The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?

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.

Randomized controlled trial of intermittent hypoxia 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 repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms. The current study aims to explore the safety, tolerability, feasibility, and net symptomatic effects of a four-week intermittent hypoxia protocol, administered at home, in individuals with PD. METHODS/DESIGN: This is a two-armed double-blinded randomized controlled trial involving 40 individuals with mild to moderate PD. Participants will receive 45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks. Co-primary endpoints include nature and total number of adverse events, and a feasibility-tolerability questionnaire. Secondary endpoints include Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II and III scores, gait tests and biomarkers indicative of hypoxic dose and neuroprotective pathway induction. DISCUSSION: This trial builds on the previous phase I trial and aims to investigate the safety, tolerability, feasibility, and net symptomatic effects of intermittent hypoxia in individuals with PD. Additionally, the study aims to explore induction of relevant neuroprotective pathways as measured in plasma. The results of this trial could provide further insight into the potential of hypoxia-based therapy as a novel treatment approach for PD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05948761 (registered June 20th, 2023).

Caregiver burden in Parkinson's disease: a mixed-methods study.

BACKGROUND: Providing informal care for a person with Parkinson's disease (PD) can be a demanding process affecting several dimensions of a caregiver's life and potentially causing caregiver burden. Despite the emerging literature on caregiver burden in people with PD, little is known about the inter-relationship between quantitative and qualitative findings. Filling this knowledge gap will provide a more holistic approach to develop and design innovations aiming at reducing or even preventing caregiver burden. This study aimed to characterize the determinants of caregiver burden among informal caregivers of persons with PD, in order to facilitate the development of tailored interventions that reduce caregiver burden. METHODS: We conducted a cross-sectional study in The Netherlands using a sequential mixed methods approach, entailing a quantitative study of 504 persons with PD and their informal caregivers as well as a qualitative study in a representative subsample of 17 informal caregivers. The quantitative study included a standardized questionnaire of caregiver burden (Zarit Burden Inventory) and patient-related (Beck Depression Inventory, State-Trait Anxiety Inventory, Acceptance of Illness Scale, MDS-Unified Parkinson's Disease Rating Scale part II on motor functions in daily life, Self-assessment Parkinson's Disease Disability Score), caregiver-related (Brief Coping Orientation to Problems Experience Inventory, Caregiver Activation Measurement, Multidimensional Scale of Perceived Social Support) and interpersonal determinants (sociodemographic variables including among others gender, age, education, marital status and working status). The qualitative study consisted of semi-structured interviews. Multivariable regression and thematic analysis were used to analyse quantitative and qualitative data, respectively. RESULTS: A total of 337 caregivers were women (66.9%), and the majority of people with PD were men (N = 321, 63.7%). The mean age of persons with PD was 69.9 (standard deviation [SD] 8.1) years, and the mean disease duration was 7.2 (SD 5.2) years. A total of 366 (72.6%) persons with PD had no active employment. The mean age of informal caregivers was 67.5 (SD 9.2) years. Most informal caregivers were female (66.9%), had no active employment (65.9%) and were the spouse of the person with PD (90.7%). The mean Zarit Burden Inventory score was 15.9 (SD 11.7). The quantitative study showed that a lack of active employment of the person affected by PD was associated with a higher caregiver burden. The qualitative study revealed cognitive decline and psychological or emotional deficits of the person with PD as additional patient-related determinants of higher caregiver burden. The following caregiver-related and interpersonal determinants were associated with higher caregiver burden: low social support (quantitative study), concerns about the future (qualitative study), the caregiving-induced requirement of restrictions in everyday life (qualitative study), changes in the relationship with the person with PD (qualitative study) and a problem-focused or avoidant coping style (both studies). Integration of both data strands revealed that qualitative findings expanded quantitative findings by (1) distinguishing between the impact of the relationship with the person with PD and the relationship with others on perceived social support, (2) revealing the impact of non-motor symptoms next to motor symptoms and (3) revealing the following additional factors impacting caregiver burden: concern about the future, perceived restrictions and limitations in performing daily activities due to the disease, and negative feelings and emotional well-being. Qualitative findings were discordant with the quantitative finding demonstrating that problem-focused was associated with a higher caregiver burden. Factor analyses showed three sub-dimensions of the Zarit Burden Inventory: (i) role intensity and resource strain, (2) social restriction and anger and (3) self-criticism. Quantitative analysis showed that avoidant coping was a determinant for all three subscales, whereas problem-solved coping and perceived social support were significant predictors on two subscales, role intensity and resource strain and self-criticism. CONCLUSIONS: The burden experienced by informal caregivers of persons with PD is determined by a complex interplay of patient-related, caregiver-related and interpersonal characteristics. Our study highlights the utility of a mixed-methods approach to unravel the multidimensional burden experienced by informal caregivers of persons with chronic disease. We also offer starting points for the development of a tailored supportive approach for caregivers.

