Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial.

Importance: Bleeding is the most common cause of preventable death after trauma. Objective: To determine the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) when used in the emergency department along with standard care vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage. Design, Setting, and Participants: Pragmatic, bayesian, randomized clinical trial conducted at 16 major trauma centers in the UK. Patients aged 16 years or older with exsanguinating hemorrhage were enrolled between October 2017 and March 2022 and followed up for 90 days. Intervention: Patients were randomly assigned (1:1 allocation) to a strategy that included REBOA and standard care (n = 46) or standard care alone (n = 44). Main Outcomes and Measures: The primary outcome was all-cause mortality at 90 days. Ten secondary outcomes included mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours; the need for definitive hemorrhage control procedures; time to commencement of definitive hemorrhage control procedures; complications; length of stay; blood product use; and cause of death. Results: Of the 90 patients (median age, 41 years [IQR, 31-59 years]; 62 [69%] were male; and the median Injury Severity Score was 41 [IQR, 29-50]) randomized, 89 were included in the primary outcome analysis because 1 patient in the standard care alone group declined to provide consent for continued participation and data collection 4 days after enrollment. At 90 days, 25 of 46 patients (54%) had experienced all-cause mortality in the REBOA and standard care group vs 18 of 43 patients (42%) in the standard care alone group (odds ratio [OR], 1.58 [95% credible interval, 0.72-3.52]; posterior probability of an OR >1 [indicating increased odds of death with REBOA], 86.9%). Among the 10 secondary outcomes, the ORs for mortality and the posterior probabilities of an OR greater than 1 for 6-month, in-hospital, and 24-, 6-, or 3-hour mortality were all increased in the REBOA and standard care group, and the ORs were increased with earlier mortality end points. There were more deaths due to bleeding in the REBOA and standard care group (8 of 25 patients [32%]) than in standard care alone group (3 of 18 patients [17%]), and most occurred within 24 hours. Conclusions and Relevance: In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone. Trial Registration: isrctn.org Identifier: ISRCTN16184981.

Use of effective contraception following provision of the progestogen-only pill for women presenting to community pharmacies for emergency contraception (Bridge-It): a pragmatic cluster-randomised crossover trial.

BACKGROUND: Unless women start effective contraception after oral emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies. We hypothesised that pharmacist provision of the progestogen-only pill as a bridging interim method of contraception with emergency contraception plus an invitation to a sexual and reproductive health clinic, in which all methods of contraception are available, would result in increased subsequent use of effective contraception. METHODS: We did a pragmatic cluster-randomised crossover trial in 29 UK pharmacies among women receiving levonorgestrel emergency contraception. Women aged 16 years or older, not already using hormonal contraception, not on medication that could interfere with the progestogen-only pill, and willing to give contact details for follow-up were invited to participate. In the intervention group, women received a 3-month supply of the progestogen-only pill (75 µg desogestrel) plus a rapid access card to a participating sexual and reproductive health clinic. In the control group, pharmacists advised women to attend their usual contraceptive provider. The order in which each pharmacy provided the intervention or control was randomly assigned using a computer software algorithm. The primary outcome was the use of effective contraception (hormonal or intrauterine) at 4 months. This study is registered, ISRCTN70616901 (complete). FINDINGS: Between Dec 19, 2017, and June 26, 2019, 636 women were recruited to the intervention group (316 [49·6%], mean age 22·7 years [SD 5·7]) or the control group (320 [50·3%], 22·6 years [5·1]). Three women (one in the intervention group and two in the control group) were excluded after randomisation. 4-month follow-up data were available for 406 (64%) participants, 25 were lost to follow-up, and two participants no longer wanted to participate in the study. The proportion of women using effective contraception was 20·1% greater (95% CI 5·2-35·0) in the intervention group (mean 58·4%, 48·6-68·2), than in the control group (mean 40·5%, 29·7-51·3 [adjusted for recruitment period, treatment group, and centre]; p=0·011).The difference remained significant after adjusting for age, current sexual relationship, and history of effective contraception use, and was robust to the effect of missing data (assuming missingness at random). No serious adverse events occurred. INTERPRETATION: Provision of a supply of the progestogen-only pill with emergency contraception from a community pharmacist, along with an invitation to a sexual and reproductive health clinic, results in a clinically meaningful increase in subsequent use of effective contraception. Widely implemented, this practice could prevent unintended pregnancies after use of emergency contraception. FUNDING: National Institute for Health Research (Health Technology Assessment Programme project 15/113/01).

Selective Caries Removal in Permanent Teeth (SCRiPT) for the treatment of deep carious lesions: a randomised controlled clinical trial in primary care.

BACKGROUND: Dental caries is one of the most prevalent non-communicable disease globally and can have serious health sequelae impacting negatively on quality of life. In the UK most adults experience dental caries during their lifetime and the 2009 Adult Dental Health Survey reported that 85% of adults have at least one dental restoration. Conservative removal of tooth tissue for both primary and secondary caries reduces the risk of failure due to tooth-restoration, complex fracture as well as remaining tooth surfaces being less vulnerable to further caries. However, despite its prevalence there is no consensus on how much caries to remove prior to placing a restoration to achieve optimal outcomes. Evidence for selective compared to complete or near-complete caries removal suggests there may be benefits for selective removal in sustaining tooth vitality, therefore avoiding abscess formation and pain, so eliminating the need for more complex and costly treatment or eventual tooth loss. However, the evidence is of low scientific quality and mainly gleaned from studies in primary teeth. METHOD: This is a pragmatic, multi-centre, two-arm patient randomised controlled clinical trial including an internal pilot set in primary dental care in Scotland and England. Dental health professionals will recruit 623 participants over 12-years of age with deep carious lesions in their permanent posterior teeth. Participants will have a single tooth randomised to either the selective caries removal or complete caries removal treatment arm. Baseline measures and outcome data (during the 3-year follow-up period) will be assessed through clinical examination, patient questionnaires and NHS databases. A mixed-method process evaluation will complement the clinical and economic outcome evaluation and examine implementation, mechanisms of impact and context. The primary outcome at three years is sustained tooth vitality. The primary economic outcome is net benefit modelled over a lifetime horizon. Clinical secondary outcomes include pulp exposure, progession of caries, restoration failure; as well as patient-centred and economic outcomes. DISCUSSION: SCRiPT will provide evidence for the most clinically effective and cost-beneficial approach to managing deep carious lesions in permanent posterior teeth in primary care. This will support general dental practitioners, patients and policy makers in decision making. Trial Registration Trial registry: ISRCTN. TRIAL REGISTRATION NUMBER: ISRCTN76503940. Date of Registration: 30.10.2019. URL of trial registry record: https://www.isrctn.com/ISRCTN76503940?q=ISRCTN76503940%20&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search .

