Assessment of Fitbit Charge 4 for sleep stage and heart rate monitoring against polysomnography and during home monitoring in Huntington's disease.

STUDY OBJECTIVES: Wearable devices, monitoring sleep stages and heart rate (HR), bring the potential for longitudinal sleep monitoring in patients with neurodegenerative diseases. Sleep quality reduces with disease progression in Huntington's disease (HD). However, the involuntary movements characteristic of HD may affect the accuracy of wrist-worn devices. This study compares sleep stage and heart rate data from the Fitbit Charge 4 (FB) against polysomnography (PSG) in participants with HD. METHODS: Ten participants with manifest HD wore a FB during overnight hospital-based PSG, and for nine of these participants continued to wear the FB for seven nights at home. Sleep stages (30s epochs) and minute-by-minute HR were extracted and compared against PSG data. RESULTS: FB-estimated total sleep and wake times, and sleep stage times were in good agreement with PSG, with intra-class correlations 0.79-0.96. However, poor agreement was observed for Wake After Sleep Onset, and the number of awakenings. FB detected wake with 68.6±15.5% sensitivity and 93.7±2.5% specificity, rapid eye movement (REM) sleep with high sensitivity and specificity (78.7±31.9%, 95.6±2.3%), and deep sleep with lower sensitivity but high specificity (56.4±28.8%, 95.0±4.8%). FB HR was strongly correlated with PSG, and the mean absolute error between FB and PSG HR data was 1.16 ± 0.42 bpm. At home, longer sleep and shorter wake times were observed compared to hospital data, while percentage sleep stage times were consistent with hospital data. CONCLUSIONS: Results suggest the potential for long-term monitoring of sleep patterns using wrist-worn wearable devices as part of symptom management in HD.

Language-Independent Acoustic Biomarkers for Quantifying Speech Impairment in Huntington's Disease.

PURPOSE: Changes in voice and speech are characteristic symptoms of Huntington's disease (HD). Objective methods for quantifying speech impairment that can be used across languages could facilitate assessment of disease progression and intervention strategies. The aim of this study was to analyze acoustic features to identify language-independent features that could be used to quantify speech dysfunction in English-, Spanish-, and Polish-speaking participants with HD. METHOD: Ninety participants with HD and 83 control participants performed sustained vowel, syllable repetition, and reading passage tasks recorded with previously validated methods using mobile devices. Language-independent features that differed between HD and controls were identified. Principal component analysis (PCA) and unsupervised clustering were applied to the language-independent features of the HD data set to identify subgroups within the HD data. RESULTS: Forty-six language-independent acoustic features that were significantly different between control participants and participants with HD were identified. Following dimensionality reduction using PCA, four speech clusters were identified in the HD data set. Unified Huntington's Disease Rating Scale (UHDRS) total motor score, total functional capacity, and composite UHDRS were significantly different for pairwise comparisons of subgroups. The percentage of HD participants with higher dysarthria score and disease stage also increased across clusters. CONCLUSION: The results support the application of acoustic features to objectively quantify speech impairment and disease severity in HD in multilanguage studies. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25447171.

Exploring critical intervention features and trial processes in the evaluation of sensory integration therapy for autistic children.

BACKGROUND: We evaluated the clinical and cost-effectiveness of manualised sensory integration therapy (SIT) for autistic children with sensory processing difficulties in a two-arm randomised controlled trial. Trial processes and contextual factors which may have affected intervention outcomes were explored within a nested process evaluation. This paper details the process evaluation methods and results. We also discuss implications for evaluation of individual level, tailored interventions in similar populations. METHODS: The process evaluation was conducted in line with Medical Research Council guidance. Recruitment, demographics, retention, adherence, and adverse effects are reported using descriptive statistics. Fidelity of intervention delivery is reported according to the intervention scoring manual. Qualitative interviews with therapists and carers were undertaken to explore the acceptability of the intervention and trial processes. Qualitative interviews with carers explored potential contamination. RESULTS: Recruitment, reach and retention within the trial met expected thresholds. One hundred thirty-eight children and carers were recruited (92% of those screened and 53.5% of those who expressed an interest) with 77.5% retained at 6 months and 69.9% at 12 months post-randomisation. The intervention was delivered with structural and process fidelity with the majority (78.3%) receiving a 'sufficient dose' of intervention. However, there was considerable individual variability in the receipt of sessions. Carers and therapists reported that trial processes were generally acceptable though logistical challenges such as appointment times, travel and COVID restrictions were frequent barriers to receiving the intervention. No adverse effects were reported. CONCLUSIONS: The process evaluation was highly valuable in identifying contextual factors that could impact the effectiveness of this individualised intervention. Rigorous evaluations of interventions for autistic children are important, especially given the limitations such as limited sample sizes and short-term follow-up as faced by previous research. One of the challenges lies in the variability of outcomes considered important by caregivers, as each autistic child faces unique challenges. It is crucial to consider the role of parents or other caregivers in facilitating access to these interventions and how this may impact effectiveness. TRIAL REGISTRATION: This trial is registered as ISRCTN14716440. August 11, 2016.

