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Abstract Background Patients, their family members and caregivers have firsthand experiences of living with or supporting someone living with a disease or medical condition. This knowledge by experience cannot be replaced by the knowledge acquired by clinicians, researchers, or other professionals through study and/or work. The Therapies for Long COVID in non-hospitalised individuals (TLC) research project was funded in the UK by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation to investigate the impact of long COVID on affected individuals. This article focuses on the implementation of PPIE for the TLC project. It provides details on the methodological approach that was adopted, the evaluation and reporting of the PPIE for the project and some previously unreported challenges we faced. Main body A PPIE Lead was appointed to coordinate PPIE for the project and facilitate communication and relationship building with the patient partners. Our overarching approach was collaborative with patient partners actively involved in the various work packages of the project.. This was achieved by recruiting PPIE members from (1) direct contacts, (2) long COVID support groups (3) a local general practitioner (GP) surgery. Although we were unable to hold face-to-face meetings due to the social restrictions during the COVID-19 pandemic, we offered patients the choice of using virtual platforms like Zoom, telephone calls, and emails for communication. We adopted a 4-tiered model for the PPIE group with each tier providing different opportunities for contributing to the project. This model helped the PPIE Lead to effectively co-ordinate PPIE activities for the project as well as provide all patient partners the opportunity to contribute to the project whilst managing their condition. PPIE for the TLC project was co-evaluated with patient partners. Conclusions Despite the challenges we encountered with the pandemic, the TLC project provided a valuable opportunity for patients to shape the design, conduct and dissemination of the research findings. The information provided in this article may be useful to other researchers and patients when planning PPIE for future health research. The implementation of PPIE in healthcare research could help ensure that the outcomes of research are those valued by and relevant to the needs of patients and other end users.

Abstract Background Left ventricular assist device (LVAD) recipients report symptom improvement but find adjusting to life with the LVAD challenging. These challenges are unique, and existing patient‐reported outcome measures (PROMs) do not reflect their experiences. This study aimed to develop a culturally relevant quality of life PROM for use with LVAD recipients in future research, design evolutions and clinical practice. Methods A three‐stage mixed‐methods approach was used to develop a PROM: stage 1 included group concept mapping (GCM); stage 2 semi‐structured qualitative interviews were conducted with 11 LVAD recipients and 10 clinicians, and a questionnaire was developed using a conceptual framework; and stage 3 used exploratory psychometric analysis of the PROM data using Rasch measurement theory. This paper presents stages 2 and 3. Results The conceptual framework consisted of four key concepts, including general health, life with the LVAD, equipment and clothing and emotional impact. Statements from interviews and GCM were used to create items for the LVAD quality of life (LVAD‐QoL). Cognitive interviews tested face validity and participant comprehension. Forty‐nine participants were recruited from three UK transplant centres. PROM data were collected and analysed using Rasch analysis. Four items displayed misfit; dependency between item sets was the biggest issue (57/485 pairwise differences). After restructuring and dealing with item misfit, the LVAD‐QoL conformed to the Rasch model, supporting the psychometric properties and quality of the LVAD‐QoL. Conclusions Using a mixed‐methods approach ensured the development of a robust and psychometrically sound tool for research, design evolution and clinical practice with LVAD recipients.

Abstract Post COVID-19 condition or long COVID is highly prevalent and often debilitating, with key symptoms including fatigue, breathlessness, and brain fog. There is currently a lack of evidence-based treatments for this highly complex syndrome. There is a need for clinical trial platforms to rapidly evaluate nonpharmacological treatments to support affected individuals with symptom management. We co-produced a mixed methods feasibility study to evaluate a multi-arm digital decentralised clinical trial (DCT) platform to assess non-pharmacological interventions for Long COVID, using pacing interventions as an exemplar. The study demonstrated that the platform was able to successfully e-consent participants, randomise them into one of four intervention arms, capture baseline data, and capture outcomes relevant to a health economic evaluation. The study also highlighted several challenges, including difficulties with recruitment, imposter participants, and high attrition rates. We highlight how these challenges can potentially be mitigated to make a fully powered DCT more feasible.

Introduction Traumatic brain injury (TBI) is a major cause of disability, with annual global incidence estimated as 69 million people. Survivors can experience long-term visual changes, altered mental state, neurological deficits and long-term effects that may be associated with mental illness. TBI is prevalent in military personnel due to gunshot wounds, and blast injury. This study aims to evaluate the relationship between evolving visual, biochemical and mental health changes in both military veterans and civilians, suffering from TBI, and detect preliminary indicators of prognosis for TBI recovery, and quality-of-life outcomes.Methods and analysis UNTANGLE is a 24-month prospective observational pilot study recruiting three patient groups: civilians with acute moderate-severe TBI, military veterans with diagnosis of a previous TBI and a control group of civilians or veterans with no history of a previous TBI. Patients will undergo visual, biochemical and mental health assessments, as well as patient-reported quality of life outcome measures over the course of a 1-year follow-up period.Ethics and dissemination Ethical approval has been obtained from the Health Research Authority and Health and Care Research Wales with a REC reference number of 23/NW/0203. The results of the study will be presented at scientific meetings and published in peer-reviewed journals, including both civilian and military-related publications. We will also present our findings at national and international meetings of learnt neuroscience and neuropsychiatry and military societies. We anticipate that our pilot study will inform a larger study on the long-term outcomes of TBI and quality of life, specific to military veterans, such that potential interventions may be accessed as quickly as possible.Trial registration number ISRCTN13276511.

