Timing of Stoma Closure in Neonates: the ToSCiN mixed-methods study.

Background: Neonates undergoing emergency abdominal surgery frequently require a stoma; closing this stoma with a second operation is an essential part of recovery. Timing of closure varies. Optimal timing is unclear and would be best resolved through a randomised controlled trial; such a trial is likely to be challenging.

Techniques to increase lumbar puncture success in newborn babies: the NeoCLEAR RCT.

Background: Lumbar puncture is an essential tool for diagnosing meningitis. Neonatal lumbar puncture, although frequently performed, has low success rates (50-60%). Standard technique includes lying infants on their side and removing the stylet 'late', that is, after the needle is thought to have entered the cerebrospinal fluid.

Frenotomy with breastfeeding support versus breastfeeding support alone for infants with tongue-tie and breastfeeding difficulties: the FROSTTIE RCT.

Background: Tongue-tie can be diagnosed in 3-11% of babies, with some studies reporting almost universal breastfeeding difficulties, and others reporting very few feeding difficulties that relate to the tongue-tie itself, instead noting that incorrect positioning and attachment are the primary reasons behind the observed breastfeeding difficulties and not the tongue-tie itself. The only existing trials of frenotomy are small and underpowered and/or include only very short-term or subjective outcomes.

Objective: To investigate whether frenotomy is clinically and cost-effective to promote continuation of breastfeeding at 3 months in infants with breastfeeding difficulties diagnosed with tongue-tie.

Treatments for Moderate-to-Severe Alopecia Areata: A Systematic Narrative Review.

Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. As a better understanding of the evidence supporting the management of AA in clinical practice is needed, we conducted a systematic literature review and subsequent narrative review to describe available evidence pertaining to the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA.

Prognostic Value of Neurotrophic Tyrosine Receptor Kinase Gene Fusions in Solid Tumors for Overall Survival: A Systematic Review and Meta-Analysis.

Purpose: Evidence suggests that neurotrophic tyrosine receptor kinase () gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult and pediatric tumor types. However, despite robust clinical response to tyrosine receptor kinase (TRK) inhibitors, the natural history and prognostic implications of fusions in solid tumors are poorly understood. It is important to evaluate their prognostic significance on survival to provide some context to the clinical effectiveness observed in clinical trials of TRK-targeted therapies.

Developing guidance for a risk-proportionate approach to blinding statisticians within clinical trials: a mixed methods study.

Background: Existing guidelines recommend statisticians remain blinded to treatment allocation prior to the final analysis and that any interim analyses should be conducted by a separate team from the one undertaking the final analysis. However, there remains substantial variation in practice between UK Clinical Trials Units (CTUs) when it comes to blinding statisticians. Therefore, the aim of this study was to develop guidance to advise CTUs on a risk-proportionate approach to blinding statisticians within clinical trials.

Planned delivery for pre-eclampsia between 34 and 37 weeks of gestation: the PHOENIX RCT.

Background: In women with late preterm pre-eclampsia (i.e. at 34 to 36 weeks' gestation), the optimal delivery time is unclear because limitation of maternal-fetal disease progression needs to be balanced against infant complications.

Assessment of infant position and timing of stylet removal to improve lumbar puncture success in neonates (NeoCLEAR): an open-label, 2 × 2 factorial, randomised, controlled trial.

Background: Newborn infants are the highest-risk age group for bacterial meningitis. Lumbar punctures are therefore frequently performed in neonates, but success rates are low (50-60%). In Neonatal Champagne Lumbar punctures Every time-A Randomised Controlled Trial (NeoCLEAR), we sought to optimise infant lumbar puncture by evaluating two modifications to traditional technique: sitting position versus lying down and early stylet removal (stylet removal after transecting the subcutaneous tissue) versus late stylet removal.

Factors associated with infection after operative vaginal birth-a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth.

Background: A recent randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth showed that women allocated prophylactic intravenous amoxicillin and clavulanic acid had a significantly lower risk of developing confirmed or suspected infection within 6 weeks after operative vaginal birth (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.49-0.

Cost-Utility Analysis of Planned Early Delivery or Expectant Management for Late Preterm Pre-eclampsia (PHOENIX).

