Background Urinary tract infections (UTIs) are the most common serious bacterial infections in febrile infants. Current UK guidelines recommend parenteral antibiotics for infants under three months with suspected UTI, despite evidence supporting oral therapy in low-risk infants. Objectives To assess whether oral antibiotics are non-inferior to parenteral antibiotics for treating suspected UTIs based on treatment failure, need for additional therapy, and secondary outcomes. Design Multicentre, randomised controlled, open-label, non-inferiority trial with embedded internal pilot. Setting Twenty one paediatric emergency departments and assessment units across the UK. Participants Infants aged 29–90 days with suspected UTI, abnormal urinalysis, and low risk of invasive bacterial infection. Exclusion criteria included prematurity, prior hospitalisation, structural renal abnormalities, and clinical signs of sepsis or meningitis. Interventions Participants were randomised 1:1 to receive either oral antibiotics or standard care with intravenous (IV) antibiotics for 36–48 hours pending urine culture results. Main outcome measures The primary outcome was the requirement for additional parenteral antibiotics within seven days of randomisation. A range of secondary outcomes were also planned, including treatment failure, time to recovery, adverse events, antibiotic adherence, quality of life, family impact, and healthcare resource use. Feasibility outcomes collected during the internal pilot included recruitment rate, site activation, protocol adherence, and retention. Clinical outcomes were collected but not powered for formal comparison. Results 27 participants were recruited between 20 May 2024 and 13 March 2025 (which included the 6 month internal pilot), representing 27% of the pilot target. Protocol adherence was high, and no cases of meningitis occurred. Two cases of bacteraemia (one per randomised group) had uncomplicated clinical courses. Oral therapy was associated with shorter hospital stays and reduced parental time off work. Conclusions While trial procedures were successfully implemented, recruitment challenges suggest that a larger randomised trial of this treatment comparison is not feasible in this setting. Trial management Northern Ireland Clinical Trials Unit (NICTU) Trial registration ISRCTN Clinical Trials Registry, ISRCTN10907780, Trial Dates 20 May 2024 to 13 March 2025

BACKGROUND:Bronchiolitis is a common viral respiratory disease of infants, with severity ranging from mild symptoms, such as coryza and feeding difficulties, to fulminant respiratory failure. Endotracheal administration of exogenous surfactant has been shown in small studies to improve gas exchange in critically ill infants with bronchiolitis. We aimed to investigate the safety and efficacy of endotracheal poractant alfa for treating critical bronchiolitis compared with a sham procedure. METHODS:BESS was a multicentre, blinded, randomised, sham-controlled, parallel-group, phase 2, superiority trial with exploratory mechanism evaluation studies. The trial was done in 15 paediatric intensive care units in the devolved National Health Service (NHS) of England, Scotland, and Northern Ireland. Preterm and term-born infants younger than 26 weeks of gestationally corrected age admitted to hospitals with bronchiolitis requiring invasive mechanical ventilation (IMV) were randomly assigned (1:1) to receive up to three doses of endotracheal poractant alfa (Curosurf) or sham intervention, allocated through web-based randomisation. Randomisation was stratified by duration of IMV before randomisation (<24 h and ≥24 h) and by site. The infants and their families, clinical care staff, Liverpool Clinical Trial Centre staff, and members of the site research teams were masked to treatment allocations. Endotracheal poractant alfa was given initially at 200 mg/kg, followed by 100 mg/kg at 12 h intervals. The primary endpoint was the duration of IMV from randomisation to final successful extubation. All infants who were successfully extubated were included in the intention-to-treat analysis. Safety outcomes were analysed in infants who had received at least one trial intervention. This trial was registered prospectively with ISRCTN (ISRCTN11746266) and EudraCT (2018-001169-18), and is completed. FINDINGS:The trial was completed after six recruitment seasons. Between Dec 18, 2018, to March 31, 2024, 1009 infants were assessed for eligibility, 232 of whom were randomly assigned to receive either endotracheal poractant alfa (n=115) or a sham intervention (n=117). 130 (56%) of 232 infants were male and 102 (44%) were female. Three infants were withdrawn from the study. None were lost to follow-up. The median duration of IMV was 64·9 h (IQR 43·2-92·1) in the endotracheal poractant alfa group and 62·0 h (39·3-95·1) in the sham intervention group. The geometric mean ratio was 1·02 (95% CI 0·84-1·24; t-test p=0·86). No clinically significant safety issues were associated with endotracheal poractant alfa and there were no deaths. INTERPRETATION:Poractant alfa, administered endotracheally to infants with early critical bronchiolitis, although safe, did not reduce the duration of IMV compared with the sham intervention. Therefore, our findings suggest that it should not be used for this indication at this dose and administration method. FUNDING:UK National Institute for Health and Care Research, UK Research and Innovation Medical Research Council, Chief Scientist Office Scotland, Health and Social Care Research and Development Division Northern Ireland, and Chiesi Farmaceutici, Italy.