THISTLE: trial of hands-on Interprofessional simulation training for local emergencies: a research protocol for a stepped-wedge clustered randomised controlled trial.

BACKGROUND: Many adverse pregnancy outcomes in the UK could be prevented with better intrapartum care. Training for intrapartum emergencies has been widely recommended but there are conflicting data about their effectiveness. Observational studies have shown sustained local improvements in perinatal outcomes associated with the use of the PRactical Obstetric Multi-Professional Training - (PROMPT) training package. However this effect needs to be investigated in the context of randomised study design in settings other than enthusiastic early adopter single-centres. The main aim of this study is to determine the effectiveness of PROMPT to reduce the rate of term infants born with low APGAR scores. METHODS: THISTLE (Trial of Hands-on Interprofessional Simulation Training for Local Emergencies) is a multi-centre stepped-wedge clustered randomised controlled superiority trial conducted across 12 large Maternity Units in Scotland. On the basis of prior observational findings all Units have been offered the intervention and have been randomly allocated in groups of four Units, to one of three intervention time periods, each six months apart. Teams of four multi-professional clinicians from each participating Unit attended a two-day PROMPT Train the Trainers (T3) programme prior to the start of their allocated intervention step. Following the T3 training, the teams commenced the implementation of local intrapartum emergency training in their own Units by the start of their allocated intervention period. Blinding has not been possible due to the nature of the intervention. The aim of the study is to follow up each Unit for at least 12-months after they have commenced their local courses. The primary outcome for the study is the proportion of Apgar scores <7 at 5 min for term vaginal or emergency caesarean section births (≥37 weeks) occurring in each of the study Units. These data will be extracted from the Information Services Division Scottish Morbidity Record 02, a national routine data collection on pregnancy and births. Mixed or marginal logistic regression will be employed for the main analysis. DISCUSSION: THISTLE is the first stepped wedge cluster randomised trial to evaluate the effectiveness of an intrapartum emergencies training programme. The results will inform training, trainers and policy going forward. TRIAL REGISTRATION: ISRCTN11640515 (registered on 09/09/2013).

Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones: the C-GALL RCT.

Background: Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be approximately 10-15%, and around 80% remain asymptomatic. At present, cholecystectomy is the default option for people with symptomatic gallstone disease. Objectives: To assess the clinical and cost-effectiveness of observation/conservative management compared with laparoscopic cholecystectomy for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones in secondary care. Design: Parallel group, multicentre patient randomised superiority pragmatic trial with up to 24 months follow-up and embedded qualitative research. Within-trial cost-utility and 10-year Markov model analyses. Development of a core outcome set for uncomplicated symptomatic gallstone disease. Setting: Secondary care elective settings. Participants: Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion. Interventions: Participants were randomised 1: 1 at clinic to receive either laparoscopic cholecystectomy or observation/conservative management. Main outcome measures: The primary outcome was quality of life measured by area under the curve over 18 months using the Short Form-36 bodily pain domain. Secondary outcomes included the Otago gallstones' condition-specific questionnaire, Short Form-36 domains (excluding bodily pain), area under the curve over 24 months for Short Form-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation. Results: Between August 2016 and November 2019, 434 participants were randomised (217 in each group) from 20 United Kingdom centres. By 24 months, 64 (29.5%) in the observation/conservative management group and 153 (70.5%) in the laparoscopic cholecystectomy group had received surgery, median time to surgery of 9.0 months (interquartile range, 5.6-15.0) and 4.7 months (interquartile range 2.6-7.9), respectively. At 18 months, the mean Short Form-36 norm-based bodily pain score was 49.4 (standard deviation 11.7) in the observation/conservative management group and 50.4 (standard deviation 11.6) in the laparoscopic cholecystectomy group. The mean area under the curve over 18 months was 46.8 for both groups with no difference: mean difference -0.0, 95% confidence interval (-1.7 to 1.7); p-value 0.996; n = 203 observation/conservative, n = 205 cholecystectomy. There was no evidence of differences in quality of life, complications or need for further treatment at up to 24 months follow-up. Condition-specific quality of life at 24 months favoured cholecystectomy: mean difference 9.0, 95% confidence interval (4.1 to 14.0), p < 0.001 with a similar pattern for the persistent symptoms score. Within-trial cost-utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1033). A non-significant quality-adjusted life-year difference of -0.019 favouring cholecystectomy resulted in an incremental cost-effectiveness ratio of £55,235. The Markov model continued to favour observation/conservative management, but some scenarios reversed the findings due to uncertainties in longer-term quality of life. The core outcome set included 11 critically important outcomes from both patients and healthcare professionals. Conclusions: The results suggested that in the short term (up to 24 months) observation/conservative management may be a cost-effective use of National Health Service resources in selected patients, but subsequent surgeries in the randomised groups and differences in quality of life beyond 24 months could reverse this finding. Future research should focus on longer-term follow-up data and identification of the cohort of patients that should be routinely offered surgery. Trial registration: This trial is registered as ISRCTN55215960. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/71) and is published in full in Health Technology Assessment; Vol. 28, No. 26. See the NIHR Funding and Awards website for further award information.

The C-GALL study assessed the benefits, in terms of symptoms, quality of life and costs, of cholecystectomy versus observation (conservative management: by the patient and general practitioner that might include dietary advice and pain management and surgery if needed). Four hundred and thirty-four patients with symptomatic gallstones were randomly allocated surgery or conservative management. The main symptom of ongoing bodily pain and some other quality-of-life measures were assessed over the next 2 years using postal questionnaires. After 2 years, 70% of those allocated to surgery had been operated on and 37% of the observation group either had an operation or were waiting for one. There was no difference in bodily pain or overall quality of life between the groups. However, participants in the surgery group reported fewer ongoing problems related to their gallstone disease or after surgery than those in the conservative management group. Surgery was, however, more costly than conservative management. The C-GALL study has shown that for some patients, a conservative management approach may be a sufficient and less costly way of managing their gallstone symptoms rather than going straight on the waiting list for surgery. More research is needed to identify which patients benefit most from surgery.