Aim: There is currently limited evidence on the costs associated with late preterm pre-eclampsia beyond antenatal care and post-natal discharge from hospital. The aim of this analysis is to evaluate the 24-month cost-utility of planned delivery for women with late preterm pre-eclampsia at 34-36 weeks' gestation compared to expectant management from an English National Health Service perspective using participant-level data from the PHOENIX trial.

Methods: Women between 34 and 36 weeks' gestation in 46 maternity units in England and Wales were individually randomised to planned delivery or expectant management.

Blinding of study statisticians in clinical trials: a qualitative study in UK clinical trials units.

Background: Blinding is an established approach in clinical trials which aims to minimise the risk of performance and detection bias. There is little empirical evidence to guide UK clinical trials units (CTUs) about the practice of blinding statisticians. Guidelines recommend that statisticians remain blinded to allocation prior to the final analysis.

Transfer of thawed frozen embryo versus fresh embryo to improve the healthy baby rate in women undergoing IVF: the E-Freeze RCT.

Background: Freezing all embryos, followed by thawing and transferring them into the uterine cavity at a later stage (freeze-all), instead of fresh-embryo transfer may lead to improved pregnancy rates and fewer complications during in vitro fertilisation and pregnancies resulting from it.

Objective: We aimed to evaluate if a policy of freeze-all results in a higher healthy baby rate than the current policy of transferring fresh embryos.

Design: This was a pragmatic, multicentre, two-arm, parallel-group, non-blinded, randomised controlled trial.

Two-year follow-up of infant and maternal outcomes after planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): A randomised controlled trial.

Objective: We evaluated the best time to initiate delivery in late preterm pre-eclampsia in order to optimise long-term infant and maternal outcomes.

Design: Parallel-group, non-masked, randomised controlled trial.

Setting: Forty-six maternity units in the UK.

An evaluation of a combined psychological and parenting intervention for HIV-positive women depressed in the perinatal period, to enhance child development and reduce maternal depression: study protocol for the Insika Yomama cluster randomised controlled trial.

Background: The combination of poverty, HIV and depression in the perinatal period represents a major public health challenge in many Southern African countries. In some areas, up to a third of HIV-positive women experience perinatal depression. Perinatal depression is associated with negative effects on parenting and key domains of child development including cognitive, behavioural and growth, especially in socio-economically disadvantaged communities.

Evaluation of the effectiveness of an incentive strategy on the questionnaire response rate in parents of premature babies: a randomised controlled Study Within A Trial (SWAT) nested within SIFT.

Background: Loss to follow-up resulting in missing outcomes compromises the validity of trial results by reducing statistical power, negatively affecting generalisability and undermining assumptions made at analysis, leading to potentially biased and misleading results. Evidence that incentives are effective at improving response rates exists, but there is little evidence regarding the best approach, especially in the field of perinatal medicine. The NIHR-funded SIFT trial follow-up of infants at 2 years of age provided an ideal opportunity to address this remaining uncertainty.

Timing of neonatal stoma closure: a survey of health professional perspectives and current practice.

Optimal timing for neonatal stoma closure remains unclear. In this study, we aimed to establish current practice and illustrate multidisciplinary perspectives on timing of stoma closure using an online survey sent to all 27 UK neonatal surgical units, as part of a research programme to determine the feasibility of a clinical trial comparing 'early' and 'late' stoma closure. 166 responses from all 27 units demonstrated concordance of opinion in target time for closure (6 weeks most commonly stated across scenarios), although there was a high variability in practice.

Baby-OSCAR: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies-a statistical analysis plan for short-term outcomes.

Background: The Baby-OSCAR trial is a multi-centre, randomised, placebo-controlled parallel group trial of early treatment of large patent ductus arteriosus (PDA) with ibuprofen in extremely preterm infants. This paper describes the statistical analysis plan for the short-term health outcomes of the Baby-OSCAR trial.

Methods And Design: This is a randomised controlled trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies improves short and long-term health and economic outcomes.

Study protocol: baby-OSCAR trial: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial.

Background: The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks' gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age.

Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19.

Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.

Methods: In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.

Economic evaluation of computerised interpretation of fetal heart rate during labour: a cost-consequence analysis alongside the INFANT study.

Objective: Economic evaluation of computerised decision-support software intended to assist in the interpretation of a cardiotocography (CTG) during birth.

Design: Individual patient level data from the INFANT study (an unmasked randomised controlled trial).

Setting: Maternity units in the UK and Ireland.