HD-DRUM, a Tablet-Based Drumming Training App Intervention for People With Huntington Disease: App Development Study.

BACKGROUND: Huntington disease (HD) is a neurodegenerative condition that leads to progressive loss of cognitive-executive and motor functions, largely due to basal ganglia (BG) atrophy. Currently, there are no therapeutic interventions tailored to address executive and motor dysfunction in people with HD. Music-based interventions may aid executive abilities by compensating for impaired BG-reliant timing and rhythm generation using external rhythmic beats. Here, we applied an integrated knowledge translation (IKT) framework to co-design a tablet-based rhythmic drumming training app (HD-DRUM) to stimulate executive and motor abilities in people with HD. OBJECTIVE: The primary aim was to develop the HD-DRUM app for at-home use that addressed the accessibility needs of people with HD and allowed for the quantification of performance improvements and adherence for controlled clinical evaluation. METHODS: The IKT framework was applied to iteratively refine the design of HD-DRUM. This process involved 3 phases of knowledge user engagement and co-design: a web-based survey of people with HD (n=29) to inform about their accessibility needs, usability testing of tablet-based touch screens as hardware solutions, and usability testing of the design and build of HD-DRUM to meet the identified accessibility needs of people affected by HD and their clinicians (n=12). RESULTS: The survey identified accessibility problems due to cognitive and motor control impairments such as difficulties in finding and navigating through information and using PC keyboards and mouses to interact with apps. Tablet-based touch screens were identified as feasible and accessible solutions for app delivery. Key elements to ensure that the app design and build met the needs of people with HD were identified and implemented. These included the facilitation of intuitive navigation through the app using large and visually distinctive buttons; the use of audio and visual cues as training guides; and gamification, positive feedback, and drumming to background music as a means to increase motivation and engagement. The co-design development process resulted in the proof-of-concept HD-DRUM app that is described here according to the Template for Intervention Description and Replication checklist. HD-DRUM can be used at home, allowing the quantification of performance improvements and adherence for clinical evaluation, matching of training difficulty to users' performance levels using gamification, and future scale-up to reach a wide range of interested users. CONCLUSIONS: Applying an IKT-based co-design framework involving knowledge user engagement allowed for the iterative refinement of the design and build of the tablet-based HD-DRUM app intervention, with the aim of stimulating BG-reliant cognitive and motor functions. Mapping the intervention against the Template for Intervention Description and Replication framework to describe complex interventions allowed for the detailed description of the HD-DRUM intervention and identification of areas that required refinement before finalizing the intervention protocol.

Exploring the issues that influence how people with rare neurological conditions engage in physical activity.

PURPOSE: People with rare neurological conditions (RNCs) struggle to achieve regular physical activity (PA). This study explored experiences of people with RNC engaging in PA, their carers, and health care professionals (HCPs) working with them. MATERIALS & METHODS: We developed three surveys: for individuals living with RNCs, their carers, and HCPs working with them. Themes from interviews with RNC charity representatives were used to co-design questions, together with people living with RNCs, their representatives, and an expert panel. Surveys were disseminated via charity mailing lists, social media accounts, and professional networks (HCPs). RESULTS: We received 436 responses (225 people with RNC, 94 carers, 117 HCPs). Most respondents with RNC achieved some level of regular PA but needed motivation to maintain it. Many felt they lacked knowledge on starting and staying active, with scarce resources and support. Most HCP respondents worked in specialist services, and overwhelmingly agreed that people with RNC should be physically active, while acknowledging lack of evidence and resources. CONCLUSIONS: We identified key barriers at environmental/organisational, interpersonal, and intrapersonal levels, highlighting a critical lack of support for people with RNC across UK health services. These factors can be targeted to increase engagement in PA.Implications for rehabilitationPeople living with rare neurological conditions experience barriers to engaging in physical activity, with some common to more prevalent neurological diseases, e.g. access and facilities, but some notable differences due to the rarity of the conditionFor people living with rare neurological conditions, and their carers, there is a lack of knowledge on safe and appropriate engagement in physical activityIncreasing the knowledge of health and exercise professionals may improve how they support people with rare neurological disease to engage with physical activity.Evidence based resources and recommendations for people living with rare neurological conditions, and professionals working with them, may facilitate engagement in physical activity.

