CONCLUSION Shift workers and particularly those with a high frequency of night shifts had a higher energy intake than day workers . Regardless of number of night shifts and years of shift work , shift workers had similar diet quality as day workers . This suggests that increased energy intake among shift workers may contribute to shift work-induced adverse health outcomes Background Increased physical activity levels benefit both an individuals ' health and productivity at work . The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention design ed to increase physical activity levels . Methods A total of 1260 participants from 44 UK worksites ( based within 5 organizations ) were recruited to a cluster r and omized controlled trial with worksites r and omly allocated to an intervention or control condition . Measurement of physical activity and other variables occurred at baseline , and at 0 months , 3 months and 9 months post-intervention . Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention . The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior , delivered in-house by nominated facilitators . Self-reported physical activity ( measured using the IPAQ short-form ) and health outcomes were assessed . Results and discussion Multilevel modelling found no significant effect of the intervention on MET minutes of activity ( from the IPAQ ) at any of the follow-up time points controlling for baseline activity . However , the intervention did significantly reduce systolic blood pressure ( B = -1.79 mm/Hg ) and resting heart rate ( B = -2.08 beats ) and significantly increased body mass index ( B = .18 units ) compared to control . The intervention was found not to be cost-effective , however the substantial variability round this estimate suggested that further research is warranted . Conclusions The current study found mixed support for this worksite physical activity intervention . The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale r and omized controlled trials in real-world setting s . Trial registration Current controlled trials IS RCT Background Dietary behaviour interventions have the potential to reduce diet-related disease . Ample opportunity exists to implement these interventions in the workplace . The overall aim is to assess the effectiveness and cost-effectiveness of complex dietary interventions focused on environmental dietary modification alone or in combination with nutrition education in large manufacturing workplace setting s. Methods / design A clustered controlled trial involving four large multinational manufacturing workplaces in Cork will be conducted . The complex intervention design has been developed using the Medical Research Council ’s framework and the National Institute for Health and Clinical Excellence ( NICE ) guidelines and will be reported using the TREND statement for the transparent reporting of evaluations with non-r and omized design s. It will draw on a soft paternalistic “ nudge ” theoretical perspective . Nutrition education will include three elements : group presentations , individual nutrition consultations and detailed nutrition information . Environmental dietary modification will consist of five elements : ( a ) restriction of fat , saturated fat , sugar and salt , ( b ) increase in fibre , fruit and vegetables , ( c ) price discounts for whole fresh fruit , ( d ) strategic positioning of healthier alternatives and ( e ) portion size control . No intervention will be offered in workplace A ( control ) . Workplace B will receive nutrition education . Workplace C will receive nutrition education and environmental dietary modification . Workplace D will receive environmental dietary modification alone . A total of 448 participants aged 18 to 64 years will be selected r and omly . All permanent , full-time employees , purchasing at least one main meal in the workplace daily , will be eligible . Changes in dietary behaviours , nutrition knowledge , health status with measurements obtained at baseline and at intervals of 3 to 4 months , 7 to 9 months and 13 to 16 months will be recorded . A process evaluation and cost-effectiveness economic evaluation will be undertaken . Discussion A ' Food Choice at Work ’ toolbox ( concise teaching kit to replicate the intervention ) will be developed to inform and guide future research ers , workplace stakeholders , policy makers and the food industry . Trial registration Current Controlled Trials , IS RCT Background The prevalence and consequences of musculoskeletal pain is considerable among healthcare workers , allegedly due to high physical work dem and s of healthcare work . Previous investigations have shown promising results of physical exercise for relieving pain among different occupational groups , but the question remains whether such physical exercise should be performed at the workplace or conducted as home-based exercise . Performing physical exercise at the workplace together with colleagues may be more motivating for some employees and thus increase adherence . On the other h and , physical exercise performed during working hours at the workplace may be costly for the employers in terms of time spend . Thus , it seems relevant to compare the efficacy of workplace- versus home-based training on musculoskeletal pain . This study is intended to investigate the effect of workplace-based versus home-based physical exercise on musculoskeletal pain among healthcare workers . Methods / Design This study was design ed as a cluster r and omized controlled trial performed at 3 hospitals in Copenhagen , Denmark . Clusters are hospital departments and hospital units . Cluster r and omization was chosen to increase adherence and avoid contamination between interventions . Two hundred healthcare workers from 18 departments located at three different hospitals is allocated to 10 weeks of 1 ) workplace based physical exercise performed during working hours ( using kettlebells , elastic b and s and exercise balls ) for 5 × 10 minutes per week and up to 5 group-based coaching sessions , or 2 ) home based physical exercise performed during leisure time ( using elastic b and s and body weight exercises ) for 5 × 10 minutes per week . Both intervention groups will also receive ergonomic instructions on patient h and ling and use of lifting aides etc . Inclusion criteria are female healthcare workers working at a hospital . Average pain intensity ( VAS scale 0 - 10 ) of the back , neck and shoulder ( primary outcome ) and physical exertion during work , social capital and work ability ( secondary outcomes ) is assessed at baseline and 10-week follow-up . Further , postural balance and mechanical muscle function is assessed during clinical examination at baseline and follow-up . Discussion This cluster r and omized trial will investigate the change in self-rated average pain intensity in the back , neck and shoulder after either 10 weeks of physical exercise at the workplace or at home . Trial registration Clinical Trials.gov ( NCT01921764 ) OBJECTIVE To evaluate the efficacy of an 8-week worksite nutrition education intervention for university staff using the Health Belief Model ( HBM ) to promote healthful dietary behaviors that reduce risks for cardiovascular disease and cancer . DESIGN 2 3 2 repeated measures baseline/posttest ex post facto research design . PARTICIPANTS Staff employees were r and omly assigned to treatment ( n = 28 ) and control groups ( n = 25 ) . INTERVENTION The intervention focused on specific health beliefs , nutrition knowledge , and dietary practice s to demonstrate treatment effect . MAIN OUTCOME MEASURES Dependent variables were specific health beliefs , nutrition knowledge , and dietary behaviors . Independent variables were demographic characteristics and group assignment . ANALYSES Tests of parametric assumptions , power analyses , analysis of variance , and Kuder-Richardson and Pearson product-moment coefficients were computed and specificity of treatment effects was assessed . RESULTS Perceived benefits of healthy nutrition practice s and nutrition knowledge related to cardiovascular disease and cancer significantly improved among the treatment participants , P < .001 . Treatment group participants also significantly reduced total calories , fat , saturated fat , and cholesterol intake ( each P < .001 ) . CONCLUSIONS The intervention appears to be related to treatment effects and significantly increased nutrition knowledge and decreased energy , fat , saturated fat , and cholesterol intake to levels consistent with national recommendations This article examines the relationship between reported social support and readiness to increase fruit and vegetable consumption , based on the Transtheoretical Stage of Change Model . Data were collected as part of the baseline assessment s for a work site intervention study promoting increased consumption of fruits and vegetables . Among workers who did not live alone , household support was significantly higher for those of Hispanic and African American heritage than other groups , and was also higher among men , nonsmokers , and those living with adults compared to those living only with children . In multivariate analyses , coworker support was significantly associated with being in preparation compared to precontemplation/contemplation . Household support was not significantly related to readiness to change in multivariate analyses . The effectiveness of work site nutrition education interventions is likely to be enhanced by teaching participants to provide social support to coworkers and family members OBJECTIVE The effects and constancy of a worksite physical exercise intervention were examined in relation to the physical fitness , perceived health status , and work ability of female service workers during periods of 1 and 5 years . METHODS The subjects comprised female home care workers divided into an intervention group ( n = 50 , mean age 41.8 ( SD 10.4 ) years ) and a control group ( n = 37 , mean age 43.3 ( SD 8.8 ) years ) . The intervention group participated in 9 months of supervised exercise intervention twice a week during the workday . Functional capacity , perceived health , and work ability were assessed at the beginning of the study and after a 1- and a 5-year period of follow-up . RESULTS In the 1-year follow-up measurements , body fat had decreased ( 4 % ) and dynamic muscle performance and maximal oxygen consumption in relation to body mass ( 30 - 38 and 7 % , respectively ) had increased in the intervention group . The differences in outcome variables between the intervention and the control groups were significant ( from P = 0.014 to P < 0.001 ) . These positive effects of worksite exercise were observed despite the age of the subjects , and the changes were consistent during a 5-year period . In the control group the decline of the work ability index ( L smean ) was about three times faster than in the intervention group during the 5-year period . CONCLUSIONS Physical exercise executed in work units can be used to improve the physical capacity of female home care aides and prevent the early decline of their work ability . In jobs that are physically dem and ing , such as home care work , early prevention must start before the age-related deterioration of health and physical capacity Background While benefits of workplace physical exercise on physical health is well known , little is known about the psychosocial effects of such initiatives . This study evaluates the effect of workplace versus home-based physical exercise on psychosocial factors among healthcare workers . Methods A total of 200 female healthcare workers ( Age : 42.0 , BMI : 24.1 ) from 18 departments at three hospitals were cluster-r and omized to 10 weeks of : 1 ) home-based physical exercise ( HOME ) performed alone during leisure time for 10 min 5 days per week or 2 ) workplace physical exercise ( WORK ) performed in groups during working hours for 10 min 5 days per week and up to 5 group-based coaching sessions on motivation for regular physical exercise . Vitality and mental health ( SF-36 , scale 0–100 ) , psychosocial work environment ( COPSOQ , scale 0–100 ) , work- and leisure disability ( DASH , 0–100 ) , control- ( Bournemouth , scale 0–10 ) and concern about pain ( Pain Catastrophizing Scale , scale 0–10 ) were assessed at baseline and at 10-week follow-up . Results Vitality as well as control and concern about pain improved more following WORK than HOME ( all p < 0.05 ) in spite of increased work pace ( p < 0.05 ) . Work- and leisure disability , emotional dem and s , influence at work , sense of community , social support and mental health remained unchanged . Between-group differences at follow-up ( WORK vs. HOME ) were 7 [ 95 % confidence interval ( 95 % CI ) 3 to 10 ] for vitality , −0.8 [ 95 % CI -1.3 to −0.3 ] for control of pain and −0.9 [ 95 % CI -1.4 to −0.5 ] for concern about pain , respectively . Conclusions Performing physical exercise together with colleagues during working hours was more effective than home-based exercise in improving vitality and concern and control of pain among healthcare workers . These benefits occurred in spite of increased work pace . Trial registration NCT01921764 at Clinical Trials.gov . Registered 10 August 2013 OBJECTIVE In this paper , we describe the aims , intervention , and design of the Work , Weight , and Wellness program , a group-r and omized worksite obesity prevention and intervention trial being conducted at 31 hotels with 11,559 employees on the isl and of Oahu in Hawaii . We report baseline prevalence of overweight and obesity , and the distribution of BMI ( kilograms per meter squared ) across sex , race , and job categories . We also describe factors that have influenced intervention adoption and employee participation . RESEARCH METHODS AND PROCEDURES The study 's primary outcome is change in BMI among hotel employees over a 2-year intervention period . The intervention includes environmental and group components that target diet , physical activity , and weight management . RESULTS Men , Pacific Isl and ers , and individuals employed in managerial or facility maintenance roles had higher prevalence of obesity and higher mean BMI than women and individuals from other races or in other occupational categories . DISCUSSION These results may be helpful in guiding choices about the adoption or design of future worksite and community interventions addressing at-risk ethnically diverse population s and are especially relevant to the hotel industry and similar industries BACKGROUND It is a common belief that physical exercise at the workplace decreases subjective health complaints and reduces sickness absence , but this is not supported by previous r and omized studies . AIMS To evaluate the effectiveness of physical exercise at the workplace . METHODS One hundred and twenty-nine employees in a community-based nursing home for the elderly were r and omized into physical exercise or control groups . A weekly exercise class consisting of light aerobic exercise , muscle strengthening and stretching was held for a 6-month period . The control group was told to continue their ordinary activity . The main outcome measures were aerobic fitness ( UKK , walking test ) , health-related quality of life ( COOP/WONCA ) and sickness absence . Blinded assessment s were carried out at baseline and following the 6-month intervention . Complete sickness absence data were collected from a community register for two comparable 7-month periods . RESULTS The average number of exercise sessions was 12 ( 0 - 26 ) . Self-reported physical activity increased in the intervention group compared with the control group ( P < 0.01 ) . Aerobic fitness improved in both groups ( P < 0.01 ) . Mean sickness absence increased from 6.8 to 15.6 days in the exercise group and from 10.4 to 14.5 in the control group . No differences between groups were found for aerobic fitness , health-related quality of life or sickness absence . CONCLUSION The intervention neither improved health-related quality of life nor reduced sickness absence Objective To evaluate the effectiveness of a worksite vitality intervention on vigorous physical activity ( VPA ) , fruit intake , aerobic capacity , mental health and need for recovery after work among older hospital workers ( ie , 45 years and older ) . Methods The 6-month intervention was evaluated using a r and omised controlled trial design . Workers who were r and omised to the intervention group ( n=367 ; control : n=363 ) received the Vital@Work intervention containing ( 1 ) a Vitality Exercise Program ( VEP ) combined with ( 2 ) three visits to Personal Vitality Coach . The VEP consisted of a weekly yoga session , a weekly workout session and weekly unsupervised aerobic exercising . Free fruit was provided at the VEP . Data on the outcome measures were collected ( ie , year 2009–2010 ) at baseline ( n=730 ) and 6 months of follow-up after baseline ( n=575 ) using question naires , accelerometers and 2 km walk tests . Effects were analysed according to the intention-to-treat principle with complete cases ( n=575 ) and imputed data ( n=730 ) using linear regression analyses . Additional analyses were performed for high yoga and workout compliance ( ie , > mean number of sessions ) . Results Effects were found for sports activities ( β=40.4 min/week , 95 % CI 13.0 to 67.7 ) and fruit intake ( β=2.7 pieces/week , 95 % CI 0.07 to 4.7 ) and were stronger for workers with high compliance to yoga ( sport : β=49.6 min/week , 95 % CI 13.9 to 85.2 ; fruit : β=3.8 pieces/week , 95 % CI 1.1 to 6.4 ) and workout sessions ( sport : β=72.9 min/week , 95 % CI 36.1 to 109.8 ; fruit : β=4.0 pieces/week , 95 % CI 1.1 to 6.4 ) . The intervention group lowered their need for recovery , when compared to controls ( β=−3.5 , 95 % CI −6.4 to −0.54 ) , with stronger effects for high workout compliance ( β=−5.3 , 95 % CI −9.3 to −1.3 ) . No effects were found on VPA , aerobic capacity or mental health . Conclusions Implementation of worksite yoga and workout facilities and minimal fruit interventions should be considered by employers to promote transitions into healthier lifestyles and thereby health Objective : To evaluate the effectiveness of a participatory approach using an employee design team for a 12-week weight-loss program with an 8-week follow-up . Methods : Twenty-four employees with mean [ st and ard error ( SE ) ] for weight 233.24 lb [ 8.16 ] , body mass index 33.29 kg/cm2 [ 0.82 ] , and age 42.7 years [ 1.5 ] participated in the study , among whom 75 % were men and 25 % women . Results : Significant reductions in weight , body mass index , and waist circumference ( among men ) were observed before and after intervention ( P < 0.05 ) . About 73 % and 68 % of the variation in weight change ( P < 0.01 ) and waist circumference ( P < 0.01 ) , respectively , were explained by Nutrition Knowledge and Exercise Confidence scores after controlling for gender and age . Conclusions : A participatory program with employee involvement result ed in positive outcomes . Increasing participants ' knowledge and providing skills to manage their weight seem to change their attitudes , result ing in better outcomes Background Imbalance between individual re sources and work dem and s can lead to musculoskeletal disorders and reduced work ability . The purpose of this study was to investigate the effect of workplace- versus home-based physical exercise on work ability among healthcare workers . Methods Two hundred female healthcare workers ( Age : 42.0 , BMI : 24.1 , work ability index [ WAI ] : 43.1 ) from 18 departments at three Danish hospitals participated ( Copenhagen , Denmark , Aug 2013—Jan 2014 ) . Participants were r and omly allocated at the cluster level to 10 weeks of : 1 ) workplace physical exercise ( WORK ) performed during working hours for 5x10 min per week and up to 5 group-based coaching sessions on motivation for regular physical exercise , or 2 ) home-based physical exercise ( HOME ) performed during leisure time for 5x10 min per week . Both groups received ergonomic counseling on patient h and ling and use of lifting aides . The main outcome measure was the change from baseline to 10-week follow-up in WAI . Results Significant group by time interaction was observed for WAI ( p < 0.05 ) . WAI at follow-up was 1.1 ( 0.3 to 1.8 ) higher in WORK compared with HOME corresponding to a small effect size ( Cohens’d = 0.24 ) . Within-group changes indicated that between-group differences were mainly caused by a reduction in WAI in HOME . Of the seven items of WAI , item 2 ( work ability in relation to the dem and s of the job ) and item 5 ( sickness absence during the past year ) were improved in WORK compared with HOME ( P < 0.05 ) . Conclusions Performing physical exercise together with colleagues at the workplace prevents deterioration of work ability among female healthcare workers . Trial registration number Clinical Trials.gov NCT01921764 . Registered 10 August 2013 Background A mismatch between individual physical capacities and physical work dem and s enhance the risk for musculoskeletal disorders , poor work ability and sickness absence , termed physical deterioration . However , effective intervention strategies for preventing physical deterioration in job groups with high physical dem and s remains to be established . This paper describes the background , design and conceptual model of the FINALE programme , a framework for health promoting interventions at 4 Danish job groups ( i.e. cleaners , health-care workers , construction workers and industrial workers ) characterized by high physical work dem and s , musculoskeletal disorders , poor work ability and sickness absence . Methods / Design A novel approach of the FINALE programme is that the interventions , i.e. 3 r and omized controlled trials ( RCT ) and 1 exploratory case-control study are tailored to the physical work dem and s , physical capacities and health profile of workers in each job-group . The RCT among cleaners , characterized by repetitive work tasks and musculoskeletal disorders , aims at making the cleaners less susceptible to musculoskeletal disorders by physical coordination training or cognitive behavioral theory based training ( CBTr ) . Because health-care workers are reported to have high prevalence of overweight and heavy lifts , the aim of the RCT is long-term weight-loss by combined physical exercise training , CBTr and diet . Construction work , characterized by heavy lifting , pushing and pulling , the RCT aims at improving physical capacity and promoting musculoskeletal and cardiovascular health . At the industrial work-place characterized by repetitive work tasks , the intervention aims at reducing physical exertion and musculoskeletal disorders by combined physical exercise training , CBTr and participatory ergonomics . The overall aim of the FINALE programme is to improve the safety margin between individual re sources ( i.e. physical capacities , and cognitive and behavioral skills ) and physical work dem and s , and thereby reduce the physical deterioration in a long term perspective by interventions tailored for each respective job-group . Discussion The FINALE programme has the potential to provide evidence -based knowledge of significant importance for public health policy and health promotion strategies for employees at high risk for physical deterioration . Trial registration sIS RCT N96241850 , NCT01015716 and OBJECTIVE To evaluate the feasibility and efficacy of a workplace-based weight loss program ( Workplace POWER-WP ) for male shift workers . METHOD A prospect i ve , two-armed r and omized controlled trial of 110 overweight/obese ( BMI 25 - 40 ) ( mean [ SD ] age = 44.4 [ 8.6 ] years ; BMI = 30.5 [ 3.6 ] ) male employees at Tomago Aluminium aged 18 - 65 . In October ( 2009 ) men were r and omized to either ( i ) WP program ( n=65 ) or ( ii ) a 14-week wait-list control group ( n=45 ) . The 3-month program involved one information session , program booklets , group-based financial incentives and an online component . Men were assessed at baseline and at 14-week follow-up for weight ( primary outcome ) , waist circumference , BMI , blood pressure , resting heart rate , self-reported physical activity and dietary variables , and physical activity and dietary cognitions . RESULTS Intention-to-treat analysis using linear mixed models revealed significant between group differences for weight loss after 14 weeks ( P < .001 , Cohen 's d = 0.34 ) . Significant intervention effects were also found for waist circumference ( P < .001 , d = 0.63 ) , BMI ( P < .001 , d = 0.41 ) , systolic blood pressure ( P = .02 , d = 0.48 ) , resting heart rate ( P < .001 , d = 0.81 ) , physical activity ( P = .03 , d = 0.77 ) , sweetened beverages ( P < .02 , d = 0.5 - 0.6 ) and physical activity-related cognitions ( P < .02 , d=0.6 ) . CONCLUSION The WP program was feasible and efficacious and result ed in significant weight loss and improved health-related outcomes and behaviours in overweight male shift workers BACKGROUND 5 a Day for Better Health is a simple message encouraging people to eat more fruits and vegetables . The Seattle 5 a Day worksite investigators design ed and evaluated an intervention , organized on stages of behavioral change , to increase worksitewide fruit and vegetable consumption . METHODS We recruited 28 worksites with cafeterias and r and omized 14 to intervention and 14 to control . The intervention addressed both changes in the work environment and individual level behavior change . In each worksite , an employee advisory board , with study interventionist assistance , implemented the program . By surveying cross-sectional sample s of 125 employees per worksite , we compared worksite mean fruit and vegetable consumption at 2-year follow-up with that at baseline . Unobtrusive site-level indicators including plate observation and cafeteria checklist were also used . RESULTS The difference at 2 years was 0.5 for the intervention worksites and 0.2 for the control worksites , with an intervention effect of 0.3 daily serving ( P < 0.05 ) . Other measures of fruit and vegetable consumption , including unobtrusive indicators , supported the effectiveness of the intervention . CONCLUSIONS This simple 5 a Day intervention is feasible and acceptable for use in worksites with cafeterias . There was a significant differential increase in fruit and vegetable consumption in the intervention worksites . This kind of worksite intervention can achieve important health benefits on a population basis , because of its potential to reach large numbers of people Obesity affects individuals physically and emotionally , contributing to direct and indirect employer costs . Targeted obesity interventions through the Diabetes Prevention Program Lifestyle Core Curriculum offered at the worksite could promote healthy lifestyle decisions result ing in weight improvement among overweight and obese employees . A pretest-posttest cohort design was used to evaluate changes in weight and body mass index among 35 Diabetes Prevention Program participants ; they achieved statistically significant changes in body weight ( p < .001 ) and body mass index ( p < .001 ) . As a process measure , Diabetes Prevention Program session attendance moderately correlated with weight loss ( r = .51 ; p = .002 ) . Many health care professionals , including occupational health nurses , can implement evidence -based worksite obesity interventions to support employee weight loss Overweight and physical inactivity are risk factors for increased disease burden and health care expenditure . Well- design ed studies are still needed to determine the treatment efficacy of worksite interventions targeting such risk factors . This r and omized controlled trial was conducted at one of Australia 's casinos in 2002 - 2003 , to investigate the effects of a comprehensive exercise and lifestyle intervention on physical fitness . Only 6.4 % of the workforce expressed interest in being study participants . Seventy-three employees ( aged 32 + /- 8 years , 51 % overweight/obese , 73 % shift workers and 52 % women ) were recruited and r and omized to treatment or wait-list control groups for 24 weeks , 44 of whom completed the intervention . Components of the intervention include supervised moderate-to-high intensity exercise including combined aerobic ( at least 20 min duration 3 days/week ) and weight-training ( for an estimated 30 min completed 2 - 3 days/week ) , and dietary/health education ( delivered via group seminars , one-on-one counselling and literature through the provision of a worksite manual ) . ANCOVA , by intention-to-treat and of study completers , found significant between-group differences in the mean waist circumference and predicted maximal oxygen uptake ( VO2max ) , favouring the intervention , but effects were concentrated in one subject . For study completers , between-group differences in the mean waist circumference ( 82.3 + /- 9.2 versus 90.5 + /- 17.8 cm , p = 0.01 ) and predicted VO2max ( 47 versus 41 ml/kg/min , p < 0.001 ) remained significant without the outlier , favouring the intervention . Higher intervention compliance predicted greater improvements in physical fitness . No significant effects on body mass or body mass index were found . This worksite intervention significantly improved waist circumference and aerobic fitness in healthy but sedentary employees , most of whom were shift workers . Worksite interventions have the potential to counter the increasing burden of overweight and obesity , particularly visceral adiposity , as well as physical inactivity ; however , substantial barriers to adoption/adherence need to be overcome for greater feasibility and impact on employee physical health Objectives Prescribed medications represent a high and increasing proportion of UK health care funds . Our aim was to quantify the influence of body mass index ( BMI ) on prescribing costs , and then the potential savings attached to implementing a weight management intervention . Methods Paper and computer-based medical records were review ed for all drug prescriptions over an 18-month period for 3400 r and omly selected adult patients ( 18 - 75 years ) stratified by BMI , from 23 primary care practice s in seven UK regions . Drug costs from the British National Formulary at the time of the review were used . Multivariate regression analysis was applied to estimate the cost for all drugs and the ‘ top ten ’ drugs at each BMI point . This allowed the total and attributable prescribing costs to be estimated at any BMI . Weight loss outcomes achieved in a weight management programme ( Counterweight ) were used to model potential effects of weight change on drug costs . Anticipated savings were then compared with the cost programme delivery . Analysis was carried out on patients with follow-up data at 12 and 24 months as well as on an intention-to-treat basis . Outcomes from Counterweight were based on the observed lost to follow-up rate of 50 % , and the assumption that those patients would continue a generally observed weight gain of 1 kg per year from baseline . Results The minimum annual cost of all drug prescriptions at BMI 20 kg/m2 was £ 50.71 for men and £ 62.59 for women . Costs were greater by £ 5.27 ( men ) and £ 4.20 ( women ) for each unit increase in BMI , to a BMI of 25 ( men £ 77.04 , women £ 78.91 ) , then by £ 7.78 and £ 5.53 , respectively , to BMI 30 ( men £ 115.93 women £ 111.23 ) , then by £ 8.27 and £ 4.95 to BMI 40 ( men £ 198.66 , women £ 160.73 ) . The relationship between increasing BMI and costs for the top ten drugs was more pronounced . Minimum costs were at a BMI of 20 ( men £ 8.45 , women £ 7.80 ) , substantially greater at BMI 30 ( men £ 23.98 , women £ 16.72 ) and highest at BMI 40 ( men £ 63.59 , women £ 27.16 ) . Attributable cost of overweight and obesity accounted for 23 % of spending on all drugs with 16 % attributable to obesity . The cost of the programme was estimated to be approximately £ 60 per patient entered . Modelling weight reductions achieved by the Counterweight weight management programme would potentially reduce prescribing costs by £ 6.35 ( men ) and £ 3.75 ( women ) or around 8 % of programme costs at one year , and by £ 12.58 and £ 8.70 , respectively , or 18 % of programme costs after two years of intervention . Potential savings would be increased to around 22 % of the cost of the programme at year one with full patient retention and follow-up . Conclusion Drug prescriptions rise from a minimum at BMI of 20 kg/m2 and steeply above BMI 30 kg/m2 . An effective weight management programme in primary care could potentially reduce prescription costs and lead to substantial cost avoidance , such that at least 8 % of the programme delivery cost would be recouped from prescribing savings alone in the first year PURPOSE A four-group r and omized controlled trial evaluated the impact of distinct workplace interventions to increase the physical activity ( PA ) and to reduce anthropometric parameters in middle-age women . METHODS One-hundred and ninety-five women age 40 - 50 yr who were employees from a university hospital and physically inactive at their leisure time were r and omly assigned to one of four groups : minimal treatment comparator ( MTC ; n = 47 ) , pedometer-based individual counseling ( PedIC ; n = 53 ) , pedometer-based group counseling ( PedGC ; n = 48 ) , and aerobic training ( AT ; n = 47 ) . The outcomes were total number of steps ( primary outcome ) , those performed at moderate intensity ( ≥ 110 steps per minute ) , and weight and waist circumference ( secondary outcomes ) . Evaluations were performed at baseline , at the end of a 3-month intervention , and 3 months after that . Data were presented as delta [ ( after 3 months-baseline ) or ( after 6 months-baseline ) ] and 95 % confidence interval . To detect the differences among the groups , a one-way ANOVA and a Holm-Sidak post hoc test was used ( P < 0.05 ) . The Cohen effect size was calculated , and an intention-to-treat approach was performed . RESULTS Only groups using pedometers ( PedIC and PedGC ) increased the total number of steps after 3 months ( P < 0.05 ) ; however , the increase observed in PedGC group ( 1475 steps per day ) was even higher than that in PedIC ( 512 steps per day , P < 0.05 ) with larger effect size ( 1.4 ) . The number of steps performed at moderate intensity also increased only in the PedGC group ( 845 steps per day , P < 0.05 ) . No PA benefit was observed at 6 months . Women su bmi tted to AT did not modify PA daily life activity but reduced anthropometric parameters after 3 and 6 months ( P < 0.05 ) . CONCLUSIONS Our results show that in the workplace setting , pedometer-based PA intervention with counseling is effective increasing daily life number of steps , whereas AT is effective for weight loss Objectives The effects of job strain and shift work on weight gain have not been studied jointly . Cross-sectional and longitudinal studies on shift work and weight gain have reported different results . This study examines potential effect modification by job strain on the link between shift work and weight gain , and concurrent and delayed effects of shift work on weight gain . Methods Data came from 52 622 women who participated in the Nurses ’ Health Study II , a prospect i ve cohort study . Using linear regression , we modelled change in body mass index ( BMI ) over 4 years as a function of change in job strain , cumulative exposure to rotating night shift previously and during the 4 years ( ie , previous and concurrent exposures ) and the interaction between job strain and concurrent shift work exposure . Age , race/ethnicity , pregnancy history , baseline BMI , job types and health behaviours at baseline were controlled for . Results Job strain and rotating shift work , concurrent and previous , all had independent associations with BMI change during the 4-year period . There was no evidence for effect modification by job strain . Concurrent and previous exposures to rotating night shift had different associations with BMI change : an inverted U-shape for concurrent exposure ( ranging from 0.01 to 0.14 kg/m2 increase ) , a dose – response for previous exposure ( −0.02 to 0.09 kg/m2 ) . Conclusions Job strain and rotating night shift work have independent contributions to weight gain . Reducing job strain and supporting night shift workers are both important intervention goals |
1,191 | 26,982,519 | Overall , we found no convincing evidence that giving supplementary oxygen to healthy term pregnant women during elective caesarean section under regional anaesthesia is either beneficial or harmful for either the mother or the foetus ' short-term clinical outcome as assessed by Apgar scores . | BACKGROUND Supplementary oxygen is routinely administered to low-risk pregnant women during an elective caesarean section under regional anaesthesia ; however , maternal and foetal outcomes have not been well established .
