Alexandra Wright-Hughes

Introduction: Managing mood, cognition and fatigue are top unmet needs reported by stroke survivors, which impact quality of life. There is currently no standardised UK care pathway to support post-stroke psychological outcomes. The ENhanced Reviews of PsychologIcal Changes (ENRICH) programme, an intervention co-designed with stroke survivors, carers and healthcare professionals, aims to fill this gap. Here, we describe the protocol for evaluating the feasibility and acceptability of ENRICH. Methods and analysis: ENRICH reviews comprise cognition, mood and fatigue assessment, personalised psychoeducation and tools to communicate results and discuss self-management strategies, delivered at 1, 3 and 6 months post-stroke. N=140 participants (N=80 patients who had a stroke, N=45 carers, N=15 healthcare professionals) will be recruited to a single-arm multicentre feasibility study. Patients who had a stroke and carers will complete demographics at baseline (T1) questionnaires of quality of life, mood and healthcare resource use at 6 months post-stroke (T2) and an optional interview on experiences of ENRICH. Process evaluation will include fidelity assessment via audio recordings. Descriptive statistics will be calculated for study outcomes. Key qualitative acceptability outcomes are sought on intervention delivery by clinicians, patients and carers. Key intervention delivery feasibility outcomes relate to training clinicians (including competency and fidelity delivering ENRICH), and review completion rates. Study feasibility outcomes will include site and participant recruitment and retention rates and completion of candidate primary outcome measures on quality of life. Ethics and dissemination: The ENRICH study was approved by a UK Research Ethics Committee (reference: 24/LO/0341). Consent procedures include a waiver of consent to the intervention itself due ENRICH’s service-level design and written informed consent/consultee advice for participants providing research data. Results will be disseminated through peer-reviewed publications, conferences and lay summaries for study participants and healthcare professionals. Results will inform whether ENRICH is acceptable to delivering clinicians and receiving patients who had a stroke and carers, and provide key insights to inform a future randomised trial to determine effectiveness. Trial registration number: ISRCTN16018388 .

Structured Background: Post-Traumatic Stress Disorder (PTSD) is a mental health condition affecting people who experience traumatic events. Trauma-exposed occupational groups report higher rates of PTSD than the general population. Current treatments, and access, often take months and may cause distress when people are required to talk about the trauma. Objective: To determine the proof of concept of FIRST, a brief, non-trauma focussed therapy, in two separate populations with employment-associated PTSD. Method: Two independent, single-arm, experimental therapy pilot trials were conducted. Trial one recruited 20 military veterans who received FIRST therapy via trained third-sector therapists. Trial two recruited 16 health and social care workers with FIRST therapy delivered by healthcare provider therapists. All participants were adults with PTSD (confirmed via CAPS-5 in trial one, and symptom score of ≥33 on the PCL5 in trial two). Primary outcomes were recruitment feasibility, retention, data quality and reduction in PTSD symptoms. Secondary outcomes were anxiety and depression symptoms, daily life functioning and perceived health status. Veterans were followed up at 12 weeks post-enrolment and healthcare workers at 8 weeks. Results: The veteran trial progression criteria to main trial were met. Seventy-nine people screened eligible, 43 attended a CAPS-5 assessment; 20 had confirmed PTSD and were enrolled. Seventeen completed therapy and 12-week outcome measures. Mean PCL-5 scores decreased from 48.7 (SD = 13.02, n=20) at baseline to 23.5 (SD = 15.30, n=17) at 12-weeks. The healthcare worker trial obtained informed consent from 16 participants, 10 commenced therapy and were included in analysis with eight completing therapy. Mean PCL-5 scores decreased from 42.60 (12.23, (n=10) at baseline to 22.00 (19.92, n=8) at 8-weeks. Conclusions: Proof of concept of FIRST was established. PTSD symptom reductions exceeded the PCL-5 minimal clinically important difference. Undertaking a fully powered randomised controlled trial of FIRST therapy is feasible within both healthcare and third sectors. Highlights: Post-traumatic stress disorder (PTSD) is more common in military veterans and health workers than the general population Therapy can be challenging to commence and complete when it requires a focus on the trauma incident FIRST offers a promising, brief, non-trauma focused therapy for the treatment of PTSD

Background The Needs Assessment Tool-Cancer (NAT-C) is a consultation guide to identify, triage and reduce unmet patient needs. Objectives We aimed to assess NAT-C fidelity, mechanisms of action and implementation issues in UK primary care as part of a clinical and cost-effectiveness cluster randomised controlled trial of the NAT-C for people with cancer compared with usual care (registration: ISRCTN15497400). Methods Design: a mixed-methods process evaluation informed by normalisation process theory (NPT). Setting: 21 participating general practices in England were randomised to be trained to conduct an NAT-C guided consultation with people with cancer (excluding those in remission). General practitioner fidelity of intervention and clinical action resulting from the NAT-C consultation was noted. Two Normalisation MeAsure Development Questionnaire surveys were distributed to trained clinicians before (Survey 1) and after delivery of ≥2 NAT-C consultations (Survey 2). Semi-structured interviews were conducted with clinicians (post delivery ≥2 NAT-C consultations) and key stakeholders in primary and cancer care. Fidelity, action and paired before/after survey data were analysed using descriptive statistics. Interview data were analysed using a deductive thematic framework approach (NPT-informed). Data were narratively synthesised with cross-tabulated key findings. Results Of the 360/376 (96%) NAT-C consultations delivered, 258/360 (72%) resulted in clinical action, including 50 (13%) external referrals. 