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Objectives: This multicentre, assessor‐blinded, two‐arm cluster randomized trial evaluated the clinical and cost‐effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in UK secondary schools. Methods: Pupils aged 11–13 years with their own mobile telephone attending secondary schools with above average free school meals eligibility were randomized (at year‐group level) to receive a lesson and twice‐daily text messages or to usual care. Year‐groups (n = 84) from 42 schools including 4680 pupils (intervention, n = 2262; control, n = 2418) were randomized. Results: In 2383 participants with valid data at baseline and 2.5 years, the primary outcome of presence of at least one treated or untreated carious lesion (D4‐6 MFT [Decayed, Missing and Filled Teeth] in permanent teeth using International Caries Detection and Assessment System) was 44.6% in the intervention group and 43.0% in control (odds ratio [OR] 1.04, 95% CI 0.85–1.26, p =.72). There were no statistically significant differences in secondary outcomes of presence of at least one treated or untreated carious lesion (D1‐6 MFT), number of D4‐6 MFT and D1‐6 MFT, plaque and bleeding scores or health‐related‐ (Child Health Utility 9D) or oral health‐related‐ quality of life (CARIES‐QC). However, twice‐daily toothbrushing, reported by 77.6% of pupils at baseline, increased at 6 months (intervention, 86.9%; control, 83.0%; OR 1.30, 95% CI 1.03–1.63, p =.03), but returned to no difference at 2.5 years (intervention, 81.0%; control, 79.9%; OR 1.05, 95% CI 0.84–1.30, p =.69). Estimated incremental costs and quality‐adjusted life‐years (QALYs) of the intervention, relative to control, were £1.02 (95% CI −1.29 to 3.23) and −0.003 (95% CI −0.009 to 0.002), respectively, with a 7% chance of being cost‐effective (£20 000/QALY gained threshold). Conclusion: There was no evidence of statistically significant difference for caries prevalence at 2.5‐years. The intervention's positive 6‐month toothbrushing behaviour change did not translate into caries reduction. (ISRCTN 12139369). COVID‐19 pandemic adversly affected follow‐up. [ABSTRACT FROM AUTHOR]

Randomised controlled trials (RCTs) can be at risk of bias. Using data from a RCT, we considered the impact of post-randomisation bias. We compared the trial primary outcome, which was administered blindly, with the secondary outcome, which was not administered blindly. From 44 schools, 522 children were randomised to receive a one-to-one maths tuition programme that was assessed using 2 outcome measures. The primary outcome measure was assessed blindly whilst the secondary outcome was delivered by the classroom teacher, and therefore this was unblinded. The effect sizes for primary and secondary outcomes were substantially different (0.33 and 1.11, respectively). Test questions that were similar between the 2 tests did not explain the difference. There was greater heterogeneity between schools for the primary outcome, compared with the secondary outcome. We conclude that, in this trial, the difference between the primary and secondary outcomes was likely to have been due to lack of blinding of testers.

In response to concern over the numeracy skills deficit displayed by student nurses, an online computer programme, "Authentic World[R]", which aims to simulate a real-life clinical environment and improve the medication dosage calculation skills of users, was developed (Founded in 2004 Authentic World Ltd is a spin out company of Glarmorgan and Cardiff Universities, Cardiff, Wales UK.). Two randomised controlled trials were conducted, each at a UK University, in order to investigate the impact of Authentic World[R] on student nurses' general numeracy abilities. All first year nursing students who gave consent were randomised equally into an intervention or control group. The intervention group were given access to Authentic World[R]. The primary outcome measure was the students' scores on a general numeracy test. The Intention to Treat (ITT) analysis in both trials revealed a small negative effect of Authentic World[R] on general numeracy, which was statistically significant in one trial. However, compliance with the intervention was very low in both trials, with only 24 and 12% of students allocated to the intervention groups spending more than 15 minutes using the programme. Providing nursing students with access to Authentic World[R] is not an effective use of resources since use of the programme appears to be very low. (Contains 2 figures and 4 tables.)

Objective: To determine the acceptability and feasibility of delivering early outpatient review following cardiac surgery and early cardiac rehabilitation (CR), compared to standard practice to establish if a future large-scale trial is achievable. Methods: A randomised controlled, feasibility trial with embedded health economic evaluation and qualitative interviews, recruited patients aged 18–80 years from two UK cardiac centres who had undergone elective or urgent cardiac surgery via a median sternotomy. Eligible, consenting participants were randomised 1:1 by a remote, centralised randomisation service to postoperative outpatient review 6 weeks after hospital discharge, followed by CR commencement from 8 weeks (control), or postoperative outpatient review 3 weeks after hospital discharge, followed by commencement of CR from 4 weeks (intervention). The primary outcome measures related to trial feasibility including recruitment, retention, CR adherence, and acceptability to participants/staff. Secondary outcome measures included health-rated quality of life using EQ-5D-5L, NHS resource-use, Incremental Shuttle Walk Test (ISWT) distance, 30- and 90-day mortality, surgical site complications and hospital readmission rates. Results: Fifty participants were randomised (25 per group) and 92% declared fit for CR. Participant retention at final follow-up was 74%; completion rates for outcome data time points ranged from 28 to 92% for ISWT and 68 to 94% for follow-up questionnaires. At each time point, the mean ISWT distance walked was greater in the intervention group compared to the control. Mean utility scores increased from baseline to final follow-up by 0.202 for the intervention (0.188 control). Total costs were £1519 for the intervention (£2043 control). Fifteen participants and a research nurse were interviewed. Many control participants felt their outpatient review and CR could have happened sooner; intervention participants felt the timing was right. The research nurse found obtaining consent for willing patients challenging due to discharge timings. Conclusion: Recruitment and retention rates showed that it would be feasible to undertake a full-scale trial subject to some modifications to maximise recruitment. Lower than expected recruitment and issues with one of the clinical tests were limitations of the study. Most study procedures proved feasible and acceptable to participants, and professionals delivering early CR. Trial registration: ISRCTN80441309 (prospectively registered on 24/01/2019). [ABSTRACT FROM AUTHOR]

Background: Proximal humerus fractures (PHF) are common and painful injuries, with the majority resulting from falls from a standing height. As with other fragility fractures, its age-specific incidence is increasing. Surgical treatment with hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) have been increasingly used for displaced 3- and 4-part fractures despite a lack of good quality evidence as to whether one type of arthroplasty is superior to the other, and whether surgery is better than non-surgical management. The PROFHER-2 trial has been designed as a pragmatic, multicentre randomised trial to compare the clinical and cost-effectiveness of RSA vs HA vs Non-Surgical (NS) treatment in patients with 3- and 4-part PHF. Methods: Adults over 65 years of age presenting with acute radiographically confirmed 3- or 4-part fractures, with or without associated glenohumeral joint dislocation, who consent for trial participation will be recruited from around 40 National Health Service (NHS) Hospitals in the UK. Patients with polytrauma, open fractures, presence of axillary nerve palsy, pathological (other than osteoporotic) fractures, and those who are unable to adhere to trial procedures will be excluded. We will aim to recruit 380 participants (152 RSA, 152 HA, 76 NS) using 2:2:1 (HA:RSA:NS) randomisation for 3- or 4-part fractures without joint dislocation, and 1:1 (HA:RSA) randomisation for 3- or 4-part fracture dislocations. The primary outcome is the Oxford Shoulder Score at 24 months. Secondary outcomes include quality of life (EQ-5D-5L), pain, range of shoulder motion, fracture healing and implant position on X-rays, further procedures, and complications. Independent Trial Steering Committee and Data Monitoring Committee will oversee the trial conduct, including the reporting of adverse events and harms. Discussion: The PROFHER-2 trial is designed to provide a robust answer to guide the treatment of patients aged 65 years or over who sustain 3- and 4-part proximal humeral fractures. The pragmatic design and recruitment from around 40 UK NHS hospitals will ensure immediate applicability and generalisability of the trial findings. The full trial results will be made available in a relevant open-access peer-reviewed journal. Trial registration: ISRCTN76296703. Prospectively registered on 5th April 2018 [ABSTRACT FROM AUTHOR]

The Addiction Recovery Questionnaire (ARQ) is derived from the views of service users, their families and friends. Data were collected from 305 participants in the UK general population and addiction services, asked to self-identify as being in one of three groups: treatment, recovery or well-functioning, and complete the ARQ. Regression and latent class analyses were used to determine that the ARQ could distinguish the three groups. Clinically significant change values were established. Although there are some discrepancies in the way individuals define their recovery, self-identification was found to be broadly valid. The ARQ is able to assign people to different stages of recovery from addiction, and provides an instrument for monitoring change and measuring outcomes in the key components of lifestyle, involvement with substance use and self-confidence. [ABSTRACT FROM AUTHOR]

Background: Globally, around 13% of children experience dental anxiety (DA). This group of patients frequently miss dental appointments, have greater reliance on treatment under general anaesthesia (GA) and have poorer oral health-related quality of life (OHRQoL) than their non-dentally anxious peers. Recently, a low-intensity cognitive behavioural therapy (CBT)-based, self-help approach has been recommended for management of childhood anxiety disorders. A feasibility study conducted in secondary care found this guided self-help CBT resource reduced DA and a randomised controlled trial was recommended. The present study aims to establish the clinical and cost-effectiveness of a guided self-help CBT intervention to reduce DA in children attending primary dental care sites compared to usual care. Methods: This 4-year randomised controlled trial will involve 600 children (aged 9–16 years) and their parent/carers in 30 UK primary dental care sites. At least two dental professionals will participate in each site. They will be assigned, using random allocation, to receive the CBT training and deliver the intervention or to deliver usual care. Children with DA attending these sites, in need of treatment, will be randomly allocated to be treated either by the intervention (CBT) or control (usual care) dental professional. Children will complete questionnaires relating to DA, OHRQoL and HRQoL before treatment, immediately after treatment completion and 12 months post-randomisation. Attendance, need for sedation/GA and costs of the two different approaches will be compared. The primary outcome, DA, will be measured using the Modified Child Dental Anxiety Scale. Scores will be compared between groups using a linear mixed model. Discussion: Treating dentally anxious patients can be challenging and costly. Consequently, these children are frequently referred to specialist services for pharmacological interventions. Longer waiting times and greater travel distances may then compound existing healthcare inequalities. This research will investigate whether the intervention has the potential to reduce DA and improve oral health outcomes in children over their life-course, as well as upskilling primary dental healthcare professionals to better manage this patient group. Trial registration: This clinical trial has been registered with an international registry and has been allocated an International Standard Randomised Controlled Trial Number (ISRCTN27579420). [ABSTRACT FROM AUTHOR]