Routine measurement of gastric residual volumes involves regularly aspirating the entire stomach contents to assess the volume and colour of the aspirate to inform feeding. This is an established practice in many United Kingdom and Australian neonatal units for preterm infants receiving gastric tube feeds. The rationale is to assess feed tolerance and to predict and potentially prevent necrotising enterocolitis, a serious gut condition. Routine measurement of gastric residual volumes may also be associated with adverse outcomes and harm, including delayed achievement of full enteral feeds and longer neonatal unit stay. Evidence to support the routine measurement of gastric residuals is poor, and previous small trials have not been generalisable to UK or Australian neonatal care. The aim of the neoGASTRIC trial is to test whether avoiding routine measurement of gastric residual volumes in preterm infants reduces the time taken for an infant to reach full enteral feeds without increasing necrotising enterocolitis. neoGASTRIC is an individually randomised controlled trial in neonatal units in the UK and Australia. A target of 7040 infants born before 34 weeks’ gestation will be randomly allocated, prior to receiving 24 h of enteral feeds > 15 ml/kg/day, on a 1:1 basis to have no routine gastric residual volumes measured, or to have gastric residual volumes measured routinely. Opt-out consent will be used with parent and staff views explored as part of an embedded process evaluation. The primary superiority outcome is time to reach full milk feeds ≥ 145 ml/kg/day for three consecutive days. Bell’s stage 2 or 3 necrotising enterocolitis following blinded adjudication will be the key secondary, non-inferiority safety outcome. Other neonatal core outcomes and health care resource use and costs prior to discharge will be evaluated. neoGASTRIC will address a research priority that affects more than 20,000 preterm infants in the United Kingdom and Australia annually. Even modest improvements in clinical outcomes and resource use could result in large clinical benefits and savings at a population level. ISRCTN 16710849. Prospectively registered on 8 February 2023.

Objectives Clinical research in emergency and critical care is vital, but recruitment and consent are complex. Research may be conducted without prior consent when patients are critically ill, and interventions are time critical. Some patients may die before research participation can be discussed with relatives, leaving the bereaved unaware of their involvement. This study explored potential communication strategies for informing bereaved relatives when a patient has died following enrolment into an emergency or critical care study without prior consent.Design and setting A mixed-methods study using a telephone survey and semi-structured interviews conducted simultaneously. The survey was conducted within a National Health Service Trust in North West England with relatives of deceased study participants. Semi-structured interviews were conducted with bereaved relatives and research and clinical staff across the UK, and medical examiner (ME)/ME officers based in England and Wales. Quantitative data were analysed descriptively, and qualitative data were analysed using reflexive thematic analysis. Data were synthesised using a constant comparison approach.Participants 11 bereaved relatives completed the survey. 53 individuals (21 research and clinical staff, 18 relatives and 14 MEs/officers) participated in semi-structured interviews.Results Although many trials do not include a process for notifying bereaved relatives about research participation, most relatives valued the opportunity to learn about their family member’s participation, emphasising the importance of transparency and trust. However, some raised concerns over the potential burden of automatic disclosure by the ME service. Offering bereaved relatives the option to receive sensitively worded information about research involvement at an appropriate time, soon after death, was recommended.Conclusion Bereaved relatives should have the choice to be informed about research participation without prior consent. Our findings support the need for transparent and sensitive communication and will contribute to future guidance for the design and conduct of adult emergency and critical care studies.

BACKGROUND:Respiratory syncytial virus (RSV) is a leading cause of infant hospitalisation due to lower respiratory tract infections. Until 2022, prevention was limited to the costly monoclonal antibody palivizumab. In August 2024, the UK introduced the RSVpreF (Abrysvo, Pfizer) maternal vaccine into its national immunisation schedule. The success of this programme depends not only on vaccine effectiveness, but also on maternal access, acceptance and uptake. OBJECTIVE:To explore maternal perspectives on the RSVpreF vaccine and identify barriers and facilitators to vaccine uptake, to inform antenatal education and public health strategies. METHODS:This qualitative analysis is based on free-text survey responses from 388 vaccine-eligible mothers of infants hospitalised with bronchiolitis, lower respiratory tract infection or acute wheeze, collected between September 2024 and March 2025 across 30 sites, as part of the BronchStop study. RESULTS:Four key themes were identified: (1) access-related barriers to vaccination, (2) insufficient RSV awareness and information to support informed decision-making, (3) vaccine safety concerns and hesitancy and (4) perception of the maternal RSV vaccine as beneficial and protective. These themes were consistent across sociodemographic groups. CONCLUSIONS:Uptake of the maternal vaccine was influenced by barriers to access, informational gaps and perceived safety concerns. Improved vaccine delivery, enhanced awareness and personalised antenatal counselling are essential to increase vaccine uptake. There is an urgent need to address structural inaccessibility and provide tailored antenatal education to address informational gaps. Ongoing qualitative research is crucial to guide targeted public health interventions ahead of future RSV seasons.

Importance:Routine assessment of gastric residual volume (GRV) to guide enteral feeding in critically ill children is widespread but not based on evidence. Perceived high gastric volumes often lead to withholding feeds, impairing nutritional delivery. Objective:To evaluate the effect of not routinely assessing GRV compared with assessments at least every 6 hours in children undergoing mechanical ventilation on the duration of mechanical ventilation and survival and achievement of nutritional targets. Design, Setting, and Participants:A pragmatic, multicenter, randomized, noninferiority trial in 23 pediatric intensive care units (PICUs) in the UK and 1 in Switzerland. A total of 4700 children aged 0 to 16 years who were receiving invasive ventilation and starting enteral feeds were recruited between June 29, 2023, and December 7, 2025, with 30-day follow-up completed on January 6, 2026. Interventions:Children were randomized (1:1) to receive usual care (GRV assessment every 6 hours) or no routine GRV assessment to guide enteral feeding. In the no routine GRV assessment group, feed tolerance was assessed using only clinical signs. All other enteral feeding practices followed local protocols. Main Outcomes and Measures:The clinical co-primary outcome (noninferiority) was a composite of survival and days free from mechanical ventilation at 30 days. The nutritional co-primary outcome (superiority) was the percentage of children meeting energy requirements by 72 hours. Results:Of the 4700 children randomized (2352 to the no routine GRV assessment group and 2348 to the usual care group), 4460 were included in the intention-to-treat analysis (median [IQR] age, 8 [1-44] months; 1925 [42.6%] females). No routine GRV assessment was noninferior to regular 6-hourly assessments for survival and days free from mechanical ventilation at 30 days (median [IQR], 25 [21-27] days in both groups; adjusted odds ratio [OR], 0.95 [95% CI, 0.86-1.05]). Results of the per-protocol analysis were consistent with the intention-to-treat analysis (adjusted OR, 1.01 [95% CI, 0.90-1.13]). The mean percentage of energy requirements achieved by 72 hours was 80.3% in the no routine GRV assessment group and 76.8% in the usual care group (adjusted mean difference, 3.2 [95% CI, 1.3-5.2] percentage points; P < .001). Conclusions and Relevance:Among critically ill children being enterally fed, not assessing GRV routinely was noninferior to regular assessments every 6 hours and significantly increased nutritional achievement at 72 hours. Trial Registration:isrctn.org Identifier: ISRCTN79668198.