14 paired before (Survey 1, n=53) and after (Survey 2, n=29) responses. Survey 1 showed positive responses across all NPT domains, but while continuing to see relevance, usefulness and legitimacy, Survey 2 highlighted concerns about insufficient resources and management support. 16 clinician participants (eight GPs, eight key stakeholders; 50% male) completed interviews. Following synthesis, we identified five themes: (1) the perceived value of the NAT-C; (2) ‘champions’ are important at all levels (practice, regionally and nationally); (3) research evidence is seen as important, but influences implementation indirectly through policy, clinical guidelines and resourced initiatives; (4) adequate resources are fundamental for implementation beyond practice level and (5) NAT-C practicalities; training is adequate, but robust functional information technology systems are needed. Conclusion Implementation requires champions and clinicians ‘buy-in’ to the patient value to legitimise use. In the context of current primary care pressures, resources were seen as essential to embed the NAT-C, but financial incentives were viewed with mixed feelings. Trial registration number ISRCTN15497400.

Objective: This paper describes the development of an Early Stroke Specialist Vocational Rehabilitation intervention to support return to work following stroke and its delivery in the RETAKE trial. Methods: Iterative three stage, target population approach to intervention development and evaluation informed by the Medical Research Council Framework. Stage 1 (Initial codevelopment): interviews with key stakeholder service providers and users’ and mapping of services supporting return to work after stroke to identify and explore barriers to and unmet needs for support; intervention codevelopment with experts and patient and public involvement (PPI). Stage 2 (Refinement): expert panel codevelopment workshops and systematic review to identify vocational rehabilitation intervention mechanisms of change in supporting return to work after stroke. Stage 3 (Testing): intervention piloting in two case studies, feasibility testing in a randomised controlled trial, acceptability interviews with stroke and employer participants. Further intervention refinement following delivery in the RETAKE randomised controlled trial. Results: Stage 1: service mapping and 25 stakeholder interviews identified service gaps and unmet needs relating to early identification of employed stroke survivors, mild stroke, and hidden disabilities. Access to timely support relied on geographical proximity to a specialist hub and tacit knowledge of complex health, education and employment services and provider roles. Return to work issues reported by stroke survivors informed Early Stroke Specialist Vocational Rehabilitation prototype design objectives. Iterative developments following piloting included fatigue management, involvement of general practitioners, work simulation and liaison with other healthcare services. Interviews with 12 recipient stroke survivors and 6 employers identified additional features including occupational therapist negotiation skills, ability to respond to changing needs over time and patient empowerment to self-re-refer. The review corroborated intervention components and mechanisms and identified additional mechanisms, for example, peer support, supported self-management. Intervention mechanisms identified across the three stages were early intervention, understanding the impact of stroke on the person, their job and work environment, vocational goal setting, implementing workplace accommodations, individual tailoring, work preparation, colocation, case co-ordination, Multidisciplinary Team (MDT) working, employer engagement and education, and responsiveness, which involved monitoring work stability, providing feedback, and responding to changing needs over time and participant self-re-referral. In RETAKE, Early Stroke Specialist Vocational Rehabilitation was successfully delivered to 95.4% of allocated participants with 75.3% compliance. Intervention commenced a median 38 days (interquartile range 23–56, range 6–216) post stroke and continued for ≤ 12 months. Participants had a median seven intervention sessions (interquartile range 4–12, range 0–37), with discharge a median 10.3 months (interquartile range 5.5–12.0, range 0–15.4) post randomisation. Most intervention sessions were delivered via telerehabilitation (51.7%), in participants’ homes (35.9%) or workplaces (6.4%). There was little difference between the number of sessions offered [mean 9.6 (standard deviation 7.46, range 0–39)] and attended [mean 9.0 (standard deviation 7.16), range 0–37]. However, occupational therapist contact with employers only occurred for 109 (36.8%) participants and employer visits occurred for 74 (25.0%). The Early Stroke Specialist Vocational Rehabilitation focus changed between the feasibility and definitive trial, with greater emphasis on current issues, fatigue management and informal psychological support, possibly due to the coronavirus disease discovered in 2019 pandemic. A programme theory and logic model illustrating the refined intervention and a description of Early Stroke Specialist Vocational Rehabilitation delivered in the RETAKE trial is reported. Conclusion: This comprehensive description of Early Stroke Specialist Vocational Rehabilitation will enable occupational therapists to implement Early Stroke Specialist Vocational Rehabilitation in practice and facilitative future evaluation. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 15/130/11.

