***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 – 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 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 Motor complications are a major source of disability for patients with advanced Parkinson 's disease . Surgical therapies provide benefit to some , but these treatments are expensive and associated with adverse effects . Current research indicates that motor complications are associated with abnormal , intermittent , pulsatile stimulation of denervated dopamine receptors using short acting dopaminergic agents such as levodopa . Retrospective studies suggest that the use of longer-acting more continuous dopaminergic therapies can improve both motor fluctuations and dyskinesia . We performed a prospect i ve , long-term ( 4-year ) trial comparing patients r and omized to receive subcutaneous infusion of the dopamine agonist lisuride  versus conventional therapy with oral levodopa and dopamine agonists . We demonstrate that patients receiving lisuride infusions experienced a significant reduction in both motor fluctuations and dyskinesia compared with patients receiving st and ard dopaminergic therapies . Benefits persisted for the 4-year duration of the study . Mean Unified Parkinson 's Disease Rating Scale scores in " ON " and " OFF " states did not significantly change between baseline and 4 years for patients in the lisuride group , but deteriorated in patients in the levodopa group . This study indicates that continuous lisuride infusion can be beneficial for patients with advanced Parkinson 's disease and reverse established motor fluctuations and dyskinesia Cabergoline is a dopaminergic agonist relatively specific for the D sub 2 receptor and much longer-acting than other dopamine agonists . We conducted a r and omized , placebo-controlled , double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson 's disease ( PD ) . The cabergoline patients had significantly better Activities of Daily Living ( p equals 0.032 ) and Motor Examination ( p equals 0.031 ) scores at the conclusion of the trial compared with the placebo group . The daily levodopa dose for the cabergoline patients decreased 18 % compared with a 3 % reduction for the placebo group ( p less than 0.001 ) . The amount of time in the ` ` on ' ' state increased more in the cabergoline group ( p equals 0.022 ) . The side-effect profile was similar to that seen with other dopamine agonists , and cabergoline was generally well tolerated . We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD . NEUROLOGY 1996;46 : 1062 - BACKGROUND Continuous dopaminergic drug delivery is an unmet medical need in advanced Parkinson 's disease . The aim of this trial- Clinical Efficacy of Pramipexole And Transdermal Rotigotine in Advanced PD (CLEOPATRA-PD)-was to assess the efficacy of adjunct treatment with rotigotine in comparison with placebo and with pramipexole in levodopa-treated patients with advanced Parkinson 's disease and wearing-off type motor fluctuations . METHODS In this r and omised controlled trial , eligible participants were r and omly assigned to receive either rotigotine ( up to 16 mg/24 h as a transdermal patch ) , pramipexole ( up to 4.5 mg/day orally ) , or placebo for 6 months . Primary efficacy variables were absolute change in total hours " off " ( assessed by home diaries ) from baseline to end of study and responder rate ( defined as the proportion of patients with > or=30 % reduction in absolute off time per day ) . Analyses were done by intention to treat . This trial is registered with the US National Institutes of Health clinical trials data base ( Clinical Trials.gov ) , number NCT00244387 . FINDINGS 204 patients were r and omly assigned to receive rotigotine , 201 to receive pramipexole , and 101 to receive placebo ; 427 ( 84 % ) completed the trial . The number of discontinuations in each group was similar ; most were for adverse events . The mean dose of rotigotine was 12.95 mg/24 h ( SD 3.54 ) , the mean dose of pramipexole was 3.1 mg/day ( 1.24 ) . Mean absolute change in off time from baseline was -2.5 h ( SE 0.20 ) with rotigotine , -2.8 h ( 0.20 ) with pramipexole , and -0.9 h ( 0.29 ) with placebo . The absolute change in off time from baseline compared with placebo was -1.58 h ( 95 % CI -2.27 to -0.90 ; p<0.0001 ) for rotigotine and -1.94 h ( -2.63 to -1.25 ; p<0.0001 ) for pramipexole .  Responder rates were 67 % ( 134 of 200 patients ) for pramipexole , 59.7 % ( 120 of 201 patients ) for rotigotine , and 35 % ( 35 of 100 patients ) for placebo . INTERPRETATION In terms of change in absolute off time , rotigotine was non-inferior to pramipexole . Continuous delivery of rotigotine as transdermal patches could offer similar efficacy to oral pramipexole in patients with fluctuating Parkinson 's disease over 6 months of treatment Three hundred and seventy-six subjects with advanced Parkinson 's disease participated in a prospect i ve , double-blind placebo-controlled study of the dopamine agonist pergolide mesylate as an adjunct to Sinemet . At 6 months , patients r and omized to pergolide had a statistically significant improvement in total Parkinson 's score , scores of activities of daily living , motor function , number of " off " hours , Hoehn and Yahr stage , and