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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 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.

The proactive inclusion of patients in the design and execution of clinical studies has been an emerging focus for decades. Such participatory research helps to design studies better, by addressing relevant research questions and defining outcomes that matter to patients. Yet, much remains to be learned about the best methods and exact impacts of patient engagement in research in general, and more specifically, about the specific challenges that come with Parkinson’s disease. Here we present the lived experiences of patient researchers living with Parkinson’s disease, as a motivation for the value of their perspectives in research and as a call to action for empirical research on how to successfully include patient researchers.

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. To explore needs of patients with PD in the palliative phase and of their family caregivers. 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. 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. 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.

Parkinson’s disease (PD) is an increasingly prevalent and progressive degenerative disease. Palliative care for PD should be integrated into the routine care for people with PD. However, PD health care professionals typically lack knowledge of palliative care, highlighting the necessity of educational programs in this field. To determine the effectiveness of a multidisciplinary blended learning program for health care professionals specialized in PD in the Netherlands. We used a pre-posttest intervention design. The intervention consisted of an e-learning in combination with an online network meeting in which the participating health care professionals discussed palliative care for PD with specialists from the field of palliative care. Outcome variables included self-rated level of knowledge (scale 1-10), familiarity with specialized palliative care services (5-point Likert scale) and the validated End-of-Life Professional Caregiver Survey (EPCS). A total of 1029 participants from sixteen different disciplines, all active in the care for people with PD, with a mean age of 45 years and 13 years of working experience, followed the blended learning program. Self-rated level of knowledge improved from 4.75 to 5.72 (0.96; p <  0.001; 95% CI change = [0.85 . . . 1.08]. Familiarity with palliative care services also increased by 1.06 (from 1.85 to 2.90; p=<0.001; 95% CI change = [1.00 . . . 1.12]). A blended learning program can improve self-rated knowledge about palliative care and its services. Such programs might be a first step towards optimal integration of palliative care expertise and services within PD-care.

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. We aim to identify factors that professionals deem important in deciding to a start disease-modifying treatment in the prodromal stage of PD. 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. 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. This study provides important insights in factors that influence decision making by professionals about starting treatment in the prodromal phase of PD.

The ongoing COVID-19 pandemic has many consequences for people with Parkinson’s disease (PD). Social distancing measures complicate regular care and result in lifestyle changes, which may indirectly cause psychological stress and worsening of PD symptoms. To assess whether the COVID-19 pandemic was associated with increased psychological distress and decreased physical activity in PD, how these changes related to PD motor and non-motor symptom severity, and what frequency and burden of COVID-related stressors were. We sent an online survey to the Personalized Parkinson Project (PPP) cohort (n = 498 PD patients) in the Netherlands. In the survey, we distinguished between COVID-related stressor load, psychological distress, PD symptom severity, and physical activity. We related inter-individual differences to personality factors and clinical factors collected before the pandemic occurred. 358 PD patients completed the survey between April 21 and May 25, 2020 (response rate 71.9%). Patients with higher COVID-related stressor load experienced more PD symptoms, and this effect was mediated by the degree of psychological distress. 46.6% of PD patients were less physically active since the COVID-19 pandemic, and reduced physical activity correlated with worse PD symptoms. Symptoms that worsened most were rigidity, fatigue, tremor, pain and concentration. Presence of neuropsychiatric symptoms (anxiety, depression) before the pandemic, as well as cognitive dysfunction and several personality traits predicted increased psychological distress during the COVID-19 pandemic. Our findings show how an external stressor (the COVID-19 pandemic) leads to a worsening of PD symptoms by evoking psychological distress as well as lifestyle changes (reduced physical activity).

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. 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. Ten bereaved family caregivers participated in this qualitative study. Semi-structured interviews were conducted and interpretative phenomenological analysis was used executed. 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. 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.

Shared decision-making (SDM) between clinicians and patients is a key component of patient experience, but measurement efforts have been hampered by a lack of valid and reliable measures that are feasible for routine use. In this study, we aim to investigate collaboRATE’s reliability, calculate required sample sizes for reliable measurement, and compare Consumer Assessment of Healthcare Providers and Systems (CAHPS) patient experience survey items to collaboRATE. CollaboRATE’s provider group-level reliability reached acceptable reliability at 190 patient reports, while the CAHPS SDM measure demonstrated similar reliability at a sample size of 124. The CAHPS communication measure reached acceptable reliability with 55 patient reports. A strong correlation was observed between collaboRATE and CAHPS communication measures (r= 0.83). As a reliable measure of SDM, collaboRATE may be useful for both building payment models that support shared clinical decision-making and encouraging data transparency with regard to provider group performance.