This study explored the lived experience of people with inflammatory bowel disease and anxiety/depression. It utilised a deductive biopsychosocial framework. Overall, 24 patients and 20 healthcare professionals from two countries participated. In the United Kingdom, the main themes included (1) bidirectional relationship between inflammatory bowel disease and mental health, (2) the need for healthcare integration and (3) lack of awareness about the disease. In Australia, (1) the 'vicious cycle' of inflammatory bowel disease and psychosocial health, (2) the need for biopsychosocial healthcare integration and (3) the stigma of a hidden disease. Better communication around mental illness is essential in improving inflammatory bowel disease healthcare. [ABSTRACT FROM AUTHOR]

Background: Dupuytren's contracture is a fibro-proliferative disease of the hands affecting over 2 million UK adults, particularly the white, male population. Surgery is the traditional treatment; however, recent studies have indicated that an alternative to surgery-collagenase clostridium histolyticum (collagenase)-is better than a placebo in the treatment of Dupuytren's contracture. There is however no robust randomised controlled trial that provides a definitive answer on the clinical effectiveness of collagenase compared with limited fasciectomy surgery. Dupuytren's intervention surgery vs collagenase trial (DISC) trial was therefore designed to fill this evidence gap.Methods/design: The DISC trial is a multi-centre pragmatic two-arm parallel-group, randomised controlled trial. Participants will be assigned 1:1 to receive either collagenase injection or surgery (limited fasciectomy). We aim to recruit 710 adult participants with Dupuytren's contracture. Potential participants will be identified in primary and secondary care, screened by a delegated clinician and if eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported patient evaluation measure assessed 1 year after treatment. Secondary outcome measures include the Unité Rhumatologique des Affections de la Main Scale, the Michigan Hand Questionnaire, EQ-5D-5L, resource use, further procedures, complications, recurrence, total active movement and extension deficit, and time to return to function. Given the limited evidence comparing recurrence rates following collagenase injection and limited fasciectomy, and the importance of a return to function as soon as possible for patients, the associated measures for each will be prioritised to allow treatment effectiveness in the context of these key elements to be assessed. An economic evaluation will assess the cost-effectiveness of treatments, and a qualitative sub-study will assess participants' experiences and preferences of the treatments.Discussion: The DISC trial is the first randomised controlled trial, to our knowledge, to investigate the clinical and cost-effectiveness of collagenase compared to limited fasciectomy surgery for patients with Dupuytren's contracture.Trial Registration: Clinical.Trials.gov ISRCTN18254597 . Registered on April 11, 2017. [ABSTRACT FROM AUTHOR]

Aims: Diabetes is two to three times more prevalent in people with severe mental illness, yet little is known about the challenges of managing both conditions from the perspectives of people living with the co‐morbidity, their family members or healthcare staff. Our aim was to understand these challenges and to explore the circumstances that influence access to and receipt of diabetes care for people with severe mental illness. Methods: Framework analysis of qualitative semi‐structured interviews with people with severe mental illness and diabetes, family members, and staff from UK primary care, mental health and diabetes services, selected using a maximum variation sampling strategy between April and December 2018. Results: In all, 39 adults with severe mental illness and diabetes (3 with type 1 diabetes and 36 with type 2 diabetes), nine family members and 30 healthcare staff participated. Five themes were identified: (a) Severe mental illness governs everyday life including diabetes management; (b) mood influences capacity and motivation for diabetes self‐management; (c) cumulative burden of managing multiple physical conditions; (d) interacting conditions and overlapping symptoms and (e) support for everyday challenges. People living with the co‐morbidity and their family members emphasised the importance of receiving support for the everyday challenges that impact diabetes management, and identified barriers to accessing this from healthcare providers. Conclusions: More intensive support for diabetes management is needed when people's severe mental illness (including symptoms of depression) or physical health deteriorates. Interventions that help people, including healthcare staff, distinguish between symptoms of diabetes and severe mental illness are also needed. [ABSTRACT FROM AUTHOR]

Aims The AUDIT-C is a brief and commonly used alcohol screening tool, with few data available on the relative validity of the three individual items in older adult populations. The aim of this study was to explore the validity of the AUDIT-C items in identifying unhealthy drinking among older people, with a view to developing a single-item screener. Methods A sample of 143 older adults (mean age = 71) were recruited from non-clinical settings in the UK. AUDIT-C scores were compared to an unhealthy drinking reference category of consuming more than the UK recommended weekly units of alcohol. Standard analyses were conducted for men and women, and for those prescribed medications for long term conditions. Results The AUDIT-C items performed well in identifying unhealthy drinking in this sample of older people, with generally high sensitivity, specificity and area under the ROC curve. No significant differences were found in the validity of the three items, though the combined sensitivity and specificity scores and ROC values for item 3 were consistently slightly lower than for items 1 and 2. The findings were similar for men and women, and for participants prescribed medications for long-term conditions. Conclusions AUDIT-C items 1 and 2 performed as well as item 3 in identifying unhealthy drinking among older people in this study. Both are reasonable single-item screener candidates, especially given relative ease of administration, with further validation study needed to examine psychometrics and how alcohol screening for older people can best be implemented in clinical settings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: People with serious mental illness (SMI) have sexual health needs but there is little evidence to inform effective interventions to address them. In fact, there are few studies that have addressed this topic for people with SMI outside USA and Brazil. Therefore, the aim of the study was to establish the acceptability and feasibility of a trial of a sexual health promotion intervention for people with SMI in the UK.Method: The RESPECT study was a two-armed randomised controlled, open feasibility trial (RCT) comparing Sexual health promotion intervention (3 individual sessions of 1 h) (I) or treatment as usual (TAU) for adults aged 18 or over, with SMI, within community mental health services in four UK cities. The main outcome of interest was the percentage who consented to participate, and retained in each arm of the trial, retention for the intervention, and completeness of data collection. A nested qualitative study obtained the views of participants regarding the acceptability of the study using individual telephone interviews conducted by lived experience researchers.Results: Of a target sample of 100, a total of 72 people were enrolled in the trial over 12 months. Recruitment in the initial months was low and so an extension was granted. However this extension meant that the later recruited participants would only be followed up to the 3 month point. There was good retention in the intervention and the study as a whole; 77.8% of those allocated to intervention (n = 28) received it. At three months, 81.9% (30 I; 29 TAU) and at 6 months, 76.3% (13 I and 16 TAU) completed the follow-up data collection. No adverse events were reported. There was good completeness of the data. The sexual health outcomes for the intervention group changed in favour of the intervention. Based on analysis of the qualitative interviews, the methods of recruitment, the quality of the participant information, the data collection, and the intervention were deemed to be acceptable to the participants (n = 22).Conclusions: The target of 100 participants was not achieved within the study's timescale. However, effective strategies were identified that improved recruitment in the final few months. Retention rates and completeness of data in both groups indicate that it is acceptable and feasible to undertake a study promoting sexual health for people with SMI. A fully powered RCT is required to establish effectiveness of the intervention in adoption of safer sex.Study Registration: ISRCTN Registry ISRCTN15747739 prospectively registered 5th July 2016. [ABSTRACT FROM AUTHOR]

Background: A thoracolumbar fracture is the most common fracture of the spinal column. Where the fracture is not obviously stable or unstable, the optimal management is uncertain. There are variations between surgeons, treating centres and within the evidence base as to whether surgical or non-surgical approaches should be used. In addition, the boundaries of this zone of uncertainty for stability are unclear. This study has been designed in response to an NIHR HTA commissioning brief to assess the feasibility of undertaking a large-scale trial to evaluate the effectiveness of surgical and non-surgical treatments for thoracolumbar fractures without neurological deficit. Methods: Assessment of feasibility will be addressed through three elements: a randomised external feasibility study, a national survey of surgeons and a qualitative study. The external feasibility study is a pragmatic, parallel-group, randomised controlled trial comparing surgical fixation (intervention) versus non-surgical management (control). Recruitment will take place in three secondary care centres in the UK. The primary outcome is recruitment rate, defined as the proportion of eligible participants who are randomised. Further outcomes related to recruitment, randomisation, drop-out, cross-over, loss to follow-up, completeness of outcome data, study processes and details of the interventions delivered will be collected. The survey of surgeons and qualitative study of clinicians, recruiting staff and patients will enhance the feasibility study, enabling a broad overview of current practice in the field in addition to perceived facilitators and barriers to running a full-scale trial. Discussion: PRESTO is a feasibility study which aims to inform methodology for a definitive trial comparing surgical fixation with non-surgical management for patients with stable thoracolumbar fractures. Trial registration: The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN12094890). Date of registration was 22/02/2018 (http://www.isrctn.com/ISRCTN12094890). [ABSTRACT FROM AUTHOR]

Background: Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit?Methods: The Cessation in Pregnancy Incentives Trial (CPIT) III is a pragmatic, 42-month, multi-centre, parallel-group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual Stop Smoking Services (SSS) support, the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy. Participants (n = 940) are pregnant smokers (age > 16 years, < 24 weeks pregnant, English speaking), who consent via telephone to take part and are willing to be followed-up in late pregnancy and 6 months after birth. The primary outcome is cotinine/anabasine-validated abstinence from smoking in late pregnancy. Secondary outcomes include engagement with SSS, quit rates at 4 weeks from agreed quit date and 6 months after birth, and birth weight. Outcomes will be analysed by intention to treat, and regression models will be used to compare treatment effects on outcomes. A meta-analysis will include data from the feasibility study in Glasgow. An economic evaluation will assess cost-effectiveness from a UK NHS perspective. Process evaluation using a case-study approach will identify opportunities to improve recruitment and learning for future implementation. Research questions include: what is the therapeutic efficacy of incentives; are incentives cost-effective; and what are the potential facilitators and barriers to implementing incentives in different parts of the UK?Discussion: This phase III trial in Scotland, England and Northern Ireland follows a successful phase II trial in Glasgow, UK. The participating sites have diverse SSS that represent most cessation services in the UK and serve demographically varied populations. If found to be acceptable and cost-effective, this trial could demonstrate that financial incentives are effective and transferable to most UK SSS for pregnant women.Trial Registration: Current Controlled Trials, ISRCTN15236311. Registered on 9 October 2017. [ABSTRACT FROM AUTHOR]

