搜索结果：The Lancet. Child & adolescent health

To assess the prevalence of obesity and related health conditions among children and adolescents aged 7-17 in the Xinjiang Uygur Autonomous Region from 2016 to 2017. The data were sourced from the 2016-2017 China Children and Lactating Mothers Nutrition and Health Surveillance Program. A total of 1112 individuals were surveyed in this study, with 754 from urban schools and 358 from rural schools. Among them, boys accounted for 49.01% and girls for 50.99%; students aged 7-11 years comprised 49.01%, and those aged 12-17 years comprised 50.99%. Obesity, central obesity, hypertension, diabetes, and dyslipidemia were defined according to the following criteria: "Screening for Overweight and Obesity Among School-Age Children and Adolescents(WS/T 586-2018)", "Threshold for High Waist Circumference Screening in Children and Adolescents Aged 7-18 Years(WS/T 611-2018)", "Blood Pressure Reference for Hypertension Screening in Chinese Children and Adolescents Aged 7-18 Years", "Guidelines for the Diagnosis and Treatment of Type 2 Diabetes in Children(2025)", and "Chinese Guidelines for Lipid Management(2023)". Referring to the clinical obesity definition and diagnostic criteria framework proposed by the Lancet Diabetes &amp; Endocrinology Commission, and considering the availability of indicators in this study, criteria for defining subclinical obesity and clinical obesity in children and adolescents were established. The general obesity rate was 3.96%, and the central obesity rate was 9.44%. According to the clinical obesity criteria, the subclinical obesity rate was 2.34%, and the clinical obesity rate was 0.45%. The general obesity rate, central obesity rate, and clinical obesity rate were higher among urban school students compared to rural school students, with all differences being statistically significant(P<0.05). The general obesity rate was higher in boys than in girls(P<0.05), while no statistically significant difference was observed in central obesity rate between genders. The obesity rate was higher in the 7-11-year-old group than in the 12-17-year-old group, whereas the central obesity rate was lower in the 7-11-year-old group compared to the 12-17-year-old group; both differences were statistically significant(P<0.05). In both boys and girls, a trend of increasing cental obesity rate and dyslipidemia rate was observed with increasing BMI(P<0.05). No association was found between BMI and hypertension. The prevalence of obesity among children and adolescents in the Xinjiang Uygur Autonomous Region shows population-specific differences and is associated with increased health risks.

Mental health problems, including depression, anxiety, and suicide, pose a substantial burden on adolescents worldwide, making prevention a priority. In China, major challenges remain in implementing and evaluating school-based mental health programmes. The Adolescent Mental Health Service Package (AMHSP) is a multicomponent, culturally adapted, evidence-informed curriculum that is grounded in Positive Youth Development and designed to reduce depressive and anxiety symptoms and enhance mental wellbeing. The aim of this study was to evaluate the AMHSP for improving adolescent mental health in routine school settings. This cluster-randomised controlled trial included public schools across ten provinces in China, with participants nested within schools and classrooms within each school randomly assigned 1:1 to either ten weekly 40-min AMHSP sessions (intervention), delivered by trained school-based mental health teachers or counsellors (facilitators) using standardised manuals and multimedia materials, or routine curriculum without additional mental health content (control). Given the nature of the school-based intervention, neither students nor facilitators were masked to group allocation, but all statistical analyses were done by an independent statistician masked to group allocation, and student self-report data were collected anonymously using secure, standardised platforms. The four primary outcomes were depressive symptoms (measured by nine-item Patient Health Questionnaire), anxiety symptoms (seven-item Generalized Anxiety Disorder Scale), subjective wellbeing (WHO Five-item Well-Being Index), and emotion regulation (ten-item Emotion Regulation Questionnaire, assessing both cognitive reappraisal and expressive suppression), which were self-reported at baseline, immediately after intervention, and at 1-month and 3-month follow-up. The primary outcome analysis of change from baseline at 3 months' follow-up in the four coprimary outcomes was analysed by linear mixed-effects models in the intention-to-treat population, which included all participants who completed at least one assessment. To control for multiple testing, we prespecified the use of the Benjamini-Hochberg false discovery rate (FDR) correction of p values. This trial was prospectively registered with the Chinese Clinical Trial Registry (ChiCTR2300076956) and has been completed. Between Oct 12, 2023 and Oct 10, 2024, 5222 students from 120 classrooms in 18 public schools (mean age 13&#xb7;6 years [SD 1&#xb7;7]; 2687 [51&#xb7;5%] girls and 2535 [48&#xb7;5%] boys) were randomly assigned to the AMHSP intervention (n=2620) or control (n=2602), completed the baseline assessments, and were included in the primary outcome analysis. At 3 months, the AMHSP intervention group showed lower depressive symptoms (standardised mean difference [SMD] -0&#xb7;09 [95% CI -0&#xb7;14 to -0&#xb7;04], pFDR=0&#xb7;0013) and anxiety symptoms (-0&#xb7;11 [-0&#xb7;16 to -0&#xb7;05], pFDR=0&#xb7;0002) relative to the control group. No differences were seen in subjective wellbeing (SMD 0&#xb7;02 [-0&#xb7;03 to 0&#xb7;08], pFDR=0&#xb7;85) or emotion regulation (cognitive reappraisal SMD 0&#xb7;03 [-0&#xb7;02 to 0&#xb7;09], pFDR=0&#xb7;33; expressive suppression -0&#xb7;08 [-0&#xb7;14 to -0&#xb7;01], pFDR=0&#xb7;10) at 3 months. No adverse events were reported. The reduction in depression and anxiety symptoms 3 months after completing ten AMHSP sessions indicates a slow but meaningful benefit of the programme and supports the potential of a low-intensity, curriculum-integrated approach to promoting adolescent mental health. Delivery of the AMHSP by trained school-based mental health teachers demonstrates a scalable strategy for early mental health promotion in schools. UNICEF.