This is an up date of a review first published in 2013 .
OBJECTIVES The primary objective was to determine whether supplementary oxygen given to low-risk term pregnant women undergoing elective caesarean section under regional anaesthesia can prevent maternal and neonatal desaturation .
The secondary objective was to compare the mean values of maternal and neonatal blood gas levels between mothers who received supplementary oxygen and those who did not ( control group ) . | Forty patients undergoing elective and emergency Caesarean section ( excluding severe fetal distress ) were divided into four groups to receive 50 % oxygen , 50 % nitrous oxide , and 0.5 % halothane ( group 1 , controls ) or 100 % oxygen supplemented by 1.5 x MAC of halothane , enflurane or isoflurane ( groups 2,3,4 , respectively ) reducing to 1.0 x MAC 5 min after induction . The umbilical venous PO2 in the oxygen-only groups was higher than in the oxygen-nitrous oxide groups , this difference reaching statistical significance when the patients in the oxygen-only groups were combined . Blood loss and uterine contractility were unaffected by the increased concentrations of volatile agents , and awareness did not occur . Improved cardiovascular stability was demonstrated in the elective high-oxygen groups . The technique is safe and warrants further study , since there are no important ethical objections To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results The use of supplemental oxygen in uncomplicated cesarean deliveries under spinal anesthesia has been thoroughly investigated during recent decades . The aim of this study was to determine the benefits for both mother and infant of administering supplemental , low-dose oxygen via a nasal cannula versus having no supplement ( i.e. , room air only ) . Healthy parturients at term undergoing elective cesarean section under spinal anesthesia were r and omly allocated into two groups : an oxygen group ( n = 170 ) , who received 3 LPM oxygen via a nasal cannula ; and a room-air group ( n = 170 ) , who were assigned to breathe room air . Maternal oxygen saturation was measured continuously by using pulse oximeter . The desaturation was determined by oxygen saturation < 94 % over 30 seconds . Umbilical cord gases and Apgar scores were collected followed delivery of the infant . All maternal desaturation events occurred in 12 parturients assigned to the room-air group . Most events were concurrent with hypotension . The umbilical venous partial pressure of oxygen was significantly higher in the oxygen group . The other blood gas measurements and Apgar scores were not significantly different between the two groups . Based on our findings , the use of supplemental oxygen could prevent maternal desaturation result ing from receiving sedation and intraoperative hypotension BACKGROUND Newborns exposed to oxygen suffer from an oxidative stress with significant alterations in the concentrations of superoxide dismutase ( SOD ) and glutathione ( GSSG ) . OBJECTIVE To investigate the biological and clinical effects of oxygen administration to delivering mothers . METHODS We conducted a r and omized , double-blinded , controlled trial on a cohort of delivering women ( n=56 ) with an uncomplicated term pregnancy . Women were r and omly assigned to one of two groups : Oxygen group or Room Air group . The Oxygen group received 100 % oxygen ( 2l/min ) via nasal cannula for at least 30 min before delivery . Subjects in the Room Air group were connected to a nasal cannula while on room air . Concentrations of SOD ( μg/g of Hb ) and GSSG ( μM/ml ) were measured in maternal and umbilical cord blood . Bivariate and multivariate analyses were used to compare the two groups using the SAS system . RESULTS Maternal SOD and GSSG did not differ between the two groups at baseline or after delivery . Concentrations of SOD and GSSG in umbilical cord blood did not differ between groups . More infants in Oxygen Group required delivery room resuscitation ( 20 % vs. 0 % , P=0.03 ) . This difference could not be explained by mode of delivery , infant sex , or other confounders . CONCLUSIONS Maternal exposure to oxygen during delivery is not associated with changes in umbilical cord SOD or GSSG . Further studies are needed to explore mechanisms responsible for the need of resuscitation in the oxygen group Spinal anesthesia recently has gained popularity for elective cesarean section . Our anesthesia service changed from epidural to spinal anesthesia for elective cesarean section in 1991 . To evaluate the significance of this change in terms of time management , costs , charges , and complication rates , we retrospectively review ed the charts of patients who had received epidural ( n = 47 ) or spinal ( n = 47 ) anesthesia for nonemergent cesarean section . Patients who received epidural anesthesia had significantly longer total operating room ( OR ) times than those who received spinal anesthesia ( 101 + /- 20 vs 83 + /- 16 min , [ mean + /- SD ] P < 0.001 ) ; this was caused by longer times spent in the OR until surgical incision ( 46 + /- 11 vs 29 + /- 6 min , P < 0.001 ) . Length of time spent in the postanesthesia recovery unit was similar in both groups . Supplemental intraoperative intravenous ( IV ) analgesics and anxiolytics were required more often in the epidural group ( 38 % ) than in the spinal group ( 17 % ) ( P < 0.05 ) . Complications were noted in six patients with epidural anesthesia and none with spinal anesthesia ( P < 0.05 ) . Average per-patient charges were more for the epidural group than for the spinal group . Although direct cost differences between the groups were negligible , there were more substantial indirect costs differences . We conclude that spinal block may provide better and more cost effective anesthesia for uncomplicated , elective cesarean sections . ( Anesth Analg 1995;80:709 - 12 Objective : To compare general , epidural and combined spinal-epidural anesthesia with respect to short-term outcome of newborns delivered by elective Cesarean section of healthy parturients with normal pregnancies . Study design : A total of 238 eight pregnant women admitted to our institution between January 1998 and July 2002 , for whom elective Cesarean section was planned after 38 weeks ' gestation , were grouped according to the kind of anesthesia used for the procedure . Maternal characteristics , birth weight , Apgar scores , and maternal and umbilical artery ( UA ) acid-base parameters were analyzed . Results : Maternal pH was significantly lower and pCO2 and pO2 were significantly higher in the general anesthetic group , compared to the other two groups ( 7.38 ± 0.03 vs. 7.43 ± 0.02 and 7.43 ± 0.05 , respectively ; 35.03 ± 3.88 mmHg vs. 29.25 ± 5.05 mmHg and 29.64 ± 4.16 mmHg , respectively ; and 224.56 ± 86.77 mmHg vs. 151.28 ± 38 mmHg and 157.36 ± 53.51 mmHg , respectively , p < 0.05 ) . The pH of the UA was higher in the general anesthetic group , compared to the spinal-epidural group ( 7.29 ± 0.02 vs. 7.26 ± 0.06 , p < 0.05 ) . The pO2 as well as O2 saturation of the UA were higher when general anesthetic was administered , compared to the two regional modalities ( 15.60 ± 5.48 mmHg vs. 9.29 ± 4.41 mmHg and 9.20 ± 4.06 mmHg , respectively ; and 17.37 ± 9.79 % vs. 7.87 ± 4.98 % and 6.90 ± 5.22 % , respectively , p < 0.05 ) . UA O2 saturation fell to zero in some cases in the combined spinal-epidural group , without an evident effect on fetal well-being . No fetal acidemia was noted in any group . Neonatal outcomes were similar in the three groups studied . Conclusions : Type of anesthesia does not influence short-term outcomes in infants born via elective Cesarean section , although differences in acid-base status of both the mother and especially the newborn recommend careful use of spinal anesthesia We investigated the necessity for administration of supplementary oxygen to mothers undergoing elective Caesarean section under spinal anaesthesia . Sixty‐nine women undergoing elective Caesarean section were r and omly allocated to one of three groups to be given either oxygen ( 40 % ) by facemask , air by facemask or oxygen at 2 l.min−1 by nasal cannulae . Umbilical arterial and venous blood sample s were taken and analysed immediately after delivery . The results showed that there were no significant differences in the umbilical arterial or venous pH , partial pressure of oxygen and partial pressure of carbon dioxide between any of the three groups . We also assessed the patient acceptability of oxygen administered by facemask vs. nasal cannulae should the need for supplementary oxygen arise . It was found that use of the facemask impeded communication BACKGROUND Oxygen supplementation is given routinely to parturients undergoing Caesarean section under regional anaesthesia . While the aim is to improve fetal oxygenation , inspiring a high oxygen fraction ( FIO2 ) can also increase free radical activity and lipid peroxidation in both the mother and baby . In this prospect i ve , r and omized , double-blind study , we investigated the effect of high inspired oxygen fraction ( FIO2 ) on maternal and fetal oxygenation and oxygen free radical activity in parturients having Caesarean section under spinal anaesthesia . METHODS Forty-four healthy parturients were r and omized to breathe either 21 % ( air group ) or 60 % oxygen ( oxygen group ) intraoperatively via a ventimask . Maternal arterial blood was collected at 5-min intervals from baseline until delivery , and umbilical arterial and venous blood was collected at delivery . We measured blood gases and the products of lipid peroxidation ( 8-isoprostane , malondialdehyde ( MDA ) , hydroperoxide ( OHP ) ) and purine metabolites . RESULTS At delivery , the oxygen group had greater maternal arterial PO2 [ mean 30.0 ( SD 6.3 ) vs 14.2 ( 1.9 ) kPa ; mean difference 15.8 kPa , 95 % confidence interval 12.9 - 18.7 kPa , P<0.001 ] and greater umbilical venous PO2 [ 4.8 ( 1.0 ) vs 4.0 ( 1.4 ) kPa ; mean difference 0.8 kPa , 95 % confidence interval 0.0 - 1.5 kPa , P=0.04 ] compared with the air group . Maternal and umbilical plasma concentrations of lipid peroxides ( 8-isoprostane , MDA , OHP ) were greater in the oxygen group than in the air group ( P<0.05 ) . CONCLUSIONS We conclude that breathing high FIO2 modestly increased fetal oxygenation but caused a concomitant increase in oxygen free radical activity in both mother and fetus We report the changes observed in a number of pulmonary function tests performed on 36 patients undergoing Caesarean section under spinal anaesthesia . The tests comprised peak expiratory flow , forced expiratory volume in one second , forced vital capacity , forced expiratory volume in one second to forced vital capacity ratio and the maximal mid‐expiratory flow . Significant changes occurred that are consistent with a restrictive ventilatory defect . These changes persisted for four hours after the induction of spinal anaesthesia . Administration of 35 % oxygen by facemask failed to change significantly fetal umbilical vein pH or partial pressure of oxygen Purpose The aim of this investigation was to determine whether supplementary oxygen provided by either nasal cannula or face mask versus room air might affect fetal oxygenation during elective cesarean section under spinal anesthesia by assessing maternal and neonatal regional cerebral oxygenation ( rSO2 ) with a cerebral oximeter . Methods Ninety parturients were r and omly allocated into three groups : two groups received 5 L/min oxygen by either nasal cannula ( Group NC , n = 30 ) or face mask ( Group FM , n = 30 ) , respectively , and the third group was allowed to breathe room air ( Group RA , n = 30 ) . After maternal mean arterial pressure , heart rate and peripheral oxygen saturation had been monitored , rSO2 was determined by cerebral oximeter . Umbilical artery ( UA ) and venous ( UV ) blood sample s were collected for blood gas analysis . Neonatal rSO2 and Apgar scores were recorded . Results The mean maternal rSO2 which was recorded 3 and 5 min after administration of the spinal block in Group FM was lower than that of Group NC ( p = 0.033 and 0.042 , respectively ) . Neonatal rSO2 , UA pH , UV pH and UA base excess ( BE ) were lower in Group FM than in the other groups ( p < 0.05 ) . The Apgar score ( 1 min ) in Group FM was lower than that of Group RA ( p = 0.046 ) . Conclusion The effect of maternal supplementary oxygen on the newborn has been demonstrated by a cerebral oximeter monitor and supported by umbilical cord blood gas analysis and Apgar scores OBJECTIVE To evaluate how often low 5-min Apgar scores ( AS(5-min ) ) at term are associated with asphyxia . STUDY DESIGN A cohort- and case-control study , including all 183 term infants with AS(5-min ) below 7 born at Lund University Hospital during 1993 - 2002 , antepartum deaths excluded . The control group included 183 r and omly selected term newborns with AS(5-min ) 9 - 10 . Cardiotocography ( CTG ) traces were assessed blinded to group and outcome . Obstetric and pediatric files were review ed . RESULTS After excluding infants with severe malformations , indications of hypoxia were found at the following rates in cases with AS(5-min ) below 4 ( N = 30 ) , scores 4 - 6 ( N = 143 ) , and controls ( N = 182)-abnormal admission CTG : 38 % , 8 % and 0.6 % ; abnormal CTG before birth : 88 % , 69 % and 18 % ; obstetrical catastrophe : 28 % , 6 % and 0.6 % ; interventions for fetal distress : 83 % , 48 % and 9 % ; cord artery pH below 7.15 : 69 % , 54 % and 7 % ; hypoxic ischemic encephalopathy or hypoxic death : 70 % , 14 % and none . All differences between each case group and controls were statistically significant ( p < 0.0001 ) . CONCLUSIONS In the absence of severe malformations , the vast majority of AS(5-min ) below 4 , and at least half of scores 4 - 6 could be attributed to birth asphyxia . Signs of hypoxia usually appeared during labor , but were present at admission in 38 % of cases with AS(5-min ) below 4 BACKGROUND AND OBJECTIVES We aim ed to investigate the effect of 21 % and 40 % oxygen supplementation on maternal and neonatal oxidative stress in elective cesarean section ( CS ) under spinal anesthesia . METHODS Eighty term parturients undergoing elective CS under spinal anesthesia were enrolled in the study . We allocated patients r and omly to breathe 21 % ( air group ) or 40 % ( oxygen group ) oxygen from the time of skin incision until the end of the operation . We collected maternal pre- and post-operative and umbilical artery ( UA ) blood sample s. Total antioxidant capacity ( TAC ) , total oxidant status ( TOS ) and the oxidative stress index ( OSI ) were measured . RESULTS Age , weight , height , parity , gestation week , spinal-skin incision time , skin incision-delivery time , delivery time , operation time , 1(st ) and 5(th ) minutes Apgar scores , and birth weight were similar between the groups ( p > 0.05 for all comparisons ) . There were no differences in preoperative TAC , TOS , or OSI levels between the groups ( p > 0.05 for all comparisons ) . Postoperative maternal TAC , TOS and OSI levels significantly increased in the oxygen group ( p = 0.047 , < 0.001 and 0.038 , respectively ) ; umbilical artery TAC levels significantly increased in the oxygen group ( p = 0.003 ) ; and umbilical artery TOS and OSI levels significantly increased in the air group ( p = 0.02 and < 0.001 , respectively ) . CONCLUSIONS The difference in impact on maternal and fetal oxidative stress of supplemental 40 % compared to 21 % oxygen m and ates further large-scale studies that investigate the role of oxygen supplementation during elective CS under spinal anesthesia BACKGROUND Controversy still exists if the administration of supplementary oxygen to patients having emergency Caesarean section ( CS ) under regional anaesthesia is beneficial or potentially harmful . Therefore , in a prospect i ve double-blinded study , we r and omized patients having emergency CS under regional anaesthesia to receive either air or 60 % oxygen until delivery and compared the effects on fetal oxygenation and lipid-peroxidation in the mother and baby . METHODS We recruited 131 women having emergency CS under regional anaesthesia . Either 21 % ( air group ) or 60 % oxygen ( oxygen group ) was administered using a Venturi-type facemask until delivery . We compared the oxygen exposure duration , umbilical arterial ( UA ) and venous ( UV ) blood gases and oxygen content , and plasma concentration of 8-isoprostane . Sub analysis was performed according to whether or not fetal compromise was considered present . RESULTS Data from 125 patients were analysed . For the oxygen group vs the air group , there were greater values for UA PO(2 ) [ mean 2.2 ( SD 0.5 ) vs 1.9 ( 0.6 ) kPa , P=0.01 ] , UA O(2 ) content [ 6.6 ( 2.5 ) vs 4.9 ( 2.8 ) ml dl(-1 ) , P=0.006 ] , UV PO(2 ) [ 3.8 ( 0.8 ) vs 3.2 ( 0.8 ) kPa , P<0.0001 ] , and UV O(2 ) content [ 12.9 ( 3.5 ) vs 10.4 ( 3.8 ) ml dl(-1 ) , P=0.001 ] . There was no difference between the groups in maternal , UA , or UV 8-isoprostane concentration . Apgar scores and UA pH were similar between the groups . Similar changes were observed regardless of whether fetal compromise was considered present ( n=37 ) or not ( n=88 ) . CONCLUSIONS Breathing 60 % oxygen during emergency CS under regional anaesthesia increased fetal oxygenation with no associated increase in lipid-peroxidation in the mother or fetus Background and objective : For many , the administration of additional oxygen to the women receiving regional anaesthesia for Caesarean section is traditional , but for others it is controversial because of doubts about its efficacy . The aim of our study was to determine if beneficial effects of maternal oxygen therapy on the fetus could be revealed using a neonatal behavioural scoring system . Methods : Sixty women with a normal singleton pregnancy beyond 36 weeks gestation , undergoing elective Caesarean section under spinal anaesthesia were r and omized into two groups : Group 1 received air and oxygen mixture through a Hudson style face mask ( FiO2 of 0.21–0.25 ) . Group 2 received FiO2 of 0.40–0.60 through an identical Hudson style face mask . Neurologic Adaptive Capacity Score on all the infants within 5 min of birth and between 10 and 24 h after the Caesarean delivery was performed . Apgar score , umbilical venous blood oxygen tension and umbilical artery st and ardized base excess were recorded . Results : Initial Neurologic Adaptive Capacity Scores at birth in Groups 1 and 2 were 32.6 ( SD 4.6 ) and 31.3 ( SD 4.3 ) , respectively . Latter scores were 36.0 ( SD 3.0 ) and 36.5 ( SD 1.9 ) , respectively . Neither were statistically significant . There were no significant differences between the groups for any of the recorded variables . Conclusions : Administering maternal oxygen using a st and ard commercial Hudson style face mask does not appear to significantly improve oxygen delivery to , nor does it influence acidosis or behavioural effects in , the normal neonate at elective Caesarean delivery with spinal anaesthesia BACKGROUND Routine administration of supplemental oxygen to parturients undergoing Caesarean section under spinal anaesthesia has been criticised in recent times . OBJECTIVES To assess the need for routine supplementary oxygen in healthy women undergoing Caesarean section under spinal anaesthesia in re source challenged setting and establish the efficacy of administration of oxygen at 4L/min . DESIGN Simple r and omized trial using sealed envelopes . SETTING The Obafemi Awolowo University Teaching Hospital ; a 580 bed hospital situated in Ile-Ife in South-western Nigeria . SUBJECTS Seventy parturients with ASA physical status I or II undergoing Caesarean section under spinal anaesthesia . MAIN OUTCOME MEASURES Outcome measures were arterial oxygen saturation ( SaO2 ) and Apgar scores at one and five minutes . RESULTS The mean pre-induction arterial oxygen saturation in the two groups were similar . There was a statistically significant difference in the mean SaO2 at one minute between the two groups , with the control group being higher ( 97.7 % + /- 1.5 % versus . 96.7 % + /- 1.5 % ; p-value = 0.008 ) . The mean least SaO2 during surgery was also higher in the control group ( 95.9 % + /- 1.5 % versus 94.9 % + /- 2.0 % , p-value = 0.015 ) . The Apgar score of the babies at one and five minutes for the study and control group were similar . CONCLUSION Healthy parturients undergoing Caesarean section under spinal anaesthesia do well without supplemental oxygen ; administration of supplemental oxygen from the common gas outlet of anaesthetic machine with the breathing circuit and st and ard anaesthetic facemask at 4L/min causes relative desaturation BACKGROUND AND OBJECTIVES Despite changes in pulmonary function , maternal oxygenation is maintained during obstetric regional blocks . But in those situations , the administration of supplementary oxygen to parturients is a common practice . Good fetal oxygenation is the main justification ; however , this has not been proven . The objective of this r and omized , prospect i ve study was to test the hypothesis of whether maternal hyperoxia is correlated with an increase in fetal gasometric parameters in elective cesarean sections . METHODS Arterial blood gases of 20 parturients undergoing spinal block with different inspired fractions of oxygen were evaluated and correlated with fetal arterial blood gases . RESULTS An increase in maternal inspired fraction of oxygen did not show any correlation with an increase of fetal partial oxygen pressure . CONCLUSIONS Induction of maternal hyperoxia by the administration of supplementary oxygen did not increase fetal partial oxygen pressure . Fetal gasometric parameters did not change even when maternal parameters changed , induced by hyperoxia , during cesarean section under spinal block BACKGROUND The benefit of administering supplementary oxygen during elective Caesarean section under regional anaesthesia is controversial . It has been hypothesized that its use would improve fetal oxygenation in the event of a prolonged uterine incision-to-delivery ( U-D ) interval . Our aim was to test this hypothesis in a prospect i ve , r and omized , double-blinded , controlled study . METHODS We allocated r and omly 204 women having elective Caesarean section under spinal anaesthesia to breathe 21 , 40 or 60 % oxygen . We recorded the U-D interval , umbilical arterial ( UA ) and venous ( UV ) blood gases and oxygen content and Apgar scores . Subgroup analysis was performed according to whether the U-D interval was prolonged ( > 180 s ) or not . RESULTS The U-D interval was < 180 s in 159 patients and > 180 s in 45 patients . There were no differences in UV or UA blood gases , oxygen content or Apgar scores between cases with and without a prolonged U-D interval . In cases without a prolonged U-D interval , administering 60 % oxygen increased UV PO(2 ) ( mean 4.3 ( SD 1.1 ) vs 3.7 ( 1.0 ) kPa , P=0.003 ) and oxygen content ( 14.4 ( 3.3 ) vs 12.9 ( 2.7 ) ml dl(-1 ) , P=0.007 ) compared with air . In cases with a prolonged U-D interval , administering 60 % oxygen increased UV PO(2 ) ( 4.6 ( 0.6 ) vs 3.9 ( 0.8 ) kPa , P=0.019 ) compared with air but there was no difference in UV oxygen content . There was no increase in the UV PO(2 ) or oxygen content when 40 % oxygen was administered compared with air . CONCLUSIONS Supplementary oxygen did not increase fetal oxygenation in cases where the U-D interval was prolonged . Our data do not support the routine administration of supplementary oxygen during elective Caesarean section for this purpose Thirty-two healthy pregnant women at term who were to undergo cesarean section following epidural anesthesia were r and omly assigned to receive preoperatively , by face mask , room air or oxygen for more than 10 minutes . Patients were kept at a left lateral tilt position of 15 degrees and were unaware which gas was administered . Oxygenation significantly increased ( p less than 0.05 ) maternal PO2 to 283 mm Hg ( SD 67 ) . The cord vein PO2 of the group receiving oxygen was 34 mm Hg ( SD 6 ) , significantly higher ( p less than 0.01 ) than the value of 26 mm Hg ( SD 7 ) in the group receiving room air . The cord artery PO2 of the oxygen group was also significantly higher ( p less than 0.05 ) at 20 mm Hg ( SD 6 ) versus 15 mm Hg ( SD 6 ) . No other cord gas values were significantly different . There was no significant difference in the cord vein-artery PO2 differential . There was no significant difference in the infants ' hematocrits determined at 4 hours of age in the two groups . All infants were in excellent condition ( 1-minute Apgar score greater than or equal to 8) Forty healthy parturients at term , undergoing elective Caesarean section , were divided into two groups to receive supplemental oxygen by either simple facemask ( Group FM , 8 L · min−1 ) or nasal prongs ( Group NP , 4 L · min−1 ) during the procedure . Anaesthesia was provided by épidural block to equivalent dermatomal levels in all patients . Maternal oxygen saturation was measured continuously with pulse oximetry and supplemental oxygen was provided to the mother after administration of the épidural test dose and continued until the end of the procedure . Following delivery of the infant and concurrent with Apgar scoring , the umbilical cord was double-clamped and arterial and venous sample s were drawn . The pH , partial pressures of O2 and CO2 and O2 saturations were measured . There was no différence in the clinical condition of the neonates , as assessed by Apgar scores , or in the acid-base and oxygenation status , as assessed by blood gas analyses between the two groups . Mean umbilical vein oxygen saturation , a measure of fetal oxygen delivery , was 46 ± 18 % ( 95 % confidence interval 39 % to 54 % ) for Group NP and 54 ± 17 % ( 95 % confidence interval 46 % to 62 % ) for Group FM , again not different . We conclude that when the clinical condition , acid-base and oxygenation status of neonates , delivered by elective Caesarean section to healthy , low-risk parturients with normal placental function under épidural anaesthesia , are evaluated , it makes no différence whether the mothers received supplemental oxygen by nasal prongs or simple facemask . RésuméQuarante parturientes saines , à terme et programmées pour une césarienne ont été reparties en deux groupes : un devant recevoir un supplément d’oxygène durant l’intervention au moyen d’une simple masque facial ( Group FM , 8 L · min−1 ) et l’autre au moyen de « lunettes » nasales ( Group NPO , 4 L · min−1 ) . L’anesthésie était réalisée au moyen d’un block épidural atteignant des niveaux sensitifs identiques pour toutes les patientes . La saturation maternelle en oxygène était constamment mesurée au moyen d’un saturomètre et un supplément d’oxygène était administré à la mère après l’administration de la dose test de l’epidurale et maintenu jusqu ’ à la fin de l’intervention chirurgicale . Après l’accouchement et concurremment à l’evaluation du score d’Apgar , un double clampage du cordon ombilical était effectué et des échantillons artériels et veineux prélevés . Le pH , les pressions partielles en O2 et en CO2 et les saturations en oxygène ont été mesurés . Entre ces deux groupes , il n’y a pas eu de différence de condition clinique pour les nouveauxnés , telle qu’évaluée par le score d’Apgar , ou de l’équilibre acido-basique et de l’oxygénation , tels qu’evalués par la gazométrie sanguine . La saturation moyenne en oxygène de sang ombilical veineux , une mesure du transport en oxygène chez le foetus , était de 46 ± 18 % ( intevalle de confiance à 95 % : 39 % à 54 % ) pour le Group NP et de 54± 17 % ( intervalle de confiance à 95 % : 46 à 62 % ) pour le Group FM , et , encore une fois , ne présentait pas de différence . Nous concluons que lorsqu’on évalue la condition clinique , l’equilibre acido-basique et l’oxygénation , chez les nouveauxnés de parturientes saines , à faible risque , présentant une fonction placentaire normale et accouchées par césarienne non urgente sous anesthésie épidurale , il n’y a pas de difference entre un simple masque facial et les « lunettes » nasales comme mode d’administration d’un supplément d’oxygène |
1,192 | 23,945,718 | Whole-grain consumption does not decrease body weight compared with control consumption , but a small beneficial effect on body fat may be present .
The relatively short duration of intervention studies ( ≤16 wk ) may explain the lack of difference in body weight and fat . | BACKGROUND Whole grains have received increased attention for their potential role in weight regulation .
A high intake has been associated with smaller weight gain in prospect i ve cohort studies , whereas the evidence from r and omized controlled studies has been less consistent .