BACKGROUND:In neonatal trials, verbal opt-out consent has been used to reduce burden on families and make recruitment more efficient and representative. It involves information provision through posters and leaflets before randomisation, and parents can verbally 'opt out' of their baby being randomised to the trial. There is limited understanding of how opt-out consent is operationalised in a multicentre neonatal trial, and its acceptability to staff and parents. OBJECTIVE:To explore views and experiences of verbal opt-out consent in neoGASTRIC, a neonatal randomised trial comparing routine and no routine measurements of gastric contents in preterm babies. METHODS:A mixed methods (questionnaires, interviews and focus groups) process evaluation within a trial. SETTING:Four UK neonatal units. PARTICIPANTS:253 participants: 167 staff (149 questionnaires; 18 across two focus groups), 86 parents (85 questionnaires; 15 interviews; 14 took part in both). RESULTS:Parents and staff supported opt-out consent in neoGASTRIC as interventions were viewed as low risk and non-invasive. Parents appreciated an appropriately timed research conversation; only 21% noticed study information banners/posters. Operationalisation of opt-out consent varied in terms of when information was provided and randomisation timing. Women approached during labour or within hours of birth reported feeling overwhelmed and lacking capacity to consider research. Some staff operationalised a modified opt-in approach. CONCLUSIONS:An appropriately timed verbal opt-out approach to consent was seen acceptable as proportionate in the neonatal context in a low-risk trial comparing different accepted clinical, non-pharmaceutical, practices. Findings informed neoGASTRIC and will guide approaches to consent in this setting.

Introduction Globally, half of all 6.2 million deaths in children are caused by acute illnesses which can be prevented if diagnosed and treated in time. We hypothesise that long elapsed travel time and delay in care can be tackled using telemedicine. The objective of this study is to determine the acceptability of linking ambulances that transport acutely ill children to a remote paediatric emergency physician using a simple audiovisual device.Methods We conducted a qualitative study to determine the acceptability of ambulance-based teleconsultation for the emergency care of acutely ill children informed by the Theoretical Framework of Acceptability. We developed semistructured guides using this framework and conducted five interviews with telemedicine physicians (TMPs), 18 interviews with parents of children who recently needed an ambulance and four focused groups with emergency medical technicians (EMTs) who transport children.Results All participants were supportive of using the telemedicine consultation during ambulance transport in the proposed trial as they felt that having access to a video-based physician would offer prompt intervention, particularly for critically ill children in crowded cities and remote regions with scarce resources. Parents believed that ambulance-based telemedicine would enhance their trust in EMTs and reduce their stress. The concerns related to the intervention included parental reluctance in using video cameras due to privacy issues, doubts about doctors’ treatment reliability, risk of miscommunication and inadequate parental education. To address these challenges, the groups proposed solutions such as joint training for EMTs and TMPs, educating parents about intervention processes, improving telecommunication infrastructure and promoting public awareness.Conclusion Parents, EMTs and TMPs mutually agreed that the use of telemedicine during ambulance transport can be successfully implemented through proper training and is acceptable in our population. All participants agreed that this intervention holds great potential to improve the survival of critically ill children.

Background Urinary tract infections (UTIs) are the most common serious bacterial infections in febrile infants. Current UK guidelines recommend parenteral antibiotics for infants under three months with suspected UTI, despite evidence supporting oral therapy in low-risk infants. Objectives To assess whether oral antibiotics are non-inferior to parenteral antibiotics for treating suspected UTIs based on treatment failure, need for additional therapy, and secondary outcomes. Design Multicentre, randomised controlled, open-label, non-inferiority trial with embedded internal pilot. Setting Twenty one paediatric emergency departments and assessment units across the UK. Participants Infants aged 29–90 days with suspected UTI, abnormal urinalysis, and low risk of invasive bacterial infection. Exclusion criteria included prematurity, prior hospitalisation, structural renal abnormalities, and clinical signs of sepsis or meningitis. Interventions Participants were randomised 1:1 to receive either oral antibiotics or standard care with intravenous (IV) antibiotics for 36–48 hours pending urine culture results. Main outcome measures The primary outcome was the requirement for additional parenteral antibiotics within seven days of randomisation. A range of secondary outcomes were also planned, including treatment failure, time to recovery, adverse events, antibiotic adherence, quality of life, family impact, and healthcare resource use. Feasibility outcomes collected during the internal pilot included recruitment rate, site activation, protocol adherence, and retention. Clinical outcomes were collected but not powered for formal comparison. Results 27 participants were recruited between 20 May 2024 and 13 March 2025 (which included the 6 month internal pilot), representing 27% of the pilot target. Protocol adherence was high, and no cases of meningitis occurred. Two cases of bacteraemia (one per randomised group) had uncomplicated clinical courses. Oral therapy was associated with shorter hospital stays and reduced parental time off work. Conclusions While trial procedures were successfully implemented, recruitment challenges suggest that a larger randomised trial of this treatment comparison is not feasible in this setting. Trial management Northern Ireland Clinical Trials Unit (NICTU) Trial registration ISRCTN Clinical Trials Registry, ISRCTN10907780, Trial Dates 20 May 2024 to 13 March 2025

