Exercise for people with Parkinson's: a practical approach.

Exercise is key to a healthy and productive life. For people with Parkinson's, exercise has reported benefits for controlling motor and non-motor symptoms alongside the use of pharmacological intervention. For example, exercise prolongs independent mobility and improves sleep, mood, memory and quality of life, all further enhanced through socialisation and multidisciplinary team support. Recent research suggests that optimally prescribed exercise programmes following diagnosis may alter neurophysiological processes, possibly slowing symptom progression.Given its benefits, professionals should encourage and motivate people with Parkinson's to exercise regularly from the time of diagnosis and provide guidance on what exercise to do. We provide examples of how the growing body of evidence on exercise for people with Parkinson's is revolutionising the services they are provided. We also highlight new resources available to help the wider support network (people such as volunteers, partners and friends of people with Parkinson's) with an interest in exercise promote a consistent message on the benefits of exercise. [Abstract copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A modular, deep learning-based holistic intent sensing system tested with Parkinson’s disease patients and controls

People living with mobility-limiting conditions such as Parkinson’s disease can struggle to physically complete intended tasks. Intent-sensing technology can measure and even predict these intended tasks, such that assistive technology could help a user to safely complete them. In prior research, algorithmic systems have been proposed, developed and tested for measuring user intent through a Probabilistic Sensor Network, allowing multiple sensors to be dynamically combined in a modular fashion. A time-segmented deep-learning system has also been presented to predict intent continuously. This study combines these principles, and so proposes, develops and tests a novel algorithm for multi-modal intent sensing, combining measurements from IMU sensors with those from a microphone and interpreting the outputs using time-segmented deep learning. It is tested on a new data set consisting of a mix of non-disabled control volunteers and participants with Parkinson’s disease, and used to classify three activities of daily living as quickly and accurately as possible. Results showed intent could be determined with an accuracy of 97.4% within 0.5 s of inception of the idea to act, which subsequently improved monotonically to a maximum of 99.9918% over the course of the activity. This evidence supports the conclusion that intent sensing is viable as a potential input for assistive medical devices

Stroke in Devon: knowledge was good, but action was poor.

BACKGROUND AND AIM: Effective implementation of early treatment strategies for stroke requires prompt admission to hospital. There are several reasons for delayed admission. Good awareness should facilitate early admission. We identified local targets for education. METHODS: Four groups, each of 40 people, completed questionnaires to determine their knowledge of stroke symptoms and risk factors, and the action they took or would take in the event of a stroke. The groups were: patients with a diagnosis of stroke or TIA (within 48 hrs of admission); patients at risk of stroke; the general population; and nurses. RESULTS: Forty per cent of stroke patients identified their stroke. Median time from onset of symptoms to seeking medical help was 30 minutes. Medical help was sought by the patient themselves in only 15% of cases. In 80% of cases the GP was called rather than an ambulance. Of the at risk group, 93% were able to list at least one symptom of acute stroke, as were 88% of the general population. An ambulance would be called by 73% of the at risk group in the event of a stroke. Patients with self reported risk factors for stroke were largely unaware of their increased risk. Only 7.5% of at risk patients acquired their stroke information from the medical profession. CONCLUSIONS: Public knowledge about stroke is good. However, stroke patients access acute services poorly. At risk patients have limited awareness of their increased risk. A campaign should target people at risk, reinforcing the diagnosis of stroke and access to medical services

Co-designing resources for knowledge based self-reflection for people living with Parkinson’s disease to better enable independent living [abstract only]

Summary Parkinson’s disease (PD) is a complex progressive neurodegenerative disease. Individuals experience PD in a variety of ways, leading to difficulty in diagnosis, acceptance and on-going management. Service provision is complex, with provider variation, often lacking ‘joined up’ provision between acute hospital and community care. This project utilised a co-design methodology to identify patient and provider needs for PD services in the Plymouth NHS Trust and develop tools, resources and service structures to meet these needs. The application of co-design in healthcare settings is fraught by challenges of power dynamics between healthcare professionals and ‘patients’. We were mindful of this throughout our process. Further, the tools and resources were intended to facilitate independent living for people with PD, yet importantly, enable them to do so from an informed position. This resulted in resources facilitating both the mobilisation of complex knowledge and self-reflection. Method Participants included: People living with Parkinson’s and their families and carers, Parkinson’s Specialist Nurses, Community care teams, Therapy Specialists, Consultant Neurologists, Finance officer, Parkinson’s Charity representatives and health services researchers from Plymouth and Exeter Universities. The co-design process was structured around five co-design workshops. 1. Initiating the collaboration: Lego Serious Play 2. Understanding the Service: Service Journey Mapping, Personas, Disease Trajectory Models, Ideal Service Maps 3. Ideas, Development, Prioritisation and Prototyping: Ideation Games, Mock-ups, Body Storming, Role Plays, Prioritisation 4. Design ‘Hack’: Prototyping 5. Presentation of prototypes, testing and planning Prior to, between and after each workshop, design studio activities were: 1. Planning and preparation 2. Data recording and analysis: interrogating the data as designers 3. Reflection: reflecting on the data and workshop as design researchers 4. Making: making resources, data collection tools and prototypes 5. Communication: ongoing communication with participants Results Five concepts developed were: a Parkinson’s Patient passport, New service and local information; a media campaign; a card deck to support self-reflection; a self-management support and general information package. Of these, the media campaign was paused awaiting national charity support. The other four concepts became the Home-based care pathway through a process of four further co-design workshops. They are being trialled with 150 patients in the South West region. Discussion Within healthcare, one of the biggest challenges is getting new ideas into practice (Greenhalgh and Wieringa, 2011). Coproduction is offered as a possible mechanism for addressing issues that cause this (Greenhalgh et al, 2016). However, the predominant epistemology in health services research devalues the voices of professionals and patients. It is questionable whether ‘real’ coproduction can happen whilst such hierarchies of evidence exist (Rose & Kalathil, 2019). We have suggested that the creative practices of design (Langley et al, 2018) used within co-design processes reduce or even remove these hierarchies, enabling effective embodiment (within prototypes) of experiential knowledge of professionals and patients and the latest scientific research knowledge. Since outputs of co-design processes embody these different forms of knowledge (Rycroft-Malone et al., 2004), they become easier to implement; reducing the translation gap. Framing design and co-design in this way (as a knowledge creation and mobilization process) has been effective for the authors, enabling them to work easily with healthcare professionals and health services researchers. It is a ‘lens’ they understand and appreciate the value of. We encourage other designers working in this space to consider framing their work in this way. Designers using co-design are also encouraged to consider their process in this way; as one of eliciting and embodying experiential knowledge of users, and service providers along with contextual knowledge and the latest research evidence from the relevant field. This can support ‘evidence-informed’ design outputs without stifling creativity and imagination