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 ß. 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).

Perspectives of people living with Parkinson's disease on personalized prediction models.

BACKGROUND: There is a great need for the development of personalized prediction models (PPMs) that can predict the rate of disease progression for persons with Parkinson's disease (PD), based on their individual characteristics. In this study, we aimed to clarify the perspective of persons diagnosed with PD on the value of such hypothetical PPMs. METHODS: We organized four focus group discussions, each including five persons with PD who were diagnosed within the last 5 years. The sessions focused on what they think of receiving a personalized prediction; what outcomes are important to them; if and how the possibility of influencing the prognosis would change the way they think of personalized predictions; how they deal with the uncertainty from a PPM; and what barriers and facilitators they expect for using a PPM. RESULTS: The wish of persons with PD for receiving personalized prognostic information was highly heterogenous, for various reasons. Most persons with PD would like to receive more personalized prognostic information, mainly to better prepare themselves and their loved ones for the future. The prediction provided should be as personalized as possible, and there should be adequate supervision and coaching by a professional when providing the information. They were particularly interested in receiving prognostic information when their interventions would be available that could subsequently influence the identified prognostic factor and thereby affect the disease course beneficially. CONCLUSION: Most persons with PD in this study want more insight into their own future by means of prediction models, provided that this is explained and supervized properly by professionals. PATIENT OR PUBLIC CONTRIBUTION: Two patient-researchers were involved in the study design, conduct of the study, interpretation of the data and in preparation of the manuscript.

The state of telemedicine for persons with Parkinson's disease.

PURPOSE OF REVIEW: The COVID-pandemic has facilitated the implementation of telemedicine in both clinical practice and research. We highlight recent developments in three promising areas of telemedicine: teleconsultation, telemonitoring, and teletreatment. We illustrate this using Parkinson's disease as a model for other chronic neurological disorders. RECENT FINDINGS: Teleconsultations can reliably administer parts of the neurological examination remotely, but are typically not useful for establishing a reliable diagnosis. For follow-ups, teleconsultations can provide enhanced comfort and convenience to patients, and provide opportunities for blended and proactive care models. Barriers include technological challenges, limited clinician confidence, and a suboptimal clinician-patient relationship. Telemonitoring using wearable sensors and smartphone-based apps can support clinical decision-making, but we lack large-scale randomized controlled trials to prove effectiveness on clinical outcomes. Increasingly many trials are now incorporating telemonitoring as an exploratory outcome, but more work remains needed to demonstrate its clinical meaningfulness. Finding a balance between benefits and burdens for individual patients remains vital. Recent work emphasised the promise of various teletreatment solutions, such as remotely adjustable deep brain stimulation parameters, virtual reality enhanced exercise programs, and telephone-based cognitive behavioural therapy. Personal contact remains essential to ascertain adherence to teletreatment. SUMMARY: The availability of different telemedicine tools for remote consultation, monitoring, and treatment is increasing. Future research should establish whether telemedicine improves outcomes in routine clinical care, and further underpin its merits both as intervention and outcome in research settings.

Translating Evidence to Advanced Parkinson's Disease Patients: A Systematic Review and Meta-Analysis.

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.

Stress and Mindfulness in Parkinson's Disease: Clinical Effects and Potential Underlying Mechanisms.

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.

Estimating the Effect of Early Treatment Initiation in Parkinson's Disease Using Observational Data.

BACKGROUND: 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.

