***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: A double-blind crossover study was performed in 12 patients with idiopathic parkinsonism to compare their response to bromocriptine with their response to previous optimal drug treatment , including levodopa . There was a 26 percent overall improvement with  bromocriptine ; rigidity , tremor , and facial expression showed the greatest response . Seven of eight patients who were taking levodopa at the beginning of the study were taken off the drug completely . Adverse reactions were transient and dose-dependent . Bromocriptine promises to be an effective new therapeutic agent in the treatment of idiopathic parkinsonism ABSTRACT – The effects of bromocriptine in patients with Parkinson 's disease manifesting various problems in levodopa therapy were tested in a double‐blind manner with the collaboration of 59 institutions . The slow and low principle was in part adopted . Either bromocriptine or placebo was added to levodopa OBJECTIVES --To establish , in a double blind manner , the antiparkinsonian effects of repeated dosing with entacapone , a peripheral COMT inhibitor . METHODS --A one month , cross over study was conducted . During the two four-week treatment periods , entacapone ( 200 mg ) or placebo was given with each levodopa dose four to 10 times daily . Motor responses were repeatedly quantified using the motor part of UPDRS . Plasma levodopa and its metabolites were measured . RESULTS --Entacapone prolonged the availability of levodopa in the plasma and thus to the brain by decreasing its peripheral O-methylation and slowing its elimination rate , without affecting the maximum plasma levodopa concentration or the time to maximum concentration . Corresponding with the pharmacokinetic findings , entacapone prolonged the duration of motor response to an individual levodopa/DDC inhibitor dose by 34 minutes ( 24 % , P = 0.001 ) and dyskinesiae by 39 minutes ( 37 % , P = 0.002 ) compared with placebo , without affecting their magnitude or starting time . Entacapone treatment result ed in a reduction of 16 % in the mean total daily levodopa dose due to dyskinesiae . Also , according to the home diaries , the mean daily " on " time increased by 2.1 hours compared with placebo , despite the lowered mean levodopa intake . CONCLUSION --The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson 's disease with levodopa related fluctuations is verified The conventional dose of deprenyl used in Parkinson 's disease is 10 mg/day , having been established by in vitro platelet studies and clinical evaluation . Twelve patients with Parkinson 's disease on treatment with L-dopa who showed evidence of wearing-off effects or motor oscillation  were studied in a double-blind , placebo-controlled , crossover trial to compare conventional doses of deprenyl with higher doses ( up to 40 mg/day ) and placebo . We did not find higher doses of deprenyl to be superior to conventional doses and in 17 % of cases treatment had to be withdrawn because of side effects We compared the efficacy , safety , an tolerability of pramipexole , an aminobenzathiazol-derived dopamine agonist with novel properties , with those of placebo in advanced PD patients with motor fluctuations under levodopa treatment .  Pramipexole improved motor function of patients during " on " and " off " periods , decreased the time spent in " off " periods , reduced the severity of " off " periods , decreased disability and PD severity during " on " and " off " periods , as assessed by the Unified Parkinson Disease Rating Scale , and permitted a reduction in levodopa dosage . Adverse effects related to the central nervous system were similar to those reported with other dopamine agonists , and the gastrointestinal and cardiovascular tolerability of the compound was satisfactory Two prospect i ve projects were started in May 1985 to evaluate the long-term effects of bromocriptine in patients with Parkinson 's disease . One of the projects is to see if combination therapy with levodopa and bromocriptine is superior to levodopa alone with regard to the prevention of late side effects of levodopa therapy . The other is to see the long-term effects of bromocriptine monotherapy .  Patients with Parkinson 's disease were allocated r and omly to either combination or levodopa group in the first project . Parkinsonian symptoms , disabilities of daily life and severity of late side effects of long-term levodopa therapy were evaluated by a semiquantitative rating scale . This communication represents the first interim report . Methods of the studies and synopsis of the results at the end of the 12th month are described . A total of 702 patients was enrolled in the study  ( combination therapy , n = 216 ; levodopa therapy , n = 200 , bromocriptine monotherapy , n = 286 ) . At the end of the 12th month , the numbers of patients who dropped out from the study were 19 , 16 and 55 in the three groups , respectively . It appears to be too early to make any definite conclusion with regard to which mode of treatment is superior , however , some evidence suggesting a superiority of the combination therapy over levodopa alone was noted in managing wearing-off phenomenon and dyskinesia . As many patients are sticking to the originally intended mode of treatment , it appears to be possible to obtain more meaningful data in several years This r and omized , double-blind trial was design ed to evaluate the efficacy of a transdermal system of piribedil on the motor symptoms of Parkinson 's disease during 3 weeks of treatment administered to three different groups : placebo , one piribedil patch ( 1 PP ) , and two ( 2 PP ) piribedil patches .  Twenty-seven patients with idiopathic Parkinson 's disease , treated with L-dopa but not sufficiently controlled , were included in this trial . The test treatment did not demonstrate any clinical efficacy on either the main end point ( Unified Parkinson 's Disease Rating Scale motor score ) or the secondary end points ( rigidity , bradykinesia , postural , and resting tremor scores ) . The main adverse events were nausea ( 11 % ) , vomiting ( 7.4 % ) , and malaise ( 7.4 % ) mainly observed in the placebo group ( four of seven patients ) . The local acceptability of the transdermal system was good . Plasma piribedil concentrations at the end of treatment were 6.74+/-1.10 and 9.31+/-3.33 ng/mL in the 1 PP and 2 PP groups , respectively . These plasma levels could account for the lack of clinical efficacy , because a previous pharmacokinetics-PD study conducted in parkinsonian patients and treated with the intravenous route demonstrated that the critical limits of activity on tremor were between 10 and 30 The addition of bromocriptine , given in divided doses up to 30 mg per day , to conventional anti-Parkinsonism therapy has been studied in a double-blind placebo controlled clinical trial in 11 patients with Parkinsonism with the " on-off " syndrome . Four patients withdrew because of side effects .  