***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: In a multinational , double-blind , placebo-controlled trial ( NCT00474058 ) , 287 subjects with Parkinson 's disease ( PD ) and unsatisfactory early-morning motor symptom control were r and omized 2:1 to receive rotigotine ( 2–16 mg/24 hr [ n = 190 ] ) or placebo ( n = 97 ) . Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks . Early-morning motor function and nocturnal sleep disturbance were assessed as co primary efficacy endpoints using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) Part III ( Motor Examination ) measured in the early morning prior to any medication intake and the modified Parkinson 's Disease Sleep Scale ( PDSS-2 ) ( mean change from baseline to end of maintenance [ EOM ] , last observation carried forward ) . At EOM , mean UPDRS Part III score had decreased by −7.0 points with rotigotine ( from a baseline of 29.6 [ st and ard deviation ( SD ) 12.3 ] and by −3.9 points with placebo ( baseline 32.0 [ 13.3 ] ) . Mean PDSS-2 total score had decreased by −5.9 points with rotigotine ( from a baseline of 19.3 [ SD 9.3 ] ) and by −1.9 points with placebo ( baseline 20.5 [ 10.4 ] ) . This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III ( treatment difference : −3.55 [ 95 % confidence interval ( CI ) −5.37 , −1.73 ] ; P = 0.0002 ) and PDSS-2 ( treatment difference : −4.26 [ 95 % CI −6.08 , −2.45 ] ; P < 0.0001 ) . The most frequently reported adverse events were nausea  ( placebo , 9 % ; rotigotine , 21 % ) , application site reactions  ( placebo , 4 % ; rotigotine , 15 % ) , and dizziness ( placebo , 6 % ; rotigotine 10 % ) . Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction result ed in significant benefits in control of both motor function and nocturnal sleep disturbances . © 2010 Movement Disorder 1 . Insomnia is an even more frequent complaint in elderly patients with Parkinson 's disease than might be expected from the effect of age alone on sleep . 2 . A double-blind , placebo-controlled trial in eleven patients with Parkinson 's disease of mean ( s.d . ) age 80(5 ) years , showed that nocturnal dosing with levodopa produced a clinical ly significant improvement in sleep both as assessed subjectively and by measurement of number of spontaneous moves in bed . 3 . Despite the long interval between tablet administration and morning assessment , walking time was faster on mornings following active treatment This open-label study ( NCT00243945 ) investigated the efficacy of rotigotine transdermal system in 54 Parkinson ’s disease ( PD ) patients with unsatisfactory control of early morning motor impairment and sleep disturbances .  Rotigotine dose was up titrated for 8 weeks and maintained for 4 weeks . Mean rotigotine dose at end of maintenance was 11.83 mg/24 h ( SD 3.86 ) . Patients had two overnight hospital stays at baseline and end of treatment during which early morning motor performance was assessed , prior to first morning dose of regular oral antiparkinsonian medication . Rotigotine  improved mean Unified Parkinson ’s Disease Rating Scale ( UPDRS ) part III score by −9.3 points , mean Timed Up and Go test duration by −1.4 s and mean morning finger tapping by 26.5 taps/min ; 46 % of patients were considered responders ( ≥30 % improvement of UPDRS III ) . Mean Nocturnal Akinesia , Dystonia and Cramps Sum Score was reduced by 61 % ; mean number of nocturias decreased by 32 % . Rotigotine also improved sleep quality . These results suggest a role for rotigotine in treatment of nocturnal and early morning motor disabilities in PD patients We developed a mobility detection system to analyze pressure changes over time during side-turns in 29 healthy volunteers ( 17 males and 12 females ) with a mean age of 46.1 ± 19.64 years ( ranging from 23 to 86 years ) in order to determine the effect of gender , age , and BMI on performance during bed postural change . Center of gravity ( COG ) location , peak pressure of counteraction , and time to reach peak pressure were the main outcomes used to gauge the ability to make a spontaneous side-turn . Men exhibited