OBJECTIVE We assessed the effects of whole-grain compared with non-whole-grain foods on changes in body weight , percentage of body fat , and waist circumference by using a meta-analytic approach . | This study was design ed as a test of the serum lipid response and dietary adaptation to recommended daily inclusion of instant oats in an otherwise regular diet . Hypercholesterolemic adults were r and omly assigned to a control or intervention group . Participants in the intervention group were given packages of instant oats and requested to eat two servings per day ( approximately two ounces dry weight ) , substituting the oats for other carbohydrate foods in order to maintain baseline calorie intake and keep weight stable . Serum lipids were measured in blood collected by venipuncture at baseline , four weeks , and eight weeks . Baseline mean total cholesterol ( TC ) levels were 6.56 mmol/L and 6.39 mmol/L for intervention and control groups , respectively . After eight weeks , mean serum total cholesterol of the intervention group was lower by -0.40 mmol/L , and mean net difference in TC between the two groups was 0.32 mmol/L ( 95 % CI : 0.09 , 0.54 ) . Low-density lipoprotein-cholesterol was similarly reduced with mean net difference of 0.25 mmol/L ( 95 % CI : 0.02 , 0.48 ) between the two groups . Mean soluble fiber intake increased along with slight self-imposed reductions in mean total fat , saturated fat , and dietary cholesterol intake in the intervention group . Neither group changed mean body weight . Daily inclusion of two ounces of oats appeared to facilitate reduction of serum total cholesterol and LDL-C in these hyperlipidemic individuals BACKGROUND Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease . OBJECTIVE We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults . DESIGN This controlled experiment compared insulin sensitivity between diets ( 55 % carbohydrate , 30 % fat ) including 6 - 10 servings/d of breakfast cereal , bread , rice , pasta , muffins , cookies , and snacks of either whole or refined grains . Total energy needs were estimated to maintain body weight . Eleven overweight or obese [ body mass index ( in kg/m(2 ) ) : 27 - 36 ] hyperinsulinemic adults aged 25 - 56 y participated in a r and omized crossover design . At the end of each 6-wk diet period , the subjects consumed 355 mL ( 12 oz ) of a liquid mixed meal , and blood sample s were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered . RESULTS Fasting insulin was 10 % lower during consumption of the whole-grain than during consumption of the refined-grain diet ( mean difference : -15 + /- 5.5 pmol/L ; P = 0.03 ) . After the whole-grain diet , the area under the 2-h insulin curve tended to be lower ( -8832 pmol.min/L ; 95 % CI : -18720 , 1062 ) than after the refined-grain diet . The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet ( 0.07 x 10(-4 ) mmol.kg(-1).min(-1 ) per pmol/L ; 95 % CI : 0.003 x 10(-4 ) , 0.144 x 10(-4 ) ) . CONCLUSION Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease BACKGROUND Whole-grain cereal foods including rye have been identified as providing significant health benefits that do not occur when refined-cereal foods are ingested . OBJECTIVES Foods ( 90 g ) containing whole-grain rye flour and whole-grain wheat flour were compared with low-fiber refined-cereal foods for their effects on markers of bowel health and the metabolic markers insulin and glucose . DESIGN Three 4-wk interventions were undertaken in a r and omized crossover design with 28 overweight men aged 40 - 65 y who had no history of bowel disease . Against a background intake of 14 g dietary fiber ( DF ) , the men were fed low-fiber cereal grain foods providing 5 g DF for a total of 19 g DF/d . High-fiber wheat foods provided 18 g DF , and high-fiber rye foods provided 18 g DF , both giving a total of 32 g DF/d . Fecal sample s ( 48-h ) and fasting and postpr and ial blood sample s were collected at the end of each period and assayed . RESULTS Both high-fiber rye and wheat foods increased fecal output by 33 - 36 % ( P = 0.004 ) and reduced fecal beta-glucuronidase activity by 29 % ( P = 0.027 ) . Postpr and ial plasma insulin was decreased by 46 - 49 % ( P = 0.0001 ) and postpr and ial plasma glucose by 16 - 19 % ( P = 0.0005 ) . Rye foods were associated with significantly ( P = 0.0001 ) increased plasma enterolactone ( 47 % and 71 % ) and fecal butyrate ( 26 % and 36 % ) , relative to wheat and low-fiber options , respectively . CONCLUSIONS High-fiber rye and wheat food consumption improved several markers of bowel and metabolic health relative to that of low-fiber food . Fiber from rye appears more effective than that from wheat in overall improvement of biomarkers of bowel health Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition BACKGROUND Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse , and characterization of this association has been obscured by method ologic inconsistencies in the assessment of whole grains . OBJECTIVE We aim ed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men . DESIGN The study was conducted in a prospect i ve cohort of 27 082 men aged 40 - 75 y at baseline in 1986 . Data on lifestyle factors were obtained periodically by using self-reported question naires , and participants measured and reported their body weight in 1986 and 1994 . RESULTS In multivariate analyses , an increase in whole-grain intake was inversely associated with long-term weight gain ( P for trend < 0.0001 ) . A dose-response relation was observed , and for every 40-g/d increment in whole-grain intake from all foods , weight gain was reduced by 0.49 kg . Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain ( P for trend = 0.01 ) , and , for every 20 g/d increase in intake , weight gain was reduced by 0.36 kg . Changes in cereal and fruit fiber were inversely related to weight gain . No associations were observed between changes in refined-grain or added germ consumption and body weight . CONCLUSIONS The increased consumption of whole grains was inversely related to weight gain , and the associations persisted after changes in added bran or fiber intakes were accounted for . This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes , but the mechanisms remain unclear . Our study aim ed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation . In a r and omized crossover study , 22 women and 8 men ( BMI 28 + /- 2 ) were given either whole-grain or refined-grain products ( 3 bread slices , 2 crisp bread slices , 1 portion muesli , and 1 portion pasta ) to include in their habitual daily diet for two 6-wk periods . Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests . 8-Iso-prostagl and in F(2alpha ) ( 8-iso PGF(2alpha ) ) , an F(2)-isoprostane , was measured in the urine as a marker of lipid peroxidation , and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation . Peripheral insulin sensitivity [ mg glucose . kg body wt(-1 ) . min(-1 ) per unit plasma insulin ( mU/L ) x 100 ] did not improve when subjects consumed whole-grain products ( 6.8 + /- 3.0 at baseline and 6.5 + /- 2.7 after 6 wk ) or refined products ( 6.4 + /- 2.9 and 6.9 + /- 3.2 , respectively ) and there were no differences between the 2 periods . Whole-grain consumption also did not affect 8-iso-PGF(2alpha ) in urine , IL-6 and C-reactive protein in plasma , blood pressure , or serum lipid concentrations . In conclusion , substitution of whole grains ( mainly based on milled wheat ) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation Hypertension , dyslipidemia and overweight contribute substantially to cardiovascular disease risk . One of the most effective methods for improving high blood pressure and lipid profiles is loss of excess weight . Other recommendations for reducing cardiovascular risk include changes in dietary micronutrient , macronutrient and fiber intakes . To better define a diet for reduction in cardiovascular risk , 43 adults ( body mass index 26.4 + /- 3.3 , range 20.5 - 33.9 kg/m(2 ) ) participated in an 8-wk study to determine the effects of two diets on weight , blood pressure , lipids and insulin sensitivity . For 2 wk , weight was maintained and all subjects consumed a control diet . For the next 6 wk , subjects consumed one of two hypocaloric diets ( maintenance energy minus 4.2 MJ/d ) : the control diet ( n = 21 ) or a diet containing oats [ 45 g/(4.2 MJ dietary energy . d ) , n = 22 ] . There was no significant difference between groups in changes in weight loss ( control -4.0 + /- 1.1 kg , oats -3.9 + /- 1.6 kg , P = 0.8 ) . The oats diet result ed in greater decreases in mean systolic blood pressure ( oats -6 + /- 7 mm Hg , control -1 + /- 10 mm Hg , P = 0.026 ) , whereas diastolic blood pressure change did not differ between the two groups ( oats -4 + /- 6 mm Hg , control -3 + /- 5 mm Hg , P = 0.8 ) . The oat diet result ed in significantly greater decreases in total cholesterol ( oats -0.87 + /- 0.47 mmol/L , control -0.34 + /- 0.5 mmol/L , P = 0.003 ) and LDL cholesterol ( oats -0.6 + /- 0.41 mmol/L , control -0.2 + /- 0.41mmol/L , P = 0.008 ) . In summary , a hypocaloric diet containing oats consumed over 6 wk result ed in greater improvements in systolic blood pressure and lipid profile than did a hypocaloric diet without oats The objective of this study was to determine the hypocholesterolemic effects of whole meal rye and white wheat breads in healthy humans with elevated serum cholesterol concentrations , and the changes in plasma glucose and insulin concentrations during rye and wheat bread periods . The subjects were 18 men and 22 women with baseline serum cholesterol concentration of 6.4+/-0.2 mmol/L. The study design was a 2x4-wk crossover trial during which each subject r and omly consumed rye and wheat breads ( 20 % of daily energy ) as part of their usual diet for 4 wk . The bread periods were separated by a 4-wk washout period . Blood sample s ( after fasting ) were collected on two consecutive days at the beginning and end of the bread periods . Serum total cholesterol decreased by 8 % ( P = 0.002 ) in men but was not significantly altered in women during the rye bread period . The wheat bread period did not affect any of the variables studied . Analysis of the serum lipids in tertiles of rye bread consumption confirmed the reduction in total cholesterol ( P = 0.048 ) in men and revealed the reduction in LDL cholesterol ( P = 0.032 ) ; both were dependent on the amount of rye bread consumed ( -2 , -14 and -10 % in total cholesterol and 0 , -12 and -12 % in LDL cholesterol ) . Neither rye nor wheat bread influenced the concentrations of glucose and insulin . In conclusion , rye bread is effective in reducing serum total and LDL cholesterol concentrations in men with elevated serum cholesterol . Good compliance with consuming a relatively large amount of rye bread in the usual diet indicates that rye bread offers a practical dietary means of reducing serum cholesterol in men BACKGROUND Although increased consumption of dietary fiber and grain products is widely recommended to maintain healthy body weight , little is known about the relation of whole grains to body weight and long-term weight changes . OBJECTIVE We examined the associations between the intakes of dietary fiber and whole- or refined-grain products and weight gain over time . DESIGN In a prospect i ve cohort study , 74,091 US female nurses , aged 38 - 63 y in 1984 and free of known cardiovascular disease , cancer , and diabetes at baseline , were followed from 1984 to 1996 ; their dietary habits were assessed in 1984 , 1986 , 1990 , and 1994 with vali date d food-frequency question naires . Using multiple models to adjust for covariates , we calculated average weight , body mass index ( BMI ; in kg/m(2 ) ) , long-term weight changes , and the odds ratio of developing obesity ( BMI > or = 30 ) according to change in dietary intake . RESULTS Women who consumed more whole grains consistently weighed less than did women who consumed less whole grains ( P for trend < 0.0001 ) . Over 12 y , those with the greatest increase in intake of dietary fiber gained an average of 1.52 kg less than did those with the smallest increase in intake of dietary fiber ( P for trend < 0.0001 ) independent of body weight at baseline , age , and changes in covariate status . Women in the highest quintile of dietary fiber intake had a 49 % lower risk of major weight gain than did women in the highest quintile ( OR = 0.51 ; 95 % CI : 0.39 , 0.67 ; P < 0.0001 for trend ) . CONCLUSION Weight gain was inversely associated with the intake of high-fiber , whole-grain foods but positively related to the intake of refined-grain foods , which indicated the importance of distinguishing whole-grain products from refined-grain products to aid in weight control 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 Himalaya 292 ( Hordeum vulgare var . Himalaya 292 ) is a novel hull-less barley variety lacking activity of a key enzyme of starch synthesis giving a grain containing less total starch , more amylose and higher total dietary fibre . Animal trials have shown that Himalaya 292 contains more resistant starch and has greater positive impact on biomarkers of large-bowel health than comparable wholegrain cereal products . The present study compared the effects of foods made from wholegrain Himalaya 292 with those made from wholegrain wheat on faecal biomarkers of bowel health in human subjects . Seventeen male and female volunteers aged 31 - 66 years consumed similar quantities of Himalaya 292 , whole-wheat or refined cereal foods daily for 4 weeks in a r and omised cross-over design . Total dietary fibre intakes from weighed food records were 45 , 32 and 21 g/d for the Himalaya 292 , whole-wheat and refined cereal periods , respectively . Compared with the refined cereal foods , consumption of Himalaya 292 foods result ed in 33 % higher faecal weight , a lowering of faecal pH from 7.24 to 6.98 , a 42 % higher faecal concentration and a 91 % higher excretion of butyrate , a 57 % higher faecal total SCFA excretion and a 33 % lower faecal p-cresol concentration . pH and butyrate concentration and excretion were also significantly different compared with wholemeal wheat . It is concluded that consumption of a diet that included foods made from Himalaya 292 supplied more fibre and improved indices of bowel health compared with refined cereal foods and , for some indices , similar wholemeal wheat foods at equivalent levels of intake OBJECTIVE Prospect i ve studies have suggested that substituting whole grain for refined grain products may lower the risk of overweight and obesity . Breakfast cereal intake is a major source of whole and refined grains and has also been associated with having a lower BMI . The aim of this study was to prospect ively assess the association between whole and refined grain breakfast cereal intakes and risk of overweight ( BMI > or= 25 kg/m(2 ) ) and weight gain . RESEARCH METHODS AND PROCEDURES We examined 17,881 U.S. male physicians 40 to 84 years of age in 1982 who were free of cardiovascular disease , diabetes mellitus , and cancer at baseline and reported measures of breakfast cereal intake , weight , and height . RESULTS Over 8 and 13 years of follow-up , respectively , men who consumed breakfast cereal , regardless of type , consistently weighed less than those who consumed breakfast cereals less often ( p value for trend = 0.01 ) . Whole and refined grain breakfast cereal intake was inversely associated with body weight gain over 8 years , after adjustment for age , smoking , baseline BMI , alcohol intake , physical activity , hypertension , high cholesterol , and use of multivitamins . Compared with men who rarely or never consumed breakfast cereals , those who consumed > or=1 serving/d of breakfast cereals were 22 % and 12 % less likely to become overweight during follow-up periods of 8 and 13 years ( relative risk , 0.78 and 0.88 ; 95 % confidence interval , 0.67 to 0.91 and 0.76 to 1.00 , respectively ) . DISCUSSION BMI and weight gain were inversely associated with intake of breakfast cereals , independently of other risk factors Recommendations for whole-grain ( WG ) intake are based on observational studies showing that higher WG consumption is associated with reduced CVD risk . No large-scale , r and omised , controlled dietary intervention studies have investigated the effects on CVD risk markers of substituting WG in place of refined grains in the diets of non-WG consumers . A total of 316 participants ( aged 18 - 65 years ; BMI > 25 kg/m2 ) consuming < 30 g WG/d were r and omly assigned to three groups : control ( no dietary change ) , intervention 1 ( 60 g WG/d for 16 weeks ) and intervention 2 ( 60 g WG/d for 8 weeks followed by 120 g WG/d for 8 weeks ) . Markers of CVD risk , measured at 0 ( baseline ) , 8 and 16 weeks , were : BMI , percentage body fat , waist circumference ; fasting plasma lipid profile , glucose and insulin ; and indicators of inflammatory , coagulation , and endothelial function . Differences between study groups were compared using a r and om intercepts model with time and WG intake as factors . Although reported WG intake was significantly increased among intervention groups , and demonstrated good participant compliance , there were no significant differences in any markers of CVD risk between groups . A period of 4 months may be insufficient to change the lifelong disease trajectory associated with CVD . The lack of impact of increasing WG consumption on CVD risk markers implies that public health messages may need to be clarified to consider the source of WG and /or other diet and lifestyle factors linked to the benefits of whole-grain consumption seen in observational studies The physiologic consequences of using white rice or mixed rice were evaluated in overweight Korean women ( body mass index > or = 25 kg/m(2 ) ) over a period of 6 weeks . Forty women between 20 and 35 years of age were r and omly divided into 2 groups who consumed 1 of 2 low-energy meal replacements containing either white rice ( WR group ) or mixture of brown rice and black rice ( BRBL group ) . The subjects were not allowed to have any food other than the low-energy meal replacement 3 times a day and snacks provided by the research er . The changes in anthropometric indices and blood parameters such as lipid levels and antioxidant activities were measured every 3 weeks during the dietary intervention . The subjects showed a significant reduction in weight , body mass index , and body fat ( % ) during the experimental period , with the BRBL group exhibiting levels of all 3 parameters significantly lower than those of the WR group ( P < .05 ) . The levels of total cholesterol and triacylglycerols decreased gradually and significantly after intervention in both groups , with no significant difference between groups . High-density lipoprotein cholesterol was significantly elevated in the BRBL group but not in the WR group . Superoxide dismutase activity was not affected by dietary intervention , but glutathione peroxidase activity in the BRBL group was higher than in the WR group , and the level of thiobarbituric acid-reactive substance was lower in the BRBL group compared to the WR group . In conclusion , meal replacement with mixed rice was superior to replacement with white rice in weight control , improving antioxidant enzyme activity , and as such , should be recommended for diet therapy in obese women Observational studies show inverse associations between intake of whole grain and adiposity and cardiovascular risk ; however , only a few dietary intervention trials have investigated the effect of whole-grain consumption on health outcomes . We studied the effect of replacing refined wheat ( RW ) with whole-grain wheat ( WW ) for 12 wk on body weight and composition after a 2-wk run-in period of consumption of RW-containing food intake . In this open-label r and omized trial , 79 overweight or obese postmenopausal women were r and omized to an energy-restricted diet ( deficit of ~1250 kJ/d ) with RW or WW foods providing 2 MJ/d . Body weight and composition , blood pressure , and concentration of circulating risk markers were measured at wk 0 , 6 , and 12 . Fecal output and energy excretion were assessed during run-in and wk 12 . Plasma alkylresorcinol analysis indicated good compliance with the intervention diets . Body weight decreased significantly from baseline in both the RW ( -2.7 ± 1.9 kg ) and WW ( -3.6 ± 3.2 kg ) groups , but the decreases did not differ between the groups ( P = 0.11 ) . The reduction in body fat percentage was greater in the WW group ( -3.0 % ) than in the RW group ( -2.1 % ) ( P = 0.04 ) . Serum total and LDL cholesterol increased by ~5 % ( P < 0.01 ) in the RW group but did not change in the WW group ; hence , the changes differed between the groups ( P = 0.02 ) . In conclusion , consumption of whole-grain products result ed in a greater reduction in the percentage fat mass , whereas body weight changes did not differ between the RW and WW groups . Serum total and LDL cholesterol , two important risk factors of cardiovascular disease , increased with RW but not WW consumption , which may suggest a cardioprotective role for whole grain Background and aims : Caloric restriction ( CR ) attenuates biological aging in animal models but there is little information on the feasibility and efficacy of CR regimens in humans . We examined the effects of consuming an insoluble cereal fiber supplement on ability to sustain CR over 1 year in healthy overweight adults . Methods : In 34 healthy overweight women and men ( BMI 25–30 kg/m2 , age 20–42 yr ) , a 30 % CR regimen meeting national recommendations for dietary fiber was provided for 24 weeks , and for an additional 24 weeks subjects were counseled to prepare the same regimen at home . During 5–10 weeks of CR , subjects were r and omized to consume an extra 20 g/day of dietary fiber from a high fiber cereal ( + F ) or to not consume additional fiber ( −F ) . After this time , all subjects were encouraged to consume the extra fiber . Outcomes included adherence to the provided and self-prepared CR regimens ( energy intake determined using doubly labeled water ) , changes in body weight , and self-reported satisfaction with the amount of consumed food . Results : During 5–10 weeks of CR when all food was provided , both + F and −F groups were highly adherent to the CR regimen and there was no significant difference between groups in energy intake ( p=0.51 ) , weight change ( p=0.96 ) , or satisfaction with amount of provided food ( p=0.08 ) . During self-prepared CR from 25 to 48 weeks , mean adherence was lower than during the food-provided phase and there was a significant association between fiber intake and % CR ( r=0.69 , p<0.001 ) , decreased BMI ( r=− 0.38 , p=0.04 ) and satisfaction with the amount of consumed food ( r=0.59 , p=0.002 ) . Conclusions : A high fiber cereal intake may facilitate CR in humans self- selecting their own food ; longer-term intervention studies are needed to confirm these findings OBJECTIVE While various weight-management approaches produce weight loss , they may differ in dietary quality . We monitored changes in nutrient intakes in overweight and obese subjects on three different weight-management programs . DESIGN R and omized clinical trial ( pilot study ) with two 12-week phases : phase 1 , weekly counseling ; phase 2 , monitoring only . SUBJECTS/ SETTING One hundred eighty nonsmoking , sedentary overweight and obese adults began this outpatient study ; 134 ( body mass index [ calculated as kg/m(2)]=30.9+/-2.4 ; age=42.3+/-1.2 years ) were used in analyses . INTERVENTION Twenty-four weeks of exercise only ( control group ) , hypocaloric diet plus exercise , or hypocaloric diet with fiber-rich whole-grain cereals plus exercise . MAIN OUTCOME MEASURES At weeks 0 , 12 , and 24 , diet quality was assessed by 3-day food records and body weight was measured . STATISTICAL ANALYSES PERFORMED Three-way analysis of variance with repeated measures . RESULTS The hypocaloric diet with fiber-rich whole-grain cereals plus exercise decreased energy intake more than exercise only ( P=0.032 ) . By week 12 , the hypocaloric diet with fiber-rich whole-grain cereals plus exercise and the hypocaloric diet plus exercise decreased total fat more than exercise only , which was sustained in the hypocaloric diet with fiber-rich whole-grain cereals plus exercise at 24 weeks ( P<0.001 ) . At weeks 12 and 24 , the hypocaloric diet with fiber-rich whole-grain cereals plus exercise reduced saturated fat intake more than exercise only . The hypocaloric diet with fiber-rich whole-grain cereals plus exercise increased total fiber , insoluble fiber ( both P<0.001 ) , magnesium ( P=0.004 ) , and vitamin B-6 ( P=0.002 ) intakes more than the hypocaloric diet plus exercise and exercise only . Calcium and vitamin E intakes were inadequate in all groups . Weight loss was similar in the hypocaloric diet with fiber-rich whole-grain cereals plus exercise and the hypocaloric diet plus exercise . CONCLUSIONS Weight-reduction strategies may be associated with reduced intake of micronutrients , such as calcium and vitamin E. However , a hypocaloric diet with fiber-rich whole-grain cereal is effective for improving or maintaining other aspects of dietary quality during weight loss The purpose of this study was to confirm and extend previous findings that serum cholesterol response to a fat-modified diet is enhanced by oat fiber . Participants ( n = 236 ) were recruited from the Continental Illinois National Bank in Chicago . Data including weight , serum lipid level , lipoproteins , and 3-day food records were collected at baseline and every 4 weeks for 12 weeks . All participants were instructed to follow the fat-modified ( Phase II ) diet recommended by the American Heart Association ( AHA ) . After 4 weeks , participants were r and omly assigned to one of two groups . While both groups continued to follow the AHA diet , Group 1 was instructed to include 2 oz ( 56 g , dry wt ) of oatmeal , isocalorically substituted for other carbohydrate foods . Group 2 served as the control and consumed no oat products throughout the study . Serum cholesterol values at baseline and after 4 weeks of the AHA diet were similar for both groups ( 203.9 and 193.0 mg/dl for Group 1 and 205.3 and 194.5 mg/dl for Group 2 ) . After 4 weeks of oatmeal intervention , mean group differences were -6.8 and -2.1 mg/dl ( P = 0.008 one-tailed t test ) for Groups 1 and 2 , respectively . Following an additional 4 weeks of oatmeal intervention , the Group 1 mean cholesterol increased slightly ( 0.9 mg/dl ) , while the Group 2 level decreased slightly ( -0.7 mg/dl ) . Overall serum cholesterol responses for the two groups from Visit 2 to Visit 4 were -6.0 and -2.8 mg/dl for Groups 1 and 2 , respectively ( P = 0.074 , one tail ) . Changes in weight were small and nonsignificant . Subgroup analyses revealed greater reductions in serum cholesterol among participants with the highest baseline serum cholesterol ( -8.0 mg/dl vs -1.7 mg/dl for Subgroups 1 and 2 , respectively ) . These data support previous findings that inclusion of oatmeal in a fat-modified diet is helpful in lowering serum cholesterol , particularly for individuals with elevated serum cholesterol levels BACKGROUND AND AIM The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies , although the mechanisms of this association are unclear . Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form . METHODS AND RESULTS Fifteen healthy individuals ( 12 M/3 F ) , mean age 54.5+/-7.6 years , BMI 27.4+/-3.0 kg/m(2 ) ( mean+/-SD ) , participated in a r and omized sequential crossover study . After 2 weeks run-in , participants were r and omly assigned to two isoenergetic diets with similar macronutrient composition , one rich in wholemeal wheat foods and the other with the same foods but in refined form ( cereal fibre 23.1 vs. 9.8 g/day ) . After the two treatment periods ( each lasting 3 weeks ) plasma glucose and lipid metabolism , antioxidant activity , acetic acid , magnesium , adipokines , incretins and high-sensitivity C-reactive protein ( hs-CRP ) were measured at fasting and for 4h after a st and ard test meal ( kcal 1103 , protein 12 % , CHO 53 % , fat 35 % ) based on wholemeal or refined wheat foods , respectively . After the two diets there were no differences in fasting nor in postpr and ial plasma parameter responses ; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal . Conversely , after the wholemeal diet both total ( -4.3 % ; p<0.03 ) and LDL ( -4.9 % ; p<0.04 ) cholesterol levels were lower than after the refined wheat diet at fasting . CONCLUSIONS Consumption of wholemeal wheat foods for 3 weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism , antioxidant status and sub- clinical inflammation markers BACKGROUND Three daily portions of whole-grain foods could lower cardiovascular disease risk , but a comprehensive intervention trial was needed to confirm this recommendation . OBJECTIVES We aim ed to assess the effects of consumption of 3 daily portions of whole-grain foods ( provided as only wheat or a mixture of wheat and oats ) on markers of cardiovascular disease risk in relatively high-risk individuals . DESIGN This was a r and omized controlled dietary trial in middle-aged healthy individuals . After a 4-wk run-in period with a refined diet , we r and omly allocated volunteers to a control ( refined diet ) , wheat , or wheat + oats group for 12 wk . The primary outcome was a reduction of cardiovascular disease risk factors by dietary intervention with whole grains , which included lipid and inflammatory marker concentrations , insulin sensitivity , and blood pressure . RESULTS We recruited a total of 233 volunteers ; 24 volunteers withdrew , and 3 volunteers were excluded . Systolic blood pressure and pulse pressure were significantly reduced by 6 and 3 mm Hg , respectively , in the whole-grain foods groups compared with the control group . Systemic markers of cardiovascular disease risk remained unchanged apart from cholesterol concentrations , which decreased slightly but significantly in the refined group . CONCLUSIONS Daily consumption of 3 portions of whole-grain foods can significantly reduce cardiovascular disease risk in middle-aged people mainly through blood pressure-lowering mechanisms . The observed decrease in systolic blood pressure could decrease the incidence of coronary artery disease and stroke by ≥15 % and 25 % , respectively . This trial was registered at clinical trials.gov as IS RCT N27657880 This r and omized , controlled trial of cholesterol lowering by an oat bran cereal containing beta glucan vs a corn cereal without soluble fiber in Hispanic Americans was conducted for 11 weeks . One-hundred fifty-two men and women , ages 30 to 70 years , with baseline low-density lipoprotein cholesterol ( LDL-C ) levels between 120 and 190 mg/dL and triglycerides < 400 mg/dL were included . After eating a National Cholesterol Education Program Step 1 diet for 5 weeks , subjects were r and omly assigned to the corn or the oat cereal for the next 6 weeks . The daily dose of beta glucan was 3 g. Consumption of oat cereal was associated with a reduction in plasma levels of both total cholesterol ( -10.9+/-21.6 mg/dL ; -4.5 % ) and LDL-C ( -9.4+/-20.3 mg/dL ; -5.3 % ) . Consumption of corn cereal did not affect either total cholesterol ( + 1.2+/-18.3 mg/dL ; 1.1 % ) or LDL-C ( + 1.2+/-17.5 mg/dL ; 2.2 % ) . Differences between the effects of the two cereals on total cholesterol and LDL-C were significant , P = .0003 and P = .0007 , respectively Foods high in dietary fiber may play an important role in regulating body weight . Few observational studies have examined the relationship between dietary fiber from different sources and body fat in older adults . Our objectives were to examine the associations among grain intake ( whole and refined ) , dietary fiber and fiber sources , and body fat among older adults . We used data from 434 free-living adults ( 177 men and 257 women ) aged between 60 and 80 y. Dietary intake was estimated from a 126-item semiquantitative FFQ . Percent body fat and percent trunk fat mass were measured by whole-body dual-energy X-ray absorptiometry . After adjustment for covariates , whole-grain intake was inversely associated with BMI [ 26.8 kg/m(2 ) ( 25.7 - 28.1 ) vs. 25.8 kg/m(2 ) ( 24.6 - 27.1 ) , ( 95 % CI ) ; P-trend = 0.08 ] , percent body fat [ 34.5 % ( 32.7 - 36.3 ) vs. 32.1 % ( 30.1 - 34.1 ) ; P-trend = 0.02 ] , and percent trunk fat mass [ 43.0 % ( 40.4 - 45.5 ) vs. 39.4 % ( 36.7 - 42.1 ) ; P-trend = 0.02 ] in the lowest compared with the highest quartile category of whole-grain intake . Refined grain intake was not associated with any measure of body fat distribution . Cereal fiber was inversely associated with BMI [ 27.3 kg/m(2 ) ( 26.1 - 28.6 ) vs. 25.4 kg/m(2 ) ( 24.3 - 26.7 ) ; P-trend = 0.012 ] , percent body fat [ 34.7 % ( 32.8 - 36.6 ) vs. 31.5 % ( 29.4 - 33.5 ) ; P-trend = 0.004 ] , and percent trunk fat mass [ 42.8 % ( 40.2 - 45.4 ) vs. 37.8 % ( 35.0 - 40.6 ) ; P-trend = 0.001 ] . No significant association was observed between intakes of total fiber , vegetable or fruit fiber , and body composition measurements . Higher intakes of cereal fiber , particularly from whole-grain sources , are associated with lower total percent body fat and percent trunk fat mass in older adults OBJECTIVE Weight loss and consumption of viscous fibers both lower low-density lipoprotein ( LDL ) cholesterol levels . We evaluated whether or not a whole-grain , ready-to-eat ( RTE ) oat cereal containing viscous fiber , as part of a dietary program for weight loss , lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone . DESIGN R and omized , parallel-arm , controlled trial . SUBJECTS/ SETTING Free-living , overweight and obese adults ( N=204 , body mass index 25 to 45 ) with baseline LDL cholesterol levels 130 to 200 mg/dL ( 3.4 to 5.2 mmol/L ) were r and omized ; 144 were included in the main analysis of participants who completed the trial without significant protocol violations . INTERVENTION Two portions per day of whole-grain RTE oat cereal ( 3 g/day oat b-glucan ) or energy-matched low-fiber foods ( control ) , as part of a reduced energy ( approximately 500 kcal/day deficit ) dietary program that encouraged limiting consumption of foods high in energy and fat , portion control , and regular physical activity . MAIN OUTCOME MEASURES Fasting lipoprotein levels , waist circumference , triceps skinfold thickness , and body weight were measured at baseline and weeks 4 , 8 , 10 , and 12 . RESULTS LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control ( -8.7+/-1.0 vs -4.3+/-1.1 % , P=0.005 ) . Total cholesterol ( -5.4+/-0.8 vs -2.9+/-0.9 % , P=0.038 ) and non-high-density lipoprotein-cholesterol ( -6.3+/-1.0 vs -3.3+/-1.1 % , P=0.046 ) were also lowered significantly more with whole-grain RTE oat cereal , whereas high-density lipoprotein and triglyceride responses did not differ between groups . Weight loss was not different between groups ( -2.2+/-0.3 vs -1.7+/-0.3 kg , P=0.325 ) , but waist circumference decreased more ( -3.3+/-0.4 vs -1.9+/-0.4 cm , P=0.012 ) with whole-grain RTE oat cereal . Larger reductions in LDL , total , and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group . CONCLUSIONS Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference |
1,193 | 32,025,512 | Our analysis revealed no significant differences between the oral mycobiome of breastfed and bottle-fed children .
As for the delivery mode , the majority of studies found a relation between fungal colonization and vaginal delivery .
Our analysis suggests that maternal breastfeeding does not seem to influence oral mycology , but vaginal delivery appears to promote oral yeast colonization in early life | Postnatal acquisition of microorganisms from maternal and environmental sources contributes to the child microbiome development .
Several studies showed that the mode of delivery and breastfeeding may have impact on the oral bacterial colonization , however , the influence on oral fungal colonization is still unknown .