Of the seven remaining , three had clinical benefit from bromocriptine with reduction in severity and frequency of fluctuations . There was , however , no statistically significant benefit of bromocriptine when the group as a whole was assessed in terms of severity or frequency of fluctuations measured by three different methods . The mean frequency of major fluctuations on placebo was 2.9/day and on bromocriptine 1.8/day ( P less than 0.1 greater than 0.05 ) . There appears to be a limited role for bromocriptine as additional therapy in the management of some patients with the on-off syndrome BACKGROUND More than 50 % of patients with Parkinson ’s disease develop motor response fluctuations ( the “ wearing off ” phenomenon ) after more than five years of levodopa therapy . Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life , thereby prolonging the efficacy of levodopa . OBJECTIVES The primary objective was to evaluate the efficacy of tolcapone in reducing “ wearing off ” in levodopa treated , fluctuating parkinsonian patients . Secondary objectives included assessment of reduction in levodopa requirements , improvement in patients ’ clinical status , duration of improvements , and tolerability of tolcapone . METHODS In this multicentre , r and omised , double blind , placebo controlled trial , 58 patients received placebo  , 60 received 100 mg tolcapone three times daily ( tid ) , and 59 received 200 mg tolcapone tid , in addition to levodopa/benserazide . RESULTS After three months with 200 mg tolcapone tid , “ off ” time decreased by 26.2 % of the baseline value , “ on ” time increased by 20.6 % ( P<0.01 v placebo ) , and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg ( P<0.01 ) . These responses were maintained up to nine months . With 100 mg tolcapone tid , “ off ” time decreased by 31.5 % ( P<0.05 ) , “ on ” time increased by 21.3 % ( P<0.01 ) , and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg ( P<0.05 ) . With 200 mg tolcapone tid , unified Parkinson ’s disease rating scale motor and total scores were significantly reduced , and quality of life ( sickness impact profile ) scores were significantly improved . Both dosages were well tolerated . Dyskinesia was the most often reported levodopa induced adverse event . Diarrhoea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study : four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhoea . CONCLUSION Tolcapone prolongs “ on ” time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage , thereby improving the efficacy of long term levodopa therapy The effect and clinical significance of tolcapone withdrawal on erythrocyte catechol-O-methyltransferase ( COMT ) activity , levodopa pharmacokinetics , and levodopa requirements were investigated in 59 patients with fluctuating parkinsonism who were r and omized to receive placebo or tolcapone 100 or 200 mg three times daily for 6 weeks .  Tolcapone withdrawal caused a transient elevation in COMT activity by 64 % in patients receiving 100 mg three times daily and by 128 % in those receiving 200 mg three times daily at approximately 1–2 weeks after discontinuation of drug . Thereafter , COMT activity was declining but did not reach baseline values by the 12-week study endpoint . However , this had no effect on plasma levodopa and 3-O-methyldopa ( 3-OMD ) concentrations or on levodopa requirements . During treatment , tolcapone  increased “ on ” time and decreased “ off ” time ; after discontinuation of study medication and levodopa dose adjustment , on and off times were similar to baseline . Withdrawal was generally well tolerated ; no patients withdrew from the trial during the posttreatment period , and no serious adverse events were observed . In conclusion , the transient increase in erythrocyte COMT activity observed after discontinuation of tolcapone is not associated with changes in peripheral levodopa metabolism and therefore has no significant clinical consequences in terms of levodopa requirements , clinical symptoms , or adverse events BACKGROUND Baseline data collected on each patient at r and omisation in controlled clinical trials can be used to describe the population of patients , to assess comparability of treatment groups , to achieve balanced r and omisation , to adjust treatment comparisons for prognostic factors , and to undertake subgroup analyses . We assessed the extent and quality of such practice s in major clinical trial reports . METHODS A sample of 50 consecutive clinical -trial reports was obtained from four major medical journals during July to September , 1997 . We tabulated the detailed information on uses of baseline data by use of a st and ard form . FINDINGS Most trials presented baseline comparability in a table . These tables were often unduly large , and about half the trials inappropriately used significance tests for baseline comparison . Methods of r and omisation , including possible stratification , were often poorly described . There was little consistency over whether to use covariate adjustment and the criteria for selecting baseline factors for which to adjust were often unclear . Most trials emphasised the simple unadjusted results and covariate adjustment usually made negligible difference . Two-thirds of the reports presented subgroup findings , but mostly without appropriate statistical tests for interaction . Many reports put too much emphasis on subgroup analyses that commonly lacked statistical power . INTERPRETATION Clinical trials need a predefined statistical analysis plan for uses of baseline data , especially covariate-adjusted analyses and subgroup analyses . Investigators and journals need to adopt improved st and ards of statistical reporting , and exercise caution when drawing conclusions from subgroup findings This r and omized , double-blind trial was design ed to define the possible relationship between piribedil plasma concentrations and the decrease of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) motor score or the switch from off to on state after single intra 
    Output:
    
Compared to placebo , adjuvant therapy reduces off-time , levodopa dose , and improves UPDRS scores in PD patients who develop motor complications on levodopa therapy .
However , this is at the expense of increased dyskinesia and numerous other side-effects .
Indirect comparisons suggest that dopamine agonist therapy may be more effective than COMTI and MAOBI therapy , which have comparable efficacy .