Clinical and cost-effectiveness of pessary self-management versus clinic-based care for pelvic organ prolapse in women: the TOPSY RCT with process evaluation.

Background: Pelvic organ prolapse is common, causes unpleasant symptoms and negatively affects women's quality of life. In the UK, most women with pelvic organ prolapse attend clinics for pessary care. Objectives: To determine the clinical effectiveness and cost-effectiveness of vaginal pessary self-management on prolapse-specific quality of life for women with prolapse compared with clinic-based care; and to assess intervention acceptability and contextual influences on effectiveness, adherence and fidelity. Design: A multicentre, parallel-group, superiority randomised controlled trial with a mixed-methods process evaluation. Participants: Women attending UK NHS outpatient pessary services, aged ≥ 18 years, using a pessary of any type/material (except shelf, Gellhorn or Cube) for at least 2 weeks. Exclusions: women with limited manual dexterity, with cognitive deficit (prohibiting consent or self-management), pregnant or non-English-speaking. Intervention: The self-management intervention involved a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a local clinic telephone helpline number. Clinic-based care involved routine appointments determined by centres' usual practice. Allocation: Remote web-based application; minimisation was by age, pessary user type and centre. Blinding: Participants, those delivering the intervention and researchers were not blinded to group allocation. Outcomes: The patient-reported primary outcome (measured using the Pelvic Floor Impact Questionnaire-7) was prolapse-specific quality of life, and the cost-effectiveness outcome was incremental cost per quality-adjusted life-year (a specifically developed health Resource Use Questionnaire was used) at 18 months post randomisation. Secondary outcome measures included self-efficacy and complications. Process evaluation data were collected by interview, audio-recording and checklist. Analysis was by intention to treat. Results: Three hundred and forty women were randomised (self-management, n = 169; clinic-based care, n = 171). At 18 months post randomisation, 291 questionnaires with valid primary outcome data were available (self-management, n = 139; clinic-based care, n = 152). Baseline economic analysis was based on 264 participants (self-management, n = 125; clinic-based care, n = 139) with valid quality of life and resource use data. Self-management was an acceptable intervention. There was no group difference in prolapse-specific quality of life at 18 months (adjusted mean difference -0.03, 95% confidence interval -9.32 to 9.25). There was fidelity to intervention delivery. Self-management was cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, with an estimated incremental net benefit of £564.32 and an 80.81% probability of cost-effectiveness. At 18 months, more pessary complications were reported in the clinic-based care group (adjusted mean difference 3.83, 95% confidence interval 0.81 to 6.86). There was no group difference in general self-efficacy, but self-managing women were more confident in pessary self-management activities. In both groups, contextual factors impacted on adherence and effectiveness. There were no reported serious unexpected serious adverse reactions. There were 32 serious adverse events (self-management, n = 17; clinic-based care, n = 14), all unrelated to the intervention. Skew in the baseline data for the Pelvic Floor Impact Questionnaire-7, the influence of the global COVID-19 pandemic, the potential effects of crossover and the lack of ethnic diversity in the recruited sample were possible limitations. Conclusions: Self-management was acceptable and cost-effective, led to fewer complications and did not improve or worsen quality of life for women with prolapse compared with clinic-based care. Future research is needed to develop a quality-of-life measure that is sensitive to the changes women desire from treatment. Study registration: This study is registered as ISRCTN62510577. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/82/01) and is published in full in Health Technology Assessment; Vol. 28, No. 23. See the NIHR Funding and Awards website for further award information.

Pelvic organ prolapse is a common and distressing condition experienced by large numbers of women. Prolapse is when the organs that are usually in the pelvis drop down into the vagina. Women experience a feeling of something coming down into the vagina, along with bowel, bladder and sexual problems. One possible treatment is a vaginal pessary. The pessary is a device that is inserted into the vagina and holds the pelvic organs back in their usual place. Women who use a vaginal pessary usually come back to clinic every 6 months to have their pessary removed and replaced; this is called clinic-based care. However, it is possible for a woman to look after the pessary herself; this is called self-management. This study compared self-management with clinic-based care. Three hundred and forty women with prolapse took part; 171 received clinic-based care and 169 undertook self-management. Each woman had an equal chance of being in either group. Women in the self-management group received a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a telephone number for their local centre. Women in the clinic-based care group returned to clinic as advised by the treating healthcare professional. Self-management was found to be acceptable. Women self-managed their pessary in ways that suited their lifestyle. After 18 months, there was no difference between the groups in women's quality of life. Women in the self-management group experienced fewer pessary complications than women who received clinic-based care. Self-management costs less to deliver than clinic-based care. In summary, self-management did not improve women's quality of life more than clinic-based care, but it did lead to women experiencing fewer complications and cost less to deliver in the NHS. The findings support self-management as a treatment pathway for women using a pessary for prolapse.

Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): pragmatic, multicentre randomised controlled trial.