A tutorial comparing different covariate balancing methods with an application evaluating the causal effects of substance use treatment programs for adolescents.

Randomized controlled trials are the gold standard for measuring causal effects. However, they are often not always feasible, and causal treatment effects must be estimated from observational data. Observational studies do not allow robust conclusions about causal relationships unless statistical techniques account for the imbalance of pretreatment confounders across groups and key assumptions hold. Propensity score and balance weighting (PSBW) are useful techniques that aim to reduce the observed imbalances between treatment groups by weighting the groups to look alike on the observed confounders. Notably, there are many methods available to estimate PSBW. However, it is unclear a priori which will achieve the best trade-off between covariate balance and effective sample size for a given application. Moreover, it is critical to assess the validity of key assumptions required for robust estimation of the needed treatment effects, including the overlap and no unmeasured confounding assumptions. We present a step-by-step guide to the use of PSBW for estimation of causal treatment effects that includes steps on how to evaluate overlap before the analysis, obtain estimates of PSBW using multiple methods and select the optimal one, check for covariate balance on multiple metrics, and assess sensitivity of findings (both the estimated treatment effect and statistical significance) to unobserved confounding. We illustrate the key steps using a case study examining the relative effectiveness of substance use treatment programs and provide a user-friendly Shiny application that can implement the proposed steps for any application with binary treatments.

A new approach to digitized cognitive monitoring: validity of the SelfCog in Huntington's disease.

Cognitive deficits represent a hallmark of neurodegenerative diseases, but evaluating their progression is complex. Most current evaluations involve lengthy paper-and-pencil tasks which are subject to learning effects dependent on the mode of response (motor or verbal), the countries' language or the examiners. To address these limitations, we hypothesized that applying neuroscience principles may offer a fruitful alternative. We thus developed the SelfCog, a digitized battery that tests motor, executive, visuospatial, language and memory functions in 15 min. All cognitive functions are tested according to the same paradigm, and a randomization algorithm provides a new test at each assessment with a constant level of difficulty. Here, we assessed its validity, reliability and sensitivity to detect decline in early-stage Huntington's disease in a prospective and international multilingual study (France, the UK and Germany). Fifty-one out of 85 participants with Huntington's disease and 40 of 52 healthy controls included at baseline were followed up for 1 year. Assessments included a comprehensive clinical assessment battery including currently standard cognitive assessments alongside the SelfCog. We estimated associations between each of the clinical assessments and SelfCog using Spearman's correlation and proneness to retest effects and sensitivity to decline through linear mixed models. Longitudinal effect sizes were estimated for each cognitive score. Voxel-based morphometry and tract-based spatial statistics analyses were conducted to assess the consistency between performance on the SelfCog and MRI 3D-T1 and diffusion-weighted imaging in a subgroup that underwent MRI at baseline and after 12 months. The SelfCog detected the decline of patients with Huntington's disease in a 1-year follow-up period with satisfactory psychometric properties. Huntington's disease patients are correctly differentiated from controls. The SelfCog showed larger effect sizes than the classical cognitive assessments. Its scores were associated with grey and white matter damage at baseline and over 1 year. Given its good performance in longitudinal analyses of the Huntington's disease cohort, it should likely become a very useful tool for measuring cognition in Huntington's disease in the future. It highlights the value of moving the field along the neuroscience principles and eventually applying them to the evaluation of all neurodegenerative diseases.

Mapping two decades of multiple sclerosis rehabilitation trials: A systematic scoping review and call to action to advance the study of race and ethnicity in rehabilitation research.

