An integrated framework of personalized medicine: from individual genomes to participatory health care

Abstract Promising research developments in both basic and applied sciences, such as genomics and participatory health care approaches, have generated widespread interest in personalized medicine among almost all scientific areas and clinicians. The term personalized medicine is, however, frequently used without defining a clear theoretical and methodological background. In addition, to date most personalized medicine approaches still lack convincing empirical evidence regarding their contribution and advantages in comparison to traditional models. Here, we propose that personalized medicine can only fulfill the promise of optimizing our health care system by an interdisciplinary and translational view that extends beyond traditional diagnostic and classification systems

Cost-Effectiveness and Cost-Utility of Early Levodopa in Parkinson's Disease

Background: In the Levodopa in EArly Parkinson's disease (LEAP) study, 445 patients were randomized to levodopa/carbidopa 100/25 mg three times per day for 80 weeks (early-start) or placebo for 40 weeks followed by levodopa/carbidopa 100/25 mg three times per day for 40 weeks (delayed-start).Objective: This paper reports the results of the economic evaluation performed alongside the LEAP-study.Methods: Early-start treatment was evaluated versus delayed-start treatment, in which the cost-effectiveness analysis (CEA) and the cost-utility analysis (CUA) were performed from the societal perspective, including health care costs among providers, non-reimbursable out-of-pocket expenses of patients, employer costs of sick leave, and lowered productivity while at work. The outcome measure for the CEA was the extra cost per unit decrease on the Unified Parkinson's Disease Rating Scale 80 weeks after baseline. The outcome measure for the CUA was the extra costs per additional quality adjusted life year (QALY) during follow-up.Results: 212 patients in the early-start and 219 patients in the delayed-start group reported use of health care resources. With savings of D 59 per patient (BCa 95% CI: -829, 788) in the early-start compared to the delayed-start group, societal costs were balanced. The early-start group showed a mean of 1.30 QALYs (BCa 95% CI: 1.26, 1.33) versus 1.30 QALYs (BCa 95% CI: 1.27, 1.33) for the delayed-start group. Because of this negligible difference, incremental cost-effectiveness and cost-utility ratios were not calculated.Conclusion: From an economic point of view, this study suggests that early treatment with levodopa is not more expensive than delayed treatment with levodopa.Neurological Motor Disorder

An integrated framework of personalized medicine: from individual genomes to participatory health care

Abstract Promising research developments in both basic and applied sciences, such as genomics and participatory health care approaches, have generated widespread interest in personalized medicine among almost all scientific areas and clinicians. The term personalized medicine is, however, frequently used without defining a clear theoretical and methodological background. In addition, to date most personalized medicine approaches still lack convincing empirical evidence regarding their contribution and advantages in comparison to traditional models. Here, we propose that personalized medicine can only fulfill the promise of optimizing our health care system by an interdisciplinary and translational view that extends beyond traditional diagnostic and classification systems

ParkinsonNet:A low-cost health care innovation with a systems approach from the Netherlands

Item does not contain fulltextParkinsonNet, a low-cost innovation to optimize care for patients with Parkinson disease, was developed in 2004 as a network of physical therapists in several regions in the Netherlands. Since that time, the network has achieved full national reach, with 70 regional networks and around 3,000 specifically trained professionals from 12 disciplines. Key elements include the empowerment of professionals who are highly trained and specialized in Parkinson disease, the empowerment of patients by education and consultation, and the empowerment of integrated multidisciplinary teams to better address and manage the disease. Studies have found that the ParkinsonNet approach leads to outcomes that are at least as good as, if not better than, outcomes from usual care. One study found a 50 percent reduction in hip fractures and fewer inpatient admissions. Other studies suggest that ParkinsonNet leads to modest but important cost savings (at least US$439 per patient annually). These cost savings outweigh the costs of building and maintaining the network. Because of ParkinsonNet's success, the program has now spread to several other countries and serves as a model of a successful and scalable frugal innovation

Dance classes improve self-esteem and quality of life in persons with Parkinson’s disease

