Background:Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson’s disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative... Show moreBackground:Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson’s disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim.Objective:To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery.Methods:Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function.Results:Eighty-three patients were included (median (interquartile range) age 63 (56–68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models.Conclusion:Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement. Show less
Van Hienen, M.M.; Kuiper, R.; Middelkoop, H.A.M.; Van Hilten, J.J.; Contarino, M.F.; Geraedts, V.J. 2022
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... Show moreBackground: 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. Show less
Lennaerts-Kats, H.; Ebenau, A.; Steen, J.T. van der; Munneke, M.; Bloem, B.R.; Vissers, K.C.P.; ... ; Groot, M.M. 2022
Background: Palliative care for persons with Parkinson's disease (PD) is developing. However, little is known about the experiences of patients with PD in the palliative phase and of their family... Show moreBackground: Palliative care for persons with Parkinson's disease (PD) is developing. However, little is known about the experiences of patients with PD in the palliative phase and of their family caregivers. Objective: To explore needs of patients with PD in the palliative phase and of their family caregivers. Methods: A mixed methods case study design. Health care professionals included patients for whom the answer on the question "Would you be surprised if this patient died in the next 12 months?" was negative. At baseline, and after six and twelve months, we conducted semi-structured interviews with patients and caregivers. Participants completed questionnaires on quality of life, disease burden, caregiver burden, grief, and positive aspects of caregiving. We analyzed quantitative data using descriptive statistics, while we used thematic analysis for qualitative data. Results: Ten patients and eight family caregivers participated, of whom five patients died during the study period. While the quantitative data reflected a moderate disease burden, the qualitative findings indicated a higher disease burden. Longitudinal results showed small differences and changes in time. Patients reported a diverse range of symptoms, such as fatigue, immobility, cognitive changes, and hallucinations, which had a tremendous impact on their lives. Nevertheless, they rated their overall quality of life as moderate to positive. Family caregivers gradually learned to cope with difficult situations such delirium, fluctuations in functioning and hallucinations. They had great expertise in caring for the person with PD but did not automatically share this with health care professionals. Patients sensed a lack of time to discuss their complex needs with clinicians. Furthermore, palliative care was rarely discussed, and none of these patients had been referred to specialist palliative care services. Conclusion: Patients with PD experienced many difficulties in daily living. Patients seems to adapt to living with PD as they rated their quality of life as moderate to positive. Family caregivers became experts in the care for their loved one, but often learned on their own. An early implementation of the palliative care approach can be beneficial in addressing the needs of patients with PD and their family caregivers. Show less
Background: Caregivers of Parkinson's disease (PD) patients provide important support during the pre- and postoperative phase of deep brain stimulation (DBS). High levels of caregiver burden have... Show moreBackground: Caregivers of Parkinson's disease (PD) patients provide important support during the pre- and postoperative phase of deep brain stimulation (DBS). High levels of caregiver burden have been reported after DBS. However, a comparison between preoperative and postoperative burden and associated factors has been insufficiently studied. Objective: To investigate the influence of DBS on caregiver burden, and to identify the differential impact of patient-related factors on caregiver burden before and after DBS. Methods: Consecutive patients referred for DBS eligibility screening or during one-year follow-up assessments were included. Caregiver burden was measured with the short Zarit Burden Interview (ZBI-12). Inverse Probability Weighting (IPW) was used to compare caregiver burden between preoperative and postoperative assessments. Results: We included 47 patients (24 screening, 23 follow-up) (median age 65 years, 29.4% female sex). DBS did not impact caregiver burden (screening: median ZBI-12 9.5 (IQR 3.25, 16.75); follow-up median ZBI-12 6 (IQR 4, 14); IPW-coefficient 0.57 (95% CI -2.75, 3.89)). Worse caregiver burden during DBS screening was associated with worse patient-related scores on depressive symptoms, anxiety, QoL, and impulsiveness. Worse scores on depressive symptoms, anxiety, apathy, postural-instability-gait-disorder, and QoL were associated with worse caregiver burden at one-year follow-up. Conclusion: DBS appears not associated with changes in caregiver burden. Various symptoms are valued differently between screening and follow-up assessments in terms of caregiver burden. Early recognition of caregivers "at risk" may improve guidance of patient-caregiver dyads throughout the DBS process. Show less
Heuvel, L. van den; Hoefsloot, W.; Post, B.; Meinders, M.J.; Bloem, B.R.; Stiggelbout, A.M.; Til, J.A. van 2022
