Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy o...Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy of a monoamine oxidase type B inhibitor (MAOBI) with levodopa or a catechol-O-methyl transferase inhibitor (COMTI) with levodopa provides benefits to PD patients. Direct comparison of efficacy and side effect profiles is complex. The aim of this study is to investigate the different AE profiles of MAOBI and COMTI combination therapies. Data used to analyze the AEs of different PD medications were retrieved from “The Boston University Medical Center’s Parkinson’s Disease and Movement Disorder Database”. Ten categories of AEs were compared between patients receiving MAOBI and COMTI combination treatment. In total, 87 subjects were included in the analysis. Out of ten AEs, the presence of dementia was signifi- cantly different between the MAOBI and COMTI groups with an OR of 6.9 (COMTI vs MAOBI, 95% CI 1.3 - 37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with an OR of 3.1 (COMTI vs MAOBI, 95% CI 1.0 - 9.8). In this retrospective database analysis of patients treated with combination treatment for PD, combination therapy of a COMTI with levodopa was more likely to be associated with dementia and motor fluctuations than a MAOBI with levodopa.展开更多
Background:The efficacy and safety of opicapone,a once-daily catechol-O-methyltransferase inhibitor,have been established in two large randomized,placebo-controlled,multinational pivotal trials.Still,clinical evidence...Background:The efficacy and safety of opicapone,a once-daily catechol-O-methyltransferase inhibitor,have been established in two large randomized,placebo-controlled,multinational pivotal trials.Still,clinical evidence from routine practice is needed to complement the data from the pivotal trials.Methods:OPTIPARK(NCT02847442)was a prospective,open-label,single-arm trial conducted in Germany and the UK under clinical practice conditions.Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3(Germany)or 6(UK)months in addition to their current levodopa and other antiparkinsonian treatments.The primary endpoint was the Clinician’s Global Impression of Change(CGI-C)after 3 months.Secondary assessments included Patient Global Impressions of Change(PGI-C),the Unified Parkinson’s Disease Rating Scale(UPDRS),Parkinson’s Disease Questionnaire(PDQ-8),and the Non-Motor Symptoms Scale(NMSS).Safety assessments included evaluation of treatment-emergent adverse events(TEAEs)and serious adverse events(SAEs).Results:Of the 506 patients enrolled,495(97.8%)took at least one dose of opicapone.Of these,393(79.4%)patients completed 3 months of treatment.Overall,71.3 and 76.9%of patients experienced any improvement on CGI-C and PGI-C after 3 months,respectively(full analysis set).At 6 months,for UK subgroup only(n=95),85.3%of patients were judged by investigators as improved since commencing treatment.UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF(mean±SD change from baseline:?3.0±4.6,p<0.0001)and motor scores during ON(?4.6±8.1,p<0.0001).The mean±SD improvements of?3.4±12.8 points for PDQ-8 and-6.8±19.7 points for NMSS were statistically significant versus baseline(both p<0.0001).Most of TEAEs(94.8%of events)were of mild or moderate intensity.TEAEs considered to be at least possibly related to opicapone were reported for 45.1%of patients,with dyskinesia(11.5%)and dry mouth(6.5%)being the most frequently reported.Serious TEAEs considered at least possibly related to opicapone were reported for 1.4%of patients.Conclusions:Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice.展开更多