Herpes simplex virus (HSV) encephalitis is characterised by inflammation and swelling of the brain, resulting in death or severe neurocognitive sequelae. HSV encephalitis is treated with the antiviral aciclovir but still has substantial mortality and morbidity. Adjunct corticosteroids are sometimes used, but whether they improve the outcome is unclear. We aimed to establish the safety and efficacy of adjunct corticosteroids in HSV encephalitis. In this multicentre, observer-blind, randomised, phase 3 trial, adults with HSV encephalitis admitted to 53 hospitals in the UK were randomly assigned to receive intravenous dexamethasone (10 mg/kg, four times daily for 4 days) plus intravenous aciclovir (10 mg/kg three times daily for at least 14 days; dexamethasone group), or intravenous aciclovir alone (control group). Eligible patients aged 16 years or older had suspected encephalitis (a febrile illness with new onset seizure, new focal neurological signs or alteration in consciousness, cognition, personality, or behaviour), with positive HSV type 1 or type 2 PCR test in CSF. Participants were randomly assigned by the trial team at the recruiting site, using a secure web-based randomisation programme. The primary outcome was verbal memory score at 26 weeks, measured by the Wechsler Memory Scale (WMS)-IV auditory memory index. Analyses of primary and secondary outcomes were performed according to the modified intention-to-treat principle, and safety analyses were based on whether participants received at least one dose of the study drug. Trial neuropsychologists assessing the primary outcome, and statisticians involved in the study's primary outcome, were masked to treatment group allocation. The trial is registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN11774734, and EudraCT, EudraCT2016-004835-19, and is completed. Between Sept 22, 2016, and Feb 2, 2022, 94 patients with HSV encephalitis were recruited, 47 (20 [43%] female and 27 [57%] male) to the dexamethasone group, and 47 (24 [51%] female and 23 [49%] male) to the control group. Dexamethasone was initiated a median 7 (IQR 4-8) days after hospital admission. Seven patients withdrew consent, and six were lost to follow-up. Thus, 81 were included in the modified intention-to-treat analysis (39 in the treatment group and 42 in the control group). The primary outcome, verbal memory score at 26 weeks, did not differ significantly between the groups (71 [SD 26] in the dexamethasone group, and 69 [SD 25] in the control group; adjusted difference 1&#xb7;77 [95% CI -9&#xb7;57 to 13&#xb7;12; p=0&#xb7;76). There were 27 adverse events involving 18 (38%) participants in the control group, and 25 adverse events involving 18 (40%) participants in the dexamethasone group. The most common serious adverse events were seizures requiring readmission to hospital (affecting one [2%] patient in the dexamethasone group and one [2%] patient in the control group) and thrombotic events, including deep vein thrombosis (affecting one [2%] patient in the dexamethasone group) and pulmonary embolism (affecting one [2%]patient in the dexamethasone group). There were no treatment-related deaths. In adults with HSV encephalitis, dexamethasone plus aciclovir had a satisfactory safety profile but did not improve verbal memory score compared with aciclovir alone. Given the established role of corticosteroids in other inflammatory encephalitides, our findings suggest that their early use in suspected encephalitis is unlikely to be harmful. Future studies should assess more targeted immunomodulatory approaches in HSV encephalitis. National Institute for Health and Care Research.

Juvenile psoriatic arthritis and enthesitis-related arthritis are two categories of juvenile idiopathic arthritis (JIA). Despite available treatments including non-steroidal anti-inflammatory drugs, glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs, a substantial proportion of people do not adequately respond to treatment or do not have long-lasting clinical remission. The aim of this trial was to show the efficacy and safety of ixekizumab in children with active enthesitis-related arthritis and juvenile psoriatic arthritis. COSPIRIT-JIA is an ongoing multicentre, open-label, phase 3 study of ixekizumab, with a randomised adalimumab reference group, in children with a diagnosis of enthesitis-related arthritis (aged 6 to <18 years) and juvenile psoriatic arthritis (aged 2 to <18 years). Eligible participants had three or more active peripheral joints (presence of swelling or limited motion with pain or tenderness) and a bodyweight of at least 10 kg. Participants received subcutaneous administration of either ixekizumab or adalimumab using a weight-based dosing regimen (ixekizumab 40-160 mg starting dose then 20-80 mg once every 4 weeks; and adalimumab 20-40 mg once every 2 weeks). The primary endpoint was the percentage of ixekizumab-treated participants meeting the JIA-American College of Rheumatology (ACR) 30 (defined as at least 30% improvement from baseline in three of any six core outcome variables, with no more than one of the other variables worsening by more than 30%) response criteria at week 16. A Bayesian analysis was used to assess JIA-ACR30 response rate at week 16. Safety data were summarised using descriptive statistics for all participants who received at least one dose of either treatment. People with lived experience of JIA were not involved in the design or conduct of this study. The trial was registered with ClinicalTrials.gov, NCT04527380. The study enrolled 101 patients (ixekizumab n=81, adalimumab n=20) between April 13, 2021, and April 2, 2024, of whom the initial 40 participants naive to biological DMARD treatment were randomly assigned 1:1 to ixekizumab or adalimumab and the additional 61 participants were assigned to ixekizumab. Of the 81 participants who received ixekizumab, 60 were biological DMARD naive (40 with enthesitis-related arthritis and 20 with juvenile psoriatic arthritis) and 21 were biological DMARD experienced (14 with enthesitis-related arthritis and seven with juvenile psoriatic arthritis). The median age of the participants in the ixekizumab group was 14 years (12&#xb7;0-15&#xb7;0), of whom 36 (44%) of 81 were female, and 69 (85%) of 81 were White. At week 16, 90% (54 of 60; 95% CI 82&#xb7;4-97&#xb7;6) of biological DMARD-naive participants and 86% (18 of 21; 70&#xb7;7-100&#xb7;0) of biological DMARD-experienced participants receiving ixekizumab had a JIA-ACR30 response. Treatment-emergent adverse events were mostly mild (46%) or moderate (36%) for the ixekizumab group, with no severe treatment-emergent adverse events reported. The safety profile was consistent with adult psoriatic arthritis or spondyloarthritis and paediatric psoriasis indications. Ixekizumab was well tolerated and effective for the treatment of children with enthesitis-related arthritis and juvenile psoriatic arthritis who are candidates for biological DMARD therapy. Eli Lilly and Company.