BACKGROUND: Multiple sclerosis (MS), is prevalent across many racial and ethnic groups, and disproportionately impacts racially minoritized populations. Rehabilitation interventions are an important component of comprehensive MS care. Yet, we do not know the extent to which MS rehabilitation trials consider race and ethnicity in defining eligibility criteria, planning recruitment strategies, selecting outcome measures, supporting intervention delivery, and designing approaches to promote adherence and retention. METHODS: We conducted a scoping review of five databases (MEDLINE, CINAHL, Cochrane Central, EMBASE, and Web of Science) to locate randomized controlled rehabilitation trials published from January 2002 to March 2022. We extracted data from relevant studies, assessed their methodological quality, and narratively summarized results. Reporting of this review is in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). RESULTS: Fifty-six studies of neurorehabilitation (n = 3), cognitive rehabilitation (n = 6), exercise training (n = 9) and self-management (n = 38) interventions were included in this review. The studies were predominantly from North America (n = 44; 73%) or Europe (n = 12; 20%) and included 4280 participants. Most participants (n = 3669; 86%) were Caucasians. Less than 10% of participants were Black (n = 282), Latinx/Hispanic (n = 60), Asian (n = 46), Indigenous (n = 7), or Arab (n = 2). Few studies discussed how race and/or ethnicity were considered in trial planning or execution. CONCLUSIONS: Without consistent and systematic attention to race and ethnicity, both in terms of trial design and reporting, it is impossible to know how MS rehabilitation interventions will translate into real-world applications. This call to action - to the MS rehabilitation research community to ensure trial and intervention processes that accommodate the needs of diverse racial and ethnic groups - is an important first step in addressing inequities in rehabilitation care for persons with MS.

Effectiveness and cost-effectiveness of a personalised self-management intervention for living with long COVID: protocol for the LISTEN randomised controlled trial.

BACKGROUND: Individuals living with long COVID experience multiple, interacting and fluctuating symptoms which can have a dramatic impact on daily living. The aim of the Long Covid Personalised Self-managemenT support EvaluatioN (LISTEN) trial is to evaluate effects of the LISTEN co-designed self-management support intervention for non-hospitalised people living with long COVID on participation in routine activities, social participation, emotional well-being, quality of life, fatigue, and self-efficacy. Cost-effectiveness will also be evaluated, and a detailed process evaluation carried out to understand how LISTEN is implemented. METHODS: The study is a pragmatic randomised effectiveness and cost-effectiveness trial in which a total of 558 non-hospitalised people with long COVID will be randomised to either the LISTEN intervention or usual care. Recruitment strategies have been developed with input from the LISTEN Patient and Public Involvement and Engagement (PPIE) advisory group and a social enterprise, Diversity and Ability, to ensure inclusivity. Eligible participants can self-refer into the trial via a website or be referred by long COVID services. All participants complete a range of self-reported outcome measures, online, at baseline, 6 weeks, and 3 months post randomisation (the trial primary end point). Those randomised to the LISTEN intervention are offered up to six one-to-one sessions with LISTEN-trained intervention practitioners and given a co-designed digital resource and paper-based book. A detailed process evaluation will be conducted alongside the trial to inform implementation approaches should the LISTEN intervention be found effective and cost-effective. DISCUSSION: The LISTEN trial is evaluating a co-designed, personalised self-management support intervention (the LISTEN intervention) for non-hospitalised people living with long COVID. The design has incorporated extensive strategies to minimise participant burden and maximise access. Whilst the duration of follow-up is limited, all participants are approached to consent for long-term follow-up (subject to additional funding being secured). TRIAL REGISTRATION: LISTEN ISRCTN36407216. Registered on 27/01/2022.

The striatum in time production: The model of Huntington's disease in longitudinal study.

The unified model of time processing suggests that the striatum is a central structure involved in all tasks that require the processing of temporal durations. Patients with Huntington's disease exhibit striatal degeneration and a deficit in time perception in interval timing tasks (i.e. for duration ranging from hundreds of milliseconds to minutes), but whether this deficit extends to time production remains unclear. In this study, we investigated whether symptomatic patients (HD, N = 101) or presymptomatic gene carriers (Pre-HD, N = 31) of Huntington's disease had a deficit in time production for durations between 4 and 10 s compared to healthy controls and whether this deficit developed over a year for patients. We found a clear deficit in temporal production for HD patients, whereas Pre-HD performed similarly to Controls. For HD patients and Pre-HD participants, task performance was correlated with grey matter volume in the amygdala and caudate, bilaterally. These results confirm that the striatum is involved in interval timing not only in perception but also in production, in accordance with the unified model of time processing. Furthermore, exploratory factor analyses on our data indicated that temporal production was associated with clinical assessments of psychomotor and executive functions. Finally, when retested twelve months later, the deficit of HD patients remained stable, although striatal degeneration was more pronounced. Thus, the simple, short and language-independent temporal production task may be a useful clinical tool to detect striatal degeneration in patients in early stages of Huntington's disease. However, its usefulness to detect presymptomatic stages or for monitoring the evolution of HD over a year seems limited.