significantly higher side-turning force ( P = 0.002 ) and back-turning force ( P = 0.002 ) compared with women . Subjects with BMI ≥27 kg/m2 had significantly higher side-turning force ( P = 0.007 ) and back-turning force ( P = 0.007 ) compared with those with BMI < 27 kg/m2 . After adjusting for other covariates , age positively correlated with back-turning time ( P = 0.033 ) and negatively correlated with side-turning speed ( P = 0.005 ) , back-turning speed ( P = 0.014 ) , side-turning force ( P = 0.010 ) , and back-turning force ( P = 0.016 ) , respectively . Turning times negatively correlated with time to reach peak pressure ( P = 0.008 ) . Our system was effective in detecting changes in turning swiftness in the bed-ridden subject We examined the effects of supplemental st and ard carbidopa/levodopa ( Std-L ) on early morning akinesia in patients with Parkinson 's disease ( PD ) who were being treated with sustained-release carbidopa/levodopa ( L-CR ) .  We compared plasma dopa levels and clinical response in 15 PD patients after a dose of Std-L and L-CR ( 2 hours later ) and after a dose of L-CR and placebo  in a double-blind , placebo-controlled , crossover study . Plasma dopa levels , total motor score , walking time , and finger tapping time were assessed every 15 minutes for the first 2 hours and then every 30 minutes for the next 3 hours . The time of onset in clinical benefit was significantly earlier with Std-L ( 47 minutes , range 15 to 75 minutes ) as the first dose as compared with L-CR ( 58 minutes , range 30 to 105 minutes ) . Similarly , there was a significant difference in the peak plasma dopa levels ( Cmax ) and the time to reach peak plasma dopa levels ( Tmax ) with administration of Std-L ( Tmax 36 minutes ; Cmax 1,501 mu g/ml ) as compared with L-CR ( Tmax 111 minutes , Cmax 1,260 mu g/ml ) . There was no significant difference in dyskinesias between the two treatment arms . An initial morning dose of Std-L alleviates the problem of delayed-onset clinical response that commonly occurs with L-CR . NEUROLOGY 1996;46 : 1059 - Objectives ‐ Nocturnal disabilities leading to fragmented sleep arising from parkinsonian off period related complications are common , under‐reported and are difficult to treat . In this study , we evaluate the use of nocturnal continuous subcutaneous overnight apomorphine infusion in Parkinson 's disease and restless legs syndrome . Methods ‐ Six parkinsonian patients and 2 patients with restless legs syndrome with nocturnal disabilities refractory to conventional oral therapy were assessed using a sleep diary while on st and ard treatment and during nocturnal apomorphine infusion . Three patients agreed to assessment s during placebo infusion with normal saline . Results ‐ Apomorphine led to a dramatic reduction of nocturnal awakenings , nocturnal off periods , pain , dystonia and nocturia in parkinsonian patients . In patients with restless legs syndrome  , apomorphine reduced nocturnal discomfort , reduced leg movements and improved pain and spasm scores significantly . Placebo infusion reproduced pain , nocturnal spasms and sleep disruption . Conclusion ‐ This study suggests that overnight apomorphine infusion may be effective in overcoming refractory nocturnal disabilities in selected patients with Parkinson 's disease and restless legs syndrome Objective : The aim of this research is to characterize further the potential motor and non-motor benefits of rotigotine reported in the double-blind , placebo-controlled RECOVER trial primary publication , by performing a post hoc exploratory analysis of patient status ( symptom improvement/worsening ) . Methods : Full RECOVER trial method ological details have already been reported . The post hoc analyses presented here are done on individual items of the PDSS-2 and PDQ-8 for all patients and two subgroups ( baseline symptomatic and highly symptomatic patients ) . Results : Ten PDSS-2 and five PDQ-8 items show significant mean treatment difference versus placebo . In the overall population , items that most favor rotigotine in percentage of patients with improvement