Archives of Disease in Childhood

ImportanceWhole genome sequencing (WGS) is increasingly used to diagnose severely ill children, yet the long-term impact of a genetic diagnosis on healthcare utilization and resource allocation remains poorly understood. ObjectiveTo determine the influence of a genetic diagnosis via WGS on long-term healthcare utilization metrics in severely ill children. DesignA retrospective cohort study using data from the Next Generation Children study (2016-2020) with record linkage and analysis of primary care records conducted between 2022 and 2024. SettingA multicenter study involving primary care and hospital records linked via the UK National Health Research Institute (NIHR) Rare Disease Bioresource, Cambridge, UK. ParticipantsA referred sample of 270 severely ill children who underwent WGS. Exposure(s)Receipt of a genetic diagnosis (87/270; 32%) compared to those who remained undiagnosed (183/270; 68%) following WGS. Main Outcome(s) and Measure(s)Comparison of 36 healthcare utilization parameters, including hospitalizations, primary care prescriptions, and diagnostic tests. ResultsAmong the 270 children analyzed, those receiving a genetic diagnosis (n=87) exhibited significantly higher overall healthcare utilization compared to undiagnosed peers (n=183). This included increased hospital admissions and outpatient visits, particularly for neurodevelopmental and seizure-related conditions. Diagnosed children received a higher volume of neurological, gastrointestinal, and nutritional prescriptions. The most pronounced differences in utilization were observed in children initially diagnosed in neonatal (NICU) or pediatric (PICU) intensive care settings. While genetic diagnosis was not associated with reduced healthcare costs during the study period, it was linked to more targeted, condition-specific medical care. Conclusions and RelevanceWGS diagnosis facilitates the integration of specialist care and the alignment of healthcare resources with the specific needs of children with complex disorders. These findings suggest that while costs may not decrease immediately, a diagnosis enables more precise and targeted clinical management. Key PointsO_ST_ABSQuestionC_ST_ABSDoes a genetic diagnosis through whole genome sequencing influence long-term healthcare utilization in severely ill children? FindingsIn this cohort study of 270 children, those who received a genetic diagnosis demonstrated significantly greater overall healthcare utilization, including more hospitalizations and targeted prescriptions, compared with undiagnosed children. MeaningA genetic diagnosis facilitates the integration of specialized, condition-specific care, helping to align healthcare resources with the individual needs of children with complex disorders.

Introduction"Encompass" is a participatory group-based intervention originating from low- and middle-income countries, co-developed with parents and professionals to enhance the wellbeing, health literacy and empowerment of caregivers of young children with complex neurodisability. We aimed to assess feasibility and acceptability of a) intervention delivery in two socially deprived United Kingdom (UK) urban areas and b) evaluation methods including data collection on programme outcomes and costs. MethodsWe conducted a mixed-methods pilot and feasibility study with caregivers of children under five years with complex neurodisability. Feasibility and acceptability of intervention delivery were assessed based on recruitment rates, group attendance, fidelity checklists and qualitative interviews with caregivers and facilitators. Feasibility and acceptability of evaluation methods were explored through follow-up rates, questionnaire completeness, and caregiver feedback on outcome measures. Data relating to implementation at organisational and system levels were explored through interviews with facilitators and key partners. Results were compared to predefined traffic light criteria (green, amber, red) to determine whether a larger scale evaluation was warranted. ResultsEight caregivers participated in the programme. Fidelity of delivery and follow-up questionnaire completion met green criteria, while recruitment and attendance met amber criteria, indicating that minor adaptations are required before scaling up. Qualitative findings demonstrated high acceptability of the programme among caregivers and facilitators, particularly valuing the co-facilitation model, participatory approach, and peer support. Flexible delivery, including online participation and communication support, enhanced accessibility for families with diverse needs. Capturing programme delivery costs was feasible and provided preliminary estimates to inform future economic evaluation. ConclusionsOur findings provide proof of principle that "Encompass" can feasibly and acceptably be delivered and evaluated with caregivers of children with complex neurodisability in an ethnically diverse UK community health setting. The findings support progression to a larger-scale evaluation, with refinements to recruitment strategies and delivery logistics. Patient or Public ContributionCaregivers with lived experience were central to developing the "Encompass" programme and this study. Four local mothers of children with complex neurodisability contributed to planning, recruitment, and sense-checking the findings.