Friedreich's ataxia is a rare, chronic, progressive, neurodegenerative condition affecting multiple organ systems, including neurological, musculoskeletal, cardiac, and endocrine systems, and is marked by low cardiopulmonary fitness. We tested the effect of exercise and NAD+ precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia. This 12-week, outpatient, phase 2, single-site (Children's Hospital of Philadelphia, Philadelphia, PA, USA), randomised, 2&#x2008;&#xd7;&#x2008;2 factorial clinical trial recruited individuals aged 10-40 years with an ejection fraction of 45% or greater who were able to exercise. A computer-generated randomisation sequence was developed by the trial statistician. Random allocation was age-stratified (<18 years vs &#x2265;18 years) to one of four groups: placebo and no exercise with attention control (weekly phone calls; henceforth placebo only), nicotinamide riboside and no exercise with attention control (henceforth nicotinamide riboside only), placebo and exercise (exercise only), and nicotinamide riboside and exercise (combination therapy). Individualised exercise plans were developed by the exercise physiologist (three aerobic and two resistance training sessions weekly), performed at the individual's home, and overseen remotely (telephone check-ins by the physiologist). Weight-based dosing of nicotinamide riboside or placebo was 300 mg (1 capsule) for weights of 24 kg up to 48 kg, 600 mg (2 capsules) for weight 48 kg up to 72 kg, and 900 mg (3 capsules) for weights of over 72 kg. The primary outcome was change in peak VO2 (L/min) during cardiopulmonary exercise testing at 12 weeks versus baseline, and the effect of treatment group was assessed in a statistical model accounting for age (stratification variable), sex, and baseline peak VO2. Stage 1 analysis tested the difference between each active treatment versus the control group, and stage 2 analysis (if combination therapy was effective) tested the difference between combination treatment and exercise alone; family-wise type 1 error was maintained <0&#xb7;05. Analyses were by intention-to-treat. Adverse events were recorded systematically. This trial is registered with ClinicalTrials.gov (NCT04192136) and is complete. Between Sept 3, 2020, and April 23, 2025, we enrolled 74 individuals, of whom 66 met the eligibility criteria and were randomly allocated to the four study groups. All participants completed the study. 33 (50%) were children (aged 10-17 years) and 33 (50%) were adults (aged &#x2265;18 years); 37 (56%) were male and 29 (44%) were female. Least mean squares for the change in peak VO2 in L/min were -0&#xb7;05 (95% CI -0&#xb7;16 to 0&#xb7;06) for the 17 participants in the control group; 0&#xb7;06 (-0&#xb7;05 to 0&#xb7;17) for the 17 participants in the nicotinamide riboside and no exercise group; 0&#xb7;11 (0&#xb7;00 to 0&#xb7;22) for the 16 participants in the placebo and exercise group; and 0&#xb7;16 (0&#xb7;05 to 0&#xb7;27) for the 16 participants in the nicotinamide riboside and exercise group. Differences between active treatment and the control group were 0&#xb7;10 (95% CI -0&#xb7;05 to 0&#xb7;26; padjusted=0&#xb7;188) for nicotinamide riboside and no exercise; 0&#xb7;16 (0&#xb7;00 to 0&#xb7;31; padjusted=0&#xb7;103) for placebo and exercise; and 0&#xb7;21 (0&#xb7;05 to 0&#xb7;36; padjusted=0&#xb7;0299) for nicotinamide riboside and exercise in combination. Combination therapy was not statistically different from exercise alone (difference -0&#xb7;05 ([95% CI -0&#xb7;10 to 0&#xb7;21]; p=0&#xb7;49). Adverse events were all mild or moderate, and included gastrointestinal symptoms, falls, upper respiratory infections, and skin rashes. At least one moderate adverse event of interest in these categories was reported by seven (41%) participants in the control group; six (35%) in the nicotinamide riboside and no exercise group; three (19%) in the placebo and exercise group; and four (25%) in the nicotinamide plus exercise group. The combination of nicotinamide riboside plus exercise for 12 weeks was safe and increased cardiopulmonary fitness in children and adults with Friedreich's ataxia. Longer studies are needed to establish whether adding nicotinamide riboside to exercise could be considered as part of a long-term, comprehensive treatment approach. US National Institutes of Health and Friedreich's Ataxia Research Alliance.

Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2&#xb7;30 million (95% uncertainty interval [UI] 2&#xb7;01 to 2&#xb7;61) breast cancer incident cases, 764&#x2008;000 deaths (672&#x2008;000 to 854&#x2008;000), and 24&#xb7;1 million (21&#xb7;3 to 27&#xb7;5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44&#xb7;2 per 100&#x2008;000 person-years [31&#xb7;2 to 58&#xb7;4]), the age-standardised mortality rate (ASMR) was the highest (24&#xb7;1 per 100&#x2008;000 [16&#xb7;8 to 31&#xb7;9]). The highest ASIR was in the high-income group (75&#xb7;7 per 100&#x2008;000 [67&#xb7;1 to 84&#xb7;0]), and the lowest ASMR was in the upper-middle-income group (11&#xb7;2 per 100&#x2008;000 [10&#xb7;2 to 12&#xb7;3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147&#xb7;2% (38&#xb7;1 to 271&#xb7;7), compared with a 1&#xb7;2% (-11&#xb7;5 to 17&#xb7;2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29&#xb7;9% (-33&#xb7;6 to -25&#xb7;9), but increased by 99&#xb7;3% (12&#xb7;5 to 202&#xb7;9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28&#xb7;3% (16&#xb7;6 to 38&#xb7;9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3&#xb7;56 million (2&#xb7;29 to 4&#xb7;83), with 1&#xb7;37 million (0&#xb7;841 to 2&#xb7;02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2&#xb7;5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.