OBJECTIVE: To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease. DESIGN: Parallel group, pragmatic randomised, superiority trial. SETTING: 20 secondary care centres in the UK. PARTICIPANTS: 434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy. INTERVENTIONS: Conservative management or surgical removal of the gallbladder. MAIN OUTCOME MEASURES: The primary patient outcome was quality of life, measured by area under the curve, over 18 months using the short form 36 (SF-36) bodily pain domain, with higher scores (range 0-100) indicating better quality of life. Other outcomes included costs to the NHS, quality adjusted life years (QALYs), and incremental cost effectiveness ratio. RESULTS: Of 2667 patients assessed for eligibility, 434 were randomised: 217 to the conservative management group and 217 to the laparoscopic cholecystectomy group. By 18 months, 54 (25%) participants in the conservative management arm and 146 (67%) in the cholecystectomy arm had received surgery. The mean SF-36 norm based bodily pain score was 49.4 (standard deviation 11.7) in the conservative management arm and 50.4 (11.6) in the cholecystectomy arm. The SF-36 bodily pain area under the curve up to 18 months did not differ (mean difference 0.0, 95% confidence interval -1.7 to 1.7; P=1.00). Conservative management was less costly (mean difference -£1033, (-$1334; -€1205), 95% credible interval -£1413 to -£632) and QALYs did not differ (mean difference -0.019, 95% credible interval -0.06 to 0.02). CONCLUSIONS: In the short term (≤18 months), laparoscopic surgery is no more effective than conservative management for adults with uncomplicated symptomatic gallstone disease, and as such conservative management should be considered as an alternative to surgery. From an NHS perspective, conservative management may be cost effective for uncomplicated symptomatic gallstone disease. As costs, complications, and benefits will continue to be incurred in both groups beyond 18 months, future research should focus on longer term follow-up to establish effectiveness and lifetime cost effectiveness and to identify the cohort of patients who should be routinely offered surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN55215960.

Clinical effectiveness of vaginal pessary self-management vs clinic-based care for pelvic organ prolapse (TOPSY): a randomised controlled superiority trial.

Background: Prolapse affects 30-40% of women. Those using a pessary for prolapse usually receive care as an outpatient. This trial determined effectiveness and cost-effectiveness of pessary self-management (SM) vs clinic-based care (CBC) in relation to condition-specific quality of life (QoL). Methods: Parallel-group, superiority randomised controlled trial, recruiting from 16 May 2018 to 7 February 2020, with follow-up to 17 September 2021. Women attending pessary clinics, ≥18 years, using a pessary (except Shelf, Gellhorn or Cube), with pessary retained ≥2 weeks were eligible. Limited manual dexterity; cognitive deficit; pregnancy; or requirement for non-English teaching were exclusions. SM group received a 30-min teaching session; information leaflet; 2-week follow-up call; and telephone support. CBC group received usual routine appointments. The primary clinical outcome was pelvic floor-specific QoL (PFIQ-7), and incremental net monetary benefit for cost-effectiveness, 18 months post-randomisation. Group allocation was by remote web-based application, minimised on age, user type (new/existing) and centre. Participants, intervention deliverers, researchers and the statistician were not blinded. The primary analysis was intention-to-treat based. Trial registration: https://doi.org/10.1186/ISRCTN62510577. Findings: The requisite 340 women were randomised (169 SM, 171 CBC) across 21 centres. There was not a statistically significant difference between groups in PFIQ-7 at 18 months (mean SM 32.3 vs CBC 32.5, adjusted mean difference SM-CBC -0.03, 95% CI -9.32 to 9.25). SM was less costly than CBC. The incremental net benefit of SM was £564 (SE £581, 95% CI -£576 to £1704). A lower percentage of pessary complications was reported in the SM group (mean SM 16.7% vs CBC 22.0%, adjusted mean difference -3.83%, 95% CI -6.86% to -0.81%). There was no meaningful difference in general self-efficacy. Self-managing women were more confident in self-management activities. There were no reported suspected unexpected serious adverse reactions, and 31 unrelated serious adverse events (17 SM, 14 CBC). Interpretation: Pessary self-management is cost-effective, does not improve or worsen QoL compared to CBC, and has a lower complication rate. Funding: National Institute for Health and Care Research, Health Technology Assessment Programme (16/82/01).

Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial.

BACKGROUND: The benefit of fractional exhaled nitric oxide (FeNO) in guiding asthma treatment is uncertain. We evaluated the efficacy of adding FeNO to symptom-guided treatment in children with asthma versus only symptom-guided treatment. METHODS: RAACENO was a multicentre, parallel, randomised, controlled, phase 3 trial done in 35 secondary care centres and 17 primary care recruitment sites (only seven primary care sites managed to recruit patients) in the UK. Patients with a confirmed asthma diagnosis, aged 6-15 years, prescribed inhaled corticosteroids, and who received a course of oral corticosteroids for at least one asthma exacerbation during the 12 months before recruitment were included. Participants were randomly assigned to either FeNO plus symptom-guided treatment (intervention) or symptom-guided treatment alone (standard care) using a 24 h in-house, web-based randomisation system. Participants and the clinical and research teams were not masked to the group allocation. A web-based algorithm gave treatment recommendations based on the Asthma Control Test (ACT) or Childhood ACT (CACT) score; current asthma treatment; adherence to study treatment in the past 3 months; and use of FeNO (in the intervention group). Follow-up occurred at 3-month intervals for 12 months. The primary outcome was any asthma exacerbation treated with oral corticosteroids in the 12 months after randomisation, assessed in the intention-to-treat population. This study is registered with the International Standard Randomised Controlled Trial Registry, ISRCTN67875351. FINDINGS: Between June 22, 2017, and Aug 8, 2019, 535 children were assessed for eligibility, 20 were ineligible and six were excluded post-randomisation. 509 children were recruited and at baseline, the mean age of participants was 10·1 years (SD 2·6), and 308 (60·5%) were male. The median FeNO was 21 ppb (IQR 10-48), mean predicted FEV1 was 89·6% (SD 18·0), and median daily dose of inhaled corticosteroids was 400 µg budesonide equivalent (IQR 400-1000). Asthma was partly or fully controlled in 256 (50·3%) of 509 participants. The primary outcome, which was available for 506 (99%) of 509 participants, occurred in 123 (48·2%) of 255 participants in the intervention group and 129 (51·4%) of 251 in the standard care group, the intention-to-treat adjusted odds ratio (OR) was 0·88 (95% CI 0·61 to 1·27; p=0·49). The adjusted difference in the percentage of participants who received the intervention in whom the primary outcome occurred compared with those who received standard care was -3·1% (-11·9% to 5·6%). In 377 (21·3%) of 1771 assessments, the algorithm recommendation was not followed. Adverse events were reported by 27 (5·3%) of 509 participants (15 in the standard care group and 12 in the intervention group). The most common adverse event was itch after skin prick testing (reported by eight participants in each group). INTERPRETATION: We found that the addition of FeNO to symptom-guided asthma treatment did not lead to reduced exacerbations among children prone to asthma exacerbation. Asthma symptoms remain the only tool for guiding treatment decisions. FUNDING: National Institute for Health Research.

Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP): a feasibility study.

BACKGROUND: Progression of dental caries can result in irreversible pulpal damage. Partial irreversible pulpitis is the initial stage of this damage, confined to the coronal pulp whilst the radicular pulp shows little or no sign of infection. Preserving the pulp with sustained vitality and developing minimally invasive biologically based therapies are key themes within contemporary clinical practice. However, root canal treatment involving complete removal of the pulp is often the only option (other than extraction) given to patients with irreversible pulpitis, with substantial NHS and patient incurred costs. The European Society of Endodontology's (ESE 2019) recent consensus statement recommends full pulpotomy, where the inflamed coronal pulp is removed with the goal of keeping the radicular pulp vital, as a more minimally invasive technique, potentially avoiding complex root canal treatment. Although this technique may be provided in secondary care, it has not been routinely implemented or evaluated in UK General Dental Practice. METHOD: This feasibility study aims to identify and assess in a primary care setting the training needs of general dental practitioners and clinical fidelity of the full pulpotomy intervention, estimate likely eligible patient pool and develop recruitment materials ahead of the main randomised controlled trial comparing the clinical and cost-effectiveness of full pulpotomy compared to root canal treatment in pre/molar teeth of adults 16 years and older showing signs indicative of irreversible pulpitis. The feasibility study will recruit and train 10 primary care dentists in the full pulpotomy technique. Dentists will recruit and provide full pulpotomy to 40 participants (four per practice) with indications of partial irreversible pulpitis. DISCUSSION: The Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP) study will address the lack of high-quality evidence in the treatment of irreversible pulpitis, to aid dental practitioners, patients and policymakers in their decision-making. The PIP feasibility study will inform the main study on the practicality of providing both training and provision of the full pulpotomy technique in general dental practice. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN17973604 . Registered on 28 January 2021. Protocol version Protocol version: 1; date: 03.02.2021.

Provision of the progestogen-only pill by community pharmacies as bridging contraception for women receiving emergency contraception: the Bridge-it RCT.

INTRODUCTION: Unless women start effective contraception after using emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies that are unable to provide ongoing contraception (apart from barrier methods which have high failure rates). This means that women need an appointment with a general practitioner or at a sexual and reproductive health clinic. We conducted a pragmatic cluster randomised cohort crossover trial to determine whether or not pharmacist provision of a bridging supply of a progestogen-only pill plus the invitation to attend a sexual and reproductive health clinic resulted in increased subsequent use of effective contraception (hormonal or intrauterine). METHODS: Twenty-nine pharmacies in three UK cities recruited women receiving emergency contraception (levonorgestrel). In the intervention, women received a 3-month supply of the progestogen-only pill (75 µg of desogestrel) plus a card that provided rapid access to a local sexual and reproductive health clinic. In the control arm, pharmacists advised women to attend their usual contraceptive provider. The primary outcome was reported use of an effective contraception (hormonal and intrauterine methods) at 4 months. Process evaluation was also conducted to inform any future implementation. RESULTS: The study took place December 2017 and June 2019 and recruited 636 women to the intervention (n = 316) and control groups (n = 320). There were no statistically significant differences in demographic characteristics between the groups. Four-month follow-up data were available for 406 participants: 63% (198/315) of the control group and 65% (208/318) of the intervention group. The proportion of participants reporting use of effective contraception was 20.1% greater (95% confidence interval 5.2% to 35.0%) in the intervention group (58.4%, 95% confidence interval 48.6% to 68.2%) than in the control group (40.5%, 95% confidence interval 29.7% to 51.3%) (adjusted for recruitment period, treatment arm and centre; p = 0.011). The proportion of women using effective contraception remained statistically significantly larger, when adjusted for age, current sexual relationship and history of past use of effective contraception, and was robust to the missing data. There were no serious adverse events. CONCLUSION: Provision of a bridging supply of the progestogen-only pill with emergency contraception from a pharmacist and the invitation to a sexual and reproductive health clinic resulted in a significant increase in self-reported subsequent use of effective contraception. This simple intervention has the potential to prevent more unintended pregnancies for women after emergency contraception. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70616901. 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. 25, No. 27. See the NIHR Journals Library website for further project information.

The emergency contraceptive pill can prevent pregnancy following unprotected sex or a burst condom; however, unless women start a regular method of contraception they remain at risk of pregnancy. Most women obtain emergency contraception from a community pharmacy (chemist), but then require an appointment with a general practitioner or at a sexual and reproductive health clinic for ongoing contraception. Getting an appointment can take time and unintended pregnancies can occur during this time. If a pharmacist could give women a small supply of a progestogen-only pill or 'mini-pill' with their emergency contraception, together with help to get an appointment at a clinic, then this might help more women to start effective contraception. We undertook a study in 29 pharmacies in Lothian, Tayside and London among women receiving emergency contraception. Pharmacists provided either their standard advice about contraception (control group) or the intervention. The intervention was a 3-month supply of the progestogen-only pill plus a rapid-access card, which, if presented at a sexual and reproductive health clinic, would help women get an appointment for contraception. The order in which the pharmacy provided either control or intervention was randomised. We conducted telephone interviews with the women 4 months later to find out what contraception they were using. A total of 636 women took part in the study, 316 in the intervention group and 320 in the control group. The proportion who said that they were using an effective method of contraception was around 20% larger in the intervention group. In addition, fewer women in this group said that they had used emergency contraception again. This study shows that community pharmacy provision of a small supply of progestogen-only pills and the invitation to attend a sexual and reproductive health clinic results in a large increase in the use of effective contraception after emergency contraception. If this became routine practice then it could help prevent unintended pregnancies.

Effect of hands-on interprofessional simulation training for local emergencies in Scotland: the THISTLE stepped-wedge design randomised controlled trial.

