Development of a novel patient reported outcome measure for health-related quality of life in amyotrophic lateral sclerosis (PROQuALS): study protocol.

BACKGROUND: Patient reported outcome measures (PROMs) can be used to assess the impact of health conditions upon an individual's health-related quality of life (HRQoL). Whilst PROMs have been used to quantify the HRQoL impact of amyotrophic lateral sclerosis (ALS), existing instruments may not fully capture what matters to people living with ALS (plwALS) or be appropriate to be used directly to inform the cost-effectiveness of new treatments. This highlights a need for a new condition-specific PROM that can both capture what's important to plwALS and be used in economic evaluation. This study has two key aims: 1) to produce a novel PROM for measuring HRQoL in plwALS (PROQuALS). 2) to value a set of items from the novel PROM to generate an associated preference-weighted measure (PWM) that will enable utility values to be generated. METHODS: A mixed-methods study design will be conducted across three stages. Stage 1 involves concept elicitation and the generation of draft PROM content from a robust and comprehensive systematic review of HRQoL in ALS, with input from plwALS. Stage 2 consists of cognitive debriefing of the draft PROM content to ascertain its content validity (Stage 2a), followed by a psychometric survey (Stage 2b) to assess statistical performance. Evidence from Stage 2 will be used to make decisions on the final content and format of the novel PROM. Stage 3 will involve valuation and econometric modeling using health economics methods to generate preference weights, so a PWM derived from the novel PROM can be used in the cost-effectiveness analyses of treatments. Patient and clinical advisory groups will have critical, collaborative input throughout the project. DISCUSSION: The novel PROM will be designed to comprehensively assess important aspects of HRQoL to plwALS and to quantify HRQoL in terms of subjective impact. The PROQuALS measure will be available for use in research and healthcare settings. The associated PWM component will extend and enable the use of PROQuALS in cost-effective analyses of new treatments for ALS. TRIAL REGISTRATION: Not applicable.

Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study.

BACKGROUND: A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes. METHODS: For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 109 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 µg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3-6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis. FINDINGS: Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32-55) was lower than in the non-VITT group (57 years; 41-62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2-4) than non-VITT patients (two, 2-3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022). INTERPRETATION: Cerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate. FUNDING: None.

End-of-life care of people with long-term neurological conditions.

Guidance and protocols of end-of-life care have been directed towards the care of patients with cancer. It is possible to extrapolate some of these to people with long-term neurological conditions, but there are obvious differences. Neurological conditions have widely different time courses of progression, making the timing of these discussions challenging. The common issues around end-of-life care include knowing when to start discussions, approaching advance planning, managing common symptoms, diagnosing the dying phase, withdrawing life-sustaining treatments, providing support for family and carers and judging how to involve specialist palliative care teams. End-of-life care needs close collaboration between neurology, specialist palliative care and general practice.

A Road Map for Remote Digital Health Technology for Motor Neuron Disease.

Despite recent and potent technological advances, the real-world implementation of remote digital health technology in the care and monitoring of patients with motor neuron disease has not yet been realized. Digital health technology may increase the accessibility to and personalization of care, whereas remote biosensors could optimize the collection of vital clinical parameters, irrespective of patients' ability to visit the clinic. To facilitate the wide-scale adoption of digital health care technology and to align current initiatives, we outline a road map that will identify clinically relevant digital parameters; mediate the development of benefit-to-burden criteria for innovative technology; and direct the validation, harmonization, and adoption of digital health care technology in real-world settings. We define two key end products of the road map: (1) a set of reliable digital parameters to capture data collected under free-living conditions that reflect patient-centric measures and facilitate clinical decision making and (2) an integrated, open-source system that provides personalized feedback to patients, health care providers, clinical researchers, and caregivers and is linked to a flexible and adaptable platform that integrates patient data in real time. Given the ever-changing care needs of patients and the relentless progression rate of motor neuron disease, the adoption of digital health care technology will significantly benefit the delivery of care and accelerate the development of effective treatments.

The optimisation of noninvasive ventilation in amyotrophic lateral sclerosis: a systematic review.

