Background Type 1 diabetes is an autoimmune disease affecting over 400,000 children and adults in the United Kingdom for which currently the only available therapy is insulin. Objective(s) To determine the efficacy and safety of the monoclonal antibody ustekinumab targeting the interleukin 12/interleukin 23 immune pathway that generates T helper 1/T helper 17 T cells to slow down the autoimmune process and preserve beta cell production in type 1 diabetes. Design Randomised, double-blind, placebo-controlled, parallel-group phase II trial. Setting Paediatric and young adult diabetes clinics across 16 sites in the United Kingdom. Participants Newly diagnosed with type 1 diabetes and aged 12–18 years. Eligibility criteria Type 1 diabetes confirmed by islet autoantibody testing, within 100 days of first insulin injection, and with residual beta cell function (stimulated C-peptide level > 0.2 nmol/l). Interventions Ustekinumab at the highest approved doses or control (saline) subcutaneously at weeks 0, 4 and 12 and subsequently every 8 weeks to week 44 (seven doses). Main outcome measures Preservation of Mixed Meal Tolerance Test stimulated 2-hour insulin C-peptide area under the curve at week 52 as compared to control (saline) treatment by analysis of covariance adjusted for baseline parameters. Randomisation 2 : 1 Remote computerised randomisation with minimisation by age and baseline C-peptide groups. Blinding Blinding of participants, investigators, laboratory and trial staff. Numbers randomised Seventy-two participants were randomised, 60% male, 18% aged 16–18 years. Recruitment Two hundred and eight potentially eligible patients were approached, and 88 patients were screened. Four participants were lost to follow-up (6%). Four participants withdrew from the treatment but attended the primary end-point assessment. Numbers analysed Six participants were missing baseline data for the primary analysis. The final analysable sample was n = 62. Outcome Ustekinumab was associated with a 49% higher endogenous stimulated insulin production than control at week 52 after adjustments for baseline factors [geometric ratio of ustekinumab to control was 1.49 (95% confidence interval 1.08 to 2.06; p = 0.02)]. Secondary analyses showed no difference in C-peptide at week 28 suggesting that the effect was ‘late’ or ‘delayed’. Ancillary analysis showed a significant reduction in activated T helper 17.1 T cells ( p < 0.001) in the treatment group which was associated with C-peptide preservation from week 28 to week 52. Harms No severe adverse events were reported and there were no differences between ustekinumab and control groups in the proportion of participants overall experiencing mild (87% vs. 88%) or moderate (32% vs. 32%) events. Limitations Sensitivity analysis showed the primary end point to be robust to exclusion of small numbers of participants with some protocol deviations and extreme values in key covariates, but not to imputation of all missing data. Conclusions Ustekinumab appears to slow down the autoimmune process providing the first clinical trial evidence that interleukin 17-secreting T cells play a pathogenic role in type 1 diabetes. Alone, it is insufficient to halt the autoimmune process. Future work Replication of this result is ongoing in a trial with a similar design in Canada. If confirmed, consideration may be given to testing other drugs targeting the interleukin 17 pathway, using ustekinumab in combination with other agents or using it earlier in the disease pathway (preclinical disease) since it is so well tolerated and simple to use. Study registration Current Controlled Trials ISRCTN14274380. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 16/36/01) and is published in full in Efficacy and Mechanism Evaluation ; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

Incisional hernia (IH) is a common complication of colorectal surgery, affecting up to 30% of patients at 2 years. Given the associated morbidity and high recurrence rates after attempted repair of IH, emphasis should be placed on prevention. There is an association between surgeon volume and outcomes in hernia surgery, yet there is little evidence regarding impact of the seniority of the surgeon performing abdominal wall closure on IH rate. The aim of our study was to assess the rates of IH at 1 year following abdominal wall closure between junior and senior surgeons in patients undergoing elective colorectal surgery.

