Do the current MS clinical course descriptors need to change and if so how? A survey of the MS community.

BACKGROUND AND OBJECTIVES: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS. METHODS: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics. RESULTS: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS. CONCLUSION: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles.

Healthy Parent Carers: Acceptability and practicability of online delivery and learning through implementation by delivery partner organisations.

BACKGROUND: Parent carers of disabled children are at increased risk of physical and mental health problems. The Healthy Parent Carers (HPC) programme is a manualised peer-led group-based programme that aims to promote parent carer health and wellbeing. Previously, the programme had been delivered in person, with recruitment and delivery managed in a research context. This study explored implementation by two delivery partner organisations in the United Kingdom. Facilitator Training and Delivery Manuals were modified for online delivery using Zoom due to COVID-19. METHODS: The study methodology utilised the Replicating Effective Programs framework. A series of stakeholder workshops informed the development of the Implementation Logic Model and an Implementation Package. After delivering the programme, delivery partner organisations and facilitators participated in a workshop to discuss experiences of implementing the programme. A wider group of stakeholders, including commissioners, Parent Carer Forums and charity organisations representatives and researchers subsequently met to consider the sustainability and potential barriers to delivering the programme outside the research context. RESULTS: This study explored implementation by two delivery partner organisations in the United Kingdom that were able to recruit facilitators, who we trained, and they recruited participants and delivered the programme to parent carers in different localities using Zoom. The co-created Implementation Logic Model and Implementation Package were subsequently refined to enable the further roll-out of the programme with other delivery partner organisations. CONCLUSIONS: This study provides insight and understanding of how the HPC programme can be implemented sustainably outside of the research context. Further research will evaluate the effectiveness of the programme and refine the implementation processes. PATIENT AND PUBLIC CONTRIBUTION: Parent carers, delivery partner organisation staff and service commissioners were consulted on the design, delivery and reporting of the research.

CycLing and EducATion (CLEAT): protocol for a single centre randomised controlled trial of a cycling and education intervention versus standard physiotherapy care for the treatment of hip osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disorder for which there is no known cure. Non-surgical management for people with mild-to-moderate hip OA focuses mainly on alleviating pain and maximising function via the National Institute for Health and Care Excellence (NICE) recommended combination of education and advice, exercise, and, where appropriate, weight loss. The CHAIN (Cycling against Hip pAIN) intervention is a group cycling and education intervention conceived as a way of implementing the NICE guidance. METHODS: CycLing and EducATion (CLEAT) is a pragmatic, two parallel arm, randomised controlled trial comparing CHAIN with standard physiotherapy care for the treatment of mild-to-moderate hip OA. We will recruit 256 participants referred to the local NHS physiotherapy department over a 24-month recruitment period. Participants diagnosed with hip OA according to NICE guidance and meeting the criteria for GP exercise referral will be eligible to participate. Primary outcome is the difference in Hip Disability and Osteoarthritis Outcome Score (HOOS) function, daily living subscale between those receiving CHAIN and standard physiotherapy care. Secondary outcomes include performance-based functional measures (40 m walking, 30s chair stand and stair climb tests), ability for patient to self-care (patient activation measure) and self-reported health-related resource use including primary and secondary care contacts. The primary economic endpoint is the number of quality adjusted life years (QALYs) at 24 weeks follow-up. The study is funded by the National Institute for Health Research, Research for Patient Benefit PB-PG-0816-20033. DISCUSSION: The literature identifies a lack of high-quality trials which inform on the content and design of education and exercise in the treatment of patients with hip OA and explore cost-effectiveness. CLEAT is a pragmatic trial which seeks to build further evidence of the clinical benefits of the CHAIN intervention compared to standard physiotherapy care within a randomised, controlled trial setting, and examine its cost-effectiveness. TRIAL REGISTRATION NUMBER: ISRCTN19778222. Protocol v4.1, 24th October 2022.

Measuring the cost-effectiveness of treatments for people with multiple sclerosis: Beyond quality-adjusted life-years.