We performed a systematic literature review on mother to child oral fungi transmission , namely regarding the association between the mode of delivery and breastfeeding in oral yeast colonization . | Human microbial communities are characterized by their taxonomic , metagenomic and metabolic diversity , which varies by distinct body sites and influences human physiology . However , when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored . We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers . A cohort of pregnant women in their early third trimester ( n = 81 ) were prospect ively enrolled for longitudinal sampling through 6 weeks after delivery , and a second matched cross-sectional cohort ( n = 81 ) was additionally recruited for sampling once at the time of delivery . Sample s across multiple body sites , including stool , oral gingiva , nares , skin and vagina were collected for each maternal – infant dyad . Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota . We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery , with the notable exception of the neonatal meconium . However , by 6 weeks after delivery , the infant microbiota structure and function had substantially exp and ed and diversified , with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity . Although minor variations in the neonatal ( immediately at birth ) microbiota community structure were associated with the cesarean mode of delivery in some body sites ( oral gingiva , nares and skin ; R2 = 0.038 ) , this was not true for neonatal stool ( meconium ; Mann – Whitney P > 0.05 ) , and there was no observable difference in community function regardless of delivery mode . For infants at 6 weeks of age , the microbiota structure and function had exp and ed and diversified with demonstrable body site specificity ( P < 0.001 , R2 = 0.189 ) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery ( P = 0.057 , R2 = 0.007 ) . We conclude that within the first 6 weeks of life , the infant microbiota undergoes substantial reorganization , which is primarily driven by body site and not by mode of delivery Importance Establishment of the infant microbiome has lifelong implication s on health and immunity . Gut microbiota of breastfed compared with nonbreastfed individuals differ during infancy as well as into adulthood . Breast milk contains a diverse population of bacteria , but little is known about the vertical transfer of bacteria from mother to infant by breastfeeding . Objective To determine the association between the maternal breast milk and areolar skin and infant gut bacterial communities . Design , Setting , and Participants In a prospect i ve , longitudinal study , bacterial composition was identified with sequencing of the 16S ribosomal RNA gene in breast milk , areolar skin , and infant stool sample s of 107 healthy mother-infant pairs . The study was conducted in Los Angeles , California , and St Petersburg , Florida , between January 1 , 2010 , and February 28 , 2015 . Exposures Amount and duration of daily breastfeeding and timing of solid food introduction . Main Outcomes and Measures Bacterial composition in maternal breast milk , areolar skin , and infant stool by sequencing of the 16S ribosomal RNA gene . Results In the 107 healthy mother and infant pairs ( median age at the time of specimen collection , 40 days ; range , 1 - 331 days ) , 52 ( 43.0 % ) of the infants were male . Bacterial communities were distinct in milk , areolar skin , and stool , differing in both composition and diversity . The infant gut microbial communities were more closely related to an infant ’s mother ’s milk and skin compared with a r and om mother ( mean difference in Bray-Curtis distances , 0.012 and 0.014 , respectively ; P < .001 for both ) . Source tracking analysis was used to estimate the contribution of the breast milk and areolar skin microbiomes to the infant gut microbiome . During the first 30 days of life , infants who breastfed to obtain 75 % or more of their daily milk intake received a mean ( SD ) of 27.7 % ( 15.2 % ) of the bacteria from breast milk and 10.3 % ( 6.0 % ) from areolar skin . Bacterial diversity ( Faith phylogenetic diversity , P = .003 ) and composition changes were associated with the proportion of daily breast milk intake in a dose-dependent manner , even after the introduction of solid foods . Conclusions and Relevance The results of this study indicate that bacteria in mother ’s breast milk seed the infant gut , underscoring the importance of breastfeeding in the development of the infant gut microbiome Infant microbiota is influenced by numerous factors , such as delivery mode , environment , prematurity and diet ( breast milk or formula ) . In addition to its nutritional value , breast milk contains bioactive substances that drive microbial colonisation and support immune system development , which are usually not present in infant formulas . Among these substances , polyamines have been described to be essential for intestinal and immune functions in newborns . However , their effect on the establishment of microbiota remains unclear . Therefore , the aim of the present study was to ascertain whether an infant formula supplemented with polyamines has an impact on microbial colonisation by modifying it to resemble that in breast-fed neonatal BALB/c mice . In a 4 d intervention , a total of sixty pups ( 14 d old ) were r and omly assigned to the following groups : ( 1 ) breast-fed group ; ( 2 ) non-enriched infant formula-fed group ; ( 3 ) three different groups fed an infant formula enriched with increasing concentrations of polyamines ( mixture of putrescine , spermidine and spermine ) , following the proportions found in human milk . Microbial composition in the contents of the oral cavity , stomach and small and large intestines was analysed by quantitative PCR targeted at fourteen bacterial genera and species . Significantly different ( P < 0·05 ) microbial colonisation patterns were observed in the entire gastrointestinal tract of the breast-fed and formula-fed mice . In addition , our findings demonstrate that supplementation of polyamines regulates the amounts of total bacteria , Akkermansia muciniphila , Lactobacillus , Bifidobacterium , Bacteroides-Prevotella and Clostridium groups to levels found in the breast-fed group . Such an effect requires further investigation in human infants , as supplementation of an infant formula with polyamines might contribute to healthy gastrointestinal tract development Background The fungi in the gastrointestinal tract , the gut mycobiota , are now recognised as a significant part of the gut microbiota , and they may be important to human health . In contrast to the adult gut mycobiota , the establishment of the early gut mycobiota has never been described , and there is little knowledge about the fungal transfer from mother to offspring . Methods In a prospect i ve cohort , we followed 298 pairs of healthy mothers and offspring from 36 weeks of gestation until 2 years of age ( 1516 sample s ) and explored the gut mycobiota in maternal and offspring sample s. Half of the pregnant mothers were r and omised into drinking probiotic milk during and after pregnancy . The probiotic bacteria included Lactobacillus rhamnosus GG ( LGG ) , Bifidobacterium animalis subsp . lactis Bb-12 and Lactobacillus acidophilus La-5 . We quantified the fungal abundance of all the sample s using qPCR of the fungal internal transcribed spacer (ITS)1 segment , and we sequenced the 18S rRNA gene ITS1 region of 90 high-quantity sample s using the MiSeq platform ( Illumina ) . Results The gut mycobiota was detected in most of the mothers and the majority of the offspring . The offspring showed increased odds of having detectable faecal fungal DNA if the mother had detectable fungal DNA as well ( OR = 1.54 , p = 0.04 ) . The fungal alpha diversity in the offspring gut increased from its lowest at 10 days after birth , which was the earliest sampling point . The fungal diversity and fungal species showed a succession towards the maternal mycobiota as the child aged , with Debaryomyces hansenii being the most abundant species during breast-feeding and Saccharomyces cerevisiae as the most abundant after weaning . Probiotic consumption increased the gut mycobiota abundance in pregnant mothers ( p = 0.01 ) . Conclusion This study provides the first insight into the early fungal establishment and the succession of fungal species in the gut mycobiota . The results support the idea that the fungal host phenotype is transferred from mother to offspring . Trial registration Clinical trials.gov Background In a recent study , supplementation of infant formula with milk fat globule membranes ( MFGM ) decreased the incidence of otitis media in infants < 6 months of age . Objectives The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed st and ard formula or breast milk . Methods In a prospect i ve double-blinded r and omized controlled trial , exclusively formula-fed infants < 2 months of age were r and omized to be fed experimental formula ( EF , n = 80 ) with reduced energy and protein and supplemented with a bovine MFGM concentrate , or st and ard formula ( SF , n = 80 ) until 6 months of age . A breast-fed reference ( BFR , n = 80 ) group was also recruited . The oral microbiota was analyzed at 4 ( n = 124 ) and 12 ( n = 166 ) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA data base of oral bacteria . Results Species richness in the oral sample s did not differ between the EF and SF groups , but partial least square modeling identified a few taxa that were significantly associated with being in either group , e.g. lower level of Moraxella catarrhalis in the EF group . Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups . Conclusions Supplementation of infant formula with MFGM yielded moderate effects on the oral microbiome . Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group A prospect i ve study was conducted to determine risk factors for fungal colonization , drug susceptibility , and association with invasive fungal infections ( IFIs ) in a neonatal unit . On admission and weekly thereafter , surveillance fungal cultures were taken from mouth , rectum , and trachea of neonates with expected stays of > 1 week . Fungal colonization was detected in 72 ( 12.1 % ) of 593 neonates during 12 months . C AND IDA ALBICANS was isolated from 42 % of colonized neonates . Although early colonization ( age 1.3 + /- 0.2 days ) was found in 2.5 % of the neonates , late colonization ( age 17.6 + /- 1.4 days ) was noted in 14.2 % of neonates hospitalized for > 5 days . Neonates born vaginally were at higher risk for early colonization than those delivered after cesarean section ( P = 0.01 ) . By multivariate logistic regression , very low birthweight was the only independent risk factor for late colonization . Ten IFIs ( nine c and idemias ) were diagnosed , yielding a rate of 1.1 % . These episodes occurred in 6.9 % of colonized neonates , compared with 0.76 % of noncolonized neonates ( P = 0.002 ) . C. ALBICANS was susceptible to azoles , but some non- ALBICANS C AND IDA spp . exhibited decreased susceptibility to these drugs In the neonate , fungal infections result in significant morbidity and mortality . For very low birth weight ( less than 1,500 g ) infants , we prospect ively determined the fungal colonization rate to be 26.7 % . In one third of infants with fungal colonies , mucocutaneous c and idiasis developed , and in 7.7 % , systemic disease developed . Two thirds of the infants had colonies in the first week of life . This colonization was probably acquired during labor and delivery , because those infants who had colonization were more often delivered vaginally than by cesarean section . Early colonization , commonly from the gastrointestinal or respiratory tract , featured C and ida albicans and C and ida tropicalis . Late colonization , occurring after 2 weeks of life ( 15.0 % of patients ) , was more likely to be cutaneous and was associated with either C and ida parapsilosis or such poor growth that the organism could not be identified . Infants with colonization only rarely had budding yeasts ( 6.1 % ) , whereas more than half of the infants with either a urinalysis showing budding yeasts or a urine culture growing fungi had invasive disease . Fungal contamination was not found on either thoracotomy tubes or catheter tips . In the low birth weight infant , fungal colonization represents a significant risk factor for cutaneous or systemic c and idiasis in these infants Abstract Background : Knowledge of fungal colonization patterns in very low birth weight infants ( VLBWI ) admitted to the neonatal intensive care unit ( NICU ) is essential in underst and ing the process of fungal infections in neonates . We analyzed prospect ively , during 2009–2010 , the patterns and dynamics of fungal colonization in VLBWI , including timing , colonization sites , and species involved . Methods : Weekly skin , oropharynx , and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU . None received antifungal prophylaxis . Results : Overall , 118 VLBWI provided 1723 sample s ; 34 ( 29 % ) had 104 positive sample s at least once during the first 10 hospitalization weeks . Thirty-nine ( 33 % ) weighed < 1000 g ; 68 were delivered by cesarean section . C and ida albicans ( 57/104 , 55 % ) and C and ida parapsilosis ( 26/104 , 25 % ) were the main fungi isolated . Eight ( 24 % ) VLBWI were colonized during the first week and 23 ( 68 % ) during the second week . No differences in colonization were recorded between cesarean section and vaginally delivered VLBWI . The colonization risk at least once during the first 10 weeks was 23 % for skin , 14 % for oropharynx , 27 % for rectum/stool , and 38 % for any anatomic site sample d. Persistent colonization was recorded in 5/34 ( 15 % ) , while transient colonization was found in 14/34 ( 41 % ) VLBWI ; 16/34 ( 47 % ) were discharged or died colonized with C and ida spp . C and idemia was diagnosed in 4 ( 3 % ) VLBWI and previous/simultaneous colonization was found in 3/4 . Conclusions : The cumulative risk of colonization , at any sample d site and at least once during follow-up , was high . Initial colonization occurred most often during the first 2 weeks of life . Colonization dynamics were characterized by various persistence , disappearance , and recolonization patterns . C and idemia was rare BACKGROUND Newborn infants in modern maternity hospitals are subject to numerous factors that affect normal intestinal colonization -- for example , cesarean delivery and antimicrobial agents . To study the duration of the effect of external factors on intestinal colonization , two groups of infants with different delivery methods were investigated . METHODS The fecal flora of 64 healthy infants was studied prospect ively . Thirty-four infants were delivered vaginally , and 30 by cesarean birth with antibiotic prophylaxis administered to their mothers before the delivery . The fecal flora was cultured on nonselective and selective media in infants 3 to 5 , 10 , 30 , 60 , and 180 days of age . Gastrointestinal signs were recorded daily by the mothers for 2 months . RESULTS The fecal colonization of infants born by cesarean delivery was delayed . Bifidobacterium-like bacteria and Lactobacillus-like bacteria colonization rates reached the rates of vaginally delivered infants at 1 month and 10 days , respectively . Infants born by cesarean delivery were significantly less often colonized with bacteria of the Bacteroides fragilis group than were vaginally delivered infants : At 6 months the rates were 36 % and 76 % , respectively ( p=0.009 ) . The occurrence of gastrointestinal signs did not differ between the study groups . CONCLUSIONS This study shows for the first time that the primary gut flora in infants born by cesarean delivery may be disturbed for up to 6 months after the birth . The clinical relevance of these changes is unknown , and even longer follow-up is needed to establish how long-lasting these alterations of the primary gut flora can be S. mutans plays a key role in dental caries . The extent to which perinatal events influence the acquisition of S. mutans is unclear . We hypothesized that several maternal factors , including the mode of delivery , influence the initial acquisition of S. mutans in infants . A prospect i ve cohort study was conducted in 156 mother-infant pairs . The study found that maternal gestational age ( p = 0.04 ) , S. mutans level ( p = 0.02 ) , caries score ( p = 0.02 ) , sexually transmitted disease ( STD ) infection experience ( p = 0.01 ) , and family income ( p = 0.03 ) had significant effects on the acquisition of S. mutans . Among infants who became infected , those delivered by Caesarean section acquired S. mutans 11.7 mos earlier than did vaginally delivered infants ( p = 0.038 ) . C-section infants harbored a single genotype of S. mutans that was identical to that of their mothers ( 100 % fidelity ) . Analysis of the data demonstrated the possible perinatal influences on infants ’ acquisition of a member of the cariogenic microbiota , and its potential effect on caries outcome |
1,194 | 32,381,001 | De-implementation interventions that engage patients within the patient-clinician interaction through patient-targeted educational material s or shared decision-making tools are effective in decreasing the use of low-value care . | Many decisions regarding health re source utilization flow through the patient-clinician interaction .
Thus , it represents a place where de-implementation interventions may have considerable effect on reducing the use of clinical interventions that lack efficacy , have risks that outweigh benefits , or are not cost-effective ( i.e. , low-value care ) .
The objective of this systematic review with meta- analysis was to determine the effect of de-implementation interventions that engage patients within the patient-clinician interaction on use of low-value care . | Background — Cardiac stress testing in patients at low risk for acute coronary syndrome is associated with increased false-positive test results , unnecessary downstream procedures , and increased cost . We judged it unlikely that patient preferences were driving the decision to obtain stress testing . Methods and Results — The Chest Pain Choice trial was a prospect i ve r and omized evaluation involving 204 patients who were r and omized to a decision aid or usual care and were followed for 30 days . The decision aid included a 100-person pictograph depicting the pretest probability of acute coronary syndrome and available management options ( observation unit admission and stress testing or 24–72 hours outpatient follow-up ) . The primary outcome was patient knowledge measured by an immediate postvisit survey . Additional outcomes included patient engagement in decision making and the proportion of patients who decided to undergo observation unit admission and cardiac stress testing . Compared with usual care patients ( n=103 ) , decision aid patients ( n=101 ) had significantly greater knowledge ( 3.6 versus 3.0 questions correct ; mean difference , 0.67 ; 95 % CI , 0.34–1.0 ) , were more engaged in decision making as indicated by higher OPTION ( observing patient involvement ) scores ( 26.6 versus 7.0 ; mean difference , 19.6 ; 95 % CI , 1.6–21.6 ) , and decided less frequently to be admitted to the observation unit for stress testing ( 58 % versus 77 % ; absolute difference , 19 % ; 95 % CI , 6%–31 % ) . There were no major adverse cardiac events after discharge in either group . Conclusions — Use of a decision aid in patients with chest pain increased knowledge and engagement in decision making and decreased the rate of observation unit admission for stress testing . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01077037 Background While some research has examined general attitudes about efforts to reduce overutilization of services , such as the Choosing Wisely ® ( CW ) initiative , little data exists regarding primary care providers ’ attitudes regarding individual recommendations . Objective We sought to identify whether particular CW recommendations were perceived by primary care providers as difficult to follow , difficult for patients to accept , or both . Design Two national surveys , one by mail to a r and om sample of 2000 U.S. primary care physicians in November 2013 , and the second electronically to a r and om sample of 2500 VA primary care providers ( PCPs ) in October – December 2014 . Participants A total of 603 U.S. primary care physicians and 1173 VA primary care providers . Response rates were 34 and 48 % , respectively . Main Measures PCP ratings of whether 12 CW recommendations for screening , testing and treatments applicable to adult primary care were difficult to follow and difficult for patients to accept ; and ratings of potential barriers to reducing overutilization . Key Results For four recommendations regarding not screening or testing in asymptomatic patients , less than 20 % of PCPs found the CW recommendations difficult to accept ( range 7.2–16.6 % ) or difficult for patients to follow ( 12.2–19.3 % ) . For five recommendations regarding testing or treatment for symptomatic conditions , however , there was both variation in reported difficulty to follow ( 9.8–32 % ) and a high level of reported difficulty for patients to accept ( 35.7–87.1 % ) . The most frequently reported barriers to reducing overuse included mal practice concern , patient requests for services , lack of time for shared decision making , and the number of tests recommended by specialists . Conclusions While PCPs found many CW recommendations easy to follow , they felt that some , especially those for symptomatic conditions , would be difficult for patients to accept . Overcoming PCPs ’ perceptions of patient acceptability will require approaches beyond routine physician education , feedback and financial incentives Objective To establish whether an interactive booklet on respiratory tract infections in children reduces reconsultation for the same illness episode , reduces antibiotic use , and affects future consulting intentions , while maintaining parental satisfaction with care . Design Pragmatic cluster r and omised controlled trial . Setting 61 general practice s in Wales and Engl and . Participants 558 children ( 6 months to 14 years ) presenting to primary care with an acute respiratory tract infection ( 7 days or less ) . Children with suspected pneumonia , asthma or a serious concomitant illness , or needing immediate hospital admission were excluded . Three withdrew and 27 were lost to follow-up , leaving 528 ( 94.6 % ) with main outcome data . Interventions Clinicians in the intervention group were trained in the use of an interactive booklet on respiratory tract infections and asked to use the booklet during consultations with recruited patients ( and provide it as a take home re source ) . Clinicians in the control group conducted their consultations as usual . Main outcome measures The proportion of children who attended a face-to-face consultation about the same illness during the two week follow-up period . Secondary outcomes included antibiotic prescribing , antibiotic consumption , future consulting intentions , and parental satisfaction , reassurance , and enablement . Results Reconsultation occurred in 12.9 % of children in the intervention group and 16.2 % in the control group ( absolute risk reduction 3.3 % , 95 % confidence interval −2.7 % to 9.3 % , P=0.29 ) . Using multilevel modelling ( at the practice and individual level ) to account for clustering , no significant difference in reconsulting was noted ( odds ratio 0.75 ; 0.41 to 1.38 ) . Antibiotics were prescribed at the index consultation to 19.5 % of children in the intervention group and 40.8 % of children in the control group ( absolute risk reduction 21.3 % , 95 % confidence interval 13.7 to 28.9 ) , P<0.001 ) . A significant difference was still present after adjusting for clustering ( odds ratio 0.29 ; 0.14 to 0.60 ) . There was also a significant difference in the proportion of parents who said they would consult in the future if their child developed a similar illness ( odds ratio 0.34 ; 0.20 to 0.57 ) . Satisfaction , reassurance , and parental enablement scores were not significantly different between the two groups . Conclusions Use of a booklet on respiratory tract infections in children within primary care consultations led to important reductions in antibiotic prescribing and reduced intention to consult without reducing satisfaction with care . Trial registration Current Controlled Trials IS RCT Background : Few interventions have proven effective in reducing the overuse of antibiotics for acute respiratory infections . We evaluated the effect of DECISION+2 , a shared decision-making training program , on the percentage of patients who decided to take antibiotics after consultation with a physician or resident . Methods : We performed a r and omized trial , clustered at the level of family practice teaching unit , with 2 study arms : DECISION+2 and control . The DECISION+2 training program included a 2-hour online tutorial followed by a 2-hour interactive seminar about shared decision-making . The primary outcome was the proportion of patients who decided to use antibiotics immediately after consultation . We also recorded patients ’ perception that shared decision-making had occurred . Two weeks after the initial consultation , we assessed patients ’ adherence to the decision , repeat consultation , decisional regret and quality of life . Results : We compared outcomes among 181 patients who consulted 77 physicians in 5 family practice teaching units in the DECISION+2 group , and 178 patients who consulted 72 physicians in 4 family practice teaching units in the control group . The percentage of patients who decided to use antibiotics after consultation was 52.2 % in the control group and 27.2 % in the DECISION+2 group ( absolute difference 25.0 % , adjusted relative risk 0.48 , 95 % confidence interval 0.34–0.68 ) . DECISION+2 was associated with patients taking a more active role in decision-making ( Z = 3.9 , p < 0.001 ) . Patient outcomes 2 weeks after consultation were similar in both groups . Interpretation : The shared decision-making program DECISION+2 enhanced patient participation in decision-making and led to fewer patients deciding to use antibiotics for acute respiratory infections . This reduction did not have a negative effect on patient outcomes 2 weeks after consultation . Clinical Trials.gov trial register no. NCT01116076 Objective To compare the effectiveness of shared decision making with usual care in choice of admission for observation and further cardiac testing or for referral for outpatient evaluation in patients with possible acute coronary syndrome . Design Multicenter pragmatic parallel r and omized controlled trial . Setting Six emergency departments in the United States . Participants 898 adults ( aged > 17 years ) with a primary complaint of chest pain who were being considered for admission to an observation unit for cardiac testing ( 451 were allocated to the decision aid and 447 to usual care ) , and 361 emergency clinicians ( emergency physicians , nurse practitioners , and physician assistants ) caring for patients with chest pain . Interventions Patients were r and omly assigned ( 1:1 ) by an electronic , web based system to shared decision making facilitated by a decision aid or to usual care . The primary outcome , selected by patient and caregiver advisers , was patient knowledge of their risk for acute coronary syndrome and options for care ; secondary outcomes were involvement in the decision to be admitted , proportion of patients admitted for cardiac testing , and the 30 day rate of major adverse cardiac events . Results Compared with the usual care arm , patients in the decision aid arm had greater knowledge of their risk for acute coronary syndrome and options for care ( questions correct : decision aid , 4.2 v usual care , 3.6 ; mean difference 0.66 , 95 % confidence interval 0.46 to 0.86 ) , were more involved in the decision ( observing patient involvement scores : decision aid , 18.3 v usual care , 7.9 ; 10.3 , 9.1 to 11.5 ) , and less frequently decided with their clinician to be admitted for cardiac testing ( decision aid , 37 % v usual care , 52 % ; absolute difference 15 % ; P<0.001 ) . There were no major adverse cardiac events due to the intervention . Conclusions Use of a decision aid in patients at low risk for acute coronary syndrome increased patient knowledge about their risk , increased engagement , and safely decreased the rate of admission to an observation unit for cardiac testing . Trial registration Clinical Trials.gov NCT01969240 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 INTRODUCTION Antibiotic overuse promotes resistant strains of bacteria and puts patients at risk for adverse reactions . Given the use of educational posters in government-sponsored public health campaigns , this study examined the effectiveness of a waiting room poster in reducing excessive antibiotic use in clinical practice . METHODS Investigators conducted a 1-month trial of an educational poster with historical controls using three private pediatric group practice s in Westchester County , New York . Children between the ages of 6 months and 10 years at the time of a visit to diagnose and treat symptoms of respiratory illness were enrolled as subjects . Antibiotic prescriptions for children with respiratory illnesses seen during the poster month were compared with prescriptions written during three 1-month historical control periods . The proportion of visits that result ed in a prescription for an antibiotic served as the outcome measure . RESULTS Overall , 326 of the 720 patients ( 45.2 % ) enrolled in the study were treated with an antibiotic . Multiple logistic regression analysis revealed no statistically significant difference in the proportion of visits result ing in an antibiotic prescription among the 4 study months ( P = .79 ) , indicating that the educational poster had no effect on antibiotic use . DISCUSSION Public education in the form of a waiting room poster was not sufficient to decrease antibiotic prescriptions . This finding has implication s for current large-scale programs and for health care providers as they continue to attempt to educate patients on the appropriate use of antibiotics Decision aids are evidence -based sources of health information that can help patients make informed treatment decisions . However , little is known about how decision aids affect health care use when they are implemented outside of r and omized controlled clinical trials . We conducted an observational study to examine the associations between introducing decision aids for hip and knee osteoarthritis and rates of joint replacement surgery and costs in a large health system in Washington State . Consistent with prior r and omized trials , our introduction of decision aids was associated with 26 percent fewer hip replacement surgeries , 38 percent fewer knee replacements , and 12 - 21 percent lower costs over six months . These findings support the concept that patient decision aids for some health conditions , for which treatment decisions are highly sensitive to both patients ' and physicians ' preferences , may reduce rates of elective surgery and lower costs OBJECTIVES To determine the effects of two computer based decision aids on decisional conflict and mode of delivery among pregnant women with a previous caesarean section . DESIGN R and omised trial , conducted from May 2004 to August 2006 . SETTING Four maternity units in south west Engl and , and Scotl and . PARTICIPANTS 742 pregnant women with one previous lower segment caesarean section and delivery expected at > or=37 weeks . Non-English speakers were excluded . INTERVENTIONS Usual care : st and ard care given by obstetric and midwifery staff . Information programme : women navigated through descriptions and probabilities of clinical outcomes for mother and baby associated with planned vaginal birth , elective caesarean section , and emergency caesarean section . Decision analysis : mode of delivery was recommended based on utility assessment s performed by the woman combined with probabilities of clinical outcomes within a concealed decision tree . Both interventions were delivered via a laptop computer after brief instructions from a research er . MAIN OUTCOME MEASURES Total score on decisional conflict scale , and mode of delivery . RESULTS Women in the information programme ( adjusted difference -6.2 , 95 % confidence interval -8.7 to -3.7 ) and the decision analysis ( -4.0 , -6.5 to -1.5 ) groups had reduced decisional conflict compared with women in the usual care group . The rate of vaginal birth was higher for women in the decision analysis group compared with the usual care group ( 37 % v 30 % , adjusted odds ratio 1.42 , 0.94 to 2.14 ) , but the rates were similar in the information programme and usual care groups . CONCLUSIONS Decision aids can help women who have had a previous caesarean section to decide on mode of delivery in a subsequent pregnancy . The decision analysis approach might substantially affect national rates of caesarean section . Trial Registration Current Controlled Trials IS RCT N84367722 INTRODUCTION The American College of Emergency Physicians embarked on the " Choosing Wisely " campaign to avoid computed tomographic ( CT ) scans in patients with minor head injury who are at low risk based on vali date d decision rules . We hypothesized that a Pediatric Mild Head Injury Care Path could be developed and implemented to reduce inappropriate CT utilization with support of a clinical decision support tool ( CDST ) and a structured parent discussion tool . METHODS A quality improvement project was initiated for 9 weeks to reduce inappropriate CT utilization through 5 interventions : ( 1 ) engagement of leadership , ( 2 ) provider education , ( 3 ) incorporation of a parent discussion tool to guide discussion during the emergency department ( ED ) visit between the parent and the provider , ( 4 ) CDST embedded in the electronic medical record , and ( 5 ) importation of data into the note to drive compliance . Patients prospect ively were enrolled when providers at a pediatric and a freest and ing ED entered data into the CDST for decision making . Rate of care path utilization and head CT reduction was determined for all patients with minor head injury based on International Classification of Diseases , Ninth Revision codes . Targets for care path utilization and head CT reduction were established a priori . Results were compared with baseline data collected from 2013 . RESULTS The CDST was used in 176 ( 77.5 % ) of 227 eligible patients . Twelve patients were excluded based on a priori criteria . Adherence to recommendations occurred in 162 ( 99 % ) of 164 patients . Head CT utilization was reduced from 62.7 % to 22 % ( odds ratio , 0.17 ; 95 % confidence interval , 0.12 - 0.24 ) where CDST was used by the provider . There were no missed traumatic brain injuries in our study group . CONCLUSION A Pediatric Mild Head Injury Care Path can be implemented in a pediatric and freest and ing ED , result ing in reduced head CT utilization and high levels of adherence to CDST recommendations 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 OBJECTIVE To assess the marginal impact of patient education on antibiotic prescribing to children with pharyngitis and adults with acute bronchitis in private office practice s. DATA SOURCES / STUDY SETTING Antibiotic prescription rates based on cl aims data from four managed care organizations in Colorado during baseline ( winter 2000 ) and study ( winter 2001 ) periods . STUDY DESIGN A nonr and omized controlled trial of a household and office-based patient educational intervention was performed . During both periods , Colorado physicians were mailed antibiotic prescribing profiles and practice s guidelines as part of an ongoing quality improvement program . Intervention practice s ( n=7 ) were compared with local and distant control practice s. DATA COLLECTION / EXTRACTION METHODS Office visits were extracted by managed care organizations using International Classification of Diseases-9- Clinical Modification codes for acute respiratory tract infections , and merged with pharmacy cl aims data based on visit and dispensing date s coinciding within 2 days . PRINCIPAL FINDINGS Adjusted antibiotic prescription rates during baseline and study periods increased from 38 to 39 percent for pediatric pharyngitis at the distant control practice s , and decreased from 39 to 37 percent at the local control practice s , and from 34 to 30 percent at the intervention practice s ( p=.18 compared with distant control practice s ) . Adjusted antibiotic prescription rates decreased from 50 to 44 percent for adult bronchitis at the distant control practice s , from 55 to 45 percent at the local control practice s , and from 60 to 36 percent at the intervention practice s ( p<.002 and p=.006 compared with distant and local control practice s , respectively ) . CONCLUSIONS In office practice s , there appears to be little room for improvement in antibiotic prescription rates for children with pharyngitis . In contrast , patient education helps reduce antibiotic use for adults with acute bronchitis beyond that achieved by physician-directed efforts Background : The number of women who select cesarean section due to fear of childbirth has increased . Role play education seems to be a helpful method to remove or reduce the fear of childbirth . Therefore , this study aim ed to investigate the effect of role play education on primiparous women 's fear of natural delivery and their decision on the mode of delivery . Material s and Methods : In this blind clinical trial , 67 primiparous women with natural pregnancy at 34–36 weeks of gestational age and with no indication of cesarean section were selected from the health care centers in Mashhad . They were r and omly assigned to two groups who underwent pre-test and post-test with the help of delivery attitude question naire to investigate their fear of childbirth and a research er-made pregnant women 's decision investigation question naire . Education through role play was conducted in the form of three scenarios during seven stages . The findings were analyzed by Fisher 's exact test and independent t-test through SPSS . Results : The two groups were significantly different concerning the fear of childbirth after the intervention ( P = 0.007 ) , and the fear score showed a higher reduction in the role play group compared to the lecture group . There was a significant difference between the two groups concerning the reduction of elective cesarean section and the decision on the mode of delivery at the time of admission in the labor room ( P = 0.000 ) . About 75 % in the lecture group and 100 % in the role play group selected natural delivery . Conclusions : In the present study , the effect of role play was more in making a decision on natural delivery , reducing the fear of childbirth , and reducing the rate of elective cesarean section . It is suggested to use role play method to educate pregnant women to reduce the rate of cesarean sections CONTEXT Ethics consultations increasingly are being used to resolve conflicts about life-sustaining interventions , but few studies have reported their outcomes . OBJECTIVE To investigate whether ethics consultations in the intensive care setting reduce the use of life-sustaining treatments delivered to patients who ultimately did not survive to hospital discharge , as well as the reactions to the consultations of physicians , nurses , and patients /surrogates . DESIGN Prospect i ve , multicenter , r and omized controlled trial from November 2000 to December 2002 . SETTING Adult intensive care units ( ICUs ) of 7 US hospitals representing a spectrum of institutional characteristics . PATIENTS Five hundred fifty-one patients in whom value-related treatment conflicts arose during the course of treatment . INTERVENTIONS Patients were r and omly assigned either to an intervention ( ethics consultation offered ) ( n = 278 ) or to usual care ( n = 273 ) . MAIN OUTCOME MEASURES The primary outcomes were ICU days and life-sustaining treatments in those patients who did not survive to hospital discharge . We examined the same measures in those who did survive to discharge and also compared the overall mortality rates of the intervention and usual care groups . We also interviewed physicians and nurses and patients /surrogates about their views of the ethics consultation . RESULTS The intervention and usual-care groups showed no difference in mortality . However , ethics consultations were associated with reductions in hospital ( -2.95 days , P = .01 ) and ICU ( -1.44 days , P = .03 ) days and life-sustaining treatments ( -1.7 days with ventilation , P = .03 ) in those patients who ultimately did not survive to discharge . The majority ( 87 % ) of physicians , nurses , and patients /surrogates agreed that ethics consultations in the ICU were helpful in addressing treatment conflicts . CONCLUSION Ethics consultations were useful in resolving conflicts that may have inappropriately prolonged nonbeneficial or unwanted treatments in the ICU IMPORTANCE The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older . The effect of direct patient education to catalyze collaborative care for reducing inappropriate prescriptions remains unknown . OBJECTIVE To compare the effect of a direct-to-consumer educational intervention against usual care on benzodiazepine therapy discontinuation in community-dwelling older adults . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized trial ( EMPOWER [ Eliminating Medications Through Patient Ownership of End Results ] study [ 2010 - 2012 , 6-month follow-up ] ) . Community pharmacies were r and omly allocated to the intervention or control arm in nonstratified , blocked groups of 4 . Participants ( 303 long-term users of benzodiazepine medication aged 65 - 95 years , recruited from 30 community pharmacies ) were screened and enrolled prior to r and omization : 15 pharmacies r and omized to the educational intervention included 148 participants and 15 pharmacies r and omized to the " wait list " control included 155 participants . Participants , physicians , pharmacists , and evaluators were blinded to outcome assessment . INTERVENTIONS The active arm received a deprescribing patient empowerment intervention describing the risks of benzodiazepine use and a stepwise tapering protocol . The control arm received usual care . MAIN OUTCOMES AND MEASURES Benzodiazepine therapy discontinuation at 6 months after r and omization , ascertained by pharmacy medication renewal profiles . RESULTS A total of 261 participants ( 86 % ) completed the 6-month follow-up . Of the recipients in the intervention group , 62 % initiated conversation about benzodiazepine therapy cessation with a physician and /or pharmacist . At 6 months , 27 % of the intervention group had discontinued benzodiazepine use compared with 5 % of the control group ( risk difference , 23 % [ 95 % CI , 14%-32 % ] ; intracluster correlation , 0.008 ; number needed to treat , 4 ) . Dose reduction occurred in an additional 11 % ( 95 % CI , 6%-16 % ) . In multivariate subanalyses , age greater than 80 years , sex , duration of use , indication for use , dose , previous attempt to taper , and concomitant polypharmacy ( 10 drugs or more per day ) did not have a significant interaction effect with benzodiazepine therapy discontinuation . CONCLUSIONS AND RELEVANCE Direct-to-consumer education effectively elicits shared decision making around the overuse of medications that increase the risk of harm in older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01148186 OBJECTIVE To evaluate the effectiveness of a nationwide media campaign to reduce antibiotic overuse among children . STUDY DESIGN Prospect i ve observational study of the pediatric population of a health maintenance organization ( HMO ) comparing antibiotic use during the baseline ( November 2004-February 2005 ) and study ( November 2005-February 2006 ) periods . METHODS During January 2006 the HMO conducted a media campaign to increase public awareness of the risks of misusing antibiotics , particularly for influenza-like diseases . Antibiotic purchasing rates during specific periods in the study winter were compared with those during corresponding periods in the baseline winter among children diagnosed with upper respiratory infection ( URI ) , otitis media ( OM ) , or pharyngitis . After the intervention , a r and om subset of the study population was surveyed by telephone to estimate the level of exposure to the campaign and attitudes toward antibiotic use . RESULTS The study population consisted of 101,401 children in the baseline winter and 84,979 in the study winter . We noted reductions in antibiotic purchasing for URI , OM , and pharyngitis during the postintervention period compared with the preintervention period ( URI odds ratio [ OR ] = 0.75 , 95 % confidence interval [ CI ] = 0.69 , 0.81 ; OM OR = 0.65 , 95 % CI = 0.59 , 0.72 ; pharyngitis OR = 0.93 , 95 % CI = 0.89 , 0.97 ) . Parents of children with URI exposed to the media campaign were more likely to agree with st and ards of appropriate antibiotic use than parents not exposed ( F(1 ) = 4.18 , P = .04 ) . CONCLUSIONS A media campaign aim ed at changing patient behavior can contribute to reducing the rate of inappropriate antibiotic use |
1,195 | 29,093,455 | Neither rTMS nor TES improved cognition .