BACKGROUND: Noninvasive ventilation (NIV) prolongs survival and quality of life in amyotrophic lateral sclerosis (ALS); however, its benefits depend upon the optimisation of both ventilation and adherence. We aimed to identify factors associated with effective initiation and ongoing use of NIV in ALS to develop evidence-based guidance and identify areas for further research. METHODS: We searched 11 electronic databases (January 1998 to May 2018) for all types of quantitative and qualitative studies. Supplementary grey literature searches were conducted. Records were screened against eligibility criteria, data were extracted from included studies and risk of bias was assessed. We present findings using a narrative synthesis. RESULTS: We screened 2430 unique records and included 52 quantitative and six qualitative papers. Factors reported to be associated with NIV optimisation included coordinated multidisciplinary care, place of initiation, selection of interfaces, ventilator modes and settings appropriate for the individual patient, and adequate secretion management. The literature indicated that patients with significant bulbar dysfunction can still derive considerable benefit from NIV if their needs are met. Research emphasises that obstructive airway events, mask leak and uncontrolled secretions should be addressed by adjustments to the interface and machine settings, and the concomitant use of cough augmentation. CONCLUSION: This review highlights that NIV optimisation requires an individualised approach to respiratory management tailored to the differing needs of each patient. Ultimately, this should lead to improved survival and quality of life. This review expands on recommendations in current international guidelines for NIV use in ALS and identifies areas for future research.

Diagnosis of spinal xanthomatosis by next-generation sequencing: identifying a rare, treatable mimic of hereditary spastic paraparesis.

Cerebrotendinous xanthomatosis is an autosomal recessive disorder of bile acid metabolism causing a range of progressive neurological symptoms. Even in the presence of the classical triad of neurological dysfunction, tendon xanthoma and early onset cataracts, the diagnosis is often missed. It can mimic more common conditions such as hereditary spastic paraparesis or multiple sclerosis, particularly if the phenotype is spinal xanthomatosis where the disease causes a spastic paraplegia. Early recognition and treatment with chenodeoxycholic acid may prevent irreversible neurological damage. The introduction of next-generation sequencing to screen for a large number of genetic disorders associated with progressive spastic paraparesis will allow earlier identification and treatment of these patients and their families, and will particularly help in atypical cases such as the patient described here.

Advances in symptom management and in monitoring disease progression in motor neuron disease.

The aim of supportive management of motor neuron disease is to improve survival, promote good quality of life and patient independence and autonomy whilst preparing for future progression and the end of life. Multidisciplinary specialist care aims to address the multifaceted and interacting biopsychosocial problems associated with motor neuron disease that leads to proven benefits in both survival and quality of life. This chapter will explore principles, structure and details of treatment options, and make recommendations for practice and for future research.

Measuring Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: A Systematic Review and Conceptual Framework.

BACKGROUND AND OBJECTIVES: The assessment of health-related quality of life (HRQoL) in patients with amyotrophic lateral sclerosis (ALS) is heterogeneous and inconsistent. The objectives of this study were (1) to develop a comprehensive conceptual framework of HRQoL in ALS and (2) map the content of existing patient-reported outcome measures (PROMs) used in ALS to this novel framework. METHODS: Our model of HRQoL in ALS (Health-related Quality of life in Amyotrophic Lateral Sclerosis, QuALS) was developed from a systematic literature review and consultative input from key stakeholders (patients, carers, and health care professionals). Five electronic databases were searched in April 2022. Primary studies of any design that assessed HRQoL in ALS by using a multi-item PROM and/or qualitative methods were identified. Using an a priori framework, HRQoL themes were extracted and iteratively modified from the content of each PROM and qualitative study quotations identified in the literature. The conceptual framework was ratified by stakeholders with lived experience and clinical experts. The QuALS framework was used to map the content of identified PROMs and qualitative studies based on thematic coverage. RESULTS: QuALS covers 3 high-level domains of HRQoL (physical, psychological, and social functioning) and consists of 7 themes (Activities; Physical Health; Autonomy; Cognition; Feelings and Emotions; Self-identity; Relationships), characterized by 42 subthemes. Of 8,220 studies identified, 274 were included in the review that informed QuALS. In these studies, 111 PROMs were used to assess at least 1 aspect of HRQoL, and 11 studies used qualitative methods. Of the 3 high-level domains, physical functioning was the most commonly assessed, particularly within ALS-specific PROMs where almost one-quarter of PROMs exclusively assessed physical functioning. None of the PROMs or qualitative studies identified assessed all aspects of HRQoL in the QuALS framework. DISCUSSION: This study presents a new comprehensive conceptual framework of HRQoL in ALS (QuALS), informed by a robust systematic review of existing literature and stakeholder input, incorporating lived experience. QuALS provides a valuable resource for researchers and clinicians interested in taking a holistic approach to assessing and understanding the full impact of ALS on HRQoL and how this may be affected by treatments.

predicTTE: An accessible and optimal tool for time-to-event prediction in neurological diseases.