OBJECTIVE:Providing adequate nutrition is a key aspect of pediatric intensive care, with enteral administration preferred. The regular measurement of gastric residual volume (GRV) to guide feeding is common, but it results in frequent feed interruptions due to a perceived high GRV. The GASTRIC-PICU (GRV to guide enteral feeding vs. routine measurement in mechanically ventilated critically ill children) randomized controlled trial aims to evaluate the clinical and cost-effectiveness of not routinely measuring GRV to guide enteral feeding compared with the usual practice of routine measurement. DESIGN:Multicenter, randomized, non-inferiority, open-label clinical trial with embedded health economic evaluation. SETTING:Twenty-three PICUs across United Kingdom, Scotland, Northern Ireland, and Switzerland. PATIENTS:Infants and children 37 weeks old or older corrected gestational age to 16 years admitted to participating PICUs, on mechanical ventilation and being enterally fed. INTERVENTION AND COMPARISON:Standard feeding protocols without routinely measuring GRV to guide feeding will be compared against standard feeding protocols with routine (at least 6-hourly) GRV measurement to guide feeding. MEASUREMENTS AND MAIN RESULTS:Randomization 1:1 between no routine GRV measurement and routine GRV measurement stratified by site, age at admission, and main reason for admission. "Research Without Prior Consent" will be used. The primary clinical outcome is a composite outcome of survival and days free from mechanical ventilation at 30 days (non-inferiority). The superiority co-primary outcome is the percentage of the child's estimated energy requirements achieved by 72 hours after randomization. The primary outcome of cost-effectiveness analysis is incremental net monetary benefits at 6 months. Baseline demographics and clinical status, daily nutritional data for the first 7 days, and discharge outcome, as well as longer-term survival and economic data will be collected. CONCLUSIONS:Trial findings will be disseminated in peer reviewed journals, via international conferences and in lay language via social media.

Importance Routine assessment of gastric residual volume (GRV) to guide enteral feeding in critically ill children is widespread but not based on evidence. Perceived high gastric volumes often lead to withholding feeds, impairing nutritional delivery. Objective To evaluate the effect of not routinely assessing GRV compared with assessments at least every 6 hours in children undergoing mechanical ventilation on the duration of mechanical ventilation and survival and achievement of nutritional targets. Design, Setting, and Participants A pragmatic, multicenter, randomized, noninferiority trial in 23 pediatric intensive care units (PICUs) in the UK and 1 in Switzerland. A total of 4700 children aged 0 to 16 years who were receiving invasive ventilation and starting enteral feeds were recruited between June 29, 2023, and December 7, 2025, with 30-day follow-up completed on January 6, 2026. Interventions Children were randomized (1:1) to receive usual care (GRV assessment every 6 hours) or no routine GRV assessment to guide enteral feeding. In the no routine GRV assessment group, feed tolerance was assessed using only clinical signs. All other enteral feeding practices followed local protocols. Main Outcomes and Measures The clinical co–primary outcome (noninferiority) was a composite of survival and days free from mechanical ventilation at 30 days. The nutritional co–primary outcome (superiority) was the percentage of children meeting energy requirements by 72 hours. Results Of the 4700 children randomized (2352 to the no routine GRV assessment group and 2348 to the usual care group), 4460 were included in the intention-to-treat analysis (median [IQR] age, 8 [1-44] months; 1925 [42.6%] females). No routine GRV assessment was noninferior to regular 6-hourly assessments for survival and days free from mechanical ventilation at 30 days (median [IQR], 25 [21-27] days in both groups; adjusted odds ratio [OR], 0.95 [95% CI, 0.86-1.05]). Results of the per-protocol analysis were consistent with the intention-to-treat analysis (adjusted OR, 1.01 [95% CI, 0.90-1.13]). The mean percentage of energy requirements achieved by 72 hours was 80.3% in the no routine GRV assessment group and 76.8% in the usual care group (adjusted mean difference, 3.2 [95% CI, 1.3-5.2] percentage points; P < .001). Conclusions and Relevance Among critically ill children being enterally fed, not assessing GRV routinely was noninferior to regular assessments every 6 hours and significantly increased nutritional achievement at 72 hours. Trial Registration isrctn.org Identifier: ISRCTN79668198

