Study protocol for a Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in Acute Variceal Bleeding (REACT-AVB trial).

INTRODUCTION: In liver cirrhosis, acute variceal bleeding (AVB) is associated with a 1-year mortality rate of up to 40%. Data on early or pre-emptive transjugular intrahepatic portosystemic stent-shunt (TIPSS) in AVB is inconclusive and may not reflect current management strategies. Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in AVB (REACT-AVB) aims to investigate the clinical and cost-effectiveness of early TIPSS in patients with cirrhosis and AVB after initial bleeding control. METHODS AND ANALYSIS: REACT-AVB is a multicentre, randomised controlled, open-label, superiority, two-arm, parallel-group trial with an internal pilot. The two interventions allocated randomly 1:1 are early TIPSS within 4 days of diagnostic endoscopy or secondary prophylaxis with endoscopic therapy in combination with non-selective beta blockers. Patients aged ≥18 years with cirrhosis and Child-Pugh Score 7-13 presenting with AVB with endoscopic haemostasis are eligible for inclusion. The primary outcome is transplant-free survival at 1 year post randomisation. Secondary endpoints include transplant-free survival at 6 weeks, rebleeding, serious adverse events, other complications of cirrhosis, Child-Pugh and Model For End-Stage Liver Disease (MELD) scores at 6 and 12 months, health-related quality of life, use of healthcare resources, cost-effectiveness and use of cross-over therapies. The sample size is 294 patients over a 4-year recruitment period, across 30 hospitals in the UK. ETHICS AND DISSEMINATION: Research ethics committee of National Health Service has approved REACT-AVB (reference number: 23/WM/0085). The results will be submitted for publication in a peer-reviewed journal. A lay summary will also be emailed or posted to participants before publication. TRIAL REGISTRATION NUMBER: ISRCTN85274829; protocol version 3.0, 1 July 2023.

Health screening clinic to reduce absenteeism and presenteeism among NHS Staff: eTHOS a pilot RCT.

Background: Staff sickness absenteeism and presenteeism (attending work while unwell) incur high costs to the NHS, are associated with adverse patient outcomes and have been exacerbated by the COVID-19 pandemic. The main causes are mental and musculoskeletal ill health with cardiovascular risk factors common. Objectives: To undertake a feasibility study to inform the design of a definitive randomised controlled trial of the effectiveness and cost effectiveness of a health screening clinic in reducing absenteeism and presenteeism amongst the National Health Service staff. Design: Individually randomised controlled pilot trial of the staff health screening clinic compared with usual care, including qualitative process evaluation. Setting: Four United Kingdom National Health Service hospitals from two urban and one rural Trust. Participants: Hospital employees who had not previously attended a pilot health screening clinic at Queen Elizabeth Hospital Birmingham. Interventions: Nurse-led staff health screening clinic with assessment for musculoskeletal health (STarT musculoskeletal; STarT Back), mental health (patient health questionnaire-9; generalised anxiety disorder questionnaire-7) and cardiovascular health (NHS health check if aged ≥ 40, lifestyle check if < 40 years). Screen positives were given advice and/or referral to services according to UK guidelines. Main outcome measures: The three coprimary outcomes were recruitment, referrals and attendance at referred services. These formed stop/go criteria when considered together. If any of these values fell into the 'amber' zone, then the trial would require modifications to proceed to full trial. If all were 'red', then the trial would be considered unfeasible. Secondary outcomes collected to inform the design of the definitive randomised controlled trial included: generalisability, screening results, individual referrals required/attended, health behaviours, acceptability/feasibility of processes, indication of contamination and costs. Outcomes related to the definitive trial included self-reported and employee records of absenteeism with reasons. Process evaluation included interviews with participants, intervention delivery staff and service providers. Descriptive statistics were presented and framework analysis conducted for qualitative data. Due to the COVID-19 pandemic, outcomes were captured up to 6 months only. Results: Three hundred and fourteen participants were consented (236 randomised), the majority within 4 months. The recruitment rate of 314/3788 (8.3%) invited was lower than anticipated (meeting red for this criteria), but screening identified that 57/118 (48.3%) randomised were eligible for referral to either general practitioner (81%), mental health (18%) and/or physiotherapy services (30%) (green). Early trial closure precluded determination of attendance at referrals, but 31.6% of those eligible reported intending to attend (amber). Fifty-one of the 80 (63.75%) planned qualitative interviews were conducted. Quantitative and qualitative data from the process evaluation indicated that the electronic database-driven screening intervention and data collection were efficient, promoting good fidelity, although needing more personalisation at times. Recruitment and delivery of the full trial would benefit from a longer development period to better understand local context, develop effective strategies for engaging with underserved groups, provide longer training and better integration with referral services. Delivery of the pilot was limited by the impact of COVID-19 with staff redeployment, COVID-research prioritisation and reduced availability of community and in-house referral services. While recruitment was rapid, it did not fully represent ethnic minority groups and truncated follow-up due to funding limitations prevented full assessment of attendance at recommended services and secondary outcomes. Conclusions: There is both a clinical need (evidenced by 48% screened eligible for a referral) and perceived benefit (data from the qualitative interviews) for this National Health Service staff health screening clinic. The three stop/go criteria were red, green and amber; therefore, the Trial Oversight Committee recommended that a full-scale trial should proceed, but with modifications to adapt to local context and adopt processes to engage better with underserved communities. Trial registration: This trial is registered as ISRCTN10237475. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/42/42) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 23. See the NIHR Funding and Awards website for further award information.