are ‘ limb pain causes waking ’ and ‘ uncomfortable in bed due to immobility ’ for PDSS-2 ; for PDQ-8 , rotigotine is most favored in ‘ difficulty dressing ’ , ‘ felt depressed ’ and ‘ difficulty getting around in public ’ . Among symptomatic and highly symptomatic patients , the PDSS-2 items that most favor rotigotine are both indicators of pain . On the PDQ-8 , the two items most favored in symptomatic patients are ‘ difficulty dressing ’ and ‘ embarrassed in public due to PD ’ , and in the highly symptomatic subgroup ‘ difficulty dressing ’ and ‘ difficulty getting around in public ’ . Conclusion : Though this trial was not powered for statistical subgroup analysis , these post hoc results indicate that treatment with rotigotine may benefit patients with sleep , pain , mood and quality -of-life issues BACKGROUND The LARGO study demonstrated that rasagiline 1 mg/day as adjunct to levodopa significantly reduces OFF time to the same magnitude as adjunct entacapone . This sub study of LARGO aim ed to assess the effect of rasagiline and entacapone on the motor symptoms of PD during the practically defined OFF state . METHODS LARGO was a r and omized , double-blind , multicenter trial that assessed the efficacy and safety of rasagiline ( 1 mg/day ) , entacapone ( 200 mg with each levodopa dose ) , and placebo in 687 levodopa-treated PD patients with motor fluctuations . A sub study of LARGO measured UPDRS motor scores in the practically defined OFF state in 32 rasagiline , 36 entacapone , and 37 placebo patients . RESULTS Treatment with rasagiline produced a significant improvement over placebo of 5.64 units in UPDRS motor OFF score ( P = 0.013 vs. placebo ) . By contrast , the effect of adjunct entacapone was not significant ( P = 0.14 vs. placebo ) . Whereas rasagiline also showed a trend in reducing the UPDRS-ADL OFF score ( P = 0.058 vs. placebo ) , no such trend was noted for entacapone ( P = 0.26 vs. placebo ) . Retrospective analysis , using the Bonferroni correction , of UPDRS motor subdomains further revealed that rasagiline , but not entacapone , significantly improved bradykinesia ( P < 0.001 ) and showed trends for improvements in facial expression , speech , and axial impairment during OFF time . CONCLUSIONS This study provides the first objective ly measured evidence that adjunct rasagiline 1 mg/day is effective in reducing the severity of motor symptoms in the OFF state . This suggests a continuous effect of rasagiline 1 mg/day throughout the day and night and is consistent with its extended duration of therapeutic action Clinical response to a new galenic formulation of levodopa plus benserazide , Madopar HBS , was studied in 25 fluctuating parkinsonians . This open study was planned in two phases . In the first phase , the administering of HBS alone result ed in a surprisingly high number of dropouts . In the second phase , Madopar st and ard in association with Madopar HBS , the follow-up period was 24 months . A stable long-lasting improvement in predictable fluctuations and their severity was maintained for the whole period without any change in drug dose . Nocturnal and early morning akinesia improved too . The study shows that Madopar HBS plus Madopar st and ard is effective in producing a prolonged and stable response in parkinsonian fluctuating patients BACKGROUND The 24-week , double-blind Efficacy and Safety Evaluation in PD-Adjunct ( EASE-PD Adjunct ) study r and omized patients with advanced Parkinson 's disease ( PD ) suboptimally controlled with levodopa to once-daily placebo or adjunctive ropinirole prolonged release ( 2 - 24 mg/day ) . We investigated the effect of ropinirole prolonged release on nocturnal symptoms in these patients . METHODS Total and grouped item PD Sleep Scale ( PDSS ) scores were analyzed post hoc in patients with baseline PDSS total scores ≤ 100 ( troublesome nocturnal symptoms ) and > 100 .  RESULTS Baseline PDSS total score was ≤ 100 in 93 of 198 ( 4 
    Output:
    
Several lines of evidence support the use of long-acting drugs or by continuous administration of short-acting agents to control symptoms .