OBJECTIVE:To assess the economic consequences of initiating full milk feeds from birth compared with intravenous fluids with gradual feeding in infants born preterm. DESIGN:Within-trial economic evaluation alongside a prospective, multicentre, randomised controlled trial (Fluids Exclusively Enteral from Day 1). A cost-consequence approach was used (revised from the planned cost-effectiveness analysis to avoid double counting length of stay within costs). SETTING:46 UK National Health Service (NHS) neonatal units. PATIENTS:Preterm infants born at 30+0to 32+6 weeks' gestation. INTERVENTIONS:Infants were allocated to either full milk feeds or gradual feeding with intravenous support within 3 hours of birth. MAIN OUTCOME MEASURE:Resource use and costs were captured from birth to 6 weeks' corrected age. Costs were assessed from an NHS and personal social services perspective. The primary clinical outcome was length of hospital stay. RESULTS:2088 infants were enrolled. There was no statistically significant difference in mean (95% CI) length of hospital stay between groups (-0.050 days (-0.638 to 0.538)). Mean total costs were £670 lower in the full milk group (95% CI: -£1562 to £223; p=0.141). Subgroup analyses suggested lower costs among infants born at 30 weeks' gestation and those below the 10th birth weight centile; no evidence of interaction was found. CONCLUSIONS:Initiating full milk feeds from birth was associated with a modest reduction in costs compared with gradual feeding. While overall hospital stays and costs were not significantly reduced, early full feeding may offer economic advantages in selected subgroups. Further research is needed to assess long-term outcomes. TRIAL REGISTRATION NUMBER:ISRCTN89654042.

Decentralised clinical trials (DCTs) may help address underrepresentation in digital mental health research, but their effectiveness in reaching underserved populations is unclear. This review assessed the reporting of equity-relevant demographic data in DCTs to identify groups at risk of exclusion and barriers and facilitators to inclusive participation. A systematic search was conducted in MEDLINE, PsycINFO, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies reporting on mental health interventions evaluated via remote, online, virtual, or hybrid DCTs, published in English from 2020-2026 (last search date: 01/07/2025), that reported participant demographics. Demographic data were extracted and summarised according to the PROGRESS-Plus framework. Demographic frequencies were compared to national population statistics. Thematic analysis identified barriers and enablers to inclusive participation in DCTs. Fifty-nine papers reporting 57 DCTs were included. Studies involved a range of mental health and neurodevelopmental conditions across the ages. Gender (100%) and age (100%) were universally reported. Reporting of other PROGRESS-Plus variables across the 57 DCTs was limited: social capital (43.9%); race/ethnicity (40.4%); occupation (36.8%); socioeconomic status (35.1%); place of residence (12.3%); religion (5.3%), and non-mental health disability (1.8%). Participants from ethnic minority backgrounds, males, unemployed individuals, and those with lower educational attainment were consistently underrepresented. While rural populations were better represented in Australian studies, data on poverty, religion, and social capital were limited and varied in representativeness. Most studies focused on adults aged 18-50 years. Thematic analysis identified key barriers including, digital exclusion, low digital literacy, cognitive and sensory challenges. Facilitators included therapist or navigator support and simplified onboarding. Equity variables are persistently underreported. DCTs do not effectively engage underserved populations in mental health research, meaning digital interventions are evaluated on unrepresentative samples. This risks perpetuating, and exacerbating, existing health inequalities, limiting the real-world impact of digital mental health solutions.

Background Randomisation in randomised controlled trials (RCTs) is intended to guard against selection bias by creating unpredictable sequences. Some randomisation methods, however, aim to achieve better balance between groups being compared at the expense of predictability. This study aims to investigate the extent to which recruiters into RCTs attempt to predict upcoming allocations, hence how concerned trialists should be about using more predictable randomisation methods. Methods We designed a short survey asking recruiters questions about the practice of predicting allocations before randomisation. The survey was circulated to R&I departments of hospitals in England involved in recruiting to randomised controlled trials. Two versions of the survey were employed, one explicitly referencing “subversion” of the randomisation, and one that did not use this word to investigate whether the framing of the research changed participants responses. A summary of counts and percentages of responses is presented. Results 122 participants responded to the survey. 30% of responders felt that they may be able to predict the next allocation in a sequence dependent on the information available, with 20% responding that they currently work on a trial where themselves or a colleague has attempted to guess the next allocation. 65 received the version that included reference to “subversion”, whilst 57 received the alternative version. There was not a notable difference in responses for the two versions. Conclusion This survey provides evidence that some recruiters do attempt to predict what the upcoming allocation will be. Whilst we do not know the motivations behind these predictions, they highlight the need for researchers to produce unpredictable allocation sequences.