Summary: Islamic religious settings (IRS) may be useful places to implement obesity interventions for Muslims. However, little is known about the level and nature of such activity in these settings. We searched bibliographic databases and grey literature, and requested grey information from Muslim organizations, local councils, and mosques in 13 selected areas in the United Kingdom. Thirty‐five interventions were identified; most were poorly described and not evaluated. Twenty‐seven interventions focused on physical activity behaviours, four on diet behaviours, one on both behaviours, and seven addressed long‐term conditions associated with obesity. Most interventions were led by volunteers from the congregation/faith leaders and were funded through donations from congregants or charity organizations. The evidence suggests that health promotion interventions in IRS have a relatively high reach. Obesity interventions are commonly delivered in UK IRS. Most target physical activity behaviours, are instigated and led by volunteers from the congregation or faith leaders, receive no public funding, and are only recorded in people's memories. High‐quality evaluations of well‐specified interventions in this context are needed. We suggest that the methods used in this review, including the learning around positionality of researchers, could be adopted by other researchers as a way to locate opportunities for effective community‐level interventions. [ABSTRACT FROM AUTHOR]

Objectives: Evidence suggests that maternal psychological distress is an under-diagnosed condition that can have lasting impacts on child outcomes. Models based solely on maternal outcomes have not found screening to be cost-effective. This research explores the effects of self-reported maternal psychological distress on children's language and behavioural development up to the age of 7. Methods: Using longitudinal survey data from 10,893 families in the UK Millennium Cohort Study, multilevel models are used to explore the differential effects of maternal diagnosed and treated depression versus untreated maternal psychological distress during the postnatal year on longer-term child outcomes. Results: Both diagnosed and treated depression and self-reported maternal psychological distress have detrimental effects on child behavioural development. Behavioural outcomes up to age 5 were better for children of women who received treatment for depression, compared with children those whose mothers' psychological distress was untreated, but this was not maintained to age 7. Little or no evidence of a difference was found between maternal psychological distress and child language development. Conclusions for Practice: This research highlights the lack of effectiveness of existing treatment for maternal psychological distress both to benefit child development and to provide long-term symptom remediation for women. Future research could aim to identify more effective treatments for both women and children. [ABSTRACT FROM AUTHOR]

Background: Lifestyle advice is widely considered as an integral component of acupuncture treatment. However, it is unclear whether lifestyle advice and related self-care are important for sustaining benefit over the longer term. In a novel secondary analysis of trial data, this paper explores the nature and impact of acupuncture-related diagnosis, and associated lifestyle advice and self-care, in patients with chronic neck pain. Design: In a three-arm, randomized, controlled multicenter trial with 12 months of follow-up, a total of 517 patients with chronic neck pain were randomized in equal proportions to acupuncture, Alexander technique, or usual care alone. Methods: For each acupuncture patient, practitioners reported treatment components that included an acupuncture-related diagnosis and provision of associated lifestyle advice. Patients reported at baseline, 3, 6, and 12 months on variables related to treatment, which included aspects of self-care, self-efficacy, and lifestyle advice acted upon, as well as pain and disability scores. Congruence between practitioner advice and patient take-up was assessed using chi-squared test. Impact of lifestyle advice and self-efficacy on outcome was evaluated using regression models. Results: Among patients randomized to acupuncture, the most common diagnostic framework involved the Zang-Fu syndromes for 139/160 (87%) patients. Lifestyle advice was provided by practitioners to 134/160 (84%) of patients, most commonly related to exercise, relaxation, diet, rest, and work. Significant congruence with patient take-up was found for diet, rest, and work. Moreover, patients in the acupuncture group improved their ability to use what they had learnt and increased their self-efficacy. In turn, these characteristics were associated with significant reductions in pain and disability scores at 12 months. Conclusion: Acupuncture-related lifestyle advice helped patients improve the way they live and care for themselves and enhanced self-efficacy and ability to use what they had learnt. These changes were associated with reductions in pain and disability at 12 months. [ABSTRACT FROM AUTHOR]

Importance: There is little evidence to guide management of depressive symptoms in older people.Objective: To evaluate whether a collaborative care intervention can reduce depressive symptoms and prevent more severe depression in older people.Design, Setting, and Participants: Randomized clinical trial conducted from May 24, 2011, to November 14, 2014, in 32 primary care centers in the United Kingdom among 705 participants aged 65 years or older with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) subthreshold depression; participants were followed up for 12 months.Interventions: Collaborative care (n=344) was coordinated by a case manager who assessed functional impairments relating to mood symptoms. Participants were offered behavioral activation and completed an average of 6 weekly sessions. The control group received usual primary care (n=361).Main Outcomes and Measures: The primary outcome was self-reported depression severity at 4-month follow-up on the 9-item Patient Health Questionnaire (PHQ-9; score range, 0-27). Included among 10 prespecified secondary outcomes were the PHQ-9 score at 12-month follow-up and the proportion meeting criteria for depressive disorder (PHQ-9 score ≥10) at 4- and 12-month follow-up.Results: The 705 participants were 58% female with a mean age of 77 (SD, 7.1) years. Four-month retention was 83%, with higher loss to follow-up in collaborative care (82/344 [24%]) vs usual care (37/361 [10%]). Collaborative care resulted in lower PHQ-9 scores vs usual care at 4-month follow-up (mean score with collaborative care, 5.36 vs with usual care, 6.67; mean difference, -1.31; 95% CI, -1.95 to -0.67; P < .001). Treatment differences remained at 12 months (mean PHQ-9 score with collaborative care, 5.93 vs with usual care, 7.25; mean difference, -1.33; 95% CI, -2.10 to -0.55). The proportions of participants meeting criteria for depression at 4-month follow-up were 17.2% (45/262) vs 23.5% (76/324), respectively (difference, -6.3% [95% CI, -12.8% to 0.2%]; relative risk, 0.83 [95% CI, 0.61-1.27]; P = .25) and at 12-month follow-up were 15.7% (37/235) vs 27.8% (79/284) (difference, -12.1% [95% CI, -19.1% to -5.1%]; relative risk, 0.65 [95% CI, 0.46-0.91]; P = .01).Conclusions and Relevance: Among older adults with subthreshold depression, collaborative care compared with usual care resulted in a statistically significant difference in depressive symptoms at 4-month follow-up, of uncertain clinical importance. Although differences persisted through 12 months, findings are limited by attrition, and further research is needed to assess longer-term efficacy.Trial Registration: isrctn.org Identifier: ISRCTN02202951. [ABSTRACT FROM AUTHOR]

The article presents a meta-analysis and systematic review on the effects of a physician's gender on communication and length of consultation with patients. It mentions its possible contribution to patient satisfaction as well as the search for Grey literature. It also notes the involvement of quality assessment and data extraction in accordance with the guidelines of the nonprofit organization, the Cochrane Collaboration.

Background: Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain. Methods/design: HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to -treat basis. Discussion: The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting. Trial registration: ISRCTN91859104. [ABSTRACT FROM AUTHOR]

Randomised controlled trials are widely accepted as the gold standard method to evaluate medical interventions, but they are still open to bias. One such bias is the effect of patient's preference on outcome measures. The aims of this study were to examine whether patients' treatment preference affected clearance of plantar warts and explore whether there were any associations between patients' treatment preference and baseline variables in the EverT trial. [ABSTRACT FROM AUTHOR]

Feasibility study: Objectives: Refine a bespoke enhanced support intervention (ESI) (including self-help materials, intervention manual and training) for implementation by community pharmacy (CP) staff to people with sub-threshold depression and long-term conditions (LTCs) based upon evidence-supported interventions in primary care Develop and refine study procedures (recruitment strategies and set up, screening, participant recruitment, assessment, suitability of outcome measures and data collection procedures) for testing in the pilot study phase Design: A case series/qualitative study Setting: UK community pharmacy Population: Adults with long-term health conditions who screen-positive for depression but who do not reach the threshold for DSM IV Moderate Depressive disorder Intervention: Enhanced support intervention (ESI) delivered by an appropriately trained community pharmacy team member involving four to six sessions over four months. ESI is a modified form of an intervention within the collaborative care framework for sub-threshold depression validated in previous studies in UK primary care which appears suitable for implementation in community settings. Sample size: 20–30 participants Outcomes: Study implementation (recruitment and attrition rates), quality of data collection at baseline and 4 months and ESI adherence (number of contacts, DNA and drop out) as per objectives 1a/b Qualitative evaluation: Semi-structured interviews with up to 10 participants and ESI facilitators and focus group(s) (range of pharmacy staff n = 8–10) will be conducted to explore the acceptability of the intervention and feasibility of the study, training and study procedures. External pilot study: Objectives: Quantify the flow of participants (eligibility, recruitment and follow-up rate) Evaluate proposed recruitment, assessment and outcome measure collection methods Examine the delivery of the enhanced support intervention in a community pharmacy setting (intervention uptake, retention and dose) to inform process evaluation Process evaluation, using semi-structured interviews with participants across a range of socio-economic settings, and pharmacy staff to explore the acceptability of the ESI within community pharmacy, elements of the intervention that were considered useful (or not) and appropriateness of study procedures Design: Pilot randomised controlled trial, including a prospective economic and qualitative evaluation Setting: As above Population: As above Intervention: As above with adaptations post feasibility study Comparator: Usual care Sample size: 100 participants Outcomes: Data will be used to estimate recruitment, intervention delivery and study completion rates as per objectives 2a–d. Definitive estimates of the effectiveness of ESI will not be made. Primary outcome: Depression severity (Patient Health Questionnaire 9) at four months. Secondary outcomes: Patient acceptance, uptake and attrition. ICD10 depression status, anxiety (GAD 7), health-related quality of life (SF-12v2) and health-state utility (EQ5D 3L) will be measured at four months. Economic evaluation: The incremental cost per QALY will be calculated from both the NHS and societal perspective. Process evaluation: Using mixed methods, potential mediators/moderators of the intervention, the acceptability (to participants and pharmacy staff), barriers and facilitators to the use of ESI in community pharmacy, and impact on usual practice will be examined. Semi-structured interviews with approximately 30 study participants, 20 pharmacy staff and eight GPs near participating pharmacies will be conducted. Trial registration: ISRCTN: ISRCTN11290592 Protocol version number: Version 4.1 (dated 16th January 2018) Study Sponsor Tees Esk and Wear Valleys NHS Foundation Trust [ABSTRACT FROM AUTHOR]

