Cluster randomised trials randomise groups of individuals, such as clinics, schools, or communities, and are used when interventions apply at the group level, when individual-level interventions risk contamination between participants, or to reflect real-world implementation. When outcomes are binary, treatment effects may be expressed as relative measures (such as odds ratios or risk ratios) or absolute measures (such as risk differences). CONSORT guidelines recommend reporting both, but risk ratios and risk differences are often underreported compared to odds ratios. Estimating these measures in cluster trials is more complex than in individually randomised trials, requiring appropriate handling of clustering, convergence issues, and small sample corrections. There is currently little empirical evidence describing which statistical methods are used to estimate these effect measures in published cluster trials. This protocol describes the planned methods for a methodological review of published cluster randomised trials. We will use an existing database of 800 trials conducted in low- and middle-income countries. From this, we will identify a subset of trials with a parallel design and a binary primary outcome. Trials reporting a risk ratio or risk difference for the primary outcome will undergo further detailed data extraction. We will summarise the methods used to estimate these effects, including how clustering and small sample sizes were handled, and whether estimates were adjusted for covariates. This review will provide the first detailed description of how risk ratios and risk differences are currently estimated and reported in cluster randomised trials. The findings will inform the development of methodological guidance and help identify gaps in reporting and implementation. This is particularly important as interest grows in improving estimand specification and the clarity of statistical analysis plans.

Aims:Intravenous (i.v.) hypertonic saline alongside i.v. loop diuretics is sometimes used to enhance diuresis in people hospitalized with heart failure (HF) but is challenging to administer. Oral sodium chloride (NaCl) supplements might be a practical alternative, but little is known about their effects in patients with HF. We performed a rapid review of the relevant evidence. Methods and results:A rapid systematic review was registered (PROSPERO: CRD420250618965) and reported following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Medline and Cochrane Central Register of Controlled Trials databases were searched for studies involving adults with HF administered with oral NaCl. Randomized and observational studies were included. Studies of oral NaCl restriction or i.v. hypertonic NaCl were excluded. All available data were extracted. Risk of bias was evaluated using Risk of Bias 2 and Risk Of Bias In Nonrandomized Studies of Interventions tools. From an initial 335 records, five studies involving 139 patients were included. Oral NaCl did not affect weight or urine volume but were associated with higher serum and urinary sodium concentrations. Some studies reported that NaCl was associated with smaller diuretic-induced increases in serum urea and creatinine, lower haematocrit, higher plasma volume, and less neurohormonal activation compared to normal NaCl intake. Clinical outcomes, including hospital length of stay and mortality, were unaffected. The quality of evidence was limited by small sample sizes and methodological heterogeneity. Conclusion:For patients with HF treated with loop diuretics, higher oral NaCl intake may increase serum and urine sodium concentration, improve renal function, and reduce neurohormonal activation. There is insufficient evidence to support oral NaCl as an adjunct to diuretic treatment. More research is needed.

Abstract Background Alzheimer’s disease is caused by modifiable and non-modifiable risk factors. Randomised controlled trials have investigated whether the strongest genetic risk factor for Alzheimer’s disease, APOE4, impacts the effectiveness of exercise on health. Systematic reviews are yet to evaluate the effect of exercise on physical and cognitive outcomes in APOE genotyped participants. A quality assessment of these randomised controlled trials is needed to understand the impact genotype has on the potential success of intervention. This systematic review aimed to determine if the APOE4 genotype influences the effectiveness of exercise-based randomised controlled trials. Method Searches on MEDLINE, EMBASE, and PsycINFO identified eligible exercise based randomised controlled trials incorporating participants with varied cognitive abilities. Quality assessments were conducted. Results Nineteen studies met the inclusion criteria for systematic review, and 3 for the meta-analysis. Very low to moderate quality evidence showed that APOE4 carriers benefitted more than APOE4 non-carriers on cognitive (e.g. executive function, learning) and physical (e.g. relative telomere length) outcomes after exercise; and that APOE4 non-carriers benefited over carriers for physical (serum BDNF, gait speed) and cognitive (global cognition, verbal memory) markers. Very low quality evidence indicated that there was no evidence of difference between APOE4 carriers and non-carriers on physical function outcomes in meta-analysis. Several areas of study design and reporting, including maintenance of relative exercise intensity and complete statistical reporting, were identified as needing improvement. Discussion This systematic review found very limited evidence to suggest that exercise interventions can benefit APOE4 carriers and non-carriers equally, though conclusions were limited by evidence quality. Further randomised controlled trials, stratifying participants by APOE status are required to better understand the relationship between APOE genotype and the effect of exercise on health-related outcomes. Trial registration This review was registered with PROSPERO (CRD42023436842). Registered on June 16, 2023.