ODYSSEY trial showed superior efficacy of dolutegravir-based antiretroviral therapy (ART) versus then-current, non-dolutegravir standard of care over 96 weeks in children and adolescents living with HIV. The aim of this ancillary analysis was to compare anthropometric and body composition outcomes, including weight, height, BMI-for-age Z score, weight-for-age and height-for-age Z scores (<14 kg), mid-upper-arm circumference (MUAC), waist circumference, hip circumference, and body fat percentage, as well as metabolic outcomes (lipids and glucose), between dolutegravir and standard of care over approximately 5 years of follow-up. In this open-label, randomised, non-inferiority trial, children (aged &#x2265;4 weeks and <18 years), weighing 3 kg or more, starting first-line ART (ODYSSEY-A) or switching to second-line ART (ODYSSEY-B) were enrolled in 29 centres in Germany, Portugal, South Africa, Spain, Thailand, Uganda, Zimbabwe, and the UK in two cohorts (children weighing &#x2265;14 kg and children weighing <14 kg). Treatment effects (dolutegravir vs standard of care) were estimated on randomised allocation, accounting for treatment switches (substantial in standard of care arm during extended follow-up) through censoring and inverse-probability-of-censoring-weights. Changes in continuous outcomes were compared using linear mixed models, accounting for correlated slope and baseline value. Proportions of participants with unfavourable outcomes were compared using logistic mixed models. ODYSSEY is registered with ClinicalTrials.gov, NCT02259127, EUDRACT, 2014-002632-14, and ISRCTN, ISRCTN91737921. Between Sept 20, 2016, and Aug 26, 2019, 792 children were randomly assigned (392 to dolutegravir and 400 to standard of care). Of 707 children in the 14 kg or more cohort, 311 received first-line ART (ODYSSEY-A; 145 [92%] of 157 received efavirenz-based ART as standard of care) and 396 received second-line ART (ODYSSEY-B; 195 [98%] of 200 received boosted protease inhibitors as standard of care). Of 85 children in the less than 14 kg cohort, 72 received first-line ART (32 [74%] of 43 received lopinavir-ritonavir as first-line or second-line standard of care). Median follow-up on randomised allocation was 287 weeks (IQR 240-311) on dolutegravir-based ART and 205 weeks (168-240) on standard of care in the 14 kg or more cohort, and 220 weeks (208-232) on dolutegravir-based ART and 144 weeks (127-192) on standard of care in the less than 14 kg cohort. In the 14 kg or more cohort, 345 (49%) were female and 362 (51%) were male, 623 (88%) were Black African, median enrolment age was 12&#xb7;2 years (IQR 9&#xb7;1 to 14&#xb7;9), weight 30&#xb7;7 kg (23&#xb7;4 to 43&#xb7;0), and BMI-for-age Z score -0&#xb7;6 (-1&#xb7;4 to 0&#xb7;1); 35 (5%) were overweight and six (1%) were obese. At week 240, adjusted mean differences (dolutegravir minus standard of care) were 1&#xb7;0 kg for weight (95% CI -0&#xb7;2 to 2&#xb7;2; p=0&#xb7;095) and 0&#xb7;4 cm for MUAC (0&#xb7;0 to 0&#xb7;8; p=0&#xb7;030), driven by differences in first-line participants, where higher increases were also observed in height, waist circumference, and hip circumference. Increases in BMI-for-age Z score, body fat percentage, and cross-sectional waist-to-height ratio were similar on dolutegravir-based ART and standard of care. Total cholesterol (-15&#xb7;3 mg/dL [-21&#xb7;0 to -9&#xb7;5]; p<0&#xb7;0001), triglycerides (-14&#xb7;4 mg/dL [-25&#xb7;2 to -3&#xb7;6]; p=0&#xb7;0089), and glucose (-4&#xb7;4 mg/dL [-6&#xb7;8 to -1&#xb7;9]; p=0&#xb7;0004) were lower with dolutegravir than standard of care. In the less than 14 kg cohort, 44 (52%) were female and 41 (48%) were male, 83 (98%) were Black African, median enrolment age was 1&#xb7;4 years (IQR 0&#xb7;6 to 2&#xb7;0), weight 8&#xb7;1 kg (5&#xb7;4-10&#xb7;0) and BMI-for-age Z score -0&#xb7;8 (-1&#xb7;9 to 0&#xb7;2); three (4%) were overweight and none obese. Changes in weight, weight-for-age, BMI-for-age and height-for-age Z scores by 192 weeks were similar on dolutegravir and standard of care; there were small differences in MUAC (0&#xb7;6 cm [-0&#xb7;1 to 1&#xb7;3]; p=0&#xb7;070) and height (-2&#xb7;5 cm [-4&#xb7;5 to -0&#xb7;5]; p=0&#xb7;016). No significant differences in lipid biomarkers were observed; glucose decreased with standard of care but not with dolutegravir. Over approximately 5 years, indices defining excessive weight gain and central adiposity were similar with dolutegravir and other anchor drugs, and lipid and glycaemia profiles with dolutegravir were reassuring, providing supporting evidence for dolutegravir-based ART as the preferred treatment in children and adolescents. Fondazione Penta ETS, ViiV Healthcare, and UK Medical Research Council.

Adolescence is a sensitive period when suicidal ideation can peak. Although traumatic life events are a well established risk factor for suicidal ideation, the role of cumulative ordinary life events across multiple dimensions, such as family, autonomy, and sexuality, remains underexplored. Crucially, no evidence is available on how multidimensional trajectories of cumulative exposure to such events relate to suicidal ideation throughout adolescence. We aimed to examine how cumulative and domain-specific trajectories of ordinary life events during adolescence relate to suicidal ideation. In this multinational, prospective cohort study, we used longitudinal data from the IMAGEN cohort, gathered from eight centres in Germany, France, Ireland, and the UK between January, 2008, and January, 2010, to model trajectories of exposure to life events during adolescence, and to quantify the association between trajectory group and suicidal ideation. Participants were assessed at ages 14, 16, 19, and 23 years, and key inclusion criteria included having the capacity to provide informed assent or consent, and having parental completion of perinatal and developmental history. Exposure to 39 life events across seven dimensions (family, accidents, distress, autonomy, deviance, sexuality, and relocation) were assessed using the Life Events Questionnaire (LEQ), administered at each of the study timepoints. Childhood maltreatment was also assessed, using the Childhood Trauma Questionnaire, administered once at age 19 years. The primary outcome was the number of participants with suicidal ideation across trajectories, assessed via a dedicated item in the LEQ at the first three timepoints. We also compared self-harm and suicidal ideation responses from the Developmental and Well-Being Assessment at the first three timepoints. Latent trajectory analysis was used to identify classes of cumulative life event exposure across repeated assessments: high, mid-high, mid-low, and low. The association between trajectory group and suicidal ideation was quantified using logistic mixed model regressions, adjusting for childhood maltreatment and demographic covariates. No individuals with lived experience of suicidality or mental health conditions were involved in the design, conduct, or reporting of this research. At baseline, 2161 adolescents, enrolled between January, 2008, and January, 2010, were included in the cohort (1106 [51&#xb7;2%] female and 1055 [48&#xb7;8%] male). Sample sizes at subsequent waves were 1581 at first follow-up (which took place between January, 2011, and January, 2012), 1474 at second follow-up (between January, 2013, and January, 2015), and 1331 at third follow-up (between January, 2016, and January, 2019). At each timepoint, the high trajectory group (1125 [52&#xb7;1%] of 2161 participants) had the highest proportion of participants with suicidal ideation (90 [8&#xb7;0%] of 1125 at pre-baseline, 127 [11&#xb7;3%] of 1125 at age 14 years, 102 [13&#xb7;4%] of 759 at age 16 years, and 78 [11&#xb7;0%] of 709 at age 19 years). After controlling for demographics and childhood maltreatment, the high trajectory group had the highest predicted probability of suicidal ideation at each timepoint. Life events in the family dimension predicted adolescent suicidal ideation (marginal R2GLMM=0&#xb7;078) more than those in all remaining dimensions combined (marginal R2GLMM=0&#xb7;073). We found that higher cumulative exposure to ordinary life events across multiple dimensions is associated with higher suicidal ideation in adolescence, with life events occurring within the family environment carrying the highest risk. These results point to the importance of evaluating different types of everyday life event exposure, not just childhood trauma or maltreatment, when assessing suicidal risk in adolescents. Abroad Advanced Study Fellowship, Chang Gung Medical Foundation, Taiwan; National Science and Technology Council, Taiwan; Medical Research Council, UK.

