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  • 1
    Online Resource
    Online Resource
    Estimating the Effect of Early Treatment Initiation in Parkinson's Disease Using Observational Data
    Wiley ; 2021
    In:  Movement Disorders Vol. 36, No. 2 ( 2021-02), p. 407-414
    Details
    In: Movement Disorders, Wiley, Vol. 36, No. 2 ( 2021-02), p. 407-414
    Abstract: Both patients and physicians may choose to delay initiation of dopamine replacement therapy in Parkinson's disease (PD) for various reasons. We used observational data to estimate the effect of earlier treatment in PD. Observational data offer a valuable source of evidence, complementary to controlled trials. Method We studied the Parkinson's Progression Markers Initiative cohort of patients with de novo PD to estimate the effects of duration of PD treatment during the first 2 years of follow‐up, exploiting natural interindividual variation in the time to start first treatment. We estimated the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III (primary outcome) and several functionally relevant outcomes at 2, 3, and 4 years after baseline. To adjust for time‐varying confounding, we used marginal structural models with inverse probability of treatment weighting and the parametric g‐formula. Results We included 302 patients from the Parkinson's Progression Markers Initiative cohort. There was a small improvement in MDS‐UPDRS Part III scores after 2 years of follow‐up for patients who started treatment earlier, and similar, but nonstatistically significant, differences in subsequent years. We found no statistically significant differences in most secondary outcomes, including the presence of motor fluctuations, nonmotor symptoms, MDS‐UPDRS Part II scores, and the Schwab and England Activities of Daily Living Scale. Conclusion Earlier treatment initiation does not lead to worse MDS‐UPDRS motor scores and may offer small improvements. These findings, based on observational data, are in line with earlier findings from clinical trials. Observational data, when combined with appropriate causal methods, are a valuable source of additional evidence to support real‐world clinical decisions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v36.2
    DOI: 10.1002/mds.28339
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2041249-6
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  • 2
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    Online Resource
    Stress and Mindfulness in Parkinson's Disease: Clinical Effects and Potential Underlying Mechanisms
    Wiley ; 2021
    In:  Movement Disorders Vol. 36, No. 1 ( 2021-01), p. 64-70
    Details
    In: Movement Disorders, Wiley, Vol. 36, No. 1 ( 2021-01), p. 64-70
    Abstract: Patients with Parkinson's disease (PD) are very vulnerable to the negative effects of psychological distress: neuropsychiatric symptoms, such as anxiety and depression, are highly prevalent in PD; motor symptoms (such as tremor) typically worsen in stressful situations; and dopaminergic medication is less effective. Furthermore, animal studies of PD suggest that chronic stress may accelerate disease progression. Adequate self‐management strategies are therefore essential to reduce the detrimental effects of chronic stress on PD. Mindfulness‐based interventions encourage individuals to independently self‐manage and adapt to the challenges created by their condition. In PD, emerging clinical evidence suggests that mindfulness‐based interventions may reduce psychological distress and improve clinical symptoms, but insight into the underlying mechanisms is lacking. In this viewpoint, we provide a systematic overview of existing mindfulness trials in PD. Furthermore, we discuss the cerebral mechanisms involved in acute and chronic stress, and the impact of mindfulness‐based interventions on these networks. In addition, we delineate a hypothetical mechanistic framework of how chronic stress may increase the susceptibility for neuropsychiatric symptoms in PD and may potentially even influence disease progression. We end with offering recommendations for future research. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v36.1
    DOI: 10.1002/mds.28345
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 3
    Online Resource
    Online Resource
    The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?