Hearing loss is a prevalent condition that impacts on social, mental and physical health, and has a significant economic burden. Hearing aids can improve the quality of life for those living with hearing loss; however, low and inconsistent use remains common. Within the National Health Service (NHS), follow-up care for new hearing aid users is highly variable and often lacks structure, which may contribute to low use. The FAMOUS trial investigates whether a structured care model for follow-up, combined with evidence-based behaviour change interventions, improves hearing aid use compared to usual care. FAMOUS is a multi-centre, two-arm parallel-group cluster randomised controlled trial (CRCT) with integral internal pilot, economic, and process evaluations. The trial involves 36 NHS audiology services and compares two types of follow-up for new adult hearing aid users: structured care, which includes personalised action plans, early monitoring, and routine follow-up at 6 weeks post-fitting, to usual care, which includes the offer of a follow-up 6–12 weeks after fitting. Recruitment is conducted through participating services over 3 months, with pseudo-anonymised routine data collected from electronic medical records of all patients who attend. Consent and outcomes are then collected from patients at 12 weeks post-fitting. For patients who provide consent to future contact, the primary outcome (self-reported daily hearing aid use) is collected at 12 months post-fitting. Secondary outcomes (quality-of-life (QoL), hearing-related disability, and economic measures) are collected at both timepoints. Qualitative interviews with a subset of patients and hearing professionals in the intervention arm will assess the acceptability and implementation of the intervention. Statistical analyses, including mixed-effects regression modelling, will be conducted under an intention-to-treat framework. FAMOUS addresses a critical evidence gap regarding the potential benefits of follow-up care for new hearing aid users. If the intervention is successful, it can be rolled out nationally using existing facilities with limited impact on resources, identified in the economic analysis, and would improve hearing aid use and quality of life for those living with hearing loss. Prospectively registered with the International Standard Randomised Controlled Trial Number (ISRCTN) 10589817. Date of registration: 01/09/2022.