Sickness absenteeism and presenteeism (attendance at work while ill, with poor work performance) are major problems in the NHS and associated with worse patient health care. The most common causes of NHS staff sickness absenteeism and presenteeism are muscular complaints and mental ill health. Poor lifestyle and illnesses associated with heart disease are also important factors. Staff health checks might improve the health of NHS staff, but no studies have included screening tests to address the most common causes of poor staff health. This pilot study tested whether it would be possible to deliver a randomised controlled trial of an NHS staff health screening clinic, where some people get the screening check and others do not (chosen at random, like flipping a coin). We used an electronic database to capture all data. Participants completed initial questionnaires either at home or at work, then attended a face-to-face screening clinic using recognised screening questionnaires and tests to detect problems with muscular, mental or heart health. We considered how NHS staff and healthcare organisations would want the screening clinic and trial to run, how a diverse range of NHS staff could best be approached, how many staff might need to be invited and what their healthcare needs would be. The study ran in four UK NHS hospitals during the COVID-19 pandemic. Two hundred and thirty-six NHS staff participated, but early trial closure due to the pandemic meant that some results were unavailable. For the primary feasibility outcomes, although recruitment rates of around 8% were lower than anticipated, half of staff screened needed referral for further health care and one-third reported intending to attend. Staff felt that the clinic addressed an important health need. The Trial Oversight Committee recommended proceeding to a full-scale trial but with modifications to address findings from the process evaluation, including ways to encourage a wider group of NHS staff to take part.

The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that continuous positive airway pressure (CPAP) could have a favorable impact on these complications. We assessed the feasibility of conducting a randomized control trial in patients with type 2 diabetes and OSA over 2 years. METHODS: We conducted an open-label multicenter feasibility randomized control trial of CPAP vs no CPAP in patients with type 2 diabetes and OSA. Patients with resting oxygen saturation < 90%, central apnea index > 15 events/h, or Epworth Sleepiness Scale ≥ 11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomly assigned, with a median (interquartile range) follow-up of 645 (545, 861) days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomly assigned to CPAP and several diabetes-related end points (chronic kidney disease, neuropathy, and quality of life). CONCLUSIONS: It was feasible to recruit, randomly assign, and achieve a high follow-up rate over 2 years in patients with OSA and type 2 diabetes. CPAP compliance might improve by a run-in period before randomization. A full randomized control trial is necessary to assess the observed favorable association between CPAP and chronic kidney disease , neuropathy, and quality of life in patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; Name: The impact of sleep disorders in patients with type 2 diabetes; URL: https://www.isrctn.com/ISRCTN12361838; Identifier: ISRCTN12361838. CITATION: Makhdom EA, Maher A, Ottridge R, et al. The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial. J Clin Sleep Med. 2024;20(6):947-957.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

A randomized trial of synthetic osmotic cervical dilator for induction of labor vs dinoprostone vaginal insert.

BACKGROUND: Induction of labor is a commonly performed obstetrical intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower in achieving cervical ripening but have a lower risk of adverse effects. OBJECTIVE: This study aimed to compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with those of dinoprostone. STUDY DESIGN: This was an open-label superiority randomized controlled trial in 4 English hospitals. Eligible participants were women ≥16 years of age undergoing induction of labor for a singleton pregnancy at ≥37 weeks' gestation with vertex presentation and intact membranes. The women were randomly assigned to receive either Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, body mass index, and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by the Bishop score. The primary outcome was failure to achieve vaginal delivery (ieor a cesarean delivery being performed). The secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible. RESULTS: Between December 19, 2017 and January 26, 2021, 674 women were randomized (337 to Dilapan-S, and 337 to dinoprostone). The trial did not reach its planned sample size of 860 participants because of restrictions on research during the COVID-19 pandemic. The primary outcome was missing for 2 women in the dinoprostone group. Failure to achieve vaginal delivery (or a cesarean delivery being performed) occurred in 126 women (37.4%) allocated to Dilapan-S and in 115 (34.3%) women allocated to dinoprostone (adjusted risk difference, 0.02; 95% confidence interval, -0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. CONCLUSION: Women undergoing induction of labor with Dilapan-S have similar rates of cesarean delivery and maternal and neonatal adverse events compared with dinoprostone.