Patient characteristics have been linked to prevalence and quality of shared decision-making (SDM) behaviors across diverse studies of varied size and focus. We aim to evaluate the extent to which patient characteristics are associated with patient-rated SDM scores as measured by collaboRATE and whether or not collaboRATE varies at the provider group level. We used the 2017 California Patient Assessment Survey data set, which included adult patients of 153 California-based medical groups receiving services between January and October 2016. Mixed-effects logistic regression evaluated relationships between collaboRATE scores and patient characteristics. We analyzed 31 265 total survey responses. Among included covariates, patients’ health status, race, primary language, and mode of survey response were significantly associated with collaboRATE scores. Case-mix adjustment is common in healthcare quality measurement and can be useful in pay-for-performance systems. For those use cases, we recommend adjusting collaboRATE scores by patients’ age, health status, gender, race, and language spoken at home, and survey response mode. However, when case-mix adjustment is not required, we suggest highlighting observed disparities across diverse patient populations to improve attention to inequities in patient experience.

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 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.

Treatment of patients with late-stage parkinsonism is often sub-optimal. To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism. 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. 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. 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.

Potential interethnic differences in drug disposition and effects between Japanese and white subjects hamper the registration in Japan of medications already used in Western countries. This double‐blind, placebo‐controlled, crossover study was conducted to compare the pharmacodynamics and pharmacokinetics of a single oral dose of nitrazepam (5 mg) in age‐ and sex‐matched Japanese (n = 8) and white (n = 8) healthy volunteers. The study was performed in centers in Japan and the Netherlands using the same methods and study design. Subjects were individually matched for gender, age, and body stature. Drug effects were measured by means of saccadic and smooth pursuit eye movements and visual analog lines obtained from the scales of Bond and Lader. There were no pharmacokinetic differences between the Japanese and white subjects. Clearance of nitrazepam was 0.91 ± 0.165 mL/min/kg and 1.17 ± 0.492 mL/min/kg, and half‐life (t1/2) was 22.1 ± 4.96 hours and 21.5 ± 7.51 hours for the Japanese and European groups, respectively. Pharmacokinetic parameters showed no significant correlation with age, height, or weight. The average time‐effect curves for the different parameters were comparable between groups. Compared with placebo, both groups showed similar significant reductions in average peak velocity and increases in saccadic inaccuracy and reaction time. Visual analog scores showed clear sedation in the white subjects, but insignificant effects in the Japanese subjects. Smooth pursuit did not change significantly in either group. Slope and intercept of the concentration‐effect relationships for saccadic peak velocity showed considerable intersubject variability, but no clear differences between groups. The pharmacokinetics and pharmacodynamics of nitrazepam were similar in matched healthy Japanese and white subjects. Interethnic comparative studies are feasible, and provide meaningful information about potential racial differences in disposition and action of drugs. Such studies can form a rational basis for comparative clinical trials.

In an investigation comprising different morphometric and numerical data with regard to the nucleoli in smears of isolated parenchymal nuclei of rat liver cells, the following facts were established.1.Within the three different ploidy classes existing in adult animals, no correlation has been observed between the nucleolar projection area and the number of nucleoli per nucleus. A considerable overlap exists between the numbers of nucleoli in the diploid, tetraploid and octoploid class, so that it is not possible to classify the nuclei of the three classes on the number of nucleoli.2.The total nucleolar projection area per nucleus in a given ploidy class varies within rather narrow limits, independently of highly variable numbers of individual nucleoli. The means of these nucleolar areas in diploid, tetraploid and octoploid nuclei, showed virtually no deviation from an 1:2:4 ratio.3.The mean numbers of nucleoli in the livers of young adult animals (8 weeks of age) are 2.37, 5.02 and 10.08 for the 2n, 4n and 8n classes, respectively. In embryos and newborn animals, the modal number of nucleoli is 4 in the diploid nucleus, while the first appearing tetraploid and octoploid nuclei, later in development, show at first 8 and 16 nucleoli respectively, the mode of which number falls quickly afterwards. The reduction in nucleolar number, undoubtedly due to fusion, proceeds continuously up to old age: in rats of 21 months, the means are reduced to 1.45 (2n class), 2.66 (4n class) and 5.85 (8n class).