Background:Emotional disorders are common in children and young people and can significantly impair their quality of life. Evidence-based treatments require a timely and appropriate diagnosis. The utility of standardised diagnostic assessment tools may aid the detection of emotional disorders, but there is limited evidence of their clinical value. Objectives:To assess the clinical effectiveness and cost effectiveness of a standardised diagnostic assessment for children and young people with emotional difficulties referred to Child and Adolescent Mental Health Services. A nested qualitative process evaluation aimed to identify the barriers and facilitators to using a standardised diagnostic assessment tool in Child and Adolescent Mental Health Services. Design:A United Kingdom, multicentre, two-arm, parallel-group randomised controlled trial with a nested qualitative process evaluation. Setting:Eight National Health Service Trusts providing multidisciplinary specialist Child and Adolescent Mental Health Services. Participants:Children and young people aged 5-17 years with emotional difficulties referred to Child and Adolescent Mental Health Services, excluding emergency/urgent referrals that required an expedited assessment. In the qualitative process evaluation, 15 young people aged 16-17 years, 38 parents/carers and 56 healthcare professionals participated in semistructured interviews. Interventions:Participants were randomly assigned (1 : 1) following referral receipt to intervention (the development and well-being assessment) and usual care, or usual care only. Main outcome measures:Primary outcome was a clinician-made diagnosis decision about the presence of an emotional disorder within 12 months of randomisation, collected from Child and Adolescent Mental Health Services clinical records. Secondary outcomes collected from clinical records included referral acceptance, time to offer and start treatment/interventions and discharge. Data were also self-reported from participants through online questionnaires at baseline, 6 and 12 months post randomisation, and the cost effectiveness of the intervention was investigated. Results:One thousand two hundred and twenty-five (1225) children and young people were randomly assigned (1 : 1) to study groups between 27 August 2019 and 17 October 2021; 615 were assigned to the intervention and 610 were assigned to the control group. Adherence to the intervention (full/partial completion of the development and well-being assessment) was 80% (494/615). At 12 months, 68 (11%) participants in the intervention group received an emotional disorder diagnosis versus 72 (12%) in the control group [adjusted risk ratio 0.94 (95% confidence interval 0.70 to 1.28); p = 0.71]. Child and Adolescent Mental Health Services acceptance of the index referral [intervention 277 (45%) vs. control 262 (43%); risk ratio: 1.06 (95% confidence interval: 0.94 to 1.19)] or any referral by 18 months [intervention 374 (61%) vs. control 352 (58%); risk ratio: 1.06 (95% confidence interval: 0.97 to 1.16)] was similar between groups. There was no evidence of any differences between groups for any other secondary outcomes. The qualitative nested process evaluation identified a number of barriers and facilitators to the use of the development and well-being assessment during the trial, particularly at the assessment and diagnosis stages of the Child and Adolescent Mental Health Services pathway. Limitations:It was not possible to mask participants, clinicians or site researchers collecting source data to treatment allocation. Conclusions:We found no evidence that completion of the development and well-being assessment aided the detection of emotional disorders in this study. Using the development and well-being assessment in this way cannot be recommended for clinical practice. Future research:To determine longer-term service use outcomes and to investigate whether receipt of a clinical diagnosis makes a difference to clinical outcomes and care/intervention receipt. Funding:This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/96/09.

Body Dysmorphic Disorder (BDD) is impairing yet often under-detected in children and young people (CYP). This paper aims to describe the characteristics and 12-month outcomes of clinically referred CYP based on their likelihood of having BDD. This paper investigated 307 CYP aged 11–17 years from the STandardised DIagnostic Assessment (STADIA) trial for CYP with emotional difficulties referred to Child and Adolescent Mental Health Services (CAMHS). CYP and/or their parents completed the Development and Wellbeing Assessment (DAWBA) to assess the likelihood of meeting diagnostic criteria for emotional disorders, including BDD. Baseline and 12-month follow-up measures were collected from self- and/or parent- reports and healthcare records. Overall, 6.2

Background The STADIA trial evaluated the effectiveness of a standardised diagnostic assessment tool for children and young people (CYP) referred to Child and Adolescent Mental Health Services. Six- and 12-month follow-up questionnaires were completed by either CYP, parents/carers or both depending on the CYP’s age. A voucher was given upon completion of the questionnaires. A Study Within A Trial (SWAT) was embedded to investigate the effect of voucher timing and value on questionnaire return. Methods Participants were randomly allocated to either: (A) receive a £10 voucher at each time point, conditional on completion of the questionnaire or (B) a £20 voucher on completion of their 12-month questionnaire. Outcomes included return of at least one questionnaire, questionnaire return at both 6- and 12-month follow-up, number of questionnaires returned (0,1,2) and time from randomisation to questionnaire return. Parent/carers, 11–15-year-olds and 16–17-year-olds were analysed separately. For each, between group comparisons were presented for each outcome along with 95% confidence intervals (CI). Results 284 participants were recruited (142 per arm). There was evidence of increased questionnaire return at both time points when giving two £10 vouchers, for 11–15-year-olds (adjusted risk ratio (ARR): 1.72 (95% confidence interval (CI):1.15 to 2.56)) and parents/carers (ARR 1.18 (95% CI:1.01 to 1.38)) but not for 16–17-year-olds (ARR 1.01 (95% CI:0.58 to 1.75)). Similarly, an increased number of questionnaires were returned for 11–15-year-olds (common odds ratio (COR): 3.25: (95% CI:1.41 to 7.52)) and parents/carers (COR 1.95 (95% CI:1.09 to 3.47)) but not for 16–17-year-olds (COR 1.18 (95% CI:0.29 to 4.77)). Discussion Smaller but regular incentives may increase questionnaire return within a trial rather than larger incentives at the end of follow-up. However, due to the small sample size, further research is required to confirm these findings both in the study population and wider population.