Immunotherapy targeting the autoimmune process in type 1 diabetes (T1D) can delay the loss of β-cells but needs to have minimal adverse effects to be an adjunct to insulin in the management of T1D. Ustekinumab binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, targeting development of T helper 1 cells and T helper 17 cells (TH1 and TH17 cells) implicated in the pathogenesis of T1D. We conducted a double-blind, randomized controlled trial of ustekinumab in 72 adolescents aged 12-18 years with recent-onset T1D. Treatment was well tolerated with no increase in adverse events. At 12 months, β-cell function, measured by stimulated C-peptide, was 49% higher in the intervention group (P = 0.02), meeting the prespecified primary outcome. Preservation of C-peptide correlated with the reduction of T helper cells co-secreting IL-17A and interferon-γ (TH17.1 cells, P = 0.04) and, in particular, with the reduction in a subset of TH17.1 cells co-expressing IL-2 and granulocyte-macrophage colony-stimulating factor (IL-2+ GM-CSF+ TH17.1 cells, P = 0.04). A significant fall in β-cell-targeted (proinsulin-specific) IL-17A-secreting T cells was also seen (P = 0.0003). Although exploratory, our data suggest a role for an activated subset of TH17.1 cells in T1D that can be targeted with minimal adverse effects to reduce C-peptide loss, which requires confirmation in a larger study. (International Standard Randomised Controlled Trial Number Registry: ISRCTN 14274380).

Background Undernutrition during the early years of life has a harmful and irreversible impact on child growth and cognitive development. Many of the interventions tested to improve outcomes across infancy have had disappointing or inconsistent impact, a common feature being the absence of any attempt to provide nutritional supplements to infants during the first six months. With increasing evidence of micronutrient deficiencies in this age group, alongside strong evidence that growth and developmental deficits begin before six months, a renewed focus on the micronutrient status of infants is required. Methods This study is a five-arm, double-blind, placebo-controlled, randomised efficacy trial of micronutrient supplementation to mothers (during pregnancy or pregnancy and lactation) and infants (Day 8 to six months of age) in rural Gambia, where rates of micronutrient deficiencies are high. 600 pregnant women (<20 weeks gestation) will be enrolled into one of five trial arms and followed to 12 months post-partum. The primary outcome will be infant brain development at six months, with micronutrient status, growth and neurocognitive development to 12 months as secondary outcomes. Discussion This novel research will identify the most efficacious way of improving micronutrient status in infancy, and assess impact on infant developmental outcomes, providing an evidence base for future effectiveness trials and policy recommendations. Trial registration ISRCTN registry (ISRCTN15063705, 09/07/2021); Pan African Clinical Trials Registry (PACTR202201552774601, 21/01/2022).

Introduction COVID-19 has caused severe disruption to clinical services in Bangladesh but the extent of this, and the impact on healthcare professionals is unclear. We aimed to assess the perceived levels of anxiety, depression and burnout among doctors and nurses during COVID-19 pandemic.Methods We undertook an online survey using RedCap, directed at doctors and nurses across four institutions in Bangladesh (The Sheikh Russel Gastro Liver Institute & Hospital (SRNGIH), Dhaka Medical College Hospital (DMCH), Mugda Medical College Hospital (MMCH) and M Abdur Rahim Medical College (MARMC) Hospital). We collected information on demographics, awareness of well-being services, COVID-19-related workload, as well as anxiety, depression and burnout using two validated questionnaires: the Hospital Anxiety and Depression Scale (HADS) and the Maslach Burnout Inventory (MBI).Results Of the 3000 participants approached, we received responses from 2705 (90.2%). There was a statistically significant difference in anxiety, depression and burnout scores across institutions (p<0.01). Anxiety, depression and burnout scores were statistically worse in COVID-19 active staff compared with those not working on COVID-19 activities (p<0.01 for HADS anxiety and depression and MBI emotional exhaustion (EE), depersonalisation (DP) and personal accomplishment (PA)). Over half of the participants exhibited some level of anxiety (SRNGIH: 52.2%; DMCH: 53.9%; MMCH: 61.3%; MARMC: 68%) with a high proportion experiencing depression (SRNGIH: 39.5%; DMCH: 38.7%; MMCH: 53.7%; MARMC: 41.1%). Although mean burnout scores were within the normal range for each institution, a high proportion of staff (almost 20% in some instances) were shown to be classified as experiencing burnout by their EE, DP and PA scores.Conclusion We identified a high prevalence of perceived anxiety, depression and burnout among doctors and nurses during the COVID-19 pandemic. This was worse in staff engaged in COVID-19-related activities. These findings could help healthcare organisations to plan for future similar events.

Introduction Acute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called ‘Electronic clinical Decision support for Acute fever Management (EDAM)’ has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan.Methods and analysis This is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM.Ethics and dissemination Results will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR).Trial registration number International Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).