Considerations for clinical trial design and conduct in the evaluation of novel advanced therapeutics in neurodegenerative disease.

The recent advances in the development of potentially disease modifying cell and gene therapies for neurodegenerative disease has resulted in the production of a number of promising novel therapies which are now moving forward to clinical evaluation. The robust evaluation of these therapies pose a significant number of challenges when compared to more traditional evaluations of pharmacotherapy, which is the current mainstay of neurodegenerative disease symptom management. Indeed, there is an inherent complexity in the design and conduct of these trials at multiple levels. Here we discuss specific aspects requiring consideration in the context of investigating novel cell and gene therapies for neurodegenerative disease. This extends to overarching trial designs that could be employed and the factors that underpin design choices such outcome assessments, participant selection and methods for delivery of cell and gene therapies. We explore methods of data collection that may improve efficiency in trials of cell and gene therapy to maximize data sharing and collaboration. Lastly, we explore some of the additional context beyond efficacy evaluations that should be considered to ensure implementation across relevant healthcare settings.

Cognitive processes of apathy in Huntington's disease show high sensitivity to disease progression.

Background: Disease-modifying treatments for Huntington's disease (HD) are entering clinical trials: there is a pressing need for objective outcome measures of disease progression. Our previous work showed an association between 2 novel, objective cognitive tasks and apathy - a core feature of disease progression in HD. Objective: Evaluate the longitudinal validity and sensitivity of the novel Persistence and Maze tasks to assess their utility as clinical outcome measures in HD. Methods: 83 participants positive for the HD gene and 54 controls performed a battery of established and novel tools, at baseline and 12 month follow up. Results: The Maze task was found to be the most sensitive measure of change at 12 months, including the current gold-standard measure (the composite disease progression score). Conclusion: The Maze task has potential as a novel outcome measure of disease progression in HD and may have utility in other major neurodegenerative diseases.

Comparison of Acoustic Voice Features Derived From Mobile Devices and Studio Microphone Recordings.

OBJECTIVES/HYPOTHESIS: Improvements in mobile device technology offer new opportunities for remote monitoring of voice for home and clinical assessment. However, there is a need to establish equivalence between features derived from signals recorded from mobile devices and gold standard microphone-preamplifiers. In this study acoustic voice features from android smartphone, tablet, and microphone-preamplifier recordings were compared. METHODS: Data were recorded from 37 volunteers (20 female) with no history of speech disorder and six volunteers with Huntington's disease (HD) during sustained vowel (SV) phonation, reading passage (RP), and five syllable repetition (SR) tasks. The following features were estimated: fundamental frequency median and standard deviation (F0 and SD F0), harmonics-to-noise ratio (HNR), local jitter, relative average perturbation of jitter (RAP), five-point period perturbation quotient (PPQ5), difference of differences of amplitude and periods (DDA and DDP), shimmer, and amplitude perturbation quotients (APQ3, APQ5, and APQ11). RESULTS: Bland-Altman analysis revealed good agreement between microphone and mobile devices for fundamental frequency, jitter, RAP, PPQ5, and DDP during all tasks and a bias for HNR, shimmer and its variants (APQ3, APQ5, APQ11, and DDA). Significant differences were observed between devices for HNR, shimmer, and its variants for all tasks. High correlation was observed between devices for all features, except SD F0 for RP. Similar results were observed in the HD group for SV and SR task. Biological sex had a significant effect on F0 and HNR during all tests, and for jitter, RAP, PPQ5, DDP, and shimmer for RP and SR. No significant effect of age was observed. CONCLUSIONS: Mobile devices provided good agreement with state of the art, high-quality microphones during structured speech tasks for features derived from frequency components of the audio recordings. Caution should be taken when estimating HNR, shimmer and its variants from recordings made with mobile devices.