Background: Chronic pelvic pain affects 2-24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.Methods: We performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18-50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16-17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13-16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.Findings: Participants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13-16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was -1·4 (SD 2·3) in the gabapentin group and -1·2 (SD 2·1) in the placebo group (adjusted mean difference -0·20 [97·5% CI -0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was -1·1 (SD 2·0) in the gabapentin group and -0·9 (SD 1·8) in the placebo group (adjusted mean difference -0·18 [97·5% CI -0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.Interpretation: This study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.Funding: National Institute for Health Research. [ABSTRACT FROM AUTHOR]

The article discusses a cost effectiveness analysis of the cost effectiveness of routine screening for postnatal depression in primary care for Great Britain's National Health Service (NHS). The researchers used a hypothetical population of women examined for postnatal depression either through routine care only or supplemented by use of formal identification method six weeks postnatally. A systematic review and bivariate meta-analysis was the source of the performance of screening instruments.

Abstract: Objective: To assess outcome reporting bias and dissemination bias in trials funded by the National Health System (NHS) Health Technology Assessment (HTA) program. Study Design and Setting: A retrospective cohort study of HTA monographs and corresponding journal publications including all clinical effectiveness randomized controlled trials published as HTA monographs between 1999 and 2005 by the NHS HTA program. Results: There was a higher median P-value (P =0.33, interquartile range [IQR]: 0.02–0.54) among trials without a journal publication compared with those with a journal publication (P =0.14, IQR: 0.007–0.43), although the difference was not statistically significant (Mann-Whitney U test, z =−0.70; P =0.48). A higher proportion of statistically significant findings were reported in journal articles when compared with the outcomes reported in the HTA monographs. Trials published in general medical journals tended to have smaller P-values (median: 0.05, IQR: 0.001–0.22) than those published in more specialist journals (median: 0.33 IQR: 0.008–0.58), although this result was not significant (Mann-Whitney U test, z =−1.63; P =0.10). Conclusions: Among journal-published trials, there were a greater proportion of statistically significant findings included in the journal reports compared with those in the HTA monographs. [Copyright &y& Elsevier]

Introduction: Chest wall trauma is commonly seen in patients admitted with both high and low-energy transfer injury. Whilst often associated with other injuries, it is also seen in isolation following simple falls in the older patient. Fixation of the chest wall grows in popularity as part of optimising patient care, particularly in terms of critical care stay. There is currently no description of the epidemiology of these injuries at a national level; nor has there been identification of factors that predict which of these patients undergoes surgery.Methods: The United Kingdom Trauma Audit & Research Network (TARN) database was analysed for the period April 2016 to 30th May 2017 for all adult patients presenting with a rib or sternal fracture. Characteristics of the population were described and a binary logistic regression model constructed to explore the influences of several explanatory variables on whether fixation was performed.Results: Of 16,638 patients with chest wall trauma, 402 underwent fixation. Most chest wall injury patients were admitted under three specialties (orthopaedics (19.1%), emergency medicine (16.6%) and general surgery (17.7%)). The odds of fixation in unilateral flail chest was 107.51 (p <0.0001), in bilateral flail or combined complexsternal fracture 47.63 (p = 0.007) and in 3 or more non-flail ribs 15.62 (p<0.0001) when compared to less than three non-flail rib fractures. The odds of fixation was higher in an MTC (p<0.0001) compared to a non-specialist hospital. The odds of fixation was higher in older patients (1.02, p<0.0001) and the more severely injured (1.02, p<0.0001).Conclusion: There is considerable variation nationally in the management of chest wall trauma. Injury type, patient age and care setting contribute to decision making in fracture fixation. This unique national dataset characterises for the first time the nature of contemporary chest wall trauma management and should help inform the design of future research on this topic. [ABSTRACT FROM AUTHOR]

The article discusses a research study which aimed to evaluate the cost-effectiveness of yoga intervention and usual care compared with usual care alone for chronic or recurrent low back pain. An overview on the prevalence of back pain in Great Britain is provided along with methods used in gathering data, determining costs of yoga intervention and health care resource, and the cost-effectiveness analysis. Results are explained indicating that 12 weekly group classes of yoga is cost-effective.

Background: Dupuytren's contracture is caused by nodules and cords which pull the fingers towards the palm of the hand. Treatments include limited fasciectomy surgery, collagenase injection and needle fasciotomy. There is limited evidence comparing limited fasciectomy with collagenase injection., Objectives: To compare whether collagenase injection is not inferior to limited fasciectomy when treating Dupuytren's contracture., Design: Pragmatic, two-arm, unblinded, randomised controlled non-inferiority trial with a cost-effectiveness evaluation and nested qualitative and photographic substudies., Setting: Thirty-one National Health Service hospitals in England and Scotland., Participants: Patients with Dupuytren's contracture of ≥ 30 degrees who had not received previous treatment in the same digit., Interventions: Collagenase injection with manipulation 1-7 days later was compared with limited fasciectomy., Main Outcome Measures: The primary outcome was the Patient Evaluation Measure score, with 1 year after treatment serving as the primary end point. A difference of 6 points in the primary end point was used as the non-inferiority margin. Secondary outcomes included: Unité Rhumatologique des Affections de la Main scale; Michigan Hand Outcomes Questionnaire; recurrence; extension deficit and total active movement; further care/re-intervention; complications; quality-adjusted life-year; resource use; and time to function recovery., Randomisation and Blinding: Online central randomisation, stratified by the most affected joint, and with variable block sizes allocates participants 1 : 1 to collagenase or limited fasciectomy. Participants and clinicians were not blind to treatment allocation., Results: Between 31 July 2017 and 28 September 2021, 672 participants were recruited ( n  = 336 per group), of which 599 participants contributed to the primary outcome analysis ( n  = 285 limited fasciectomy; n  = 314 collagenase). At 1 year (primary end point) there was little evidence to support rejection of the hypothesis that collagenase is inferior to limited fasciectomy. The difference in Patient Evaluation Measure score at 1 year was 5.95 (95% confidence interval 3.12 to 8.77; p  = 0.49), increasing to 7.18 (95% confidence interval 4.18 to 10.88) at 2 years. The collagenase group had more complications ( n  = 267, 0.82 per participant) than the limited fasciectomy group ( n  = 177, 0.60 per participant), but limited fasciectomy participants had a greater proportion of 'moderate'/'severe' complications (5% vs. 2%). At least 54 participants (15.7%) had contracture recurrence and there was weak evidence suggesting that collagenase participants recurred more often than limited fasciectomy participants (odds ratio 1.39, 95% confidence interval 0.74 to 2.63). At 1 year, collagenase had an insignificantly worse quality-adjusted life-year gain (-0.003, 95% confidence interval -0.006 to 0.0004) and a significant cost saving (-£1090, 95% confidence interval -£1139 to -£1042) than limited fasciectomy with the probability of collagenase being cost-effective exceeding 99% at willingness to pay thresholds of £20,000-£30,000 per quality-adjusted life-year. At 2 years, collagenase was both significantly less effective (-0.048, 95% confidence interval -0.055 to -0.040) and less costly (-£1212, 95% confidence interval -£1276 to -£1147). The probability of collagenase being cost-effective was 72% at the £20,000 threshold but limited fasciectomy became the optimal treatment at thresholds over £25,488. The Markov model found the probability of collagenase being cost-effective at the lifetime horizon dropped below 22% at thresholds over £20,000. Semistructured qualitative interviews found that those treated with collagenase considered the outcome to be acceptable, though not perfect. The photography substudy found poor agreement between goniometry and both participant and clinician taken photographs, even after accounting for systematic differences from each method., Limitations: Impacts of the COVID-19 pandemic resulted in longer waits for Dupuytren's contracture treatment, meaning some participants could not be followed up for 2 years. This resulted in potential underestimation of Dupuytren's contracture recurrence and/or re-intervention rates, which may particularly have impacted the clinical effectiveness and long-term Markov model findings., Conclusions: Among adults with Dupuytren's contracture, collagenase delivered in an outpatient setting is less effective but more cost-saving than limited fasciectomy. Further research is required to establish the longer-term implications of both treatments., Future Work: Recurrence and re-intervention usually occur after 1 year, and therefore follow-up to 5 years or more could resolve whether the differences observed in the Dupuytren's interventions surgery versus collagenase trial to 2 years worsen., Study Registration: Current Controlled Trials ISRCTN18254597., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/102/04) and is published in full in Health Technology Assessment ; Vol. 28, No. 78. See the NIHR Funding and Awards website for further award information.