Background: Self-harm is common in adolescents and a major public health concern. Evidence for effective interventions is lacking. An individual participant data meta-analysis has potential to provide more reliable estimates of the effects of therapeutic interventions than conventional meta-analyses and to explore which treatments are best suited to certain groups. Methods: A systematic review and individual participant data meta-analysis of randomised controlled trials of therapeutic interventions to reduce repeat self-harm in adolescents with a history of self-harm and who had presented to clinical services. We searched Cochrane Library, EMBASE, trial registers and other databases for randomised controlled trials published in January 2022. Eligible randomised controlled trials compared any therapeutic intervention against a control, aimed to reduce self-harm in adolescents (11–18 years old), with past self-harm presenting to clinical services, and collected outcome data on self-harm or suicide attempts. Interventions reviewed were grouped into nine categories: cognitive–behavioural therapy; dialectical behaviour therapy; family therapy; group therapy; mentalisation based, psychodynamic, cognitive analytic therapy; multisystemic therapy; problem-solving, psychoeducation, support; postcards, tokens, documents (postcards/tokens); and other single session, brief interventions. Control interventions were all either treatment as usual or enhanced treatment as usual and were not usually well described. There were no ‘no treatment’ controls except in the postcard/document/token studies. Primary outcome was repetition of self-harm at 12 months. Other outcomes included repetition of self-harm at other time points, overall mental health, depressive symptoms, thoughts of suicide, quality of life and death. Two-stage random-effects individual participant data meta-analyses were conducted overall and by intervention, and to examine interaction between treatment received and participant characteristics. Secondary analyses incorporated aggregate data from randomised controlled trials without individual participant data. Metaregression explored moderating study effects. Results: We identified 39 eligible studies, from 10 countries, where we sought individual participant data (18 studies with full sample eligibility, 21 with partial sample eligibility). We obtained individual participant data from 26 studies of 3448 eligible participants. We used published data from a further seven studies where individual participant data were not available for a combined individual participant data aggregate data meta-analysis (698 participants). For our primary outcome, repetition of self-harm, only six studies were rated as low risk of bias. There was no evidence that intervention/s were more or less effective than controls at preventing repeat self-harm by 12 months using individual participant data (odds ratios 1.06, 95% confidence interval 0.86 to 1.31) or individual participant data + aggregate data (odds ratios 1.02, 95% confidence interval 0.82 to 1.27) and no evidence of heterogeneity of treatment effects on study and treatment factors. We found no evidence that intervention was more or less effective than control for secondary outcomes, except general psychopathology and suicidal ideation at 12 and 6 months, respectively. Across all interventions, participants with multiple prior self-harm episodes showed evidence of improved treatment effect on self-harm repetition 6–12 months after randomisation [odds ratios 0.33 (95% confidence interval 0.12 to 0.94), studies = 9, n = 1771]. Modest evidence suggesting differential treatment effects based on participants’ age, gender, self-harm method, and anxiety levels are noted. Limitations: A significant limitation was missing individual participant data where authors were unable to share data; we offset this by including published data in secondary individual participant data plus aggregate meta-analysis. A wide range of interventions were evaluated and lacked replication. There was variability in the definitions and timings of outcomes, measures used for data collection, and available moderator data, with little consistency across studies. Conclusions: More attention needs to be paid to seeking appropriate consent from study participants for data-sharing. We found no evidence that any therapeutic intervention (overall or by intervention) was more or less effective than control for reducing repeat self-harm. We are therefore unable to recommend any specific intervention to prevent repetition of self-harm in adolescents. We observed evidence and trends indicating more effective interventions within specific subgroups. Analysis was constrained due to scarcity of data concerning common baseline characteristics, outcomes, and follow-up lengths. We recommend efficient, adaptive platform trial designs to tackle research questions and ascertain the most effective interventions for different groups, covering available treatments. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/117/11.

