Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subje...Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-time.Subjects received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total score.Results:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was demonstrated.The incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole IR.The safety profiles of pramipexole ER and IR were similar.These results were based on comparable mean daily doses and durations of treatment for both formulations.展开更多
Objective:To study the relationship between sleep disturbances and symptoms in patients with Parkinson’s disease(PD).Methods:The Parkinson’s Disease Sleep Scale-Chinese Version(PDSS-CV)was used to evaluate the sleep...Objective:To study the relationship between sleep disturbances and symptoms in patients with Parkinson’s disease(PD).Methods:The Parkinson’s Disease Sleep Scale-Chinese Version(PDSS-CV)was used to evaluate the sleep disturbances of PD patients in a cross sectional study.The Unified Parkinson’s Disease Rating Scale(UPDRS)parts II-IV,and the Hoehn&Yahr(H&Y)stage were used to determine the level of motor function in PD and the severity of PD.The Spearman correlation and a multiple regression analysis were used to identify the relationship between sleep disturbances and symptoms of PD.The quantities derived from the UPDRS and the H&Y stage and disease duration were compared between groups of patients either with or without sleep disturbances identified by the PDSS.This study was conducted from December 2011 to March 2012 at the First Affiliated Hospital of Sun Yat-sen University,in Guangzhou.Results:A total of 136 PD patients were included in this study.The overall total PDSS score in PD patients was 107.58±23.35 points(range:30–146).There were significant differences in the disease duration,the H&Y stage,and the UPDRS section subscores between groups of patients either with or without sleep disturbances(Kruskal-Wallis Test,p<0.05).There were significant negative correlations between PDSS scores and the UPDRS subscores,the H&Y stage and the disease duration(Spearman correlation,p<0.05).The multiple regression analysis indicated that sleep disturbances identified by the PDSS were only associated with daily life activity,tremor intensity and clinical fluctuation(R2=0.22,F(3,132)=12.4,p<0.001).The correlations were also significant when the contribution of the other two factors was excluded using partial correlations.Conclusions:The level of daily life activity and the occurrences of tremor and clinical fluctuation are likely to be important factors that lead to PD patients’sleep disturbances.This study may elucidate an important clue for the relationship between sleep disturbances and PD symptoms.展开更多
Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,an...Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been evaluated.Methods As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 months.Secondary goals included numbers of CD4+T cells and monocytes and motor functions.Hematologic,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/kg.After 2 years,drug use was discon-tinued for 3 months.This was then followed by an additional 6 months of treatment.Results Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone pain.On drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment.Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased.In the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin signaling.This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.Conclusions Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment.Confirmation in larger patient populations is planned in a future phase II evaluation.展开更多
目的探讨合并脑微出血(CMBs)以及不同部位CMBs帕金森病(PD)患者的临床特点以及CMBs对PD患者认知功能的影响。方法收集2016-09—2018-03于苏州高新区人民医院、南京医科大学附属苏州医院就诊的PD患者112例,根据是否合并CMBs病灶分为PD合...目的探讨合并脑微出血(CMBs)以及不同部位CMBs帕金森病(PD)患者的临床特点以及CMBs对PD患者认知功能的影响。方法收集2016-09—2018-03于苏州高新区人民医院、南京医科大学附属苏州医院就诊的PD患者112例,根据是否合并CMBs病灶分为PD合并CMBs组和PD不合并CMBs组。进一步根据CMBs所处的分布区域分为单纯脑叶CMBs和非单纯脑叶CMBs亚组。比较各组患者临床特征、统一帕金森病评分量表(UPDRS)评分、Hoehn-Yahr(H-Y)分级、蒙特利尔认知评估量表(MoCA)等差异。采用非条件Logistics回归分析影响PD认知功能障碍的相关因素。结果与PD未合并CMBs组(n=81)比较,PD合并CMBs组(n=31)患者MoCA评分更低、服用左旋多巴等效剂量更大,侧脑室周围白质病(periventricular white matter hyperintensity,PWMH)和深部白质病变(deep white matter hyperintensity,DWPH)的Fazekas得分均更高(均P<0.05)。与单纯脑叶CMBs亚组(n=10)比较,非单纯脑叶CMBs组患者MocA评分以及视空间与执行、语言项目评分升高(P<0.05或P<0.01),非单纯脑叶CMBs组体位性低血压比例升高(P<0.05)。非条件多因素Logistic回归分析显示,CMBs是PD患者认知障碍的重要影响因素之一。结论合并CMBs的PD患者认知功能更差,对药物反应性越差,脑白质病变和腔隙性脑梗死的程度越重。CMBs对PD患者的认知功能产生一定影响,且CMBs的分布区域不同,认知损害的领域及程度也有所不同。展开更多
基金Boehringer lngelheim lnternational GmbH sponsored this study.