INTRODUCTION:Childhood mortality in the emergency setting is disproportionately high in low-income and middle-income countries (LMIC), with limited research dedicated to improving timely interventions, especially for critically ill children during transport. To perform essential prehospital paediatric research, there is a need for a tailored consent process, which reflects the specific needs and concerns of participants in this challenging research context. OBJECTIVE:The objective is to prospectively investigate stakeholder perceptions and preferences regarding consent processes for a specific paediatric ambulance-based telemedicine trial. METHODS:Exploratory qualitative study design using face-to-face semistructured interviews and focus group discussions. Data were analysed using thematic analysis. Participants included healthcare providers (paediatric telemedicine physicians and emergency medical technicians) and parents of children who required emergency transportation in Karachi, Pakistan. RESULTS:47 participants, ranging from 19 to 47 years old, were involved in in-depth interviews or focus group discussions. The participants comprised 29 healthcare workers and 18 parents. Among them, 9 were women and 38 were men. Expressing diverse attitudes towards different consent methods, the majority recommended a prospective written informed consent approach to build trust and provide legal protection. Participants understood the situational incapacity that occurs in emergency settings, emphasised the importance of keeping the consent brief and recommended a subsequent contact in 2-3 days after the emergency transport to reconfirm consent and answer any questions. CONCLUSION:Our interpretation of the findings revealed that participants preferred a staged consent process for telemedicine trials in LMIC paediatric emergency settings.

The Covid-19 pandemic profoundly disrupted societal systems, prompting community groups, voluntary organizations and employers to adapt rapidly to emerging needs. Here we present findings of a study conducted in the North West of England, exploring how groups and organisations adapted and responded to local needs at this time. We conducted semi-structured interviews with ‘key informants’ within local community voluntary, charity, faith or social enterprise (VCFSE) sector groups and organisations (n = 19) and large/ medium employers within any sector (n = 6). Interview transcripts were analysed thematically by a team of academic researchers and ‘Public Advisers’ with knowledge of local communities. Our findings reveal that community-based VCFSE groups and organisations played a critical role in addressing immediate needs such as food insecurity, isolation, and health vulnerabilities. This response was motivated by a strong sense of responsibility for the wellbeing of the clients and communities they served, and was enabled by their strong community networks, local knowledge, and ability to increase system capacity through collaboration. However, in a context of increased wellbeing needs later in the pandemic, many struggled to restart their core business, constrained by depleted resources and difficulties in interpreting and applying government ‘Covid-secure’ legislation and guidance. The study underscores the importance of local resilience, highlighting the VCFSE sector’s central role in addressing inequalities exacerbated by crises. It calls for substantial long-term investment to sustain this vital infrastructure, which is critical not only for recovery but also for preparedness for future societal shocks.

Improving the inclusion of under-served groups in clinical trials is increasingly being seen as a priority area for research funders and regulators. Adults who lack capacity to make an informed decision about taking part in trials are recognised as an under-served group. Researchers struggle to navigate the complex ethical, legal, and methodological issues surrounding trials involving adults lacking capacity to consent, leading to frequent exclusion of this population. Researchers have identified a need for greater knowledge about designing and conducting trials involving this population. Building on the CONSULT research programme, we developed stakeholder-informed training to help researchers design more inclusive trials. The CONSULT e-learning was developed in collaboration with a group of researchers with topic expertise and a lay advisory group with lived experience. It was developed over four phases: (1) establishing researchers’ training needs using an online survey; (2) developing the e-learning content including illustrative case studies, videos, and links to resources and further reading; (3) iterative piloting and refining of the content; (4) dissemination of the e-learning and initial evaluation. A set of informational materials about the e-learning were also developed. Informed by the stakeholder survey (n = 82), the CONSULT e-learning consists of four key modules covering the legal and ethical frameworks, consent and consultation processes, and methodological considerations, with the key role of public involvement threaded throughout. It was launched at a webinar (December 2024), with a post-webinar survey (n = 29) showing an increase in awareness about the importance of including adults lacking capacity in trials where they are a relevant population. Researchers also signalled their commitment to changing their research practice, suggesting that the e-learning has a role in facilitating greater inclusion of this under-served population in trials. The CONSULT e-learning is available online: www.capacityconsentresearch.com/training . Alongside tools such as the INCLUDE Impaired Capacity to Consent Framework, the CONSULT e-learning course aims to support researchers to develop the knowledge and skills needed to design and conduct higher-quality trials that are more inclusive of adults who lack capacity to consent. Further engagement, including with funders who increasingly require inclusion as a condition of funding, is needed.

Introduction Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard first-line treatment for atonic PPH. The PPH rate is increasing, and this may be partially related to the overuse of oxytocics in labour. Laboratory studies on myometrium suggest that repeated use of oxytocics leads to the saturation of oxytocin receptors and reduced therapeutic efficacy of oxytocin. Carboprost (a prostaglandin analogue) is usually reserved for second-line management of atonic PPH. A systematic review comparing the efficacy of carboprost and conventional uterotonics for PPH prophylaxis found that carboprost was associated with less blood loss, but around 15% of women experienced side effects. The study’s aim is to compare intramuscular carboprost with intravenous oxytocin for the initial treatment of PPH. In addition, to assess the cost-effectiveness of both treatments, participants’ views on the two treatments and the consent process.Methods and analysis COPE is a double-blind, double-dummy, randomised controlled trial that aims to recruit 2000 women (1:1 allocation, stratified by mode of birth) across 20 hospitals in the UK. Due to the emergency nature of PPH, COPE uses a research without prior consent (RWPC) model. Randomisation and treatment will occur if eligibility criteria are met once bleeding starts. Postnatal consent will be sought for disclosure of identifiable data and continued follow-up. Clinical efficacy outcomes will be collected at 24 and 48 hours or at hospital discharge, if sooner. Questionnaires will also be collected at 24 hours and 4 weeks postrandomisation. Cost-effectiveness will be based on the incremental cost per quality-adjusted life-year, calculated from the perspective of the NHS and personal social services.Ethics and dissemination This study has been approved by the Coventry and Warwickshire Research Ethics Committee (REC) (18/WM/0227) and the Health Research Authority. Results will be disseminated via peer-reviewed publications.Trial registration number ISRCTN16416766.