Time-to-event prediction is a key task for biological discovery, experimental medicine, and clinical care. This is particularly true for neurological diseases where development of reliable biomarkers is often limited by difficulty visualising and sampling relevant cell and molecular pathobiology. To date, much work has relied on Cox regression because of ease-of-use, despite evidence that this model includes incorrect assumptions. We have implemented a set of deep learning and spline models for time-to-event modelling within a fully customizable 'app' and accompanying online portal, both of which can be used for any time-to-event analysis in any disease by a non-expert user. Our online portal includes capacity for end-users including patients, Neurology clinicians, and researchers, to access and perform predictions using a trained model, and to contribute new data for model improvement, all within a data-secure environment. We demonstrate a pipeline for use of our app with three use-cases including imputation of missing data, hyperparameter tuning, model training and independent validation. We show that predictions are optimal for use in downstream applications such as genetic discovery, biomarker interpretation, and personalised choice of medication. We demonstrate the efficiency of an ensemble configuration, including focused training of a deep learning model. We have optimised a pipeline for imputation of missing data in combination with time-to-event prediction models. Overall, we provide a powerful and accessible tool to develop, access and share time-to-event prediction models; all software and tutorials are available at www.predictte.org.

Family experiences of antenatal counselling of spina bifida: a systematic review.

OBJECTIVE: To describe families' experiences of antenatal counselling of spina bifida. DESIGN: Systematic review. METHODS: MEDLINE, CINAHL, PsycINFO and Embase databases were searched using a combination of Medical Subject Headings and text/abstract terms. Case reports, survey results and qualitative interview data were included. The quality of research was evaluated using the Critical Appraisal Skills Programme checklist. RESULTS: 8 papers were included. Families described shock and grief at diagnosis, with some immediately offered termination of pregnancy (TOP) even though they knew little about the condition. Positive and negative aspects of care were found. Teams that were gentle, kind and empathetic, who did not use jargon, and highlighted positive and negative aspects of the baby's life were seen favourably. Callous language, and overly negative or incorrect counselling was not, particularly if there was pressure to agree to TOP. Families based their decisions on how they would cope, the effect on siblings and the baby's likely quality of life. Prenatal surgery was viewed positively. The views of families who chose TOP, were happy with their care, partners, families, and the LGBTQ+ community were under-represented in the literature. CONCLUSIONS: Unlike other conditions where limited data on outcome exist or the spectrum is genuinely broad, the outcomes of children with spina bifida is well described. Poor aspects of antenatal counselling were described frequently by families, and further work is needed to capture the full spectrum of views on antenatal counselling, how it can be improved, and what training and resources healthcare professionals need to perform it better.

Monkeypox encephalitis with transverse myelitis in a female patient.

The 2022 monkeypox outbreak has affected 110 countries worldwide, outside of classic endemic areas (ie, west Africa and central Africa). On July 23, 2022, the outbreak was classified by WHO as a public health emergency of international concern. Clinical presentation varies from mild to life-changing symptoms; neurological complications are relatively uncommon and there are few therapeutic interventions for monkeypox disease. In this Grand Round, we present a case of monkeypox with encephalitis complicated by transverse myelitis in a previously healthy woman aged 35 years who made an almost complete recovery from her neurological symptoms after treatment with tecovirimat, cidofovir, steroids, and plasma exchange. We describe neurological complications associated with orthopoxvirus infections and laboratory diagnosis, the radiological features in this case, and discuss treatment options.

Psychometric Properties of LUN-MS: A New Questionnaire to Identify the Unmet Needs of People With Multiple Sclerosis.