Background: The presence of dental caries impacts on children's daily lives, particularly among those living in deprived areas. There are successful interventions across the United Kingdom for young children based on toothbrushing with fluoride toothpaste. However, evidence is lacking for oral health improvement programmes in secondary-school pupils to reduce dental caries and its sequelae., Objectives: To determine the clinical and cost effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in secondary-school pupils., Design: A multicentre, school-based, assessor-blinded, two-arm cluster randomised controlled trial with an internal pilot and embedded health economic and process evaluations., Setting: Secondary schools in Scotland, England and Wales with above-average proportion of pupils eligible for free school meals. Randomisation occurred within schools (year-group level), using block randomisation stratified by school., Participants: Pupils aged 11-13 years at recruitment, who have their own mobile telephone., Interventions: Two-component intervention based on behaviour change theory: (1) 50-minute lesson delivered by teachers, and (2) twice-daily text messages to pupils' mobile phones about toothbrushing, compared with routine education., Main Outcome Measures: Primary outcome: presence of at least one treated or untreated carious lesion using D ICDAS4-6 MFT (Decayed, Missing and Filled Teeth) in any permanent tooth, measured at pupil level at 2.5 years. Secondary outcomes included: number of D ICDAS4-6 MFT; presence and number of D ICDAS1-6 MFT; plaque; bleeding; twice-daily toothbrushing; health-related quality of life (Child Health Utility 9D); and oral health-related quality of life (Caries Impacts and Experiences Questionnaire for Children)., Results: Four thousand six hundred and eighty pupils (intervention, n  = 2262; control, n  = 2418) from 42 schools were randomised. The primary analysis on 2383 pupils (50.9%; intervention 1153, 51.0%; control 1230, 50.9%) with valid data at baseline and 2.5 years found 44.6% in the intervention group and 43.0% in control had obvious decay experience in at least one permanent tooth. There was no evidence of a difference (odds ratio 1.04, 95% confidence interval 0.85 to 1.26, p  = 0.72) and no statistically significant differences in secondary outcomes except for twice-daily toothbrushing at 6 months (odds ratio 1.30, 95% confidence interval 1.03 to 1.63, p  = 0.03) and gingival bleeding score (borderline) at 2.5 years (geometric mean difference 0.92, 95% confidence interval 0.85 to 1.00, p  = 0.05). The intervention had higher incremental mean costs (£1.02, 95% confidence interval -1.29 to 3.23) and lower incremental mean quality-adjusted life-years (-0.003, 95% confidence interval -0.009 to 0.002). The probability of the intervention being cost-effective was 7% at 2.5 years. However, in two subgroups, pilot trial schools and schools with higher proportions of pupils eligible for free school meals, there was an 84% and 60% chance of cost effectiveness, respectively, although their incremental costs and quality-adjusted life-years remained small and not statistically significant. The process evaluation revealed that the intervention was generally acceptable, although the implementation of text messages proved challenging. The COVID-19 pandemic hampered data collection. High rates of missing economic data mean findings should be interpreted with caution., Conclusions: Engagement with the intervention and evidence of 6-month change in toothbrushing behaviour was positive but did not translate into a reduction of caries. Future work should include work with secondary-school pupils to develop an understanding of the determinants of oral health behaviours, including toothbrushing and sugar consumption, particularly according to free school meal eligibility., Trial Registration: This trial is registered as ISRCTN12139369., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/166/08) and is published in full in Health Technology Assessment ; Vol. 28, No. 52. See the NIHR Funding and Awards website for further award information.

Background: Young adults represent a third of the United Kingdom prison population and are at risk of poor health outcomes, including drug and alcohol misuse, self-harm and suicide. Court diversion interventions aim to reduce the negative consequences of criminal sanctions and address the root causes of offending. However, evidence of their effectiveness has not yet been established. The Gateway programme, issued as a conditional caution, aimed to improve the life chances of young adults committing low-level offences. Participants agreed not to reoffend during the 16-week caution and, following a needs assessment, received individual support from a Gateway navigator and attended two workshops encouraging analysis of own behaviour and its consequences., Objective: To evaluate the effectiveness and cost-effectiveness of Gateway in relation to health and well-being of participants compared to usual process (court summons or a different conditional caution)., Design, Setting and Participants: Pragmatic, multisite, parallel-group, superiority randomised controlled trial with two 6-month internal pilots and a target sample size of 334. Randomisation between Gateway and usual process was on a 1 : 1 basis. Four Hampshire Constabulary sites recruited 18- to 24-year-old residents of Hampshire and Isle of Wight who were questioned for an eligible low-level offence. Semistructured interviews were also held with a sample of Gateway programme participants, staff and police study recruiters., Main Outcome Measures: Primary outcome was the Warwick-Edinburgh Mental Wellbeing Scale score at 12 months. Secondary outcomes included health status, alcohol and drug use, recidivism and resource use., Results: Recruitment commenced in October 2019 and the trial stopped in April 2021. A total of 191 participants were recruited, with 109 randomised to Gateway and 82 to usual process. Due to an initial overestimation of potentially eligible young people and low retention rates, recruitment targets were adjusted, and a range of mitigating measures introduced. Although recruitment broadly met study progression criteria [35/50 (70%) Pilot 1: 64/74 (86%) Pilot 2], retention was low throughout (overall: data collected at week 4 was 50%: at week 16 it was 50%: 1-year 37%). Low retention was multifactorial, with one of the main barriers being difficulties contacting participants. It was therefore not possible to complete the randomised controlled trial or the health economics analyses. Qualitative interviews held with 58 individuals yielded rare insights into the benefits and limitations of this type of intervention, as well as barriers and facilitators in relation to recruitment in this setting., Limitations: Despite close collaboration with the police to address recruitment and consent issues, expansion of the inclusion criteria and recruitment area and introducing other measures, the researchers were unable to collect sufficient data within an acceptable timeframe., Conclusions: The Gateway study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. The experience gained indicates that randomised controlled trials of interventions, with a health-related outcome, are possible in this setting but point towards the need for conservative recruitment and retention estimates in this target population. Other study designs should be considered. The qualitative evaluation provided a range of valuable lessons for those seeking to design similar interventions or conduct research in similar settings., Study Registration: This study is registered as ISRCTN11888938., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research ; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.

Introduction: Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently, bDMARDs are withheld during the perioperative period due to potential infection risk. However, this predisposes patients to IA flares and loss of disease control. The question of whether to stop or continue bDMARDs in the perioperative period has not been adequately addressed in a randomised controlled trial (RCT)., Methods and Analysis: PERISCOPE is a multicentre, superiority, pragmatic RCT investigating the stoppage or continuation of bDMARDs. Participants will be assigned 1:1 to either stop or continue their bDMARDs during the perioperative period. We aim to recruit 394 adult participants with IA. Potential participants will be identified in secondary care hospitals in the UK, screened by a delegated clinician. If eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported PROMIS-29 (Patient Reported Outcome Measurement Information System) over the first 12 weeks postsurgery. Secondary outcome measures are as follows: PROMIS - Health Assessment Questionnaire (PROMIS-HAQ), EQ-5D-5L, Disease activity: generic global Numeric Rating Scale (patient and clinician), Self-Administered Patient Satisfaction scale, Health care resource use and costs, Medication use, Surgical site infection, delayed wound healing, Adverse events (including systemic infections) and disease-specific outcomes (according to IA diagnosis). The costs associated with stopping and continuing bDMARDs will be assessed. A qualitative study will explore the patients' and clinicians' acceptability and experience of continuation/stoppage of bDMARDs in the perioperative period and the impact postoperatively., Ethics and Dissemination: Ethical approval for this study was received from the West of Scotland Research Ethics Committee on 25 April 2023 (REC Ref: 23/WS/0049). The findings from PERISCOPE will be submitted to peer-reviewed journals and feed directly into practice guidelines for the use of bDMARDs in the perioperative period., Trial Registration Number: ISRCTN17691638., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Randomised controlled trials ('trials') are susceptible to poor participant recruitment and retention. Studies Within A Trial are the strongest methods for testing the effectiveness of strategies to improve recruitment and retention. However, relatively few of these have been conducted., Objectives: PROMoting THE Use of Studies Within A Trial aimed to facilitate at least 25 Studies Within A Trial evaluating recruitment or retention strategies. We share our experience of delivering the PROMoting THE Use of Studies Within A Trial programme, and the lessons learnt for undertaking randomised Studies Within A Trial., Design: A network of 10 Clinical Trials Units and 1 primary care research centre committed to conducting randomised controlled Studies Within A Trial of recruitment and/or retention strategies was established. Promising recruitment and retention strategies were identified from various sources including Cochrane systematic reviews, the Study Within A Trial Repository, and existing prioritisation exercises, which were reviewed by patient and public members to create an initial priority list of seven recruitment and eight retention interventions. Host trial teams could apply for funding and receive support from the PROMoting THE Use of Studies Within A Trial team to undertake Studies Within A Trial. We also tested the feasibility of undertaking co-ordinated Studies Within A Trial, across multiple host trials simultaneously., Setting: Clinical trials unit-based trials recruiting or following up participants in any setting in the United Kingdom were eligible., Participants: Clinical trials unit-based teams undertaking trials in any clinical context in the United Kingdom., Interventions: Funding of up to £5000 and support from the PROMoting THE Use of Studies Within A Trial team to design, implement and report Studies Within A Trial., Main Outcome Measures: Number of host trials funded., Results: Forty-two Studies Within A Trial were funded (31 host trials), across 12 Clinical Trials Units. The mean cost of a Study Within A Trial was £3535. Twelve Studies Within A Trial tested the same strategy across multiple host trials using a co-ordinated Study Within A Trial design, and four used a factorial design. Two recruitment and five retention strategies were evaluated in more than one host trial. PROMoting THE Use of Studies Within A Trial will add 18% more Studies Within A Trial to the Cochrane systematic review of recruitment strategies, and 79% more Studies Within A Trial to the Cochrane review of retention strategies. For retention, we found that pre-notifying participants by card, letter or e-mail before sending questionnaires was effective, as was the use of pens, and sending personalised text messages to improve questionnaire response. We highlight key lessons learnt to guide others planning Studies Within A Trial, including involving patient and public involvement partners; prioritising and selecting strategies to evaluate and elements to consider when designing a Study Within A Trial; obtaining governance approvals; implementing Studies Within A Trial, including individual and co-ordinated Studies Within A Trials; and reporting Study Within A Trials., Limitations: The COVID-19 pandemic negatively impacted five Studies Within A Trial, being either delayed ( n  = 2) or prematurely terminated ( n  = 3)., Conclusions: PROMoting THE Use of Studies Within A Trial significantly increased the evidence base for recruitment and retention strategies. When provided with both funding and practical support, host trial teams successfully implemented Studies Within A Trial., Future Work: Future research should identify and target gaps in the evidence base, including widening Study Within A Trial uptake, undertaking more complex Studies Within A Trial and translating Study Within A Trial evidence into practice., Study Registration: All Studies Within A Trial in the PROMoting THE Use of Studies Within A Trial programme had to be registered with the Northern Ireland Network for Trials Methodology Research Study Within A Trial Repository., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/55/80) and is published in full in Health Technology Assessment ; Vol. 28, No. 2. See the NIHR Funding and Awards website for further award information.