Introduction Despite mitigation efforts, exertional heat stroke (EHS) is known to occur in military personnel during training and operations. It has significant potential to cause preventable morbidity and mortality. International consensus from sports medicine organisations supports treating EHS with early rapid cooling by immersing the casualty in cold water. However, evidence remains sparse and the practice is not yet widespread in the UK. Methods Following changes to enable on-site ice cold water immersion (ICWI) at the Royal Marines Commando Training Centre, Lympstone, UK, we prospectively gathered data on 35 patients treated with ICWI over a 3-year period. These data included the incidence of adverse events (e.g. death, cardiac arrest or critical care admission) as the primary outcome. Basic anthropometric data, cooling rates achieved and biochemical and haematological test results on days 0–5 were also gathered and analysed. Results Despite being a cohort of patients in whom we might expect significant morbidity and mortality based on the severity of EHS at presentation, none experienced a serious adverse event. In this cohort with rapid initiation of effective cooling, biochemical derangement appeared less severe than that reported in previous studies. Higher body mass index (BMI) was associated with a lower cooling rate across a range of values previously reported as potentially of clinical significance. Conclusions This case series supports recent updates to UK military guidance that ICWI should be more widely adopted for the treatment of EHS. Clinicians should be aware of likely patterns of blood test abnormalities in the days following EHS. Further work should seek to establish the impact of lower rates of cooling and develop strategies to optimise cooling in patients with higher BMI.

Abstract Background Experimental studies of wound healing often use survival analysis and time to event outcomes or differences in wound area at a specific time point. However, these methods do not use a potentially large number of observations made over the course of a trial and may be inefficient. A model-based approach can leverage all trial data, but there is little guidance on appropriate models and functional forms to describe wound healing. Methods We derive a general statistical model and review a wide range of plausible mathematical models to describe wound healing. We identify a range of possible derived estimands and their derivation from the models. Using data from a trial of an intervention to promote ulcer healing in patients affected by leprosy that included three measurement methods repeated across the course of the study, we compare the goodness-of-fit of the models using a range of methods and estimate treatment effects and healing rate functions with the best-fitting models. Results Overall, we included 5,581 ulcer measurements of 1,578 unique images from 130 patients. We examined the performance of a range of models. The square root, log square root, and log quadratic models were the best fitting models across all outcome measurement methods. The estimated treatment effects magnitude and sign varied by time post-randomisation, model type, and outcome type, but across all models there was little evidence of effectiveness. The estimated effects were significantly more precise than non-parametric alternatives. For example, estimated differences from the three outcome measurements at 42-days post-randomisation were − 0.01 cm2 (-0.77, 0.74), -0.44 cm2 (-1.64, 0.76), and 0.11 cm2 (-0.87, 1.08) using a non-parametric method versus − 0.03 cm2 (-0.14, 0.06), 0.06 cm2 (-0.05, 0.17), and 0.03 cm2 (-0.07, 0.17) using a square-root model. Conclusions Model-based analyses can dramatically improve the precision of estimates but care must be taken to carefully compare and select the best fitting models. The (log) square-root model is strongly recommended reflecting advice from a century ago.

Introduction Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. Methods and analysis RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60–100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8–14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. Study design Clinical trial protocol V.2.2 October 2020. Ethics and dissemination Ethical approval has been obtained from HRA—Wales.The results will be presented at an international and national scientific conferences and in a peer-reviewed journals. Trial registration number ISRCTN Number: ISRCTN16682024 .