Each year, an estimated 1&#xb7;9 million children (aged 0-9 years) and adolescents (aged 10-19 years) develop tuberculosis disease. Tuberculosis ranks among the top ten causes of death in children younger than 5 years. The primary driver of tuberculosis-related mortality in children and young adolescents is the failure to detect and treat the disease; more than 95% of tuberculosis deaths occur in children who were never initiated on tuberculosis treatment. To increase the quantity and quality of tuberculosis research required to strengthen clinical care and public health practice, the Child and Adolescent TB Working Group and its Secretariat at the WHO led a modified Delphi consensus process to generate core research principles and priorities along each step of the tuberculosis care cascade. An 11-member writing group drafted an initial list of principles and priorities, which were ranked by members of the consensus panel in each Delphi round. Principles and priorities that did not meet the consensus threshold were modified based on written qualitative feedback from the consensus panel and one-time input from other members of the Child and Adolescent TB Working Group at the group's 2024 annual meeting. Eight research principles and 21 research priorities emerged from two Delphi rounds. The research priorities have strong potential for translation into interventions, particularly in relation to diagnostics, shorter regimens, and tuberculous meningitis. With recently reduced tuberculosis research funding, these principles and priorities will focus research efforts to maximise clinical and public health impact.

Prolonged glucocorticoid therapy is the standard initial treatment for idiopathic nephrotic syndrome in children, but is associated with marked toxic effects. We aimed to assess whether a novel treatment protocol with mycophenolate mofetil is as effective as standard therapy with prednisone, while reducing the burden of glucocorticoid-related side-effects. INTENT was a multicentre, open-label, randomised, controlled, parallel-group, non-inferiority, phase 3 trial done in 37 community, municipal, and university hospitals in Germany. Patients aged 1-10 years with a first episode of steroid-sensitive nephrotic syndrome were randomly assigned (1:1) by a centralised web-based tool to receive either mycophenolate mofetil or prednisone (standard treatment), after remission induced by prednisone or prednisolone at a dose of 60 mg/m2 body surface area (maximum 80 mg/day) within 28 days. Block randomisation (block size of eight) was stratified by age (<7 years or &#x2265;7 years). Mycophenolate mofetil was given at 1200 mg/m2 body surface area per day, twice daily, as a suspension (200 mg/mL) for a total treatment duration of 12 weeks. Prednisone was administered once, twice, or three times daily for 6 weeks at 60 mg/m2 body surface area per day (maximum 80 mg). Thereafter, prednisone was given for a further 6 weeks at 40 mg/m2 body surface area (maximum 60 mg) once daily in the morning on alternate days. The primary endpoint was the occurrence of a treated relapse during the 24-months of follow-up in the modified intention-to-treat population. The non-inferiority margin was 15%. This trial is registered with the European Union Drug Regulating Authorities Clinical Trials database (EudraCT 2014-001991-76) and has been completed. Between Oct 12, 2015, and April 23, 2021, 497 patients were screened for eligibility, 272 of whom were randomly assigned (136 to each group). The modified intention-to-treat population comprised 269 patients, of whom 173 (64%) were boys and 96 (36%) were girls (median age 4&#xb7;0 years [IQR 2&#xb7;0-5&#xb7;0]). Mycophenolate mofetil was non-inferior to prednisone for the primary endpoint of treated relapse (106 [79&#xb7;1%] of 134 vs 101 [74&#xb7;8%] of 135; difference 4&#xb7;3% [90% CIs -4&#xb7;2 to 12&#xb7;7]; p=0&#xb7;019). At the end of the first 12 weeks of treatment, fewer glucocorticoid-related side-effects were observed in the mycophenolate mofetil group than the prednisone group, including arterial hypertension (78 [59&#xb7;1%] of 132 vs 115 [87&#xb7;1%] of 132; difference -28&#xb7;0% [95% CI -37&#xb7;7 to -17&#xb7;5]), lower BMI (BMI Z score 0&#xb7;16 [SD 0&#xb7;85] vs 1&#xb7;41 [1&#xb7;02]; difference -1&#xb7;24 [-1&#xb7;47 to -1&#xb7;02]), and fewer psychological abnormalities (37 [27&#xb7;8%] of 133 vs 77 [57&#xb7;9%] of 133; difference -30&#xb7;1% [-40&#xb7;9 to -18&#xb7;4]). More patients in the mycophenolate mofetil group than in the prednisone group developed infections (93 [69&#xb7;9%] of 133 vs 74 [55&#xb7;6%] of 133; difference 14&#xb7;3% [2&#xb7;7 to 25&#xb7;5]) and there was no statistically significant difference in the number of patients who developed at least one gastrointestinal disorder (22 [16&#xb7;5%] of 133 vs 13 [9&#xb7;8%] of 133; difference 6&#xb7;8% [-1&#xb7;5 to 14&#xb7;8]). Our findings suggest that mycophenolate mofetil is non-inferior to standard prednisone treatment, with reduced glucocorticoid-related toxic effects. These findings could modify the initial standard of care for patients with steroid-sensitive nephrotic syndrome. German Federal Ministry of Education and Research.