PurposeCaregivers of children with complex neurodisability frequently experience high caregiving demands, social isolation, unmet support needs, and reduced wellbeing. This paper explores caregivers perceptions of the impact of "Encompass", a ten-modular, community-based group support programme for caregivers of children under five with complex neurodisability, co-facilitated by an expert parent. Materials and methodsThis study formed part of a pilot and feasibility study conducted in two socially disadvantaged, ethnically diverse urban areas in the United Kingdom. Outcome measures were collected pre-intervention, post-intervention and at three-month follow-up to explore caregiver wellbeing, empowerment, activation, and quality of life. Semi-structured qualitative interviews were conducted within three months of programme completion. Interview data were analysed using deductive coding informed by the "Encompass" programme theory alongside inductive analysis to explore mechanisms and unanticipated benefits. Results and conclusionsSeven participating caregivers described improved wellbeing, increased confidence in caring for their child, navigating services, advocating for their family and engaging in the community. Peer support, shared learning and expert parent facilitation were key identified mechanisms of impact. Data from outcome measures showed patterns of improvement post-intervention, with less consistent eYects at follow-up. Findings confirmed the key change mechanisms, informing future iterations and other caregiver group programmes. Trial RegistrationClinicalTrials.gov Identifier: NCT06310681

PurposeWhile genomic testing is integral to pediatric inborn errors of immunity (IEI) care, few studies have examined strategies to support its optimal delivery. This study aimed to characterize a pediatric IEI cohort and assess the impact of implementing a mainstream model-of-care (MoC). Materials/MethodsComprehensive chart audit was conducted for patients ([&le;]18y) who received IEI genomic testing in Queensland, Australia, from 2017-2025. Descriptive analyses captured demographic and clinical characteristics, genomic testing and results, and management outcomes. Inferential analyses assessed changes in genomic practices pre-MoC (<2021) and post-MoC ([&ge;]2021). Results322 patients met eligibility criteria (n=481 genomic test). Diagnostic yield (27.6%) varied by testing indication, with the highest rate among phagocytic defects (n=4/4;100%) and severe combined immunodeficiency (n=8/10;80%). Very-early-onset inflammatory bowel disease had the lowest diagnostic yield (n=3/68;4.4%), prompting changes to testing criteria. Molecular diagnosis resulted in management changes for 90.5% patients. Genomic testing was widely used pre-MoC (n=251 genomic tests). All outcomes significantly improved pre-and post-MoC (p<0.05): duplicate testing decreased (13.9% to 0%); variants of uncertain significance reduced (37.7% to 7.1%); informed consent documentation increased (70.5% to 88.4%); and diagnostic yield increased (16.2% to 27.4%). ConclusionTargeted interventions are needed to support delivery of genomic testing and strengthen service effectiveness.

Objectives: Acute gastroenteritis is a leading cause of pediatric emergency department (ED) visits. While ondansetron reduces vomiting, intravenous rehydration, and hospital admissions, its efficacy when initiated at triage remains unclear. We aimed to evaluate whether triage nurse-initiated administration of ondansetron in children with suspected gastroenteritis reduces the proportion of patients requiring observation following initial physician assessment. Methods: We conducted a randomized, double-blind, placebo-controlled trial in a tertiary pediatric ED in Canada. Children aged 6 months to 17 years presenting with morae than 3 episodes of vomiting in the preceding 24 hours (including 1 within 2 hours of arrival), were eligible. At triage, we randomized participants to receive liquid ondansetron or a color- and taste-matched placebo. The primary outcome was the proportion of patients requiring observation after the first physician evaluation. Secondary outcomes included post-intervention vomiting, ED length of stay, patient comfort, and 48-hour return visits. The trial was registered at ClinicalTrials.gov (NCT03052361). Results: Recruitment was stopped prematurely due to the COVID-19 pandemic. Ninety-one participants were randomized to ondansetron (n= 44) or placebo (n= 47). Overall, 40 patients (45%) were discharged immediately after the initial physician assessment, with no difference between the ondansetron and placebo groups (44% vs. 45%; absolute difference -1%, 95% CI: -20% to 19%). No significant differences were observed in all secondary outcomes. Conclusion: In this trial, triage nurse-initiated ondansetron administration did not reduce the need for ED observation in children with presumed gastroenteritis. While being underpowered, this study could inform researchers planning larger clinical trials.