No effects for stimulation parameters on motor or cognitive function were observed . | Parkinson 's disease ( PD ) is a neurodegenerative disorder affecting motor and cognitive abilities .
There is no cure for PD , therefore identifying safe therapies to alleviate symptoms remains a priority .
This meta- analysis quantified the effectiveness of repetitive transcranial magnetic stimulation ( rTMS ) and transcranial electrical stimulation ( TES ) to improve motor and cognitive dysfunction in PD . | Transcranial direct current stimulation ( tDCS ) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation . Anodal tDCS enhances and cathodal stimulation reduces excitability . Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation , while cathodal tDCS hyperpolarises cortical neurones . However , not much is known about the ion channels and receptors involved in these effects . Thus , the impact of the sodium channel blocker carbamazepine , the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested . tDCS- protocol s inducing excitability alterations ( 1 ) only during tDCS and ( 2 ) eliciting long-lasting after-effects were applied after drug administration . Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS . Flunarizine result ed in similar changes . Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation , which elicits no after-effects , but prevented the induction of long-lasting after-effects independent of their direction . These results suggest that , like in other animals , cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation , thus modulating the conductance of sodium and calcium channels . Moreover , they suggest that the after-effects may be NMDA receptor dependent . Since NMDA receptors are involved in neuroplastic changes , the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting . The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS , which may have important future clinical applications BACKGROUND Carefully design ed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation ( TMS ) in psychiatric disorders . A major method ological concern is the design of the " sham " control for TMS . An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment . Strategies employed so far include alterations in the position of the stimulating coil , but there has been little systematic study of their validity . In this study , we investigated the effects of different coil positions on cortical activation and scalp sensation . METHODS In nine normal subjects , single TMS pulses were administered at a range of intensities with a " figure eight " coil held in various positions over the left primary motor cortex . Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle . Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed . RESULTS None of the coil positions studied met the criteria for an ideal sham . Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex . CONCLUSIONS The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive " stimulation . " Further research is needed to develop the best sham condition for a range of applications OBJECTIVE Several studies have shown that repetitive transcranial magnetic stimulation ( rTMS ) over the dorsolateral prefrontal cortex ( DLPFC ) is effective in the treatment of depression in patients with Parkinson disease ( PD ) . However , since research into the effect of this type of rTMS regime on motor function is limited , we studied the effect of rTMS over the DLPFC on the motor functions in PD patients . METHODS Thirteen patients were r and omly assigned into 2 groups , one receiving real-rTMS ( 90 % of resting motor threshold , 10 Hz , 450 pulses-day for 10 consecutive days ) over the DLPFC contralateral to the more affected side , and the other group receiving sham-rTMS . Assessment included a clinical motor evaluation using part III of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and several motor tasks . The UPDRS was applied before and after 10 days of rTMS . Finger tapping , reach movement , grip movement and gait were measured in each session before and after the rTMS over the 10 day period . RESULTS Statistical analysis ( ANOVA for repeated measures ; group * day * side * rTMS ) only showed a significant effect for finger tapping , reach movement and gait for the factor day . No significant change was reported for the UPDRS in any group . CONCLUSIONS Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status , and the improvement in performance of motor tasks can be attributed to the effects of practice . SIGNIFICANCE rTMS over the DLPFC did not lead to any motor improvement in PD patients OBJECTIVE To investigate the dopamine-dependent effect of combining transcranial direct current stimulation ( tDCS ) with visually cued gait training on cortical excitability and functional mobility in individuals with Parkinson 's disease . DESIGN A pilot , r and omized , double-blind , controlled trial . METHODS Twenty-two patients with Parkinson 's disease were r and omly assigned to 2 groups : ( i ) active anodal tDCS over the supplementary motor area ( experimental group ) , or ( ii ) sham tDCS ( control group ) . After tDCS , both groups participated in a visually cued gait training . Functional mobility was evaluated with the Timed Up and Go test ( TUG ) . Cortical excitability was assessed by active motor threshold and motor-evoked potential amplitudes elicited by transcranial magnetic stimulation in patients in on and off medication states . RESULTS In the TUG test both groups achieved improvements either in on or off medication condition compared with baseline . However , for both medication conditions , these gains were maintained only in the experimental group during 1-month follow-up , compared with baseline . In the experimental group , enhancement of cortical excitability was observed at post-intervention and 1-month follow-up ( both only for the " on " phase ) compared with baseline . CONCLUSION These findings suggest that tDCS , independent of dopaminergic medication state , might prolong the positive effect induced by cued gait training on functional mobility PURPOSE The aim of this study was to investigate the site-specific effects of repetitive transcranial magnetic stimulation ( rTMS ) on freezing of gait ( FOG ) in patients with parkinsonism . METHODS Twenty patients with parkinsonism and FOG were included . A single session of 10 Hz rTMS was applied over three different cortical regions of the dominant hemisphere : the primary motor cortex of the lower leg ( M1-LL ) , the supplementary motor area ( SMA ) , and the dorsolateral prefrontal cortex ( DLPFC ) . We also performed sham stimulation as a control . The Timed Up and Go ( TUG ) test , Turn Steps and Turn Time in 180 ° turning , Unified Parkinson 's Disease Rating Scale ( UPDRS ) part III , FOG Question naire ( FOG-Q ) , and motor evoked potential ( MEP ) studies were performed before and after each intervention . RESULTS There were significant improvements in TUG test times after rTMS over the M1-LL and the DLPFC . Improvement was significantly greater after the M1-LL stimulation than sham condition . The M1-LL and DLPFC stimulation also result ed in significant improvements in both the number of Turn Steps and Turn Time . UPDRS-III scores were significantly decreased after the M1-LL and DLPFC stimulation . CONCLUSIONS Use of 10 Hz rTMS on the M1-LL and DLPFC is therapeutically effective for FOG in patients with parkinsonism Objective : To investigate the safety and efficacy of intermittent theta-burst stimulation ( iTBS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background : Progression of PD is characterized by the emergence of motor deficits , which eventually respond less to dopaminergic therapy and pose a therapeutic challenge . Repetitive transcranial magnetic stimulation ( rTMS ) has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS . Methods : In this r and omized , double-blind , sham-controlled study , we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks ( evidence Class I ) . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and additional clinical , neuropsychological , and neurophysiologic measures . Results : We investigated 26 patients with mild to moderate PD : 13 received iTBS and 13 sham stimulation . We found beneficial effects of iTBS on mood , but no improvement of gait , bradykinesia , UPDRS , and other measures . EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity . Few reported discomfort or pain and one experienced tinnitus during real stimulation . Conclusion : iTBS of the motor and prefrontal cortices appears safe and improves mood , but failed to improve motor performance and functional status in PD . Classification of evidence : This study provides Class I evidence that iTBS was not effective for gait , upper extremity bradykinesia , or other motor symptoms in PD Background Depression is one of the most common psychiatric illnesses worldwide , but is nevertheless preventable . Since the children of parents who have depression are at greatest risk of developing depression themselves , prevention programmes for this population are a major public health priority . Here we report the study protocol of a r and omised controlled trial of a group-based psychological intervention for families with i ) at least one parent who suffers ( or has suffered ) from depression and ii ) at least one child who has no current or previous psychiatric diagnosis . Methods / Design Eligible families will be r and omly allocated to receive either a German adaptation of the 12-session cognitive-behavioural Raising Healthy Children intervention ( Gesund und glücklich aufwachsen ; N = 50 ) , or no intervention ( usual care ; N = 50 ) . The primary outcome ( child diagnosis of an episode of depression ) will be assessed at 15-month follow-up . The secondary outcomes ( child psychopathological symptoms ) will be assessed immediately following completion of the intervention ( 6-months ) , as well as at 9- and 15-month follow-up . We hypothesise that children in the intervention condition , compared with those who do not receive the intervention , will show fewer symptoms of psychopathology , and be less likely to meet diagnostic criteria for a depressive episode , at follow-up . Discussion Despite their elevated risk of developing depression , there is little formal support available for the children of parents with depression . This study provides an important step in the development of more effective depression prevention measures , which are needed if the personal , social and economic burden of depression is to be reduced . Trial registration Clinical Trials NCT02115880 . Registered April 7 2014 Weak transcranial direct current stimulation ( tDCS ) induces persisting excitability changes in the human motor cortex . These plastic excitability changes are selectively controlled by the polarity , duration and current strength of stimulation . To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity , we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine ( CBZ ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan ( DMO ) . Monitored by transcranial magnetic stimulation ( TMS ) , motor cortical excitability changes of up to 40 % were achieved in the drug-free condition . Increase of cortical excitability could be selected by anodal stimulation , and decrease by cathodal stimulation . Both types of excitability change lasted several minutes after cessation of current stimulation . DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation , strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity . In contrast , CBZ selectively eliminated anodal effects . Since CBZ stabilizes the membrane potential voltage-dependently , the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials . Similar to the induction of established types of short- or long-term neuroplasticity , a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS . On the basis of these results , we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects , leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation Objective . To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background . Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy . rTMS has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy . Methods . In this r and omized , double blind , sham-controlled study , the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , and additional clinical , neurophysiological , and neuropsychological parameters . In addition , the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram ( EMG-EEG ) monitoring during and after stimulation . Results . The authors investigated 26 patients with mild to moderate PD : 13 received 50-Hz rTMS and 13 sham stimulation . The 50-Hz rTMS did not improve gait , bradykinesia , and global and motor UPDRS , but there appeared a short-lived “ on”-state improvement in activities of daily living ( UPDRS II ) . The 50-Hz rTMS lengthened the cortical silent period , but other neurophysiological and neuropsychological measures remained unchanged . EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity . There were no adverse effects . Conclusion . It appears that 50-Hz rTMS of the motor cortices is safe , but it fails to improve motor performance and functional status in PD . Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research Based on several open-label and case studies , repetitive transcranial magnetic stimulation ( rTMS ) seems to have an antidepressive effect on patients with Parkinson 's disease ( PD ) . However , this hypothesis requires further confirmation . We conducted a r and omized , double-blind placebo-controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) on depression and various motor and nonmotor features of PD . Twenty-two PD patients with mild or moderate depressive episodes were assigned into two groups , one receiving real-rTMS ( 90 % of resting motor threshold , 5 Hz , 600 pulses-a-day for 10 days ) over the left DLPFC , and another group receiving sham-rTMS . An investigator blinded to the treatment performed three video-taped examinations on each patient : before stimulation ( baseline ) , 1 day ( short term ) , and 30 days after treatment session ended ( long-term effect ) . Mini-Mental State Examination , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn-Yahr , Epworth Sleepiness , Visual Analog and Montgomery-Asberg Depression Rating Scales ( MADRS ) , Beck Depression Inventory ( BDI ) , and Trail making and Stroop tests were applied . In the actively treated group , not only depression rating scales showed significant improvement 30 days after treatment ended ( BDI by 44.4 % and MADRS by 26.1 % ) , but also the accuracy of Stroop test ( by 16 % ) . We could also demonstrate an insignificant improvement in UPDRS-III by 7.5 points ( 31.9 % , P = 0.06 ) . In the sham-treated group none of the examined tests and scales improved significantly after sham stimulation . Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment . However , this result should be confirmed in patients with severe depression by further clinical trials Background Progression of Parkinson 's disease ( PD ) is characterised by motor deficits which eventually respond less to dopaminergic therapy and thus pose a therapeutic challenge . Deep brain stimulation has proven efficacy but carries risks and is not possible in all patients . Non-invasive brain stimulation has shown promising results and may provide a therapeutic alternative . Objective To investigate the efficacy of transcranial direct current stimulation ( tDCS ) in the treatment of PD . Design R and omised , double blind , sham controlled study . Setting Research institution . Methods The efficacy of anodal tDCS applied to the motor and prefrontal cortices was investigated in eight sessions over 2.5 weeks . Assessment over a 3 month period included timed tests of gait ( primary outcome measure ) and bradykinesia in the upper extremities , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Serial Reaction Time Task , Beck Depression Inventory , Health Survey and self- assessment of mobility . Results Twenty-five PD patients were investigated , 13 receiving tDCS and 12 sham stimulation . tDCS improved gait by some measures for a short time and improved bradykinesia in both the on and off states for longer than 3 months . Changes in UPDRS , reaction time , physical and mental well being , and self-assessed mobility did not differ between the tDCS and sham interventions . Conclusion tDCS of the motor and prefrontal cortices may have therapeutic potential in PD but better stimulation parameters need to be established to make the technique clinical ly viable . This study was publicly registered ( clinical trials.org : NCT00082342 ) The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation ( rTMS ) applied over the left dorsal premotor cortex ( PMd ) and left dorsolateral prefrontal cortex ( DLPFC ) on choice reaction time in a noise-compatibility task , and cognitive functions in patients with Parkinson ’s disease ( PD ) . Clinical motor symptoms of PD were assessed as well . Ten patients with PD entered a r and omized , placebo-controlled study with a crossover design . Each patient received 10 Hz stimulation over the left PMd and DLPFC ( active stimulation sites ) and the occipital cortex ( OCC ; a control stimulation site ) in the OFF motor state , i.e. at least after 12 h of dopaminergic drugs withdrawal . Frameless stereotaxy was used to target the optimal position of the coil . For the evaluation of reaction time , we used a noise-compatibility paradigm . A short battery of neuropsychological tests was performed to evaluate executive functions , working memory , and psychomotor speed . Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson ’s Disease Rating Scale . Statistical analysis revealed no significant effect of rTMS applied over the left PMd and /or DLPFC in patients with PD in any of the measured parameters . In this study , we did not observe any effect of one session of high frequency rTMS applied over the left PMd and /or DLPFC on choice reaction time in a noise-compatibility task , cognitive functions , or motor features in patients with PD . rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects Dysfunction of the basal ganglia-thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson 's disease ( PD ) . Using high-frequency repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) , we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD . In this double-blind placebo-controlled study , 99 patients were enrolled and assigned r and omly to SMA-stimulation and sham-stimulation groups . For SMA stimulation , 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110 % active motor threshold for leg muscles in one session . The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS . Each session of intervention was carried out once a week for the first 8 weeks . The SMA stimulation , in contrast to the sham stimulation , engendered significant improvements in total scores and motor scores of the Unified Parkinson 's Disease Rating Scale . Mean improvements in motor scores were 4.5 points in the SMA-stimulation group and -0.1 points in the sham-stimulation group . Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients ; SMA is a potential stimulation site for PD treatment Dopamine is implicated in movement , learning , and motivation , and in illnesses such as Parkinson 's disease , schizophrenia , and drug addiction . Little is known about the control of dopamine release in humans , but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures . Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral prefrontal cortex in healthy human subjects . Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal cau date nucleus compared with rTMS of the left occipital cortex . There were no changes in binding in the putamen , nucleus accumbens , or right cau date . This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral cau date nucleus . This finding has implication s for the therapeutic and research use of rTMS in neurological and psychiatric disorders The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear . Using repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) in a group of patients with advanced Parkinson disease , the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion . rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias , whereas 5-Hz rTMS induced a slight but not significant increase Background Parkinson ’s disease ( PD ) results from a loss of dopamine in the brain , leading to movement dysfunctions such as bradykinesia , postural instability , resting tremor and muscle rigidity . Furthermore , dopamine deficiency in PD has been shown to result in maladaptive plasticity of the primary motor cortex ( M1 ) . Progressive resistance training ( PRT ) is a popular intervention in PD that improves muscular strength and results in clinical ly significant improvements on the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) . In separate studies , the application of anodal transcranial direct current stimulation ( a-tDCS ) to the M1 has been shown to improve motor function in PD ; however , the combined use of tDCS and PRT has not been investigated . Methods / design We propose a 6-week , double-blind r and omised controlled trial combining M1 tDCS and PRT of the lower body in participants ( n = 42 ) with moderate PD ( Hoehn and Yahr scale score 2–4 ) . Supervised lower body PRT combined with functional balance tasks will be performed three times per week with concurrent a-tDCS delivered at 2 mA for 20 minutes ( a-tDCS group ) or with sham tDCS ( sham group ) . Control participants will receive st and ard care ( control group ) . Outcome measures will include functional strength , gait speed and variability , balance , neurophysiological function at rest and during movement execution , and the UPDRS motor subscale , measured at baseline , 3 weeks ( during ) , 6 weeks ( post ) , and 9 weeks ( retention ) . Ethical approval has been granted by the Deakin University Human Research Ethics Committee ( project number 2015 - 014 ) , and the trial has been registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12615001241527 ) . Discussion This will be the first r and omised controlled trial to combine PRT and a-tDCS targeting balance and gait in people with PD . The study will eluci date the functional , clinical and neurophysiological outcomes of combined PRT and a-tDCS . It is hypothesised that combined PRT and a-tDCS will significantly improve lower limb strength , postural sway , gait speed and stride variability compared with PRT with sham tDCS . Further , we hypothesise that pre-frontal cortex activation during dual-task cognitive and gait/balance activities will be reduced , and that M1 excitability and inhibition will be augmented , following the combined PRT and a-tDCS intervention . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12615001241527 . Registered on 12 November 2015 Background . Parkinson disease ( PD ) is characterized by hypometric movements result ing from loss of dopaminergic neurons in the substantia nigra . PD leads to decreased activation of the supplementary motor area ( SMA ) ; the net result of these changes is a poverty of movement . The present study determined the impact of 5 Hz repetitive transcranial magnetic stimulation ( rTMS ) over the SMA on a fine motor movement , h and writing ( writing cursive “ l”s ) , and on cortical excitability , in individuals with PD . Methods . In a cross-over design , ten individuals with PD were r and omized to receive either 5 Hz or control stimulation over the SMA . Immediately following brain stimulation right h and ed writing was assessed . Results . 5 Hz stimulation increased vertical size of h and writing and diminished axial pressure . In addition , 5 Hz rTMS significantly decreased the threshold for excitability in the primary motor cortex . Conclusions . These data suggest that in the short term 5 Hz rTMS benefits functional fine motor task performance , perhaps by altering cortical excitability across a network of brain regions . Further , these data may provide the foundation for a larger investigation of the effects of noninvasive brain stimulation over the SMA in individuals with PD Transcranial direct current stimulation ( tDCS ) is a non-invasive technique for inducing prolonged functional changes in the human cerebral cortex . This simple and safe neurostimulation technique for modulating motor functions in Parkinson ’s disease could extend treatment option for patients with movement disorders . We assessed whether tDCS applied daily over the cerebellum ( cerebellar tDCS ) and motor cortex ( M1-tDCS ) improves motor and cognitive symptoms and levodopa-induced dyskinesias in patients with Parkinson ’s disease ( PD ) . Nine patients ( aged 60–85 years ; four women ; Hoehn & Yahr scale score 2–3 ) diagnosed as having idiopathic PD were recruited . To evaluate how tDCS ( cerebellar tDCS or M1-tDCS ) affects motor and cognitive function in PD , we delivered bilateral anodal ( 2 mA , 20 min , five consecutive days ) and sham tDCS , in r and om order , in three separate experimental sessions held at least 1 month apart . In each session , as outcome variables , patients underwent the Unified Parkinson ’s Disease Rating Scale ( UPDRS III and IV ) and cognitive testing before treatment ( baseline ) , when treatment ended on day 5 ( T1 ) , 1 week later ( T2 ) , and then 4 weeks later ( T3 ) , at the same time each day . After patients received anodal cerebellar tDCS and M1-tDCS for five days , the UPDRS IV ( dyskinesias section ) improved ( p < 0.001 ) . Conversely , sham tDCS , cerebellar tDCS , and M1-tDCS left the other variables studied unchanged ( p > 0.05 ) . Despite the small sample size , our preliminary results show that anodal tDCS applied for five consecutive days over the motor cortical areas and cerebellum improves parkinsonian patients ’ levodopa-induced dyskinesias To study the efficacy of 0.2-Hz repetitive transcranial magnetic stimulation ( rTMS ) on Parkinson 's disease ( PD ) , 85 patients with PD were enrolled into three groups : 1 ) . motor cortical , 2 ) . occipital , and 3 ) . sham stimulation . A round coil was centered over the vertex in motor cortical stimulation , and over the inion in occipital stimulation . In one session , 100 stimuli of 0.2-Hz rTMS at an intensity of 1.1 times active motor threshold ( AMT ) were given . In sham stimulation , electric currents were given with electrodes fixed on the head to mimic the sensation in real stimulation . Each session was carried out once a week for the first 8 weeks . The Unified Parkinson Disease Rating Scale ( UPDRS ) , Hamilton Rating Scale for Depression ( HRSD ) and subjective score ( visual analogue scale ) were assessed . There were no significant differences in clinical features among the three groups . Total and motor score of UPDRS were improved to the same extent by rTMS over Cz , inion , and sham stimulation . HRSD was improved by rTMS over Cz and sham stimulation in the same manner . Subjective score was not significantly improved by any methods of stimulation . 0.2-Hz rTMS at an intensity of 1.1 x AMT has only a placebo effect on PD . Our realistic sham stimulation maneuver must produce powerful placebo effects as a real stimulation OBJECTIVE To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson 's disease ( PD ) . METHODS Repetitive transcranial magnetic stimulation ( rTMS ) was performed on the left motor cortical area corresponding to the right h and in 12 ' off-drug ' patients with PD . The effects of subthreshold rTMS applied at 0.5 Hz ( 600 pulses ) or at 10 Hz ( 2000 pulses ) using a ' real ' or a ' sham ' coil were compared to those obtained by a single dose of l-dopa . The assessment included a clinical evaluation by the Unified Parkinson 's Disease Rating Scale and timed motor tasks , and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques . RESULTS ' Real ' rTMS at 10 or 0.5 Hz , but not ' sham ' stimulation , improved motor performance . High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation , while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking . Concomitantly , 10 Hz rTMS increased intracortical facilitation , while 0.5 Hz rTMS restored intracortical inhibition . CONCLUSIONS Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds . The effects on cortical excitability were opposite to previous observations made in healthy subjects , suggesting a reversed balance of cortical excitability in patients with PD compared to normals . However , the underlying mechanisms of these changes remain to determine , as well as the relationship with clinical presentation and response to l-dopa therapy . SIGNIFICANCE The present study gives some clues to appraise the role of the primary motor cortex in PD . Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application , but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD Objective : To explore the efficacy and stimulation frequency dependence of repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) in Parkinson disease ( PD ) . Methods : In this r and omized , double-blind , sham-controlled , multicenter study with a parallel design , a weekly intervention was performed 8 times . The effects were monitored up to 20 weeks . By central registration , participants were assigned to 1 of 3 arms of the study : low-frequency ( 1-Hz ) rTMS , high-frequency ( 10-Hz ) rTMS , and realistic sham stimulation . The primary end point was the score change of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) part III from the baseline . Several nonmotor symptom scales such as the Hamilton Rating Scale for Depression , apathy score , and nonmotor symptoms question naire were defined as secondary end points . Results : Of the 106 patients enrolled , 36 were allocated to 1-Hz rTMS , 34 to 10-Hz rTMS , and 36 to realistic sham stimulation . Results show 6.84-point improvement of the UPDRS part III in the 1-Hz group at the last visit of the 20th week . Sham stimulation and 10-Hz rTMS improved motor symptoms transiently , but their effects disappeared in the observation period . Changes in nonmotor symptoms were not clear in any group . No severe adverse event was reported . Conclusions : The 1-Hz rTMS over the SMA was effective for motor , but not nonmotor , symptoms in PD . Level of evidence : This study provides Class I evidence that 1-Hz rTMS over the SMA is effective for motor symptoms in PD Parkinson ’s disease is a movement disorder whose principal symptoms are tremor , rigidity , bradykinesia and postural instability . Initially , drugs like l-dopa or dopaminergic agonists are able to control these symptoms , but with the progress of the disease these drugs become less effective . Previous studies have reported that repetitive transcranial magnetic stimulation ( rTMS ) can improve these motor symptoms . The objective of this study was to investigate the neural mechanisms through which 25 Hz rTMS may improve motor symptoms in Parkinson ’s disease . In a double-blind placebo-controlled study , we evaluated the effects of 25 Hz . rTMS in 10 Parkinson ’s disease patients . Fifteen rTMS sessions were performed over the primary cortex on both hemispheres ( one after the other ) during a 12-week period . The patients were studied using functional magnetic resonance imaging during performance of a simple tapping and a complex tapping task , 1 week before the administration of the first rTMS session and just after the last session . rTMS improved bradykinesia , while functional magnetic resonance imaging showed different cortical patterns in prefrontal cortex when patients performed the complex tapping test . Furthermore , the improvement in bradykinesia is associated with cau date nucleus activity increases in simple tapping . Finally , we observed a relative change in functional connectivity between the prefrontal areas and the supplementary motor area after rTMS . These results show a potential beneficial effect of repetitive transcranial magnetic stimulation on bradykinesia in Parkinson ’s disease which is substantiated by neural changes observed in functional magnetic resonance imaging 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 . We studied the effects of 0.2 Hz repetitive transcranial magnetic stimulation ( rTMS ) successively performed 6 times for 2 weeks in 12 patients with idiopathic Parkinson 's disease ( PD ) . Ten patients received rTMS to the bilateral frontal cortex ( frontal rTMS ) and six patients received rTMS to the bilateral occipital cortex ( occipital rTMS ) . Before and after rTMS , we evaluated regional cerebral blood flow ( rCBF ) using 99m-Tc-ECD single photon emission computed tomography ( SPECT ) and clinical tests . In an analysis with statistic parametric mapping , both frontal and occipital rTMS reduced rCBF in the cortical areas around the stimulated site . The activities of daily living ( ADL ) and motor scores of Unified Parkinson 's Disease Rating Scale ( UPDRS ) , pronation-supination movements , and buttoning up significantly improved after frontal rTMS than before it , while occipital rTMS had no significant effects in clinical tests . The findings of the present study suggest that successive 0.2 Hz rTMS has outlasting inhibitory effects on neuronal activity around the stimulated cortical areas . Because there were no significant relations between improved clinical tests and reduced rCBF , we speculate that the indirect effects of 0.2 Hz rTMS on subcortical structures are related to improved parkinsonian symptoms . Further studies recruiting large numbers of subjects are required to confirm the efficacy of 0.2 Hz rTMS on PD BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) has been reported to be clinical ly effective for treating motor symptoms in Parkinson 's disease ( PD ) . Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD . OBJECTIVE We assessed the effects of high-frequency ( HF ) rTMS over the primary motor ( M1 ) foot area on motor symptoms , depression and apathy scales , and sensory symptoms in PD . METHODS We investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a r and omized , double-blind cross-over trial compared with sham stimulation . Motor effects were evaluated using the Unified Parkinson 's Disease Rating Scale part III ( UPDRS-III ) , the self- assessment motor score , the visual analog scale ( VAS ) , the 10-m walking test , and finger tapping . Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale , the Apathy Scale , and quantitative sensory testing . RESULTS HF-rTMS significantly improved UPDRS-III ( P < 0.001 ) , VAS ( P < 0.001 ) , the walking test ( P = 0.014 ) , self- assessment motor score ( P = 0.010 ) , and finger tapping measurement ( P < 0.05 ) compared to sham stimulation . In contrast , no significant improvement was observed in depression and apathy scales . Consecutive days of rTMS did not significantly increase the improvement in motor symptoms . There were no adverse effects following rTMS on patients with PD . CONCLUSIONS We confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD . In addition , daily repeated stimulation was not significantly more effective than a single session of stimulation , but may be effective for maintaining the improvement in motor symptoms in patients with PD Abstract The therapeutic effect of repetitive transcranial magnetic stimulation ( rTMS ) on clinical performance was assessed by a double-blind study in 9 patients with Parkinson 's disease ( PD ) . Nine other patients underwent sham stimulation as controls . The modified Hoehn and Yahr ( H&Y ) staging scale , the Schwab and Engl and Activities of Daily Living ( ADL ) scale , and the Unified Parkinson 's disease rating scale ( UPDRS ) were used to assess changes of clinical performance . Patients were assessed prior to and following 2 months of rTMS . In addition , the mechanism of rTMS was investigated by dopamine and homovanillic acid ( HVA ) in the lumbar cerebrospinal fluid ( CSF ) of 17 patients before and after therapeutic rTMS for three or four months . rTMS was applied manually to the frontal areas 60 times per session , i. e. , 30 times per side using a large circular coil , a pulse intensity of 700 V , and a frequency of 0.2 Hz . Sessions were continued once a week for 2 months . The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS . In contrast , all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months , while the Schwab and Engl and ADL Scale scores increased significantly . In the second CSF sample from patients receiving rTMS , HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinson 's disease and that it may act via inhibition of dopaminergic systems Cortical excitability of the primary motor cortex is altered in patients with Parkinson 's disease ( PD ) . Therefore , modulation of cortical excitability by high frequency repetitive transcranial magnetic stimulation ( rTMS ) of the motor cortex might result in beneficial effects on motor functions in PD . The present study aims to evaluate the effect of rTMS of the motor cortex on motor functions in patients with PD . Thirty-six unmedicated PD patients were included consecutively in this study . The patients were assigned in a r and omized pattern to one of two groups , one group receiving real-rTMS ( suprathreshold 5-Hz , 2000 pulses once a day for 10 consecutive days ) and the second group receiving sham-rTMS using closed envelopes . Total motor section of Unified Parkinson 's Disease Rating Scale ( UPDRS ) , walking speed , and self- assessment scale were performed for each patient before rTMS and after the first , fifth , 10th sessions , and then after 1 month . Evaluation of these measures was performed blindly without knowing the type of rTMS . anova for repeated measurements revealed a significant time effect for the total motor UPDRS , walking speed and self- assessment scale during the course of the study in the group of patients receiving real-rTMS ( P = 0.0001 , 0.001 , and 0.002 ) , while no significant changes were observed in the group receiving sham-rTMS except in self- assessment scale ( P = 0.019 ) . A 10-day course of real-rTMS result ed in statistically significant long-term improvement of the motor functions in comparison with the sham-rTMS . The rTMS could have a therapeutic role of for PD patients Ten unmedicated patients with Parkinson 's disease received sub-threshold 5-Hz repetitive transcranial magnetic stimulation ( rTMS ) over the primary motor h and area ( M1(H AND ) ) contralaterally to the more affected upper limb . Compared to a midfrontal sham-rTMS , real-rTMS over M1(H AND ) was associated with a significant decrease in the global motor UPDRS score 1 h after the cessation of rTMS . This was mainly due to a clinical improvement in the arm contralaterally to the stimulated M1(H AND ) . These preliminary data suggest that focal rTMS of M1(H AND ) may have a therapeutic potential in PD Repetitive transcranial magnetic stimulation ( rTMS ) can modulate cortical excitability and activation and consequently may affect clinical symptoms in neurological conditions characterized by altered motor cortex functions . There are conflicting reports whether low-frequency rTMS has any clinical effects in Parkinson 's disease ( PD ) . Ten patients with PD had rTMS ( 1800 stimuli at just below active motor threshold intensity ) at 1Hz rate delivered over the motor cortex for four consecutive days on two separate occasions . On one of these real rTMS was used and on the other sham rTMS ( placebo ) was used . Evaluations with UPDRS Part 3 ( Motor Scale ) were done in practically defined off-phase at the baseline and one day after the end of each of the treatment series . Neither total Motor Scale scores nor subscores for axial symptoms , rigidity , bradykinesia , and tremor showed any significant difference . The results do not confirm presence of residual beneficial clinical after-effects of consecutive daily applications of low-frequency rTMS on motor symptoms in PD , at least when 1800 stimuli at subthreshold intensity are applied for four days Previous studies in patients with Parkinson 's disease have reported that a single session of repetitive transcranial magnetic stimulation ( rTMS ) can improve some or all of the motor symptoms for 30 to 60 minutes . A recent study suggested that repeated sessions of rTMS lead to effects that can last for at least 1 month . Here we report data that both confirm and extend this work . Fifty-five unmedicated PD patients were classified into four groups : two groups ( early and late PD ) received 25 Hz rTMS bilaterally on the motor arm and leg areas ; other groups acted as control for frequency ( 10 Hz ) and for site of stimulation ( occipital stimulation ) . All patients received six consecutive daily sessions ( 3,000 pulses for each session ) . The first two groups then received a further three booster sessions ( 3 consecutive days of rTMS ) after 1 , 2 , and 3 months , while the third group had only one additional session after the first month . Unified Parkinson 's Disease Rating Scale ( UPDRS ) , walking time , key-tapping speed , and self- assessment scale were measured for each patient before and after each rTMS session and before and after the monthly sessions . Compared to occipital stimulation , 25 Hz rTMS over motor areas improved all measures in both early and late groups ; the group that received 10 Hz rTMS improved more than the occipital group but less than the 25 Hz groups . The effect built up gradually during the sessions and was maintained for 1 month after , with a slight reduction in efficacy . Interestingly , the effect was restored and maintained for the next month by the booster sessions . We conclude that 25 Hz rTMS can lead to cumulative and long-lasting effects on motor performance IMPORTANCE Many medications have anticholinergic effects . In general , anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy . However , a few studies suggest that anticholinergics may be associated with an increased risk for dementia . OBJECTIVE To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve population -based cohort study using data from the Adult Changes in Thought study in Group Health , an integrated health care delivery system in Seattle , Washington . We included 3434 participants 65 years or older with no dementia at study entry . Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003 . Beginning in 2004 , continuous replacement for deaths occurred . All participants were followed up every 2 years . Data through September 30 , 2012 , were included in these analyses . EXPOSURES Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure , which was defined as the total st and ardized daily doses ( TSDDs ) dispensed in the past 10 years . The most recent 12 months of use was excluded to avoid use related to prodromal symptoms . Cumulative exposure was up date d as participants were followed up over time . MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer disease using st and ard diagnostic criteria . Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics , health behaviors , and health status , including comorbidities . RESULTS The most common anticholinergic classes used were tricyclic antidepressants , first-generation antihistamines , and bladder antimuscarinics . During a mean follow-up of 7.3 years , 797 participants ( 23.2 % ) developed dementia ( 637 of these [ 79.9 % ] developed Alzheimer disease ) . A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease ( test for trend , P < .001 ) . For dementia , adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 ( 95 % CI , 0.74 - 1.16 ) for TSDDs of 1 to 90 ; 1.19 ( 95 % CI , 0.94 - 1.51 ) for TSDDs of 91 to 365 ; 1.23 ( 95 % CI , 0.94 - 1.62 ) for TSDDs of 366 to 1095 ; and 1.54 ( 95 % CI , 1.21 - 1.96 ) for TSDDs greater than 1095 . A similar pattern of results was noted for Alzheimer disease . Results were robust in secondary , sensitivity , and post hoc analyses . CONCLUSIONS AND RELEVANCE Higher cumulative anticholinergic use is associated with an increased risk for dementia . Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time |
1,196 | 28,797,556 | The most consistent longitudinal effect observed was increased insular cortex activity following mindfulness‐based interventions .
In contrast to previous review s , we did not find robust evidence for increased activity in specific prefrontal cortex sub‐regions .
These findings suggest that mindfulness interventions are associated with changes in functioning of the insula , plausibly impacting awareness of internal reactions ‘ in‐the‐moment ’ . | Highlights Systematic review of the impact of mindfulness based interventions on brain activity .
ABSTRACT Mindfulness‐based interventions are increasingly used in the treatment and prevention of mental health conditions .
Despite this , the mechanisms of change for such interventions are only beginning to be understood , with a number of recent studies assessing changes in brain activity .
The aim of this systematic review was to assess changes in brain functioning associated with manualised 8‐session mindfulness interventions . | Objective : We compared mindfulness-based cognitive therapy ( MBCT ) with both cognitive psychological education ( CPE ) and treatment as usual ( TAU ) in preventing relapse to major depressive disorder ( MDD ) in people currently in remission following at least 3 previous episodes . Method : A r and omized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU , CPE plus TAU , and TAU alone , and data were analyzed for the 255 ( 93 % ; MBCT = 99 , CPE = 103 , TAU = 53 ) retained to follow-up . MBCT was delivered in accordance with its published manual , modified to address suicidal cognitions ; CPE was modeled on MBCT , but without training in meditation . Both treatments were delivered through 8 weekly classes . Results : Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up , hazard ratio for MBCT vs. CPE = 0.88 , 95 % CI [ 0.58 , 1.35 ] ; for MBCT vs. TAU = 0.69 , 95 % CI [ 0.42 , 1.12 ] . However , severity of childhood trauma affected relapse , hazard ratio for increase of 1 st and ard deviation = 1.26 ( 95 % CI [ 1.05 , 1.50 ] ) , and significantly interacted with allocated treatment . Among participants above median severity , the hazard ratio was 0.61 , 95 % CI [ 0.34 , 1.09 ] , for MBCT vs. CPE , and 0.43 , 95 % CI [ 0.22 , 0.87 ] , for MBCT vs. TAU . For those below median severity , there were no such differences between treatment groups . Conclusion : MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma , but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression Background : Social anxiety disorder ( SAD ) is characterized by distorted self-views . The goal of this study was to examine whether mindfulness-based stress reduction ( MBSR ) alters behavioral and brain measures of negative and positive self-views . Methods : Fifty-six adult patients with generalized SAD were r and omly assigned to MBSR or a comparison aerobic exercise ( AE ) program . A self-referential encoding task was administered at baseline and post-intervention to examine changes in behavioral and neural responses in the self-referential brain network during functional magnetic resonance imaging . Patients were cued to decide whether positive and negative social trait adjectives were self-descriptive or in upper case font . Results : Behaviorally , compared to AE , MBSR produced greater decreases in negative self-views , and equivalent increases in positive self-views . Neurally , during negative self versus case , compared to AE , MBSR led to increased brain responses in the posterior cingulate cortex ( PCC ) . There were no differential changes for positive self versus case . Secondary analyses showed that changes in endorsement of negative and positive self-views were associated with decreased social anxiety symptom severity for MBSR , but not AE . Additionally , MBSR-related increases in dorsomedial prefrontal cortex ( DMPFC ) activity during negative self-view versus case were associated with decreased social anxiety related disability and increased mindfulness . Analysis of neural temporal dynamics revealed MBSR-related changes in the timing of neural responses in the DMPFC and PCC for negative self-view versus case . Conclusion : These findings suggest that MBSR attenuates maladaptive habitual self-views by facilitating automatic ( i.e. , uninstructed ) recruitment of cognitive and attention regulation neural networks . This highlights potentially important links between self-referential and cognitive-attention regulation systems and suggests that MBSR may enhance more adaptive social self-referential processes in patients with SAD IMPORTANCE Currently , fewer than 40 % of patients treated for major depressive disorder achieve remission with initial treatment . Identification of a biological marker that might improve these odds could have significant health and economic impact . OBJECTIVE To identify a c and i date neuroimaging " treatment-specific biomarker " that predicts differential outcome to either medication or psychotherapy . DESIGN Brain glucose metabolism was measured with positron emission tomography prior to treatment r and omization to either escitalopram oxalate or cognitive behavior therapy for 12 weeks . Patients who did not remit on completion of their phase 1 treatment were offered enrollment in phase 2 comprising an additional 12 weeks of treatment with combination escitalopram and cognitive behavior therapy . SETTING Mood and anxiety disorders research program at an academic medical center . PARTICIPANTS Men and women aged 18 to 60 years with currently untreated major depressive disorder . INTERVENTION R and omized assignment to 12 weeks of treatment with either escitalopram oxalate ( 10 - 20 mg/d ) or 16 sessions of manual-based cognitive behavior therapy . MAIN OUTCOME AND MEASURE Remission , defined as a 17-item Hamilton depression rating scale score of 7 or less at both weeks 10 and 12 , as assessed by raters blinded to treatment . RESULTS Positive and negative predictors of remission were identified with a 2-way analysis of variance treatment ( escitalopram or cognitive behavior therapy ) × outcome ( remission or nonresponse ) interaction . Of 65 protocol completers , 38 patients with clear outcomes and usable positron emission tomography scans were included in the primary analysis : 12 remitters to cognitive behavior therapy , 11 remitters to escitalopram , 9 nonresponders to cognitive behavior therapy , and 6 nonresponders to escitalopram . Six limbic and cortical regions were identified , with the right anterior insula showing the most robust discriminant properties across groups ( effect size = 1.43 ) . Insula hypometabolism ( relative to whole-brain mean ) was associated with remission to cognitive behavior therapy and poor response to escitalopram , while insula hypermetabolism was associated with remission to escitalopram and poor response to cognitive behavior therapy . CONCLUSIONS AND RELEVANCE If verified with prospect i ve testing , the insula metabolism-based treatment-specific biomarker defined in this study provides the first objective marker , to our knowledge , to guide initial treatment selection for depression . TRIAL REGISTRATION Registered at clinical trials.gov ( NCT00367341 ) OBJECTIVE Military deployment can have profound effects on physical and mental health . Few studies have examined whether interventions prior to deployment can improve mechanisms underlying resilience . Mindfulness-based techniques have been shown to aid recovery from stress and may affect brain-behavior relationships prior to deployment . The authors examined the effect of mindfulness training on resilience mechanisms in active-duty Marines preparing for deployment . METHOD Eight Marine infantry platoons ( N=281 ) were r and omly selected . Four platoons were assigned to receive mindfulness training ( N=147 ) and four were assigned to a training-as-usual control condition ( N=134 ) . Platoons were assessed at baseline , 8 weeks after baseline , and during and after a stressful combat training session approximately 9 weeks after baseline . The mindfulness training condition was delivered in the form of 8 weeks of Mindfulness-Based Mind Fitness Training ( MMFT ) , a program comprising 20 hours of classroom instruction plus daily homework exercises . MMFT emphasizes interoceptive awareness , attentional control , and tolerance of present-moment experiences . The main outcome measures were heart rate , breathing rate , plasma neuropeptide Y concentration , score on the Response to Stressful Experiences Scale , and brain activation as measured by functional MRI . RESULTS Marines who received MMFT showed greater reactivity ( heart rate [ d=0.43 ] ) and enhanced recovery ( heart rate [ d=0.67 ] , breathing rate [ d=0.93 ] ) after stressful training ; lower plasma neuropeptide Y concentration after stressful training ( d=0.38 ) ; and attenuated blood-oxygen-level-dependent signal in the right insula and anterior cingulate . CONCLUSIONS The results show that mechanisms related to stress recovery can be modified in healthy individuals prior to stress exposure , with important implication s for evidence -based mental health research and treatment OBJECTIVE To examine whether mindfulness-based cognitive therapy ( MBCT ) increases momentary positive emotions and the ability to make use of natural rewards in daily life . METHOD Adults with a life-time history of depression and current residual depressive symptoms ( mean age = 43.9 years , SD = 9.6 ; 75 % female ; all Caucasian ) were r and omized to MBCT ( n = 64 ) or waitlist control ( CONTROL ; n = 66 ) in a parallel , open-label , r and omized controlled trial . The Experience Sampling Method was used to measure momentary positive emotions as well as appraisal of pleasant activities in daily life during 6 days before and after the intervention . Residual depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale ( Hamilton , 1960 ) . RESULTS MBCT compared to CONTROL was associated with significant increases in appraisal s of positive emotion ( b * = .39 ) and activity pleasantness ( b * = .22 ) as well as enhanced ability to boost momentary positive emotions by engaging in pleasant activities ( b * = .08 ; all ps < .005 ) . Associations remained significant when corrected for reductions in depressive symptoms or for reductions in negative emotion , rumination , and worry . In the MBCT condition , increases in positive emotion variables were associated with reduction of residual depressive symptoms ( all ps < .05 ) . CONCLUSIONS MBCT is associated with increased experience of momentary positive emotions as well as greater appreciation of , and enhanced responsiveness to , pleasant daily-life activities . These changes were unlikely to be pure epiphenomena of decreased depression and , given the role of positive emotions in resilience against depression , may contribute to the protective effects of MBCT against depressive relapse BACKGROUND Preliminary research findings have shown that mindfulness-based cognitive therapy improves anxiety and depressive symptoms in bipolar disorder . In this study , we further investigated the effects of MBCT in bipolar disorder , in a controlled fMRI study . METHOD Twenty three patients with bipolar disorder underwent neuropsychological testing and functional MRI . Sixteen of these patients were tested before and after an eight-week MBCT intervention , and seven were wait listed for training and tested at the same intervals . The results were compared with 10 healthy controls . RESULTS Prior to MBCT , bipolar patients reported significantly higher levels of anxiety and symptoms of stress , scored significantly lower on a test of working memory , and showed significant BOLD signal decrease in the medial PFC during a mindfulness task , compared to healthy controls . Following MBCT , there were significant improvements in the bipolar treatment group , in measures of mindfulness , anxiety and emotion regulation , and in tests of working memory , spatial memory and verbal fluency compared to the bipolar wait list group . BOLD signal increases were noted in the medial PFC and posterior parietal lobe , in a repeat mindfulness task . A region of interest analysis revealed strong correlation between signal changes in medial PFC and increases in mindfulness . LIMITATIONS The small control group is a limitation in the study . CONCLUSION These data suggest that MBCT improves mindfulness and emotion regulation and reduces anxiety in bipolar disorder , corresponding to increased activations in the medial PFC , a region associated with cognitive flexibility and previously proposed as a key area of pathophysiology in the disorder The possibility of individualized treatment prediction has profound implication s for the development of personalized interventions for patients with anxiety disorders . Here we utilize r and om forest classification and pre-treatment functional magnetic resonance imaging ( fMRI ) data from individuals with generalized anxiety disorder ( GAD ) and panic disorder ( PD ) to generate individual subject treatment outcome predictions . Before cognitive behavioral therapy ( CBT ) , 48 adults ( 25 GAD and 23 PD ) reduced ( via cognitive re appraisal ) or maintained their emotional responses to negative images during fMRI scanning . CBT responder status was predicted using activations from 70 anatomically defined regions . The final r and om forest model included 10 predictors contributing most to classification accuracy . A similar analysis was conducted using the clinical and demographic variables . Activations in the hippocampus during maintenance and anterior insula , superior temporal , supramarginal , and superior frontal gyri during re appraisal were among the best predictors , with greater activation in responders than non-responders . The final fMRI-based model yielded 79 % accuracy , with good sensitivity ( 0.86 ) , specificity ( 0.68 ) , and positive and negative likelihood ratios ( 2.73 , 0.20 ) . Clinical and demographic variables yielded poorer accuracy ( 69 % ) , sensitivity ( 0.79 ) , specificity ( 0.53 ) , and likelihood ratios ( 1.67 , 0.39 ) . This is the first use of r and om forest models to predict treatment outcome from pre-treatment neuroimaging data in psychiatry . Together , r and om forest models and fMRI can provide single-subject predictions with good test characteristics . Moreover , activation patterns are consistent with the notion that greater activation in cortico-limbic circuitry predicts better CBT response in GAD and PD |
1,197 | 27,766,724 | This meta- analysis showed a robust improvement of gait and FOG by STN-DBS for more than 4 years in the Med-Off/Stim-On condition .
No beneficial effect was found for the On state of medication .