numerous parameters of parkinsonian function including bradykinesia , rigidity , gait , and dexterity . This benefit was obtained with the addition of a mean dose of 2.94 mg of pergolide , which permitted a 24.7 % reduction in dose of levodopa . Adverse reactions were , for the most part , mild , reversible , and not of major clinical significance . No significant cardiac or electrocardiographic abnormalities were detected . This study demonstrates that pergolide mesylate , as an adjunct to levodopa , is an effective antiparkinsonian agent that provides clinical improvement while permitting a reduction in levodopa dose Objectives : To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease ( PD ) for motor fluctuations and quality of life ( QoL ) . Methods : Twenty-four patients with motor fluctuations and dyskinesia were studied in a r and omized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/carbidopa gel for 3 + 3 weeks . Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from −3 to 0 to + 3 ( from severe “ off ” to “ on ” to “ on ” with severe dyskinesia ) . Patient self- assessment of motor performance and QoL was done using an electronic diary . Results : Median percentage of ratings in a functional “ on ” interval ( −1 to + 1 ) was increased from 81 to 100 % by infusion therapy ( p < 0.01 ) . This improvement was accompanied by a decrease in “ off ” state ( p < 0.01 ) and no increase in dyskinesia . Median Unified Parkinson 's Disease Rating Scale score decreased from 53 to 35 in favor of infusion ( p < 0.05 ) . QoL was improved , using the two instruments : Parkinson 's Disease Question naire-39 and 15D Quality of Life Instrument ( p < 0.01 ) . Adverse events were similar for both treatment strategies . Conclusions : Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinical ly superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations . Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease BACKGROUND Levodopa is the most effective therapy for Parkinson 's disease , but chronic treatment is associated with the development of potentially disabling motor complications . Experimental studies suggest that motor complications are due to non-physiological , intermittent administration of the drug , and can be reduced with continuous delivery . We aim ed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube . METHODS In our 12-week , r and omised , double-blind , double-dummy , double-titration trial , we enrolled adults ( aged ≥ 30 years ) with advanced Parkinson 's disease and motor complications at 26 centres in Germany , New Zeal and , and the USA . Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube , and were then r and omly allocated ( 1:1 ) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo . R and omisation was stratified by site , with a mixed block size of 2 or 4 . The primary endpoint was change from baseline to final visit in motor off-time . We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome . We assessed efficacy in a full- analysis set of participants with data for baseline and at least one post-baseline assessment , and imputed missing data with the last observation carried forward approach . We assessed safety in r and omly allocated patients who underwent the percutaneous gastrojejunostomy procedure . This study is registered with Clinical Trials.gov , numbers NCT00660387 and NCT0357994 . FINDINGS From baseline to 12 weeks in the full- analysis set , mean off-time decreased by 4.04 h ( SE 0.65 ) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2.14 h ( 0.66 ) for 31 patients allocated to immediate-release oral levodopa-carbidopa ( difference -1.91 h [ 95 % CI -3.05 to -0.76 ] ; p=0.0015 ) . Mean on-time without troublesome dyskinesia increased by 4.11 h ( SE 0.75 ) in the intestinal gel group and 2.24 h ( 0.76 ) in the immediate-release oral group ( difference 1.86 [ 95 % CI 0.56 to 3.17 ] ; p=0.0059 ) . In the safety analyses 35 ( 95 % ) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events ( five [ 14 % ] serious ) , as did 34 ( 100 % ) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group ( seven [ 21 % ] serious ) , mainly associated with the percutaneous gastrojejunostomy tube . INTERPRETATION Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson 's disease with motor complications . Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date , and our study is , to our knowledge , the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study . FUNDING AbbVie The Stalevo Reduction in Dyskinesia Evaluation in Parkinson 's Disease ( STRIDE-PD ) study compared the initiation of levodopa ( l-dopa ) therapy with l-dopa/carbidopa ( LC ) versus l-dopa/carbidopa/entacapone ( LCE ) in patients with Parkinson 's disease . In the current study , the STRIDE-PD study population was investigated to determine the effect of l-dopa dose and other risk factors on the development of dyskinesia and wearing-off . Patients were r and omized to receive LCE  ( n=373 ) or LC ( n=372 ) . Blinded assessment s for dyskinesia and wearing-off were performed at 3-month intervals for the 134- to  
    Output:
    
The present study showed that CDS was beneficial in the treatment of PD patients with motor complications .
But the incidence of the side events is more common than placebo