Co-designed research in paediatric HSCT is limited. We sought to determine research priorities which represent the shared priorities of patients, parents, carers, and healthcare professionals (HCP) within Australia, New Zealand, the Netherlands and United Kingdom. An international, multiphase priority-setting methodology was implemented in partnership with the James Lind Alliance and delivered over an 18-month period. Part 1: an international scoping survey asked respondents to submit their research uncertainties related to paediatric HSCT. Part 2: summarising and evidence-checking the submitted uncertainties. Part 3: interim prioritisation survey. Part 4: consensus workshop. In the first international scoping survey, 667 topic ideas were suggested (45% by consumers, 55% by HCP), which were categorized into 80 summary questions. After systematic literature review, 35 summary questions were judged to be true uncertainties (i.e. not answered by existing evidence). These 35 uncertainties were included in a second interim prioritisation survey, completed by 224 participants. From those, a shortlist of 19 questions was drawn. After a multistakeholder workshop, consensus was reached on the top 10 priorities. The PSP identified important research gaps in the management of paediatric HSCT. Priority areas included: implementing personalised medicine approaches, improving immune recovery and adjunct interventions such as exercise, nutrition and microbiome-directed strategies.

BackgroundNeonatal disorders such as post-infectious hydrocephalus exhibit a higher incidence in Africa, where the intricate relationships between genetic ancestry, environmental exposures, and other risk factors likely contribute to the increased incidence. MethodsTo start to characterize the common genetic architecture of Ugandan infants, we analyzed genome sequencing data from 1,030 Ugandan infants recruited from studies targeting neonatal sepsis and hydrocephalus. We employed genetic admixture analysis and integrated geospatial data to examine the relationships between genetic backgrounds and disease prevalence within this cohort. ResultsOur results identified four distinct genetic admixture groups, each correlating strongly with specific geographic distributions across Uganda. Notably, a predominance of one admixture group, most common in northern Uganda, was overrepresented in the participants with post-infectious hydrocephalus. ConclusionThis study underscores the importance of genetic factors in disease manifestation at the population level, and a role for such precision public health approaches in complex neonatal disorders in African populations.

BackgroundCaregiver skills training programmes are well-researched in the fields of autism and intellectual disability, but children with motor disorders such as cerebral palsy remain underrepresented despite their high prevalence. These caregivers face unique challenges, and group programmes may provide family-centred care through information provision, problem-solving and peer support. MethodsSystematic searches of five databases (CINAHL, Medline, Embase, PsychINFO and ERIC) were conducted for interventional studies of group programmes aiming to improve the skills, confidence and wellbeing of caregivers of children with neurodisability focusing on motor disorders. Data were extracted on study and intervention characteristics and outcomes. Risk of bias was assessed, effect sizes calculated, and results summarised descriptively using forest plots. ResultsOf 6093 studies identified, 21 studies met inclusion criteria (nine randomised-controlled trials, two quasi-experimental and ten pre-post designs). Most reported on programmes developed in resource-constrained settings and addressed caregiver skills, coping strategies, or health-promoting behaviours. Outcomes were grouped according to caregiver wellbeing, caregiver skills and confidence, and social support and family functioning. Child outcomes were reported separately. Most caregiver outcomes showed positive effects, though most studies had high risk of bias due to self-reported outcomes and lack of blinding of intervention allocation and outcome measurement. DiscussionGroup-based training programmes show promise for improving caregiver skills and wellbeing. Clinicians and stakeholders in high-income countries may learn from these innovations in low-resource settings. Future research should strengthen protocol reporting, address attrition, control for confounding factors, and establish a core set of caregiver-reported outcomes to better capture programme impact. Systematic review registrationPROSPERO registration CRD42024595002