Background Ulcerative colitis is an autoimmune reaction to imbalanced colonic microbiome in genetically predisposed patients. There have been four published randomised controlled trials of faecal microbiota transplant versus placebo in ulcerative colitis; three being positive. However, the methodology used varied and mechanistic data were sparse. Objective To identify an optimal faecal microbiota transplant delivery route to test in a future efficacy-powered randomised controlled trial. Design Prospective, multicentre, open-label, parallel-group, randomised pilot study. Participants were randomised in a 1 : 1 ratio to faecal microbiota transplant by nasogastric or by colonoscopy, minimised by partial Mayo score and current smoking status. Setting Three secondary care hospitals in the United Kingdom. Participants Thirty adult patients with mild to moderately active ulcerative colitis (partial Mayo score of ≥4 and ≤8). Interventions Faecal microbiota transplant samples were prepared at the University of Birmingham Microbiome Treatment Centre and administered to participants either via a nasogastric tube on 4 consecutive days repeated after a month (nasogastric) or by colonoscopy followed by 7 weekly enemas (COLON). Each treatment course was from a single matched donor. Participants and researchers underwent qualitative interviews regarding the faecal microbiota transplant experience. Main outcome measure Composite assessment of qualitative and quantitative data based on efficacy, acceptability and safety. Clinical response (primary measure of efficacy) was defined as a ≥3 point and ≥30% reduction in full Mayo score from randomisation to week 8 and a ≥1 point reduction in rectal bleeding subscore or absolute rectal bleeding subscore of 0 or 1. Results Thirty ulcerative colitis patients were randomised: 16 to nasogastric; 14 to COLON. Seven participants in the nasogastric arm and two in the COLON arm withdrew from treatment and clinical follow-up. Eight of 16 (50%) nasogastric participants were adherent compared to 12/14 (86%) COLON participants. Clinical response data were available for 20 of 30 randomised participants. Clinical response was seen in 2/8 (25%) nasogastric participants versus 9/12 (75%) COLON participants: adjusted risk ratio 2.94 (95% CI 0.84 to 10.30). Adverse events were reported in 11/16 (69%) nasogastric participants versus 11/14 (79%) COLON participants. There were three serious adverse events in two nasogastric participants. Faecal microbiota transplant was deemed an acceptable treatment for ulcerative colitis, with greater participant and clinician acceptability for the COLON route. Faecal microbiota transplant responders had a greater reduction in faecal calprotectin compared to non-responders (t-test p = 0.03) and increase in faecal microbiome diversity (Shannon diversity p < 0.01). In the whole cohort, a negative association between faecal calprotectin and diversity was seen (Kendall’s tau z = −2.8231, p = 0.004757). There were increases in faecal acetate (p = 0.05) and butyrate (p = 0.03) after faecal microbiota transplant intervention, but these were not associated with clinical response. A limitation was that this was an open-label pilot study, which was not powered to assess for efficacy of faecal microbiota transplant. Conclusions Faecal microbiota transplant delivered by the colonic route was considered safe and better tolerated than the nasogastric route. The colonic route was preferred by both participants and clinicians. Mechanistic signals indicated reduction in colonic inflammation and increased microbiome diversity in faecal microbiota transplant responders. Future work An efficacy-powered randomised controlled trial. Trial registration This trial is registered as ISRCTN74072945 and EudraCT 2015-005753-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/179/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 14. See the NIHR Funding and Awards website for further award information. Plain language summary Ulcerative colitis, a chronic inflammatory condition affecting the colon, results from the body’s immune response to imbalance in colonic microbes (microbiota). Faecal microbiota transplantation involves transferring processed donated stool samples from carefully screened healthy donors to ulcerative colitis patients aiming to correct the imbalance and reduce inflammation. There have been four trials comparing faecal microbiota transplant with placebo (dummy no treatment) to treat ulcerative colitis, and one which investigated faecal microbiota transplant with dietary intervention. Three of these studies showed encouraging benefit for faecal microbiota transplant. However, these studies varied in the methods used, with faecal microbiota transplant delivered either to the stomach or colon, or both. The aim of this study was to identify the best route of faecal microbiota transplant administration before undertaking a large-scale trial comparing faecal microbiota transplant with placebo. Between March 2018 and 30 April 2019 ulcerative colitis patients from three hospitals were randomly allocated to receive faecal microbiota transplant via either a tube inserted through the nose into the stomach on 4 consecutive days repeated after a month (nasogastric group; 16 participants) or by colonoscopy followed by 7 weekly enemas (COLON group; 14 participants). Faecal microbiota transplant was well accepted, with both patients with ulcerative colitis and healthcare staff stating a preference for the colonic route. Only 8 of 16 in the nasogastric group completed the study compared to 12 of 14 in the COLON group. Altogether, 9/12 (75%) in the COLON group improved compared with 2/8 (25%) in the nasogastric group. The majority of participants [11/14 (79%) COLON vs. 11/16 (69%) nasogastric] had mild, short-lived side effects following faecal microbiota transplant. There were three serious adverse events. Faecal calprotectin (indicating colonic inflammation) fell in responders and stool samples showed an increase in the number of microbial species after faecal microbiota transplant. At the end of the study, a recommendation was made by the Independent Oversight Committee to proceed to a large placebo-controlled randomised trial using the colonic route. Scientific summary Background Ulcerative colitis (UC) results from an exaggerated immune response to an imbalanced (dysbiotic) colonic microbiome in genetically predisposed patients. At the inception of this study, there had been four published randomised controlled trials (RCTs) comparing faecal microbiota transplantation (FMT) with placebo to treat UC in adults. Of these four seminal studies, three involved delivery of FMT via the colonic route and one a combination of delivery to the foregut and colon. This latter study was the only one of the four not to show a difference in efficacy compared to placebo. Foregut-delivered FMT is extensively and successfully used in clinical practice to treat Clostridioides difficile infection (CDI). From the results of the UC trials, FMT appeared to have therapeutic potential for UC. However, the methodology employed in these studies was varied and, taking into account the efficacy of FMT delivered to the foregut to treat CDI, there was uncertainty regarding the best route of delivery in the context of UC. Objectives The aims of this pilot study were as follows: to determine which FMT administration route [nasogastric (NG) or colonic (COLON)] should be investigated in a randomised double-blind, placebo-controlled trial to determine whether a full-scale RCT was feasible. In order to achieve these aims, the pilot study had the following clinical objectives. To assess the following: whether FMT by the NG route induces clinical response in patients with active UC whether FMT by the COLON route induces clinical response in patients with active UC tolerability and safety which route of FMT delivery (if any) was suitable to investigate in a full-scale RCT. The aims of the qualitative research were to assess the following: patient and clinician acceptability of FMT (NG route) patient and clinician acceptability of FMT (COLON route). The aims of the nested-mechanistic substudy were to assess the