OBJECTIVE:To determine the feasibility of a trial investigating the optimal timing for the birth of women with a suspected late preterm and term SGA baby using either angiogenic biomarker-led care or standard care. DESIGN:A mixed methods study including a randomised feasibility trial, interviews, questionnaires and economic analysis. SETTING:Two tertiary maternity hospitals in the UK. POPULATION:Women with suspected SGA pregnancies between 32+0 weeks gestation and 37+6 weeks gestation. METHODS:Women were randomised in a 3:1 ratio to biomarker-led care versus standard care. Biomarker tests were either revealed, with birth delayed until 40 weeks if normal (sFlt-1/PlGF < 38 pg/mL) and considered from 37 weeks if abnormal (sFlt-1/PlGF ≥ 38 pg/mL), or concealed alongside standard care. MAIN OUTCOME MEASURES:Primary outcome was the feasibility of the study measured through the recruitment rate and adherence. Secondary outcomes were the qualitative, proof-of-concept and economic analyses. RESULTS:Out of 128 women invited to participate 78 women were recruited giving a recruitment rate of 60.1% (95% confidence interval 52%-69%). Sixty-seven of the 78 women consented to randomisation. Sixteen parents and 12 clinicians were interviewed. Fourty parents completed a questionnaire. Participants, partners and clinicians viewed the study as acceptable but experienced challenges in participation and delivering the study. There were no significant adverse events or differences in neonatal outcomes. Collection of health economics data was feasible. CONCLUSIONS:The clinical, qualitative and economic results support the acceptability of utilising sFlt-1/PlGF to refine SGA management after 32+0 weeks but the feasibility is less certain.

Objectives Platform trials were used successfully in adult populations during the COVID-19 pandemic. By testing multiple treatments within a single trial, platform trials can help identify the most effective treatments (and any interactions between treatments) for patients more quickly and with less burden for patients and their families. The aim of this qualitative research was to inform the design of the first adaptive platform trial for paediatric intensive care in the UK with young people, parents/carers and paediatric intensive care unit (PICU) staff.Design Qualitative semistructured focus group study. Data were analysed using reflexive thematic analysis.Participants Young people, parents/carers, and PICU medical, nursing and research staff.Setting The UK.Results A total of 86 participants (18 young people; 15 parents/carers; 53 PICU staff) took part in 1 of 10 focus groups between May and September 2023. Participants viewed the proposed PICU platform trial and use of research without prior consent to be acceptable. Findings provide insight into how the PICU platform trial should be designed and operationalised, including having a broad and inclusive population eligible for inclusion onto the platform trial, with different inclusion and exclusion criteria for each domain; starting the trial with no more than three domains and prioritising the outcomes of Child quality of life and Survival (all participants). Optimal governance structure and suggestions about how any challenges to the success of the full trial can be overcome are also presented.Conclusions Young people, parents/carers and PICU staff viewed the proposed PICU platform trial to be acceptable. These key stakeholders supported us with the design of an adaptive platform trial for PICU that has a rigorous methodology, yet can be operationalised in a family-centred way, to provide high-quality evidence that can support clinical decision-making and guide the treatment of critically ill children. Our findings have informed the PICU platform trial protocol.

Head and neck cancer (HaNC) can be debilitating, resulting in high symptom burden. Physical activity (PA) can improve quality of life; however, less than 9