BackgroundStandardised Diagnostic Assessment tools, such as the Development and Well‐Being Assessment (DAWBA), may aid detection and diagnosis of emotional disorders but there is limited real‐world evidence of their clinical or cost effectiveness.MethodsWe conducted a multicentre, two‐arm parallel group randomised controlled trial in eight large National Health Service Trusts in England providing multidisciplinary specialist Child and Adolescent Mental Health Services (CAMHS). Participants (5–17 year‐olds with emotional difficulties referred to CAMHS) were randomly assigned (1:1), following referral receipt, to either receive the DAWBA and assessment‐as‐usual (intervention group) or assessment‐as‐usual (control group). Data were self‐reported by participants (parents and/or young person, depending on age) at baseline, 6‐ and 12‐month post‐randomisation and collected from clinical records up to 18 months post‐randomisation. The primary outcome was a clinician‐made diagnosis decision about the presence of an emotional disorder within 12 months of randomisation. Trial registration: ISRCTN15748675.ResultsIn total, 1,225 children and young people (58% female sex) were randomised (615 intervention; 610 control). Adherence to the intervention (full/partial completion) was 80% (494/615). At 12 months, 68 (11%) participants in the intervention group received an emotional disorder diagnosis versus 72 (12%) in the control group (adjusted risk ratio (RR) 0.94 [95% CI 0.70, 1.28]). The intervention was not cost effective. There was no evidence of any differences between groups for service‐related or participant‐reported secondary outcomes, for example, CAMHS acceptance of the index referral (intervention 277 (45%) versus control 262 (43%); RR: 1.06 [95% CI: 0.94, 1.19]) was similar between groups.ConclusionsAs delivered in this pragmatic trial, we found no evidence for the effectiveness or cost effectiveness of using a Standardised Diagnostic Assessment tool in aiding the detection of emotional disorders or clinical outcomes in clinically referred children and young people. Despite regular efforts to encourage clinicians to view the DAWBA report and consider its findings as part of assessment and diagnosis, we did not collect data on usage and therefore cannot confirm the extent to which clinicians did this. As a pragmatic trial that aimed to test the effectiveness of incorporating the DAWBA into usual practice and clinical care, our study found that, in the format as delivered in this trial, there was no impact on diagnosis or clinical outcomes.

Objective Catheter-related sepsis (CRS) is a major complication with significant morbidity and mortality. Evidence is lacking regarding the most appropriate antiseptic for skin disinfection before percutaneous central venous catheter (PCVC) insertion in preterm neonates. To inform the feasibility and design of a definitive randomised controlled trial (RCT) of two antiseptic formulations, we conducted the Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) feasibility study to assess catheter colonisation, sepsis, and skin morbidity. Design Feasibility RCT. Setting Two UK tertiary-level neonatal intensive care units. Patients Preterm infants born <34 weeks’ gestation scheduled to undergo PCVC insertion. Interventions Skin disinfection with either 2% chlorhexidine gluconate (CHG)-aqueous or 2% CHG-70% isopropyl alcohol (IPA) before PCVC insertion and at removal. Primary outcome Proportion in the 2% CHG-70% IPA arm with a colonised catheter at removal. Main feasibility outcomes Rates of: (1) CRS, catheter-associated sepsis (CAS), and CRS/CAS per 1,000 PCVC days; (2) recruitment and retention; (3) data completeness. Safety outcomes Daily skin morbidity scores recorded from catheter insertion until 48 hours post-removal. Results 116 babies were randomised. Primary outcome incidence was 4.1% (95% confidence interval: 0.9% to 11.5%). Overall catheter colonisation rate was 5.2% (5/97); CRS 2.3/1000 catheter days; CAS 14.8/1000 catheter days. Recruitment, retention and data completeness were good. No major antiseptic-related skin injury was reported. Conclusions A definitive comparative efficacy trial is feasible, but the very low catheter colonisation rate would make a large-scale RCT challenging due to the very large sample size required. ARCTIC provides preliminary reassurance supporting potential safe use of 2% CHG-70% IPA and 2% CHG-aqueous in preterm neonates. Trial registration number ISRCTN82571474.