Introduction: Dance can reduce motor symptoms in persons with Parkinson’s disease (PD). However, the effect on psychosocial wellbeing, including self-esteem and quality of life is less clear. Methods: Forty-nine persons with PD (Hoehn and Yahr stage 1–4) participated in weekly dance classes for a consecutive period of 22 weeks, 36 participants completed the classes. Two baseline measurements (T1a and T1b) were performed during a 2-week control period prior to the dance classes. Post-measurements (T2) were performed immediately after 22 weeks of dance classes. Primary outcome was self-esteem as measured with the Rosenberg Self-Esteem Score. Results: Self-esteem scores were stable across the two baseline measurements and improved significantly after the dance classes (1.5 points improvement between T1b and T2, 95% CI 0.3, 2.7; p = 0.012). Additionally, quality of life as measured with the Parkinson’s Disease Questionnaire 39 improved significantly (3.4 points reduction between T1b and T2, 95%CI − 5.7, − 1.2; p = 0.003) as did motor symptoms as measured with the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale—part III (6.2 points reduction between T1b and T2, 95%CI − 10.1, − 2.4; p = 0.002). Balance confidence as measured with the Activities-Specific Balance Confidence Scale did not change. Discussion and conclusions: Dance classes seem to improve self-esteem, quality of life and motor symptoms in persons with PD. These effects should be investigated further in a randomized clinical trial. Clinical message: Dance classes may be a valuable complementary treatment option in people with PD to improve not only motor symptoms, but also self-esteem and quality of life

Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson’s disease: study rationale and protocol

Background Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. Methods/Design In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis. Discussion This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. Trial registration ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).Health and Social Development, Faculty of (Okanagan)Non UBCHealth and Exercise Sciences, School of (Okanagan)ReviewedFacultyResearche

The prevalence and determinants of neuropsychiatric symptoms in late‐stage Parkinsonism

© 2020 International Parkinson and Movement Disorder SocietyBackground: Late-stage parkinsonism and Parkinson's disease (PD) are insufficiently studied population. Although neuropsychiatric symptoms (eg, psychosis, depression, anxiety, behavioral problems) are frequently present, their prevalence and clinical predictors remain unknown. Objective: To determine the prevalence and predictors of neuropsychiatric symptoms in late-stage PD. Methods: We conducted a multinational study of patients with PD with ≥7 years disease duration and either a Hoehn and Yahr stage ≥4 or a Schwab and England score ≤ 50% in the on stage. Neuropsychiatric symptoms were assessed through interviews with carers using the Neuropsychiatric Inventory, with a frequency × severity score ≥ 4, indicating clinically relevant symptoms. The determinants analyzed were demographic characteristics, medication, and motor and nonmotor symptoms. Univariate and multivariate logistic analyses were performed on predictors of clinically relevant neuropsychiatric symptoms. Results: A total of 625 patients were recruited in whom the Neuropsychiatric Inventory could be completed. In 92.2% (576/625) of the patients, at least 1 neuropsychiatric symptom was present, and 75.5% (472/625) had ≥1 clinically relevant symptom. The most common clinically relevant symptoms were apathy (n = 242; 38.9%), depression (n = 213; 34.5%), and anxiety (n = 148; 23.8%). The multivariate analysis revealed unique sets of predictors for each symptom, particularly the presence of other neuropsychiatric features, cognitive impairment, daytime sleepiness. Conclusion: Neuropsychiatric symptoms are common in late-stage PD. The strongest predictors are the presence of other neuropsychiatric symptoms. Clinicians involved in the care for patients with late-stage PD should be aware of these symptoms in this specific disease group and proactively explore other psychiatric comorbidities once a neuropsychiatric symptom is recognized.The Care of late-stage Parkinsonism-study (CLaSP) is being funded by the European Commission (Joint Programme–Neurodegenerative DiseaseResearch “European Research Projects for the Evaluation of Health Care Policies, Strategies and Interventions for Neurodegenerative Diseases”) through national funding bodies in all 6 countries(Economic and Social Research Council ES/L009250/1; BMBF, Marburg, Germany 01ED1403A, Munich, Germany 01ED1403B; Bordeaux, France, ANR-13-JPHC-0001-07; Lisbon, Portugal, HC/0002/2012; Lund, Sweden, HC-559-002; Nijmegen, Hol-land, 733051003). A.L.A.J.H. was supported by the Groenhuysen organization and Stichting Beroepsopleiding Huisartsen. A.S. was supported by the National Institute for Health Research University College London/University College London Hospital Biomedical Research Centre.info:eu-repo/semantics/publishedVersio

Optimizing Treatment in Undertreated Late-Stage Parkinsonism : A Pragmatic Randomized Trial

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