Selective fetal growth restriction (sFGR) affects 10–15% of monochorionic twin pregnancies, leading to adverse perinatal outcomes such as stillbirth and cerebral palsy, with early-onset cases posing significant management challenges1, 2. Should the smaller twin not survive, the cotwin faces an approximately 15% risk of death and a 26% risk of neurological disability1. For managing early-onset sFGR, three primary strategies are considered: expectant management, which entails vigilant observation without direct intervention; selective termination of the smaller twin, to potentially improve the prognosis for the larger twin; and the use of placental laser photocoagulation, to disconnect the twins' shared blood vessels, aiming to mitigate risks associated with vascular connections. Each approach comes with its own set of risks and ethical dilemmas: expectant management can place a heavy emotional toll on parents due to the uncertainty of the twins' survival; selective termination might not align with some parents' values; and placental laser photocoagulation is technically challenging and has not yet been proved efficacious in sFGR cases as clearly as it has in other situations, such as twin-to-twin transfusion syndrome. Management options, diagnostic criteria, monitoring protocols and gestational age at birth for cases of sFGR vary amongst fetal medicine units3, 4. To date, the management of these cases has been guided by results obtained from retrospective cohorts5-7, meta-analyses8, 9 and guidelines1, 10, 11. In the Clinical Trials database, we found only one randomized controlled trial (RCT) that aimed to compare laser ablation and expectant management in monochorionic twins with sFGR12, 13, but the trial stopped recruitment prematurely. Our meta-analysis in 20198, encompassing 16 observational studies and 786 monochorionic twin pregnancies, examined perinatal outcomes according to management options and we concluded that, while expectant management was deemed reasonable for Type-I sFGR, laser ablation in Type-II/III sFGR was associated with higher mortality rates but lower morbidity. Therefore, we suggested a potential role for fetal therapy in severe cases of sFGR occurring at a gestational age far from viability. More recently, Buskmiller et al.9 compared perinatal outcomes following expectant management with those following laser ablation in a meta-analysis which included six studies and 299 monochorionic pregnancies with sFGR. They reported that laser ablation was linked to a higher risk of fetal death for the growth-restricted twin compared with expectant management (risk ratio (RR), 2.50; 95% CI, 1.43–4.37). However, laser treatment was associated with reduced abnormal neuroimaging findings in the normally growing twin (RR, 0.25; 95% CI, 0.07–0.97). Only one of the included studies was a RCT, while the others were observational cohorts, highlighting the need for an appropriately designed clinical trial to address this knowledge gap. The National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA)-funded FERN study, 'Intervention or Expectant Management for Early Onset Selective Fetal Growth Restriction in Monochorionic Twin Pregnancy', is a feasibility prospective mixed-methods cohort study comprising three distinct work packages (WP), to determine the acceptability and feasibility of conducting a RCT comparing the outcomes of intervention vs expectant management for early-onset sFGR in monochorionic twin pregnancies14. In this Opinion, we report the output of the FERN WP3 stakeholders' consensus meeting for determining the acceptability and feasibility of the proposed RCT. We also explore the feasibility of different study designs. Key stakeholders, including both UK-based and international FERN study grant co-applicants, collaborators, principal investigators of the study sites, sponsor representatives, Patient and Public Involvement and Engagement (PPIE) representatives, trialists and study statisticians, as well as parents with experience of a monochorionic twin pregnancy with sFGR, were invited to participate in the consensus development meeting. The clinical stakeholders included both fetal medicine specialists and neonatologists. We invited stakeholders to a hybrid face-to-face/virtual platform meeting hosted at the Royal College of Obstetricians and Gynaecologists in London in July 2023. The meeting was led by the FERN project's Chief Investigator and facilitated by an independent member who was not involved in the project and abstained from voting. The meeting followed a prespecified agenda, which included brief presentations of the results from WP2 (qualitative study) and WP3 (clinician survey) (Figure 1). The core group developed questions regarding the acceptability (willingness of parents and clinicians to participate in a trial of this nature) and feasibility (e.g. ability to recruit and randomize participants to intervention, retention and generalizability) of a RCT comparing the outcomes of intervention vs expectant management for early-onset sFGR in monochorionic twin pregnancies (Table S1). The questions were structured around several scenarios, including cases with abnormal or normal umbilical artery Doppler of the smaller twin and categorizations based on the type of sFGR (Type I, II or III). For each scenario, stakeholders were asked to vote on the acceptability and feasibility of conducting such a RCT, with options being 'No', 'Unsure' and 'Yes'. A priori, it was decided that if there were 50% or more votes of 'Yes' (for acceptability and/or feasibility) for each scenario, this would warrant further discussion about the plausibility of a trial. All stakeholders were treated as a unified group; i.e. the results were not categorized by stakeholder group. If the responses to all scenarios were not favorable (< 50% votes for acceptability and/or feasibility), then this would suggest that a trial was not acceptable or feasible. If particular scenarios were voted favorable (> 50% acceptability and/or feasibility) and others were not, then this was would suggest that a trial might be possible 'under certain conditions'. The poll was conducted using Poll Everywhere software (https://www.polleverywhere.com/). The proceedings of this meeting were undertaken as part of the ongoing FERN study, which received ethical approval from the Health Research Authority Southwest – Cornwall and Plymouth Ethics Committee. Out of the 80 stakeholders invited to the meeting, 28 participated in the consensus meeting, of whom 22 participated in the voting (Table S2). This work package focused on qualitative research, including interviews and focus groups with parents and clinicians to explore trial design, acceptability, feasibility and decision-making related to intervention or conservative management. Participants agreed that it is essential to answer the research question for two purposes: (1) to enable clinicians to counsel parents confidently about management options for monochorionic twin pregnancy affected by sFGR; and (2) to provide parents with more information to help them in making difficult decisions with respect to an affected pregnancy. However, neither parents nor clinicians found a RCT of intervention vs expectant management to be acceptable in this case. A few clinicians expressed support for a RCT, but most agreed it would be challenging to recruit participants. Various factors that influence parents' and clinicians' decision-making when the potential outcomes include death or serious disability include: inconsistency in clinical practice, the changing (evolving or inconsistent) nature of sFGR during pregnancy and the desire for more information before making decisions; the detailed findings from WP2 were published recently15. This international cross-sectional survey of 113 clinicians aimed to identify current practices in managing sFGR in monochorionic twin pregnancies. For early-onset sFGR in monochorionic diamniotic twin pregnancies, there was a general trend to manage Type-I sFGR expectantly, with weekly surveillance. However, there was variation in the monitoring and management of Type-II and Type-III sFGR cases. Overall, the