BACKGROUND: It is a familiar story. A promising multiple sclerosis (MS) treatment clears the three regulatory hurdles of safety, quality and efficacy, only to fall at the fourth: cost-effectiveness. This has led to concerns about the validity of the measures typically used to quantify treatment effects in cost-effectiveness analyses and in 2012, in the United Kingdom, the National Institute for Health and Care Excellence called for an improvement in the cost-effectiveness framework for assessing MS treatments. OBJECTIVE AND METHODS: This review describes what is meant by cost-effectiveness in health/social care funding decision-making, and usual practice for assessing treatment benefits. RESULTS: We detail the use of the quality-adjusted life-year (QALY) in resource allocation decisions, and set out limitations of this approach in the context of MS. CONCLUSION: We conclude by highlighting methodological and policy developments which should aid addressing these limitations.

Exploring the Factors that Influence Workforce Participation for People with Multiple Sclerosis: A Discrete Choice Experiment.

Purpose Research indicates that employment is beneficial for people with multiple sclerosis (MS). However, people with MS typically face reduced workforce participation compared to the general population. Using a discrete choice experiment (DCE) we explored which factors are most important in influencing employment choices of people with MS, and whether the relative importance of factors differs between subgroups. Methods Attributes and levels for the DCE were developed using a systematic literature review and public involvement techniques with people with MS. In an online survey, respondents were asked to choose between two hypothetical job scenarios described using six attributes. We used a large, national register (the UK MS Register), to recruit participants aged 18-64 years with a diagnosis of MS. Choice data were analysed using multinomial logit and latent class models. Results Analyses were based on responses from 2350 people with MS. The preferred model specification was a latent class model, with three classes of respondent. The relative importance of attributes varied between classes, with one giving the greatest weight to the impact of work on other aspects of their lives, the second to having supportive bosses and colleagues, and the third to job flexibility. The classes differed significantly in terms of age and gender, type of MS, and socio-economic status. Conclusions Significant heterogeneity was apparent among people with MS regarding the factors that influence their employment decisions. Attributes concerning the impact of work, attitudes in the workplace and job flexibility appear more influential than those concerning physical workplace adaptations.

What Difference Does It Make? A Comparison of Health State Preferences Elicited From the General Population and From People With Multiple Sclerosis.

BACKGROUND: A major debate in the quality-adjusted life-year (QALY) literature concerns whose preferences should be used to estimate health state values (HSVs) and to calculate QALYs. OBJECTIVES: This study explores differences between public and patient values for multiple sclerosis (MS) health states, described using an MS-specific classification system (Multiple Sclerosis Impact Scale-8 Dimensions [MSIS-8D]). METHODS: The MSIS-8D is an existing preference-based measure of health-related quality of life in MS, which has 2 tariffs of HSVs, based on the preferences of a representative sample of the UK general population (n = 1702) and of people with MS living in the United Kingdom (n = 1635), elicited using the time trade-off technique. Here, we explore differences between HSVs by sample type, using descriptive statistics and multivariate regression methods. RESULTS: Overall, the survey of people with MS produced significantly higher HSVs; estimated values ranged from 0.079 to 0.883 for the general population survey and from 0.138 to 0.894 for the MS survey. Differences in HSVs were more pronounced for severe health states. The difference between patient and public values varied across the dimensions of the MSIS-8D. People with MS placed greater importance on cognition than the general population, leading to lower HSVs when impairment was at a worse level; the reverse was true for the daily activities, fatigue, and depression dimensions. CONCLUSIONS: We identified significant differences in HSVs by sample type. Using patient rather than public values may influence the results of economic evaluations, depending on the dimensions of health-related quality of life affected by the intervention being assessed, and may therefore have important consequences for reimbursement decisions.

Health State Values Derived from People with Multiple Sclerosis for a Condition-Specific Preference-Based Measure: Multiple Sclerosis Impact Scale-Eight Dimensions-Patient Version (MSIS-8D-P).

