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- Balzer-Geldsetzer, Monika, et al.
(författare)
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Study protocol: Care of Late-Stage Parkinsonism (CLaSP): a longitudinal cohort study
- 2018
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a chronic progressive disorder leading to increasing disability. While the symptoms and needs of patients in the early stages of their disease are well characterized, little information is available on patients in the late stage of the disease. Methods/design: The Care of Late-Stage Parkinsonism (CLaSP) study is a longitudinal, multicenter, prospective cohort study to assess the needs and provision of care for patients with late stage Parkinsonism and their carers in six European countries (UK, France, Germany, Netherlands, Portugal, Sweden). In addition, it will compare the effectiveness of different health and social care systems. Patients with Parkinsonism with Hoehn and Yahr stage ≥IV in the "On"-state or Schwab and England stage 50% or less are evaluated at baseline and three follow-up time-points. Standardised questionnaires and tests are applied for detailed clinical, neuropsychological, behavioural and health-economic assessments. A qualitative study explores the health care needs and experiences of patients and carers, and an interventional sub-study evaluates the impact of specialist recommendations on their outcomes. Discussion: Through the combined assessment of a range of quantitative measures and qualitative assessments of patients with late stage parkinsonism, this study will provide for the first time comprehensive and in-depth information on the clinical presentation, needs and health care provision in this population in Europe, and lay the foundation for improved outcomes in these patients. Trial registration: The protocol was registered at ClinicalTrials.gov as NCT02333175 on 07/01/2015.
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- Hommel, Adrianus L.A.J., et al.
(författare)
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Optimizing Treatment in Undertreated Late-Stage Parkinsonism : A Pragmatic Randomized Trial
- 2020
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 10:3, s. 1171-1184
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment of patients with late-stage parkinsonism is often sub-optimal. Objective: To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism. Methods: Ninety-one patients with late-stage parkinsonism considered undertreated were included in apragmatic a pragmatic multi-center randomized-controlled trial with six-month follow-up. The intervention group received a letter with treatment recommendations to their primary clinician based on an extensive clinical assessment. Controls received care as usual. The primary outcome was the Unified Parkinson Disease Rating Scale (UPDRS)part-II (Activities of Daily Living). Other outcomes included quality-of-life (PDQ-8), mental health (UPDRS-I), motor function (UPDRS-III), treatment complications (UPDRS-IV), cognition (Mini-mental-state-examination), non-motor symptoms (Non-Motor-Symptoms-scale), health status (EQ-5D-5L) and levodopa-equivalent-daily-dose (LEDD). We also assessed adherence to recommendations. In addition to intention-to-treat analyses, a per-protocol analysis was conducted. Results: Sample size calculation required 288 patients, but only 91 patients could be included. Treating physicians followed recommendations fully in 16 (28%) and partially in 21 (36%) patients. The intention-to-treat analysis showed no difference in primary outcome (between-group difference=-1.2, p=0.45), but there was greater improvement for PDQ-8 in the intervention group (between-group difference=-3.7, p=0.02). The per-protocol analysis confirmed these findings, and showed less deterioration in UPDRS-part I, greater improvement on UPDRS-total score and greater increase in LEDD in the intervention group. Conclusions: The findings suggest that therapeutic gains may be reached even in this vulnerable group of patients with late-stage parkinsonism, but also emphasize that specialist recommendations need to be accompanied by better strategies to implement these to further improve outcomes.
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- Kruse, Christopher, et al.
(författare)
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Care of Late-Stage Parkinsonism : Resource Utilization of the Disease in Five European Countries
- 2024
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Ingår i: Movement Disorders. - 0885-3185. ; 39:3, s. 571-584
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. Objective: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. Methods: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. Results: During the 3-month period, the costs were €20,573 (France), €19,959 (Germany), €18,319 (the Netherlands), €25,649 (Sweden), and €12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. Conclusion: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned.
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- Moss, J, et al.
(författare)
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Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5068-
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Tidskriftsartikel (refereegranskat)abstract
- Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics.
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- Sombers, L A, et al.
(författare)
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High Osmolarity and L-DOPA Augment Release via the Fusion Pore in PC12 Cells
- 2007
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Ingår i: Chemphyschem. - : Wiley. - 1439-4235 .- 1439-7641. ; 8:17, s. 2471-2477
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Tidskriftsartikel (refereegranskat)abstract
- We have amperometrically measured dopamine release from rat pheochromocytoma cells (PC12 cells) in high osmolarity conditions with and without L-3,4-dihydroxyphenylalanine (L-DOPA) treatment. We observe an increase in the number of release events displaying a prespike feature or foot when the cells are stimulated in high osmolarity saline. We also see an increase in foot area and duration when cells are stimulated in high osmolarity saline, or high osmolarity saline subsequent to incubation with the dopamine precursor L-DOPA in isotonic saline, which serves to increase the vesicle size. The data suggest that membrane biophysics are an important component in defining the rate, duration and amount of neurotransmitter release via the fusion pore.
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- Wittenberg, N J, et al.
(författare)
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Short-Chain Alcohols Promote Accelerated Membrane Distention in a Dynamic Liposome Model of Exocytosis
- 2008
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 24:6, s. 2637-2642
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Tidskriftsartikel (refereegranskat)abstract
- We have used amperometric measurements in a model system consisting of two liposomes connected with a membrane nanotube to monitor catechol release during artificial exocytosis and thereby to elucidate the effect of small-chain alcohols on this dynamic membrane process. To determine the rate of membrane shape change, catechol release during membrane distention was monitored amperometrically, and the presence of alcohols in the buffer was shown to accelerate the membrane distention process in a concentration-dependent manner. Compression isotherms for the same lipid composition in the absence and presence of ethanol and 1-propanol were measured to determine how these short-chain alcohols affect the lipid packing in monolayers. The isotherms show a marked decrease in lipid packing density that is dependent on the particular alcohol and its concentration. Comparison of the electrochemical and isotherm results suggests a correlation between decreasing lipid packing density and increasing rates of membrane shape change.
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