Health-related quality of life in Parkinson's disease patients in northeastern Sicily, Italy An ecological perspective

Parkinson＇s disease has a negative impact on health-related quality of life in Parkinson＇s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopaminergic drugs are the variables that most affect health-related quality of life. The ecological model of human development focuses attention on both individual and social environmental factors as targets for health interventions. From this perspective, the aim of this cross-sectional survey was to evaluate the influence of gender, family size and perceived autonomy on health-related quality of life in Parkinson＇s disease patients in nOrtheastern Sicily, Italy. Ninety Parkinson＇s disease patients, attending the Movement Disorders Clinic at IRCCS Centro Neurolesi ＂Bonino-Pulejo＂ （Messina）, were consecutively enrolled. The Unified Parkinson Disease Rating Scale motor subscale （UPDRS-Ⅲ） scores, the Parkinson Disease Questionnaire-39 Item scores （as a disease-specific measure of health-related quality of life）, scores on the Short Form （36） Health Survey Questionnaire （as a generic measure）, and answers to a brief checklist were recorded. A total of 85 Parkinson＇s disease patients （49% males and 51% females; mean age 70.8 ± 8.6 years mean UPDRS-Ⅲ 24.15 ± 6.55; mean disease duration 5.52 ± 4.65 years） completed the booklet of questionnaires. In the multivariate regression analysis, we included clinical and social variables as independent predictors of health-related quality of life. Our results suggest a potential compounding effect of ecological intrapersonal and interpersonal levels on health-related quality of life outcomes. Gender, self-evaluated autonomy and family size significantly impacted health-related quality of life. If quality of life is used as an indicator of treatment outcomes, an ecological perspective of the case history will be important to disclose relevant prognostic information and trigger personalized health care interventions.

Relative exchangeable copper,a high-quality biomarker for differentiation of Traditional Chinese Medicine syndrome in Wilson's disease

OBJECTIVE:To investigate the value of relative exchangeable copper(REC)in diagnosing Wilson's disease(WD)and to determine its significance in the differentiation of Traditional Chinese Medicine(TCM)syndrome.METHODS:A total of 78 patients with WD were recruited on the same day of the medical visit,and among them,32 were suffering from non-WD(N-WD)and 37 were heterozygous ATP7B carriers(HC)enrolled as controls.Molecular genetic testing was performed for diagnosing WD and HC.Additionally,REC levels in different TCM syndromes were investigated.The correlation between REC and serum ceruloplasmin(Cp),serum copper oxidase(CO),and 24-h urinary copper was analyzed using the Global Assessment Scale and Unified Wilson's Disease Rating Scale and the significance of REC in WD diagnosis was investigated.Resting-state functional magnetic resonance imaging was used to assess the clinical symptoms of WD and analyze its severity in different TCM syndromes.RESULTS:REC determination helped in significantly distinguishing patients with N-WD or HC from those with WD with a cut-off of 21.15%.Furthermore,the comparative analysis of REC ratios among different TCM syndromes showed markedly high REC levels in the dampness-heat internal accumulation syndrome group.Additionally,the seed-based functional connectivity value from the putamen to the cerebellum was significantly correlated with TCM syndromes.CONCLUSION:REC level is a high-quality biomarker for diagnosing WD that effectively reflects disease severity and plays an essential role in deciding on treatment strategies and prognosis.Furthermore,REC levels are closely related to TCM syndromes in WD;thus,it is a potential objective quantitative indicator for distinguishing TCM syndromes in WD.

The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson’s disease: a randomized, double-blind, double-dummy, parallel-group study

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.

Tremor and clinical fluctuation are related to sleep disorders in Chinese patients with Parkinson’s disease

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.

An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety,tolerability,and immune biomarkers from limited case numbers

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.

The transmission mechanism theory of disease dynamics:Its aims,assumptions and limitations

Most of the progress in the development of single scale mathematical and computational models for the study of infectious disease dynamics which now span over a century is build on a body of knowledge that has been developed to address particular single scale descriptions of infectious disease dynamics based on understanding disease transmission process.Although this single scale understanding of infectious disease dynamics is now founded on a body of knowledge with a long history,dating back to over a century now,that knowledge has not yet been formalized into a scientific theory.In this article,we formalize this accumulated body of knowledge into a scientific theory called the transmission mechanism theory of disease dynamics which states that at every scale of organization of an infectious disease system,disease dynamics is determined by transmission as the main dynamic disease process.Therefore,the transmission mechanism theory of disease dynamics can be seen as formalizing knowledge that has been inherent in the study of infectious disease dynamics using single scale mathematical and computational models for over a century now.The objective of this article is to summarize this existing knowledge about single scale modelling of infectious dynamics by means of a scientific theory called the transmission mechanism theory of disease dynamics and highlight its aims,assumptions and limitations.

Quantitative evaluation of severity of behavioral and psychological symptoms of dementia in patients with vascular dementia

To quantitatively evaluate severity of behavioral and psychological symptoms of dementia(BPSD)for vascular dementia(VD).Changes of 51 patients with VD in BPSD between the first and 24th week were assessed using the Neuropsychiatric Inventory(NPI)and the behavioral pathology in Alzheimer’s disease(BEHAVE-AD)rating scale,in detrended fluctuation analysis(DFA)represented by diurnal activity(DA),evening activity(EA),and nocturnal activity(NA),and the relationships were analyzed.The subscores of activity disturbances,diurnal rhythm disturbances,and anxieties and phobias in the BEHAVE-AD score,and that of agitation,irritability,and sleep disorder in the NPI score were significantly increased compared with the first week,as was for the changes for EA in the DFA value.A linear correlation was observed between the changes of activity disturbances plus anxieties and phobias,and those of DA,and between the development of diurnal rhythm and those of EA,the vehement and autism scores and those of DA,and the difference in sleep disorder scores and those of EA,respectively.Analysis of DA,NA,and EA may reflect the fluctuational degrees of VD-BPSD,can provide a useful assessment of VD-BPSD accompanied by clinical scores for VD.