Evaluation of a shared decision-making strategy with online decision aids in surgical and orthopaedic practice: study protocol for the E-valuAID, a multicentre study with a stepped-wedge design.

BACKGROUND: Inguinal hernia repair, gallbladder removal, and knee- and hip replacements are the most commonly performed surgical procedures, but all are subject to practice variation and variable patient-reported outcomes. Shared decision-making (SDM) has the potential to reduce surgery rates and increase patient satisfaction. This study aims to evaluate the effectiveness of an SDM strategy with online decision aids for surgical and orthopaedic practice in terms of impact on surgery rates, patient-reported outcomes, and cost-effectiveness. METHODS: The E-valuAID-study is designed as a multicentre, non-randomized stepped-wedge study in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis in six surgical and six orthopaedic departments. The primary outcome is the surgery rate before and after implementation of the SDM strategy. Secondary outcomes are patient-reported outcomes and cost-effectiveness. Patients in the usual care cluster prior to implementation of the SDM strategy will be treated in accordance with the best available clinical evidence, physician's knowledge and preference and the patient's preference. The intervention consists of the implementation of the SDM strategy and provision of disease-specific online decision aids. Decision aids will be provided to the patients before the consultation in which treatment decision is made. During this consultation, treatment preferences are discussed, and the final treatment decision is confirmed. Surgery rates will be extracted from hospital files. Secondary outcomes will be evaluated using questionnaires, at baseline, 3 and 6 months. DISCUSSION: The E-valuAID-study will examine the cost-effectiveness of an SDM strategy with online decision aids in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis. This study will show whether decision aids reduce operation rates while improving patient-reported outcomes. We hypothesize that the SDM strategy will lead to lower surgery rates, better patient-reported outcomes, and be cost-effective. TRIAL REGISTRATION: The Netherlands Trial Register, Trial NL8318, registered 22 January 2020. URL: https://www.trialregister.nl/trial/8318 .

Home-based monitoring of falls using wearable sensors in Parkinson's disease.

INTRODUCTION: 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.

The association between patients' preferred treatment after the use of a patient decision aid and their choice of eventual treatment.

OBJECTIVE: To investigate the association between patients' preferred treatment and eventual treatment. Second, to compare patients with surgical treatment to watchful waiting in order to identify predictive factors for surgery. METHODS: A single-centre retrospective study was performed between December 2015 and August 2018. Patients (≥18 years) who used a patient decision aid (PDA) for gallstones or inguinal hernia were included. After their first surgical consultation, patients received access to an online PDA. The patients' preferred treatment after the PDA was compared with their choice of eventual treatment. Multivariable regression analyses were performed for predictive factors for surgery. RESULTS: In total, 567 patients with gallstones and 585 patients with an inguinal hernia were included. Of the patients with gallstones, 121 (21%) preferred watchful waiting, 367 (65%) preferred surgery, and 79 (14%) were not sure. The patients' preferred treatment was performed in 85.9%. Frequent pain attacks (OR 2.1, 95% CI 1.1-3.9, P = .020) and preference for surgery (OR 4.4, 95% CI 1.9-10.1, P = .001) independently predicted surgery. Of the patients with an inguinal hernia, 77 (13.2%) preferred watchful waiting, 452 (78.8%) preferred surgery, and 56 (9.6%) were not sure. The patients' preferred treatment was performed in 86.0%. The preference for surgery (OR 5.2, 95% CI 2.5-10.6, P < .001) independently predicted surgery and worry about complications predicted avoidance of surgery (OR 0.5, 95% CI 0.2-1.0, P = .037). CONCLUSION: This study, reflecting current clinical care, shows that patients' preferred treatment after using a PDA matches their eventual treatment choice in 86% of patients with gallstones or an inguinal hernia. In these patients, symptoms and patients' preference for surgery independently predicts eventual choice of surgery.

Real-Life Gait Performance as a Digital Biomarker for Motor Fluctuations: The Parkinson@Home Validation Study.