BACKGROUND:The majority of colorectal cancers (CRCs) are detected after symptomatic presentation to primary care. Given the shared symptoms of CRC and benign disorders, it is challenging to manage the risk of missed diagnosis. Colonoscopy resources cannot keep pace with increasing demand. There is a pressing need for access to simple triage tools in primary care to help prioritise patients for referral.AIM:To evaluate the performance of a novel spectroscopy-based CRC blood test in primary care.DESIGN & SETTING:Mixed-methods pilot study of test performance and GP focus group discussions in South Wales.METHOD:Patients on the urgent suspected cancer (USC) pathway were recruited for the Raman spectroscopy (RS) test coupled to machine learning classification ('Raman-CRC') to identify CRC within the referred population. Qualitative focus group work evaluated the acceptability of the test in primary care by thematic analysis of focus group theorising.RESULTS:A total of 532 patients aged ≥50 years referred on the USC pathway were recruited from 27 GP practices. Twenty-nine patients (5.0%) were diagnosed with CRC. Raman-CRC identified CRC with sensitivity 95.7%, specificity 69.3% with area under curve (AUC) of 0.80 compared with colonoscopy as the reference test (248 patients). Stage I and II cancers were detected with 78.6% sensitivity. Focus group themes underlined the convenience of a blood test for the patient and the test's value as a risk assessment tool in primary care.CONCLUSION:The findings support this novel, non-invasive, blood-based method to prioritise those patients most likely to have CRC. Raman-CRC may accelerate access to diagnosis with potential to improve cancer outcomes.

Guidelines recommend early intensive low-density lipoprotein cholesterol (LDL-C)-lowering following ST-elevation myocardial infarction (STEMI). This real-world study aimed to determine whether patients are receiving intensive LDL-C-lowering therapies and the proportion who could be discharged from hospital on proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs) post-STEMI.

Background: Quality of life (QoL) is a crucial and core outcome in studies assessing the effectiveness of treatments for cryptoglan-dular anal fistula. Despite the extensive impact of anal fistula on QoL, there is a lack of patient-centred, disease-specific QoL measurement instruments. This study describes the development of a disease-specific measurement instrument that can accurately measure QoL for patients with cryptoglandular anal fistula. Methods: Semi-structured qualitative patient interviews were used to generate items for the draft instrument, which then went through successive rounds of cognitive interviews in order to refine its wording and structure. Individual item and overall scale content validity was determined by asking experts to rate the relevance of each item and those deemed irrelevant were removed. The final instrument then underwent psychometric testing and test– retest analysis to determine its sensitivity and stability. Results: A total of 148 patients were involved in item generation, scale development and psychometric testing. A 22-item measurement instrument has been developed, scored on a scale of 0– 100, where 0 indicates the worst QoL and 100 demonstrates perfect QoL. The scale demonstrates excellent internal consistency (Cronbach-α = 0.927), strong content and construct validity (correlation with perianal disease activity index = −0.713, Hospital Anxiety and Depression Anxiety [−0.659] and Depression [−0.673] subscales and Short Form-12 physical [0.609] and mental [0.589] component scales) and strong reliability and responsiveness. Conclusion: We have developed an Anal Fistula Quality of Life scale (AF-QoL), a comprehensive, disease-specific patient-reported outcome measure (PROM) assessing QoL in patients with cryptoglan-dular anal

Severe sepsis is a time critical condition which is known to have a high mortality rate. Evidence suggests that early diagnosis and early administration of antibiotics can reduce morbidity and mortality from sepsis. The prehospital phase of emergency medical care may provide the earliest opportunity for identification of sepsis and delivery of life-saving treatment for patients. We aimed to assess the feasibility of (1) paramedics recognising and screening patients for severe sepsis, collecting blood cultures and administering intravenous antibiotics; and (2) trial methods in order to decide whether a fully-powered trial should be undertaken to determine safety and effectiveness of this intervention. Paramedics were trained in using a sepsis screening tool, aseptic blood culture collection and administration of intravenous antibiotics. If sepsis was suspected, paramedics randomly allocated patients to intervention or usual care using scratchcards. Patients were followed up at 90 days using linked anonymised data to capture length of hospital admission and mortality. We collected self-reported health-related quality of life at 90 days. We pre-specified criteria for deciding whether to progress to a fully-powered trial based on: recruitment of paramedics and patients; delivery of the intervention; retrieval of outcome data; safety; acceptability; and success of anonymised follow-up. Seventy-four of the 104 (71.2%) eligible paramedics agreed to take part and 54 completed their training (51.9%). Of 159 eligible patients, 146 (92%) were recognised as eligible by study paramedics, and 118 were randomised (74% of eligible patients, or 81% of those recognised as eligible). Four patients subsequently dissented to be included in the trial (3%), leaving 114 patients recruited to follow-up. All recruited patients were matched to routine data outcomes in the Secure Anonymised Information Linkage Databank. Ninety of the 114 (79%) recruited patients had sepsis or a likely bacterial infection recorded in ED. There was no evidence of any difference between groups in patient satisfaction, and no adverse reactions reported. There were no statistically significant differences between intervention and control groups in Serious Adverse Events (ICU admissions; deaths). This feasibility study met its pre-determined progression criteria; an application will therefore be prepared and submitted for funding for a fully-powered multi-centre randomised trial. Trial registration: ISRCTN36856873 sought 16th May 2017; https://doi.org/10.1186/ISRCTN36856873