Background There exist many different methods of allocating participants to treatment groups during a randomised controlled trial. Although there is research that explores trial characteristics that are associated with the choice of method, there is still a lot of variety in practice not explained. This study used qualitative methods to explore more deeply the motivations behind researchers’ choice of randomisation, and which features of the method they use to evaluate the performance of these methods. Methods Data was collected from online focus groups with various stakeholders involved in the randomisation process. Focus groups were recorded and then transcribed verbatim. A thematic analysis was used to analyse the transcripts. Results Twenty-five participants from twenty clinical trials units across the UK were recruited to take part in one of four focus groups. Four main themes were identified: how randomisation methods are selected; researchers’ opinions of the different methods; which features of the method are desirable and ways to measure method features. Most researchers agree that the randomisation method should be selected based on key trial characteristics; however, for many, a unit standard is in place. Opinions of methods were varied with some participants favouring stratified blocks and others favouring minimisation. This was generally due to researchers’ perception of the effect these methods had on balance and predictability. Generally, predictability was considered more important than balance as adjustments cannot be made for it; however, most researchers felt that the importance of these two methods was dependent on the design of the study. Balance is usually evaluated by tabulating variables by treatment arm and looking for perceived imbalances, predictability was generally considered much harder to measure, partly due to differing definitions. Conclusion There is a wide variety in practice on how randomisation methods are selected and researcher’s opinions on methods. The difference in practice observed when looking at randomisation method selection can be explained by a difference in unit practice, and also by a difference in researchers prioritisation of balance and predictability. The findings of this study show a need for more guidance on randomisation method selection.

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. METHODS:This study employed a mixed methods approach involving three stages: (I) a quantitative study using a cohort of 200 studies (from a major UK funder published between 2016 and 2020) to assess the impact of blinding statisticians on the proportion of trials reporting a statistically significant finding for the primary outcome(s); (II) a qualitative study using focus groups to determine the perspectives of key stakeholders on the practice of blinding trial statisticians; and (III) combining the results of stages I and II, along with a stakeholder meeting, to develop guidance for UK CTUs. RESULTS:After screening abstracts, 179 trials were included for review. The results of the primary analysis showed no evidence that involvement of an unblinded trial statistician was associated with the likelihood of statistically significant findings being reported, odds ratio (OR) 1.02 (95% confidence interval (CI) 0.49 to 2.13). Six focus groups were conducted, with 37 participants. The triangulation between stages I and II resulted in developing 40 provisional statements. These were rated independently by the stakeholder group prior to the meeting. Ten statements reached agreement with no agreement on 30 statements. At the meeting, various factors were identified that could influence the decision of blinding the statistician, including timing, study design, types of intervention and practicalities. Guidance including 21 recommendations/considerations was developed alongside a Risk Assessment Tool to provide CTUs with a framework for assessing the risks associated with blinding/not blinding statisticians and for identifying appropriate mitigation strategies. CONCLUSIONS:This is the first study to develop a guidance document to enhance the understanding of blinding statisticians and to provide a framework for the decision-making process. The key finding was that the decision to blind statisticians should be based on the benefits and risks associated with a particular trial.