Pre-operative levodopa responsiveness of global motor performance ( UPDRS-III ) is the strongest predictor of the effect of deep brain stimulation on gait | The aim of this meta- analysis was to summarize the short- and long-term effects of bilateral deep brain stimulation of the subthalamic nucleus ( STN-DBS ) on gait and freezing of gait ( FOG ) in Parkinson 's disease and to detect predictors of post-stimulation outcome . | The effects of deep brain stimulation ( DBS ) on balance in people with Parkinson 's disease ( PD ) are not well established . This study examined whether DBS r and omized to the subthalamic nucleus ( STN ; n = 11 ) or globus pallidus interna ( GPi ; n = 10 ) improved compensatory stepping to recover balance after a perturbation . The st and ing surface translated backward , forcing subjects to take compensatory steps forward . Kinematic and kinetic responses were recorded . PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS , combined with off and on levodopa medication . Responses were compared with PD-control subjects ( n = 8) tested over the same timescale and 17 healthy control subjects . Neither DBS nor levodopa improved the stepping response . Compensatory stepping in the best-treated state after surgery ( DBS+DOPA ) was similar to the best-treated state before surgery ( DOPA ) for the PD-GPi group and the PD-control group . For the PD-STN group , there were more lateral weight shifts , a delayed foot-off , and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery . Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery , whereas the number of falls in the GPi and PD-control groups were unchanged . DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group BACKGROUND Low-frequency , bilateral stimulation of the subthalamic nucleus can improve axial symptoms of advanced Parkinson 's disease ( PD ) , but it is not particularly effective for segmental symptoms . METHODS The optimal contacts for low-frequency ( 60 Hz ) and high-frequency ( 130 Hz ) single monopolar stimulation were determined . Then , in a r and omized , double-blind , prospect i ve crossover manner , 60-Hz and 130-Hz stimulations via the respective optimal contacts were compared for immediate efficacy in improving the motor function of patients with PD . RESULTS The optimal contacts for 60-Hz stimulation were situated more ventrally than those for 130-Hz stimulation ( P = 0.038 ) . Under the respective optimal , single monopolar stimulation , 60 Hz provided superior efficacy over 130 Hz in improving the total Unified Parkinson 's Disease Rating Scale motor score ( P < 0.001 ) and the akinesia ( P = 0.011 ) and axial motor signs ( P = 0.012 ) subscores without compromising the therapeutic effect on tremor and rigidity . CONCLUSIONS Low-frequency stimulation via the optimal contacts is effective in improving overall motor function of patients with PD OBJECT Difficulty with step initiation , called " start hesitation , " is related to gait bradykinesia and is an early hallmark of gait freezing in Parkinson disease ( PD ) . Authors of this study investigated the effects of deep brain stimulation ( DBS ) and levodopa on step initiation before and 6 months after DBS surgery in 29 patients with PD who were r and omized to either the bilateral subthalamic nucleus ( STN ) or globus pallidus internus ( GPi ) as the DBS site . METHODS The authors measured the amplitude and duration of anticipatory postural adjustments ( APAs ) , the feed-forward postural preparation that precedes the onset of voluntary step initiation , based on center-of-pressure displacements on a force plate . They also measured the length and velocity of the first step using a motion analysis system to study kinematics . Some of the patients ( 22 ) were from a large , multicenter , double-blind clinical trial , and all patients in the study ( 29 , PD-DBS group ) were r and omized to DBS in either the bilateral STN ( 15 patients ) or bilateral GPi ( 14 patients ) . Differences in step initiation were investigated in 2 conditions before surgery ( off/on levodopa ) and in 4 conditions after surgery ( off/on levodopa combined with off/on DBS ) . Twenty-eight elderly healthy control volunteers ( CTRL group ) were also tested , and 9 control volunteers with PD who met the criteria for DBS ( PD-C group ) were tested at baseline and 6 months later . RESULTS Patients in the PD-DBS group had smaller amplitudes and longer duration s of APAs compared with those in the 28 healthy control volunteers in all conditions . Before surgery , APAs improved with levodopa . After surgery , the APAs were significantly worse than in the best-treatment state before surgery ( DOPA condition ) , and responsiveness to levodopa decreased . No differences in APAs were detected between the STN and GPi groups . A comparison with PD control volunteers who did not undergo DBS surgery confirmed that a deterioration in step preparation was not related to disease progression . Step length and velocity were smaller in the PD-DBS group than in controls in all conditions . Before surgery , levodopa improved the length and velocity of the first step . Both step length and velocity were unchanged in the best-treatment state before surgery ( DOPA condition ) as compared with after surgery ( DBS+DOPA ) , with only step velocity in the STN group getting worse after surgery . CONCLUSIONS Six months of DBS in the STN or GPi impaired anticipatory postural preparation for step initiation , the opposite effect as with levodopa . Deep brain stimulation disrupted postural preparation more than step execution , suggesting independent motor pathways for preparation and execution of gait . Although turning the stimulators on after surgery combined with levodopa benefited the postural preparation to step , a comparison of pre- and postsurgery conditions suggests that either the surgery itself or 6 months of continuous stimulation may lead to an alteration of circuits or plastic changes that impair step initiation BACKGROUND High frequency stimulation ( HFS ) of the subthalamic nucleus ( STN-DBS ) has been shown to have little impact on postural control and gait improvements in Parkinson 's disease ( PD ) . There is a lack of consensus and quantitative evidence to suggest that stimulating STN at a lower frequency ( LFS ) as compared to HFS will be superior in improving symptoms . OBJECTIVE /HYPOTHESIS To determine if postural control and gait characteristics of persons with PD improve at an LFS ( 60 Hz ) compared to HFS ( > 100 Hz ) . We hypothesized that persons with PD would perform better on postural control and gait measures at LFS . METHODS Nineteen participants with bilateral STN-DBS underwent UPDRS , static and dynamic postural control using gait initiation , and gait evaluations in three stimulation conditions ( baseline voltage stable across conditions : OFF , LFS of 60 Hz , and HFS of > 100 Hz ) . Additionally 10/19 participants were also stimulated at 30 Hz and 60 Hz and at higher voltages . A one-way ANOVA was performed to compare the conditions . RESULTS Total UPDRS-III score , step length and velocity during gait initiation , and gait speed significantly improved during 60 Hz and > 100 Hz conditions when compared to the OFF condition ( P < 0.05 ) . There were no significant differences between 60 Hz and > 100 Hz conditions . Using LFS at higher voltage showed no improvement over > 100 Hz condition . CONCLUSIONS The positive effects of both LFS and HFS on postural control and gait were similar and clinical changes were relatively small . LFS may not help improve postural control , and gait particularly for persons with PD who do not develop gait-related disorders after HFS Postural instability is a sign of progression of Parkinson 's disease ( PD ) and often resistant to levodopa treatment . To explore the effect of bilateral deep brain stimulation ( DBS ) of the subthalamic nucleus ( STN ) on postural stability and gait , full body gait analyses were performed without medication , OFF and ON DBS in eight PD patients and 12 healthy age-matched controls . DBS setting was changed at least 3 hours before gait analysis . To describe asymmetry most and least affected sides ( MAS and LAS ) were rated with the Unified Parkinson 's Disease Rating Scale , motor part and quantitative gait analysis with the Vicon 612 gait analysis system . Stride length and gait velocity but not cadence improved ON DBS . The distances between the heel markers and center of mass ( COM ) were asymmetric and reduced OFF DBS . STN DBS increased the distances significantly and reduced asymmetry . The improvement in heel to COM distance was larger on the MAS compared with the LAS . OFF DBS knee momentum asymmetry was inversed so that LAS was more impaired than MAS . ON DBS asymmetry improved . PD patients OFF DBS place the heel too close to COM . The most affected body side has the most impaired swing and the result is a smaller knee moment on the opposite and least affected body side and an asymmetric gait pattern with disturbed balance OFF STN DBS . The asymmetry OFF DBS improved ON DBS . We suggest that DBS facilitates symmetric gait and thereby improves balance during gait Deep brain stimulation of the subthalamic nucleus represents the most important innovation for treatment of advanced Parkinson 's disease . Prospect i ve studies have shown that although the beneficial effects of this procedure are maintained at 5 years , axial motor features and cognitive decline may occur in the long term after the implants . In order to address some unsolved questions raised by previous studies , we evaluated a series of 20 consecutive patients who received continuous stimulation for 8 years . The overall motor improvement reported at 5 years ( 55.5 % at Unified Parkinson 's Disease Rating Scale-motor part , P < 0.001 compared with baseline ) was only partly retained 3 years later ( 39 % , P < 0.001 , compared with baseline ; -16.5 % , P < 0.01 , compared with 5 years ) , with differential effects on motor features : speech did not improve and postural stability worsened ( P < 0.05 ) . The preoperative levodopa equivalent daily dose was reduced by 58.2 % at 5 years and by 60.3 % at 8 years . In spite of subtle worsening of motor features , a dramatic impairment in functional state ( -56.6 % at Unified Parkinson 's Disease Rating Scale-Activities of Daily Living , P < 0.01 ) emerged after the fifth year of stimulation . The present study did not reveal a predictive value of preoperative levodopa response , whereas few single features at baseline ( such as gait and postural stability motor scores and the preoperative levodopa equivalent daily dose ) could predict long-term motor outcome . A decline in verbal fluency ( slightly more pronounced than after 5 years ) was detected after 8 years . A significant but slight decline in tasks of abstract reasoning , episodic memory and executive function was also found . One patient had developed dementia at 5 years with further progression at 8 years . Executive dysfunction correlated significantly with postural stability , suggesting interplay between axial motor deterioration and cognition . Eight years after surgery , no significant change was observed on scales assessing depression or anxiety when compared with baseline . At 8 years , there was no significant increase of side-effects when compared with 5-year follow-up . In conclusion , deep brain stimulation of the subthalamic nucleus is a safe procedure with regard to cognitive and behavioural morbidity over long-term follow-up . However , the global benefit partly decreases later in the course of the disease , due to progression of Parkinson 's disease and the appearance of medication- and stimulation-resistant symptoms Gait and balance disturbances typically emerge in advanced Parkinson ’s disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation . Therefore , advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead . Here , we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with st and ard subthalamic nucleus stimulation . Twelve patients were enrolled in this 2 × 2 cross-over double-blind r and omized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with st and ard subthalamic nucleus stimulation . The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson ’s Disease Rating Scale score ( Scale II items 13–15 , Scale III items 27–31 ) at ‘ 3-week follow-up ’ . Secondary outcome measures specifically addressed freezing of gait , balance , quality of life , non-motor symptoms and neuropsychiatric symptoms . For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the ‘ 3-week follow-up ’ . The secondary endpoints , however , revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait , whereas balance impairment remained unchanged . The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe , and of note , no clinical ly relevant neuropsychiatric adverse effect was observed . Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no ‘ global ’ effect on axial motor domains . However , this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and , therefore , highly warrants a subsequent phase III r and omized controlled trial Abstract .Subthalamic nucleus ( STN ) stimulation , a recent surgical approach to Parkinson ’s disease ( PD ) , has been shown to be effective in relieving motor symptoms . The present study carried out a full body gait analysis , during overground walking , on ten PD patients with bilaterally implanted STN stimulation devices . Walking performance was analyzed on the same day , in four conditions ( Stim Off – Med Off , Stim On – Med Off , Stim Off – Med On , Stim On – Med On ) . The results showed that , on average , STN stimulation alone ( S+M− ) and l -dopa alone ( S-M+ ) , significantly increased gait speed , stride length and the lower limb joint Range of Motion ( ROM ) with respect to the basal condition ( S−M− ) ; also cadence was found to play a role in velocity increase , particularly when l -dopa was administered . Both treatments improved pelvis and trunk kinematics , and power production at the ankle and hip joints . The combination of the two treatments ( S+M+ ) produced an additional effect on gait speed , stride length , ROM of knee and ankle joints , pelvis obliquity and trunk inclination . Given the additive and synergistic effects , it can be hypothesized that the two treatments have different mechanisms of action . Our results confirm the findings of earlier studies that employed treadmill walking BACKGROUND Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson 's disease have been well documented , the long-term outcomes of the procedure are unknown . METHODS We conducted a five-year prospect i ve study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus . Patients were assessed at one , three , and five years with levodopa ( on medication ) and without levodopa ( off medication ) , with use of the Unified Parkinson 's Disease Rating Scale . Seven patients did not complete the study : three died , and four were lost to follow-up . RESULTS As compared with base line , the patients ' scores at five years for motor function while off medication improved by 54 percent ( P<0.001 ) and those for activities of daily living improved by 49 percent ( P<0.001 ) . Speech was the only motor function for which off-medication scores did not improve . The scores for motor function on medication did not improve one year after surgery , except for the dyskinesia scores . On-medication akinesia , speech , postural stability , and freezing of gait worsened between year 1 and year 5 ( P<0.001 for all comparisons ) . At five years , the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced , as compared with base line ( P<0.001 for each comparison ) . The average scores for cognitive performance remained unchanged , but dementia developed in three patients after three years . Mean depression scores remained unchanged . Severe adverse events included a large intracerebral hemorrhage in one patient . One patient committed suicide . CONCLUSIONS Patients with advanced Parkinson 's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication . There was no control group , but worsening of akinesia , speech , postural stability , freezing of gait , and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson 's disease BACKGROUND The effect of the surgical site of DBS on balance and gait in Parkinson 's Disease ( PD ) is uncertain . This is the first double-blind study of subjects r and omized to either the STN ( N = 14 ) or GPi ( N = 14 ) who were assessed on a range of clinical balance measures . METHODS Balance testing occurred before and 6 months postsurgery . A control PD group was tested over the same period without surgery ( N = 9 ) . All subjects were tested on and off medication and DBS subjects were also tested on and off DBS . The Postural Instability and Gait Disability items of the UPDRS and additional functional tests , which we call the Balance and Gait scale , were assessed . Activities of Balance Confidence and Activities of Daily Living question naires were also recorded . RESULTS Balance was not different between the best-treated states before and after DBS surgery for both sites . Switching DBS on improved balance scores , and scores further improved with medication , compared to the off state . The GPi group showed improved performance in the postsurgery off state and better ratings of balance confidence after surgery , compared to the STN group . CONCLUSIONS Clinical measures of balance function for both the STN and GPi sites showed that balance did not improve beyond the best medically treated state before surgery . Both clinical balance testing in the off/off state and self-reported balance confidence after surgery showed better performance in the GPi than the STN group Deep brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson 's disease . The benefits of bilateral subthalamic stimulation are well documented , and some studies reported outcomes with a follow-up of 5 to 6 years ; nevertheless , few data are available beyond 5 years . We report a long-term prospect i ve evaluation of 14 consecutive parkinsonian patients , treated by bilateral subthalamic stimulation for at least 9 years . Motor symptoms , activity of daily living , and motor complications were evaluated by means of the Unified Parkinson 's Disease Rating Scale , while cognition and mood were assessed with a specific neuropsychological test battery ; medication intake , stimulation parameters , comorbidity , and adverse events were also recorded . Patients were evaluated before surgery and at 1 , 5 , and ≥ 9 years after surgery . At last follow-up , deep brain stimulation significantly improved the motor score by 42 % compared to baseline , whereas activities of daily living were no longer improved ; there was a 39 % reduction in the dosage of dopaminergic drugs and a 59 % improvement of L-dopa-related motor complications . The neuropsychological assessment showed that 4 patients ( 29 % ) developed a significant cognitive decline over the follow-up period . These results indicate a persistent effect of deep brain stimulation of the subthalamic nucleus on the cardinal motor symptoms in advanced Parkinson 's disease patients in the long-term ; however , a worsening of patients ' disability , mainly due to disease progression , was observed Axial symptoms such as freezing of gait and falls are common manifestations of advanced Parkinson ’s disease ( PD ) and are partially responsive to medical treatment . High-frequency ( ≥130 Hz ) deep brain stimulation ( DBS ) of the subthalamic nucleus ( STN ) is highly efficacious in ameliorating appendicular symptoms in PD . However , it is typically less effective in improving axial symptomatology , especially in the long term . We have studied the effects of low-frequency stimulation ( LFS ) ( ≤80 Hz ) for improving speech , gait and balance dysfunction in the largest patient population to date . PD patients with bilateral STN-DBS and resistant axial symptoms were switched from chronic 130 Hz stimulation to LFS and followed up to 4 years . Primary outcome measures were total motor UPDRS scores , and axial and gait subscores before and after LFS . Bivariate analyses and correlation coefficients were calculated for the different conditions . Potential predictors of therapeutic response were also investigated . Forty-five advanced PD patients who had high frequency stimulation ( HFS ) for 39.5 ± 27.8 consecutive months were switched to LFS . LFS was kept on for a median period of 111.5 days before the assessment . There was no significant improvement in any of the primary outcomes between HFS and LFS , although a minority of patients preferred to be maintained on LFS for longer periods of time . No predictive factors of response could be identified . There was overall no improvement from LFS in axial symptoms . This could be partly due to some study limitations . Larger prospect i ve trials are warranted to better clarify the impact of stimulation frequency on axial signs OBJECTIVE : A prospect i ve cohort study to evaluate the efficacy of bilateral subthalamic nucleus deep brain stimulation ( STN-DBS ) on freezing of gait ( FOG ) in patients with advanced Parkinson 's disease . METHODS : Patients ( n = 10 ) with advanced Parkinson 's disease were surgically implanted with microelectrodes to facilitate STN-DBS . Evaluations of FOG , motor function , activities of daily living and neuropsychological function were carried out in on-medication and off-medication states ( with and without levodopa treatment ) , before surgery and at 6 and 12 months postoperatively . RESULTS : STN-DBS was associated with significant improvement in FOG score and neuropsychological function at both 6 and 12 months postoperatively , compared with preoperatively . Significant postoperative improvements were also observed in motor function and activities of daily living . Daily levodopa dosage was significantly lower at both 6 and 12 months postoperatively . CONCLUSIONS : STN-DBS improved FOG in patients with advanced Parkinson 's disease . The significant reduction in levodopa dosage and improvement in neuropsychological function may be the reason for the therapeutic effect seen with STN-DBS Background Freezing of gait ( FOG ) is a debilitating gait disorder in Parkinson 's disease ( PD ) with partial responsiveness to dopaminergic medication . To date , notions about the effects of subthalamic deep brain stimulation ( STN-DBS ) on FOG remain controversial . Objectives To compare the effects of bilateral STN-DBS and continued best medical treatment ( BMT ) on FOG occurrence , FOG severity and clinical outcomes in PD patients at 6 and 12 months follow-up . Methods In this prospect i ve , controlled study , 41 PD patients with at least 5 years disease duration participated . Twenty-four subjects ( 20 with FOG ) were treated with STN-DBS and seventeen ( 15 with FOG ) continued BMT . The primary outcome was the New Freezing of Gait Question naire ( NFOGQ ) at 6 months postsurgery . Other outcomes were the NFOGQ at 12 months and clinical outcomes ( Unified Parkinson 's Disease Rating Scale III ( UPDRS III ) , timed gait , falls and quality of life ) at both time points . Results STN-DBS increased the likelihood to convert from being a freezer to a non-freezer at 6 and 12 months follow-up ( relative risk reduction=0.4 ) . However , 45 % of baseline freezers still experienced FOG 6 and 12 months postsurgery although with reduced severity . Three baseline non-freezers ( 1/2 BMT-treated , 2/4 STN-DBS-treated ) developed FOG during follow-up . STN-DBS-induced benefits on FOG were mostly mediated by baseline levodopa equivalent dose , altered medication-intake and reduced motor fluctuations . Conclusions In contrast to continued BMT , STN-DBS reduced FOG occurrence and severity at 6 months postsurgery with largely sustained effects at 12 months follow-up . Longer follow-up periods are needed to test whether FOG improvements after STN-DBS persist with disease progression Postural control requires precise integration of sensory inputs and motor output , but clinical assessment s of postural control do not differentiate between these . Previously , we found that this differentiation is important in Parkinson 's disease ( PD ) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability . In this study , we address several questions that emerged from that work in 28 different patients with PD off and on medication , before and after bilateral subthalamic nucleus deep brain stimulation ( B-STN DBS ) : ( 1 ) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory-deprived conditions ? ( 2 ) Are more specific measures of motor aspects of postural control using dynamic posturography ( postural movement velocity [ MV ] and reaction time [ RT ] ) abnormal in PD as seen clinical ly using the Postural Instability and Gait Disorder score of the Unified Parkinson 's Disease Rating Scale ? ( 3 ) What is the effect of B-STN DBS versus medication on sensory versus motor aspects of postural instability in PD ? The results included ( 1 ) substantially more patients ( 39 % ) versus controls ( 5 % ) exhibited postural instability in conditions of limited sensory feedback ; ( 2 ) postural MV and postural RT were abnormal off medication preoperatively ( N(subset ) = 23 ; P < 0.001 for both ) ; ( 3 ) B-STN DBS improved abnormal sensory aspects of postural instability ( P < 0.05 ) and postural MV ( P = 0.005 ) , whereas medication did not . Neither B-STN DBS nor medication improved postural RT . For the group as a whole , STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control ( P = 0.003 ) The effects of subthalamic nucleus ( STN ) deep brain stimulation ( DBS ) on fall risk in patients with Parkinson 's disease ( PD ) currently remain unclear . Although several gait parameters , such as gait speed , have shown improvement with DBS , some studies have reported an increased fall risk following DBS . The purpose of this study was to examine the effect of bilateral DBS on gait variability , a marker of fall risk . The gait of 13 patients with idiopathic PD was analyzed to determine the influence of DBS , levodopa and both therapies together . Following treatment with both levodopa and STN DBS , subjects displayed improved gait speed , reduced gait variability ( enhanced stability ) , and lower Unified Parkinson 's Disease Rating Scale ( UPDRS ) scores . Although UPDRS scores improved with STN DBS alone , parallel improvements were not seen for gait variability . These findings suggest that different mechanisms may contribute to performance on UPDRS motor testing and gait stability in response to DBS BACKGROUND Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson 's disease . The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure . We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna ( pallidal stimulation ) or subthalamic nucleus ( subthalamic stimulation ) . METHODS At seven Veterans Affairs and six university hospitals , we r and omly assigned 299 patients with idiopathic Parkinson 's disease to undergo either pallidal stimulation ( 152 patients ) or subthalamic stimulation ( 147 patients ) . The primary outcome was the change in motor function , as blindly assessed on the Unified Parkinson 's Disease Rating Scale , part III ( UPDRS-III ) , while patients were receiving stimulation but not receiving antiparkinsonian medication . Secondary outcomes included self-reported function , quality of life , neurocognitive function , and adverse events . RESULTS Mean changes in the primary outcome did not differ significantly between the two study groups ( P=0.50 ) . There was also no significant difference in self-reported function . Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation ( P=0.02 ) . One component of processing speed ( visuomotor ) declined more after subthalamic stimulation than after pallidal stimulation ( P=0.03 ) . The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation ( P=0.02 ) . Serious adverse events occurred in 51 % of patients undergoing pallidal stimulation and in 56 % of those undergoing subthalamic stimulation , with no significant between-group differences at 24 months . CONCLUSIONS Patients with Parkinson 's disease had similar improvement in motor function after either pallidal or subthalamic stimulation . Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation . ( Clinical Trials.gov numbers , NCT00056563 and NCT01076452 . OBJECT The effect of deep brain stimulation ( DBS ) for Parkinson disease ( PD ) on balance is unclear . The goal of this study was to investigate how automatic postural responses ( APRs ) were affected in patients r and omized to either subthalamic nucleus ( STN ) or globus pallidus internus ( GPi ) surgery . METHODS The authors tested 24 patients with PD who underwent bilateral DBS , 9 control patients with PD who did not undergo DBS , and 17 age-matched control volunteers . The electrode placement site was r and omized and blinded to the patients and to the experimenters . Kinematic , kinetic , and electromyographic recordings of postural responses to backward disequilibrium via forward translations of the st and ing surface were recorded in the week prior to surgery while the patients were off ( OFF ) and on ( ON ) antiparkinsonian medication ( levodopa ) , and then 6 months after surgery in 4 conditions : 1 ) off medication with DBS switched off ( OFF/OFF ) ; 2 ) off medication with DBS on ( DBS ) ; 3 ) on medication with DBS off ( DOPA ) ; and 4 ) with both medication and DBS on ( DBS+DOPA ) . Stability of the automatic postural response ( APR ) was measured as the difference between the displacement of the center of pressure and the projected location of the center of body mass . RESULTS Patients with PD had worse APR stability than controls . Turning the DBS on at either site improved APR stability compared with the postoperative OFF condition by lengthening the tibialis response , whereas medication did not show an appreciable effect . The STN group had worse APR stability in their best functional state ( DBS+DOPA ) 6 months after the DBS procedure compared with their best functional state ( ON levodopa ) before the DBS procedure . In contrast , the GPi group and the PD control group showed no change over 6 months . The APR stability impairment in the STN group was associated with smaller tibialis response amplitudes , but there was no change in response latency or coactivation with gastrocnemius . CONCLUSIONS Turning the DBS current on improved APR stability for both STN and GPi sites . However , there was a detrimental DBS procedural effect for the STN group , and this effect was greater than the benefit of the stimulating current , making overall APR stability functionally worse after surgery for the STN group |
1,198 | 17,594,378 | 1 ) In the disc displacement group with pain , multimodal therapy was not superior to explanation and advice .
There was no superiority of multimodal therapy including splints as compared with simple care .
A slightly better outcome was reported for a combination of education and home physical therapy regimen than for patient education alone . (
3 ) In temporom and ibular pain patients with major psychological disturbances , patients benefited more from a combined therapeutic approach compared with simple care .
Current research suggests that individuals without major psychological symptoms do not require more than simple therapy .
In contrast , patients with major psychological involvement need multimodal , interdisciplinary therapeutic strategies . | BACKGROUND Pain is the most common motivation for patients with temporom and ibular disorders ( TMDs ) to seek care .
Therapeutic options range from patient education to joint surgery .
OBJECTIVES To conduct a systematic review of articles reporting on simple and multimodal management strategies in TMD patients . | The outcome of different treatment modalities after 7 years was investigated in a selected group of 50 patients with craniom and ibular disorders of muscular origin . To minimize the possible effects of selection on the clinical material , the selected treatment group was compared to a consecutive group of patients in terms of age , gender , intensity/ duration of pain , and socioeconomic profile . Both groups were comparable in most respects , but the selected group had a longer duration and a higher intensity of pain at baseline . There were more men in the consecutive group than in the selected group . A combined treatment approach result ed in a better outcome than single treatments . Sixty-five percent of all patients in the selected group reported improvement at the 7-year follow-up . All of the 19 patients who received counseling combined with different occlusal treatments improved . Forty-three percent of the patients treated otherwise showed improvement . Patients who were aware of stress responded better to treatment To assess the differential efficacy of two commonly used treatments for temporom and ibular disorders ( TMD ) , intraoral appliances ( IAs ) and biofeedback ( BF ) , separately and in combination , two studies were conducted . The first study directly compared IA treatment , a combination of biofeedback and stress management ( BF/SM ) , and a waiting list control group in a sample of 80 TMD patients . Both treatments were determined to be equally credible to patients , ruling out this potential threat to the validity of the results obtained . The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment , but at a 6-month follow-up the IA group significantly relapsed , especially in depression , whereas the BF/SM maintained improvements on both pain and depression and continued to improve . The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients . The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone , particularly in pain reduction , at the 6-month follow-up . These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained BACKGROUND Treatment recommendations for patients with painful temporom and ibular disorders ( TMDs ) range from conservative treatments such as physiotherapy to aggressive and irreversible treatments such as restorative reconstruction and joint surgery . METHODS The authors r and omized 200 subjects diagnosed with TMD into three groups : usual conservative , dentist-prescribed self-care treatment without any intraoral splint appliance ( UT ) ; UT plus a conventional flat-plane hard acrylic splint ( HS ) ; and UT plus a soft vinyl ( a low-cost athletic mouth guard ) splint ( SS ) . Subjects completed question naires and clinical examinations at three , six and 12 months . RESULTS The authors observed no significant differences among the groups in TMD-related pain levels or other common signs and symptoms of TMD at baseline ( BL ) or at any follow-up . The changes from BL were comparable for all three groups . The authors did not note any significant differences at any follow-up for compliance with study protocol s or for occurrences of adverse effects from either splint type . For HS versus SS , there were significant differences in rates of splint use , but these differences were not accompanied by differences in either self-reported symptoms or in clinical findings . CONCLUSIONS All patients improved over time , and traditional splint therapy offered no benefit over the SS splint therapy . Neither splint therapy provided a greater benefit than did self-care treatment without splint therapy . CLINICAL IMPLICATION S These findings suggest that clinicians who treat patients with TMD should consider prescribing low-cost nonsplint self-care therapy for most patients & 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 In a r and omized trial the effects of occlusal appliance and relaxation therapy , each combined with brief information , were compared with brief information only , in adolescents with temporom and ibular disorder ( TMD ) pain . One-hundred- and -twenty-two adolescents ( 93 F and 29 M aged 12 - 18 years ) were r and omly assigned to one of the following 3 groups : brief information + occlusal appliance ( BI + OA ) , brief information + relaxation therapy ( BI + RT ) , or brief information ( BI ) . Included were subjects reporting pain once a week or more often , in addition to receiving a diagnosis of TMD according to the Research Diagnostic Criteria ( RDC/TMD ) . They were evaluated before and after treatment and at a 6-month follow-up by means of self-reports and clinical assessment . The result revealed a significantly higher reduction in frequency of pain , in pain intensity ( visual analog scale [ VAS ] ) , and in a composite pain index ( intensity x frequency ) for patients treated with BI + OA compared with those treated with BI alone . In the BI + OA group , 60 % of the patients attained a clinical ly significant improvement ( at least 50 % or more ) on the pain index , a significantly higher proportion compared to that obtained in the other 2 treatment groups . Analgesic consumption was also significantly more reduced in the BI + OA group compared to the BI group . However , no significant differences were found between the treatment groups in jaw opening or in muscle and TMJ tenderness scores . Occlusal appliance was found to be superior to both relaxation therapy and brief information regarding pain reduction and can therefore be recommended when treating adolescents with TMD pain & NA ; The course of pain associated with temporom and ibular disorders ( TMD ) and other chronic pain conditions is typically episodic . Its expression may influence when a person seeks treatment , for example , when the level of pain flares up or exceeds its characteristic severity . Improvement in pain status subsequent to entering treatment may be due to : ( 1 ) specific effects of treatment ; ( 2 ) non‐specific effects of treatment ( ‘ placebo effects ’ ) ; or ( 3 ) regression to the mean . Due to regression to the mean , uncontrolled evaluation of treatment in persons self‐selected by a pain flare‐up may lead to erroneous conclusions concerning effects of treatment by patients , providers , and /or research ers . For this report , the magnitude of regression to the mean due to self‐ selection for treatment is estimated by comparing subjects who sought treatment for TMD pain ( n = 147 ) to a r and om sample of subjects with TMD pain not seeking treatment ( n = 95 . Among subjects seeking treatment , a significant 14.7‐point reduction in VAS pain intensity was observed at 1‐year follow‐up . A control group of TMD subjects not seeking treatment showed no mean reduction in pain intensity but reported lower pain intensity at baseline than the group seeking care . When both groups of subjects were stratified on baseline VAS pain values , the reduction in pain increased as the baseline pain level increased , but no differences between comparable treated and untreated cases in the extent of improvement were observed . The before‐after differences in both groups may be attributed to regression to the mean . We conclude that before‐after differences in pain intensity can be large and that such improvement may be largely due to regression to the mean . This suggests the need for research which differentiates change due to regression to the mean ( due to homeostatic processes , r and om within‐subject variation , or measurement error ) from change due to specific and non‐specific effects of treatment . In clinical practice , the personal experience of patients and clinicians who observe improvement after initiation of treatment should be regarded as an unreliable guide to treatment efficacy due to regression to the mean . This phenomenon may contribute to the proliferation and continued use of treatments of unproven efficacy for pain management and suggests caution in the use of costly or risky pain treatments the efficacy of which is unknown AIMS To test the usefulness of tailoring cognitive-behavioral therapy ( CBT ) for patients with temporom and ibular disorders ( TMD ) who demonstrated poor psychosocial adaptation to their TMD condition , independent of physical diagnosis . METHODS A r and omized clinical trial compared a 6-session CBT intervention delivered in conjunction with the usual TMD treatment to the usual conservative treatment by TMD specialist dentists . For study inclusion , Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) , Axis II criteria , were used to target patients with elevated levels of TMD pain-related interference with daily activities , independent of physical diagnosis ( i.e. , Axis I ) . RESULTS At the post-treatment assessment , about 4 months after the baseline evaluations , the comprehensive care group , when compared to the usual treatment group , showed significantly lower levels of characteristic pain intensity , significantly higher self-reported ability to control their TMD pain , and a strong trend ( P = .07 ) toward lower pain-related interference in daily activities . From post-intervention to 1-year follow-up , all subjects showed improvement . At the 1-year follow-up , the comprehensive care group , while not losing any of its early gains , was not significantly different from the usual care group with regard to reported levels of pain , ability to control pain , and levels of interference in activities . For many of these psychosocially disabled TMD patients , pain and interference 1 year after treatment remained at the same or higher levels than those observed at baseline among a group of patients selected for a separate r and omized clinical trial on the basis of better psychosocial adaptation . CONCLUSION The 6-session CBT intervention for patients with heightened psychologic and psychosocial disability was effective in improving pain-related variables over the course of the CBT in conjunction with usual treatment , but was too brief an intervention to result in further improvement after the sessions ended . Patient ratings of treatment satisfaction and helfulness were high for both groups , but they were significantly higher for the comprehensive care group OBJECTIVE The purpose of this study was to identify the appropriate treatment element for initial anterior disc displacement without reduction subjects . STUDY DESIGN Sixty-nine consecutive patients with temporom and ibular joint disc displacement without reduction confirmed on magnetic resonance images were r and omly divided into 3 experimental treatment groups . The treatment of group 1 consisted of short-term nonsteroidal anti-inflammatory drugs and self-care instructions ( palliative care group ) ; group 2 , nonsteroidal anti-inflammatory drugs , self-care instructions , and occlusal appliance and mobilization therapy ( physical medicine group ) ; and group 3 , no treatment ( control group ) . Outcomes were assessed by means of a 5-item question naire that evaluated ( 1 ) symptom improvement , ( 2 ) difficulty of treatment , and ( 3 ) satisfaction with treatment during the 8-week observation period . RESULTS Improvement scores in the palliative care group were significantly better than those in the physical medicine group or the no-treatment group . Satisfaction scores showed no significant difference among the 3 groups . Difficulty from treatment for the physical medicine group was significantly greater than that for other 2 groups . CONCLUSION These data suggest that palliative care would be more appropriate as the initial therapy to treat painful anterior disc displacement without reduction AIMS To compare the short-term efficacy of patient education only versus the combination of patient education and home exercises for the treatment of myofascial pain of the jaw muscles . MATERIAL S AND METHODS Seventy myogenous temporom and ibular disorder patients were assigned to 2 treatment groups . One group received patient education supplemented by general information about self-care of the jaw musculature . The other group received both education and a home physical therapy program . Treatment contrast , calculated from the mean normalized relative changes in anamnestic and clinical scores , was used to determine treatment success . Clinical outcome measures included pressure pain threshold ( PPT ) of the masseter , anterior temporalis , and Achilles tendon ; pain-free maximal jaw opening ; and pain on chewing , spontaneous muscle pain , and headache as rated on visual analog scales . RESULTS After 3 months the success rate was 57 % for the group that received education only and 77 % for the group that received both education and home physical therapy ( P = .157 ) . The patients were then redivided into 2 groups : successfully treated patients and unsuccessfully treated patients . In the unsuccessfully treated group , pain-free maximal jaw opening increased significantly more among those who had been in the education and physical therapy group than among those who had been in the education-only group ( P = .019 ) . The change in PPT was significantly greater in successfully treated patients than in unsuccessfully treated patients ( .009 < P < .039 ) , independent of the treatment modality , with higher PPTs among successful patients . There were no significant differences between the successfully and unsuccessfully treated groups or between treatment modalities for any other variable . CONCLUSION Over a period of 3 months , the combination of education and a home physical therapy regimen , as used in this protocol , is slightly more clinical ly effective than education alone for the treatment of myofascial pain of the jaw muscles Forty-eight dysfunctional patients ( i.e. , high levels of pain , interference , and affective distress and low levels of perceived control ) with temporom and ibular disorders ( TMDs ) were r and omly assigned either to a treatment consisting of an intraoral appliance ( IA ) and stress management with biofeedback ( SM ) plus nondirective , supportive counseling ( SC ) -- IA + SM + SC -- or to a customized treatment that included cognitive therapy ( CT ) with the IA and SM -- IA + SM + CT . Both treatment groups reported statistically significant reductions on a set of physical , psychosocial , and behavioral measures posttreatment and at a 6-month follow-up . However , the intervention that included CT demonstrated significantly greater reductions in pain , depression , and medication use . Only the groups receiving the treatment that included the CT demonstrated continued improvements to the follow-up on pain associated with muscle palpation , self-reported pain severity , depression , and use of medications . These results support the efficacy of the tailored treatment for dysfunctional TMD The common methods for treating anterior disk displacement without reduction ( ADDwor ) are not based on r and omized controlled clinical trials . Our study evaluated non-surgical treatments in 69 MRI-confirmed ADDwor subjects ( m/f = 6/63 ) . Subjects were r and omly assigned to a control group and one of two treatment groups . Outcomes included maximum mouth opening , visual analogue scale of pain , and daily activity limitation . Calibrated examiners collected data at the initial interview and at 0 , 2 , 4 , and 8 weeks of treatment . At the eight-week point , within-group improvements were present for all variables , for all groups . Between-group differences were not highly evident , with only mean daily activity limitation for the self-care/NSAID group being significantly lower than that of the occlusal appliance/jaw mobilization + self-care/NSAID group at the two- and four-week time-points . These results suggest that ADDwor subjects will improve with only minimal treatment intervention , and no significant difference was evident for the treatments tested and the control condition |
1,199 | 22,791,100 | In patients with colorectal cancer ( CRC ) undergoing surgery , ABTs are associated with adverse clinical outcomes , including increased mortality . | OBJECTIVE To determine the effect of allogeneic blood transfusion ( ABT ) on clinical outcomes in patients with colorectal cancer undergoing surgery .