WP3 clinician survey demonstrated considerable variation in diagnosis, monitoring and management options and an unmet need to generate robust evidence by high-quality research to address these uncertainties. The detailed findings from the WP3 clinician survey were published recently16. The poll results showed a clear consensus among stakeholders that it was neither acceptable nor feasible to conduct a RCT in the proposed format to evaluate the management of sFGR in these pregnancies (Table S1). The 50% 'Yes' threshold was not met for any scenario. Given the clear consensus among stakeholders that conducting a RCT in the proposed format to evaluate sFGR management was neither acceptable nor feasible, the discussion then focused on the barriers to delivering such a trial. These factors have the potential to impact negatively recruitment and randomization and subsequently affect patient retention in the proposed RCT, thereby significantly reducing trial feasibility. Since patient randomization and 'testing' of the protocol were not part of this feasibility study, these issues would require further exploration during a pilot phase incorporated into any subsequent trial. We discussed alternative study designs in which randomization is not necessary to answer the study question. However, the importance of RCTs as the gold standard for comparing treatments due to their comparison of two identical groups cannot be overemphasized. While considering the above study designs, other deliberations would include issues surrounding data quality control and data management, the choice of primary outcomes, both short-term and long-term, the use of composite outcome measures and data linkage with healthcare records as a potential strategy to address the rarity of the condition. The FERN stakeholders' group agreed that, while a RCT comparing the outcomes of intervention vs expectant management in early-onset sFGR may not be feasible or acceptable in the proposed format, alternative study designs such as propensity-score matching or an international multicenter observational cohort study may be plausible and appear promising to address this research question. The consensus meeting was very useful in determining the challenges to the proposed RCT. It provided a forum to address and deliberate on several challenging topics related to a future study design. Moreover, the meeting enabled us to gauge support and engagement for the proposed trial, extending beyond the insights from focus groups and interviews. While the relatively small number of stakeholders available for voting is a limitation, the view and results of the stakeholder group were consistent with those echoed in the WP2 focus group interviews and WP3 clinician interviews, reinforcing the validity of the consensus reached. This work is independent research funded by the National Institute for Health Research (NIHR Health Technology Assessment, NIHR128596 – FERN: Intervention or Expectant Management for Early Onset Selective Fetal Growth Restriction in Monochorionic Twin Pregnancy). The FERN Study acknowledges the support of the UK Clinical Research Network (UKCRN). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. A. Khalil, Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK; Fetal Medicine Unit, Liverpool Women's Hospital, University of Liverpool, Liverpool, UK S. Prasad, Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, UK J. J. Kirkham, Centre for Biostatistics, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK R. Jackson, Department of Statistics, Liverpool Clinical Trials Unit, University of Liverpool, Liverpool, UK K. Woolfall, Institute of Population Health, Department of Public Health, Policy and Systems, University of Liverpool, Liverpool, UK T. K. Mitchell, Institute of Population Health, Department of Public Health, Policy and Systems, University of Liverpool, Liverpool, UK M. Popa, Institute of Population Health, Department of Public Health, Policy and Systems, University of Liverpool, Liverpool, UK O. Yaghi, Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, UK T. Ricketts, Harris Wellbeing of Women Research Centre, Department of Women's and Children's Health, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK R. Ashcroft, City Law School, University of London, London, UK C. Bailie, Fetal Medicine, Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, UK E. Blennerhasset, Liverpool Women's NHS Foundation Trust, Liverpool, UK A. Breeze, Fetal Medicine Unit, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, UK A. Cameron, University of Glasgow, Glasgow, Scotland, UK N. Fenwick, Twins Trust, Woking, UK M. C. Haak, Department of Obstetrics, Fetal Medicine Unit, Leiden University Medical Center, Leiden, The Netherlands A. Healey, King's Health Economics, Health Service, and Population Research Department, King's College London, London, UK K. Hecher, University Medical Center Hamburg-Eppendorf, Department of Obstetrics and Fetal Medicine, Hamburg, Germany S. Leven, Twins Trust, Woking, UK E. Lopriore, Department of Paediatrics, Division of Neonatology, Leiden University Medical Center, Leiden, The Netherlands S. Meher, Birmingham Women's and Children's NHS Foundation Trust, Edgbaston, Birmingham, UK J. Mendoza, PPIE co-applicant, FERN project, Harris Wellbeing of Women Research Centre, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK T. Mousa, Department of Maternal and Fetal Medicine, University of Leicester, Leicester, UK S. Newell, Fetal Medicine Unit, St Michael's Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol, UK A. T. Papageorghiou, Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK H. Samarage, Fetal Medicine Unit, Northwick Park Hospital, London, UK J. Sandall, Division of Women's Health, King's College, London, Women's Health Academic Centre, King's Health Partners, St. Thomas' Hospital, London, UK M. Turner, Harris Wellbeing of Women Research Centre, Department of Women's and Children's Health, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK M. Watson, PPIE co-applicant, FERN project, Harris Wellbeing of Women Research Centre, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK Table S1 Poll questions designed to assess the acceptability and feasibility of a randomized controlled trial of intervention vs expectant in the management of selective fetal growth restriction (sFGR) in monochorionic twin pregnancies Table S2 Stakeholders who participated in the consensus meeting Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Pulmonary hypertension (PH) in newborn babies is a relatively rare, heterogeneous condition that has high associated mortality in the neonatal period and beyond. There are limited evidence-based strategies to treat or prevent this condition. Over the last two decades, there has been an increase in the number of studies assessing new therapies and treatment strategies in babies with PH. However, comparison of different treatments between studies is limited by inconsistency in outcome reporting. To address this issue, we aim to develop a core outcome set (COS) for neonates and infants less than 3 months of age, corrected for prematurity, diagnosed with PH, through international consensus with key stakeholders including parents and/or guardians, healthcare professionals and researchers. The development of the COS will be divided into two stages: (1) identification of potential outcomes through a mixed methods systematic literature review and qualitative interviews with parents and/or guardians of babies with pulmonary hypertension; (2) determining core outcomes through an online Delphi survey and consensus meeting. An advisory group with global membership including parents and/or guardians, healthcare professionals, and researchers recruited internationally was formed to guide the COS. The methodology utilized to develop a neonatal PH COS aims to ensure applicability and adoption in international settings and relevance across disciplines. The COS will help to improve trial design and homogeneity of outcomes reported in neonatal trials of PH. This will translate into higher-quality evidence for therapeutic strategies for PH in neonates.