***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant  treatment for tardive dyskinesia ( TD ) conducted by the Department of Veteran Affairs Cooperative Studies Program . One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia . Dyskinetic h and movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient . In the present report , we describe the training procedures and results of a multi-center reliability assessment of this procedure . Data from nine study centers comprising 45 individual patients with six trials each ( three from left h and and three from right h and ) were reanalyzed by an independent investigator and the results were subjected to reliability assessment . For the statistic of interest ( average coefficient of variation over trials 2 and 3 for each h and , then take the larger of these two values ) , we found very high intraclass correlation coefficients for reliability over all patients across sites ( ICC = 0.995 ) . We also calculated the reliability of the measures across trials within patient for each combination of h and ( right , left , dominant ) , rater group ( site , control ) , and trials set ( all three , trials 2 and 3 ) . For a given h and and trial set , the reliability of the site raters was similar to that of the control . This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training Tardive dyskinesia ( TD ) is a serious , often disabling , movement disorder that is caused by medications that block dopamine receptors ( i.e. , neuroleptics , anti-emetics ) . There is currently no st and ard treatment approach for physicians confronted with such patients . This may be the result of notions that TD is disappearing because of the switch to second-generation antipsychotic agents and that it is largely reversible . In this article we demonstrate that second-generation antipsychotics do , indeed , cause TD and , in fact , the frequency is likely higher than expected because of growing off-label uses and a tripling of prescriptions written in the last 10 years . In addition , studies demonstrate that TD actually remits in only a minority of patients when these drugs are withdrawn . Furthermore , neuroleptic agents are often utilized to treat TD , despite prolonged exposure being a risk factor for irreversibility . The outcome of these trends is a growing population afflicted with TD . We review non-neuroleptic agents that have shown positive results in small , early-phase , blinded trials , including tetrabenazine , amantadine , levetiracetam , piracetam , clonazepam , propranolol , vitamin B6 , and Ginkgo biloba . Other options , such as botulinum toxin and  deep brain stimulation  , will also be discussed , and a suggested treatment algorithm is provided . While these agents are reasonable treatment options at this time there is a need , with a concerted effort between neurology and psychiatry , for full-scale drug development , including multicenter , r and omized , blinded trials to confirm the effectiveness of the agents that were positive in phase 2 trials and the development of newer ones OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Abstract : Free radicals may be involved in the pathogenesis of tardive dyskinesia ( TD ) .  Vitamin E , a free radical scavenger , has been reported to improve symptoms of TD . The present study was design ed to replicate this finding in a group of Chinese patients with TD , and to examine the effect of vitamin E treatment on blood superoxide dismutase ( SOD ) , a critical enzyme in the detoxification of free radicals . Forty-one in patients with TD completed a double-blind , placebo-controlled , parallel-group study of vitamin E. Twenty-two of the patients were r and omly assigned to receive a fixed dose of 1200 IU/d vitamin E , and 19 were assigned to a placebo for 12 weeks . Patients were assessed primarily using the Abnormal Involuntary Movement Scale ( AIMS ) at baseline , weeks 6 and 12 . Blood SOD levels were measured by radioimmunometric assay before and after treatment . The results showed that the reduction in AIMS score from baseline was significantly higher with vitamin E treatment compared with placebo ( 45.9 % vs. 4.3 % ) . Blood SOD levels were significantly increased after treatment with vitamin E ( P = 0.001 ) , but no change with placebo treatment ( P < 0.05 ) . These results support earlier findings of the efficacy of vitamin E in the treatment of TD . Moreover , the efficacy of vitamin E may be due to its ability to increase SOD level , which may reduce oxidative injure in tardive dyskinesia The authors compared vitamin E with placebo in a double-blind r and omized crossover study of 27 patients with tardive dyskinesia . Each treatment period lasted for 6 weeks . Vitamin E showed no differences from placebo in the treatment of tardive dyskinesia One of the major problems associated with long-term neuroleptic treatment is persistent tardive dyskinesia ( TD ) , for which there is no satisfactory treatment . We have recently proposed that some cases of TD are associated with neuronal dysfunction result ing from excess free radical production occurring during catecholamine metabolism . We therefore decided to assess the efficacy of a powerful free radical scavenging agent , alpha-tocopherol ( vitamin E ) , on the clinical signs of TD . We treated 15 patients with persistent TD with alpha-tocopherol and matched placebo in a r and omized crossover design . Patients demonstrated a significant overall reduction in scores on the Abnormal Involuntary Movements Scale ( AIMS ) after treatment with alpha-tocopherol , but not after placebo . The mean reduction in the AIMS score with alpha-tocopherol was 43 percent , with seven patients showing a greater than 50 percent reduction in their dyskinesia . There was also a trend for a decrease in scores on the Brief Psychiatric Rating Scale , but no change was observed in scores on the Simpson-Angus Scale for Extrapyramidal Side Effects . Our findings are consistent with the possibility that alpha-tocopherol is beneficial in the treatment of some patients with TD , but further research is necessary to establish the efficacy of this agent BACKGROUND Several studies have found that alpha-tocopherol ( vitamin E ) can effectively treat  tardive dyskinesia ( TD ) .  A limitation of these trials is their short treatment duration s ( maximum of 12 weeks ) , which do not allow us to address the effects of long-term treatment . METHODS To participate , patients had to have TD and be on stable oral medications . The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E ( 1600 IU per day ) or placebo .  RESULTS Using the Abnormal Involuntary Movements Scale ( AIMS ) score ( sum of items # 1 - 7 ) to measure TD severity , the study found a significant difference ( 3 points ) in mean AIMS scores , in favor of vitamin E , starting at 10 weeks of treatment and continuing through the full 36 weeks . We used linear mixed-effects regression to quantify the impact of several covariates , and found that treatment assignment . TD duration , and chlorpromazine equivalents had significant effects on decreasing the AIMS score . CONCLUSIONS The study 's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks . These findings are in direct contrast to those of VA Cooperative Study # 394 , a much larger , long-term , multi-site study , conducted by many of the same investigators , in which Vitamin E was not superior to placebo OBJECTIVE Vitamin E ( alpha-tocopherol ) , a free-radical scavenger , has been reported to improve symptoms of tardive dyskinesia . The authors attempted to replicate this finding under more controlled conditions in a larger study group . METHOD Fifteen in patients and six out patients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind , placebo-controlled crossover study . Abnormal Involuntary Movement Scale ( AIMS ) examinations of these patients were videotaped and rated independently by two trained raters . Levels of neuroleptic medication and vitamin E were measured during both treatment periods . Eighteen patients who demonstrated high blood levels of  vitamin E were included in the data analysis . RESULTS  Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo . For all 18 patients , there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo . In agreement with previous studies , however , the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo . There were no changes in neuroleptic levels during vitamin E treatment . CONCLUSIONS Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less . This effect was not due to an increase in blood levels of neuroleptic medications Eleven patients with tardive dyskinesia were treated in a double-blind study of vitamin E or placebo for 12 weeks . Abnormal Involuntary Movement Scale ( AIMS ) ratings were performed before and after treatment . Patients receiving vitamin E showed a significant reduction in their AIMS scale score , but patients receiving placebo showed no significant change . Vitamin E had a helpful effect even for patients whose tardive dyskinesia was mild and long-term Changes in serum creatine phosphokinase have been associated with exacerbation of tardive dyskinesia . Vitamin E , a drug suggested to be effective in the treatment of tardive dyskinesia , has been implicated as a possible cause of increased creatine phosphokinase levels .  Ten patients with long-term tardive dyskinesia were treated with vitamin E in a double-blind , placebo-controlled crossover study .  Vitamin E blood levels and creatine phosphokinase serum levels were monitored at various phases during the study . There were no significant differences between vitamin E and placebo treated patients in their abilities to affect tardive dyskinesia or to influence creatine phosphokinase levels . These data do not support the hypothesis that administration of vitamin E may alter creatine phosphokinase levels in patients with long-term tardive dyskinesia Alpha-tocopherol ( vitamin E ) has been found to be effective in the treatment of  tardive dyskinesia ( TD ) .  Studies to date have been short in duration and have not found long-term carryover effects of vitamin E. The present study examined the persistence of the effects of vitamin E after longer term ( 36-week ) treatment was discontinued . Vitamin E significantly improved TD over this period . However , the effects of vitamin E persisted so that TD scores approached baseline only 
    Output:
    
No trials reported on social confidence , social inclusion , social networks , or personalised quality of life , outcomes design ated important to patients .
Small trials of limited quality suggest that vitamin E may protect against deterioration of TD .
There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established .