BackgroundWell-child visits (WCVs) are essential for preventive care, yet missed appointments often lead to delayed interventions. We developed and validated models to predict next-visit nonattendance using routine electronic health record data. MethodsUsing data from two Chicago-area pediatric practices, Practice A (1,215 patients; 3,654 visits) and Practice B (1,271 patients; 3,044 visits), we compared regularized logistic regression, random forest, and XGBoost models. Predictors included visit context, prior utilization, and patient characteristics. Models were trained on Practice A and validated on Practice B. ResultsMissed-next-visit rates were 16.2%(A) and 20.7%(B). In external validation, performance was similar across models (AUC 0.66-0.68). At the threshold maximizing F1 score, recall ranged from 0.54-0.71. The LASSO logistic regression model identified six key predictors: timepoint, visit delay, prior no-shows, schedule lead time, new patient status, and immunization refusal. SHAP values confirmed these process measures as among the most influential features across all models. ConclusionPredicting WCV nonattendance is feasible using routine data. A simple logistic regression model performs comparably to complex algorithms, offering a practical pathway for clinical integration. By identifying at-risk families during a current appointment, this may enable clinicians to provide proactive support to support preventive care before a lapse occurs. ImpactO_LIMissed well-child visits are common, leading to an increasing number of preventable acute care visits, delayed recognition of developmental delays, and missed opportunities to initiate early intervention C_LIO_LIA multimodal approach is needed to support well-child visit attendance C_LIO_LIMachine learning is an emerging tool to predict well-child visit no show rates with implications for future interventions to support families at risk for missing well-child visits and promote positive health outcomes C_LI

BackgroundThere are concerns that glucagon-like peptide-1 receptor agonists (GLP1s) increase the risk of acute pancreatitis. MethodsWe searched Medline and clinicaltrials.gov in March 2026 for placebo-controlled randomized trials of semaglutide and tirzepatide reporting the incidence of acute pancreatitis, according to a pre-specified protocol (PROSPERO ID 1346039). The primary analysis used a fixed-effect Mantel-Haenszel odds ratio. Heterogeneity was assessed using Cochrans Q and I-squared. Results1635 studies were found, 31 placebo-controlled trials of which were included, totalling 40,274 patients. There were 59 acute pancreatitis events in GLP1 groups (of 22,841 patients) and 50 in placebo groups (of 17,433 patients). The pooled fixed-effect Mantel-Haenszel odds ratio was 0.99 (95% confidence interval 0.67 to 1.45; p=0.95). Active-treatment exposure totaled 51,346 patient-years, including 47,749 patient-years for semaglutide and 3,598 patient-years for tirzepatide. Sensitivity analysis for risk ratio, and subgroup analysis divided by drug class, disease focus, or dose, did not reveal any significant differences. ConclusionsSemaglutide and tirzepatide were not associated with an increased risk of acute pancreatitis versus placebo. These findings are reassuring, but small differences in risk cannot be fully excluded given the rarity of events. Given the rapidly-evolving nature of this field and the importance of the dataset, this review will be updated as further randomized trials are published.