Many governments around the world subsidise upgrades to poorly insulated homes, yet the extent to which these energy-efficiency improvements reduce health risks remains unclear. We aimed to provide the first large-scale evidence on whether such retrofits lower the use of respiratory health-care services, particularly for children and other vulnerable individuals. We leveraged a large-scale natural experiment in which public housing units across the Netherlands were retrofitted between 2012 and 2021. Upgrades included insulation and mechanical ventilation and were implemented in homes eligible on the basis of poor energy efficiency and construction before the early 1990s. Treatment assignment was based on technical factors and was therefore shown to be unrelated to health outcomes, and opting out was not possible. We followed up 2 million individuals over 10 years, totalling approximately 12 million person-years-a sample size that provided high statistical power (95% CIs narrow enough to detect relative risk changes in medication use as small as 1%). Individual-level medication data were obtained from health insurers. Medication use and other health-care outcomes among 180&#x2009;000 tenants in retrofitted homes were compared with those in not-yet-retrofitted homes using a staggered difference-in-differences design with individual fixed effects. The primary outcomes were the use of prescription respiratory-system medications: asthma or chronic obstructive pulmonary disease drugs, cough remedies, and antihistamines. Antihistamine use declined by 1&#xb7;87% (95% CI 0&#xb7;19-3&#xb7;55; p=0&#xb7;029) after retrofits. Among children younger than 18 years, respiratory medication use fell by 3&#xb7;76% (1&#xb7;04-6&#xb7;48; p=0&#xb7;0067). Specifically, after 5 years, asthma medication use was reduced by 6&#xb7;91% (-0&#xb7;04 to 13&#xb7;85; p=0&#xb7;051). No statistically significant effects were found for non-respiratory medication outcomes and health-care costs. Energy-efficiency upgrades led to measurable reductions in respiratory medication use, especially for children. These benefits probably reflect reduced exposure to indoor dampness and bad air quality. Childhood asthma reduction is a crucial co-benefit of energy-efficiency home upgrades. NWO Dutch Research Council, RVO Netherlands Enterprise Agency, and Villum Fonden.

The Lancet Child and Adolescent Health Committee on the Future of Neonatology has published an important document on the future of neonatology to highlight the significant challenges hindering the development of research in this field of medicine. The number of preclinical and clinical studies in neonatology is insufficient due to a lack of interest from industry and insufficient support from public agencies. In many countries, neonatology is not formally recognized as a medical specialty, which fosters a shortage of academic positions, with negative effects on both neonatology research and the training of young neonatologists. This situation is exacerbated by excessive bureaucracy, which hinders productive interaction with regulatory agencies and ethics committees and makes conducting randomized controlled clinical trials excessively expensive. The lack of shared standardized outcome definitions and the limited use of real-world data contribute to making neonatology research more difficult. We support the Commission&#x2019;s proposal for a Global Alliance for Innovation in Neonatal Health (GAINH), which would include neonatologists, former patients, families, industry, and public bodies, such as governments and universities, to address and remove barriers to advancing neonatal health through high-impact research and innovation.

Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations. In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates. The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286&#xb7;2 deaths (95% uncertainty interval 267&#xb7;9-310&#xb7;5) per 100&#x2008;000 in 2020 and 250&#xb7;0 deaths (233&#xb7;2-272&#xb7;5) per 100&#x2008;000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78&#xb7;0 years (77&#xb7;7-78&#xb7;1) in 2019 to 74&#xb7;3 years (74&#xb7;0-74&#xb7;4) in 2020. It steadily recovered to 78&#xb7;8 years (78&#xb7;5-79&#xb7;2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4&#xb7;19 years, between 2019 and 2020. There was a net gain of 12&#xb7;4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2&#xb7;61 years), stroke (1&#xb7;63 years), neonatal disorders (1&#xb7;26 years), transport injuries (0&#xb7;88 years), and neoplasms (0&#xb7;64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4&#xb7;0% increase in rate between 2019 and 2023 and led to a net loss of 0&#xb7;04 years in life expectancy since 1990. Diabetes led to a net loss of 0&#xb7;09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic. The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system. Gates Foundation.

Stark socioeconomic health inequalities exist in the UK, with families from ethnic minority backgrounds disproportionally affected. Robust evidence is needed on interventions that can improve family wellbeing. We aimed to assess the effectiveness and cost-effectiveness of a group-based parenting intervention (Strengthening Families, Strengthening Communities [SFSC]) in enhancing parental mental wellbeing. We conducted a randomised, multicentre, waiting list controlled trial of a parenting intervention in socially and ethnically diverse urban areas in England. Participants were invited from 34 areas and were randomly assigned with an allocation ratio of 1&#xb7;154:1&#xb7;000 to the SFSC parenting programme or waiting list control. The randomisation sequence was made by a researcher using an online algorithm and was stratified by site, parent gender, and self-referral status. Researchers collecting outcome data and those analysing data were masked to randomisation but participants were not. Participants were any adult caregivers (aged &#x2265;18 years) of children aged 3-18 years. The intervention was delivered in weekly, 3-h group sessions over 13 weeks. The primary outcome was parental mental wellbeing assessed with the Warwick-Edinburgh Mental Well-Being Scale at post-intervention and a 6-month follow-up. Cost-effectiveness was evaluated using a within-trial cost-utility analysis. All analyses were conducted on an intention-to-treat basis. The trial was prospectively registered (ISRCTN15194500). Between Aug 5, 2019, and Dec 17, 2022, 1214 individuals were screened for eligibility, of whom 674 participants were randomised to the waiting list control (n=314) and to the intervention group (n=360). Most participants were women (641 [95%]; 33 [5%] men) and from diverse social and ethnic minority backgrounds (350 [52%] had a household income less than &#xa3;20&#x2008;000 per year and 420 [62%] from ethnic minority groups). The attrition rate at the 6-month follow-up was 30% (200 participants). Participants in the intervention group reported higher mental wellbeing at both post-intervention (mean difference 1&#xb7;89 [95% CI 0&#xb7;64-3&#xb7;13]) and the 6-month follow-up (1&#xb7;66 [0&#xb7;30-3&#xb7;02]) compared with the waiting list control group. The mean cost per participant attending the SFSC programme was &#xa3;1081. There were three adverse events recorded, all in the control group and unrelated to the intervention. The SFSC parenting programme can improve parental mental wellbeing in a diverse sample of families living in disadvantaged areas across England, with no significant increase in cost. Evidence-based parenting interventions, such as SFSC, should be implemented at scale to promote family and child health. UK National Institute for Health and Care Research (NIHR).