Justifying sample size for a pilot trial is a reporting requirement, but few pilot trials report a clear rationale for their chosen sample size. Unlike full-scale trials, pilot trials should not be designed to test effectiveness, and so, conventional sample size justification approaches do not apply. Rather, pilot trials typically specify a range of primary and secondary feasibility objectives. Often, these objectives relate to estimation of parameters that inform the sample size justification for the full-scale trial, many of which are binary. These binary outcomes are referred to as "feasibility outcomes" and include expected prevalence of the primary trial outcome, primary outcome availability, or recruitment or retention proportions.For pilot cluster trials, sample size calculations depend on the number of clusters, the cluster sizes, the anticipated intra-cluster correlation coefficient for the feasibility outcome and the anticipated proportion for that outcome. Of key importance is the intra-cluster correlation coefficient for the feasibility outcome. It has been suggested that correlations for feasibility outcomes are larger than for clinical outcomes measuring effectiveness. Yet, there is a dearth of information on realised values for these correlations.In this tutorial, we demonstrate how to justify sample size in external pilot cluster trials where the objective is to estimate a binary feasibility outcome. We provide sample size calculation formulae for a variety of scenarios, make available an R Shiny app for implementation, and compile a report of intra-cluster correlations for feasibility outcomes from a convenience sample. We demonstrate that unless correlations are very low, external pilot cluster trials can be made more efficient by including more clusters and fewer observations per cluster.

Background Alzheimer's disease is the most common form of dementia and has multiple causes, including modifiable and non-modifiable risk factors. Randomized controlled trials have investigated whether the strongest genetic risk factor for Alzheimer’s disease, APOE4, impacts the effectiveness of exercise on health outcomes. To date, there are no systematic reviews evaluating the effect of exercise on physical and cognitive outcomes in APOE genotyped participants. A thorough assessment of the quality of these randomised controlled trials is needed to understand the impact genotype has on the potential success of intervention. This systematic review aimed to determine if the APOE4 genotype influences the effectiveness of exercise-based randomised controlled trials. Method Searches on MEDLINE, EMBASE, and PsycINFO identified eligible exercise based randomised controlled trials incorporating participants with varied cognitive abilities. Quality assessments were conducted. Results 21 studies met the inclusion criteria for systematic review, and 11 studies in the meta-analysis. Within the current review, six studies reported that, after exercise, APOE4 carriers showed improvement in cognitive (e.g., executive function and learning) and physical (e.g., relative telomere length, inflammatory markers) outcomes. The benefits for APOE4 non-carriers over carriers were limited to a smaller range of outcomes but were seen in physical (serum BDNF, gait speed) and cognitive (global cognition, verbal memory) markers in four studies. The meta-analysis indicated that physical activity levels (16.04% higher in exercise than control group), executive function (19.34% higher in exercise than control group), and quality of life (3.05% higher in exercise than control group) increased following exercise intervention. Physiological health outcomes were not dependent on APOE genotype. The overall quality of evidence was low-to-moderate, and several areas of study design and reporting were identified as needing improvement. Discussion This systematic review demonstrates that the physiological and cognitive health of both APOE4 carriers and non-carriers respond to exercise interventions, suggesting that exercise can be beneficial regardless of APOE status. Further randomised controlled trials, stratifying participants by APOE status, and exploring optimal exercise are required to better understand the relationship between carrying APOE and the effect of exercise on health-related outcomes. Registration: This review was registered with PROSPERO (CRD420234368420).