OBJECTIVE: To assess whether the implementation of an intrapartum training package (PROMPT (PRactical Obstetric Multi-Professional Training)) across a health service reduced the proportion of term babies born with Apgar score <7 at 5 min (<75mins). DESIGN: Stepped-wedge cluster randomised controlled trial. SETTING: Twelve randomised maternity units with ≥900 births/year in Scotland. Three additional units were included in a supplementary analysis to assess the effect across Scotland. The intervention commenced in March 2014 with follow-up until September 2016. INTERVENTION: The PROMPT training package (Second edition), with subsequent unit-level implementation of PROMPT courses for all maternity staff. MAIN OUTCOME MEASURES: The primary outcome was the proportion of term babies with Apgar<75mins. RESULTS: 87 204 eligible births (99.2% with an Apgar score), of which 1291 infants had an Apgar<75mins were delivered in the 12 randomised maternity units. Two units did not implement the intervention. The overall Apgar<75mins rate observed in the 12 randomised units was 1.49%, increasing from 1.32% preintervention to 1.59% postintervention. Once adjusted for a secular time trend, the 'intention-to-treat' analysis indicated a moderate but non-significant reduction in the rate of term babies with an Apgar scores <75mins following PROMPT training (OR=0.79 95%CI(0.63 to 1.01)). However, some units implemented the intervention earlier than their allocated step, whereas others delayed the intervention. The content and authenticity of the implemented intervention varied widely at unit level. When the actual date of implementation of the intervention in each unit was considered in the analysis, there was no evidence of improvement (OR=1.01 (0.84 to 1.22)). No intervention effect was detected by broadening the analysis to include all 15 large Scottish maternity units. Units with a history of higher rates of Apgar<75mins maintained higher Apgar rates during the study (OR=2.09 (1.28 to 3.41)) compared with units with pre-study rates aligned to the national rate. CONCLUSIONS: PROMPT training, as implemented, had no effect on the rate of Apgar <75mins in Scotland during the study period. Local implementation at scale was found to be more difficult than anticipated. Further research is required to understand why the positive effects observed in other single-unit studies have not been replicated in Scottish maternity units, and how units can be best supported to locally implement the intervention authentically and effectively. TRIAL REGISTRATION NUMBER: ISRCTN11640515.

The TOPSY pessary self-management intervention for pelvic organ prolapse: a study protocol for the process evaluation.

BACKGROUND: Process evaluations have become a valued component, alongside clinical trials, of the wider evaluation of complex health interventions. They support understanding of implementation, and fidelity, related to the intervention and provide valuable insights into what is effective in a practical setting by examining the context in which interventions are implemented. The TOPSY study consists of a large multi-centre randomised controlled trial comparing the effectiveness of pessary self-management with clinic-based care in improving women's condition-specific quality of life, and a nested process evaluation. The process evaluation aims to examine and maximise recruitment to the trial, describe intervention fidelity and explore participants' and healthcare professionals' experiences. METHODS: The trial will recruit 330 women from approximately 17 UK centres. The process evaluation uses a mixed-methods approach. Semi-structured interviews will be conducted with randomised women (18 per randomised group/n = 36), women who declined trial participation but agreed to interview (non-randomised women) (n = 20) and healthcare professionals recruiting to the trial (n ~ 17) and delivering self-management and clinic-based care (n ~ 17). The six internal pilot centres will be asked to record two to three recruitment discussions each (total n = 12-18). All participating centres will be asked to record one or two self-management teaching appointments (n = 30) and self-management 2-week follow-up telephone calls (n = 30). Process data (quantitative and qualitative) will be gathered in participant completed trial questionnaires. Interviews will be analysed thematically and recordings using an analytic grid to identify fidelity to the intervention. Quantitative analysis will be predefined within the process evaluation analysis plan. DISCUSSION: The wide variety of pessary care delivered across the UK for women with pelvic organ prolapse presents specific localised contexts in which the TOPSY interventions will be implemented. Understanding this contextual variance is central to understanding how and in what circumstances pessary self-management can be implemented (should it be effective). The inclusion of non-randomised women provides an innovative way of collecting indispensable information about eligible women who decline trial participation, allowing broader contextualisation and considerations of generalisability of trial findings. Methodological insights from examination of recruitment processes and mechanisms have the potential to inform recruitment mechanisms and future recruitment strategies and study designs. TRIAL REGISTRATION: ISRCTN62510577 . Registered on 6 October 2017.

Clinical and cost-effectiveness of vaginal pessary self-management compared to clinic-based care for pelvic organ prolapse: protocol for the TOPSY randomised controlled trial.

BACKGROUND: Pelvic organ prolapse (or prolapse) is a common condition in women where the pelvic organs (bladder, bowel or womb) descend into the vagina and cause distressing symptoms that adversely affect quality of life. Many women will use a vaginal pessary to treat their prolapse symptoms. Clinic-based care usually consists of having a pessary fitted in a primary or secondary care setting, and returning approximately every 6 months for healthcare professional review and pessary change. However, it is possible that women could remove, clean and re-insert their pessary themselves; this is called self-management. This trial aims to assess if self-management of a vaginal pessary is associated with better quality of life for women with prolapse when compared to clinic-based care. METHODS: This is a multicentre randomised controlled trial in at least 17 UK centres. The intervention group will receive pessary self-management teaching, a self-management information leaflet, a follow-up phone call and access to a local telephone number for clinical support. The control group will receive the clinic-based pessary care which is standard at their centre. Demographic and medical history data will be collected from both groups at baseline. The primary outcome is condition-specific quality of life at 18 months' post-randomisation. Several secondary outcomes will also be assessed using participant-completed questionnaires. Questionnaires will be administered at baseline, 6, 12 and 18 months' post-randomisation. An economic evaluation will be carried out alongside the trial to evaluate cost-effectiveness. A process evaluation will run parallel to the trial, the protocol for which is reported in a companion paper. DISCUSSION: The results of the trial will provide robust evidence of the effectiveness of pessary self-management compared to clinic-based care in terms of improving women's quality of life, and of its cost-effectiveness. TRIAL REGISTRATION: ISRCTN Registry ISRCTN62510577 . Registered on June 10, 2017.

Open urethroplasty versus endoscopic urethrotomy for recurrent urethral stricture in men: the OPEN RCT.