Background:The use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical studies.This study is to investigate the effica...Background:The use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical studies.This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson’s disease,as a product registration study.Methods:This 16-week,randomized,double-blind,parallel-group,multicenter,placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson’s disease and motor fluctuations.The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks.Secondary endpoints were Clinical Global Impressions–Improvement(CGI-I),and change in Unified Parkinson’s Disease Rating Scale(UPDRS)Activities of daily living(ADL)and Motor scores.Patient well-being(EQ-5D),and the frequency of adverse events were also assessed.Results:In total,324 levodopa-treated patients were randomized to rasagiline 1 mg/day(n=165)or placebo(n=159).Over 16 weeks,rasagiline statistically significantly reduced the mean[95% confidence interval]total daily OFF time versus placebo(−0.5 h[−0.92,−0.07];p=0.023).There were also statistically significant improvements versus placebo in CGI-I(−0.4 points[−0.61,−0.22];p<0.001),UPDRS-ADL OFF(−1.0 points[−1.75,−0.27];p=0.008),and UPDRS-Motor ON(−1.6 points[−3.05,−0.14];p=0.032)scores,as well as the EQ-5D utility index(p<0.05).Rasagiline was safe and well tolerated.Conclusions:In levodopa-treated Chinese patients with Parkinson’s disease and motor fluctuations,adjunct rasagiline 1 mg/day statistically significantly reduced OFF time,and improved daily function and overall well-being,versus placebo.Consistent with findings in other countries,adjunct rasagiline was proven efficacious and well tolerated in Chinese patients.展开更多
Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain...Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI （PD-MCI） relative to cognitively normal PD patients （PD-CN） and healthy control （HC） subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation （ALFF） values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyms of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores, and the ALFF values in the left superior frontal gyms were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.展开更多
目的系统评价吡贝地尔治疗帕金森病(PD)的有效性和安全性。方法计算机检索Cochrane Library、Medline、Embase、中国生物医学文献数据库(CBM),查找以吡贝地尔治疗PD的随机对照试验(RCT),对纳入的RCT进行质量评价,采用Rev Man 5.1软件进...目的系统评价吡贝地尔治疗帕金森病(PD)的有效性和安全性。方法计算机检索Cochrane Library、Medline、Embase、中国生物医学文献数据库(CBM),查找以吡贝地尔治疗PD的随机对照试验(RCT),对纳入的RCT进行质量评价,采用Rev Man 5.1软件进行Meta分析。结果共纳入10项RCT,包括578例PD患者。Meta分析结果提示,吡贝地尔组的有效率明显高于对照组[RR=1.30,95%CI(1.15,1.46),P<0.0001];吡贝地尔组的UPDRSⅠ评分改善程度高于对照组[MD=-1.98,95%CI(-2.77,-1.18),P<0.00001]。吡贝地尔组的UPDRSⅡ评分和UPDRSⅢ评分改善与对照组无统计学差异(P>0.05)。吡贝地尔组的HAMD评分改善程度高于对照组[MD=-4.95,95%CI(-7.32,-2.57),P<0.0001]。吡贝地尔组的总不良事件、消化道症状和头晕发生率与对照组均无统计学差异(P>0.05)。结论吡贝地尔能够明显改善PD患者的运动症状和抑郁情绪,提高有效率,且不增加不良事件的发生。展开更多
文摘Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy of a monoamine oxidase type B inhibitor (MAOBI) with levodopa or a catechol-O-methyl transferase inhibitor (COMTI) with levodopa provides benefits to PD patients. Direct comparison of efficacy and side effect profiles is complex. The aim of this study is to investigate the different AE profiles of MAOBI and COMTI combination therapies. Data used to analyze the AEs of different PD medications were retrieved from “The Boston University Medical Center’s Parkinson’s Disease and Movement Disorder Database”. Ten categories of AEs were compared between patients receiving MAOBI and COMTI combination treatment. In total, 87 subjects were included in the analysis. Out of ten AEs, the presence of dementia was signifi- cantly different between the MAOBI and COMTI groups with an OR of 6.9 (COMTI vs MAOBI, 95% CI 1.3 - 37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with an OR of 3.1 (COMTI vs MAOBI, 95% CI 1.0 - 9.8). In this retrospective database analysis of patients treated with combination treatment for PD, combination therapy of a COMTI with levodopa was more likely to be associated with dementia and motor fluctuations than a MAOBI with levodopa.
基金The study was funded by BIALThree authors(JFR,DM and PSS)were employed by the funder and participated in the study design,data collection,data management,and data analysis+1 种基金The funder of the study had no other role in data interpretation or in the decision to submit the manuscript for publicationBIAL also supported reporting of study results by procuring medical writing support.