OBJECTIVE: In economic evaluation, health outcomes are commonly quantified using quality-adjusted life-years (QALYs) derived from the preferences of a sample of the general population. It can be argued that this approach ignores the preferences of people with experience of the condition, and that patient preferences have a place in the valuation of health outcomes. Here we report the estimation of a preference-based index for an existing condition-specific preference-based measure for multiple sclerosis (MS), the MSIS-8D, based on the preferences of people with MS. STUDY DESIGN: Internet time trade-off (TTO) survey, eliciting preferences from people with MS. METHODS: We elicited preferences from a sample of people with MS (N = 1635) across 169 MSIS-8D health states, using the TTO technique. We fitted ordinary least squares and random effects models to the survey data to estimate values for all health states described by the MSIS-8D. RESULTS: The new patient-derived index (the MSIS-8D-P) provides values ranging from 0.893 for the best possible health state to 0.138 for the worst state. The MSIS-8D-P exhibits good discriminative validity, identifying expected significant differences between groups based on presence/absence of MS, type of MS, and duration since diagnosis. CONCLUSIONS: The MSIS-8D-P index of values for MS-specific health states provides an opportunity to estimate QALYs based on patient preferences, for use in economic evaluations of treatments for MS. More broadly, it adds to the methods and data available to consider the health-related quality of life of people with MS to inform resource allocation and individual-level decisions regarding treatments for MS.

Health Utilities for Multiple Sclerosis.

OBJECTIVES: To estimate health state utility values (HSUVs) for multiple sclerosis (MS) by key demographic and clinical characteristics. METHODS: Data from a UK prospective, longitudinal, cohort study of people with MS were used for analysis. Patient-reported outcomes on the EuroQol five-dimensional questionnaire (EQ-5D) and the six-dimensional health state short form (SF-6D) (derived from 36-item short form health survey), SF-36 were used to estimate HSUVs by age, sex, MS type, time since diagnosis, disease severity (Expanded Disability Status Scale score), and relapse characteristics. RESULTS: The cohort (n = 1,441) (11,778 returned questionnaires) was representative of the UK population with MS. Data indicated that primary and secondary progressive MS were associated with lower HSUVs than relapsing-remitting MS and that HSUVs decreased by disease severity. This was particularly apparent for the EQ-5D, with mean estimates ranging from 0.846 to 0.025 for Expanded Disability Status Scale scores 0 to 8, compared to mean SF-6D estimates ranging from 0.702 to 0.529. Experiencing a relapse in the previous 6 months had a significant impact on HSUVs, with mean decrements of 0.076 for the EQ-5D and 0.052 for the SF-6D. CONCLUSIONS: These findings demonstrate the negative impact of MS on health-related quality of life, especially as the condition progresses, and indicate the substantial influence of varying features of relapses on HSUVs. This is the first report of SF-6D values for a UK MS population and the first time that EQ-5D data have been presented in such detail for people with MS. The representative nature of the sample means that these data can be used to offer decision makers more precise estimates of the effectiveness and cost-effectiveness of MS treatments.

Mental Imagery to Reduce Alcohol-related harm in patients with alcohol use disorder and alcohol-related liver damaGE: the MIRAGE randomised pilot trial results.

OBJECTIVE: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving. We conducted a multicentre randomised pilot trial of treatment as usual (TAU) versus FIT+TAU in people admitted to hospital with ARLD and AUD. DESIGN: Participants were randomised to TAU (a single session of brief intervention) or FIT+TAU (TAU with one hospital-based FIT session then eight telephone sessions over 6 months). Pilot outcomes included recruitment rate and retention at day 180. Secondary outcomes included fidelity of FIT delivery, alcohol use, and severity of alcohol dependence. RESULTS: Fifty-four participants (mean age 49; 63% male) were recruited and randomised, 28 to TAU and 26 to FIT+TAU. The retention rate at day 180 was 43%. FIT was delivered adequately by most alcohol nurses. 50% of intervention participants completed FIT sessions 1 and 2. There were no differences in alcohol use or severity of alcohol dependence between treatment groups at day 180. CONCLUSION: Participants with ARLD and AUD could be recruited to a trial of FIT versus FIT+TAU. However, retention at day 180 was suboptimal. Before conducting a definitive trial of FIT in this patient group, modifications in the intervention and recruitment/retention strategy must be tested. TRIAL REGISTRATION NUMBER: ISRCTN41353774.