文摘Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-time.Subjects received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total score.Results:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was demonstrated.The incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole IR.The safety profiles of pramipexole ER and IR were similar.These results were based on comparable mean daily doses and durations of treatment for both formulations.
基金This study was supported by grants from the Guangdong Natural Science Foundation(No.10151008901000187)the Guangdong Science and Technology Foundation(No.2010B080701107).
文摘Objective:To study the relationship between sleep disturbances and symptoms in patients with Parkinson’s disease(PD).Methods:The Parkinson’s Disease Sleep Scale-Chinese Version(PDSS-CV)was used to evaluate the sleep disturbances of PD patients in a cross sectional study.The Unified Parkinson’s Disease Rating Scale(UPDRS)parts II-IV,and the Hoehn&Yahr(H&Y)stage were used to determine the level of motor function in PD and the severity of PD.The Spearman correlation and a multiple regression analysis were used to identify the relationship between sleep disturbances and symptoms of PD.The quantities derived from the UPDRS and the H&Y stage and disease duration were compared between groups of patients either with or without sleep disturbances identified by the PDSS.This study was conducted from December 2011 to March 2012 at the First Affiliated Hospital of Sun Yat-sen University,in Guangzhou.Results:A total of 136 PD patients were included in this study.The overall total PDSS score in PD patients was 107.58±23.35 points(range:30–146).There were significant differences in the disease duration,the H&Y stage,and the UPDRS section subscores between groups of patients either with or without sleep disturbances(Kruskal-Wallis Test,p<0.05).There were significant negative correlations between PDSS scores and the UPDRS subscores,the H&Y stage and the disease duration(Spearman correlation,p<0.05).The multiple regression analysis indicated that sleep disturbances identified by the PDSS were only associated with daily life activity,tremor intensity and clinical fluctuation(R2=0.22,F(3,132)=12.4,p<0.001).The correlations were also significant when the contribution of the other two factors was excluded using partial correlations.Conclusions:The level of daily life activity and the occurrences of tremor and clinical fluctuation are likely to be important factors that lead to PD patients’sleep disturbances.This study may elucidate an important clue for the relationship between sleep disturbances and PD symptoms.
基金supported by National Institute of Neurological Disorders and Stroke Grant 5 R01NS034239-25 and private donations provided through the University of Nebraska Foundation.
文摘Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been evaluated.Methods As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 months.Secondary goals included numbers of CD4+T cells and monocytes and motor functions.Hematologic,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/kg.After 2 years,drug use was discon-tinued for 3 months.This was then followed by an additional 6 months of treatment.Results Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone pain.On drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment.Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased.In the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin signaling.This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.Conclusions Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment.Confirmation in larger patient populations is planned in a future phase II evaluation.
文摘目的探讨合并脑微出血(CMBs)以及不同部位CMBs帕金森病(PD)患者的临床特点以及CMBs对PD患者认知功能的影响。方法收集2016-09—2018-03于苏州高新区人民医院、南京医科大学附属苏州医院就诊的PD患者112例,根据是否合并CMBs病灶分为PD合并CMBs组和PD不合并CMBs组。进一步根据CMBs所处的分布区域分为单纯脑叶CMBs和非单纯脑叶CMBs亚组。比较各组患者临床特征、统一帕金森病评分量表(UPDRS)评分、Hoehn-Yahr(H-Y)分级、蒙特利尔认知评估量表(MoCA)等差异。采用非条件Logistics回归分析影响PD认知功能障碍的相关因素。结果与PD未合并CMBs组(n=81)比较,PD合并CMBs组(n=31)患者MoCA评分更低、服用左旋多巴等效剂量更大,侧脑室周围白质病(periventricular white matter hyperintensity,PWMH)和深部白质病变(deep white matter hyperintensity,DWPH)的Fazekas得分均更高(均P<0.05)。与单纯脑叶CMBs亚组(n=10)比较,非单纯脑叶CMBs组患者MocA评分以及视空间与执行、语言项目评分升高(P<0.05或P<0.01),非单纯脑叶CMBs组体位性低血压比例升高(P<0.05)。非条件多因素Logistic回归分析显示,CMBs是PD患者认知障碍的重要影响因素之一。结论合并CMBs的PD患者认知功能更差,对药物反应性越差,脑白质病变和腔隙性脑梗死的程度越重。CMBs对PD患者的认知功能产生一定影响,且CMBs的分布区域不同,认知损害的领域及程度也有所不同。