Background: Behavioural and cognitive interventions remain credible approaches in addressing loneliness and depression. There was a need to rapidly generate and assimilate trial-based data during COVID-19., Objectives: We undertook a parallel pilot RCT of behavioural activation (a brief behavioural intervention) for depression and loneliness (Behavioural Activation in Social Isolation, the BASIL-C19 trial ISRCTN94091479). We also assimilate these data in a living systematic review (PROSPERO CRD42021298788) of cognitive and/or behavioural interventions., Methods: Participants (≥65 years) with long-term conditions were computer randomised to behavioural activation (n=47) versus care as usual (n=49). Primary outcome was PHQ-9. Secondary outcomes included loneliness (De Jong Scale). Data from the BASIL-C19 trial were included in a metanalysis of depression and loneliness., Findings: The 12 months adjusted mean difference for PHQ-9 was -0.70 (95% CI -2.61 to 1.20) and for loneliness was -0.39 (95% CI -1.43 to 0.65).The BASIL-C19 living systematic review (12 trials) found short-term reductions in depression (standardised mean difference (SMD)=-0.31, 95% CI -0.51 to -0.11) and loneliness (SMD=-0.48, 95% CI -0.70 to -0.27). There were few long-term trials, but there was evidence of some benefit (loneliness SMD=-0.20, 95% CI -0.40 to -0.01; depression SMD=-0.20, 95% CI -0.47 to 0.07)., Discussion: We delivered a pilot trial of a behavioural intervention targeting loneliness and depression; achieving long-term follow-up. Living meta-analysis provides strong evidence of short-term benefit for loneliness and depression for cognitive and/or behavioural approaches. A fully powered BASIL trial is underway., Clinical Implications: Scalable behavioural and cognitive approaches should be considered as population-level strategies for depression and loneliness on the basis of a living systematic review., Competing Interests: Competing interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests. DE and CCG were committee members for the NICE Depression Guideline (update) Development Group between 2015 and 2022, and SiG was a member between 2015 and 2018. SiG, PC and DM are supported by the NIHR Yorkshire and Humberside Applied Research Collaboration (ARC) and DE is supported by the North East and North Cumbria ARCs. CCG is part funded by West Midland ARC., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To determine the effectiveness of sending Christmas cards to participants in randomised controlled trials to increase retention rate at follow-ups, and to explore the feasibility of doing a study within a trial (SWAT) across multiple host trials simultaneously., Design: Randomised SWAT conducted simultaneously across eight host trials., Setting: Eight randomised controlled trials researching various areas including surgery and smoking cessation., Participants: 3223 trial participants who were still due at least one follow-up from their host randomised controlled trial., Intervention: Participants were randomised (1:1, separately by each host trial) to either received a Christmas card in mid-December 2019 or to not receive a card., Main Outcome Measure: Proportion of participants completing their next follow-up (retention rate) within their host randomised controlled trial., Results: 1469 participants (age 16-94 years; 70% (n=1033) female; 96% (813/847) white ethnicity) across the eight host randomised controlled trials were involved in the analysis (cut short owing to covid-19). No evidence was found of a difference in retention rate between the two arms for any of the host trials when analysed separately or when the results were combined (85.3% (639/749) for cards versus 85.4% (615/720) for no card; odds ratio 0.96, 95% confidence interval 0.71 to 1.29; P=0.77). No difference was observed when comparing just participants who were due a follow-up in the 30 days after receiving the card (odds ratio 0.96, 0.42 to 2.21). No evidence of a difference in time to complete the questionnaire was found (hazard ratio 1.01, 95% confidence interval 0.91 to 1.13; P=0.80). These results were robust to post hoc sensitivity analyses. The cost of this intervention was £0.76 (€0.91; $1.02) per participant, and it will have a carbon footprint of approximately 140 g CO 2 equivalent per card. One benefit of this approach was the need to only submit one ethics application., Conclusions: Sending Christmas cards to participants in randomised controlled trials does not increase retention. Undertaking a SWAT within multiple randomised controlled trials at the same time is, however, possible. This approach should be used more often to build an evidence base to support selection of recruitment and retention strategies. Although no evidence of a boost to retention was found, embedding a SWAT in multiple host trials simultaneously has been shown to be possible., Study Registration: SWAT repository https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding from the MRC PROMETHEUS programme to support this work; no financial relationship with any organisation that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Older adults, including those with long-term conditions (LTCs), are vulnerable to social isolation. They are likely to have become more socially isolated during the Coronavirus Disease 2019 (COVID-19) pandemic, often due to advice to "shield" to protect them from infection. This places them at particular risk of depression and loneliness. There is a need for brief scalable psychosocial interventions to mitigate the psychological impacts of social isolation. Behavioural activation (BA) is a credible candidate intervention, but a trial is needed., Methods and Findings: We undertook an external pilot parallel randomised trial (ISRCTN94091479) designed to test recruitment, retention and engagement with, and the acceptability and preliminary effects of the intervention. Participants aged ≥65 years with 2 or more LTCs were recruited in primary care and randomised by computer and with concealed allocation between June and October 2020. BA was offered to intervention participants (n = 47), and control participants received usual primary care (n = 49). Assessment of outcome was made blind to treatment allocation. The primary outcome was depression severity (measured using the Patient Health Questionnaire 9 (PHQ-9)). We also measured health-related quality of life (measured by the Short Form (SF)-12v2 mental component scale (MCS) and physical component scale (PCS)), anxiety (measured by the Generalised Anxiety Disorder 7 (GAD-7)), perceived social and emotional loneliness (measured by the De Jong Gierveld Scale: 11-item loneliness scale). Outcome was measured at 1 and 3 months. The mean age of participants was aged 74 years (standard deviation (SD) 5.5) and they were mostly White (n = 92, 95.8%), and approximately two-thirds of the sample were female (n = 59, 61.5%). Remote recruitment was possible, and 45/47 (95.7%) randomised to the intervention completed 1 or more sessions (median 6 sessions) out of 8. A total of 90 (93.8%) completed the 1-month follow-up, and 86 (89.6%) completed the 3-month follow-up, with similar rates for control (1 month: 45/49 and 3 months 44/49) and intervention (1 month: 45/47and 3 months: 42/47) follow-up. Between-group comparisons were made using a confidence interval (CI) approach, and by adjusting for the covariate of interest at baseline. At 1 month (the primary clinical outcome point), the median number of completed sessions for people receiving the BA intervention was 3, and almost all participants were still receiving the BA intervention. The between-group comparison for the primary clinical outcome at 1 month was an adjusted between-group mean difference of -0.50 PHQ-9 points (95% CI -2.01 to 1.01), but only a small number of participants had completed the intervention at this point. At 3 months, the PHQ-9 adjusted mean difference (AMD) was 0.19 (95% CI -1.36 to 1.75). When we examined loneliness, the adjusted between-group difference in the De Jong Gierveld Loneliness Scale at 1 month was 0.28 (95% CI -0.51 to 1.06) and at 3 months -0.87 (95% CI -1.56 to -0.18), suggesting evidence of benefit of the intervention at this time point. For anxiety, the GAD adjusted between-group difference at 1 month was 0.20 (-1.33, 1.73) and at 3 months 0.31 (-1.08, 1.70). For the SF-12 (physical component score), the adjusted between-group difference at 1 month was 0.34 (-4.17, 4.85) and at 3 months 0.11 (-4.46, 4.67). For the SF-12 (mental component score), the adjusted between-group difference at 1 month was 1.91 (-2.64, 5.15) and at 3 months 1.26 (-2.64, 5.15). Participants who withdrew had minimal depressive symptoms at entry. There were no adverse events. The Behavioural Activation in Social Isolation (BASIL) study had 2 main limitations. First, we found that the intervention was still being delivered at the prespecified primary outcome point, and this fed into the design of the main trial where a primary outcome of 3 months is now collected. Second, this was a pilot trial and was not designed to test between-group differences with high levels of statistical power. Type 2 errors are likely to have occurred, and a larger trial is now underway to test for robust effects and replicate signals of effectiveness in important secondary outcomes such as loneliness., Conclusions: In this study, we observed that BA is a credible intervention to mitigate the psychological impacts of COVID-19 isolation for older adults. We demonstrated that it is feasible to undertake a trial of BA. The intervention can be delivered remotely and at scale, but should be reserved for older adults with evidence of depressive symptoms. The significant reduction in loneliness is unlikely to be a chance finding, and replication will be explored in a fully powered randomised controlled trial (RCT)., Trial Registration: ISRCTN94091479., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: DE and CCG are current committee members for the NICE Depression Guideline (update) Development Group, and SG was a member between 2015-18. SG, PC and DMcM are supported by the NIHR Yorkshire and Humberside Applied Research Collaboration (ARC) and DE is supported by the North East and North Cumbria ARCs.

Rationale: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up., Approach: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation., Reflection: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution., Discussion: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale., Competing Interests: Competing interests: JW reports grants, personal fees and other from AstraZeneca, other from Astellas, other from Boehringer Ingelheim, other from Lilly, other from Napp, grants, personal fees and other from Novo Nordisk, other from Sanofi, grants, personal fees and other from Takeda, other from Rhythm Pharma, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Smoking contributes to health inequalities for people with severe mental illness (SMI). Although smoking cessation interventions are effective in the short term, there are few long-term trial-based estimates of abstinence. The SCIMITAR trials programme includes the largest trial to date of a smoking cessation intervention for people with SMI, but this was underpowered to detect anticipated long-term quit rates. By pooling pilot and full-trial data we found that quit rates were maintained at 12 months (OR = 1.67, 95% CI 1.02-2.73, P = 0.04). Policymakers can now be confident that bespoke smoking cessation interventions produce successful short- and long-term quitting.