Evaluation of the prehospital use of a Valsalva assist device in the emergency treatment of supraventricular tachycardia (EVADE SVT): study protocol for a stepped wedge cluster randomised controlled trial.

INTRODUCTION: Patients with episodes of supraventricular tachycardia (SVT), a common heart arrhythmia, are often attended by ambulance services. International guidelines advocate treatment with the Valsalva manoeuvre (VM), but this simple physical treatment has a low success rate, with most patients requiring conveyance to hospital. The Valsalva Assist Device (VAD) is a simple device that might help practitioners and patients perform a more effective VM and reduce the need for patients to be taken to hospital. METHODS AND ANALYSIS: This stepped wedge cluster randomised controlled trial, conducted within a UK ambulance service, compares the current standard VM with a VAD-delivered VM in stable adult patients presenting to the ambulance service with SVT. The primary outcome is conveyance to hospital; secondary outcomes measures include cardioversion rates, duration of ambulance care and number of subsequent episodes of SVT requiring ambulance service care. We plan to recruit approximately 800 patients, to have 90% power to detect an absolute reduction in conveyance rate of 10% (from 90% to 80%) between the standard VM (control) and VAD-delivered VM (intervention). Such a reduction in conveyance would benefit patients, the ambulance service and receiving emergency departments. It is estimated potential savings would pay for devices for the entire ambulance trust within 7 months. ETHICS AND DISSEMINATION: The study has been approved by the Oxford Research Ethics Committee (reference 22/SC/0032). Dissemination will be through peer-reviewed journal publication, presentation at national and international conferences and by the Arrhythmia Alliance, a patient support charity. TRIAL REGISTRATION NUMBER: ISRCTN16145266.

The SWiFT trial (Study of Whole Blood in Frontline Trauma)-the clinical and cost effectiveness of pre-hospital whole blood versus standard care in patients with life-threatening traumatic haemorrhage: study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Early blood transfusion improves survival in patients with life-threatening bleeding, but the optimal transfusion strategy in the pre-hospital setting has yet to be established. Although there is some evidence of benefit with the use of whole blood, there have been no randomised controlled trials exploring the clinical and cost effectiveness of pre-hospital administration of whole blood versus component therapy for trauma patients with life-threatening bleeding. The aim of this trial is to determine whether pre-hospital leukocyte-depleted whole blood transfusion is better than standard care (blood component transfusion) in reducing the proportion of participants who experience death or massive transfusion at 24 h. METHODS: This is a multi-centre, superiority, open-label, randomised controlled trial with internal pilot and within-trial cost-effectiveness analysis. Patients of any age will be eligible if they have suffered major traumatic haemorrhage and are attended by a participating air ambulance service. The primary outcome is the proportion of participants with traumatic haemorrhage who have died (all-cause mortality) or received massive transfusion in the first 24 h from randomisation. A number of secondary clinical, process, and safety endpoints will be collected and analysed. Cost (provision of whole blood, hospital, health, and wider care resource use) and outcome data will be synthesised to present incremental cost-effectiveness ratios for the trial primary outcome and cost per quality-adjusted life year at 90 days after injury. We plan to recruit 848 participants (a two-sided test with 85% power, 5% type I error, 1-1 allocation, and one interim analysis would require 602 participants-after allowing for 25% of participants in traumatic cardiac arrest and an additional 5% drop out, the sample size is 848). DISCUSSION: The SWiFT trial will recruit 848 participants across at least ten air ambulances services in the UK. It will investigate the clinical and cost-effectiveness of whole blood transfusion versus component therapy in the management of patients with life-threatening bleeding in the pre-hospital setting. TRIAL REGISTRATION: ISRCTN: 23657907; EudraCT: 2021-006876-18; IRAS Number: 300414; REC: 22/SC/0072, 21 Dec 2021.

A rehabilitation intervention to improve recovery after an episode of delirium in adults over 65 years (RecoverED): study protocol for a multi-centre, single-arm feasibility study.