following: whether FMT by either route is associated with a change in faecal calprotectin as a surrogate marker of colonic inflammation changes in the colonic microbiome induced by FMT via each route changes in the metabolome [short-chain fatty acids (SCFAs)] induced by FMT via each route effect of diet (donors) time from stool donation to treatment. Methods In this prospective, multicentre, open-label, parallel group, randomised pilot study, adult patients with mild to moderate active UC (partial Mayo score of ≥4 and ≤8) were recruited from three centres in the UK (Birmingham, Glasgow and St Mark’s, London). Patients were randomised to receive FMT delivered either via a NG tube for delivery to the stomach (foregut-NG) on 4 consecutive days repeated after a month or by a combination of delivery through a colonoscope followed by 7 weekly enemas (hindgut-COLON). All participants underwent a treatment schedule using FMT derived, in each case, from a single donor. The primary outcome was a composite assessment of both qualitative and quantitative data based on efficacy, acceptability and safety. Clinical response (primary measure of efficacy) was defined as a ≥3 point and a ≥30% reduction in full Mayo score from randomisation to week 8 and a ≥1 point reduction in the rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1. Patient and clinician acceptability of FMT and preference of treatment route was assessed through semi-structured qualitative research interviews. Interviews also explored reasons for adherence to treatment allocation and patients’ perspectives on FMT and trial experience. Participants were interviewed face to face or by telephone at two time points, first following the screening visit and prior to randomisation, and second after the 12-week follow-up period. Safety was assessed by the number of participants experiencing adverse events (AEs) and serious adverse events (SAEs). For the translational research, stool samples were taken from participants at baseline and then at 2 weekly intervals throughout the study to assess microbiome diversity (by 16S rRNA sequencing) and to examine the effect of FMT on faecal calprotectin. Donor stool samples were also analysed by 16S rRNA sequencing. Biopsy samples were taken from the colon at the time of endoscopy (baseline and week 8) to analyse mucosa-associated microbiome by 16S rRNA sequencing. SCFA levels in stool samples were also measured throughout the study and blood was taken from participants to look for changes in C-reactive protein (CRP) in response to FMT. Donors were asked to fill in a dietary questionnaire in order to look for associations between dietary components in their habitual diet and the efficacy of their donated FMT samples. Results Thirty patients with UC were randomised between March 2018 and April 2019; 16 to NG; 14 to COLON route. Seven participants in the NG arm and two participants in the colonic arm withdrew from the study. Clinical response was achieved in a higher proportion of participants in the colonic arm [9/12 (75%)] compared with the NG arm [2/8 (25%)]; [adjusted risk ratio 2.94 (95% confidence interval, 0.84 to 10.30)]. In the colonic arm, 12/14 (86%) participants were considered adherent compared with 8/16 (50%) in the NG arm. AEs were reported in 11/14 (79%) participants in the colonic arm and 11/16 (69%) in the NG arm. There were three SAEs in two participants in the NG arm, and none in the colonic arm. Qualitative research found a high level of enthusiasm for the trial among both patients and staff. Patients were more positive about the colonic treatment route than the NG route, both before randomisation and after the patients had been through the study. Lower calprotectin levels, implying reduced colonic inflammation, averaged over the last half of the treatment course (weeks 4, 6 and 8), were seen in the responders (N = 11, mean 508.6 mg/kg) versus the non-responders (N = 9, mean 853.6 mg/kg) (p = 0.03). Furthermore, there was a negative association between faecal microbiome alpha diversity [rarefied total operational taxonomic unit (OTU) richness] and calprotectin levels (p < 0.01). This is the first time that change in faecal calprotectin, a widely used clinical inflammatory biomarker in UC, has been reported in response to FMT in inflammatory bowel disease (IBD). With respect to SCFAs, there were significant and large increases observed in the concentration of acetate (45% increase, p = 0.05) and butyrate (57% increase, p = 0.03) across all participants (N = 19) from baseline to week 2 following FMT treatment. This effect was also observed over the course of the entire FMT treatment period from baseline to 8 weeks (N = 16, acetate 21% increase, p = 0.02; butyrate 39% increase, p = 0.08). Significant changes were not observed for the other SCFAs measured, notably propionate (2 weeks p = 0.46, 8 weeks p = 0.36). The observed increase in acetate and butyrate was not associated with clinical response, and in fact when restricted to the responder group (N = 9) changes at both 2 and 8 weeks were no longer significant, although increases were still observed. Across all participants that completed FMT to day 56, and for whom baseline and week 8 DNA was available (N = 13), there was no significant change in faecal microbiome alpha diversity, as measured by rarefied Shannon diversity of 3% OTUs (p = 0.43). However, when restricted to the colonic arm only (N = 8), there was a significant increase in alpha diversity (p = 0.01) observed after FMT. Again, for those participants in the colonic arm that responded to FMT, there was a significant increase in alpha diversity (rarefied Shannon diversity, p < 0.01) compared to those who did not. No differences were seen in alpha diversity of mucosa-associated bacteria pre and post treatment. Donor microbiome diversity, as measured by rarefied 16S rRNA gene Shannon diversity, varied substantially between donors. There was a non-significant positive association between clinical response and donor diversity (p = 0.19) with the treatment arm taken into account. In this pilot study, CRP values were lower at baseline in the colonic arm (4.2 mg/l) compared with the NG arm (11.3 mg/l). Similarly, CRP values at weeks 4, 6 and 8 were also lower in the colonic arm than in the NG arm. With regard to data derived from diet questionnaires administered to donors, higher milk and milk product intakes were associated with higher alpha diversity, but this was not statistically significant. The mean number of days from stool donation to FMT treatment was similar in participants who achieved a clinical response compared with those who did not achieve a clinical response. There was no association between time from stool donation and treatment, and clinical response when added to the primary intention-to-treat analysis model. Conclusion This pilot study suggests that in patients with active UC, FMT delivered via the colonic route appears to be safe and better tolerated with signals suggesting greater efficacy compared to the NG route. The pilot study was welcomed by patients and clinicians, and FMT appears, at least in the short term, to be safe and well tolerated. On review of these data, the Independent Oversight Committee recommended progressing to the planned placebo-controlled randomised trial, which would be powered to assess efficacy, and would have enabled more detailed mechanistic studies to assess for strains engrafting from donors to recipients, which are associated with clinical response. Patients remain very interested in FMT as a potential treatment for UC as this microbiome manipulation affords an alternative therapy to immune system suppression as a means to treat UC. The trial management group involved in this pilot believe that further studies to assess the efficacy of FMT in UC with a focus on understanding mechanisms are warranted as the first step towards developing precision live biotherapeutics for IBD. Trial registration This trial is registered as ISRCTN74072945 and EudraCT 2015-005753-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/179/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 14. See the NIHR Funding and Awards website for further award information.