Background: Frozen shoulder causes pain and stiffness. It affects around 10% of people in their fifties and is slightly more common in women. Costly and invasive surgical interventions are used, without high-quality evidence that these are effective., Objectives: To compare the clinical effectiveness and cost-effectiveness of three treatments in secondary care for adults with frozen shoulder; to qualitatively explore the acceptability of these treatments to patients and health-care professionals; and to update a systematic review to explore the trial findings in the context of existing evidence for the three treatments., Design: This was a pragmatic, parallel-group, multicentre, open-label, three-arm, randomised superiority trial with unequal allocation (2 : 2 : 1). An economic evaluation and a nested qualitative study were also carried out., Setting: The orthopaedic departments of 35 hospitals across the UK were recruited from April 2015, with final follow-up in December 2018., Participants: Participants were adults (aged ≥ 18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation in the affected shoulder to < 50% of the opposite shoulder, and with plain radiographs excluding other pathology., Interventions: The inventions were early structured physiotherapy with a steroid injection, manipulation under anaesthesia with a steroid injection and arthroscopic capsular release followed by manipulation. Both of the surgical interventions were followed with post-procedural physiotherapy., Main Outcome Measures: The primary outcome and end point was the Oxford Shoulder Score at 12 months post randomisation. A difference of 5 points between early structured physiotherapy and manipulation under anaesthesia or arthroscopic capsular release or of 4 points between manipulation under anaesthesia and arthroscopic capsular release was judged clinically important., Results: The mean age of the 503 participants was 54 years; 319 were female (63%) and 150 had diabetes (30%). The primary analyses comprised 473 participants (94%). At the primary end point of 12 months, participants randomised to arthroscopic capsular release had, on average, a statistically significantly higher (better) Oxford Shoulder Score than those randomised to manipulation under anaesthesia (2.01 points, 95% confidence interval 0.10 to 3.91 points; p  = 0.04) or early structured physiotherapy (3.06 points, 95% confidence interval 0.71 to 5.41 points; p  = 0.01). Manipulation under anaesthesia did not result in statistically significantly better Oxford Shoulder Score than early structured physiotherapy (1.05 points, 95% confidence interval -1.28 to 3.39 points; p  = 0.38). No differences were deemed of clinical importance. Serious adverse events were rare but occurred in participants randomised to surgery (arthroscopic capsular release, n  = 8; manipulation under anaesthesia, n  = 2). There was, however, one serious adverse event in a participant who received non-trial physiotherapy. The base-case economic analysis showed that manipulation under anaesthesia was more expensive than early structured physiotherapy, with slightly better utilities. The incremental cost-effectiveness ratio for manipulation under anaesthesia was £6984 per additional quality-adjusted life-year, and this intervention was probably 86% cost-effective at the threshold of £20,000 per quality-adjusted life-year. Arthroscopic capsular release was more costly than early structured physiotherapy and manipulation under anaesthesia, with no statistically significant benefit in utilities. Participants in the qualitative study wanted early medical help and a quicker pathway to resolve their shoulder problem. Nine studies were identified from the updated systematic review, including UK FROST, of which only two could be pooled, and found that arthroscopic capsular release was more effective than physiotherapy in the long-term shoulder functioning of patients, but not to the clinically important magnitude used in UK FROST., Limitations: Implementing physiotherapy to the trial standard in clinical practice might prove challenging but could avoid theatre use and post-procedural physiotherapy. There are potential confounding effects of waiting times in the trial., Conclusions: None of the three interventions was clearly superior. Early structured physiotherapy with a steroid injection is an accessible and low-cost option. Manipulation under anaesthesia is the most cost-effective option. Arthroscopic capsular release carries higher risks and higher costs., Future Work: Evaluation in a randomised controlled trial is recommended to address the increasing popularity of hydrodilatation despite the paucity of high-quality evidence., Trial Registration: Current Controlled Trials ISRCTN48804508., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 71. See the NIHR Journals Library website for further project information.

Background: Alcohol interventions are important to the developing public health role of community pharmacies. The Medicines and Alcohol Consultation (MAC) is a new intervention, co-produced with community pharmacists (CPs) and patients, which involves a CP practice development programme designed to integrate discussion of alcohol within existing NHS medicine review services. We conducted a pilot trial of the MAC and its delivery to investigate all study procedures to inform progression to a definitive trial., Methods: This cluster pilot RCT was conducted in 10 community pharmacies in Yorkshire, UK, with a CP from each who regularly conducted Medicine Use Review (MUR) and New Medicine Service (NMS) consultations. Randomisation was conducted using a secure remote randomisation service. Intervention CPs (n = 5) were trained to deliver the MAC in MUR/NMS consultations. Control CPs (n = 5) provided these services as usual. Consecutive MUR/NMS patients were asked by CPs to participate, screened for eligibility (consumption of alcohol at least twice per week), and baseline data collected for those eligible. A two-month follow-up telephone interview was conducted. Blinding of CPs was not possible, but patients were blinded to the alcohol focus of the trial. Primary outcomes were total weekly UK units (8 g of ethanol per unit) of alcohol consumption in the week prior to follow-up, and confidence in medications management. Trial procedures were assessed by recruitment, attrition, and follow-up rates., Results: 260 patients were approached by CPs to take part in the trial, 68% (n = 178) were assessed for eligibility and 30% (n = 54) of these patients were eligible. Almost all eligible patients (n = 51; 94%) consented to participate, of whom 92% (n = 47) were followed-up at 2 months; alcohol consumption was lower in the intervention arm and confidence in medication management reduced slightly for both groups. Exploration of recall issues at follow-up showed a high level of agreement between a two-item quantity/frequency measure and 7-day guided recall of alcohol consumption., Conclusions: The pilot trial demonstrates the feasibility of implementing the MAC in community pharmacy and trial recruitment and data collection procedures. However, decommissioning of MURs means that it is not possible to conduct a definitive trial of the intervention in this service., Trial Registration: ISRCTN57447996.

Background: Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection., Methods: In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508., Findings: Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release)., Interpretation: All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective., Funding: The National Institute for Health Research Health Technology Assessment programme., (Copyright © 2020 The Author(s). Publishedx by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: GPs are rarely actively involved in healthcare provision for children and young people (CYP) with life-limiting conditions (LLCs). This raises problems when these children develop minor illness or require management of other chronic diseases., Aim: To investigate the association between GP attendance patterns and hospital urgent and emergency care use., Design and Setting: Retrospective cohort study using a primary care data source (Clinical Practice Research Datalink) in England. The cohort numbered 19 888., Method: CYP aged 0-25 years with an LLC were identified using Read codes (primary care) or International Classification of Diseases 10 th Revision (ICD-10) codes (secondary care). Emergency inpatient admissions and accident and emergency (A&E) attendances were separately analysed using multivariable, two-level random intercept negative binomial models with key variables of consistency and regularity of GP attendances., Results: Face-to-face GP surgery consultations reduced, from a mean of 7.12 per person year in 2000 to 4.43 in 2015. Those consulting the GP less regularly had 15% (95% confidence interval [CI] = 10% to 20%) more emergency admissions and 5% more A&E visits (95% CI = 1% to 10%) than those with more regular consultations. CYP who had greater consistency of GP seen had 10% (95% CI = 6% to 14%) fewer A&E attendances but no significant difference in emergency inpatient admissions than those with lower consistency., Conclusion: There is an association between GP attendance patterns and use of urgent secondary care for CYP with LLCs, with less regular GP attendance associated with higher urgent secondary healthcare use. This is an important area for further investigation and warrants the attention of policymakers and GPs, as the number of CYP with LLCs living in the community rises., (©The Authors.)

Background: People with serious mental illness have sexual health needs, but there is limited evidence regarding effective interventions to promote their sexual health., Objectives: To develop a sexual health promotion intervention for people with serious mental illness, and to conduct a feasibility trial in order to establish the acceptability and parameters for a fully powered trial., Design: A two-armed randomised controlled, open feasibility study comparing usual care alone with usual care plus the adjunctive intervention., Setting: Five community mental health providers in Leeds, Barnsley, Brighton and London., Participants: Adults aged ≥ 18 years with serious mental illness and receiving care from community mental health teams., Interventions: A remote, web-based computer randomisation system allocated participants to usual care plus the RESPECT (Randomised Evaluation of Sexual health Promotion Effectiveness informing Care and Treatment) intervention (three sessions of 1 hour) (intervention arm) or usual care only (control arm). The intervention was an interactive manualised package of exercises, quizzes and discussion topics focusing on knowledge, motivation and behavioural intentions to adopt safer sexual behaviours., Main Outcome Measures: Feasibility parameters including establishing the percentage of people who were eligible, consented and were retained in each arm of the trial, retention for the intervention, as well as the completeness of the data collection. Data were collected on knowledge, motivation to adopt safer sexual behaviour, sexual behaviour, sexual stigma, sexual health service use and quality of life. Data were collected at baseline and then at 3 months and 6 months post randomisation., Results: Of a target of 100 participants, 72 people participated in the trial over 12 months. Of the 36 participants randomised to the intervention arm, 27 received some of the intervention (75.0%). At 3 months, 59 of the 72 participants completed follow-up questionnaires (81.9%) (30 participants from the intervention arm and 29 participants from the control arm). Only the first 38 participants were followed up at 6 months. However, data were collected on 29 out of 38 participants (76.3% retention): 13 in the intervention arm and 16 in the control arm. No adverse events were reported. Participant feedback confirmed that both the design and the intervention were acceptable. The economic analysis indicated high completion rates and completeness of data among participants who continued the trial., Conclusions: Despite the limitations, the findings suggest that it is both acceptable and feasible to undertake a sexual health promotion study for people with serious mental illness., Future Work: A fully powered randomised controlled trial would be required to establish the clinical effectiveness of the intervention., Trial Registration: Current Controlled Trials ISRCTN15747739., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 65. See the NIHR Journals Library website for further project information., Competing Interests: Catherine Hewitt reports being a member of the National Institute for Health Research Health Technology Assessment Commissioning Board.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: The reports from cohort studies comparing outcomes after revascularisation for chronic limb threatening ischaemia (CLTI) between men and women remain controversial. Anatomical and clinical disease severity is often heterogeneous, and treatment choice influenced by a variety of clinician and patient factors. The aim was to compare outcomes in men and women entered into the only randomised study comparing bypass and angioplasty for infra-inguinal disease causing severe limb ischaemia., Methods: Data were obtained from BASIL-1 trial case record forms. Baseline demographics were compared, and Cox proportional hazard models were used to examine the relationship between sex and amputation free survival (AFS), overall survival (OS), and freedom from major adverse limb events (FF-MALE) using a per-protocol analysis. Data were analysed using a per-protocol analysis., Results: A total of 452 patients were randomised into the BASIL-1 trial from 1999 to 2004. At randomisation, women were older and less likely to be smokers, to have diabetes, or to be on recommended best medical therapy. Men were more likely to present with gangrene. Ankle brachial pressure index (ABPI), post-revascularisation length of hospital stay, and 30 day morbidity and mortality were similar for men and women. At three years, female sex was associated with significantly better AFS (HR 0.65, 95% CI 0.47-0.89, p < .01), OS (HR 0.66 95% CI 0.46-0.95, p = .02) and FF-MALE (HR 0.74, 95% CI 0.57-0.96, p = .02)., Conclusion: In the BASIL-1 trial, women had similar short term but better long term outcomes after revascularisation. Sex is an important consideration when developing early, evidence based treatment pathway and revascularisation strategies for CLTI, and is an independent risk factor for outcomes following revascularisation as well as development of symptomatic PAD., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: Almost one-half of 12-15 year olds living in deprived areas of the UK have dental caries (tooth decay) with few oral health promotion programmes aimed at children of this age. Mobile phone-based interventions such as short messaging service (SMS) interventions have been found effective at changing certain behaviours and improving health outcomes. This protocol describes the BRIGHT Trial, investigating the clinical and cost-effectiveness of a behaviour change intervention-classroom-based session (CBS) embedded in the curriculum and a series of SMS delivered to participants twice daily to remind them to brush their teeth, compared to usual curriculum and no SMS-to reduce the prevalence of dental caries in young people from deprived areas., Objectives: To investigate the clinical and cost-effectiveness of a complex intervention to improve the oral health of young people living in deprived areas., Methods/design: This is a school-based, assessor-blinded, two-arm cluster-randomised controlled trial with an internal pilot trial. Overall, the trial will involve approximately 5040 11-13 year olds in 42 schools with a 3-year follow-up. The trial will take place in secondary schools in England, Scotland and Wales. The primary outcome is the presence of carious lesions in permanent teeth at 3 years. Secondary outcomes are: number of carious teeth, frequency of twice-daily toothbrushing, plaque levels, gingivitis, child health-related quality of life and oral health-related quality of life. A cost-utility analysis will be conducted., Discussion: The findings of the trial have implications for embedding oral health interventions into school curricula guidance produced by national bodies, including departments for education and dental public health and guideline-development organisations., Trial Registration: ISRCTN registry, ISRCTN12139369 . Registered on 10 May 2017.