Department of General Surgery, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Birmingham, UK Department of Trauma and Emergency General Surgery, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Birmingham, UK Medical Statistics and Trial Methodology, NIHR Surgical Reconstruction and Microbiology Research Centre, Mindelsohn Way, Birmingham, UK Department of Anaesthesiology, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Birmingham, UK

OBJECTIVES:The use of routine remote follow-up of patients with chronic kidney disease (CKD) is increasing exponentially. It has been suggested that online electronic patient-reported outcome measures (ePROMs) could be used in parallel, to facilitate real-time symptom monitoring aimed at improving outcomes. We tested the feasibility of this approach in a pilot trial of ePROM symptom monitoring versus usual care in patients with advanced CKD not on dialysis.DESIGN:A 12-month, parallel, pilot randomised controlled trial (RCT) and qualitative substudy.SETTING AND PARTICIPANTS:Queen Elizabeth Hospital Birmingham, UK. Adult patients with advanced CKD (estimated glomerular filtration rate ≥6 and ≤15 mL/min/1.73 m2, or a projected risk of progression to kidney failure within 2 years ≥20%).INTERVENTION:Monthly online ePROM symptom reporting, including automated feedback of tailored self-management advice and triggered clinical notifications in the advent of severe symptoms. Real-time ePROM data were made available to the clinical team via the electronic medical record.OUTCOMES:Feasibility (recruitment and retention rates, and acceptability/adherence to the ePROM intervention). Health-related quality of life, clinical data (eg, measures of kidney function, kidney failure, hospitalisation, death) and healthcare utilisation.RESULTS:52 patients were randomised (31% of approached). Case report form returns were high (99.5%), as was retention (96%). Overall, 73% of expected ePROM questionnaires were received. Intervention adherence was high beyond 90 days (74%) and 180 days (65%); but dropped beyond 270 days (46%). Qualitative interviews supported proof of concept and intervention acceptability, but highlighted necessary changes aimed at enhancing overall functionality/scalability of the ePROM system.LIMITATIONS:Small sample size.CONCLUSIONS:This pilot trial demonstrates that patients are willing to be randomised to a trial assessing ePROM symptom monitoring. The intervention was considered acceptable; though measures to improve longer-term engagement are needed. A full-scale RCT is considered feasible.TRIAL REGISTRATION NUMBER:ISRCTN12669006 and the UK NIHR Portfolio (CPMS ID: 36497).

Mother-to-baby transmission of group B Streptococcus (GBS) is the main cause of early-onset infection. We evaluated whether, in women with clinical risk factors for early neonatal infection, the use of point-of-care rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotic exposure compared with usual care, where antibiotics are administered due to those risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture. We undertook a parallel-group cluster randomised trial, with nested test accuracy study and microbiological sub-study. UK maternity units were randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. Within units assigned to rapid testing, vaginal-rectal swabs were taken from women with risk factors for vertical GBS transmission in established term labour. The trial primary outcome was the proportion of women receiving intrapartum antibiotics to prevent neonatal early-onset GBS infection. The accuracy of the rapid test was compared against the standard of selective enrichment culture in diagnosing maternal GBS colonisation. Antibiotic resistance profiles were determined in paired maternal and infant samples. Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) were in usual care units. There was no evidence of a difference in the rates of intrapartum antibiotic prophylaxis (relative risk 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. No serious adverse events were reported. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%), respectively. Babies born to mothers who carried antibiotic-resistant Escherichia coli were more likely to be colonised with antibiotic-resistant strains than those born to mothers with antibiotic-susceptible E. coli. The use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits. ISRCTN74746075 . Prospectively registered on 16 April 2015

Introduction Concussion is a complex pathophysiological process with a wide range of non-specific signs and symptoms. There are currently no objective diagnostic tests to identify concussion, and diagnosis relies solely on history and examination. Recent research has identified a unique panel of microRNAs (miRNAs) that distinguish between concussed and non-concussed rugby players. This study aims to assess the diagnostic utility of salivary miRNAs in concussion for a sample of UK National Health Service patients and whether well-established sports-related concussion (SRC) assessment tools may be translated into the emergency department (ED).Methods and analysis Concussion in Non-athletes: Assessment of Cognition and Symptomatology is a single-centre, prospective, two-phase cohort study. The concussed cohort will consist of participants with maxillofacial trauma and concurrent concussion. The control cohort will consist of participants with isolated limb trauma and no evidence of concussion. Participants will be recruited in the ED and saliva samples will be taken to identify the presence of miRNAs. The SRC assessments being investigated include the Sports Concussion Assessment Test, Fifth Edition (SCAT5), the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and the ImPACT Quick. Follow-up will be at 24–48 hours in-hospital and remotely via telephone and email at 14 days and 6 months.Ethics and dissemination Ethical approval was granted in February 2021 by the West Midlands Coventry & Warwickshire Research Ethics Committee (ref 20/WM/0299). The investigators intend to submit their study findings for publication in peer-reviewed journals and to disseminate study findings via presentation at academic meetings. The results will also form part of a doctorate thesis, registered at the University of Birmingham.