BACKGROUND: Delirium affects over 20% of all hospitalised older adults. Delirium is associated with a number of adverse outcomes following hospital admission including cognitive decline, anxiety and depression, increased mortality and care needs. Previous research has addressed prevention of delirium in hospitals and care homes, and there are guidelines on short-term treatment of delirium during admission. However, no studies have addressed the problem of longer-term recovery after delirium and it is currently unknown whether interventions to improve recovery after delirium are effective and cost-effective. The primary objective of this feasibility study is to test a new, theory-informed rehabilitation intervention (RecoverED) in older adults delivered following a hospital admission complicated by delirium to determine whether (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible. METHODS: The study is a multi-centre, single-arm feasibility study of a rehabilitation intervention with an embedded process evaluation. Sixty participants with delirium (aged > 65 years old) and carer pairs will be recruited from six NHS acute hospitals across the UK. All pairs will be offered the intervention, with follow-up assessments conducted at 3 months and 6 months post-discharge home. The intervention will be delivered in participants' own homes by therapists and rehabilitation support workers for up to 10 intervention sessions over 12 weeks. The intervention will be tailored to individual needs, and the chosen intervention plan and goals will be discussed and agreed with participants and carers. Quantitative data on reach, retention, fidelity and dose will be collected and summarised using descriptive statistics. The feasibility outcomes that will be used to determine whether the study meets the criteria for progression to a definitive randomised controlled trial (RCT) include recruitment, delivery of the intervention, retention, data collection and acceptability of outcome measures. Acceptability of the intervention will be assessed using in-depth, semi-structured qualitative interviews with participants and healthcare professionals. DISCUSSION: Findings will inform the design of a pragmatic multi-centre RCT of the effectiveness and cost-effectiveness of the RecoverED intervention for helping the longer-term recovery of people with delirium compared to usual care. TRIAL REGISTRATION: The feasibility study was registered: ISRCTN15676570.

Using the Multiple Sclerosis Impact Scale to estimate health state utility values: mapping from the MSIS-29, version 2, to the EQ-5D and the SF-6D.

OBJECTIVES: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a psychometrically validated patient-reported outcome measure increasingly used in trials of treatments for multiple sclerosis. However, it is non-preference-based and not amenable for use across policy decision-making contexts. Our objective was to statistically map from the MSIS-29, version 2, to the EuroQol five-dimension (EQ-5D) and the six-dimension health state short form (derived from short form 36 health survey) (SF-6D) to estimate algorithms for use in cost-effectiveness analyses. METHODS: The relationships between MSIS-29, version 2, and EQ-5D and SF-6D scores were estimated by using data from a cohort of people with multiple sclerosis in South West England (n=672). Six ordinary least squares (OLS), Tobit, and censored least adjusted deviation (CLAD) regression analyses were conducted on estimation samples, including the use of subscale and item scores, squared and interaction terms, and demographics. Algorithms from models with the smallest estimation errors (mean absolute error [MAE], root mean square error [RMSE], normalized RMSE) were then assessed by using separate validation samples. RESULTS: Tobit and CLAD. For the EQ-5D, the OLS models including subscale squared terms, and item scores and demographics performed comparably (MAE 0.147, RMSE 0.202 and MAE 0.147, RMSE 0.203, respectively), and estimated scores well up to 3 years post-baseline. Estimation errors for the SF-6D were smaller (OLS model including squared terms: MAE 0.058, RMSE 0.073; OLS model using item scores and demographics: MAE 0.059, RMSE 0.08), and the errors for poorer health states found with the EQ-5D were less pronounced. CONCLUSIONS: We have provided algorithms for the estimation of health state utility values, both the EQ-5D and SF-6D, from scores on the MSIS-29, version 2. Further research is now needed to determine how these algorithms perform in practical decision-making contexts, when compared with observed EQ-5D and SF-6D values.

Usability and acceptability of a cognitive training intervention (SMART) for people with multiple sclerosis (MS): A prefeasibility formative evaluation.