Background: In Parkinson's disease (PD), several disease-modifying treatments are being tested in (pre-)clinical trials. To successfully implement such treatments, it is important to have insight... Show moreBackground: In Parkinson's disease (PD), several disease-modifying treatments are being tested in (pre-)clinical trials. To successfully implement such treatments, it is important to have insight into factors influencing the professionals' decision to start disease-modifying treatments in persons who are in the prodromal stage of PD.Objective: We aim to identify factors that professionals deem important in deciding to a start disease-modifying treatment in the prodromal stage of PD.Methods: We used a discrete choice experiment (DCE) to elicit preferences of neurologists and last-year neurology residents regarding treatment in the prodromal phase of PD. The DCE contained 16 hypothetical choice sets in which participants were asked to choose between two treatment options. The presented attributes included treatment effect, risk of severe side-effects, risk of mild side-effects, route of administration, and annual costs.Results: We included 64 neurologists and 18 last year neurology residents. Participants attached most importance to treatment effect and to the risk of severe side-effects. Participants indicated that they would discuss one of the presented treatments in daily practice more often in persons with a high risk of being in the prodromal phase compared to those with a moderate risk. Other important factors for deciding to start treatment included the amount of evidence supporting the putative treatment effect, the preferences of the person in the prodromal phase, and the life expectancy.Conclusion: This study provides important insights in factors that influence decision making by professionals about starting treatment in the prodromal phase of PD. Show less
Background: In Parkinson's disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential... Show moreBackground: In Parkinson's disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but their impact remains unclear with limited application in research or clinical practice.Objective: To critically evaluate PD subtyping systems.Methods: We conducted a systematic review of PD subtypes, assessing the characteristics of the studies reporting a subtyping system for the first time. We completed a critical appraisal of their methodologic quality and clinical applicability using standardized checklists.Results: We included 38 studies. The majority were cross-sectional (n = 26, 68.4%), used a data-driven approach (n = 25, 65.8%), and non-clinical biomarkers were rarely used (n = 5, 13.1%). Motor characteristics were the domain most commonly reported to differentiate PD subtypes. Most of the studies did not achieve the top rating across items of a Methodologic Quality checklist. In a Clinical Applicability Checklist, the clinical importance of differences between subtypes, potential treatment implications and applicability to the general population were rated poorly, and subtype stability over time and prognostic value were largely unknown.Conclusion: Subtyping studies undertaken to date have significant methodologic shortcomings and most have questionable clinical applicability and unknown biological relevance. The clinical and biological signature of PD may be unique to the individual, rendering PD resistant to meaningful cluster solutions. New approaches that acknowledge the individual-level heterogeneity and that are more aligned with personalized medicine are needed. Show less
Background: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa.Objective: To survey the accessible... Show moreBackground: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa.Objective: To survey the accessible MD clinical training in these regions.Methods: We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practice. Participants also shared their suggestions and needs.Results: The survey was completed in 31/49 countries. Structured postgraduate MD programs in neurology exist in 20 countries; structured neurology subspecialty training exists in 14 countries and is being developed in two additional countries. Certified neurology subspecialty training was reported to exist in 7 countries. Recommended reading lists, printed books, and other materials are the most popular educational tools, while courses, lectures, webinars, and case presentations are the most popular learning formats. Mandatory activities and skills to be certified were not defined in 15/31 countries. Most participants expressed their need for a mandatory postgraduate MD program and for certified MD sub-specialization programs in neurology.Conclusion: Certified postgraduate and subspecialty training exists only in a minority of European countries and was not found in the surveyed Egypt and Tunisia. MD training should be improved in many countries. Show less
Lennaerts-Kats, H.; Ebenau, A.; Steppe, M.; Steen, J.T. van der; Meinders, M.J.; Vissers, K.; ... ; Bloem, B.R. 2020