An International Multi-Stakeholder Delphi Survey Study on the Design of Disease Modifying Parkinson’s Disease Trials

Background: Design of disease modification (DM) trials for Parkinson’s disease (PD) is challenging. Successful delivery requires a shared understanding of priorities and practicalities. Objective: To seek stakeholder consensus on phase 3 trials’ overall goals and structure, inclusion criteria, outcome measures, and trial delivery and understand where perspectives differ. Methods: An international expert panel comprising people with Parkinson’s (PwP), care partners (CP), clinical scientists, representatives from industry, funders and regulators participated in a survey-based Delphi study. Survey items were informed by a scoping review of DM trials and PwP input. Respondents scored item agreement over 3 rounds. Scores and reasoning were summarized by participant group each round until consensus, defined as≥70% of at least 3 participant groups falling within the same 3-point region of a 9-point Likert scale. Results: 92/121 individuals from 13 countries (46/69 PwP, 13/18 CP, 20/20 clinical scientists, representatives from 8/8 companies, 4/5 funders, and 1/1 regulator) completed the study. Consensus was reached on 14/31 survey items: 5/8 overall goals and structure, 1/8 Eligibility criteria, 7/13 outcome measures, and 1/2 trial delivery items. Extent of stakeholder endorsement for 428 reasons for scores was collated across items. Conclusions: This is the first systematic multi-stakeholder consultation generating a unique repository of perspectives on pivotal aspects of DM trial design including those of PwP and CP. The panel endorsed outcomes that holistically measure PD and the importance of inclusive trials with hybrid delivery models. Areas of disagreement will inform mitigating strategies of researchers to ensure successful delivery of future trials

Noninvasive options for 'wearing-off' in Parkinson's disease: a clinical consensus from a panel of UK Parkinson's disease specialists

In the past 4 years, two adjunctive treatment options to levodopa have been licensed for use in the UK in patients with Parkinson's disease (PD) and motor fluctuations: opicapone, a third-generation catechol-O-methyl transferase inhibitor, and safinamide, a monoamine oxidase B inhibitor. This clinical consensus outlines the practical considerations relating to motor fluctuations and managing wearing-off in patients with PD, and provides a clinical insight to adjunctive treatment options, including opicapone and safinamide. Practice-based opinion was provided from a multidisciplinary steering Group of eight UK-based movement disorder and PD specialists, including neurologists, geriatricians and a nurse specialist, from England, Scotland and Wales

Genome-wide Analysis of Motor Progression in Parkinson Disease

BACKGROUND AND OBJECTIVES: The genetic basis of Parkinson disease (PD) motor progression is largely unknown. Previous studies of the genetics of PD progression have included small cohorts and shown a limited overlap with genetic PD risk factors from case-control studies. Here, we have studied genomic variation associated with PD motor severity and early-stage progression in large longitudinal cohorts to help to define the biology of PD progression and potential new drug targets. METHODS: We performed a GWAS meta-analysis of early PD motor severity and progression up to 3 years from study entry. We used linear mixed-effect models with additive effects, corrected for age at diagnosis, sex, and the first 5 genetic principal components to assess variability in axial, limb, and total Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores. RESULTS: We included 3,572 unrelated European ancestry patients with PD from 5 observational cohorts and 1 drug trial. The average AAO was 62.6 years (SD = 9.83), and 63% of participants were male. We found an average increase in the total MDS-UPDRS III score of 2.3 points/year. We identified an association between PD axial motor progression and variation at the GJA5 locus at 1q12 (β = -0.25, SE = 0.04, p = 3.4e-10). Exploration of the regulation of gene expression in the region (cis-expression quantitative trait loci [eQTL] analysis) showed that the lead variant was associated with expression of ACP6, a lysophosphatidic acid phosphatase that regulates mitochondrial lipid biosynthesis (cis-eQTL p-values in blood and brain RNA expression data sets: <10-14 in eQTLGen and 10-7 in PsychEncode). DISCUSSION: Our study highlights the potential role of mitochondrial lipid homeostasis in the progression of PD, which may be important in establishing new drug targets that might modify disease progression

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease:Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

BACKGROUND: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach.OBJECTIVE: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials.METHODS: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory.RESULTS: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages.CONCLUSION: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.</p

Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson's disease

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to Phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson's disease is appealing but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in PD, a multi-arm platform trial must also specifically consider the heterogeneous nature of PD, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm, however in PD there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of pre-defined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of PD patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson's disease

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

BACKGROUND: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. OBJECTIVE: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. METHODS: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. RESULTS: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. CONCLUSION: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges