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Background: Around 2 million people in the UK suffer from Long COVID (LC). Of concern is the disease impact on productivity and informal care burden. This study aimed to quantify and value productivity losses and informal care receipt in a sample of LC patients in the UK., Methods: The target population comprised LC patients referred to LC specialist clinics. The questionnaires included a health economics questionnaire (HEQ) measuring productivity impacts, informal care receipt and service utilisation, EQ-5D-5L, C19-YRS LC condition-specific measure, and sociodemographic and COVID-19 history variables. Outcomes were changes from the incident infection resulting in LC to the month preceding the survey in paid work status/h, work income, work performance and informal care receipt. The human capital approach valued productivity losses; the proxy goods method valued caregiving hours. The values were extrapolated nationally using published prevalence data. Multilevel regressions, nested by region, estimated associations between the outcomes and patient characteristics., Results: 366 patients responded to HEQ (mean LC duration 449.9 days). 51.7% reduced paid work hours relative to the pre-infection period. Mean monthly work income declined by 24.5%. The average aggregate value of productivity loss since incident infection was £10,929 (95% bootstrap confidence interval £8,844-£13,014) and £5.7 billion (£3.8-£7.6 billion) extrapolated nationally. The corresponding values for informal caregiving were £8,726 (£6,247-£11,204) and £4.8 billion (£2.6-£7.0 billion). Multivariate analyses found significant associations between each outcome and health utility and C19-YRS subscale scores., Conclusion: LC significantly impacts productivity losses and provision of informal care, exacerbated by high national prevalence of LC., (© 2023. The Author(s).)

Artificial intelligence (AI) could revolutionise health care, potentially improving clinician decision making and patient safety, and reducing the impact of workforce shortages. However, policymakers and regulators have concerns over whether AI and clinical decision support systems (CDSSs) are trusted by stakeholders, and indeed whether they are worthy of trust. Yet, what is meant by trust and trustworthiness is often implicit, and it may not be clear who or what is being trusted. We address these lacunae, focusing largely on the perspective(s) of clinicians on trust and trustworthiness in AI and CDSSs. Empirical studies suggest that clinicians' concerns about their use include the accuracy of advice given and potential legal liability if harm to a patient occurs. Onora O'Neill's conceptualisation of trust and trustworthiness provides the framework for our analysis, generating a productive understanding of clinicians' reported trust issues. Through unpacking these concepts, we gain greater clarity over the meaning ascribed to them by stakeholders; delimit the extent to which stakeholders are talking at cross purposes; and promote the continued utility of trust and trustworthiness as useful concepts in current debates around the use of AI and CDSSs., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Randomised controlled trials are designed to assess the superiority, equivalence or non-inferiority of a new health technology, but which trial design should be used is not always obvious in practice. In particular, when using equivalence or non-inferiority designs, multiple outcomes of interest may be important for the success of a trial, despite the fact that usually only a single primary outcome is used to design the trial. Benefit-risk methods are used in the regulatory clinical trial setting to assess multiple outcomes and consider the trade-off of the benefits against the risks, but are not regularly implemented in publicly funded trials., Objectives: The aim of the project is to aid the design of clinical trials with multiple outcomes of interest by defining when each trial design is appropriate to use and identifying when to use benefit-risk methods to assess outcome trade-offs (qualitatively or quantitatively) in a publicly funded trial setting., Methods: A range of methods was used to elicit expert opinion to answer the project objectives, including a web-based survey of relevant researchers, a rapid review of current literature and a 2-day consensus workshop of experts (in 2019)., Results: We created a list of 19 factors to aid researchers in selecting the most appropriate trial design, containing the following overarching sections: population, intervention, comparator, outcomes, feasibility and perspectives. Six key reasons that indicate a benefit-risk method should be considered within a trial were identified: (1) when the success of the trial depends on more than one outcome; (2) when important outcomes within the trial are in competing directions (i.e. a health technology is better for one outcome, but worse for another); (3) to allow patient preferences to be included and directly influence trial results; (4) to provide transparency on subjective recommendations from a trial; (5) to provide consistency in the approach to presenting results from a trial; and (6) to synthesise multiple outcomes into a single metric. Further information was provided to support the use of benefit-risk methods in appropriate circumstances, including the following: methods identified from the review were collated into different groupings and described to aid the selection of a method; potential implementation of methods throughout the trial process were provided and discussed (with examples); and general considerations were described for those using benefit-risk methods. Finally, a checklist of five pieces of information that should be present when reporting benefit-risk methods was defined, with two additional items specifically for reporting the results., Conclusions: These recommendations will assist research teams in selecting which trial design to use and deciding whether or not a benefit-risk method could be included to ensure research questions are answered appropriately. Additional information is provided to support consistent use and clear reporting of benefit-risk methods in the future. The recommendations can also be used by funding committees to confirm that appropriate considerations of the trial design have been made., Limitations: This research was limited in scope and should be considered in conjunction with other trial design methodologies to assess appropriateness. In addition, further research is needed to provide concrete information about which benefit-risk methods are best to use in publicly funded trials, along with recommendations that are specific to each method., Study Registration: The rapid review is registered as PROSPERO CRD42019144882., Funding: Funded by the Medical Research Council UK and the National Institute for Health and Care Research as part of the Medical Research Council-National Institute for Health and Care Research Methodology Research programme.

Background: Tinnitus is the awareness of a sound in the ear or head in the absence of an external source. It affects around 10-15% of people and current treatment options are limited. Experimental treatments include various forms of electrical stimulation of the brain. Currently, there is no consensus on the outcomes that should be measured when investigating the efficacy of this type of intervention for tinnitus. This study seeks to address this by establishing a Core Domain Set: a common standard of what specific tinnitus-related complaints are critical and important to assess in all clinical trials of electrical stimulation-based interventions for tinnitus., Methods: A two-round online survey will be conducted, followed by a stakeholder consensus meeting to identify a Core Domain Set. Participants will belong to one of two stakeholder groups: healthcare users with lived experience of tinnitus, and professionals with relevant clinical, commercial, or research experience., Discussion: This study will establish a Core Domain Set for the evaluation of electrical stimulation-based interventions for tinnitus via an e-Delphi study. The resulting Core Domain Set will act as a minimum standard for reporting in future clinical trials of electrical stimulation interventions for tinnitus. Standardisation will facilitate comparability of research findings., (© 2022. The Author(s).)

Background: Single-sided deafness (SSD) has functional, psychological, and social consequences. Interventions for adults with SSD include hearing aids and auditory implants. Benefits and harms (outcome domains) of these interventions are until now reported inconsistently in clinical trials. Inconsistency in reporting outcome measures prevents meaningful comparisons or syntheses of trial results. The Core Rehabilitation Outcome Set for Single-Sided Deafness (CROSSSD) international initiative used structured communication techniques to achieve consensus among healthcare users and professionals working in the field of SSD. The novel contribution is a set of core outcome domains that experts agree are critically important to assess in all clinical trials of SSD interventions., Methods: A long list of candidate outcome domains compiled from a systematic review and published qualitative data, informed the content of a two-round online Delphi survey. Overall, 308 participants from 29 countries were enrolled. Of those, 233 participants completed both rounds of the survey and scored each outcome domain on a 9-point scale. The set of core outcome domains was finalised via a web-based consensus meeting with 12 participants. Votes involved all stakeholder groups, with an approximate 2:1 ratio of professionals to healthcare users participating in the Delphi survey, and a 1:1 ratio participating in the consensus meeting., Results: The first round of the survey listed 44 potential outcome domains, organised thematically. A further five outcome domains were included in Round 2 based on participant feedback. The structured voting at round 2 identified 17 candidate outcome domains which were voted on at the consensus meeting. Consensus was reached for a core outcome domain set including three outcome domains: spatial orientation, group conversations in noisy social situations, and impact on social situations. Seventy-seven percent of the remaining Delphi participants agreed with this core outcome domain set., Conclusions: Adoption of the internationally agreed core outcome domain set would promote consistent assessment and reporting of outcomes that are meaningful and important to all relevant stakeholders. This consistency will in turn enable comparison of outcomes reported across clinical trials comparing SSD interventions in adults and reduce research waste. Further research will determine how those outcome domains should best be measured., (© 2022. The Author(s).)

Background: Previous studies have detailed the technical, learning and soft skills healthcare staff deploy to deliver quality improvement (QI). However, research has mainly focused on management and leadership skills, overlooking the skills frontline staff use to improve care. Our research explored which skills mattered to frontline health practitioners delivering QI projects., Study Design: We used a theory-driven approach, informed by communities of practice, knowledge-in-practice-in-context and positive deviance theory. We used case studies to examine skill use in three pseudonymised English hospital Trusts, selected on the basis of Care Quality Commission rating. Seventy-three senior staff orientation interviews led to the selection of two QI projects at each site. Snowball sampling obtained a maximally varied range of 87 staff with whom we held 122 semistructured interviews at different stages of QI delivery, analysed thematically., Results: Six overarching 'Socio-Organisational Functional and Facilitative Tasks' (SOFFTs) were deployed by frontline staff. Several of these had to be enacted to address challenges faced. The SOFFTs included: (1) adopting and promulgating the appropriate organisational environment; (2) managing the QI rollercoaster; (3) getting the problem right; (4) getting the right message to the right people; (5) enabling learning to occur; and (6) contextualising experience. Each task had its own inherent skills., Conclusion: Our case studies provide a nuanced understanding of the skills used by healthcare staff. While technical skills are important, the ability to judge when and how to use wider skills was paramount. The provision of QI training and fidelity to the improvement programme may be less of a priority than the deployment of SOFFT skills used to overcome barriers. QI projects will fail if such skills and resources are not accessed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hyperhidrosis is a common skin condition characterized by excessive sweating, which can negatively impact on quality of life. It is under-researched compared with other conditions of similar prevalence., Aim: To generate a Top 10 list of research priorities for the treatment and management of hyperhidrosis, with equal input from people with hyperhidrosis and healthcare professionals (HCPs)., Methods: A priority setting partnership (PSP) was established and processes from the James Lind Alliance Handbook were followed. An online survey asked participants what questions they would like research to answer. These questions were grouped into 'indicative questions', which were ranked in a second survey of 45 indicative questions. The top 23 questions were then taken to a final workshop event attended by key stakeholders, and ranked to generate the Top 10 list of research priorities., Results: There were 592 questions submitted by 268 respondents for the first survey. For the second survey, 286 participants ranked the indicative questions in order of priority. At the final workshop, the Top 10 list was generated. The top three priorities were: (i) Are there any safe and effective permanent solutions for hyperhidrosis? (ii) What is the most effective and safe oral treatment (drugs taken by mouth) for hyperhidrosis? and (iii) What are the most effective and safe ways to reduce sweating in particular areas of the body?, Conclusions: There are many unanswered research questions that both people with hyperhidrosis and HCPs would like to see answered. The results from this PSP will help to ensure future research funding can be directed to these areas of priority., (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction: Long COVID, a new condition whose origins and natural history are not yet fully established, currently affects 1.5 million people in the UK. Most do not have access to specialist long COVID services. We seek to optimise long COVID care both within and outside specialist clinics, including improving access, reducing inequalities, helping self-management and providing guidance and decision support for primary care. We aim to establish a 'gold standard' of care by systematically analysing current practices, iteratively improving pathways and systems of care., Methods and Analysis: This mixed-methods, multisite study is informed by the principles of applied health services research, quality improvement, co-design, outcome measurement and learning health systems. It was developed in close partnership with patients (whose stated priorities are prompt clinical assessment; evidence-based advice and treatment and help with returning to work and other roles) and with front-line clinicians. Workstreams and tasks to optimise assessment, treatment and monitoring are based in three contrasting settings: workstream 1 (qualitative research, up to 100 participants), specialist management in 10 long COVID clinics across the UK, via a quality improvement collaborative, experience-based co-design and targeted efforts to reduce inequalities of access, return to work and peer support; workstream 2 (quantitative research, up to 5000 participants), patient self-management at home, technology-supported monitoring and validation of condition-specific outcome measures and workstream 3 (quantitative research, up to 5000 participants), generalist management in primary care, harnessing electronic record data to study population phenotypes and develop evidence-based decision support, referral pathways and analysis of costs. Study governance includes an active patient advisory group., Ethics and Dissemination: LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS study is sponsored by the University of Leeds and approved by Yorkshire & The Humber-Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Participants will provide informed consent. Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers., Trial Registration Number: NCT05057260, ISRCTN15022307., Competing Interests: Competing interests: MS is advisor to WHO for long COVID policy in Europe. TG is member of the UK long COVID national task force and member of the National Institute for Health and Care Excellence (NICE) postacute COVID guideline oversight committee and Independent SAGE member. SdeL is the Director of the Oxford-RCGP RSC (primary care surveillance network); has received grants through his University from AstraZeneca, Eli Lilly, GSK, MSD, NovoNordisk, Sanofi, Seqirus and Takeda; and has sat on advisory boards for AstraZeneca, Sanofi and Seqirus. CR Member of Society of Occupational Medicine Taskforce on long COVID; member of WHO guideline development group on rehabilitation for post-COVID condition; community representative on the Access to COVID-19 Tools Accelerator (ACT-A) committee; member of long COVID support employment group (unpaid advocacy work for workers with long COVID); and has undertaken paid work for Nestle, advising on support for employees with long COVID., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Health research agendas are often set by researchers or by industry and may not reflect the needs and priorities of end users. This priority-setting partnership (PSP) for epilepsy was undertaken to identify the most pressing unanswered questions about epilepsy and seizures from the perspective of people with epilepsy (PWE) and their care providers., Methods: Using the methodology developed by the James Lind Alliance (JLA), evidence uncertainties were gathered via online surveys from stakeholders across Canada. Submissions were formed into summary questions and checked against existing evidence to determine if they were true uncertainties. Verified uncertainties were then ranked by patients, caregivers, and healthcare providers and a final workshop was held to reach a consensus on the top 10 priorities., Results: The final top 10 list reflects the priority areas of focus for research as identified by the Canadian epilepsy community, including genetic markers for diagnosis and treatment, concerns about living with the long-term effects of epilepsy, and addressing knowledge gaps in etiology and treatment approaches., Conclusion: This project represents the first systematic evidence of patient- and clinician-centered research priorities for epilepsy. The results of this priority-setting exercise provide an opportunity for researchers and funding agencies to align their agendas with the values and needs of the epilepsy community in order to improve clinical outcomes and quality of life (QOL) for PWE., Competing Interests: Declaration of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Hyperacusis is commonly defined as reduced tolerance to everyday sounds leading to avoidance behavior and disrupting normal functioning. Hyperacusis is prevalent in children. However, the literature on the manifestation and impact of hyperacusis on children is scant. This qualitative study examined online discussion forums to understand the lived experiences of hyperacusis in children from a parent or carer perspective., Method: Posts from publicly available online discussion forums were thematically analyzed. Online searching identified 219 potentially relevant conversation threads across 18 forums and involving 1,436 forum users. A total number of 170 eligible conversation threads, containing 1,834 messages, were used in the analysis., Results: Thematic analysis of the data generated six themes: personal and health information about the child, onset and prognosis, bothersome sounds and characteristics, reactions, coping strategies, and impact. Hyperacusis onset was associated with loud noise, physical trauma, or stress. Bothersome sounds were categorized in terms of appliances, vehicles, public places, nature, and very loud sounds. Children's reactions included panic, shaking, and screaming. Strategies to manage hyperacusis included ear defenders, building up tolerance, and school adaptations. Hyperacusis had an impact on various aspects of the child's life including academic performance and social development., Conclusions: This is the first study to account for the lived experiences of children experiencing hyperacusis from a parent/carer perspective using online forum data. These findings expand on existing research on the manifestation of hyperacusis in children and provide a basis for further work improving clinical assessment and management.

Background: Shock-absorbing flooring may minimise impact forces incurred from falls to reduce fall-related injuries; however, synthesized evidence is required to inform decision-making in hospitals and care homes., Methods: This is a Health Technology Assessment mixed methods systematic review of flooring interventions targeting older adults and staff in care settings. Our search incorporated the findings from a previous scoping review, MEDLINE, AgeLine, and Scopus (to September 2019) and other sources. Two independent reviewers selected, assessed, and extracted data from studies. We assessed risk of bias using Cochrane and Joanna Briggs Institute tools, undertook meta-analyses, and meta-aggregation., Results: 20 of 22 included studies assessed our outcomes (3 Randomised Controlled Trials (RCTs); 7 observational; 5 qualitative; 5 economic), on novel floors (N = 12), sports floors (N = 5), carpet (N = 5), and wooden sub-floors (N = 1). Quantitative data related to 11,857 patient falls (9 studies), and 163 staff injuries (1 study). One care home-based RCT found a novel underlay produced similar injurious falls rates (high-quality evidence) and falls rates (moderate-quality evidence) to a plywood underlay with vinyl overlay and concrete sub-floors. Very low-quality evidence suggested that shock-absorbing flooring may reduce injuries in hospitals (Rate Ratio 0.55, 95% CI 0.36 to 0.84, 2 studies; 27.1% vs. 42.4%; Risk Ratio (RR) = 0.64, 95% CI 0.44 to 0.93, 2 studies) and care homes (26.4% vs. 33.0%; RR 0.80, 95% CI 0.70 to 0.91, 3 studies), without increasing falls. Economic evidence indicated that if injuries are fewer and falls not increased, then shock-absorbing flooring would be a dominant strategy. Fracture outcomes were imprecise; however, hip fractures reduced from 30 in 1000 falls on concrete to 18 in 1000 falls on wooden sub-floors (OR 0.59, 95% CI 0.45 to 0.78; one study; very low-quality evidence). Staff found moving wheeled equipment harder on shock-absorbing floors leading to workplace adaptations. Very low-quality evidence suggests staff injuries were no less frequent on rigid floors., Conclusion: Evidence favouring shock-absorbing flooring is uncertain and of very low quality. Robust research following a core outcome set is required, with attention to wider staff workplace implications., Trial Registration: PROSPERO CRD42019118834 ., (© 2022. The Author(s).)

Introduction: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?', Methods and Analysis: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years., Ethics and Dissemination: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences., Trial Registration Number: ISRCTN85731188., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: This study investigated the content, quality and value of feedback given to applicants who applied to one of four research programmes in the UK funded (or jointly funded) by the National Institute for Health Research (NIHR)., Methods: A mixed-method phased approach was conducted using document analysis and an online survey. Phase 1 examined 114 NIHR applicant feedback documents comprised written feedback from funding committees and external peer-reviewers and a conceptual framework of the key components of feedback was developed using content analysis. Phase 2 was an online survey completed by 113 NIHR applicants. Frequencies of responses to closed questions were calculated. Perceptions of quality and value of feedback were identified using content analysis of open-text responses., Results: In phase 1, a conceptual framework was developed with seven overarching categories: 'Study structure and quality'; 'Team and infrastructure'; 'Acceptability to patients and professionals'; 'Study justification and design'; 'Risks and contingencies'; 'Outputs'; 'Value for money'. A higher frequency of feedback was provided at stage 2 and for successful applications across the majority of components. In phase 2, frequency data showed that opinion on feedback was dependent on funding outcome. Content analysis revealed four main themes: 'Committee transparency'; 'Content validity and reliability'; 'Additional support'; Recognition of effort and constraints'., Conclusions: This study provides key insights and understanding into the quality, content and value of feedback provided to NIHR applicants. The study identified key areas for improvement that can arise in NIHR funding applications, as well as in the feedback given to applicants that are applicable to other funding organisations. These findings could be used to inform funding application guidance documents to help researchers strengthen their applications and used more widely by other funders to inform their feedback processes., Competing Interests: Competing interests: All of the authors are employed by the Wessex Institute, University of Southampton and worked within the National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre (NETSCC) at the time when study was conducted. This work was supported by the NETSCC through its Research on Research Programme. SF is also employed by the University of Southampton as an Associate Professor of Public Health and KF also holds a postdoctoral Fellowship funded by the NIHR. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous product placement trials in supermarkets are limited in scope and outcome data collected. This study assessed the effects on store-level sales, household-level purchasing, and dietary behaviours of a healthier supermarket layout., Methods and Findings: This is a prospective matched controlled cluster trial with 2 intervention components: (i) new fresh fruit and vegetable sections near store entrances (replacing smaller displays at the back) and frozen vegetables repositioned to the entrance aisle, plus (ii) the removal of confectionery from checkouts and aisle ends opposite. In this pilot study, the intervention was implemented for 6 months in 3 discount supermarkets in England. Three control stores were matched on store sales and customer profiles and neighbourhood deprivation. Women customers aged 18 to 45 years, with loyalty cards, were assigned to the intervention (n = 62) or control group (n = 88) of their primary store. The trial registration number is NCT03518151. Interrupted time series analysis showed that increases in store-level sales of fruits and vegetables were greater in intervention stores than predicted at 3 (1.71 standard deviations (SDs) (95% CI 0.45, 2.96), P = 0.01) and 6 months follow-up (2.42 SDs (0.22, 4.62), P = 0.03), equivalent to approximately 6,170 and approximately 9,820 extra portions per store, per week, respectively. The proportion of purchasing fruits and vegetables per week rose among intervention participants at 3 and 6 months compared to control participants (0.2% versus -3.0%, P = 0.22; 1.7% versus -3.5%, P = 0.05, respectively). Store sales of confectionery were lower in intervention stores than predicted at 3 (-1.05 SDs (-1.98, -0.12), P = 0.03) and 6 months (-1.37 SDs (-2.95, 0.22), P = 0.09), equivalent to approximately 1,359 and approximately 1,575 fewer portions per store, per week, respectively; no differences were observed for confectionery purchasing. Changes in dietary variables were predominantly in the expected direction for health benefit. Intervention implementation was not within control of the research team, and stores could not be randomised. It is a pilot study, and, therefore, not powered to detect an effect., Conclusions: Healthier supermarket layouts can improve the nutrition profile of store sales and likely improve household purchasing and dietary quality. Placing fruits and vegetables near store entrances should be considered alongside policies to limit prominent placement of unhealthy foods., Trial Registration: ClinicalTrials.gov NCT03518151 (pre-results)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:No funding was received from the supermarket involved in this study and all analyses were conducted independently, without involvement of supermarket staff. CV, SC, DPN, KB, GM and JL have no conflicts of interest to declare. JB has received grant research support from Danone Nutricia Early Life Nutrition. CC has has received consultancy, lecture fees and honoraria from AMGEN, GKS, Alliance for Better Bone Health, MSD, Eli Lilly, Pfizer, Novartis, Servier, Medtronic and Roche. The study described in this manuscript is not related to these conflicted relationships.

Background: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges., Objectives: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials., Design: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout., Setting: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines., Results: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect., Conclusions: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial., Limitations: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS., Future Work: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space., Funding: Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council-National Institute for Health Research Methodology Research programme.

Background: Clinical trials that assess the benefits and harms of an intervention do so by measuring and reporting outcomes. Inconsistent selection and diversity in the choice of outcomes make it challenging to directly compare interventions. To achieve an agreed core set of outcomes, a consensus methodology is recommended, comprising a web-based Delphi survey and a face-to-face consensus meeting. However, UK government regulations to control the pandemic prohibited plans for a face-to-face consensus meeting as part of the Core Rehabilitation Outcome Set for Single-Sided Deafness (CROSSSD) study., Objective: This study aims to evaluate the modifications made by the CROSSSD study team to achieve consensus using web-based methods, but with minimal deviation from the original study protocol., Methods: The study team worked with health care users and professionals to translate the planned face-to-face consensus meeting in a web-based format, preserving the key elements of the nominal group technique. A follow-up survey gathered evaluation feedback on the experiences of the 22 participating members. Feedback covered premeeting preparation, the process of facilitated discussions and voting, ability to contribute, and perceived fairness of the outcome., Results: Overall, 98% (53/54) of feedback responses agreed or strongly agreed with the statements given, indicating that the web-based meeting achieved its original goals of open discussion, debate, and voting to agree with a core outcome set for single-sided deafness. Hearing-impaired participants were fully engaged, but there were some methodological challenges. For the participants, challenges included building rapport, understanding, and delivering the tasks in hand. For the study team, challenges included the need for thorough preparation and management of the unpredictability of tasks on the day., Conclusions: Sharing our experiences and lessons learned can benefit future core outcome set developers. Overcoming the challenges of delivering a web-based consensus exercise in the face of the pandemic can be applied more generally to maximize inclusiveness, enhance geographical access, and reduce research costs., (©Roulla Katiri, Deborah A Hall, Derek J Hoare, Kathryn Fackrell, Adele Horobin, Nóra Buggy, Nicholas Hogan, Pádraig T Kitterick, Core Rehabilitation Outcome Set For Single-Sided Deafness (CROSSSD) Initiative. Originally published in JMIR Formative Research (https://formative.jmir.org), 19.08.2021.)

Introduction: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK., Methods and Analysis: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA 1c ; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs., Ethics and Dissemination: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media., Trial Registration Number: ISRCTN10170306., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Competing interests: JW is receiving consultancy payments from NHSX AI Lab for advising on the validation and evaluation of AI systems for the NHS, but the views shared in this article are his own. The authors declare no other competing interest that might be relevant to the views expressed in this article.

Systems thinking provides new ways of seeing the world, focusing attention on the relationship between elements in complex systems and the spaces inbetween. Haynes study shows that many policy-makers valued systems thinking as a new way to approach old problems. But they also wanted greater focus on useful policy solutions. This raises interesting questions about the tensions between complexity and simple, action-oriented solutions and how evidence is used in decision-making. Backstage understanding of the complexity of policy problems is matched with the frontstage need to focus on what works. This reflects trends in recent public policy for evidence centres providing decision-makers with toolkits and dashboards of 'proven' interventions. There are good examples of evaluations using systems thinking allowing for complexity while addressing policy-maker needs to be accountable for public investment and decisions. Strategic communication skills are needed to provide compelling stories which embrace systems thinking without losing clarity and impact., (© 2021 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: To review comparisons of the effectiveness of endovascular stent grafting (ESG) against open surgical repair (OSR) for treatment of chronic arch or descending thoracic aortic aneurysms (TAA)., Design: Systematic review and meta-analysis DATA SOURCES: MEDLINE, EMBASE, CENTRAL, WHO International Clinical Trials Routine data collection, current controlled trials, clinical trials and the NIHR portfolio were searched from January 1994 to March 2020., Eligibility Criteria for Selective Studies: All identified studies that compared ESG and OSR, including randomised controlled trials (RCTs), quasi-randomised and non-RCTs, comparative cohort studies and case-control studies matched on main outcomes were sought. Participants had to receive elective treatments for arch/descending (TAA). Studies were excluded where other thoracic aortic conditions (eg, rupture or dissection) were reported, unless results for patients receiving elective treatment for arch/descending TAA reported separately., Data Extraction and Synthesis: Data were extracted by one reviewer and checked by another. Risk of Bias was assessed using the ROBINS-I tool. Meta-analysis was conducted using random effects. Where meta-analysis not appropriate, results were reported narratively., Results: Five comparative cohort studies met inclusion criteria, reporting 3955 ESG and 21 197 OSR patients. Meta-analysis of unadjusted short-term (30 day) all-cause mortality favoured ESG (OR 0.75; 95% CI 0.55 to 1.03)). Heterogeneity identified between larger and smaller studies. Sensitivity analysis of four studies including only descending TAA showed no statistical significance (OR 0.73, 95% CI 0.45 to 1.18)), moderate heterogeneity. Meta-analysis of adjusted short-term all-cause mortality favoured ESG (OR 0.71, 95% CI 0.51 to 0.98)), no heterogeneity. Longer-term (beyond 30 days) survival from all-cause mortality favoured OSR in larger studies and ESG in smaller studies. Freedom from reintervention in the longer-term favoured OSR. Studies reporting short-term non-fatal complications suggest fewer events following ESG., Conclusions: There is limited and increasingly dated evidence on the comparison of ESG and OSR for treatment of arch/descending TAA., Prospero Registration Number: CRD42017054565., Competing Interests: Competing interests: LV reports grants from NIHR Health Technology Assessment Programme, during the conduct of the study; and being a member of the NIHR Health Technology Assessment Programme Clinical Trials and Evaluation Panel from 2015 to 2018. CF reports grants from DoH NIHR HTA Programme, during the conduct of the study. PC reports grants from NIHR, outside the submitted work. SL reports grants from NIHR, during the conduct of the study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Depending on the treatment to be investigated, a clinical trial could be designed to assess objectives of superiority, equivalence or non-inferiority. The design of the study is affected by many different elements including the control treatment, the primary outcome and associated relationships. In some studies, there could be more than one outcome of interest. In these situations, benefit-risk methodologies could be used to assess the outcomes simultaneously and consider the trade-off between the benefits against the risks of a treatment. Benefit-risk is used within the regulatory industry but seldom included within publicly funded clinical trials within the UK. This project aims to gain an expert consensus on how to select the appropriate trial design (e.g. superiority) and when to consider including benefit-risk methods., Methods: The project will consist of four work packages: 1. A web-based survey to elicit current experiences and opinions, 2. A rapid literature review to assess any current recommendations, 3. A two-day consensus workshop to gain agreement on the recommendations, and 4. Production of a guidance document., Discussion: The aim of the project is to provide a guideline for clinical researchers, grant funding bodies and reviewers for grant bodies for how to select the most appropriate trial design and when it is appropriate to consider using benefit-risk methods. The focus of the guideline will be on publicly funded trials however, the vision is that the work will be applicable across research settings and we will connect with other organisations and committees as appropriate.

Innovations in decision-making practice for allocation of funds in health research are emerging; however, it is not clear to what extent these are used. This study aims to better understand current decision-making practices for the allocation of research funding from the perspective of UK and international health funders. An online survey (active March-April 2019) was distributed by email to UK and international health and health-related funding organisations (e.g., biomedical and social), and was publicised on social media. The survey collected information about decision-making approaches for research funding allocation, and covered assessment criteria, current and past practices, and considerations for improvements or future practice. A mixed methods analysis provided descriptive statistics (frequencies and percentages of responses) and an inductive thematic framework of key experiences. Thirty-one responses were analysed, representing government-funded organisations and charities in the health sector from the UK, Europe and Australia. Four themes were extracted and provided a narrative framework. 1. The most reported decision-making approaches were external peer review, triage, and face-to-face committee meetings; 2. Key values underpinned decision-making processes. These included transparency and gaining perspectives from reviewers with different expertise (e.g., scientific, patient and public); 3. Cross-cutting challenges of the decision-making processes faced by funders included bias, burden and external limitations; 4. Evidence of variations and innovations from the most reported decision-making approaches, including proportionate peer review, number of decision-points, virtual committee meetings and sandpits (interactive workshop). Broadly similar decision-making processes were used by all funders in this survey. Findings indicated a preference for funders to adapt current decision-making processes rather than using more innovative approaches: however, there is a need for more flexibility in decision-making and support to applicants. Funders indicated the need for information and empirical evidence on innovations which would help to inform decision-making in research fund allocation., Competing Interests: All of the authors are employed by the Wessex Institute, University of Southampton and work within the National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre (NETSCC). SF is also employed by the University of Southampton as an Associate Professor of Public Health and KF also holds a Post-Doctoral Fellowship funded by the NIHR. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Healthcare policy-makers are expected to develop 'evidence-based' policies. Yet, studies have consistently shown that, like clinical practitioners, they need to combine many varied kinds of evidence and information derived from divergent sources. Working in the complex environment of healthcare decision-making, they have to rely on forms of (practical, contextual) knowledge quite different from that produced by researchers. It is therefore important to understand how and why they transform research-based evidence into the knowledge they ultimately use., Methods: We purposively selected four healthcare-commissioning organisations working with external agencies that provided research-based evidence to assist with commissioning; we interviewed a total of 52 people involved in that work. This entailed 92 interviews in total, each lasting 20-60 minutes, including 47 with policy-making commissioners, 36 with staff of external agencies, and 9 with freelance specialists, lay representatives and local-authority professionals. We observed 25 meetings (14 within the commissioning organisations) and reviewed relevant documents. We analysed the data thematically using a constant comparison method with a coding framework and developed structured summaries consisting of 20-50 pages for each case-study site. We iteratively discussed and refined emerging findings, including cross-case analyses, in regular research team meetings with facilitated analysis. Further details of the study and other results have been described elsewhere., Results: The commissioners' role was to assess the available care provision options, develop justifiable arguments for the preferred alternatives, and navigate them through a tortuous decision-making system with often-conflicting internal and external opinion. In a multi-transactional environment characterised by interactive, pressurised, under-determined decisions, this required repeated, contested sensemaking through negotiation of many sources of evidence. Commissioners therefore had to subject research-based knowledge to multiple 'knowledge behaviours'/manipulations as they repeatedly re-interpreted and recrafted the available evidence while carrying out their many roles. Two key 'incorporative processes' underpinned these activities, namely contextualisation of evidence and engagement of stakeholders. We describe five Active Channels of Knowledge Transformation - Interpersonal Relationships, People Placement, Product Deployment, Copy, Adapt and Paste, and Governance and Procedure - that provided the organisational spaces and the mechanisms for commissioners to constantly reshape research-based knowledge while incorporating it into the eventual policies that configured local health services., Conclusions: Our new insights into the ways in which policy-makers and practitioners inevitably transform research-based knowledge, rather than simply translate it, could foster more realistic and productive expectations for the conduct and evaluation of research-informed healthcare provision.

[This corrects the article DOI: .]., (©Tobias N Bonten, Anneloek Rauwerdink, Jeremy C Wyatt, Marise J Kasteleyn, Leonard Witkamp, Heleen Riper, Lisette JEWC van Gemert-Pijnen, Kathrin Cresswell, Aziz Sheikh, Marlies P Schijven, Niels H Chavannes, EHealth Evaluation Research Group. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.08.2020.)

Background: Despite the increase in use and high expectations of digital health solutions, scientific evidence about the effectiveness of electronic health (eHealth) and other aspects such as usability and accuracy is lagging behind. eHealth solutions are complex interventions, which require a wide array of evaluation approaches that are capable of answering the many different questions that arise during the consecutive study phases of eHealth development and implementation. However, evaluators seem to struggle in choosing suitable evaluation approaches in relation to a specific study phase., Objective: The objective of this project was to provide a structured overview of the existing eHealth evaluation approaches, with the aim of assisting eHealth evaluators in selecting a suitable approach for evaluating their eHealth solution at a specific evaluation study phase., Methods: Three consecutive steps were followed. Step 1 was a systematic scoping review, summarizing existing eHealth evaluation approaches. Step 2 was a concept mapping study asking eHealth researchers about approaches for evaluating eHealth. In step 3, the results of step 1 and 2 were used to develop an "eHealth evaluation cycle" and subsequently compose the online "eHealth methodology guide.", Results: The scoping review yielded 57 articles describing 50 unique evaluation approaches. The concept mapping study questioned 43 eHealth researchers, resulting in 48 unique approaches. After removing duplicates, 75 unique evaluation approaches remained. Thereafter, an "eHealth evaluation cycle" was developed, consisting of six evaluation study phases: conceptual and planning, design, development and usability, pilot (feasibility), effectiveness (impact), uptake (implementation), and all phases. Finally, the "eHealth methodology guide" was composed by assigning the 75 evaluation approaches to the specific study phases of the "eHealth evaluation cycle.", Conclusions: Seventy-five unique evaluation approaches were found in the literature and suggested by eHealth researchers, which served as content for the online "eHealth methodology guide." By assisting evaluators in selecting a suitable evaluation approach in relation to a specific study phase of the "eHealth evaluation cycle," the guide aims to enhance the quality, safety, and successful long-term implementation of novel eHealth solutions., (©Tobias N Bonten, Anneloek Rauwerdink, Jeremy C Wyatt, Marise J Kasteleyn, Leonard Witkamp, Heleen Riper, Lisette JEWC van Gemert-Pijnen, Kathrin Cresswell, Aziz Sheikh, Marlies P Schijven, Niels H Chavannes, EHealth Evaluation Research Group. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 12.08.2020.)

Objective: The project aims to build a framework for conducting clinical trials for long-term interplanetary missions to contribute to innovation in clinical trials on Earth, especially around patient involvement and ownership., Methods: We conducted two workshops in which participants were immersed in the speculative scenario of an interplanetary mission in which health problems emerged that required medical trials to resolve. The workshops used virtual reality and live simulation to mimic a zero-gravity environment and visual perception shifts and were followed by group discussion., Results: Some key aspects for the framework that emerged from the workshops included: (a) approaches to be inclusive in the management of the trial, (b) approaches to be inclusive in designing the research project (patient preference trials, n-of-1 trials, designing clinical trials to be part of a future prospective meta-analysis, etc), (c) balancing the research needs and the community needs (eg, allocation of the participants based on both research and community need), (d) ethics and partnerships (ethics and consent issues and how they relate to partnerships and relationships)., Conclusion: In identifying some key areas that need to be incorporated in future planning of clinical trials for interplanetary missions, we also identified areas that are relevant to engaging patients in clinical trials on Earth. We will suggest using the same methodology to facilitate more in-depth discussions on specific aspects of clinical trials in aerospace medicine. The methodology can be more widely used in other areas to open new inclusive conversations around innovating research methodology., (© 2020 The Authors. Journal of Evidence-Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

The studyHodkinson A, Kontopantelis E, Adeniji C, et al. Accelerometer- and pedometer-based physical activity interventions among adults with cardiometabolic conditions: a systematic review and meta-analysis JAMA Network Open 2019;2:e1912895.This study was funded by the NIHR School for Primary Care Research (project number 390 ESWG Workstream 3).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000880/pedometers-can-help-people-get-more-active-as-part-of-an-exercise-programme., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Recruitment and retention of participants in randomised controlled trials (RCTs) is a key determinant of success but is challenging. Trialists and UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) are increasingly exploring the use of digital tools to identify, recruit and retain participants. The aim of this UK National Institute for Health Research (NIHR) study was to identify what digital tools are currently used by CTUs and understand the performance characteristics required to be judged useful., Methods: A scoping of searches (and a survey with NIHR funding staff), a survey with all 52 UKCRC CTUs and 16 qualitative interviews were conducted with five stakeholder groups including trialists within CTUs, funders and research participants. A purposive sampling approach was used to conduct the qualitative interviews during March-June 2018. Qualitative data were analysed using a content analysis and inductive approach., Results: Responses from 24 (46%) CTUs identified that database-screening tools were the most widely used digital tool for recruitment, with the majority being considered effective. The reason (and to whom) these tools were considered effective was in identifying potential participants (for both Site staff and CTU staff) and reaching recruitment target (for CTU staff/CI). Fewer retention tools were used, with short message service (SMS) or email reminders to participants being the most reported. The qualitative interviews revealed five themes across all groups: 'security and transparency'; 'inclusivity and engagement'; 'human interaction'; 'obstacles and risks'; and 'potential benefits'. There was a high level of stakeholder acceptance of the use of digital tools to support trials, despite the lack of evidence to support them over more traditional techniques. Certain differences and similarities between stakeholder groups demonstrated the complexity and challenges of using digital tools for recruiting and retaining research participants., Conclusions: Our studies identified a range of digital tools in use in recruitment and retention of RCTs, despite the lack of high-quality evidence to support their use. Understanding the type of digital tools in use to support recruitment and retention will help to inform funders and the wider research community about their value and relevance for future RCTs. Consideration of further focused digital tool reviews and primary research will help to reduce gaps in the evidence base.

The studyPalmer R, Dimairo M, Cooper C, et al. Self-managed, computerised speech and language therapy for patients with chronic aphasia post-stroke compared with usual care or attention control (Big CACTUS): a multicentre, single-blinded, randomised controlled trial. Lancet Neurol 2019;18:821-33.This project was funded by the NIHR Health Technology Assessment Programme (project number 12/21/01) and the Tavistock Trust for Aphasia.To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000864/after-a-stroke-computerised-speech-and-language-therapy-can-help-people-find-words., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyPowell J, Atherton H, Williams V, et al. Using online patient feedback to improve NHS services: the INQUIRE multimethod study. Health Serv Deliv Res 2019;7:38.This project was funded by the NIHR Health Services and Delivery Research programme (project number HS&DR 14/04/48).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000861/online-patient-feedback-is-mostly-positive-but-is-not-being-used-effectively., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyThe CRASH-3 Trial Collaborators . Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet 2019;394:1713-23.This trial was funded by NIHR Health Technology Assessment Programme (project number 14/190/01), JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and the Wellcome Trust (Joint Global Health Trials scheme).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000870/tranexamic-acid-following-mild-to-moderate-traumatic-brain-injury-is-safe-and-reduces-deaths., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The studyHewlett S, Almeida C, Ambler N, et al. Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT). Ann Rheum Dis 2019;78:465-72.Hewlett S, Almeida C, Ambler N, et al. Group cognitive behavioural programme to reduce the impact of rheumatoid arthritis fatigue: the RAFT RCT with economic and qualitative evaluations. Health Technol Assess 2019;23:57.This project was funded by the NIHR Health Technology Assessment Programme (project number 11/112/01).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000860/group-cognitive-behavioural-courses-may-reduce-fatigue-from-rheumatoid-arthritis., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyCleland LC, McComb L, Kee F, et al. Effects of 20 mph interventions on a range of public health outcomes: a meta-narrative evidence synthesis. J Transp Health 2019. doi:10.1016/j.jth.2019.100633This project was funded by the NIHR Policy Research Programme (project number 17/149/19).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000853/twenty-mph-speed-zones-reduce-the-danger-to-pedestrians-and-cyclists., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyDambha-Miller H, Day AJ, Strelitz J, et al. Behaviour change, weight loss and remission of Type 2 diabetes: a community-based prospective cohort study. Diabet Med 2019. doi:10.1111/dme.14122This project was funded by the NIHR Health Technology Assessment Programme (project number 08/116/300) as well as the Wellcome Trust (grant number: G061895), the Epidemiology Unit programme (MC_UU_12015/4), and the National Health Service R&D support funding.To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000841/weight-loss-after-type-2-diabetes-diagnosis-boosts-chance-of-remission., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Chronic neuropathic low back pain (CNLBP) is a debilitating condition in which established medical treatments seldom alleviate symptoms. Evidence demonstrates that high-frequency 10 kHz spinal cord stimulation (SCS) reduces pain and improves health-related quality of life in patients with failed back surgery syndrome (FBSS), but evidence of this effect is limited in individuals with CNLBP who have not had surgery. The aim of this multicentre randomised trial is to assess the clinical and cost-effectiveness of 10 kHz SCS for this population., Methods: This is a multicentre, double-blind, randomised, sham-controlled trial with a parallel economic evaluation. A total of 96 patients with CNLBP who have not had spinal surgery will be implanted with an epidural lead and a sham lead outside the epidural space without a screening trial. Patients will be randomised 1:1 to 10 kHz SCS plus usual care (intervention group) or to sham 10 kHz SCS plus usual care (control group) after receiving the full implant. The SCS devices will be programmed identically using a cathodal cascade. Participants will use their handheld programmer to alter the intensity of the stimulation as per routine practice. The primary outcome will be a 7-day daily pain diary. Secondary outcomes include the Oswestry Disability Index, complications, EQ-5D-5 L, and health and social care costs. Outcomes will be assessed at baseline (pre-randomisation) and at 1 month, 3 months and 6 months after device activation. The primary analyses will compare primary and secondary outcomes between groups at 6 months, while adjusting for baseline outcome scores. Incremental cost per quality-adjusted life year (QALY) will be calculated at 6 months and over the lifetime of the patient., Discussion: The outcomes of this trial will inform clinical practice and healthcare policy on the role of high-frequency 10 kHz SCS for use in patients with CNLBP who have not had surgery., Trial Registration: Clinicaltrials.gov, NCT03470766. Registered on 20 March 2018., Disclaimer: The views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The NIHR had no role in the study design, writing of the manuscript or the decision to submit for publication., Roles and Responsibilities: AK, SP, DP, SW, RST, AC, SE, LM, RD and JF all contributed to the trial design and to securing trial funding. AK, JR, SP, DP, and SE are involved in the recruitment, the intervention and the follow-up. SW will perform data collection and analysis. RST will be responsible for the statistical analysis, and RD will be responsible for the health economic analysis. All authors read and approved the final manuscript.

The studyChappell LC, Brocklehurst P, Green ME, et al. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet 2019;394:1181-90.This project was funded by the NIHR Health Technology Assessment Programme (project number 12/25/03).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000838/mothers-benefit-from-a-planned-earlier-delivery-for-late-pre-eclampsia., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyCabral C, Horwood J, Symonds J, et al. Understanding the influence of parent-clinician communication on antibiotic prescribing for children with respiratory tract infections in primary care: a qualitative observational study using a conversation analysis approach. BMC Fam Pract 2019;20:102.This project was funded by the NIHR School for Primary Care Research Programme (project number SPCR204).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000829/gps-assessment-not-parental-expectation-drives-antibiotic-prescribing., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyCooper K, Breeman S, Scott NW, et al. Laparoscopic supracervical hysterectomy versus endometrial ablation for women with heavy menstrual bleeding (HEALTH): a parallel-group, open-label, randomised controlled trial. Lancet 2019;394:1425-36.The study was funded by the NIHR Health Technology Assessment Programme (project number 12/35/23).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000837/keyhole-hysterectomy-is-effective-for-women-with-heavy-menstrual-bleeding., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019)., Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking., Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology., Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety., Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

The studyEvans JT, Walker R, Evans W, Blom AW, Sayers A, Whitehouse MRHow long does a knee replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up.Published on 16 February 2019 Lancet 2019;393:655-63This study was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol.To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000776/more-than-80-of-total-knee-replacements-can-last-for-25-years., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyHow long does a hip replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-upEvans JT, Evans JP, Walker R, Blom AW, Whitehouse MR, Sayers APublished on 16 February 2019 Lancet 2019;393:647-54This study was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000781/more-than-50-of-hip-replacements-appear-to-last-25-years., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyButler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 2019;381:111-20.This research was funded by the NIHR Technology Assessment Programme (project number 12/33/12). The testing machines used in the study were loaned to researchers by the manufacturer, who also provided training on their use. The manufacturer had no other role in any part of the trial.To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000820/crp-testing-safely-reduces-antibiotic-use-for-copd-flare-ups., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyBeard D, Davies L, Cook J, et al. The clinical and cost-effectiveness of total versus partial knee replacement in patients with medial compartment osteoarthritis (TOPKAT): 5-year outcomes of a randomised controlled trial. Lancet 2019;394:746-56.The study was funded by the NIHR Health Technology Assessment Programme (project number 08/14/08).To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000824/partial-knee-replacement-could-be-first-choice-in-some-patients., Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The studyLyttle MD, Rainford NEA, Gamble C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet 2019;393:2125-34.This trial was funded by the NIHR Health Technology Assessment Programme (project number 12/127/134).To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000790/levetiracetam-vs-phenytoin-in-stopping-childrens-prolonged-epileptic-seizures., Competing Interests: Competing interests The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)