Background Education outcomes predict life chances. However, poverty, ill-health and disability are barriers to achievement. We examined determinants of academic attainment of children with and without major congenital anomalies in state-funded mainstream schools at ages 11 and 16 (key stages [KS] 2 and 4). Methods and Findings Routinely collected electronic records for children born in Wales 01/01/1998-31/12/2007 until 31/12/2019 were linked in the Secure Anonymised Information Linkage (SAIL) Databank. Education outcomes were explored using logistic regression, adjusting for: anomalies, maternal and child deprivation, prescribing, hospitalisation, gestation length, childs sex, and special education needs (SEN) provision. Children with anomalies were less likely to achieve academic standards: however, attainment was more closely associated with affluence. At age 11, 81.87% (7167/8754) with and 93.80% (232,450/247,814) without anomalies passed (odds ratio [OR] 0.30, 95% confidence intervals [CI] 0.28-0.32). At age 16, 46.76% (2070/4427) with and 56.10% (69,732/124,300) without anomalies achieved 5 General Certificates of Secondary Education (GCSEs) at grades C-A* including English/Welsh, Maths and Science (EWMS) (OR 0.69, 0.65-0.73). Discrepancies narrowed in adjusted analyses, particularly when SEN provision was accounted: aOR 0.72 (0.66-0.78) at KS2, and aOR 0.93, (0.87-1.00) for 5 GCSEs C-A* with EWMS. These GCSEs were achieved by 29.65% (307/1034) children with anomalies and 38.42% (10,875/28,305) of unaffected children in the most deprived quintile{dagger}: in the most affluent quintile, figures were 67.57% (547/810) and 74.98% (16,978/22,644). Children with anomalies, receiving maximum SEN support, eligible for Free School Meals (FSM) were the least successful: 5/192 (2.6%) passed 5 GCSEs C-A* with EWMS, as did 37/354 (10.4%) ineligible for FSM. The strongest associations with these GCSEs were SEN statements (aOR 0.07, 0.06-0.07), FSM eligibility (aOR 0.39, 0.37-0.41), and epilepsy (aOR 0.60, 0.45-0.80). However, data were unavailable for 15-18% of children, mainly those educated outside mainstream schools, and some co-morbidities. Generalisation of findings to other countries rests with readers. Conclusions Many children with anomalies from affluent households succeeded. The children left behind lived with poverty and ill-health from congenital anomalies and/or epilepsy. SEN provision mitigated the impact of disadvantage, but poor children with anomalies were unlikely to succeed. {dagger}taking maternal Welsh Index of Multiple Deprivation (WIMD) 2014 at birth.

BackgroundAtopic diseases are estimated to affect 30-40% of the global population. However, the potential protective effect of hypoallergenic infant formula against conditions such as atopic dermatitis (AD), cows milk protein allergy (CMPA), and asthma remains uncertain. ObjectiveTo conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating hypoallergenic formula for atopic disease prevention in high-risk infants. The primary outcome was AD and secondary outcomes were CMPA and asthma. MethodsA systematic review and meta-analysis was conducted according to PRISMA 2020. RCTs involving high-risk infants were identified through PubMed, Cochrane Library, and Web of Science. Exclusion criteria included interventions not initiated at birth, enrolment of sick infants, and non-RCTs. Pooled Relative Risks (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. ResultsWe included 9 RCTs that enrolled high-risk infants. The meta-analysis found a borderline significant protective effects of AD (RR=0.78 [0.59-1.03], p=0.059; I2=46.5%), a significant protective effect of hypoallergenic formula in prevention of CMPA (RR=0.51 [0.27-0.97], p=0.0228; I2=37.3%), and no significant risk reduction for asthma (RR=0.78 [0.51-1.20], p=0.059; I2=37.5%). ConclusionThis systematic review and meta-analysis found no statistically significant protective effect of hypoallergenic formula for AD or asthma, though a non-significant trend toward risk reduction was observed. A significant risk reduction was seen for CMPA (RR{approx}0.5), although not all diagnoses were confirmed by oral food challenge. These findings suggest potential patient-specific benefits, but larger, well-designed RCTs are needed to confirm them.

Purpose To systematically review population preferences for expanded carrier screening programmes to inform service delivery and health policy. Methods PubMed, CINAHL, and Scopus were searched from 1995 to 2025 on carrier screening for autosomal or X-linked recessive genetic conditions across adult general populations. Included studies elicited preferences on attributes regarding the design or delivery of carrier screening programs. We extracted preferences for each attribute, mapped qualitative findings to these preferences, assessed risk of bias and performed meta-analysis on the willingness-to-pay for screening using Bayesian multilevel modelling. All findings are reported in 2024 USD. Results Thirty one studies, including 16 quantitative, 11 qualitative, and 4 mixed-methods studies were included. Participants expressed preferences for which conditions to include in ECS, joint vs individual screening, the value of information provided before screening, in-person over online counselling, type of healthcare provider, and preconception testing. Willingness-to-pay was right-skewed with 9% of participants not willing to pay any amount, a median of $107 and an interquartile range between $41 and $226. Most studies demonstrated a high risk of bias. Conclusions We report preferences of the general population regarding expanded carrier screening programmes, including suggested amounts for copayment if subsidised by the health system.