Background: The aim of fistula surgery is to eradicate the disease while preserving anal sphincter function. The efficacy of the Surgisis ® anal fistula plug (Cook Medical, Bloomington, IN, USA) in the treatment of trans-sphincteric fistula-in-ano has been variably reported., Objectives: To undertake a randomised comparison of the safety and efficacy of the Surgisis anal fistula plug in comparison with surgeon's preference for the treatment of trans-sphincteric anal fistulas., Design: A randomised, unblinded, parallel-arm, prospective, multicentre clinical trial., Setting: Hospitals in the UK NHS involving colorectal surgeons accredited by the Association of Coloproctology of Great Britain and Ireland., Participants: Adult patients suffering from trans-sphincteric fistula-in-ano of cryptoglandular origin., Interventions: Patients were randomised on a 1 : 1 basis to either the fistula plug or the surgeon's preference [e.g. fistulotomy, cutting seton, advancement flap or ligation of intersphincteric fistula tract (LIFT) procedure]., Main Outcome Measures: The primary outcome measure was quality of life as measured by the Faecal Incontinence Quality of Life (FIQoL) questionnaire at 12-month follow-up. Secondary outcome measures included clinical and radiological fistula healing rates, faecal incontinence rates, complications rates, reintervention rates and cost-effectiveness., Results: Between May 2011 and March 2016, 304 participants were recruited (152 fistula plug vs. 152 surgeon's preference). No difference in FIQoL score between the two trial groups was seen at the 6-week, 6-month or 12-month follow-up. Clinical evidence of fistula healing was reported in 66 of 122 (54%) participants in the fistula plug group and in 66 of 119 (55%) participants in the surgeon's preference group at 12 months. Magnetic resonance imaging (MRI) showed fistula healing in 54 of 110 (49%) participants in the fistula plug group and in 63 of 112 (56%) participants in the surgeon's preference group. Variation in 12-month clinical healing rates was observed: 55%, 64%, 75%, 53% and 42% for fistula plug, cutting seton, fistulotomy, advancement flap and LIFT procedure, respectively. Faecal incontinence rates were low at baseline, with small improvement in both groups post treatment. Complications and reinterventions were frequent. The mean total costs were £2738 [standard deviation (SD) £1151] in the fistula plug group and £2308 (SD £1228) in the surgeon's preference group. The average total quality-adjusted life-years (QALYs) gain was much smaller in the fistula plug group (0.829, SD 0.174) than in the surgeon's preference group (0.790, SD 0.212). Using multiple imputation and probabilistic sensitivity analysis, and adjusting for differences in baseline EuroQol-5 Dimensions, three-level version utility, there was a 35-45% chance that the fistula plug was as cost-effective as surgeon's preference over a range of thresholds of willingness to pay for a single QALY of £20,000-30,000., Limitations: Limitations include a smaller sample size than originally calculated, a lack of blinding that perhaps biased patient-reported outcomes and a lower compliance rate with MRI at 12-month follow-up., Conclusions: The Surgisis anal fistula plug is associated with similar FIQoL score to surgeon's preference at 12-month follow-up. The higher costs and highly uncertain and small gains in QALYs associated with the fistula plug mean that this technology is unlikely to be considered a cost-effective use of resources in the UK NHS., Future Work: Further in-depth analysis should consider the clinical and MRI characteristics of fistula-in-ano in an attempt to identify predictors of fistula response to treatment., Trial Registration: Current Controlled Trials ISRCTN78352529., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 21. See the NIHR Journals Library website for further project information., Competing Interests: David G Jayne was a member of the Health Technology Assessment (HTA) Surgery Themed Call Board from 2012 to 2013 and a member of the Efficacy and Mechanism Evaluation Strategy Group from 2015 to 2018. John Scholefield was a member of the HTA Surgery Themed Call Board from 2012 to 2013. Claire T Hulme was a member of the HTA Commissioning Board from 2012 to 2017.

Background: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness., Methods: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete., Findings: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13)., Interpretation: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting., Funding: National Institute for Health Research Health Technology Assessment Programme., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Tubal ectopic pregnancy (tEP) is the most common life-threatening condition in gynaecology. Treatment options include surgery and medical management. Stable women with tEPs with pre-treatment serum human chorionic gonadotrophin (hCG) levels < 1000 IU/L respond well to outpatient medical treatment with intramuscular methotrexate. However, tEPs with hCG > 1000 IU/L can take significant time to resolve with methotrexate and require multiple outpatient monitoring visits. In pre-clinical studies, we found that tEP implantation sites express high levels of epidermal growth factor receptor. In early-phase trials, we found that combination therapy with gefitinib, an orally active epidermal growth factor receptor antagonist, and methotrexate resolved tEPs without the need for surgery in over 70% of cases, did not cause significant toxicities, and was well tolerated. We describe the protocol of a randomised trial to assess the efficacy of combination gefitinib and methotrexate, versus methotrexate alone, in reducing the need for surgical intervention for tEPs., Methods and Analysis: We propose to undertake a multi-centre, double-blind, placebo-controlled, randomised trial (around 70 sites across the UK) and recruit 328 women with tEPs (with pre-treatment serum hCG of 1000-5000 IU/L). Women will be randomised in a 1:1 ratio by a secure online system to receive a single dose of intramuscular methotrexate (50 mg/m 2 ) and either oral gefitinib or matched placebo (250 mg) daily for 7 days. Participants and healthcare providers will remain blinded to treatment allocation throughout the trial. The primary outcome is the need for surgical intervention for tEP. Secondary outcomes are the need for further methotrexate treatment, time to resolution of the tEP (serum hCG ≤ 15 IU/L), number of hospital visits associated with treatment (until resolution or scheduled/emergency surgery), and the return of menses by 3 months after resolution. We will also assess adverse events and reactions until day of resolution or surgery, and participant-reported acceptability at 3 months., Discussion: A medical intervention that reduces the need for surgery and resolves tEP faster would be a favourable treatment alternative. If effective, we believe that gefitinib and methotrexate could become standard care for stable tEPs., Trial Registration: ISRCTN Registry ISRCTN67795930 . Registered 15 September 2016.

Introduction: Falls and fall-related injuries are a serious cause of morbidity and cost to society. Environmental hazards are implicated as a major contributor to falls among older people. A recent Cochrane review found an environmental assessment, undertaken by an occupational therapist, to be an effective approach to reducing falls. However, none of the trials included a cost-effectiveness evaluation in the UK setting. This protocol describes a large multicentre trial investigating the clinical and cost-effectiveness of environmental assessment and modification within the home with the aim of preventing falls in older people., Methods and Analysis: A two-arm, modified cohort randomised controlled trial, conducted within England, with 1299 community-dwelling participants aged 65 years and above, who are at an increased risk of falls. Participants will be randomised 2:1 to receive either usual care or home assessment and modification. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by monthly patient self-report falls calendars. Secondary self-reported outcome measures include: the proportion of single and multiple fallers, time to first fall over a 12-month period, quality of life (EuroQoL EQ-5D-5L) and health service utilisation at 4, 8 and 12 months. A nested qualitative study will examine the feasibility of providing the intervention and explore barriers, facilitators, workload implications and readiness to employ these interventions into routine practice. An economic evaluation will assess value for money in terms of cost per fall averted., Ethics and Dissemination: This study protocol (including the original application and subsequent amendments) received a favourable ethical opinion from National Health Service West of Scotland REC 3. The trial results will be published in peer-reviewed journals and at conference presentations. A summary of the findings will be sent to participants., Trial Registration Number: ISRCTN22202133; Pre-results., Competing Interests: Competing interests: CH declares membership of the HTA Commissioning board, and SEL declares membership of the HTA Prioritisation board. No other competing interests are declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)