Co-designing personalised self-management support for people living with long Covid: The LISTEN protocol.

BACKGROUND: Long Covid is recognised as a complex condition characterised by multiple, interacting and fluctuating symptoms which impact everyday life in diverse ways. The extent of symptom clusters and variability supports interventions that can accommodate heterogeneity, such as personalised self-management support. This approach is also advocated by people living with long Covid and guidelines published by the UK's National Institute for Health and Care Excellence. Long Covid Personalised Self-managemenT support co-design and EvaluatioN (LISTEN) is one of 15 research projects funded by the UK's National Institute of Health Research long Covid research programme. LISTEN aims to work with people living with or recovered from long Covid to co-design self-management resources, and a training programme for rehabilitation practitioners to deliver personalised support. The intervention will focus on people not hospitalised for Covid. The protocol presented here details the co-design of the LISTEN intervention which, on completion, will be evaluated in a randomised controlled trial. METHODS: The study will utilise an Accelerated Experience-Based Co-Design approach, and involve 30 people from England and Wales with lived experience of long Covid, and 15 rehabilitation practitioners living with, or supporting people with, long Covid. Through online meetings, participants will share their stories of long Covid, their challenges and strategies to live better with or recover from long Covid, their priorities for self-management resources and the practitioner training andcreate, review and refine these resources and the training. Throughout, LISTEN will draw upon the UK standards of public involvement in research. DISCUSSION: If effective and cost-effective, the intervention will be available across the UK's National Health Service. The first of its kind, this study could make a difference to the lives of people with long Covid. To ensure impact, we have developed strategies to involve people from diverse backgrounds and mitigate potential barriers to involvement.

Physical activity and exercise outcomes in Huntington's disease (PACE-HD): results of a 12-month trial-within-cohort feasibility study of a physical activity intervention in people with Huntington's disease.

INTRODUCTION: While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention. METHODS: Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.S. Assessments were completed at baseline and 12 months and linked to Enroll-HD cohort data. Participants at three sites (cohort) received no contact between baseline and 12 month assessments. Participants at three additional sites (RCT) were randomized to PA intervention or control group. The intervention consisted of 18 sessions delivered over 12 months; control group participants received no intervention, however both groups completed monthly exercise/falls diaries and 6-month assessments. RESULTS: 274 participants were screened, 204 met inclusion criteria and 116 were enrolled (59 in cohort; 57 in RCT). Retention rates at 12-months were 84.7% (cohort) and 79.0% (RCT). Data completeness at baseline ranged from 42.3 to 100% and at 12-months 19.2-85.2%. In the RCT, there was 80.5% adherence, high intervention fidelity, and similar adverse events between groups. There were differences in fitness, walking endurance and self-reported PA at 12 months favoring the intervention group, with data completeness >60%. Participants in the cohort had motor and functional decline at rates comparable to previous studies. CONCLUSION: Predefined progression criteria indicating feasibility were met. PACE-HD lays the groundwork for a future, fully-powered within cohort trial, but approaches to ensure data completeness must be considered. CLINICALTRIALS: GOV: NCT03344601.

Monitoring and Managing Lifestyle Behaviors Using Wearable Activity Trackers: Mixed Methods Study of Views From the Huntington Disease Community.