Abstract Background Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies. Methods An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the ‘Think Aloud’ method with patient advisory group members and Research Nurses to assess the usability of the system. Results Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials. Conclusion By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development. Trial registration: ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507

Introduction Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care.Methods and analysis Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients’ submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system.Ethics and dissemination Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups.Trial registration number ISCTRN11232653.

Plain English summary The World Health Organisation defines Long COVID as a condition which impacts people 3 months after they first had COVID-19. Some of the symptoms that characterise Long COVID symptoms include fatigue, breathlessness and brain fog. These symptoms have a major impact on people’s health and quality of life. Today, over 2 million people in the United Kingdom suffer from Long COVID and there is a lack of drugs and non-drugs treatment. However, some non-drugs treatments which aim to manage fatigue in other conditions, such as pacing, could be used with people with Long COVID. In this paper, we report how we co-produced a study which tested whether or not it is feasible for people who have Long COVID to use a pacing resource and report their symptoms using an electronic platform. After a meeting to review existing non-drugs treatments, the research team and a group of patient partners agreed on co-developing a clinical trial platform to test different pacing resources. The research team then met with the patient partners twice a week to co-design the study during which people with Long COVID will use the pacing resources and report their symptoms. They also co-designed the study documents and how to report its results. Co-producing a study with patient partners was effective and influenced important aspects of the study.

Objectives: Real-world evidence (RWE) generation can be enhanced by including patient-reported outcomes (PROs). Methods for collecting and using PRO data in the real-world setting are currently underdeveloped and there is no international guidance specific to its use in this context. This study explored stakeholders' perspectives and needs for using PROs in RWE generation. Barriers, facilitators, and opportunities for wider use of PROs in real-world studies were also investigated. Methods: Online semi-structured interviews were conducted with international stakeholders: patients, patient advocates, regulators, payers, clinicians, academic researchers, and industry experts. Interviews were recorded, transcribed verbatim and analysed using NVivo 20. Thematic analysis was conducted based on the updated Consolidated Framework for Implementation Research (CFIR). Results: Twenty-three interviews were conducted. Participants confirmed that the use of PROs in RWE generation is not yet well established. Participants expressed a mixed level of confidence in the value of PROs collected in a real-world setting. Operational challenges associated with collecting routine PRO data to inform care delivery at the individual level (e.g., setting up infrastructure) need to be addressed. Methodological and other challenges (e.g., financing research) associated with collecting prospective de novo data in a real-world setting should be considered to facilitate PRO utilisation in real-world studies. Conclusions: Several opportunities and challenges were identified regarding the broader use of PROs in RWE research. Joint efforts from different stakeholders are needed to maximise PRO implementation, with consideration given to each stakeholders’ specific needs (e.g., by developing good practices).

Objectives The use of electronic patient-reported outcome (ePRO) systems to support the management of patients with chronic kidney disease is increasing. This mixed-methods study aimed to comprehensively identify existing and developing ePRO systems, used in nephrology settings globally, ascertaining key characteristics and factors for successful implementation.Study design ePRO systems and developers were identified through a scoping review of the literature and contact with field experts. Developers were invited to participate in a structured survey, to summarise key system characteristics including: (1) system objectives, (2) population, (3) PRO measures used, (4) level of automation, (5) reporting, (6) integration into workflow and (7) links to electronic health records/national registries. Subsequent semistructured interviews were conducted to explore responses.Setting and participants Eligible systems included those being developed or used in nephrology settings to assess ePROs and summarise results to care providers. System developers included those with a key responsibility for aspects of the design, development or implementation of an eligible system.Analytical approach Structured survey data were summarised using descriptive statistics. Interview transcripts were analysed using Codebook Thematic Analysis using domains from the Consolidated Framework for Implementation Research.Results Fifteen unique ePRO systems were identified across seven countries; 10 system developers completed the structured survey and 7 participated in semistructured interviews. Despite system heterogeneity, reported features required for effective implementation included early and sustained patient involvement, clinician champions and expanding existing electronic platforms to integrate ePROs. Systems demonstrated several common features, with the majority being implemented within research settings, thereby affecting system implementation readiness for real-world application.Conclusions There has been considerable research investment in ePRO systems. The findings of this study outline key system features and factors to support the successful implementation of ePROs in routine kidney care.Cite Now

Abstract Background The support provided by people with the same condition, including inflammatory bowel diseases (IBD), has the potential to improve a range of psychosocial outcomes by allowing people with the disease to receive emotional support as well as to learn coping strategies from more experienced peers. The aim of this systematic review was to summarise the evidence on peer support interventions and their effectiveness on people with IBD. Methods Bibliographic databases, conference proceedings, grey literature, and clinical trial registers were searched from inception to November 2021. Comparative and single-arm studies that evaluated interventions that were solely or contained in part peer support, for people with IBD and/or their carers of any age and in any setting were included. Effectiveness was evaluated using outcomes relating to physical and psychosocial function, disease control and healthcare utilisation. Data for each outcome were tabulated and presented in a narrative synthesis. Study design specific tools were used to assess risk of bias. Study selection and risk of bias assessment were undertaken by two reviewers independently. Results Fourteen completed studies and five ongoing studies met the inclusion criteria. Substantial heterogeneity was observed in the studies in relation to the intervention type and peer support was usually part of a wider intervention. All but one study analysed the total effect of the intervention, so it was not possible to fully isolate the effect of the peer support alone. The appropriateness of outcomes and outcome measurement tools for the assessment of effects was a further key issue. As such, overall, no significant evidence of beneficial effects of peer support interventions on quality of life and other psychosocial outcomes was found. Conclusions New randomised controlled trials designed to isolate the effects of peer support are needed to evaluate the (net) effects of peer support only. Agreement on the outcomes to be targeted, and the choice of reliable and validated measurement tools for standalone peer support interventions would provide a focus for further intervention design and evaluation. Systematic review registration The protocol was accepted in the international prospective register of systematic reviews (PROSPERO CRD42020168817).