Coronary artery disease (CAD) and acute coronary syndromes (ACS) remain a leading cause of death in people with type 1 diabetes mellitus (T1DM). We explored clinical characteristics and outcomes of patients with T1DM and ACS.

Dear Editor, With an average 156 days of rain a year in the United Kingdom (UK), it's no surprise that when the sun comes out, the British approach is to 'make the most of it'. Spend a sunny day at any UK beach and you'll see several sunburns at the end of the day. But summer is fast approaching here, and dermatologists and healthcare professionals continue to stress that skin cancer prevention is of upmost importance.1 Skin cancer, including melanoma and non-melanoma (keratinocyte), is increasing rapidly at a rate of 8% annually and now comprises half of all cancers in England and Wales.1 Accounting for an increasing proportion of workload, the disease is impacting dermatology services, causing care for other skin conditions to suffer, and waiting lists to grow. However, with estimates that 86% of melanomas are preventable with less sun exposure2 there is hope. Most skin cancers result from excess ultraviolet (UV) light exposure and severe sunburn as a child greatly increases risk of future skin cancer.3 Combine this with the fact that childhood is when individuals start to develop responsibility for health-related behaviours including attitudes to tanning, teaching children about enjoying the sun safely and skin cancer prevention makes sense. In line with this, supported by a recent systematic review which showed educational programmes appeared effective for improving sun protection outcomes in children under 18,4 major health bodies including World Health Organization, British Association of Dermatologists and National Institute for Health and Care Excellence, all recommend sun safety education and guidance in schools. Yet while prevention and education are clearly key, in the UK both sun safety knowledge and behaviour need to increase if future skin cancer rates are to decrease.5 Additionally, there has been very little research done in UK primary schools4 perhaps given the variable weather and the particular challenges in promoting sun safety in a 'maritime climate'. In England, it's now a statutory requirement to teach primary school children about safe exposure to the sun. However, in Wales, it's a different story. Despite a strong policy focus on prevention activities, and calls from both the public and charities that schools have clear plans in place, in Wales, it is still not mandatory to teach children how to enjoy the sun safely and there is no blanket guidance to keep children protected. Informal discussions with several Healthy Schools Co-ordinators based at Public Health Wales suggest schools in Wales would welcome any additional support in this key area. Unfortunately, while Cancer Research UK and the Wales-based Tenovus Cancer Care previously offered resources and guidance to schools, both charities have cut their sun safety education and prevention activities due to other priorities. The English-based charity Skcin has a free sun safe schools accreditation scheme available to schools in Wales, although their resources are not available in Welsh which may pose a deterrent to registration, especially for Welsh speaking schools. While many will argue that the risks of a child getting sunburnt at school are minimal, the benefits of a sun safety policy in schools reach beyond the classroom. Due to the increased risk of damage from sun exposure at a young age children should be free to enjoy the weather safely, wherever they are. Providing children with a sun safe school environment, educating them on sun protective behaviours and encouraging healthy attitudes towards tanning from an early age are all ways to empower them to take control over their health. We have recently won funding from Health and Care Research Wales for Sunproofed, a 2-year scoping study6 to better understand the landscape of skin cancer prevention in primary schools in Wales. Bringing together both quantitative and qualitative methods and using anonymised, routine data, we will discover what if any, sun safety policies currently exist, the benefits, barriers and facilitators to teaching sun safety in school and what support schools need in this area. A key output of this research will be to use study findings to co-produce guidance on best methods for implementing sun safety policies in Welsh schools. While we acknowledge the long-term benefits of any intervention that tackles skin cancer prevention will take years to become apparent, we are pleased Welsh Government have recognised the importance of this work. Teaching children how to be safe in the sun has the potential to improve sun protection outcomes,4 potentially reversing growing rates of skin cancer and saving both resources and lives. And when the rain stops in Wales? Young people will be well placed to protect themselves. Julie Peconi: Conceptualization (lead); Funding acquisition (lead); Project administration (lead); Writing – original draft (lead). Greg Fegan: Conceptualization (supporting); Funding acquisition (supporting); Project administration (supporting); Writing – review & editing (equal). Rachel Abbott: Conceptualization (supporting); Funding acquisition (supporting); Project administration (supporting); Writing – review & editing (equal). Health and Care Research Wales [HRG-20-1708(P)]. None to declare. Although this letter focuses on our opinion, the study we reference in the letter, Sunproofed has received ethical approval from Swansea University's Medical School Research Ethics Sub-Committee. Not applicable.