Background: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the central nervous system (CNS), increasing in incidence and prevalence across both developed and developing countries. Cognitive difficulties are common in MS sufferers with 70% experiencing difficulties in higher-level brain functioning such as planning, attention, problem solving, and memory. Computerised cognitive training programmes may hold promise as a treatment option for improving cognitive function in people with MS, subject to exploring and addressing potential barriers to usability and acceptability. Methods: This study aimed to test the usability and acceptability of a computerised cognitive training intervention-Strengthening Mental Abilities Through Relational Training (SMART) -for people with MS, through a mostly qualitative prefeasibility design ( n= 12). There were two phases of testing: (1) initial usability testing via a think-aloud protocol ( n= 6) and (2) alpha-testing to assess experienced acceptability over a four-week period of engagement ( n= 6). Data from the two phases were subjected to Framework Analysis, wherein we deductively applied the Health IT Usability Evaluation Model and Theoretical Framework of Acceptability to assess usability and acceptability, respectively. Results: Results show SMART to have satisfactory usability with participants reacting positively to the formatting, visuality, and process of the interface. Minor suggestions were made on how best to adapt SMART for people with MS, but the programme and facilitative support were generally perceived to be acceptable, with participants expressing positive feelings about taking part in the intervention, despite associated burdens. Conclusions: This prefeasibility study provides preliminary evidence of the usability and acceptability of SMART as a computerised cognitive training programme for people with MS. We conclude that we can now move forward with a feasibility trial of SMART, with the intention of proceeding to a definitive trial with cost-effectiveness analysis.

AIMS: We are developing a new 'brain training' treatment to help people with multiple sclerosis (MS) who have problems with thinking skills ( e.g., problem-solving, attention, and memory). This study aimed to test whether the training (called 'Strengthening Mental Abilities Through Relational Training' ['SMART']) is suitable for people with MS. Specifically, we assessed whether SMART was easy to use and acceptable for use in their everyday lives. BACKGROUND: MS is a long-term condition that affects the nervous system, with the number of cases increasing in both developed and developing countries. MS affects an individual's thinking skills, which can affect their ability to go about their everyday lives. Brain training has potential for improving thinking skills in people with MS, provided ease of use and factors impacting willingness to use the training are explored. Design and methods used: This study used a mix of methods, such as scores from objective tests and verbal feedback, to explore whether SMART is easy to use and acceptable for people with MS. The study had two phases: think-aloud interviews (participants provided feedback on whether the training interface and guidance were easy to use) and then the alpha-testing phase (participants tested the training over time, and then gave feedback on acceptability). Common and salient themes were identified in both phases. RESULTS: Participants found SMART to be suitably easy to use and acceptable for use by people with MS. Participants thought that the interface was visually appealing, and easy to operate and navigate. Participants made minor suggestions for improving the intervention, but feedback was generally positive, despite demands on time and energy. DISCUSSION: SMART appears to be suitable for people with MS. We conclude that we can go ahead with the next phase of testing SMART, as a possible treatment for improving thinking skills in people with MS.

Strengthening Mental Abilities with Relational Training (SMART) in multiple sclerosis (MS): study protocol for a feasibility randomised controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic condition of the central nervous system, affecting around 1 in every 600 people in the UK, with 130 new diagnoses every week. Cognitive difficulties are common amongst people with MS, with up to 70% experiencing deficits in higher-level brain functions-such as planning and problem-solving, attention, and memory. Cognitive deficits make it difficult for people with MS to complete everyday tasks and limit their abilities to work, socialise, and live independently. There is a clear need-and recognised research priority-for treatments that can improve cognitive functioning in people with MS. The absence of effective cognitive interventions exacerbates burdens on the services accessed by people with MS-requiring these services to manage sequelae of untreated cognitive deficits, including reduced quality of life, greater disability and dependence, and poorer adherence to disease-modifying treatments. Our planned research will fill the evidence gap through developing-and examining the feasibility of trialling-a novel online cognitive rehabilitation programme for people with MS (SMART). The SMART programme directly trains relational skills (the ability to flexibly relate concepts to one another) based on theory that these skills are critical to broader cognitive functioning. METHODS: The primary objective of this study aims to conduct a feasibility study to inform the development of a definitive trial of SMART for improving cognitive functioning in people with MS. The secondary objective is to develop the framework for a cost-effectiveness analysis alongside a definitive trial, and the exploratory objective is to assess the signal of efficacy. DISCUSSION: As a feasibility trial, outcomes are unlikely to immediately effect changes to NHS practice. However, this is a necessary step towards developing a definitive trial-and will give us a signal of efficacy, a prerequisite for progression to a definitive trial. If found to be clinically and cost-effective, the latter trial could create a step-change in MS cognitive rehabilitation-improving service delivery and optimising support with limited additional resources. TRIAL REGISTRATION: Registration ID: ClnicalTrials.gov: NCT04975685-registered on July 23rd, 2021. PROTOCOL VERSION: 2.0, 25 November 2021.