Introduction Postoperative radiological surveillance following primary resection of a soft tissue sarcoma (sarcoma of the retroperitoneum, abdomen, pelvis, trunk or extremities) is standard of care in all international high-volume sarcoma centres in the world. The intensity of postoperative surveillance imaging is highly varied and knowledge of the impact of surveillance and surveillance intensity on patients’ quality of life is limited. The aim of this systematic review is to summarise the experiences of patients and their relatives/caregivers of postoperative radiological surveillance following resection of a primary soft tissue sarcoma and its impact on their quality of life.Methods and analysis We will systematically search MEDLINE, EMBASE, PsycINFO, CINAHL Plus and Epistemonikos. Hand searching of reference lists of included studies will be conducted. Further searches will be performed via Google Scholar, to reveal further studies within unpublished ‘grey’ literature. Two reviewers will independently screen the titles and abstracts following the eligibility criteria. After retrieval of the full text of the selected studies, the methodological quality will be appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research and the Center for Evidence-Based Management checklist for Critical Appraisal of a Cross-Sectional Study. Data on the study population, relevant themes and conclusions will be extracted from the selected papers, and a narrative synthesis will be conducted.Ethics and dissemination The systematic review does not require ethics approval. The findings of the proposed work will be published in a peer-reviewed journal and disseminated widely to patients, clinicians and allied health professionals through the Sarcoma UK website, the Sarcoma Patient Advocacy Global Network and the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group. In addition, the outcomes of this research will be presented at national and international conferences.PROSPERO registration number CRD42022375118.

Introduction The use of electronic patient-reported outcome (ePRO) systems to capture PRO data in clinical trials is increasing; however, their feasibility, acceptability and utility in clinical trials of advanced therapy medicinal products (ATMPs) are not yet well understood. This protocol describes a qualitative study that aims to evaluate the feasibility and acceptability of ePRO data capture using a trial-specific ePRO system (the PROmics system) within an advanced therapy trial involving patients with immune-mediated inflammatory disease (rheumatoid arthritis, lupus, primary sclerosing cholangitis (PSC) and Crohn’s disease).Methods and analysis This protocol for a remote, qualitative, interview-based feasibility study is embedded within the POLARISE trial, a single-arm, phase II, multisite ATMP basket trial in the UK. 10–15 patients enrolled in the POLARISE trial and 10–15 research team members at the trial sites will be recruited. Participants will take part in semistructured interviews which will be transcribed verbatim and analysed thematically according to the framework method. Data collection and analysis will occur concurrently and iteratively. Researcher triangulation will be used to achieve a consensus-based analysis, enhancing rigour and trustworthiness.Ethics and dissemination This study was approved by the London—West London and GTAC Research Ethics Committee (Ref: 21/LO/0475). Informed consent will be obtained from all participants prior to data collection. The study findings will be published in peer-review journals and disseminated via conference presentations and other media. Our patient and public involvement and engagement group and ATMP stakeholder networks will be consulted to maximise dissemination and impact.Trial registration number ISRCTN80103507.

Introduction Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4–12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.Methods and analysis A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.Ethics and dissemination Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.Trial registration number 1567490.

Introduction Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as ‘post COVID-19 syndrome’, ‘post-COVID condition’ or more commonly ‘Long COVID’. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.Aims This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.Methods and analysis Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.Ethics and dissemination This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.PROSPERO registration number The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).

Abstract Background Patient-reported outcomes (PROs) are increasingly collected in clinical trials as they provide unique information on the physical, functional and psychological impact of a treatment from the patient’s perspective. Recent research suggests that PRO trial data have the potential to inform shared decision-making, support pharmaceutical labelling claims and influence healthcare policy and practice. However, there remains limited evidence regarding the actual impact associated with PRO trial data and how to maximise PRO impact to benefit patients and society. Thus, our objective was to qualitatively explore international stakeholders’ perspectives surrounding: a) the impact of PRO trial data, b) impact measurement metrics, and c) barriers and facilitators to effectively maximise the impact of PRO trial data upon patients and society. Methods Semi-structured interviews with 24 international stakeholders were conducted between May and October 2018. Data were coded and analysed using reflexive thematic analysis. Results International stakeholders emphasised the impact of PRO trial data to benefit patients and society. Influence on policy-impact, including changes to clinical healthcare practice and guidelines, drug approval and promotional labelling claims were common types of PRO impact reported by interviewees. Interviewees suggested impact measurement metrics including: number of pharmaceutical labelling claims and interviews with healthcare practitioners to determine whether PRO data were incorporated in clinical decision-making. Key facilitators to PRO impact highlighted by stakeholders included: standardisation of PRO tools; consideration of health utilities when selecting PRO measures; adequate funding to support PRO research; improved reporting and dissemination of PRO trial data by key opinion leaders and patients; and development of legal enforcement of the collection of PRO data. Conclusions Determining the impact of PRO trial data is essential to better allocate funds, minimise research waste and to help maximise the impact of these data for patients and society. However, measuring the impact of PRO trial data through metrics is a challenging task, as current measures do not capture the total impact of PRO research. Broader international multi-stakeholder engagement and collaboration is needed to standardise PRO assessment and maximise the impact of PRO trial data to benefit patients and society.