BACKGROUND Perioperative ABTs may be associated with adverse clinical outcomes . | In 1973 the observation was published that in patients who had received non specific blood transfusions before kidney transplantation graft survival was improved . An immunosuppressive effect of blood transfusion was suggested . Indeed , modulation on the cellular and humoral immunologic system has been demonstrated during the last decade . But this immunomodulation effect might worsen the prognosis after cancer surgery . Whereas in several experimental studies in animals the negative influence was confirmed , clinical investigations on the other h and are contradictive . In our retrospective study we analysed the follow-up of 273 patients ( 158 men , 115 women ; average age 66 years ) on which we had performed a curative resection of their colorectal carcinoma . 182 patients had received nonspecific r and om blood transfusions . The survival rate for patients with blood transfusions was significantly worse in comparison to the non-transfused group ( 43 % versus 73 % , respectively ) . Even when we subdivided our patients into tumor stage , differentiation and localisation , the negative influence of transfused blood was confirmed . We conclude that beside the risk of transmitting hepatitis or HIV the immunosuppressive effect is a strong argument to restrict the indication for blood transfusion After curative resection of colorectal cancer , immediate short-term postoperative intraportal adjuvant chemotherapy reduces the relative risk of recurrence and death in the non-transfused patient significantly , when compared to transfused patients without chemotherapy . This is demonstrated in a multivariate analysis using the Cox model on a group of 469 patients who have been intraoperatively r and omized to receive either intraportal chemotherapy for 7 days or no further treatment . The transfused patients with chemotherapy and those receiving neither transfusions nor chemotherapy had a relative risk of recurrence and death situated in between the two groups mentioned above , not statistically different from either of them . In the setting of this study , 7 days postoperative intraportal chemotherapy seems particularly effective in the non-transfused patients BACKGROUND Benchmarking transfusion activity may help to eliminate inappropriate use of blood products . The goal of this study was to measure and to compare the current transfusion practice and to identify predictors of transfusion in public hospitals to develop strategies to optimize transfusion practice s. STUDY DESIGN AND METHODS This was a prospect i ve observational study in 18 r and omly selected public hospitals from April 2004 to February 2005 . Primary outcome measures were the amount of intra- and postoperative blood components transfused and intercenter variability of transfusion rate . Secondary outcome measures were prevalence of preoperative anemia , calculated perioperative blood loss , and lowest measured perioperative hemoglobin ( Hb ) level . RESULTS Adult patients undergoing primary unilateral total hip replacement ( THR , n = 1401 ) , primary unilateral knee replacement ( TKR , n = 1296 ) , hemicolectomy ( HECOC , n = 148 ) , and coronary artery bypass graft ( CABG ) surgery ( n = 777 ) were enrolled . Due to the small number , data of HECOC patients were not fully analyzed . In the remaining procedures , there was a large intercenter variability in the percentage of patients who received transfusions : THR 16 to 85 percent , TKR 12 to 87 percent , and CABG 37 to 63 percent . In the patients who received transfusions , the number of red blood cells ( RBC ) units transfused varied significantly . There was also a considerable intercenter variability in RBC loss . The prevalence of preoperative anemia was 19 percent and identical in both sexes . The incidence of preoperative anemia was three times higher in patients who received transfusions compared to those who did not . CONCLUSION This study demonstrates a high intercenter variability in RBC transfusions and RBC loss in st and ard surgical procedures . Whereas the variability in blood loss remains largely unexplained , the main predictors for allogeneic RBC transfusions are preoperative and nadir Hb and surgical RBC loss The aim of this prospect i ve study was to evaluate if there was a statistical correlation between allogeneic blood transfusion and postoperative infections , and if this could have a dose-dependent pattern . The evaluation was based on multiple logistic and receiver operating characteristics ( ROC ) curve analyses . On hospital admission the following parameters were determined in 267 consecutive patients with colorectal cancer : hemoglobin , serum albumin , serum cholinesterase activity , total iron binding capacity and weight loss . Duration of operation , operative blood loss , amount of transfused blood , Dukes ' cancer stage and occurrence of postoperative infections were also recorded . One hundred and thirty-two patients ( 49.4 % ) were given perioperatively allogeneic blood . Postoperative infections developed in 47 ( 17.6 % ) patients . Multivariate analysis identified allogeneic blood transfusion as the only variable related to the occurrence of postoperative infections ( p < 0.05 ) . ROC curve analysis showed that the risk for the occurrence of infection was significantly higher in patients transfused one unit of blood ( p < 0.01 ) . Moreover , a significant trend between increasing number of transfused blood units and susceptibility to infection was found ( p < 0.00019 ) R and om‐donor blood transfusions are deliberately given before cadaver renal allografting to improve allograft survival . Since host modifications that improve the outcome of an allograft might be associated with a decreased ability of the host to control cancer growth , the relationship between blood transfusions and the outcome of 146 Dukes ' stages A , B , and C colon cancers treated by resection during the years 1974 to 1979 was studied . It was found that 65 patients ( 45 % ) had been transfused and that at 5 years , overall survival was significantly better in the nontransfused patients compared to the transfused patients ( 0.68 and 0.51 5‐year product limit survival fractions respectively ; P = 0.03 for unadjusted log‐rank comparison of entire survival curves ) . Relative risk of death due to cancer in transfused patients versus nontransfused patients was 2.3 ( P = 0.05 ) when controlled for sex , age , stage , histologic differentiation , cancer location , and preresection hemoglobin level using Cox regression analysis . Thus , blood transfusion appears to be an additional important prognostic variable . The hypothesis suggested but not proven by these data that the outcome for some malignancies may be related to the immunomodulating effects of blood transfusions needs further study . Cancer 55:1195‐1201 , 1985 Clinical studies report reduced recurrence-free survival and increased cancer-related death after surgical treatment for cancer , when peri-operative blood transfusions were given . In this study we collected transfusion data of 212 patients who participated in a prospect i ve study of two different resection techniques for colorectal cancer . One hundred and fifty-eight patients were transfused and 54 were not . The follow-up period for almost all patients was 5 years . The 5-year survival rate was 52 % both for the transfused patients and the nontransfused patients . For subgroups of patients with Dukes ' B and Dukes ' C tumours no statistically significant differences were found . In the group of patients that were transfused the number of transfusions did not affect survival . In this study we could not confirm the deleterious effect of peri-operative blood transfusions on survival PURPOSE Allogeneic blood transfusions have reportedly been associated with a poor prognosis in patients with curatively resected cancer . To control for immunosuppression induced by a speculatively causal allogeneic blood transfusion , we design ed a r and omized study in which the control group received autologous blood transfusions not related to any condition of immunosuppression . PATIENTS AND METHODS One hundred twenty patients with potentially curative resectable colorectal cancer and the capability to predeposit autologous blood were r and omly selected to receive either st and ard allogeneic blood transfusion or predeposited autologous blood . RESULTS In curatively resected cancer patients , the number who needed allogeneic blood transfusions was reduced from 60 % in the allogeneic blood group to 33 % in the autologous blood group ( P = .009 ) . After a median follow-up duration of 22 months ( range , 8 to 48 ) tumor recurrence was observed in 28.9 % of the allogeneic blood group and 16.7 % of the autologous blood group . Life-table analysis established a tendency toward a shorter tumor-free survival for the allogeneic blood group ( log-rank P = .11 ) . The problem with this analysis was the strong association of allogeneic blood transfusions with tumor recurrence , which interfered in 33 % of patients in the autologous blood group who required additional allogeneic blood transfusions . Multivariate analysis of established risk factors for tumor recurrence and surgery-related variables reflecting potential immunosuppressive conditions showed that only pT stage ( relative risk , 6.61 ; 95 % confidence interval [ CI ] , 1.82 to 23.99 ; P = .004 ) , pN stage ( relative risk , 8.39 ; 95 % CI , 3.15 to 22.33 ; P < .001 ) , and the need for allogeneic blood ( relative risk , 6.18 ; 95 % CI , 2.20 to 17.37 ; P < .001 ) were independent predictors of tumor recurrence . Subgroup analysis of patients who received a transfusion of < or = 2 U blood found a significantly higher risk of tumor recurrence in the allogeneic blood group ( relative risk , 5.16 ; 95 % CI , 1.13 to 23.62 ; P = .034 ) , which was reduced to borderline significance ( relative risk , 3.54 ; 95 % CI , 0.76 to 16.51 ; P = .107 ) by adjustment for tumor ( T ) and node ( N ) stage . CONCLUSION As indicated by these first results , the blood transfusion modality has a significant effect on tumor recurrence after surgical treatment of colorectal cancer . A change in the practice of blood transfusion might thus potentially surpass the impact of any recent adjuvant treatment strategies The relationship between blood transfusion , disease-free survival , and other potential prognostic factors was prospect ively studied in 339 consecutive patients with colorectal cancer . Admission and discharge hematocrit , Dukes ' stage , and blood loss were significantly related to both blood transfusion and disease-free survival . Using Cox proportional hazards model , however , the association of transfusion with disease-free survival was significant ( p = 0.0196 ) after controlling for age , sex , blood loss , procedure , tumor differentiation , stage , admission hematocrit , duration of surgery , length of the specimen , and tumor size . Dukes ' stage ( p < 0.0001 ) and blood transfusion ( p < 0.0001 ) were the only variables independently related to disease-free survival . Forty per cent ( 44 ) of the 110 patients who received transfusions developed cancer recurrence , compared with 22 % ( 50 ) of the 229 patients who did not receive blood ( p < 0.0001 ) . Five-year disease-free survival of the transfused patients was 57 % , compared with 77 % for nontransfuscd patients . Patients who developed recurrence received an average of twice as much blood as patients without recurrence ( 1.26 versus 0.61 units , p = 0.0128 ) . Peri-operative blood transfusion is a significant independent prognostic factor for colorectal cancer BACKGROUND Previous studies on patients with hip fractures and in patients with colorectal cancer have documented that perioperative transfusion is associated with a significant increase in postoperative infection rate . Therefore , we sought to investigate the incidence of preoperative and postoperative anemia in noncardiac surgical patients and to determine if transfusion is an independent risk factor for infection and adverse outcome postoperatively . METHODS Prospect i ve data from the National Veterans Administration Surgical Quality Improvement Program ( NSQIP ) was collected on 6301 noncardiac surgical patients at the Veterans Affairs Maryl and Healthcare System from 1995 to 2000 . RESULTS The mean age of the study cohort was 61 + /- 13 . Descriptive data revealed 95 % were male , 44 % used tobacco , 19 % were diabetic , 9 % had COPD , 9 % used alcohol , 3 % used steroids , 1.7 % had a diagnosis of cancer , and 1.2 % had ascites . Preoperative anemia ( hematocrit less than 36 ) was found in 33.9 % and postoperative anemia was found in 84.1 % of the study cohort . In the postoperative period , 32.5 % of patients had a hematocrit of 26 - 30 , and 26.5 % had a hematocrit of 21 - 25 . Mean units of blood transfused in the perioperative period ranged from 0.1 + /- 0.9 in patients without anemia to 2.7 + /- 2.9 in those with anemia . Incidence of pneumonia increased from 2.6 to 5 % with increasing degree of anemia . Multiple logistic regression analysis documented that low preoperative hematocrit , low postoperative hematocrit , and increased blood transfusion rates were associated with increased mortality ( P < 0.01 ) , increased postoperative pneumonia ( P < or = 0.05 ) , and increased hospital length of stay ( P < 0.05 ) . CONCLUSION There is a high incidence of preoperative and postoperative anemia in surgical patients , with a coincident increase in blood utilization . These factors are associated with increased risk for perioperative infection and adverse outcome ( mortality ) in surgical patients . Consideration should be given to preoperative diagnosis and correction of anemia with iron , vitamin B12 , folate supplementation , or administration of recombinant human erythropoietin Because perioperative blood transfusions have been shown to have an impaired effect on survival in patients with colorectal cancer , we examined retrospectively the records of 882 patients who had undergone curative operations : 170 patients had distant metastases at the time of operation . Of the 499 patients with colonic cancer 332 ( 67 % ) had received perioperative blood transfusions . The corresponding figure for the 213 patients with rectal cancer was 190 ( 89 % ) . Colonic tumors recurred in 45 % of the patients who received blood transfusions and in 39 % of those who did not . Corresponding figures for tumors in the rectum were 54 % and 55 % . When dividing the patients with colonic cancer into different subgroups according to Dukes ' grade we found differences in survival rates . The poorer survival for transfused patients was , however , only significant for those with Dukes ' A tumors ( p less than 0.05 ) . This difference disappeared when the influence of age was eliminated . The estimated risk ratio of recurrence and death was 1.23 with the 95 % confidence interval ( 0.99 , 1.53 ) when taking Dukes ' grade , current age and localization into account . Blood transfusion should be avoided if possible until adequate prospect i ve studies have been carried out PURPOSE Recombinant human erythropoietin ( rHuEPO ) is the st and ard of care for patients with chemotherapy-related anemia . Intravenous ( IV ) iron improves hemoglobin ( Hb ) response and decreases dosage requirements in patients with anemia of kidney disease , but its effect has not been studied in r and omized trials in cancer patients . METHODS This prospect i ve , multicenter , open-label , r and omized trial enrolled 157 patients with chemotherapy-related anemia ( Hb < or= 105 g/L , serum ferritin < or= 450 pmol/L or < or= 675 pmol/L with transferrin saturation < or= 19 % ) receiving subcutaneously rHuEPO 40000 U once weekly to : ( 1 ) . no-iron ; ( 2 ) . oral iron 325 mg twice daily ; ( 3 ) iron dextran repeated 100 mg IV bolus ; or ( 4 ) iron dextran total dose infusion ( TDI ) . Hb and quality of life ( QOL ) were measured at baseline and throughout . RESULTS All groups showed Hb ( P < .0001 ) increases from baseline . Mean Hb increases for both IV iron groups were greater ( P < .02 ) than for no-iron and oral iron groups . The percentage of patients with hematopoietic responses was higher ( P < .01 ) in both IV iron groups ( each case 68 % ) compared with no-iron ( 25 % ) and oral iron ( 36 % ) groups . IV iron groups showed increases in energy , activity , and overall QOL from baseline , compared with a decrease in energy and activity for no-iron group and no change in activity or overall QOL for oral iron group . CONCLUSION rHuEPO increases Hb levels and improves QOL in patients with chemotherapy-related anemia . Magnitude of Hb increase and QOL improvement is significantly greater if IV iron is added AIMS It is still debated whether perioperative blood transfusion alters the incidence of disease recurrence or otherwise affects the prognosis after curative resection of malignant tumours . We conducted a prospect i ve observational study of patients with colorectal cancer to provide data on the effect of blood transfusion and the related perioperative cytokine response on long-term prognosis . MATERIAL S AND METHODS Perioperative blood sample s were obtained from 117 patients with colorectal cancer undergoing potentially curative resection . Factors associated with perioperative blood transfusion were assessed , and their relationship with early postoperative systemic responses of tumour growth factors and long-term prognosis were evaluated . RESULTS Independent factors associated with perioperative blood transfusion were preoperative anaemia , operative blood loss and the development of postoperative infectious complication . The patients receiving transfusions were subdivided according to the independent factors . Group A comprised 19 patients who received blood transfusions because of preoperative anaemia and Group B comprised 16 patients who received blood transfusions because of excessive operative blood loss . Group B patients showed exaggerated postoperative systemic induction of interleukin (IL)-6 and IL-6-triggered tumour growth factors , such as hepatocyte growth factor and vascular cell adhesion molecule-1 . Intraoperative blood transfusion under intense surgical stress was associated with poor prognosis , whereas preoperative blood transfusion for correcting anaemia or intraoperative blood transfusion under less invasive surgery was not associated with survival . Multivariate analysis using the Cox proportional hazards method showed that a significant independent risk was demonstrated for blood transfusion , T stage , lymph-node metastasis and perioperative peak levels of IL-6 . CONCLUSION Blood transfusion and intense surgical stress might synergistically affect the long-term prognosis after curative resection of colorectal cancer . Postoperative exaggerated systemic inductions of IL-6 may indicate the critical situation that could lead to disease recurrence Clinical and experimental studies indicate that transfusion of allogeneic blood has immunomodulating properties , and that the behaviour of some tumours may be influenced by the immune system of the host . Eighty‐seven patients who had undergone ‘ curative ’ resection of cancer of the colon or rectum were studied retrospectively to determine whether blood transfusion adversely affected the rate of cancer recurrence . Fifty‐three patients ( 61 per cent ) were transfused and 34 were not . The transfused and non‐transfused groups were comparable in terms of age , sex , duration of follow‐up , mode of presentation , stage of disease and haemoglobin level at discharge from hospital , and differed in admission haemoglobin and distribution of tumour locations ( right‐ or left‐sided colonic or rectal tumours ) . Recurrent malignancy was detected in 36 per cent of transfused patients and 26 per cent of non‐transfused patients ( P > 0·1 ) . There was no association between the number of transfusions and recurrence for any tumour site or stage . The incidence of recurrence was significantly higher in those patients who received transfusions during surgery than in those who received transfusion either before or after surgery ( χ2 = 7·01 , d.f . = 1 , P>0·01 ) or no transfusions ( χ2 = 4·23 , d.f . = 1 , P>0·05 ) . The study indicates that factors influencing the need for blood transfusion during operation had a greater bearing on prognosis than receipt of a blood transfusion per se and that future prospect i ve studies investigating the association between transfusion and cancer recurrence need to determine accurately the indications for transfusion PURPOSE : This study examined the effect of blood transfusion on the prognosis of patients undergoing surgery for colorectal cancer . METHODS : Potentially curative resections for colorectal cancer were performed in 266 patients who were followed prospect ively , with a minimum follow-up of 41 months . They were divided into transfused ( n=121 ) and nontransfused ( n=145 ) groups according to their perioperative blood transfusion requirements . RESULTS : There were significantly more rectal tumors ( χ2=9.5 , df=1 , P=0.002 ) and fixed tumors ( χ2=4.5 , df=1,P=0.03 ) in the transfused group . There was no statistically significant difference between the two groups with regard to recurrence-free survival ( χ2=1.1 , df=1,P=0.3 ) and overall survival ( χ2=2.8 , df=1,P=0.09 ) . CONCLUSION : In this study we have found no statistically significant effect of perioperative blood transfusion on the prognosis of colorectal cancer patients Extended experimental studies revealed different immunological mechanisms which are possibly responsible for blood transfusion-associated immunosuppressive conditions . To expect a clinical impact of these mechanisms on the course of tumor disease , it is necessary to postulate ( 1 ) that immunological mechanisms have a significant role in controlling tumor growth and ( 2 ) that blood transfusion-induced immunmodulation is long lasting . Both postulates are supported by recent reports and are the rationale s of clinical studies indicating that blood transfusion is a risk factor for postoperative infections and tumor recurrence . Since all studies have been retrospective or uncontrolled , we performed a prospect i ve controlled study in r and omized groups of patients suffering from colorectal cancer and compared the effects of allogeneic and autologous blood transfusions . The results indicate that patients treated with allogeneic blood transfusion had significantly higher rates of postoperative infectious complications than patients who received autologous blood . Our preliminary follow-up observations found a trend towards higher tumor-free survival in patients treated with autologous blood which is statistically significant in subgroup analysis Purpose . To investigate effects of blood transfusion , with/without leucocyte depletion , on duration of hospital stay , need for respiratory support , mortality and long-term survival after curative surgery for colorectal cancer . Methods . The trial was a prospect i ve , r and omised , multicenter study . Six hundred and forty two patients with colorectal cancer were included . Blood transfusion was given when needed during and /or after operation , r and omised to packed red blood cells ( RBC ) or leucocyte-depleted red blood cells ( LDB ) using leucocyte filtration . Assisted ventilation in ICU , hospital stay , malignant and non-malignant specific mortality and overall survival were outcome measures . Results . The RBC group had higher need for assisted ventilation post-operatively ( 8.1 % vs. 3.6 % ) and significantly higher proportion of patients with prolonged ( > 20 days ) hospital stay . After median follow-up time of 99.5 months there was no significant difference in mortality or long-term survival between the groups . The median cumulative survival time of 55 months in LDB vs. 36 months in RBC group did not reach significance level . Non-transfused patients had a significantly lower proportion of prolonged hospital stay , and significantly increased survival , compared to transfused patients . Conclusion . Leucocyte depleted transfusions improved the postoperative course following surgery for colorectal cancer , compared with packed red blood cell transfusions BACKGROUND : Perioperative blood transfusion and subsequent development of postoperative infectious complications may lead to poor prognosis of patients with colorectal cancer . It has been suggested that the development of postoperative infectious complications may be related to the storage time of the transfused blood . Therefore , we studied the relationship between blood storage time and the development of disease recurrence and long-term survival after colorectal cancer surgery . METHODS : Preoperative and postoperative data were prospect ively recorded in 740 patients undergoing elective resection for primary colorectal cancer . None of the patients received preoperative or postoperative chemotherapy or radiation therapy . Endpoints were overall survival and disease recurrence in the subgroup of patients operated on with curative intention who also survived the first 30 days after operation . Storage of buffy-coat-depleted red cells suspended in saline , adenine , glucose , and mannitol blood for 21 days was used as cut-off point . RESULTS : Median follow-up was 6.8 years ( range , 5.4 years to 7.9 years ) , and median overall survival was 4.6 years for 288 nontransfused patients and 3.0 years for 452 transfused patients ( P=0.004 ) . The survival of patients receiving blood exclusively stored < 21 days was 2.5 years . For patients receiving any blood stored ≥21 days , survival was 3.7 years ( P=0.12 ) . Among patients with curative resection ( n=532 ) , the hazard ratio of disease recurrence was 1.5 ( 95 percent CI ; 1.1 to 2.2 ) and 1.0 ( 95 percent CI ; 0.7 to 1.4 ) in the two transfused groups , respectively , compared with the nontransfused group after multivariable correction for patient age , gender , colonic/rectal tumor localization , Dukes classification , blood loss , and postoperative infectious complications . CONCLUSION : Transfusion of buffy-coat-depleted red cells suspended in saline , adenine , glucose , and mannitol blood stored for < 21 days may be an independent risk factor for development of recurrence after elective colorectal cancer surgery In retrospective studies , perioperative blood transfusions were associated with poor prognosis after surgery for cancer and were a major independent risk factor for postoperative bacterial infection . Leucocyte-depleted , in contrast to buffy-coat-depleted , blood has no immunosuppressive effects in transplantation and so might lack detrimental effects on cancer prognosis and postoperative infections . We studied this hypothesis in a controlled trial by r and omly allocating patients to receive either leucocyte-depleted red cells or packed cells without buffy coat when blood was needed . Between 1987 and 1990 , 871 eligible patients with colorectal cancer , including 697 patients operated upon with curative intent , were r and omised in the 16 participating hospitals . Neither the eligible group nor the curative group showed significant differences between the two trial transfusions in survival , disease-free survival , cancer recurrence rates , or overall infection rates after an average follow-up of 36 months . Patients who had a curative resection and who received blood of any sort had a lower 3-year survival than non-transfused patients ( 69 % vs 81 % , p = 0.001 ) and a higher infection rate ( 39 % vs 24 % , p < 0.001 ) . Colorectal cancer recurrence rates , however , were not influenced by blood transfusion ( 30 % vs 26 % , p = 0.22 ) . These combined observations confirm the association between blood transfusion and poor patient survival but indicate that the relation is not due to promotion of cancer Perioperative blood transfusion has been reported to adversely affect survival in cancer patients , but the evidence is inconclusive and may be an epiphenomenon . From the Large Bowel Cancer Project , 961 patients who underwent curative resection and left hospital alive have been review ed to compare the effect of perioperative blood transfusion on outcome ; 591 patients ( 61 % ) had been given a blood transfusion while 370 ( 39 % ) had not been transfused . Some clinical variables were equally distributed between the two groups ; ie age , sex , obstruction , perforation , tumour differentiation . Three other variables known to influence patient prognosis were not equally distributed , ie tumour site , Dukes ' stage and tumour mobility . Patients with tumours of the rectum and rectosigmoid , with Dukes ' stage C lesions and with some degree of tumour fixation were more likely to have received blood transfusions . Using the logrank method of multivariate analysis to allow for differences in distribution of all those variables known to affect prognosis , there was no survival disadvantage for those patients who had received perioperative blood transfusion . Furthermore , there were no overall differences between the two groups of patients in their risk of developing local tumour recurrence or distant metastases . The distribution of metastases differed : in the ' transfused ' group only 37 % of distant metastases were found in the liver , while 71 % were found in this site in the ' not transfused ' group ( chi 2 = 18.46 , d.f . = 1 , P less than 0.001 ) . By contrast , there was a larger proportion of patients with lung metastases in the transfused group ( 27 % vs 11 % ) ( chi 2 = 5.59 , d.f . = 1 , P less than 0.05 ) . Therefore , these data do not support the concept of an overall deleterious effect of blood transfusion on patient survival , but suggest that blood given in the perioperative period may change the biology of the metastatic process To evaluate whether blood transfusion exerts an adverse influence on cancer evolution , a prospect i ve clinical and immunologic investigation was carried out on 58 surgical patients with gastric or colorectal adenocarcinoma . None had had previous transfusion ; 35 received perioperative transfusion . Among preoperative variables , only red cell count and hemoglobin concentration were significantly reduced in the patients transfused at operation . Other clinical characteristics and immunologic functions ( except interferon-gamma release ) did not differ significantly from those of untransfused patients . The survival rate of transfused patients , although shorter , was not significantly different from that of untransfused patients . Immunologic tests done after surgery on 30 patients ( 17 transfused and 13 untransfused ) did not show significant differences in the two groups . Significant increases in interleukin-2-stimulated production and immunoglobulin M synthesis were observed in transfused patients after surgery . Patients transfused perioperatively with more than 3 units of blood had some evidence of decreased immune function , but differences were not significant . While shorter survival and some immunologic changes may correlate with the number of transfusions , more patients must be studied to determine whether this relationship will be confirmed OBJECTIVE To assess the effects of perioperative blood transfusion on cancer related survival and infective complications after radical operations for colorectal cancer . DESIGN Retrospective study . SETTING District hospital in Sweden . SUBJECTS 217 patients who fulfilled the criteria for inclusion , out of 392 consecutive patients operated on for colorectal cancer between 1975 and 1979 . MAIN OUTCOME MEASURES Morbidity and cancer related mortality depending on whether blood was transfused and , if so , how much . RESULTS Dukes ' stage ( p < 0.001 ) , rectal tumours ( p < 0.05 ) and the number of units transfused ( p < 0.05 ) were significantly associated with cancer related mortality . Patients with rectal cancer transfused with 1 - 2 units had significantly better survival than those transfused with more than 4 units ( p < 0.05 ) , but this was not the case for colonic tumours . There was no significant association between blood transfusion and the incidence of infective complications . CONCLUSION Though there seems to be an association between the number of units of blood transfused and cancer related survival in patients with rectal cancer , this does not necessarily imply causation . We recommend that until this is clarified by large , prospect i ve investigations , autologous blood should be used whenever possible , and unnecessary blood transfusion should be avoided More recently a number of retrospective analyses in rather ill defined patient population s demonstrated an association between perioperative blood transfusion and recurrence after curative resection of colorectal cancer . In the r and omized trial ( SAKK 40/81 ) ( adjuvant cytotoxic intraportal infusion versus no further treatment ) we evaluated the transfusion status in a well defined , prospect ively documented and controlled patient population . Of 457 patients , 353 ( 77.2 % ) received either pre- , intra- or postoperatively blood transfusions . After a median follow-up of 4 years , the transfused patients developed significantly more recurrences ( 38.2 % ) than patients without blood transfusions ( 23.1 % ) , the death-rate being 33.7 % versus 23.0 % , respectively . Patients without transfusion but treated with adjuvant intraportal chemotherapy are strikingly doing better ( 10.5 % recurrences ) than patients with perioperative blood transfusion not having an adjuvant treatment ( 44.5 % recurrences ) Objectives To examine prospect ively the prevalence of iron deficiency among new patients presenting with colorectal cancer and to compare transferrin saturation and serum ferritin as markers of iron deficiency in this group of patients The immunosuppressive effect of allogeneic blood transfusions can be associated with a poor prognosis for cancer patients . Predeposit autologous blood transfusions could be a solution to overcome this putative deleterious effect . We performed a r and omised clinical study to compare the effects of autologous with allogeneic blood transfusions in colorectal cancer patients . There was no significant difference in disease-free survival between both r and omisation arms . However , the transfused patients had a significantly shorter disease-free interval as compared with the non-transfused patients . This association of transfusions with recurrent disease was only the case for local recurrences , whereas the incidence of distant metastases was unaffected . We conclude that the use of a predeposit autologous blood transfusion programme does not improve the prognosis in colorectal cancer patients . The negative association between blood transfusions and cancer recurrence is only true for local recurrences , which suggests that not the blood transfusions themselves but rather the circumstances necessitating them are the real predictors of prognosis |
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