Background: We developed a 29-item Questionnaire, Long-term Unmet Needs in MS (LUN-MS) to identify the unmet needs of people with multiple sclerosis (pwMS). Objective: To assess acceptability, test-retest reliability, internal consistency, and validity of the LUN-MS. Methods: Participants completed the LUN-MS and MSIS-29 twice, four weeks apart. Acceptability was assessed by looking at the response rate in each time point. Reliability was calculated by comparing the response during the two time points using Cohen's weighted kappa. Using principal component analysis, the dimensionality of the questionnaire's items was reduced, to five domains and the internal consistency of each domain was assessed using Cronbach's alpha. Concurrent validity was tested by comparing the total LUN-MS score against MSIS-29 and EQ-5D-3L using Pearson's product-moment correlation coefficient. Results: Among 88 participants, rate of completion at time points-1 and 2 was 96 and 80% respectively. Test-retest reliability for individual items was between fair to near-perfect (weighted Cohen's kappa 0.39-0.81). The unmet needs could be divided into five internally consistent domains (Cronbach's alpha 0.83-0.74): neuropsychological, ambulation, physical, interpersonal relationship and informational. Concurrent validity with MSIS-29 (r = 0.705, P < .001) and EQ-5D-3L (r = 0.617, P < .001) were good. Conclusion: LUN-MS is a reliable, valid, and acceptable tool to identify the unmet needs of pwMS.

Impact of the covid-19 pandemic on amyotrophic lateral sclerosis care in the UK.

The Covid-19 pandemic has impacted healthcare. Our aim was to identify how amyotrophic lateral sclerosis (ALS) care in the UK has been affected by the pandemic by exploring the experiences of people living with ALS (plwALS), healthcare professionals (HCPs) working with plwALS, and ALS care centers. Three surveys were carried out to explore the experiences of plwALS, HCPs and ALS care centers during the pandemic. Quantitative data were analyzed using descriptive and inferential statistics and triangulated with the qualitative data which were analyzed thematically. Responses from 53 plwALS, 73 HCPs and 23 ALS care centers were analyzed. Five main themes were identified: keeping safe, losses, negative emotions, delivering care and alternative care delivery in a pandemic. PlwALS and HCPs felt that care was sub-optimal as a result of the pandemic. Changes to care included longer waiting times and face-to-face appointments being canceled or replaced by virtual consultations. While benefits of virtual consultations were reported, concerns were raised about incomplete clinical assessments and the disruption of provision of testing and interventions. ALS care has changed as a result of the pandemic. Patients have had a lack of face-to-face contact with HCPs and have experienced delays to investigations and treatments. PlwALS and HCPs were concerned about the impact of this change, but the long-term implications remain unclear. We propose recommendations for HCPs caring for plwALS, that will promote continuity of evidenced based care in the context of a pandemic.

Delivery of noninvasive ventilation to people living with motor neuron disease in the UK.

Objective: Noninvasive ventilation (NIV) improves survival and quality of life in motor neuron disease (MND), but many patients fail to receive effective ventilation. This study aimed to map the respiratory clinical care for MND patients at a service and individual healthcare professional (HCP) level to understand where attention may be needed to ensure all patients receive optimal care. Methods: Two online surveys of HCPs working with MND patients in the UK were conducted. Survey 1 targeted HCPs providing specialist MND care. Survey 2 targeted HCPs working in respiratory/ventilation services and community teams. Data were analysed using descriptive and inferential statistics. Results: Responses from 55 HCPs providing specialist MND care who worked at 21 MND care centres and networks and 13 Scotland Health Boards were analysed from Survey 1. Responses from 85 HCPs from respiratory/ventilation services and 73 HCPs from community teams, representing 97 services, were analysed from Survey 2. Significant differences in practice were identified at each stage of the respiratory care pathway as well as evidence of the need for improvement. This included when patients were referred to respiratory services, the time taken waiting to commence NIV, the availability of sufficient NIV equipment and provision of services, particularly out of hours. Conclusion: We have highlighted significant disparity in MND respiratory care practices. Increased awareness of the factors that influence NIV success and the performance of individuals and services is important for optimal practice.

Digital peer-to-peer support programme for informal caregivers of people living with motor neuron disease: study protocol for a multi-centre parallel group, single-blinded (outcome assessor) randomised controlled superiority trial.