BackgroundAnti-seizure medications (ASMs) are widely used in neonatal intensive care, but there is limited evidence for their safety and long-term outcomes. Phenobarbital is the only ASM generally recommended for use in neonates, but it has been linked with adverse effects in infants. Other anti-seizure medications, such as fosphenytoin, levetiracetam, and midazolam are used off-label in this population. MethodsWe performed a retrospective observational study of 18,548 infants in intensive care at an academic medical center, examining links between neonatal ASM exposure and neurological outcomes over the follow-up period of median 4{middle dot}5 years (IQR 1{middle dot}6 - 9{middle dot}2 years). The real-world clinical data included comprehensive maternal, perinatal, and medication data. The outcomes of interest were cerebral palsy, epilepsy, intellectual disability, and visual impairment. Multivariable cause-specific Cox models were used to estimate hazard ratios (HRs) for phenobarbital, levetiracetam, midazolam, and fosphenytoin exposure. Models were adjusted for major perinatal confounders, including gestational age, birth weight, mode of delivery, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and stroke. FindingsExposure to the median cumulative dose of phenobarbital was associated with increased HR for epilepsy (HR 1{middle dot}35; 95% CI, 1{middle dot}11-1{middle dot}62, p = 0{middle dot}002) visual impairment (HR 1{middle dot}20; 95% CI, 0{middle dot}99-1{middle dot}45, p = 0{middle dot}06), and intellectual disability (HR 1{middle dot}18; 95% CI, 0{middle dot}99-1{middle dot}41, p = 0{middle dot}06). In contrast, levetiracetam was associated with smaller risk increases for cerebral palsy (HR 1{middle dot}13; 95% CI, 1{middle dot}03-1{middle dot}23, p = 0{middle dot}006, epilepsy (HR 1{middle dot}14; 95% CI 1{middle dot}05-1{middle dot}24, p = 0{middle dot}002 and visual impairment (HR 1{middle dot}18; 95% CI 1{middle dot}11-1{middle dot}26, p <0{middle dot}0001). Midazolam exposure was associated with slightly increased risk of intellectual disability (HR 1{middle dot}09, 95% CI, 1{middle dot}02- 1{middle dot}16). Results for fosphenytoin were statistically not significant. We did not find evidence of a dose-dependent effect of phenobarbital, but increased maximum phenobarbital blood concentration were associated with elevated hazard ratios for cerebral palsy (HR 1{middle dot}48; 95% CI, 1{middle dot}07-2{middle dot}06, p = 0{middle dot}02 for 50 {micro}mol/l increase) and epilepsy (HR 1{middle dot}64; 95% CI, 1{middle dot}14-2{middle dot}35, p = 0{middle dot}007 for 50 {micro}mol/l increase). InterpretationThe results align with previous findings linking phenobarbital to neurodevelopmental harm and emphasize the need for its cautious use in neonates. Levetiracetam had more favorable safety profile. These findings highlight the potential of real-world data to inform evidence-based neonatal pharmacotherapy when randomized trials are impractical. FundingThe Foundation for Pediatric Research (Finland), the Association of Friends of the University Childrens Hospitals (Lastenklinikoiden Kummit ry), and internal institutional funding.