Background: There are over 200,000 hospital attendances for self-harm per annum in the United Kingdom at an estimated annual cost of £133–162M. Systematic reviews prior to commencing the study suggested that brief psychological interventions are effective in reducing psychological distress after self-harm and reduce repetition of self-harm. Objective: The SafePIT trial was designed to evaluate the effectiveness and cost-effectiveness of self-harm-focused psychological therapy plus standard care versus standard care alone. Design: Pragmatic, multicentre individually randomised controlled trial of brief psychodynamic-interpersonal therapy compared with standard care with internal pilot, cost-effectiveness and process evaluation. Setting and participants: People aged over 18 years who attend hospital after intentional self-harm with a history of ≤ 3 episodes in the last 12 months. Intervention: Individual psychodynamic-interpersonal therapy, delivered face to face or by video conferencing by liaison mental health nurses, over four (or fewer by mutual agreement) 50-minute weekly sessions with two optional boosters. Main outcome measures: The primary outcome was time from randomisation to first repetition of self-harm leading to hospital attendance. Secondary outcomes (at 6 and 12 months) included rate of repetition of self-harm leading to hospital attendance; self-reported self-harm using questionnaires and Short Message Service; psychological distress and clinically significant improvement (Clinical Outcomes in Routine Evaluation – Outcome Measure); anxiety (Generalised Anxiety Disorder-7); hopelessness (Beck Hopelessness Scale); interpersonal function (Inventory of Interpersonal Problems-32) and quality of life (EuroQol-5 Dimensions, five-level version; Recovering Quality of Life; Clinical Outcomes in Routine Evaluation-6D). Results: The planned sample size was 770 participants. The trial closed to recruitment early in January 2023 at the end of the 12-month internal pilot, with 22 randomised participants, 12 allocated to psychodynamic-interpersonal therapy and 10 to standard care. Due to the early trial closure, trial follow-up was curtailed to 6 months, and analyses are restricted to descriptive statistics. Seven of 12 participants allocated to psychodynamic-interpersonal therapy started therapy, and four completed therapy. Participant-reported secondary outcomes were completed for nine (40.9%) participants at 6 months. Repetition of self-harm leading to hospital presentation could be assessed for 18 participants and occurred in two participants in the psychodynamic-interpersonal therapy arm (18.2%) and no participants in the standard care arm within 6 months of randomisation. Economic findings indicated no substantive changes in health-related quality of life, or primary and secondary care resource usage across arms or over time. Intervention costs were highly sensitive to assumptions regarding the number of patients that would be treated per therapist in real-world role out of intervention. Limitations: The study was unable to recruit the necessary sample size, preventing the trial from progressing. The trial met with several challenges. Conclusions: Trial timelines coincided with the start of the second wave of the COVID-19 pandemic, causing substantial delays, difficulties with recruitment and, ultimately, its early closure. Although the trial closed early and with insufficient participants to proceed with full statistical analysis, our experiences and recommendations can inform future trial design and delivery. Future work: Self-harm remains a major risk factor for suicide, and provision of cost-effective interventions for people who self-harm is a key part of the government’s Suicide Prevention Strategy. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR131334.