BACKGROUND: Peer support is effective in improving psychological well-being of family caregivers of people with conditions such as dementia, cancer, and brain injury. However, there are limited data on effective psychological interventions for family caregivers of people living with motor neurone disease. Our objective is to evaluate the efficacy of a virtual peer support programme for improving caregiver psychological wellbeing and caregiving related outcomes. METHODS: We will conduct a multi-centre parallel group randomised controlled superiority trial. Using a multi-modal recruitment strategy, we will recruit informal caregivers from UK MND clinics, in-patient units, and hospices. We will randomise (1:1, stratified by gender) participants to either a 12-week virtual peer support programme or usual care comprising provision of online information resources publicly available via the MND Association website. Peer support programme elements will be delivered via a secure digital e-platform aTouchAway™ (Aetonix, Canada). Our target sample size is 160 (80 each arm). Our primary outcome is the Hospital Anxiety and Depression Scale (HADS) assessed at 12 weeks (primary endpoint). Secondary outcomes that will also be assessed at 12 weeks include the Zarit Burden Interview, Pearlin Mastery Scale, Personal Gain Scale, Positive Affect Scale, and the Brief COPE. Outcome assessors will be blinded to allocation. Tertiary outcomes include perceived usability (1 item 9-point Likert scale) and acceptability (semi-structured qualitative interviews) of the peer support programme. Intervention fidelity measures will comprise frequency, type (text, audio, video), and duration (audio and video) of peer support contact downloaded from the aTouchAway AWS server. We will use a mixed-effects linear model to test the effect of the intervention on the primary outcome. Secondary outcomes will be analysed using linear regression. We have ethical approval (21/NW/0269) from the North-West Research Ethics Committee, UK. DISCUSSION: This single-blinded randomised controlled trial will determine the effect of a virtual peer support programme on caregiver psychological wellbeing and caregiver burden. This study will examine the impact of a virtual peer support intervention on quality-of-life measures in informal caregivers of individuals with MND living in the community. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04695210.

Telehealth in long-term neurological conditions: the potential, the challenges and the key recommendations.

Long-term neurological conditions (LTNCs) cause physical and psychological symptoms that have a significant impact on activities of daily living and quality of life. Multidisciplinary teams are effective at providing treatment for people with LTNCs; however, access to such services by people with disabilities can be difficult and as a result, good quality care is not universal. One potential solution is telehealth. This review describes the potential of telehealth to support people with LTNCs, the challenges of designing and implementing these systems, and the key recommendations for those involved in telehealth to facilitate connected services that can benefit patients, carers and healthcare professionals. These recommendations include understanding the problems posed by LTNCs and the needs of the end-user through a person-centred approach. We discuss how to work collaboratively and use shared learning, and consider how to effectively evaluate the intervention at every stage of the development process.

Patient perspectives on digital healthcare technology in care and clinical trials for motor neuron disease: an international survey.

INTRODUCTION: To capture the patient's attitude toward remote monitoring of motor neuron disease (MND) in care and clinical trials, and their concerns and preferences regarding the use of digital technology. METHODS: We performed an international multi-centre survey study in three MND clinics in The Netherlands, the United Kingdom, and Australia. The survey was co-developed by investigators and patients with MND, and sent to patients by e-mail or postal-mail. The main topics included: patients' attitude towards remote care, participating in decentralized clinical trials, and preferences for and concerns with digital technology use. RESULTS: In total, 332 patients with MND participated. A majority of patients indicated they would be happy to self-monitor their health from home (69%), be remotely monitored by a multidisciplinary care team (75%), and would be willing to participate in clinical trials from home (65%). Patients considered respiratory function and muscle strength most valuable for home-monitoring. The majority of patients considered the use of at least three devices/apps (75%) once a week (61%) to be acceptable for home-monitoring. Fifteen percent of patients indicated they would not wish to perform home-measurements; reporting concerns about the burden and distress of home-monitoring, privacy and data security. CONCLUSION: Most patients with MND exhibited a positive attitude toward the use of digital technology in both care and clinical trial settings. A subgroup of patients reported concerns with home-monitoring, which should be addressed in order to improve widespread adoption of remote digital technology in clinical MND care.

Exploring patient and public involvement in motor neuron disease research.