IMPORTANCE Serious traumatic injury is a leading cause of death and disability globally, with most survivors known to develop chronic pain. OBJECTIVE To describe early variables associated with poor long-term outcome for posttrauma pain and create a clinical screening tool for this purpose. DESIGN, SETTING, AND PARTICIPANTS This was a prospective cohort study at a major trauma center hospital in England. Recruitment commenced in December 2018 and ceased in March 2020. Participants were followed up for 12 months. Patients aged 16 years or older who were hospitalized because of acute musculoskeletal trauma within the preceding 14 days were included. Data were analyzed from March to December 2021. EXPOSURE Acute musculoskeletal trauma requiring admittance to a major trauma center hospital. MAIN OUTCOMES AND MEASURES A poor outcome was defined as Chronic Pain Grade II or higher and measured at both 6 months (primary time point) and 12 months. A broad range of candidate variables potentially associated with outcomes were used, including surrogates for pain mechanisms, quantitative sensory testing, and psychosocial factors. Univariable models were used to identify the variables most likely to be associated with poor outcome, which were entered into multivariable models. A clinical screening tool (nomogram) was derived from 6-month results. RESULTS In total, 1590 consecutive patients were assessed for eligibility, of whom 772 were deemed eligible and 124 (80 male [64.5%]; mean [SD] age, 48.9 [18.8] years) were recruited. At 6 months, 19 of 82 respondents (23.2%) reported a good outcome, whereas at 12 months 27 of 44 respondents (61.4%) reported a good outcome. At 6 months on univariable analysis, an increase in total posttraumatic stress symptoms (odds ratio [OR], 2.09; 95% CI, 1.33-3.28), pain intensity average (OR, 2.87; 95% CI, 1.37-6.00), number of fractures (OR, 2.79; 95% CI, 1.02-7.64), and pain extent (OR, 4.67; 95% CI, 1.57-13.87) were associated with worse outcomes. A multivariable model including those variables had a sensitivity of 0.93, a specificity of 0.54, and C-index of 0.92. CONCLUSIONS AND RELEVANCE A poor long-term pain outcome from musculoskeletal traumatic injuries may be estimated by measures recorded within days of injury. These findings suggest that posttraumatic stress symptoms, pain spatial distribution, perceived average pain intensity, and number of fractures are good candidates for a sensitive multivariable model and derived clinical screening tool.