Background: Many patients with ulcerative colitis report ongoing diarrhoea even when their disease is stable and in remission. Design: MODULATE was a pragmatic, multicentre, seamless, adaptive, phase 2/3 open-label, parallel-group, multiarm multistage randomised controlled trial. Setting and participants: People aged over 18 years with stable ulcerative colitis who had diarrhoea, recruited from secondary care sites in the United Kingdom. Interventions: The control arm consisted of modified first-line dietary advice given to all patients with irritable bowel syndrome; the first interventional arm was amitriptyline, a tricyclic antidepressant, which at low doses slows colonic transit; the second intervention was loperamide, an antidiarrhoeal drug also thought to slow colonic transit; the third was ondansetron, an antiemetic thought to slow colonic transit; and the fourth was a diet low in fermentable oligo-, di-, and mono-saccharides and polyols, which is thought to reduce bloating and gas within the small intestine. All patients randomised to an interventional arm were to receive treatment for 6 months. Main outcome measures: Primary outcome measures: Phase 2: Improvement in diarrhoea measured using the Gastrointestinal Symptom Rating Scale-irritable bowel syndrome questionnaire at 8 weeks post randomisation: improvement defined as those reporting minor discomfort from diarrhoea or less (scoring ≤ 2 on the diarrhoea subscale). Secondary outcome measures: Phases 2 and 3: Measured at both 8 weeks and 6 months: Improvement in diarrhoea measured using the Gastrointestinal Symptom Rating Scale-irritable bowel syndrome. Blood for C-reactive protein, stool for faecal calprotectin at 6 months only, reviewing case notes for escalation of medical therapy for ulcerative colitis. Anxiety and depression, via the Hospital Anxiety and Depression Scale. Results: The MODULATE trial opened in December 2021 and closed in January 2023. Of the eight secondary care sites that completed contracting, only four opened to recruitment during this time, and one person was randomised. Trial timelines coincided with the start of the COVID-19 pandemic, causing substantial delays and, ultimately, its early closure. During this time, the trial underwent two major redesign phases, enabling a fully remote participant pathway incorporating electronic consent, remote data capture, posted blood and stool sample kits for eligibility screening, delivery of the dietary intervention via telephone or video call platform, postage of trial investigational medicinal products directly to participants’ homes and all trial follow-up appointments conducted via telephone. The second phase of redesign pushed the trial towards a fully decentralised model. However, this stage was not implemented due to the decision to close the trial early. Limitations: The study was unable to recruit the necessary sample size, preventing the trial from progressing. The trial met with several challenges. The Trial Steering Committee’s root cause analysis concluded that the pandemic was the leading factor in trial closure, especially regarding our ability to recruit both sites and participants. Conclusions: Although the trial closed early and with insufficient participants to proceed with full statistical analysis, lessons were learnt that could potentially inform future remote trial design and decentralised participant pathways. Future work: MODULATE was a commissioned call in response to a priority question identified by people living with ulcerative colitis. The question remains important and unanswered; trials to address it are needed. Given the recruitment difficulties we experienced, consideration should be given to conducting these in both primary and secondary care. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/33/03.

Background: Return-to-work is a major goal achieved by fewer than 50% stroke survivors. Evidence on how to support return-to-work is lacking. Aims: This study aimed to evaluate the clinical effectiveness of Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care (UC) (i.e. usual NHS rehabilitation) versus UC alone for helping people return-to-work after stroke. Methods: This pragmatic, multicentre, individually randomized controlled trial with embedded economic and process evaluations compared ESSVR with UC in 21 NHS stroke services across England and Wales. Eligible participants were aged ⩾ 18 years, in work at stroke onset, hospitalized with new stroke and within 12 weeks of stroke. People not intending to return-to-work were excluded. Participants were randomized (5:4) to individually tailored ESSVR delivered by stroke specialist occupational therapists for up to 12 months or usual National Health Service rehabilitation. Primary outcome was self-reported return-to-work for ⩾ 2 h per week at 12 months. Primary and safety analyses were done in the intention-to-treat population. Results: Between 1 June 2018, and 7 March 2022, 583 participants (M _age 54.1 years (SD 11.0), 69% male) were randomized to ESSVR (n = 324) or UC (n = 259). Primary outcome data were available for 454 (77.9%) participants. Intention-to-treat analysis showed no evidence of a difference in the proportion of participants returned-to-work at 12 months (165/257 (64.2%) ESSVR vs 117/197 (59.4%) UC; adjusted odds ratio 1.12 (95% CI: 0.75–1.68), p = 0.5678). There was some indication that older participants and those with more post-stroke impairment were more likely to benefit from ESSVR (interaction p = 0.0239 and p = 0.0959, respectively). Conclusion: To our knowledge, this is the largest trial of a stroke vocational rehabilitation (VR) intervention ever conducted. We found no evidence that ESSVR conferred any benefits over UC in improving return-to-work rates 12 months post-stroke. Return-to-work (for at least 2 h per week) rates were higher than in previous studies (64.2% ESSVR vs 59.4% UC) at 12 months and more than double that observed in our feasibility trial (26%). Interpretation of findings was limited by a predominantly mild–moderate sample of participants and the COVID-19 pandemic. The pandemic impacted the trial, ESSVR and UC delivery, altering the work environment and employer behavior. These changes influenced our primary outcome and the meaning of work in people’s lives; all pivotal to the context of ESSVR delivery and its mechanisms of action. Data access: Data available on reasonable request. Registration: ISRCTN12464275.