BACKGROUND: There are early indications that lifestyle behaviors, specifically physical activity and sleep, may be associated with the onset and progression of Huntington disease (HD). Wearable activity trackers offer an exciting opportunity to collect long-term activity data to further investigate the role of lifestyle, physical activity, and sleep in disease modification. Given how wearable devices rely on user acceptance and long-term adoption, it is important to understand users' perspectives on how acceptable any device might be and how users might engage over the longer term. OBJECTIVE: This study aimed to explore the perceptions, motivators, and potential barriers relating to the adoption of wearable activity trackers by people with HD for monitoring and managing their lifestyle and sleep. This information intended to guide the selection of wearable activity trackers for use in a longitudinal observational clinical study. METHODS: We conducted a mixed methods study; this allowed us to draw on the potential strengths of both quantitative and qualitative methods. Opportunistic participant recruitment occurred at 4 Huntington's Disease Association meetings, including 1 international meeting and 3 United Kingdom-based regional meetings. Individuals with HD, their family members, and carers were invited to complete a user acceptance questionnaire and participate in a focus group discussion. The questionnaire consisted of 35 items across 8 domains using a 0 to 4 Likert scale, along with some additional demographic questions. Average questionnaire responses were recorded as positive (score>2.5), negative (score<1.5), or neutral (score between 1.5 and 2.5) opinions for each domain. Differences owing to demographics were explored using the Kruskal-Wallis and Wilcoxon rank sum tests. Focus group discussions (conducted in English) were driven by a topic guide, a vignette scenario, and an item ranking exercise. The discussions were audio recorded and then analyzed using thematic analysis. RESULTS: A total of 105 completed questionnaires were analyzed (47 people with HD and 58 family members or carers). All sections of the questionnaire produced median scores >2.5, indicating a tendency toward positive opinions on wearable activity trackers, such as the devices being advantageous, easy and enjoyable to use, and compatible with lifestyle and users being able to understand the information from trackers and willing to wear them. People with HD reported a more positive attitude toward wearable activity trackers than their family members or caregivers (P=.02). A total of 15 participants participated in 3 focus groups. Device compatibility and accuracy, data security, impact on relationships, and the ability to monitor and self-manage lifestyle behaviors have emerged as important considerations in device use and user preferences. CONCLUSIONS: Although wearable activity trackers were broadly recognized as acceptable for both monitoring and management, various aspects of device design and functionality must be considered to promote acceptance in this clinical cohort.

Postural control and gait measures derived from wearable inertial measurement unit devices in Huntington's disease: Recommendations for clinical outcomes.

BACKGROUND: Postural control impairments begin early in Huntington's disease yet measures most sensitive to progression have not been identified. The aims of this study were to: 1) evaluate postural control and gait in people with and without Huntington's disease using wearable sensors; and 2) identify measures related to diagnosis and clinical severity. METHODS: 43 individuals with Huntington's disease and 15 age-matched peers performed standing with feet together and feet apart, sitting, and walking with wearable inertial sensors. One-way analysis of variance determined differences in measures of postural control and gait between early and mid-disease stage, and non-Huntington's disease peers. A random forest analysis identified feature importance for Huntington's disease diagnosis. Stepwise and ordinal regressions were used to determine predictors of clinical chorea and tandem walking scores respectively. FINDINGS: There was a significant main effect for all postural control and gait measures comparing early stage, mid stage and non-Huntington's disease peers, except for gait cycle duration and step duration. Total sway, root mean square and mean velocity during sitting, as well as gait speed had the greatest importance in classifying disease status. Stepwise regression showed that root mean square during standing with feet apart significantly predicted clinical measure of chorea, and ordinal regression model showed that root mean square and total sway standing feet together significantly predicted clinical measure of tandem walking. INTERPRETATIONS: Root mean square measures obtained in sitting and standing using wearable sensors have the potential to serve as biomarkers of postural control impairments in Huntington's disease.

Understanding the support experiences of families of children with autism and sensory processing difficulties: A qualitative study.

BACKGROUND: Support, such as information, advice and therapies, can play a vital role in the lives of families of autistic children. However, little is known about the support experiences of UK parents and carers. AIM: To explore experiences of and access to support for families of children with autism and sensory processing difficulties, from the perspective of parents and carers. METHODS: Semi-structured, timeline-assisted interviews were conducted with parents/carers of 30 children aged 5-11, exploring experiences of support. Framework analysis was used to identify themes in the interview data. RESULTS: Support varied widely and was not accessed equitably. Specialist autism support, together with support from other parents and voluntary organizations, was perceived as more useful than statutory and nonspecialist provision. Unmet support needs included an ongoing point of contact for information and advice for parents, and access to direct therapy and specialist mental health provision for children. CONCLUSIONS: Findings emphasize the need for a clear pathway of support following autism diagnosis, autism-specific training for professional service providers and specialist provision tailored to the needs of autistic children. PATIENT OR PUBLIC CONTRIBUTION: An advisory group of four parents of children with autism provided feedback on study procedures and materials, including participant information sheets and timeline completion instructions.

Translating cell therapies for neurodegenerative diseases: Huntington's disease as a model disorder.

There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease-specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment. Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington's disease as a specific example, and suggest potential strategies to address these challenges. Huntington's disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington's disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells for Huntington's Disease and the European Huntington's Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington's disease.