Objectives: Patient and public involvement (PPI) is a relatively new practice whereby researchers involve patients and the public in the conduct of their research. The Sheffield Motor Neurone Disorders Research Advisory Group (SMNDRAG) is one of the first groups to specialise in motor neuron disease (MND). Its members include people living with MND, carers, relatives, volunteers, clinicians, and scientists. Our aim was to explore the experiences of those who participate in, organise and work with the SMNDRAG. Methods: We conducted 13 semi-structured interviews: 10 with members of the SMNDRAG and three with researchers who have worked with the group. We used thematic analysis to identify ways in which the group influenced research and the barriers and enablers to PPI. Results: A number of motivations for participating in the SMNDRAG were reported but the majority were altruistic. The SMNDRAG offered individuals psychosocial and intellectual benefits. The SMNDRAG has overcome a number of practical and psychological barriers to developing a successful and effective collaborative partnership resulting in a positive impact on research and researchers at each stage of the research process. For example, the group identified research priorities which ensured that research was patient-focused. However, several barriers remain, including the lack of diversity within the group and the perception that PPI participation requires a "certain type of person." Conclusions: PPI can make a valuable contribution to all aspects of research and can have a positive impact on those involved. We recommend ways in which PPI can and should be incorporated into research.

Process evaluation and exploration of telehealth in motor neuron disease in a UK specialist centre.

OBJECTIVES: To evaluate the processes involved in using a novel digitally enabled healthcare system (telehealth in motor neuron disease (TiM)) in people living with motor neuron disease (MND) and their informal carers. We examined TiM implementation, potential mechanisms of impact and contextual factors that might influence TiM implementation or impact. DESIGN: An 18-month, single-centre process evaluation within a randomised, pilot and feasibility study. INTERVENTION: TiM plus usual care versus usual care alone. SETTING: A specialist UK MND care centre. PARTICIPANTS: 40 patients with MND and 37 primary informal carers. PRIMARY AND SECONDARY OUTCOME MEASURES: Patient, carer and staff outcomes and experiences using semistructured interviews. Descriptive data on implementation and use of TiM. RESULTS: The TiM was acceptable and accessible to patients, carers and staff. Intervention uptake and adherence were good: 14 (70%) patients completed a TiM session at least fortnightly. Barriers to TiM use (such as technology experience and disability) were overcome with well-designed technology and face-to-face training. Reported potential benefits of TiM included improved communication and care coordination, reassurance, identification of complications and the potential for TiM to be an alternative or addition to clinic. Benefits depended on patients' current level of needs or disability. The main challenges were the large number of alerts that were generated by TiM, how the clinicians responded to these alerts and the mismatch between patient/carer expectations and nurses actions. This could be improved by better communication systems and adjusting the alerts algorithm. CONCLUSION: TiM has the potential to facilitate access to specialist care, but further iterative developments to the intervention and process evaluations of the TiM in different services are required. TRIAL IDENTIFIER NUMBER: ISRCTN26675465.

Using telehealth in motor neuron disease to increase access to specialist multidisciplinary care: a UK-based pilot and feasibility study.

OBJECTIVES: Care of patients with motor neuron disease (MND) in a specialist, multidisciplinary clinic is associated with improved survival, but access is not universal. We wanted to pilot and establish the feasibility of a definitive trial of a novel telehealth system (Telehealth in Motor neuron disease, TiM) in patients with MND. DESIGN: An 18-month, single-centre, mixed-methods, randomised, controlled pilot and feasibility study. INTERVENTION: TiM telehealth plus usual care versus usual care. SETTING: A specialist MND care centre in the UK. PARTICIPANTS: Patients with MND and their primary informal carers. PRIMARY AND SECONDARY OUTCOME MEASURES: Recruitment, retention and data collection rates, clinical outcomes including participant quality of life and anxiety and depression. RESULTS: Recruitment achieved the target of 40 patients and 37 carers. Participant characteristics reflected those attending the specialist clinic and included those with severe disability and those with limited experience of technology. Retention and data collection was good. Eighty per cent of patients and 82% of carer participants reported outcome measures were completed at 6 months. Using a longitudinal analysis with repeated measures of quality of life (QoL), a sample size of 131 per arm is recommended in a definitive trial. The methods and intervention were acceptable to participants who were highly motivated to participate to research. The low burden of participation and accessibility of the intervention meant barriers to participation were minimal. However, the study highlighted difficulties assessing the associated costs of the intervention, the challenge of recruitment in such a rare disease and the difficulties of producing rigorous evidence of impact in such a complex intervention. CONCLUSION: A definitive trial of TiM is feasible but challenging. The complexity of the intervention and heterogeneity of the patient population means that a randomised controlled trial may not be the best way to evaluate the further development and implementation of the TiM. TRIAL REGISTRATION NUMBER: ISRCTN26675465.