BACKGROUND: Men who suffer recurrence of bulbar urethral stricture have to decide between endoscopic urethrotomy and open urethroplasty to manage their urinary symptoms. Evidence of relative clinical effectiveness and cost-effectiveness is lacking. OBJECTIVES: To assess benefit, harms and cost-effectiveness of open urethroplasty compared with endoscopic urethrotomy as treatment for recurrent urethral stricture in men. DESIGN: Parallel-group, open-label, patient-randomised trial of allocated intervention with 6-monthly follow-ups over 24 months. Target sample size was 210 participants providing outcome data. Participants, clinicians and local research staff could not be blinded to allocation. Central trial staff were blinded when needed. SETTING: UK NHS with recruitment from 38 hospital sites. PARTICIPANTS: A total of 222 men requiring operative treatment for recurrence of bulbar urethral stricture who had received at least one previous intervention for stricture. INTERVENTIONS: A centralised randomisation system using random blocks allocated participants 1 : 1 to open urethroplasty (experimental group) or endoscopic urethrotomy (control group). MAIN OUTCOME MEASURES: The primary clinical outcome was control of urinary symptoms. Cost-effectiveness was assessed by cost per quality-adjusted life-year (QALY) gained over 24 months. The main secondary outcome was the need for reintervention for stricture recurrence. RESULTS: The mean difference in the area under the curve of repeated measurement of voiding symptoms scored from 0 (no symptoms) to 24 (severe symptoms) between the two groups was -0.36 [95% confidence interval (CI) -1.78 to 1.02; p = 0.6]. Mean voiding symptom scores improved between baseline and 24 months after randomisation from 13.4 [standard deviation (SD) 4.5] to 6 (SD 5.5) for urethroplasty group and from 13.2 (SD 4.7) to 6.4 (SD 5.3) for urethrotomy. Reintervention was less frequent and occurred earlier in the urethroplasty group (hazard ratio 0.52, 95% CI 0.31 to 0.89; p = 0.02). There were two postoperative complications requiring reinterventions in the group that received urethroplasty and five, including one death from pulmonary embolism, in the group that received urethrotomy. Over 24 months, urethroplasty cost on average more than urethrotomy (cost difference £2148, 95% CI £689 to £3606) and resulted in a similar number of QALYs (QALY difference -0.01, 95% CI -0.17 to 0.14). Therefore, based on current evidence, urethrotomy is considered to be cost-effective. LIMITATIONS: We were able to include only 69 (63%) of the 109 men allocated to urethroplasty and 90 (80%) of the 113 men allocated to urethrotomy in the primary complete-case intention-to-treat analysis. CONCLUSIONS: The similar magnitude of symptom improvement seen for the two procedures over 24 months of follow-up shows that both provide effective symptom control. The lower likelihood of further intervention favours urethroplasty, but this had a higher cost over the 24 months of follow-up and was unlikely to be considered cost-effective. FUTURE WORK: Formulate methods to incorporate short-term disutility data into cost-effectiveness analysis. Survey pathways of care for men with urethral stricture, including the use of enhanced recovery after urethroplasty. Establish a pragmatic follow-up schedule to allow national audit of outcomes following urethral surgery with linkage to NHS Hospital Episode Statistics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98009168. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 61. See the NIHR Journals Library website for further project information.

The urethra carries urine from the bladder to the tip of the penis. Men can develop a condition called urethral stricture when part of the urethra narrows due to scarring. This can lead to difficulties in passing urine and can recur. There are two operations for urethral stricture. The standard approach is endoscopic urethrotomy. The alternative is open urethroplasty. This study wanted to find out which operation was preferable in terms of symptom control, time before further surgery and which operation was best value for the NHS. All aspects of the study were informed by patients. Two hundred and twenty-two men who had received at least one previous operation for stricture took part. The choice of operation was decided by chance (randomisation). Of these men, 113 were randomised to urethrotomy and 109 were randomised to urethroplasty. Following their operation, the men filled in questionnaires every 3­6 months for 2 years about their symptoms and if any further surgery was needed. The two groups were then compared. Of the 222 men who took part, 159 provided enough information for inclusion in the comparison (90 were in the urethrotomy group and 69 were in the urethroplasty group). The improvement over time in urinary symptoms was similar for the two groups. Men in the urethrotomy group were twice as likely to need a further operation over the 2-year study period. Very few men experienced serious complications. This study showed that both operations led to symptom improvement for men with recurrent urethral stricture. Urethroplasty, however, appears unlikely to offer good value for money for the NHS. Men needing treatment for recurrent urethral stricture can use this information to weigh up the pros and cons of each operation to decide with their clinical team which one to undergo.

Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial).

BACKGROUND: Urethral stricture affects 0.9% of men. Initial treatment is urethrotomy. Approximately, half of the strictures recur within 4 yr. Options for further treatment are repeat urethrotomy or open urethroplasty. OBJECTIVE: To compare the effectiveness and cost-effectiveness of urethrotomy with open urethroplasty in adult men with recurrent bulbar urethral stricture. DESIGN, SETTING, AND PARTICIPANTS: This was an open label, two-arm, patient-randomised controlled trial. UK National Health Service hospitals were recruited and 222 men were randomised to receive urethroplasty or urethrotomy. INTERVENTION: Urethrotomy is a minimally invasive technique whereby the narrowed area is progressively widened by cutting the scar tissue with a steel blade mounted on a urethroscope. Urethroplasty is a more invasive surgery to reconstruct the narrowed area. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the profile over 24 mo of a patient-reported outcome measure, the voiding symptom score. The main clinical outcome was time until reintervention. RESULTS AND LIMITATIONS: The primary analysis included 69 (63%) and 90 (81%) of those allocated to urethroplasty and urethrotomy, respectively. The mean difference between the urethroplasty and urethrotomy groups was -0.36 (95% confidence interval [CI] -1.74 to 1.02). Fifteen men allocated to urethroplasty needed a reintervention compared with 29 allocated to urethrotomy (hazard ratio [95% CI] 0.52 [0.31-0.89]). CONCLUSIONS: In men with recurrent bulbar urethral stricture, both urethroplasty and urethrotomy improved voiding symptoms. The benefit lasted longer for urethroplasty. PATIENT SUMMARY: There was uncertainty about the best treatment for men with recurrent bulbar urethral stricture. We randomised men to receive one of the following two treatment options: urethrotomy and urethroplasty. At the end of the study, both treatments resulted in similar and better symptom scores. However, the urethroplasty group had fewer reinterventions.