BACKGROUND: Wearable sensors have been used successfully to characterize bradykinetic gait in patients with Parkinson disease (PD), but most studies to date have been conducted in highly controlled laboratory environments. OBJECTIVE: This paper aims to assess whether sensor-based analysis of real-life gait can be used to objectively and remotely monitor motor fluctuations in PD. METHODS: The Parkinson@Home validation study provides a new reference data set for the development of digital biomarkers to monitor persons with PD in daily life. Specifically, a group of 25 patients with PD with motor fluctuations and 25 age-matched controls performed unscripted daily activities in and around their homes for at least one hour while being recorded on video. Patients with PD did this twice: once after overnight withdrawal of dopaminergic medication and again 1 hour after medication intake. Participants wore sensors on both wrists and ankles, on the lower back, and in the front pants pocket, capturing movement and contextual data. Gait segments of 25 seconds were extracted from accelerometer signals based on manual video annotations. The power spectral density of each segment and device was estimated using Welch's method, from which the total power in the 0.5- to 10-Hz band, width of the dominant frequency, and cadence were derived. The ability to discriminate between before and after medication intake and between patients with PD and controls was evaluated using leave-one-subject-out nested cross-validation. RESULTS: From 18 patients with PD (11 men; median age 65 years) and 24 controls (13 men; median age 68 years), ≥10 gait segments were available. Using logistic LASSO (least absolute shrinkage and selection operator) regression, we classified whether the unscripted gait segments occurred before or after medication intake, with mean area under the receiver operator curves (AUCs) varying between 0.70 (ankle of least affected side, 95% CI 0.60-0.81) and 0.82 (ankle of most affected side, 95% CI 0.72-0.92) across sensor locations. Combining all sensor locations did not significantly improve classification (AUC 0.84, 95% CI 0.75-0.93). Of all signal properties, the total power in the 0.5- to 10-Hz band was most responsive to dopaminergic medication. Discriminating between patients with PD and controls was generally more difficult (AUC of all sensor locations combined: 0.76, 95% CI 0.62-0.90). The video recordings revealed that the positioning of the hands during real-life gait had a substantial impact on the power spectral density of both the wrist and pants pocket sensor. CONCLUSIONS: We present a new video-referenced data set that includes unscripted activities in and around the participants' homes. Using this data set, we show the feasibility of using sensor-based analysis of real-life gait to monitor motor fluctuations with a single sensor location. Future work may assess the value of contextual sensors to control for real-world confounders.

Measuring Parkinson's disease over time: The real-world within-subject reliability of the MDS-UPDRS.

BACKGROUND: 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.

Reduced Elective Operation Rates and High Patient Satisfaction After the Implementation of Decision Aids in Patients with Gallstones or an Inguinal Hernia.

BACKGROUND: For both gallbladder removal and inguinal hernia repair, it is important to include patients' perspective in the decision-making process, as watchful waiting is an accepted alternative in selected patients. The aim of this study was to evaluate operation rates before and after implementation of decision aids (DAs) and to assess patient compliance with the use of DAs. METHODS: A single-centered retrospective study was performed, including all patients ≥18 years referred to the surgical outpatient clinic with symptomatic gallstones or an inguinal hernia between January 2014 and December 2017. Operation rates before and after implementation of DAs (December 2015) were compared. In addition, patient compliance with the use of DAs and satisfaction with final treatment were assessed. RESULTS: Overall, 1625 patients with gallstones and 1798 patients with an inguinal hernia were included. After implementation, DAs were provided to 512 patients (63.1%) with gallstones of whom 80.7% (413/512) used the DA and to 528 patients (58.8%) with an inguinal hernia, which was used by 80.7% (426/528). Before implementation, the operation rate in patients with gallstones was 72.0% (586/814) and after implementation 56.7% (460/811) (- 15.3%, p < 0.001). The operation rate in patients with an inguinal hernia decreased from 77.8% (700/900) to 64.6% (580/898) (- 13.2%, p < 0.001). Patient satisfaction with final treatment was high (9/10). CONCLUSION: Implementation of DAs in the surgical outpatient clinic for patients with gallstones or an inguinal hernia is associated with reduced elective operation rates and is associated with high DA compliance.

Implementation of the three good questions-A feasibility study in Dutch hospital departments.