Relacorilant is a selective glucocorticoid receptor modulator designed to reduce excess cortisol activity by competing with cortisol for glucocorticoid receptor binding, mitigating the clinical manifestations of endogenous hypercortisolism (Cushing's syndrome). The aim of this study was to assess the efficacy and safety of relacorilant in adults with endogenous hypercortisolism. This multicentre, phase 3, double-blind, placebo-controlled, randomised-withdrawal study enrolled adults with endogenous hypercortisolism and hypertension, hyperglycaemia, or both and was conducted at 77 study centres across 11 countries. Key inclusion criteria included being aged 18-80 years with at least two clinical signs or symptoms of hypercortisolism. In the open-label phase, patients received oral, once-daily relacorilant (escalation from 100 mg up to 400 mg) for 22 weeks. Patients who met response criteria were randomly assigned (1:1) by the interactive web response system to continue relacorilant 400 mg (or highest tolerated dose) or placebo for 12 weeks in the randomised-withdrawal phase. Participants and investigators were masked to treatment assignment. The primary outcome was the proportion of patients who lost hypertension response during the randomised-withdrawal phase compared between relacorilant and placebo at week 12. As per protocol, this outcome was assessed in all participants who received at least one dose of study drug in the study period (intention-to-treat population). Missing randomised-withdrawal week 12 values were considered a loss of response. Safety was assessed in all enrolled patients who received at least one dose of study drug in that period. This study is registered with ClinicalTrials.gov, NCT03697109. Between Oct 16, 2018, and April 15, 2024, 404 patients were screened, 152 were enrolled, and 95 completed the open-label relacorilant phase. 62 patients met response criteria and were randomly assigned to relacorilant (30 total participants [21 met hypertension response criteria]) or placebo (32 total participants [22 met hypertension response criteria]). In the 30 participants in the relacorilant group, the mean age was 46&#xb7;6 years (SD 11&#xb7;0), 22 (73%) were female, and eight (27%) were male. In the 32 participants in the placebo group, the mean age was 48&#xb7;8 years (SD 14&#xb7;4), 26 (81%) were female, and six (19%) were male. During the randomised-withdrawal phase, significantly more patients with baseline hypertension who were randomly assigned to placebo lost hypertension control compared with those who continued relacorilant (proportion difference 34%; odds ratio 0&#xb7;17 [95% CI 0&#xb7;04-0&#xb7;77]; p=0&#xb7;022). In the randomised-withdrawal phase safety population, the most common adverse events in the 30 participants given relacorilant and the 32 participants given placebo were back pain (5 [17%] vs 6 [19%]), acne (3 [10%] vs 0), arthralgia (3 [10%] vs 3 [9%]), bursitis (3 [10%] vs 0), headache (3 [10%] vs 4 [13%]), and insomnia (0 vs 4 [13%]). There were no cases of excessive glucocorticoid receptor antagonism, adrenal insufficiency, vaginal bleeding associated with endometrial hypertrophy, drug-induced hypokalaemia, or drug-induced QT interval prolongation. Patients treated with relacorilant were more likely to maintain hypertension control compared with patients treated with placebo. The findings support consideration of relacorilant as a therapeutic option to reduce the harmful and debilitating effects of endogenous hypercortisolism. Corcept Therapeutics.

Low-cost and scalable behavioural interventions to prevent HIV among young people in Africa are needed. As access to smartphones grows, digital interventions will become increasingly viable. We assessed the efficacy of an interactive narrative-based smartphone game (Tumaini) designed to increase age and condom use at first sex. In this two-arm, non-blinded, individually randomised trial, participants aged 12-14 years were recruited at community level in Kisumu, Kenya. Sex-stratified block randomisation (1:1; block size of 10) was undertaken by study staff with no contact with participants. For three 5-7-week gameplay periods during school holidays in the first 3 years, participants in the intervention group received Tumaini and participants in the control group received Brainilis, a maths game, on study-provided low-cost smartphones. Participants were followed-up for 45 months, completing a baseline survey and 12 follow-up surveys. Assignment was known to trial staff but masked to data analysts. The primary outcome was a binary measure of high-risk sexual debut (no condom use) versus low-risk (condom use) or no sexual debut, assessed at endline in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04437667, where it is suspended pending extension. Between Oct 1 and Dec 3, 2020, 996 adolescents (mean age 14&#xb7;0 years [SD 0&#xb7;6]; 499 in the intervention group and 497 in the control group) were enrolled. At endline, 974 (485 in the intervention group and 489 in the control group, and 484 female and 490 male) completed the study and were included in the intention-to-treat analysis. Excluding those reporting sexual debut before baseline, 10% (41 of 409) of participants in the control group reported a high-risk sexual debut compared with 6% (23 of 407) of participants in the intervention group (risk ratio [RR] 0&#xb7;56 [95% CI 0&#xb7;34-0&#xb7;92]). For female participants, 10% (21 of 207) in the control group and 3% (seven of 206) in the intervention group reported a high-risk sexual debut (RR 0&#xb7;34 [95% CI 0&#xb7;15-0&#xb7;77]). For male participants, this outcome was not significantly different, with 10% (20 of 202) of participants in the control group versus 8% (16 of 201) of participants in the intervention group reporting a high-risk sexual debut (RR 0&#xb7;80 [95% CI 0&#xb7;43-1&#xb7;51]). There was no difference in experience of or age at sexual debut. No serious adverse events resulted from trial participation. The results of the study provide evidence to support the potential of digital behavioural HIV prevention, serious games for sexual health, and pre-sexual risk intervention among adolescents in sub-Saharan Africa. US National Institute of Mental Health and Emory Center for AIDS Research.