Background: Family caregivers provide the majority of care for people with Parkinson's disease (PD) in the palliative care phase. For many this is a demanding experience, affecting their quality of... Show moreBackground: Family caregivers provide the majority of care for people with Parkinson's disease (PD) in the palliative care phase. For many this is a demanding experience, affecting their quality of life.Objective: We set out to map the experiences of bereaved family caregivers during the period of informal care in the palliative care phase as well as after the death of their loved one with PD.Methods: Ten bereaved family caregivers participated in this qualitative study. Semi-structured interviews were conducted and interpretative phenomenological analysis was used executed.Results: We identified four main themes. 1) Feeling like a professional caregiver: while caring for a person with PD, the family caregivers took over many roles and tasks of the person with PD. 2) Healthcare professionals do not always know what PD really means: most interviewees had negative experiences with knowledge and understanding of PD of, especially, (practice) nurses. 3) Being on your own: many respondents had felt highly responsible for their loved one's care and lacked time and space for themselves. Grief and feelings of guilt were present during the caregiving period and after death. 4) Being behind the times: to provide palliative care in line with patients' preferences and to feel prepared for the palliative care phase of PD, proactive palliative care planning was considered important. However, the interviewees told that this was most often not provided.Conclusion: These findings indicate that caring for a person with PD in the palliative care phase is a demanding experience for family caregivers. They experience psychological problems for many years before and after the death of the person with PD. Increasing healthcare professionals' awareness of family and bereaved caregivers' needs may mitigate these long-term detrimental effects. Show less
Orthostatic hypotension (OH) is a common non-motor feature of Parkinson's disease that may cause unexplained falls, syncope, lightheadedness, cognitive impairment, dyspnea, fatigue, blurred vision,... Show moreOrthostatic hypotension (OH) is a common non-motor feature of Parkinson's disease that may cause unexplained falls, syncope, lightheadedness, cognitive impairment, dyspnea, fatigue, blurred vision, shoulder, neck, or low-back pain upon standing. Blood pressure (BP) measurements supine and after 3 minutes upon standing screen for OH at bedside. The medical history and cardiovascular autonomic function tests ultimately distinguish neurogenic OH, which is due to impaired sympathetic nerve activity, from non-neurogenic causes of OH, such as hypovolemia and BP lowering drugs. The correction of non-neurogenic causes and exacerbating factors, lifestyle changes and non-pharmacological measures are the cornerstone of OH treatment. If these measures fail, pharmacological interventions (sympathomimetic agents and/or fludrocortisone) should be introduced stepwise depending on the severity of symptoms. About 50% of patients with neurogenic OH also suffer from supine and nocturnal hypertension, which should be monitored for with in-office, home and 24 h-ambulatory BP measurements. Behavioral measures help prevent supine hypertension, which is eventually treated with non-pharmacological measures and bedtime administration of short-acting anti-hypertensive drugs in severe cases. If left untreated, OH impacts on activity of daily living and increases the risk of syncope and falls. Supine hypertension is asymptomatic, but often limits an effective treatment of OH, increases the risk of hypertensive emergencies and, combined with OH, facilitates end-organ damage. A timely management of both OH and supine hypertension ameliorates quality of life and prevents short and long-term complications in patients with Parkinson's disease. Show less
Heuvel, L. van den; Dorsey, R.R.; Prainsack, B.; Post, B.; Stiggelbout, A.M.; Meinders, M.J.; Bloem, B.R. 2020
Clinical decision making for Parkinson's disease patients is supported by a combination of three distinct information resources: best available scientific evidence, professional expertise, and the... Show moreClinical decision making for Parkinson's disease patients is supported by a combination of three distinct information resources: best available scientific evidence, professional expertise, and the personal needs and preferences of patients. All three sources have clear value but also share several important limitations, mainly regarding subjectivity, generalizability and variability. For example, current scientific evidence, especially from controlled clinical trials, is often based on selected study populations, making it difficult to translate the outcome to the care for individual patients in everyday clinical practice. Big data, including data from real-life unselected Parkinson populations, can help to bridge this information gap. Fine-grained patient profiles created from big data have the potential to aid in identifying therapeutic approaches that will be most effective given each patient's individual characteristics, which is particularly important for a disorder characterized by such tremendous interindividual variability as Parkinson's disease. In this viewpoint, we argue that big data approaches should be acknowledged and harnessed, not to replace existing information resources, but rather as a fourth and complimentary source of information in clinical decision making, helping to represent the full complexity of individual patients. We introduce the `quadruple decision making' model and illustrate its mode of action by showing how this can be used to pursue precision medicine for persons living with Parkinson's disease. Show less
Schipper, L.J. de; Hafkemeijer, A.; Grond, J. van der; Marinus, J.; Henselmans, J.M.L.; Hilten, J.J. van 2019