文摘Background:The efficacy and safety of opicapone,a once-daily catechol-O-methyltransferase inhibitor,have been established in two large randomized,placebo-controlled,multinational pivotal trials.Still,clinical evidence from routine practice is needed to complement the data from the pivotal trials.Methods:OPTIPARK(NCT02847442)was a prospective,open-label,single-arm trial conducted in Germany and the UK under clinical practice conditions.Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3(Germany)or 6(UK)months in addition to their current levodopa and other antiparkinsonian treatments.The primary endpoint was the Clinician’s Global Impression of Change(CGI-C)after 3 months.Secondary assessments included Patient Global Impressions of Change(PGI-C),the Unified Parkinson’s Disease Rating Scale(UPDRS),Parkinson’s Disease Questionnaire(PDQ-8),and the Non-Motor Symptoms Scale(NMSS).Safety assessments included evaluation of treatment-emergent adverse events(TEAEs)and serious adverse events(SAEs).Results:Of the 506 patients enrolled,495(97.8%)took at least one dose of opicapone.Of these,393(79.4%)patients completed 3 months of treatment.Overall,71.3 and 76.9%of patients experienced any improvement on CGI-C and PGI-C after 3 months,respectively(full analysis set).At 6 months,for UK subgroup only(n=95),85.3%of patients were judged by investigators as improved since commencing treatment.UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF(mean±SD change from baseline:?3.0±4.6,p<0.0001)and motor scores during ON(?4.6±8.1,p<0.0001).The mean±SD improvements of?3.4±12.8 points for PDQ-8 and-6.8±19.7 points for NMSS were statistically significant versus baseline(both p<0.0001).Most of TEAEs(94.8%of events)were of mild or moderate intensity.TEAEs considered to be at least possibly related to opicapone were reported for 45.1%of patients,with dyskinesia(11.5%)and dry mouth(6.5%)being the most frequently reported.Serious TEAEs considered at least possibly related to opicapone were reported for 1.4%of patients.Conclusions:Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice.
文摘Background:The use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical studies.This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson’s disease,as a product registration study.Methods:This 16-week,randomized,double-blind,parallel-group,multicenter,placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson’s disease and motor fluctuations.The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks.Secondary endpoints were Clinical Global Impressions–Improvement(CGI-I),and change in Unified Parkinson’s Disease Rating Scale(UPDRS)Activities of daily living(ADL)and Motor scores.Patient well-being(EQ-5D),and the frequency of adverse events were also assessed.Results:In total,324 levodopa-treated patients were randomized to rasagiline 1 mg/day(n=165)or placebo(n=159).Over 16 weeks,rasagiline statistically significantly reduced the mean[95% confidence interval]total daily OFF time versus placebo(−0.5 h[−0.92,−0.07];p=0.023).There were also statistically significant improvements versus placebo in CGI-I(−0.4 points[−0.61,−0.22];p<0.001),UPDRS-ADL OFF(−1.0 points[−1.75,−0.27];p=0.008),and UPDRS-Motor ON(−1.6 points[−3.05,−0.14];p=0.032)scores,as well as the EQ-5D utility index(p<0.05).Rasagiline was safe and well tolerated.Conclusions:In levodopa-treated Chinese patients with Parkinson’s disease and motor fluctuations,adjunct rasagiline 1 mg/day statistically significantly reduced OFF time,and improved daily function and overall well-being,versus placebo.Consistent with findings in other countries,adjunct rasagiline was proven efficacious and well tolerated in Chinese patients.
基金supported by the National Natural Science Foundation of China(81271429 and 81571228)
文摘Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI （PD-MCI） relative to cognitively normal PD patients （PD-CN） and healthy control （HC） subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation （ALFF） values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyms of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores, and the ALFF values in the left superior frontal gyms were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.
文摘目的系统评价吡贝地尔治疗帕金森病(PD)的有效性和安全性。方法计算机检索Cochrane Library、Medline、Embase、中国生物医学文献数据库(CBM),查找以吡贝地尔治疗PD的随机对照试验(RCT),对纳入的RCT进行质量评价,采用Rev Man 5.1软件进行Meta分析。结果共纳入10项RCT,包括578例PD患者。Meta分析结果提示,吡贝地尔组的有效率明显高于对照组[RR=1.30,95%CI(1.15,1.46),P<0.0001];吡贝地尔组的UPDRSⅠ评分改善程度高于对照组[MD=-1.98,95%CI(-2.77,-1.18),P<0.00001]。吡贝地尔组的UPDRSⅡ评分和UPDRSⅢ评分改善与对照组无统计学差异(P>0.05)。吡贝地尔组的HAMD评分改善程度高于对照组[MD=-4.95,95%CI(-7.32,-2.57),P<0.0001]。吡贝地尔组的总不良事件、消化道症状和头晕发生率与对照组均无统计学差异(P>0.05)。结论吡贝地尔能够明显改善PD患者的运动症状和抑郁情绪,提高有效率,且不增加不良事件的发生。