Abstract Background Transient ischaemic attack (TIA) and minor stroke are often considered transient events; however, many patients experience residual problems and reduced quality of life. Current follow-up healthcare focuses on stroke prevention and care for other long-term problems is not routinely provided. We aimed to explore patient and healthcare provider (HCP) experiences of residual problems post-TIA/minor stroke, the impact of TIA/minor stroke on patients’ lives, and current follow-up care and sources of support. Methods This qualitative study recruited participants from three TIA clinics, seven general practices and one community care trust in the West Midlands, England. Semi-structured interviews were conducted with 12 TIA/minor stroke patients and 24 HCPs from primary, secondary and community care. Data was analysed using framework analysis. Results A diverse range of residual problems were reported post-TIA/minor stroke, including psychological, cognitive and physical impairments. Consultants and general practitioners generally lacked awareness of these long-term problems; however, there was better recognition among nurses and allied HCPs. Residual problems significantly affected patients’ lives, including return to work, social activities, and relationships with family and friends. Follow-up care was variable and medically focused. While HCPs prioritised medical investigations and stroke prevention medication, patients emphasised the importance of understanding their diagnosis, individualised support regarding stroke risk, and addressing residual problems. Conclusion HCPs could better communicate information about TIA/minor stroke diagnosis and secondary stroke prevention using lay language, and improve their identification of and response to important residual impairments affecting patients.

Abstract Background Patient-reported outcomes (PROs) are commonly collected in clinical trials and should provide impactful evidence on the effect of interventions on patient symptoms and quality of life. However, it is unclear how PRO impact is currently realised in practice. In addition, the different types of impact associated with PRO trial results, their barriers and facilitators, and appropriate impact metrics are not well defined. Therefore, our objectives were: i) to determine the range of potential impacts from PRO clinical trial data, ii) identify potential PRO impact metrics and iii) identify barriers/facilitators to maximising PRO impact; and iv) to examine real-world evidence of PRO trial data impact based on Research Excellence Framework (REF) impact case studies. Methods Two independent investigators searched MEDLINE, EMBASE, CINAHL+, HMIC databases from inception until December 2018. Articles were eligible if they discussed research impact in the context of PRO clinical trial data. In addition, the REF 2014 database was systematically searched. REF impact case studies were included if they incorporated PRO data in a clinical trial. Results Thirty-nine publications of eleven thousand four hundred eighty screened met the inclusion criteria. Nine types of PRO trial impact were identified; the most frequent of which centred around PRO data informing clinical decision-making. The included publications identified several barriers and facilitators around PRO trial design, conduct, analysis and report that can hinder or promote the impact of PRO trial data. Sixty-nine out of two hundred nine screened REF 2014 case studies were included. 12 (17%) REF case studies led to demonstrable impact including changes to international guidelines; national guidelines; influencing cost-effectiveness analysis; and influencing drug approvals. Conclusions PRO trial data may potentially lead to a range of benefits for patients and society, which can be measured through appropriate impact metrics. However, in practice there is relatively limited evidence demonstrating directly attributable and indirect real world PRO-related research impact. In part, this is due to the wider challenges of measuring the impact of research and PRO-specific issues around design, conduct, analysis and reporting. Adherence to guidelines and multi-stakeholder collaboration is essential to maximise the use of PRO trial data, facilitate impact and minimise research waste. Trial registration Systematic Review registration PROSPERO CRD42017067799.

Introduction Patient-reported outcomes (PROs) are measures of a person’s own views of their health, functioning and quality of life. They are typically assessed using validated, self-completed questionnaires known as patient-reported outcome measures (PROMs). PROMs are used in healthcare settings to support care planning, clinical decision-making, patient–practitioner communication and quality improvement. PROMs have a potential role in the delivery of social care where people often have multiple and complex long-term health conditions. However, the use of PROMs in this context is currently unclear. The objective of this scoping review is to explore the evidence relating to the use of PROMs in adult social care.Methods and analyses The electronic databases Medline (Ovid), PsychInfo (Ovid), ASSIA (ProQuest), Social Care Online (SCIE), Web of Science and EMBASE (Ovid) were searched on 29 September 2020 to identify eligible studies and other publically available documents published since 2010. A grey literature search and hand searching of citations and reference lists of the included studies will also be undertaken. No restrictions on study design or language of publication will be applied. Screening and data extraction will be completed independently by two reviewers. Quality appraisal of the included documents will use the Critical Appraisal Skills Programme and AACODS (Authority, Accuracy, Coverage, Objectivity, Date, Significance) checklists. A customised data charting table will be used for data extraction, with analysis of qualitative data using the framework method. The review findings will be presented as tables and in a narrative summary.Ethics and dissemination Ethical review is not required as scoping reviews are a form of secondary data analysis that synthesise data from publically available sources. Review findings will be shared with service users and other relevant stakeholders and disseminated through a peer-reviewed publication and conference presentations. This protocol is registered on the Open Science Framework (www.osf.io).

Objective Surgical site infection (SSI) affects up to 25% of primary surgical wounds. Dressing strategies may influence SSI risk. The Bluebelle study assessed the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of different dressing strategies to reduce SSI in primary surgical wounds.Design A pilot, factorial RCT.Setting Five UK hospitals.Participants Adults undergoing abdominal surgery with a primary surgical wound.Interventions Participants were randomised to ‘simple dressing’, ‘glue-as-a-dressing’ or ‘no dressing’, and to the time at which the treatment allocation was disclosed to the surgeon (disclosure time, before or after wound closure).Primary and secondary outcome measures Feasibility outcomes focused on recruitment, adherence to randomised allocations, reference assessment of SSI and response rates to participant-completed and observer-completed questionnaires to assess SSI (proposed primary outcome for main trial), wound experience and symptoms, and quality of life (EQ-5D-5L).Results Between March and November 2016, 1115 patients were screened; 699 (73.4%) were eligible and approached, 415 (59.4%) consented and 394 (35.3%) were randomised (simple dressing=133, glue=129 and ‘no dressing’=132). Non-adherence to dressing allocation was 2% (3/133), 6% (8/129) and 15% (20/132), respectively. Adherence to disclosure time was 99% and 86% before and after wound closure, respectively. The overall rate of SSI (reference assessment) was 18.1% (51/281). Response rates to the Wound Healing Questionnaire and other questionnaires ranged from >90% at 4 days to 68% at 4–8 weeks.Conclusions A definitive RCT of dressing strategies including ‘no dressing’ is feasible. Further work is needed to optimise questionnaire response rates.Trial registration number 49328913; Pre-results.