Mental Imagery to Reduce Alcohol-related harm in patients with alcohol dependence and alcohol-related liver damaGE: the MIRAGE pilot trial protocol.

INTRODUCTION: In the UK, alcohol use is the main driver of chronic liver disease and each year results in over 1 million unplanned hospital admissions and over 25 000 deaths from alcohol-related liver disease (ArLD). The only effective treatment to prevent progression of liver damage is reducing or ceasing alcohol consumption. Psychological and pharmacological therapies for alcohol misuse are ineffective in patients with ArLD. Functional imagery training (FIT) is a novel psychological therapy that builds on motivational interviewing techniques with multisensory imagery. This pilot trial aims to test the feasibility of training alcohol liaison nurses to deliver FIT therapy and of recruiting and retaining patients with ArLD and alcohol dependence to a randomised trial of FIT and treatment as usual (TAU) versus TAU alone. METHODS AND ANALYSIS: This is a randomised pilot trial of FIT and TAU versus TAU alone in 90 patients with ArLD and alcohol dependence admitted to one of four UK centres. The primary objectives are to estimate rates of screening, recruitment, randomisation, retention, adherence to FIT/TAU and a preliminary assessment of the FIT intervention in the ArLD population. Data from the pilot study will be used to finalise the design of a definitive randomised controlled trial to assess the effectiveness and cost-effectiveness of FIT. The proposed primary outcome measure for the definitive trial is self-reported alcohol use assessed using timeline follow-back. ETHICS AND DISSEMINATION: Research ethics approval was given by the Yorkshire and Humber-Bradford Leeds Research Ethics Committee (reference: 21/YH/0044). Eligible patients will be approached and written informed consent obtained prior to participation. Results will be disseminated through peer-reviewed open access journals, international conferences and a lay summary published on the Trials Unit website and made available to patient groups. TRIAL REGISTRATION NUMBER: ISRCTN41353774.

The impact of social isolation on the health status and health-related quality of life of older people.

PURPOSE: To investigate for socially isolated older people, and older people at risk of social isolation: (1) health status and health-related quality of life (HRQL); (2) the relationship between social isolation and health status/HRQL; (3) the relationship between two alternative measures of health status/HRQL. METHODS: Older people at risk of social isolation (n = 393) completed the EQ-5D and the SF-12. Multiple regression analyses were performed to examine the relationship between levels of social isolation and health status/HRQL, controlling for demographic/clinical characteristics. The agreement between EQ-5D and SF-6D (SF-12) scores was explored using descriptive psychometric techniques. RESULTS: Health status and health state values were much lower than UK general population age-matched norms. After controlling for depression, physical co-morbidities, age, gender, living alone status, employment and accommodation, social isolation was significantly associated, to a degree that was clinically relevant, with EQ-5D DSI, SF-6D (SF-12) and SF-12 MCS scores. The potential for ceiling effects on the EQ-5D with this population was identified. CONCLUSION: This work highlights the burden that social isolation may have on the health and well-being of older people. The potential HRQL gains from addressing social isolation may be considerable, with those at risk of social isolation also a key target group.

An evaluation of the effectiveness of a community mentoring service for socially isolated older people: a controlled trial.