In Uganda, low resources for mental health provision combine with disadvantage and inadequate supports for family and community-based care. Catalysed by the need to reduce overcrowded psychiatric hospital wards and frequent readmissions at Butabika National Referral Mental Hospital (BNRMH) in Kampala, the nongovernment organisation YouBelong Uganda (YBU) developed the YouBelong Home (YBH) intervention. YBH is a theoretically eclectic pre and post hospital discharge intervention. This paper reports on qualitative findings of the project Curtailing Hospital Readmissions for Patients with Severe Mental Illness in Africa (CHaRISMA), which explored how to refine the YBH intervention. The project was funded by a UK Joint Global Health Trials (JGHT) Development Grant. Data was collected through structured interviews with service users and caregivers, reflective practice by the YBH implementing team and a stakeholder focus group. A summary of refinements to the YBH intervention follows the TIDieR format (Template for Intervention Description and Replication).

Background Skin cancer, including melanoma and non-melanoma (keratinocyte), is increasing in incidence in the UK. Accounting for half of all cancers in England and Wales, the disease significantly impacts overstretched dermatology services. Research suggests that 86% of melanoma is preventable with modified sun exposure. Educating children about sun safety in schools can help prevent skin cancer and is recommended by major health organisations. In England, teaching sun safety in primary schools is compulsory, while in Wales this is left to school discretion. Aims Understand how primary schools in Wales are responding to growing skin cancer rates and explore the effectiveness of sun safety policies in schools on knowledge and behaviour. Methods Sunproofed is a mixed-methods scoping study comprising 5 work packages (WP) using survey and routine electronic health record (EHR) data supplemented by qualitative case studies. Objective(s) are to: WP1: Discover if primary schools in Wales have sun safety policies; policy characteristics; determine factors that may influence their presence and identify areas where schools need support. WP2: Determine what EHR data is available regarding the incidence of sunburn in primary school children and the feasibility of using this data to evaluate the impact of sun safety policies. WP3: Understand the impact of sun safety policies on sun-safe knowledge and behaviour amongst children, parents, teachers, and school management; identify barriers and facilitators to schools implementing sun safety policies. WP4: Co-produce guidance regarding sun safety policies and best methods for implementation in schools. WP5: Disseminate guidance and findings widely to ensure impact and uptake. Discussion Skin cancer rates are increasing in the UK, straining limited resources. Sunproofed has the potential to inform the development of future prevention activities, both in Wales and beyond. This could reduce the number of skin cancer cases in the future and keep people healthier for longer.