BACKGROUND:Mother-to-baby transmission of group B Streptococcus (Streptococcus agalactiae) is the main cause of early-onset infection. OBJECTIVES:We investigated if intrapartum antibiotic prophylaxis directed by a rapid intrapartum test reduces maternal and neonatal antibiotic use, compared with usual care (i.e. risk factor-directed antibiotics), among women with risk factors for vertical group B Streptococcus transmission, and examined the accuracy and cost-effectiveness of the rapid test. DESIGN:An unblinded cluster randomised controlled trial with a nested test accuracy study, an economic evaluation and a microbiology substudy. SETTING:UK maternity units were randomised to either a strategy of rapid test or usual care. PARTICIPANTS:Vaginal and rectal swabs were taken from women with risk factors for vertical group B Streptococcus transmission in established term labour. The accuracy of the GeneXpert® Dx IV GBS rapid testing system (Cepheid, Maurens-Scopont, France) was compared with the standard of selective enrichment culture in diagnosing maternal group B Streptococcus colonisation. MAIN OUTCOME MEASURES:Primary outcomes were rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection and accuracy estimates of the rapid test. Secondary outcomes were maternal antibiotics for any indication, neonatal antibiotic exposure, maternal antibiotic duration, neonatal group B Streptococcus colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and cost-effectiveness of the strategies. RESULTS:Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units and 906 mothers (951 babies) participated in usual-care units. There were no differences in the rates of intrapartum antibiotic prophylaxis for preventing early-onset group B Streptococcus infection in the rapid test units (41%, 297/716) compared with the usual-care units (36%, 328/906) (risk ratio 1.16, 95% confidence interval 0.83 to 1.64). There were no differences between the groups in intrapartum antibiotic administration for any indication (risk ratio 0.99, 95% confidence interval 0.81 to 1.21). Babies born in the rapid test units were 29% less likely to receive antibiotics (risk ratio 0.71, 95% confidence interval 0.54 to 0.95) than those born in usual-care units. The sensitivity and specificity of the rapid test were 86% (95% confidence interval 81% to 91%) and 89% (95% confidence interval 85% to 92%), respectively. In 14% of women (99/710), the rapid test was invalid or the machine failed to provide a result. In the economic analysis, the rapid test was shown to be both less effective and more costly and, therefore, dominated by usual care. Sensitivity analysis indicated potential lower costs for the rapid test strategy when neonatal costs were included. No serious adverse events were reported. CONCLUSIONS:The Group B Streptococcus 2 (GBS2) trial found no evidence that the rapid test reduces the rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection. The rapid test has the potential to reduce neonatal exposure to antibiotics, but economically is dominated by usual care. The accuracy of the test is within acceptable limits. FUTURE WORK:The role of routine testing for prevention of neonatal infection requires evaluation in a randomised controlled trial. TRIAL REGISTRATION:Current Controlled Trials ISRCTN74746075. 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. 26, No. 12. See the NIHR Journals Library website for further project information.

Objectives To assess the feasibility of an intervention of midwifery support for antenatal pelvic floor muscle exercises (PFME) to prevent postnatal urinary incontinence (UI).Design Feasibility and pilot cluster randomised controlled trial. Clusters were community midwifery teams.Setting Community maternity antenatal care.Participants One hundred seventy-five women; 186 midwives.Intervention Midwifery training and resources for midwives and women to support antenatal PFME. Control clusters continued standard care.Outcomes Women reporting: that their midwife explained how to do PFME, PFME adherence and postpartum UI. Midwives reporting: pre-post-training PFME confidence, intervention acceptability. Fidelity of training delivery and implementation.Results Ninety-five midwives in intervention clusters; 91 midwives in control clusters. Of 998 women sent questionnaires, 175 responded: 15.8% in intervention, 16.4% in control clusters. Women’s characteristics in both trial arms were similar and characteristics of respondents and non-respondents were similar. Sixty-five percent (95% CI 56.9% to 72.4%) of women in intervention clusters reported their midwife explained how to do PFME vs 38% (95% CI 24.6% to 51.2%) in control clusters. Fifty percent (95% CI 24.1% to 77.1%) of women in intervention clusters vs 38% (95% CI 12.4% to 67.1%) in control clusters reported doing enough PFME to potentially prevent UI. Fourty-four percent (95% CI 32.0% to 56.1%) of women in intervention clusters reported UI vs 54% (95% CI 42.2% to 65.8%) in control clusters.Intervention training was delivered with fidelity and received positively. Midwives reported improvements in PFME confidence/knowledge (median increase of at least 1 point on a 0–4 scale for each of eight questions). Midwives (26%) most frequently reported insufficient time as an implementation barrier.Conclusions This pilot trial produced consistent new findings that training and resourcing midwives to teach and support pregnant women to undertake PFME is acceptable and feasible for women and midwives. It increased the number of women who are informed about PFME, with potential to improve PFME adherence and reduce postpartum UI. Recent changes to the National Health Service perinatal pelvic healthcare means a full trial is not possible.Trial registration number ISRCTN10833250.

Introduction Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established. Methods We evaluated the ‘second generation’ autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images. Results The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment. Conclusion Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy. Trial registration ISRCTN14933421. Date of trial registration: 16 June 2020.