***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: BACKGROUND Continuous infusion of levodopa-carbidopa intestinal gel ( LCIG ) can effectively manage motor and non-motor complications in advanced Parkinson 's disease ( PD ) . Healthcare costs , quality of life ( QoL ) , effectiveness , and tolerability were assessed in routine care treatment with LCIG . METHODS The seventy-seven patients enrolled in this prospect i ve , open-label , 3-year study in routine medical care were LCIG-naïve ( N = 37 ) , or had previous LCIG treatment for < 2 ( N = 22 ) , or ≥2 ( N = 18 ) years . Healthcare costs were collected monthly . PD symptoms and QoL were assessed with the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , 39-item Parkinson 's Disease Question naire ( PDQ-39 ) , and EuroQoL 5-Dimension Visual Analog Scale ( EQ-5D VAS ) ; LCIG dose , safety , and tolerability were monitored . RESULTS Mean monthly costs per patient ( € 8226 ± 5952 ) were similar across cohorts , remained steady during 3-year follow-up , and increased with PD severity and QoL impairment . In LCIG-naïve patients , significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months ( n = 24 ; UPDRS , p = 0.033 ; PDQ-39 , p = 0.049 ) . Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts . Small changes in mean daily LCIG dose were observed . Adverse events were common and generally related to the device , procedure , levodopa , or laboratory evaluations . CONCLUSIONS Costs in LCIG-treated patients were stable over 3 years . LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time . The long-term safety was consistent with the established LCIG profile Motor complications in Parkinson 's disease ( PD ) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation . l-dopa-carbidopa intestinal gel ( LCIG ) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube ( PEG-J ) , which reduces l-dopa-plasma – level fluctuations and can translate to reduced motor complications . We present final results of the largest international , prospect i ve , 54-week , open-label LCIG study . PD patients with severe motor fluctuations ( > 3 h/day “ off ” time ) despite optimized therapy received LCIG monotherapy . Additional PD medications were allowed > 28 days post-LCIG initiation . Safety was the primary endpoint measured through adverse events ( AEs ) , device complications , and number of completers . Secondary endpoints included diary-assessed off time , “ on ” time with/without troublesome dyskinesia , UPDRS , and health-related quality -of-life ( HRQoL ) outcomes .  Of 354 enrolled patients , 324 ( 91.5 % ) received PEG-J and 272 ( 76.8 % ) completed the study . Most AEs were mild/moderate and transient ; complication of device insertion ( 34.9 % ) was the most common . Twenty-seven ( 7.6 % ) patients withdrew because of AEs . Serious AEs occurred in 105 ( 32.4 % ) , most commonly complication of device insertion ( 6.5 % ) . Mean daily off time decreased by 4.4 h/65.6 % ( P < 0.001 ) . On time without troublesome dyskinesia increased by 4.8 h/62.9 % ( P < 0.001 ) ; on time with troublesome dyskinesia decreased by 0.4 h/22.5 % ( P = 0.023 ) . Improvements persisted from week 4 through study completion . UPDRS and HRQoL outcomes were also improved throughout . In the advanced PD population , LCIG 's safety profile consisted primarily of AEs associated with the device/procedure , l-dopa/carbidopa , and advanced PD . LCIG was generally well tolerated and demonstrated clinical ly significant improvements in motor function , daily activities , and HRQoL sustained over 54 weeks . © 2014 The Authors . Movement Disorders published by Wiley Periodicals , Inc. on behalf of International Parkinson and Movement Disorder Society 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 In a double-blind , double-dummy , double-titration Phase 3 trial in advanced Parkinson ’s disease ( PD ) patients , the efficacy and safety of Levodopa-carbidopa intestinal gel ( LCIG ) infusion were characterized relative to immediate-release oral levodopa-carbidopa ( LC-oral ) treatment . We present in this report the comparative pharmacokinetic profiles of LCIG and LC-oral from this pivotal study . The results presented in this report clearly demonstrate that LCIG results in lower variability and fluctuations in levodopa and carbidopa plasma concentrations compared to LC-oral . The superior pharmacokinetic profiles with LCIG were consistent with its improved efficacy compared to LC-oral as demonstrated in this study Objective : The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of a levodopa/carbidopa gel ( Duodopa ) to examine pharmacological properties of this treatment . Methods : The modeling involved pooling data from 3 studies ( on advanced Parkinson disease ) and fixing some parameters to values found in literature . The first study involved 12 patients studied on 3 occasions each and was previously published . The second study involved 3 patients on 2 occasions . A bolus dose was given after a washout during night . Plasma sample s and motor ratings ( clinical assessment of motor function on a 7-point treatment response scale ranging from " very off " to " very hyperkinetic " ) were collected until the clinical effect returned to baseline . The third study involved 5 patients on 3 occasions receiving 5 different dose levels . Different structural models were evaluated using the nonlinear mixed-effects modeling program NONMEM VI . Population mean parameter values , and interindividual , interoccasion , and residual variabilities were estimated . Results : Absorption of the levodopa/carbidopa gel can be adequately described with first-order absorption with bioavailability and lag time . Estimated population parameter values were a mean absorption time of 28.5 minutes , a lag time of 2.9 minutes , and a bioavailability of 88 % . The pharmacodynamic model for motor ratings had the following population values : a half-life of effect delay of 21 minutes , a concentration at 50 % effect of 1.55 mg/L , an Emax of 2.39 U on the treatment response scale , and a sigmoidicity of the Emax function of 11.6 . Conclusions : For the typical unmedicated subject , it will take 51.4 minutes until the peak levodopa effect is reached after a bolus dose . This delay is , like the magnitude of the effect , highly variable in this patient group . The residual error magnitudes of 20 % for levodopa concentrations and 0.92 U ( SD ) for motor ratings indicate that the models developed provide predictions of a relevant quality . The developed model may be a first step toward model-guided treatment individualization of duodenal infusion of levodopa 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 Introduction Continuous delivery of levodopa – carbidopa intestinal gel ( LCIG ) by percutaneous endoscopic gastrojejunostomy ( PEG-J ) in advanced Parkinson ’s disease ( PD ) patients reduces variability in plasma levels , providing better control of motor fluctuations ( “ on ” and “ off ” states ) . The MONOTREAT study assessed the effect of LCIG on activities of daily living , motor and non-motor symptoms , and quality of life in advanced PD patients . Methods This prospect i ve , observational study included patients with advanced , levodopa-responsive PD with either 2–4 h of “ off ” time or 2 h of dyskinesia daily . Patients received LCIG via PEG-J for 16 h continuously . Effect 
    Output:
    
Conclusions : Continuous delivery of LCIG may offer a promising option for PD patients .