    Wiley ; 2024
    In:  Movement Disorders Vol. 39, No. 2 ( 2024-02), p. 273-293
    Details
    In: Movement Disorders, Wiley, Vol. 39, No. 2 ( 2024-02), p. 273-293
    Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder for which only symptomatic treatments are available. Both preclinical and clinical studies suggest that moderate hypoxia induces evolutionarily conserved adaptive mechanisms that enhance neuronal viability and survival. Therefore, targeting the hypoxia response pathway might provide neuroprotection by ameliorating the deleterious effects of mitochondrial dysfunction and oxidative stress, which underlie neurodegeneration in PD. Here, we review experimental studies regarding the link between PD pathophysiology and neurophysiological adaptations to hypoxia. We highlight the mechanistic differences between the rescuing effects of chronic hypoxia in neurodegeneration and short‐term moderate hypoxia to improve neuronal resilience, termed “hypoxic conditioning”. Moreover, we interpret these preclinical observations regarding the pharmacological targeting of the hypoxia response pathway. Finally, we discuss controversies with respect to the differential effects of hypoxia response pathway activation across the PD spectrum, as well as intervention dosing in hypoxic conditioning and potential harmful effects of such interventions. We recommend that initial clinical studies in PD should focus on the safety, physiological responses, and mechanisms of hypoxic conditioning, as well as on repurposing of existing pharmacological compounds. © 2023 International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v39.2
    DOI: 10.1002/mds.29688
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2024
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  • 4
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    Online Resource
    Personalizing decision-making for persons with Parkinson’s disease: where do we stand and what to improve?
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Neurology Vol. 269, No. 7 ( 2022-07), p. 3569-3578
    Details
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 269, No. 7 ( 2022-07), p. 3569-3578
    Abstract: The large variety in symptoms and treatment effects across different persons with Parkinson’s disease (PD) warrants a personalized approach, ensuring that the best decision is made for each individual. We aimed to further clarify this process of personalized decision-making, from the perspective of medical professionals. Methods We audio-taped 52 consultations with PD patients and their neurologist or PD nurse-specialist, in 6 outpatient clinics. We focused coding of the transcripts on which decisions were made and on if and how decisions were personalized. We subsequently interviewed professionals to elaborate on how and why decisions were personalized, and which decisions would benefit most from a more personalized approach. Results Most decisions were related to medication, referral or lifestyle. Professionals balanced clinical factors, including individual (disease-) characteristics, and non-clinical factors, including patients’ preference, for each type of decision. These factors were often not explicitly discussed with the patient. Professionals experienced difficulties in personalizing decisions, mostly because evidence on the impact of characteristics of an individual patient on the outcome of the decision is unavailable. Categories of decisions for which professionals emphasized the importance of a more personalized perspective include choices not only for medication and advanced treatments, but also for referrals, lifestyle and diagnosis. Conclusions Clinical decision-making is a complex process, influenced by many different factors that differ for each decision and for each individual. In daily practice, it proves difficult to tailor decisions to individual (disease-) characteristics, probably because sufficient evidence on the impact of these individual characteristics on outcomes is lacking.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-022-10969-4
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1421299-7
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  • 5
    Online Resource
    Online Resource
    Home‐Based Monitoring of Falls Using Wearable Sensors in Parkinson's Disease
    Wiley ; 2020
    In:  Movement Disorders Vol. 35, No. 1 ( 2020-01), p. 109-115
    Details
    In: Movement Disorders, Wiley, Vol. 35, No. 1 ( 2020-01), p. 109-115
    Abstract: Falling is among the most serious clinical problems in Parkinson's disease (PD). We used body‐worn sensors (falls detector worn as a necklace) to quantify the hazard ratio of falls in PD patients in real life. Methods We matched all 2063 elderly individuals with self‐reported PD to 2063 elderly individuals without PD based on age, gender, comorbidity, and living conditions. We analyzed fall events collected at home via a wearable sensor. Fall events were collected either automatically using the wearable falls detector or were registered by a button push on the same device. We extracted fall events from a 2.5‐year window, with an average follow‐up of 1.1 years. All falls included were confirmed immediately by a subsequent telephone call. The outcomes evaluated were (1) incidence rate of any fall, (2) incidence rate of a new fall after enrollment (ie, hazard ratio), and (3) 1‐year cumulative incidence of falling. Results The incidence rate of any fall was higher among self‐reported PD patients than controls (2.1 vs. 0.7 falls/person, respectively; P   〈  .0001). The incidence rate of a new fall after enrollment (ie, hazard ratio) was 1.8 times higher for self‐reported PD patients than controls (95% confidence interval, 1.6–2.0). Conclusion Having PD nearly doubles the incidence of falling in real life. These findings highlight PD as a prime “falling disease.” The results also point to the feasibility of using body‐worn sensors to monitor falls in daily life. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v35.1