Background: Incisional hernias can cause chronic pain and complications and affect quality of life. Surgical repair requires health-care resources and has a significant associated failure rate. A prospective, multicentre, single-blinded randomised controlled trial was conducted to investigate the clinical effectiveness and cost-effectiveness of the Hughes abdominal closure method compared with standard mass closure following surgery for colorectal cancer. The study randomised, in a 1 : 1 ratio, 802 adult patients (aged ≥ 18 years) undergoing surgical resection for colorectal cancer from 28 surgical departments in UK centres. Intervention: Hughes abdominal closure or standard mass closure. Main outcome measures: The primary outcome was the incidence of incisional hernias at 1 year, as assessed by clinical examination. Within-trial cost-effectiveness and cost–utility analyses over 1 year were conducted from an NHS and a social care perspective. A key secondary outcome was quality of life, and other outcomes included the incidence of incisional hernias as detected by computed tomography scanning. Results: The incidence of incisional hernia at 1-year clinical examination was 50 (14.8%) in the Hughes abdominal closure arm compared with 57 (17.1%) in the standard mass closure arm (odds ratio 0.84, 95% confidence interval 0.55 to 1.27; p = 0.4). In year 2, the incidence of incisional hernia was 78 (28.7%) in the Hughes abdominal closure arm compared with 84 (31.8%) in the standard mass closure arm (odds ratio 0.86, 95% confidence interval 0.59 to 1.25; p = 0.43). Computed tomography scanning identified a total of 301 incisional hernias across both arms, compared with 100 identified by clinical examination at the 1-year follow-up. Computed tomography scanning missed 16 incisional hernias that were picked up by clinical examination. Hughes abdominal closure was found to be less cost-effective than standard mass closure. The mean incremental cost for patients undergoing Hughes abdominal closure was £616.45 (95% confidence interval –£699.56 to £1932.47; p = 0.3580). Quality of life did not differ significantly between the study arms at any time point. Limitations: As this was a pragmatic trial, the control arm allowed surgeon discretion in the approach to standard mass closure, introducing variability in the techniques and equipment used. Intraoperative randomisation may result in a loss of equipoise for some surgeons. Follow-up was limited to 2 years, which may not have been enough time to see a difference in the primary outcome. Conclusions: Hughes abdominal closure did not significantly reduce the incidence of incisional hernias detected by clinical examination and was less cost-effective at 1 year than standard mass closure in colorectal cancer patients. Computed tomography scanning may be more effective at identifying incisional hernias than clinical examination, but the clinical benefit of this needs further research. Future work: An extended follow-up using routinely collected NHS data sets aims to report on incisional hernia rates at 2–5 years post surgery to investigate any potential mortality benefit of the closure methods. Furthermore, the proportion of incisional hernias identified by a computed tomography scan (at 1 and 2 years post surgery), but not during clinical examination (occult hernias), proceeding to surgical repair within 3–5 years after the initial operation will be explored. Trial registration: This trial is registered as ISRCTN25616490. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 34. See the NIHR Journals Library website for further project information.

Background: Far less is known about the reasons for hospitalization or mortality during and after hospitalization among school-aged children than among under-fives in low- and middle-income countries. This study aimed to describe common types of illness causing hospitalisation; inpatient mortality and post-discharge mortality among school-age children at Kilifi County Hospital (KCH), Kenya. Methods: A retrospective cohort study of children 5−12 years old admitted at KCH, 2007 to 2016, and resident within the Kilifi Health Demographic Surveillance System (KHDSS). Children discharged alive were followed up for one year by quarterly census. Outcomes were inpatient and one-year post-discharge mortality. Results: We included 3,907 admissions among 3,196 children with a median age of 7 years 8 months (IQR 74−116 months). Severe anaemia (792, 20%), malaria (749, 19%), sickle cell disease (408, 10%), trauma (408, 10%), and severe pneumonia (340, 8.7%) were the commonest reasons for admission. Comorbidities included 623 (16%) with severe wasting, 386 (10%) with severe stunting, 90 (2.3%) with oedematous malnutrition and 194 (5.0%) with HIV infection. 132 (3.4%) children died during hospitalisation. Inpatient death was associated with signs of disease severity, age, bacteraemia, HIV infection and severe stunting. After discharge, 89/2,997 (3.0%) children died within one year during 2,853 child-years observed (31.2 deaths [95%CI, 25.3−38.4] per 1,000 child-years). 63/89 (71%) of post-discharge deaths occurred within three months and 45% of deaths occurred outside hospital. Post-discharge mortality was positively associated with weak pulse, tachypnoea, severe anaemia, HIV infection and severe wasting and negatively associated with malaria. Conclusions: Reasons for admissions are markedly different from those reported in under-fives. There was significant post-discharge mortality, suggesting hospitalisation is a marker of risk in this population. Our findings inform guideline development to include risk stratification, targeted post-discharge care and facilitate access to healthcare to improve survival in the early months post-discharge in school-aged children.

Introduction Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications. Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis. Methods and analysis This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D. Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible. Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1. MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work. Ethics and dissemination This trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018. The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences. Trial registration number ISRCTN14274380.