Background Patient-reported outcome measures (PROMs) are commonly used in eczema clinical trials. Several trials have used PROMs weekly for symptom monitoring. However, the increased frequency of patient-reported symptom monitoring may prompt participants to enhance the self-management of eczema and increase standard topical treatment use that can lead to improvements in outcomes over time. This is concerning as weekly symptom monitoring may constitute an unplanned intervention, which may mask small treatment effects and make it difficult to identify changes in the eczema resulting from the treatment under investigation. Objectives To evaluate the effect of weekly patient-reported symptom monitoring on participants' outcomes and to inform the design of future eczema trials. Methods This was an online parallel-group nonblinded randomized controlled trial. Parents/carers of children with eczema and young people and adults with eczema were recruited online, excluding people scoring < 3 points on the Patient Oriented Eczema Measure (POEM), to avoid floor effects. Electronic PROMs were used for data collection. Participants were allocated using online randomization (1 : 1) to weekly POEM for 7 weeks (intervention) or no POEM during this period (control). The primary outcome was change in eczema severity based on POEM scores, assessed at baseline and week 8. Secondary outcomes included change in standard topical treatment use and data completeness at follow-up. Analyses were conducted according to randomized groups in those with complete data at week 8. Results A total of 296 participants were randomized from 14 September 2021 to 16 January 2022 ( 71% female, 77% white, mean age 26.7 years). The follow-up completion rate was 81.7% [n = 242; intervention group, n = 118/147 ( 80.3%); control group n = 124/149 (83.2%)]. After adjusting for baseline disease severity and age, eczema severity improved in the intervention group (mean difference in POEM score -1.64, 95% confidence interval -2.91 to -0.38; P = 0.01). No between-group differences were noted in the use of standard topical treatments and data completeness at follow-up. Conclusions Weekly patient-reported symptom monitoring led to a small perceived improvement in eczema severity.

To understand whether the mental health of children and young people (CYP) with and without attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) were differentially affected by COVID-19. We analysed data (n = 6507) from the Co-Space study, a UK web-based longitudinal survey. CYP with ADHD (n = 160;2.5%), ASD (n = 465;7%), and ADHD + ASD (n = 155;2.4%) were compared with a reference group (n = 5727;88%) using parent-completed questionnaires [Strengths and Difficulties Questionnaire (SDQ) & Pandemic Anxiety Scale (PAS)]. Baseline to 1-month follow-up differences were compared using linear regression models. CYP with ADHD and/or ASD had higher scores at baseline than other CYP. At follow-up, CYP with ASD showed small but significant improvements in symptoms (SDQ), compared with the reference group. CYP with ASD experienced a worsening of disease anxiety (PAS) and CYP with ADHD a deterioration in functional impairment. These findings indicate a mixed pattern of pandemic-related impact for CYP with ADHD and/or ASD.

Hierarchical models are recommended for meta-analysis of test accuracy studies. Hierarchical models such as the bivariate and hierarchical summary receiver operating characteristic models are recommended for test accuracy meta-analysis. The models can be fitted in a frequentist or Bayesian statistics framework. This chapter presents analyses performed using both frequentist and Bayesian approaches wherever possible. It provides an overview of how to fit the hierarchical models within a frequentist framework using three software packages (SAS, Stata and R) and within a Bayesian framework using rjags. The chapter also provides suggestions on meta-analyses of problematic or atypical data sets, including simplifying hierarchical models for meta-analysis of sparse data. Using a Cochrane Review of diagnostic test accuracy as an example, it then illustrates latent class meta-analysis and concludes with a summary and information on additional resources.

Introduction Emotional disorders (such as anxiety and depression) are associated with considerable distress and impairment in day-to-day function for affected children and young people and for their families. Effective evidence-based interventions are available but require appropriate identification of difficulties to enable timely access to services. Standardised diagnostic assessment (SDA) tools may aid in the detection of emotional disorders, but there is limited evidence on the utility of SDA tools in routine care and equipoise among professionals about their clinical value. Methods and analysis A multicentre, two-arm, parallel group randomised controlled trial, with embedded qualitative and health economic components. Participants will be randomised in a 1:1 ratio to either the Development and Well-Being Assessment SDA tool as an adjunct to usual clinical care, or usual care only. A total of 1210 participants (children and young people referred to outpatient, specialist Child and Adolescent Mental Health Services with emotional difficulties and their parent/carers) will be recruited from at least 6 sites in England. The primary outcome is a clinician-made diagnosis about the presence of an emotional disorder within 12 months of randomisation. Secondary outcomes include referral acceptance, diagnosis and treatment of emotional disorders, symptoms of emotional difficulties and comorbid disorders and associated functional impairment. Ethics and dissemination The study received favourable opinion from the South Birmingham Research Ethics Committee (Ref. 19/WM/0133). Results of this trial will be reported to the funder and published in full in the Health Technology Assessment (HTA) Journal series and also submitted for publication in a peer reviewed journal. Trial registration number ISRCTN15748675; Pre-results.