OBJECTIVES: To determine the feasibility of pragmatic implementation strategies for three good questions (in Dutch: Drie Goede Vragen; 3GV. What are my options; what are the risks and benefits related to these options; and what does this mean for my situation?) to increase shared decision-making (SDM) efforts in Dutch secondary care, and identify barriers and facilitators of implementation. METHODS: Convergent mixed-method design: pre-post surveys with patients attending one of six clinical departments in a Dutch Hospital, post-intervention interviews with patients and health-care professionals. Primary outcomes: feasibility (reach, use of 3GV). SECONDARY OUTCOMES: SDM, experiences with 3GV and decision making. Interviews focused on barriers and facilitators of 3GV use. Interviews were content coded and categorized into determinants of behaviour change. RESULTS: 35% of the respondents who had heard of 3GV (52%) used all three questions. 3GV use did not lead to more SDM (SDMQ9 M = Δ0.3;SE = 2.2) but patients felt empowered to decide (88%) and to SDM (86%). Barriers were as follows: time investment, other SDM projects and perception that the need to use 3GV differs per patient/consultation. Respondents preferred to use 3GV as they saw fit for the consultation, instead of literally asking them. Facilitators: easy, accessible information materials that can be flexibly used. CONCLUSION: Implementation of 3GV seemed feasible, although influenced by contextual characteristics (eg type of decisions, patients, on-going interventions). 3GV contributed to important elements of SDM, and respondents were willing to apply them in a way that suited their situation. PRACTICE IMPLICATIONS: We recommend continuation of current and new implementation strategies to enable 3GV implementation in secondary care.

Palliative care for persons with Parkinson's disease: a qualitative study on the experiences of health care professionals.

BACKGROUND: Parkinson's disease (PD) is a chronic and neurodegenerative disease associated with a wide variety of symptoms. The risk of complications increases with progression of the disease. These complications have a tremendous impact on the quality of life of people with PD. The aim of this study was to examine health care professionals' experiences of potential barriers and facilitators in providing palliative care for people with PD in the Netherlands. METHODS: This was a qualitative descriptive study. The data were collected from 10 individual in-depth interviews and three focus groups (n = 29) with health care professionals. Health care professionals were selected based on a positive answer to the question: "In the past 2 years, did you treat or support a person with PD who subsequently died?" The data were analyzed by thematic text analysis. RESULTS: Health care professionals supported the development of a palliative care system for PD but needed to better understand the essence of palliative care. In daily practice, they struggled to identify persons' needs due to interfering PD-specific symptoms such as cognitive decline and communication deficits. Timely addressing the personal preferences for providing palliative care was identified as an important facilitator. Health care professionals acknowledged being aware of their lack of knowledge and of their little competence in managing complex PD. Findings indicate a perceived lack of care continuity, fragmentation of services, time pressure and information discontinuity. CONCLUSIONS: Health care professionals experienced several facilitators and barriers to the provision of palliative care to people with PD. There is a need to improve the knowledge on complex PD and the continuity of information, as well as optimize coordination and deliver care based on a persons' preferences. Additional training can help to become more knowledgeable and confident.

Unveiling the invisible: a qualitative interview study on the impact of young onset Parkinson's disease on (ex-partners).

INTRODUCTION: Living with young onset Parkinson's disease (YOPD) not only affects the persons with YOPD, but also their families. Although caregiver burden has been researched in Parkinson's disease in general, little is known about the specific impact of having an (ex-)partner with YOPD. This exploratory study aimed to explore the impact of having an (ex-)partner with YOPD on daily life. MATERIALS AND METHODS: We used a qualitative approach including semi-structured interviews with 16 (ex-)partners of people with YOPD. Interviews were audio-taped and transcribed verbatim. Qualitative thematic analysis was used to analyze the interview data. RESULTS: Qualitative analysis revealed nine themes to describe the impact of having an (ex-)partner with YOPD: (1) Psychosocial impact, (2) Impact on taking care of children, (3) Impact on working life, (4) Impact on intimacy and (sexual) relationships, (5) Impact on daily life, (6) Acceptance and other coping strategies, (7) Thoughts about the future, (8) Autonomy and (9) Caregiver support. DISCUSSION: This study provides important findings that will inform future interventions that aim to reduce or even prevent caregiver burden, as well as to inform healthcare professionals to recognize the needs of caregivers of people with YOPD.