Pragmatic cluster randomised cohort cross-over trial to determine the effectiveness of bridging from emergency to regular contraception: the Bridge-It study protocol.

INTRODUCTION: Oral emergency contraception (EC) can prevent unintended pregnancy but it is important to start a regular method of contraception. Women in the UK usually access EC from a pharmacy but then need a subsequent appointment with a general practitioner or a sexual and reproductive health (SRH) service to access regular contraception. Unintended pregnancies can occur during this time. METHODS AND ANALYSIS: Bridge-It is a pragmatic cluster randomised cohort cross-over trial designed to determine whether pharmacist provision of a bridging supply of a progestogen-only pill (POP) plus rapid access to a local SRH clinic, results in increased uptake of effective contraception and prevents more unintended pregnancies than provision of EC alone. Bridge-It involves 31 pharmacies in three UK regions (London, Lothian and Tayside) aiming to recruit 626-737 women. Pharmacies will give EC (levonorgestrel) according to normal practice and recruit women to both intervention and the control phases of the study. In the intervention phase, pharmacists will provide the POP (desogestrel) and offer rapid access to an SRH clinic. In the control phase, pharmacists will advise women to attend a contraceptive provider for contraception (standard care).Women will be asked 4 months later about contraceptive use. Data linkage to abortion registries will provide abortion rates over 12 months. The sample size is calculated on the primary outcome of effective contraception use at 4 months (yes/no) with 90% power and a 5% level of significance. Abortion rates will be an exploratory secondary analysis. Process evaluation includes interviews with pharmacists, SRH clinicians and women. Cost-effectiveness analysis will use a healthcare system perspective and be expressed as incremental cost-effectiveness ratio. ETHICS AND DISSEMINATION: Ethical approval was received from South East Scotland REC June 2017. Results will be published in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN70616901.

Male synthetic sling versus artificial urinary sphincter trial for men with urodynamic stress incontinence after prostate surgery (MASTER): study protocol for a randomised controlled trial.

BACKGROUND: Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed - a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness. METHODS/DESIGN: Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to identify problems or need for further treatment. DISCUSSION: A robust examination of the comparative effectiveness of the male synthetic sling will provide high-quality evidence to determine whether or not it should be adopted widely in the NHS. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Registry: Number ISRCTN49212975 . Registered on 22 July 2013. First patient randomised on 29 January 2014.

HEALTH: laparoscopic supracervical hysterectomy versus second-generation endometrial ablation for the treatment of heavy menstrual bleeding: study protocol for a randomised controlled trial.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem affecting approximately 1.5 million women in England and Wales with a major impact on their physical, emotional, social and material quality of life. It is the fourth most common reason why women attend gynaecology outpatient clinics and accounts for one-fifth of all gynaecology outpatient referrals. Initial treatment in primary care is medical - either by means of oral or injected medication or the levonorgestrel-intrauterine system (Mirena®). If medical treatment fails then surgical treatment can be offered, either endometrial ablation (EA), which destroys the lining of the cavity of the uterus (endometrium), or hysterectomy, i.e. surgical removal of the uterus. While effective, conventional hysterectomy is invasive and carries a risk of complications due to injury to other pelvic structures. The procedure can be simplified and complications minimised by undertaking a 'supracervical' hysterectomy where the cervix is left in situ and only the body of the uterus removed. Recent advances in endoscopic technologies have facilitated increased use of laparoscopic supracervical hysterectomy (LASH) which can be performed as a day-case procedure and is relatively easy for the surgeon to learn. HEALTH (Hysterectomy or Endometrial AbLation Trial for Heavy menstrual bleeding) aims to address the question 'Is LASH superior to second generation EA for the treatment of HMB in terms of clinical and cost effectiveness?' METHODS/DESIGN: Women aged < 50 years, with HMB, in whom medical treatment has failed and who are eligible for EA will be considered for trial entry. We aim to recruit women from approximately 30 active secondary care centres in the UK NHS who carry out both surgical procedures. All women who consent will complete a diary of pain symptoms from day 1 to day 14 after surgery, postal questionnaires at six weeks and six months after surgery and 15 months post randomisation. Healthcare utilisation questions will also be completed at the six-week, six-month and 15-month time-points. DISCUSSION: Measuring the comparative effectiveness of LASH vs EA will provide the robust evidence required to determine whether the new technique should be adopted widely in the NHS. TRIAL REGISTRATION: International Standard Randomised Controlled Trials, ISRCTN49013893 . Registered on 28 January 2014.

A pragmatic group sequential, placebo-controlled, randomised trial to determine the effectiveness of glyceryl trinitrate for retained placenta (GOT-IT): a study protocol.

INTRODUCTION: A retained placenta is diagnosed when the placenta is not delivered following delivery of the baby. It is a major cause of postpartum haemorrhage and treated by the operative procedure of manual removal of placenta (MROP). METHODS AND ANALYSIS: The aim of this pragmatic, randomised, placebo-controlled, double-blind UK-wide trial, with an internal pilot and nested qualitative research to adjust strategies to refine delivery of the main trial, is to determine whether sublingual glyceryl trinitrate (GTN) is (or is not) clinically and cost-effective for (medical) management of retained placenta. The primary clinical outcome is need for MROP, defined as the placenta remaining undelivered 15 min poststudy treatment and/or being required within 15 min of treatment due to safety concerns. The primary safety outcome is measured blood loss between administration of treatment and transfer to the postnatal ward or other clinical area. The primary patient-sided outcome is satisfaction with treatment and a side effect profile. The primary economic outcome is net incremental costs (or cost savings) to the National Health Service of using GTN versus standard practice. Secondary outcomes are being measured over a range of clinical and economic domains. The primary outcomes will be analysed using linear models appropriate to the distribution of each outcome. Health service costs will be compared with multiple trial outcomes in a cost-consequence analysis of GTN versus standard practice. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North-East Newcastle & North Tyneside 2 Research Ethics Committee (13/NE/0339). Dissemination plans for the trial include the Health Technology Assessment Monograph, presentation at international scientific meetings and publication in high-impact, peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISCRTN88609453; Pre-results.