Climate change is a substantial global health threat in the 21st century, disproportionately affecting low-income and middle-income countries (LMICs), which face significant climate risks, pre-existing vulnerabilities, and have relatively few interventions in place. With a scarcity of research in LMICs, and diminishing development assistance, setting priorities to address climate change-related health impacts on women and children is both urgent and prudent. We consulted 88 climate and health researchers between 2022 and 2024 to generate relevant questions regarding climate change impacts on women and children's health and potential solutions. A diverse group of 52 experts prioritised a shortlist of 70 questions using the Child Health and Nutrition Research Initiative method. The top three priorities included vulnerability mapping, integrating climate metrics into surveillance, and long-term heat exposure effects. This Health Policy underscores key knowledge gaps in climate-related health outcomes affecting women and children in LMICs, and suggests a focused research agenda for guiding global investments in resilience and adaptation.

Early discontinuation of empirical antibiotics in adults with high-risk febrile neutropenia based on clinical stability and defervescence, irrespective of neutrophil count, has been shown to reduce antibiotic exposure without compromising safety. We aimed to evaluate this approach in children with cancer, a population for which randomised trials in high-income settings are lacking. We conducted an investigator-initiated, multicentre, open-label, randomised, superiority trial in three paediatric haematology-oncology centres in Denmark. Patients aged 0-17 years receiving intensive chemotherapy and presenting with fever during high-risk neutropenia (absolute neutrophil count <0&#xb7;5&#x2009;&#xd7;&#x2009;109 cells per L anticipated to last &#x2265;7 additional days) were eligible. Patients with microbiologically documented infection were excluded. Fever episodes were randomly assigned (1:1) to either early discontinuation of intravenous antibiotics after 48 h of defervescence and clinical stability (short treatment group), or continuation until neutrophil recovery with a maximum of 10 days per episode (long treatment group). Randomisation was done using a computer-generated sequence embedded in a dedicated electronic data capture system, stratified by site, via block randomisation with random block size (of four, six, or eight). The randomisation sequence was concealed until allocation, and investigators were unaware of group assignment until completion of randomisation. The primary endpoint was the number of days on antibiotics within 28 days after the first treatment initiation. Main analyses were done in the intention-to-treat population. Safety was assessed by infection-related serious adverse events, including bacteraemia, focal infection, sepsis, and death. The trial was registered with ClinicalTrials.gov, NCT04637464, and is completed. Between Nov 26, 2020, and Jan 28, 2025, febrile episodes were systematically screened for eligibility; 88 febrile episodes in 70 children were randomly assigned (45 to the short treatment group and 43 to the long treatment group) and included in the intention-to-treat analysis. 37 (42%) episodes were in female participants and 51 (58%) were in male participants. The time on antibiotic treatment within the 28-day follow-up was a mean of 8&#xb7;1 days (SD 5&#xb7;9) in the short treatment group versus 13&#xb7;5 days (6&#xb7;2) in the long treatment group, leading to an estimated difference of -4&#xb7;0 days (95% CI -6&#xb7;0 to -1&#xb7;9; p=0&#xb7;0002). Serious adverse events occurred in ten (22%) of 45 episodes in the short treatment group and nine (21%) of 43 in the long treatment group (risk ratio 1&#xb7;06 [95% CI 0&#xb7;46-2&#xb7;47]). No deaths occurred. Early discontinuation of intravenous antibiotics regardless of neutrophil recovery reduced unnecessary antibiotic exposure without indications of compromised safety. Although the study was not powered to detect differences in rare safety outcomes, it provides evidence for this approach in the management of children with cancer and high-risk febrile neutropenia. Danish Childhood Cancer Foundation, Danish Cancer Society, Innovation Fund Denmark.

Automated insulin delivery (AID) systems have been shown to improve glycaemic outcomes in people with type 1 diabetes managed with insulin pump therapy. No randomised studies have evaluated the benefits of tubeless AID in both adults and children with suboptimal glycaemia compared with multiple daily injections. We aimed to evaluate the safety and efficacy of a tubeless AID system compared with multiple daily injections in this population. RADIANT was a multicentre, international, parallel-group, open-label, randomised, controlled trial done in 19 hospitals in the UK, Belgium, and France. Participants aged 4-70 years with type 1 diabetes managed with multiple daily injections and continuous glucose monitoring and who had HbA1c levels of 7&#xb7;5-11% (58-97 mmol/mol) were randomly assigned (2:1) to tubeless AID or control (multiple daily injections) using a permuted-block design. Participant and study teams were not masked to group allocation. The primary outcome was the adjusted between-group difference in HbA1c at 13 weeks assessed for superiority. Primary and safety outcomes were assessed in the modified intention-to-treat population (all randomly assigned participants). The study is registered with ClinicalTrials.gov, NCT05923827, and has been completed. Between Sept 11, 2023, and April 26, 2024, 188 participants were randomly assigned to the AID group (n=125) or the control group (n=63). The AID group had a greater reduction in HbA1c, from 8&#xb7;1% (SD 0&#xb7;7; 65 mmol/mol [SD 7&#xb7;7]) at baseline to 7&#xb7;2% (0&#xb7;6; 55 mmol/mol [6&#xb7;6]) at 13 weeks, compared with the control group, from 8&#xb7;1% (0&#xb7;6; 65mmol/mol [6&#xb7;6]) at baseline to 8&#xb7;0% (0&#xb7;7; 64 mmol/mol [7&#xb7;7]) at 13 weeks, with an adjusted mean difference of -0&#xb7;8% (95% CI -1&#xb7;0 to -0&#xb7;6; -8&#xb7;7 mmol/mol [95% CI -10&#xb7;9 to -6&#xb7;6]; p<0&#xb7;0001). During the 13-week trial, no episodes of severe hypoglycaemia or diabetic ketoacidosis occurred in either treatment group. 39 adverse events were reported among 28 participants in the AID group, and three adverse events among three participants in the control group. Two serious adverse events (Kawasaki disease and acute coronary syndrome) occurred in the AID group unrelated to the study device or procedure. Results from this trial show the clinical efficacy of direct transition from multiple daily injections to tubeless AID in adults and children with type 1 diabetes, with no safety concerns, supporting AID as a therapeutic option within standard of care for people with type 1 diabetes. Insulet Corporation.