    DOI: 10.1002/mds.27830
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 6
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    Measuring Parkinson's disease over time: The real‐world within‐subject reliability of the MDS‐UPDRS
    Wiley ; 2019
    In:  Movement Disorders Vol. 34, No. 10 ( 2019-10), p. 1480-1487
    Details
    In: Movement Disorders, Wiley, Vol. 34, No. 10 ( 2019-10), p. 1480-1487
    Abstract: An important challenge in Parkinson's disease research is how to measure disease progression, ideally at the individual patient level. The MDS‐UPDRS, a clinical assessment of motor and nonmotor impairments, is widely used in longitudinal studies. However, its ability to assess within‐subject changes is not well known. The objective of this study was to estimate the reliability of the MDS‐UPDRS when used to measure within‐subject changes in disease progression under real‐world conditions. Methods Data were obtained from the Parkinson's Progression Markers Initiative cohort and included repeated MDS‐UPDRS measurements from 423 de novo Parkinson's disease patients (median follow‐up: 54 months). Subtotals were calculated for parts I, II, and III (in on and off states). In addition, factor scores were extracted from each part. A linear Gaussian state space model was used to differentiate variance introduced by long‐lasting changes from variance introduced by measurement error and short‐term fluctuations. Based on this, we determined the within‐subject reliability of 1‐year change scores. Results Overall, the within‐subject reliability ranged from 0.13 to 0.62. Of the subscales, parts II and III (OFF) demonstrated the highest within‐subject reliability (both 0.50). Of the factor scores, the scores related to gait/posture (0.62), mobility (0.45), and rest tremor (0.43) showed the most consistent behavior. Conclusions Our results highlight that MDS‐UPDRS change scores contain a substantial amount of error variance, underscoring the need for more reliable instruments to forward our understanding of the heterogeneity in PD progression. Focusing on gait and rest tremor may be a promising approach for an early Parkinson's disease population. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v34.10
    DOI: 10.1002/mds.27790
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 7
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    Translating Evidence to Advanced Parkinson's Disease Patients: A Systematic Review and Meta‐Analysis
    Wiley ; 2021
    In:  Movement Disorders Vol. 36, No. 6 ( 2021-06), p. 1293-1307
    Details
    In: Movement Disorders, Wiley, Vol. 36, No. 6 ( 2021-06), p. 1293-1307
    Abstract: In the advanced stages of Parkinson's disease (PD), patients frequently experience disabling motor complications. Treatment options include deep brain stimulation (DBS), levodopa‐carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI). Choosing among these treatments is influenced by scientific evidence, clinical expertise, and patient preferences. To foster patient engagement in decision‐making among the options, scientific evidence should be adjusted to their information needs. We conducted a systematic review from the patient perspective. First, patients selected outcomes for a treatment choice: quality of life, activities of daily living, ON and OFF time, and adverse events. Second, we conducted a systematic review and meta‐analysis for each treatment versus best medical treatment using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Finally, the evidence was transformed into comprehensible and comparable information. We converted the meta‐analysis results into the number of patients (per 100) who benefit clinically from an advanced treatment per outcome, based on the minimal clinically important difference and the cumulative distribution function. Although this approach allows for a comparison of outcomes across the three device‐aided therapies, they have never been compared directly. The interpretation is hindered by the relatively short follow‐up time in the included studies, usually less than 12 months. These limitations should be clarified to patients during the decision‐making process. This review can help patients integrate the evidence with their own preferences, and with their clinician's expertise, to reach an informed decision. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v36.6
    DOI: 10.1002/mds.28599
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2041249-6
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