Abstract Background Facilitation is a promising implementation intervention, which requires theory-informed evaluation. This paper presents an exemplar of a multi-country realist process evaluation that was embedded in the first international randomised controlled trial evaluating two types of facilitation for implementing urinary continence care recommendations. We aimed to uncover what worked (and did not work), for whom, how, why and in what circumstances during the process of implementing the facilitation interventions in practice. Methods This realist process evaluation included theory formulation, theory testing and refining. Data were collected in 24 care home sites across four European countries. Data were collected over four time points using multiple qualitative methods: observation (372 h), interviews with staff (n = 357), residents (n = 152), next of kin (n = 109) and other stakeholders (n = 128), supplemented by facilitator activity logs. A combined inductive and deductive data analysis process focused on realist theory refinement and testing. Results The content and approach of the two facilitation programmes prompted variable opportunities to align and realign support with the needs and expectations of facilitators and homes. This influenced their level of confidence in fulfilling the facilitator role and ability to deliver the intervention as planned. The success of intervention implementation was largely dependent on whether sites prioritised their involvement in both the study and the facilitation programme. In contexts where the study was prioritised (including release of resources) and where managers and staff support was sustained, this prompted collective engagement (as an attitude and action). Internal facilitators’ (IF) personal characteristics and abilities, including personal and formal authority, in combination with a supportive environment prompted by managers triggered the potential for learning over time. Learning over time resulted in a sense of confidence and personal growth, and enactment of the facilitation role, which resulted in practice changes. Conclusion The scale and multi-country nature of this study provided a novel context to conduct one of the few trial embedded realist-informed process evaluations. In addition to providing an explanatory account of implementation processes, a conceptual platform for future facilitation research is presented. Finally, a realist-informed process evaluation framework is outlined, which could inform future research of this nature. Trial registration Current controlled trials ISRCTN11598502.

Abstract Background Health care practice needs to be underpinned by high quality research evidence, so that the best possible care can be delivered. However, evidence from research is not always utilised in practice. This study used the Promoting Action on Research Implementation in Health Services (PARIHS) framework as its theoretical underpinning to test whether two different approaches to facilitating implementation could affect the use of research evidence in practice. Methods A pragmatic clustered randomised controlled trial with embedded process and economic evaluation was used. The study took place in four European countries across 24 long-term nursing care sites, for people aged 60 years or more with documented urinary incontinence. In each country, sites were randomly allocated to standard dissemination, or one of two different types of facilitation. The primary outcome was the documented percentage compliance with the continence recommendations, assessed at baseline, then at 6, 12, 18, and 24 months after the intervention. Data were analysed using STATA15, multi-level mixed-effects linear regression models were fitted to scores for compliance with the continence recommendations, adjusting for clustering. Results Quantitative data were obtained from reviews of 2313 records. There were no significant differences in the primary outcome (documented compliance with continence recommendations) between study arms and all study arms improved over time. Conclusions This was the first cross European randomised controlled trial with embedded process evaluation that sought to test different methods of facilitation. There were no statistically significant differences in compliance with continence recommendations between the groups. It was not possible to identify whether different types and “doses” of facilitation were influential within very diverse contextual conditions. The process evaluation (Rycroft-Malone et al., Implementation Science. doi: 10.1186/s13012-018-0811-0) revealed the models of facilitation used were limited in their ability to overcome the influence of contextual factors. Trial registration Current Controlled Trials ISRCTN11598502. Date 4/2/10. The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 223646.

Plain English summary What is the problem and why is this important? Mini-strokes are similar to full strokes, but symptoms last less than 24 h. Many people (up to 70%) have long-term problems after a mini-stroke, such as anxiety; depression; problems with brain functioning (like memory loss); and fatigue (feeling tired). However, the current healthcare pathway only focuses on preventing another stroke and care for other long-term problems is not routinely given. Without proper treatment, people with long-term problems after a mini-stroke could have worse quality of life and may find it difficult to return to work and their social activities. What is the aim of the research? We wanted to understand the research priorities of patients, health care professionals and key stakeholders relating to the long-term impact of mini-stroke. How did we address the problem? We invited patients, clinicians, researchers and other stakeholders to attend a meeting. At the meeting people discussed the issues relating to the long-term impact of mini-stroke and came to an agreement on their research priorities. There were three stages: (1) people wrote down their individual research suggestions; (2) in smaller groups people came to an agreement on what their top research questions were; and (3) the whole group agreed final research priorities. What did we find? Eleven people attended who were representatives for patients, GPs, stroke consultants, stroke nurses, psychologists, the Stroke Association (charity) and stroke researchers, The group agreed on eleven research questions which they felt were the most important to improve health and well-being for people who have had a mini-stroke. The eleven research questions encompass a range of categories, including: understanding the existing care patients receive (according to diagnosis and geographical location); exploring what optimal care post-TIA/minor stroke should comprise (identifying and treating impairments, information giving and support groups) and how that care should be delivered (clinical setting and follow-up pathway); impact on family members; and education/training for health care professionals. Abstract Background Clinical management after transient ischaemic attack (TIA) and minor stroke focuses on stroke prevention. However, evidence demonstrates that many patients experience ongoing residual impairments. Residual impairments post-TIA and minor stroke may affect patients’ quality of life and return to work or social activities. Research priorities of patients, health care professionals and key stakeholders relating to the long-term impact of TIA and minor stroke are unknown. Methods Our objective was to establish the top shared research priorities relating to the long-term impact of TIA and minor stroke through stakeholder-centred consensus. A one-day priority setting consensus meeting took place with representatives from different stakeholder groups in October 2016 (Birmingham, UK). Nominal group technique was used to establish research priorities. This involved three stages: (i) gathering research priorities from individual stakeholders; (ii) interim prioritisation in three subgroups; and (iii) final priority setting. Results The priority setting consensus meeting was attended by 11 stakeholders. The individual stakeholders identified 34 different research priorities. During the interim prioritisation exercise, the three subgroups generated 24 unique research priorities which were discussed as a whole group. Following the final consensus discussion, 11 shared research priorities were unanimously agreed. The 11 research questions encompass a range of categories, including: understanding the existing care patients receive (according to diagnosis and geographical location); exploring what optimal care post-TIA/minor stroke should comprise (identifying and treating impairments, information giving and support groups) and how that care should be delivered (clinical setting and follow-up pathway); impact on family members; and education/training for health care professionals. Conclusions Eleven different research priorities were established through stakeholder-centred consensus. These research questions could usefully inform the research agenda and policy decisions for TIA and minor stroke. Inclusion of stakeholders in setting research priorities is important to increase the relevance of research and reduce research waste.