Background In the UK, approximately 8% of live births are preterm (before 37 weeks gestation), more than 90% of whom are born between 30 and 36 weeks, forming the largest proportion of a neonatal units’ workload. Neonatologists are cautious in initiating full milk feeds for preterm infants due to fears of necrotising enterocolitis (NEC). There is now evidence to dispute this fear. Small studies have shown that feeding preterm infants full milk feeds enterally from birth could result in a shorter length of hospital stay, which is important to parents, clinicians and NHS services without increasing the risk of NEC. This trial aims to investigate whether full milk feeds initiated in the first 24 h after birth reduces the length of hospital stay in comparison to introduction of gradual milk feeding with IV fluids or parenteral nutrition. Methods FEED1 is a multi-centre, open, parallel group, randomised, controlled superiority trial of full milk feeds initiated on the day of birth versus gradual milk feeds for infants born at 30 +0 to 32 +6 (inclusive) weeks gestation. Recruitment will take place in around 40 UK neonatal units. Mothers will be randomised 1:1 to full milk feeds, starting at 60 ml/kg day, or gradual feeds, as per usual local practice. Mother’s expressed breast milk will always be the first choice of milk, though will likely be supplemented with formula or donor breast milk in the first few days. Feeding data will be collected until full milk feeds are achieved (≥ 140 ml/kg/day for 3 consecutive days). The primary outcome is length of infant hospital stay. Additional data will be collected 6 weeks post-discharge. Follow-up at 2 years (corrected gestational age) is planned. The sample size is 2088 infants to detect a between group difference in length of stay of 2 days. Accounting for multiple births, this requires 1700 women to be recruited. Primary analysis will compare the length of hospital stay between groups, adjusting for minimisation variables and accounting for multiple births. Discussion This trial will provide high-quality evidence on feeding practices for preterm infants. Full milk feeds from day of birth could result in infants being discharged sooner. Trial registration ISRCTN ISRCTN89654042 . Prospectively registered on 23 September 2019: ISRCTN is a primary registry of the WHO ICTRP network, and all items from the WHO Trial Registration dataset are included.

The Covid-19 pandemic and mitigation approaches, including lockdowns and school closures, are thought to have negatively impacted children and young people’s (CYP) mental health. However, the impact for clinically referred CYP is less clear. We investigated differences in the mental health of CYP referred to specialist Child and Adolescent Mental Health Services (CAMHS) before and since the onset of the pandemic. Using baseline data (self- and parent- completed Mood and Feelings Questionnaire and Strengths and Difficulties Questionnaire) from an ongoing RCT (STADIA; ISRCTN: 15748675) in England involving 5–17-year-olds with emotional difficulties recently referred to CAMHS (non-urgent referrals), with repeated cross-sectional comparisons of CYP (n = 1028) recruited during 5 different time periods: (1) Before schools were closed (Group 1 (pre-pandemic); n = 308; 27.08.2019–20.03.2020). (2) Early pandemic period until schools fully re-opened, which included the first national lockdown, its easing and the summer holidays (Group 2 (in-pandemic); n = 183; 21.03.2020–31.08.2020). (3) The following school-term—schools fully re-opened and remained open, including during the second national lockdown (Group 3 (in-pandemic); n = 204; 01.09.2020–18.12.2020). (4) Schools closed as part of the third national lockdown (Group 4 (in-pandemic); n = 101; 05.01.2021–07.03.2021). (5) Schools re-opened and remained open, until the school summer holidays (Group 5 (in-pandemic); n = 232; 08.03.2021–16.07.2021). Most CYP scored above cutoff for emotional problems and depression, with three-quarters meeting criteria for a probable disorder (‘caseness’). The groups did not differ on parent-rated mental health measures. However, self-rated emotional problems, depression, functional impairment and caseness appeared to be higher amongst participants recruited in the two periods following school re-openings. In particular, functional impairment and caseness were greater in Group 5 compared with Group 2. Although symptom severity or impairment did not change in the initial pandemic period, self-reported difficulties were greater during the periods after schools re-opened. This suggests possible greater stresses in the adjustment to re-starting school following recurrent lockdowns and school closures.