BACKGROUND: Social isolation affects a significant proportion of older people and is associated with poor health outcomes. The current evidence base regarding the effectiveness of interventions targeting social isolation is poor, and the potential utility of mentoring for this purpose has not previously been rigorously evaluated. The purpose of this study was to examine the effectiveness of a community-based mentoring service for improving mental health, social engagement and physical health for socially isolated older people. METHODS: This prospective controlled trial compared a sample of mentoring service clients (intervention group) with a matched control group recruited through general practice. One hundred and ninety five participants from each group were matched on mental wellbeing and social activity scores. Assessments were conducted at baseline and at six month follow-up. The primary outcome was the Short Form Health Survey v2 (SF-12) mental health component score (MCS). Secondary outcomes included the SF-12 physical health component score (PCS), EuroQol EQ-5D, Geriatric Depression Score (GDS-10), social activity, social support and morbidities. RESULTS: We found no evidence that mentoring was beneficial across a wide range of participant outcomes measuring health status, social activity and depression. No statistically significant between-group differences were observed at follow-up in the primary outcome (p = 0.48) and in most secondary outcomes. Identifying suitable matched pairs of intervention and control group participants proved challenging. CONCLUSIONS: The results of this trial provide no substantial evidence supporting the use of community mentoring as an effective means of alleviating social isolation in older people. Further evidence is needed on the effectiveness of community-based interventions targeting social isolation. When using non-randomised designs, there are considerable challenges in the recruitment of suitable matches from a community sample. TRIAL REGISTRATION: SCIE Research Register for Social Care 105923.

What drives differences in preferences for health states between patients and the public? A qualitative investigation of respondents' thought processes.

Cost-effectiveness analyses using quality-adjusted life-years (QALYs) are used in decision-making regarding which interventions are available via many national healthcare systems. QALYs are calculated based on health state values provided by preference elicitation techniques. Several national decision-making bodies recommend that health state values should be based on preferences elicited from general populations, rather than from patients. Previous studies have shown systematic differences between health state values elicited from members of the general population and from patients. Various explanations for this phenomenon have been proposed, however empirical evidence for these is scarce. We aimed to explore possible reasons for discrepancies between public and patient valuations by undertaking qualitative cognitive interviews, asking 14 members of the general population and 12 people with multiple sclerosis (MS) to think aloud while completing a preference elicitation task (time trade-off) for MS-related health states. The interviews were undertaken between December 2016 and October 2017 in the South West region of England, and were analysed using the Framework Method. As anticipated, we found that participants with MS had more experience of health problems and used this experience to consider how they might adapt to the health states over time, and which dimensions of health-related quality of life were most important to them. We found no evidence that participants with MS were less affected by framing effects and focusing illusions, more likely to prioritise non-physical dimensions of health, or more prone to loss aversion, endowment effects and non-compensatory decision-making. These findings contribute to our understanding of how patients and members of the general population respond to preference elicitation exercises, and why their preferences may differ, and may help to inform developing areas of research, such as the joint presentation of cost-effectiveness results from multiple perspectives, and the use of preferences elicited from patients for experienced health states.

Involving Patients in Health Economics Research: "The PACTS Principles".

Discussion of public and patient involvement (PPI) in health economics (HE) research is growing. There is much literature on PPI principles and standards, but little specifically regarding involving patients in HE research. Here, we outline "PACTS", a set of principles, developed with a PPI group, for considering patient involvement in HE research. Planning: Involvement is best built in to research plans from the outset. This includes setting specific goals for involvement activities, and clearly communicating the background and purpose of involvement. Approach selection: We describe two main approaches to involvement-discussion-based and task-based. Discussion-based approaches are useful for generating broad insights and revealing "unknown unknowns". Task-based approaches offer a more focused means of shedding light on "known unknowns". Continuous involvement: Involving patients throughout the research process and across a range of projects helps build expertise for patients and insight for HE researchers. Team building: Meaningful involvement creates a shared sense of ownership of the research and, over time, helps to develop a team ethos, enhancing the positive impacts of involvement. Sensitivity: HE research can be perceived as technical and impersonal. Addressing this requires sensitivity, clarity, and an honest and open approach. There is increased recognition that patient contributors are experts at providing a "lived experience" perspective, in the way that clinicians are experts at providing an overview of conditions and HEs are experts in the methodology of their discipline. We hope these "PACTS Principles" complement existing PPI approaches and provide a useful foundation for health economists considering patient involvement.