Abstract Background Surgical site infections (SSIs) are common, occurring in up to 25% of > 4 million operations performed in England each year. Previous trials of the effect of wound dressings on the risk of developing a SSI are of poor quality and underpowered. Methods/Design This study is a feasibility and pilot trial to examine the feasibility of a full trial that will compare simple dressings, no dressing and tissue-glue as a dressing. It is examining the overall acceptability of trial participation, identifying opportunities for refinement, testing the feasibility of and validating new outcome tools to assess SSI, wound management issues and patients’ wound symptom experiences. It is also exploring methods for avoiding performance bias and blinding outcome assessors by testing the feasibility of collecting wound photographs taken in theatre immediately after wound closure and, at 4–8 weeks after surgery, taken by participants themselves or their carers. Finally, it is identifying the main cost drivers for an economic evaluation of dressing types. Integrated qualitative research is exploring acceptability and reasons for non-adherence to allocation. Adults undergoing primary elective or unplanned abdominal general surgery or Caesarean section are eligible. The main exclusion criteria are abdominal or other major surgery less than three months before the index operation or contraindication to dressing allocation. The trial is scheduled to recruit for nine months. The findings will be used to inform the design of a main trial. Discussion This pilot trial is the first pragmatic study to randomise participants to no dressing or tissue-glue as a dressing versus a simple dressing. Early evidence from the ongoing pilot shows that recruitment is proceeding well and that the interventions are acceptable to participants. Combined with the qualitative findings, the findings will inform whether a main, large trial is feasible and, if so, how it should be designed. Trial registration ISRCTN49328913 . Registered on 20 October 2015.

Introduction Imbalance of the gut microbiome is key to the pathogenesis of ulcerative colitis (UC). Faecal microbiota transplant (FMT) is the transfer of homogenised and filtered faeces from a healthy individual to the gastrointestinal tract of a patient with disease. Published datasets show a positive signal for the use of FMT to treat UC, but the optimal route and dose of FMT remain unanswered.Methods and analysis This prospective, multi-centre open-label, randomised pilot study will assess two possible routes of FMT delivery, via the nasogastric (NG) route or by delivery to the COLON, in 30 patients with active UC recruited from three sites in the UK. Stool will be collected from healthy screened donors, processed, frozen and stored under a Medicines and Healthcare products Regulatory Agency (MHRA) “specials” manufacturing licence held at the University of Birmingham Microbiome Treatment Centre. Thawed FMT samples will be administered to patients either via eight nasogastric infusions given initially over 4 days starting on the day of randomisation, and then again for 4 days in week 4 for foregut delivery (total of 240 g of stool) or via one colonoscopic infusion followed by seven weekly enemas according to the hindgut protocol (total of 360 g of stool). Patients will be followed up weekly for 8 weeks, and then at 12 weeks. The aims of this pilot study are (1) to determine which FMT administration route (NG or COLON) should be investigated in a randomised double-blind, placebo-controlled trial and (2) to determine if a full randomised controlled trial is feasible. The primary outcome will be a composite assessment of both qualitative and quantitative data based on efficacy (clinical response), acceptability and safety. At the end of the pilot study, decisions will be made regarding the feasibility of a full randomised double-blind, placebo-controlled trial and, if deemed feasible, which route of administration should be used in such a study.Ethics and dissemination Ethical approval for this study has been obtained from the East Midlands-Nottingham Research Ethics Committee (REC 17/EM/0274). At the end of the study, findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals.Trial registration number ISRCTN74072945

Objectives To describe the novel concept of, and methods for developing, a ‘universal-reporter’ outcome measure (UROM); a single questionnaire for completion by patients and/or healthcare professionals (HCPs) when views on the same subject are required.Design A mixed methods study with three phases—phase I: identification of relevant content domains from existing clinical tools, patient questionnaires and in-depth interviews with multistakeholders; phase II: item development using a novel approach that considered plain language in conjunction with medical terminology; and phase III: pretesting with multistakeholders using cognitive interviews.Setting A case study in surgical wound assessment undertaken in two UK hospital trusts and one university setting.Participants Patients who had recently undergone general abdominal surgery and healthcare professionals involved in post-surgical wound care.Results Phase I: In the example case study, 19 relevant content domains were identified from two clinical tools, two patient questionnaires and 19 multistakeholder interviews (nine patients, 10 HCPs). Phase II: Domains were operationalised into items and subitems (secondary components to collect further information, if relevant). The version after pretesting had 16 items, five of which included further subitems. Plain language in conjunction with medical terminology was applicable in nine (27%) items/subitems. Phase III: Pretesting with 28 patients and 14 HCPs found that the UROM was acceptable to both respondent groups. An unanticipated secondary finding of the study was that the combined use of plain language and medical terminology during questionnaire development may be a useful, novel technique for evaluating item interpretation and thereby identifying items with inadequate content validity.Conclusion UROMs are a novel approach to outcome assessment that are acceptable to both patients and HCPs. Combining plain language and medical terminology during item development is a recommended technique to improve accuracy of item interpretation and content validity during questionnaire design. More work is needed to further validate this novel approach and explore the application of UROMs to other settings.