BackgroundRecurrent sore throat affects a small minority of adults but can cause substantial morbidity. Evidence to guide tonsillectomy eligibility in adults is limited, and current criteria are extrapolated from paediatric populations. We aimed to describe the epidemiology, management, and prognosis of adult sore throat in UK primary care. MethodsUsing CPRD Aurum (2010-2020 adults with a first coded episode of sore throat or tonsillitis were identified and matched to controls. Episode frequency, antibiotic use, ENT referral, and tonsillectomy were analysed. Predictors of recurrent episodes ([&ge;]3 in 365 days), referral, and tonsillectomy were assessed using time-to-event, multinomial logistic, and multilevel mixed-effects regression models. FindingsOf 4.45 million adults, 1.70 million (38.3%) had [&ge;]1 episode; most (61.5%) had only one, but 4.1% experienced [&ge;]3 within 1 year. Recurrent episodes were more common in younger females and those from more deprived areas. Only 21,869 patients (0.5% of the exposed cohort) underwent tonsillectomy, and just 25.7% of these met Paradise criteria at any time; conversely, only 13.9% of those meeting criteria underwent surgery. Patients who had a tonsillectomy tended to be younger, female, and from less deprived areas. Pre-tonsillectomy episode rates were unexpectedly low, but the data indicated that individuals with high baseline burden continue to experience elevated episode rates over several years. ConclusionsRecurrent sore throat is uncommon, but those affected face substantial disease burden. Current tonsillectomy patterns are poorly aligned with disease burden and show inequities by deprivation. Earlier identification of adults likely to develop recurrent episodes, and more timely surgical intervention, may improve patient outcomes and the cost-effectiveness of tonsillectomy.

BackgroundKlebsiella pneumoniae is a common cause of neonatal sepsis in Africa, and is frequently hospital acquired. We recently reported an outbreak of multidrug-resistant K. pneumoniae sepsis amongst neonates at a rural hospital in The Gambia, West Africa, involving 57 cases and case fatality of 60%. Here we undertook a retrospective pathogen genomic epidemiology study of clinical and environmental K. pneumoniae isolated during the outbreak, to identify the outbreak strain, refine the epidemic curve, confirm the environmental sources of contamination, monitor control of the outbreak, and characterise the outbreak strain in the context of the local and global pathogen population. Methods and FindingsWe sequenced all blood culture isolates identified as K. pneumoniae from patients aged 0-59 months (n=51 available, 77% from neonates), together with K. pneumoniae cultured from environmental samples during the outbreak investigation (n=16), and 56 stored blood culture surveillance isolates available from the previous decade (34 from neonates). Sequencing was performed using Oxford Nanopore Technologies (ONT) Mk10 flowcells and a PromethION instrument, yielding mostly complete genomes (79%). Genomic analysis revealed 23% of isolates were K. quasipneumoniae and identified the outbreak strain as K. pneumoniae ST39 with capsular (K) locus KL62. This strain was responsible for 29 cases (16 fatalities) and was identified in three samples of intravenous fluids collected from the neonatal ward during the investigation. It harboured a [~]187 kbp IncF plasmid carrying the extended-spectrum beta-lactamase (ESBL) gene blaCTX-M-15 and aac(3)-IId, encoding resistance to third-generation cephalosporins and gentamicin, respectively. The outbreak strain was not identified amongst historical surveillance isolates, and it was distinct from a KL23-ST39 strain responsible for an earlier outbreak at the Sir Edward Francis Small Teaching Hospital in Banjul, the countrys capital 7 years prior. Comparing the outbreak strain with publicly available genome data for ST39 and its associated sublineage (SL) 39, we observed SL39 has diversified into three common clonal groups, each associated with multiple K types, that have spread across Africa, Asia and Europe and have been associated with outbreaks of neonatal sepsis in Africa and elsewhere. We find SL39 is typically multidrug resistant, however the specific ESBL and carbapenemase genes vary by geographic location. ConclusionsPathogen whole-genome sequencing refined our understanding of the outbreak, allowing more precise identification to refine case numbers and case fatality calculations, and for precise identification of multi-use intravenous fluid bags as the source of the outbreak despite other samples being culture-positive for unrelated K. pneumoniae. This highlights the importance of infection prevention and control in reducing neonatal fatalities in low-resource settings, and the critical risk associated with multi-use reagents and equipment when caring for vulnerable neonates. The genomic analysis enabled us to identify and characterise the outbreak strain at high resolution, and together with global data highlights SL39 as an emerging high-risk multidrug-resistant, globally distributed clone of K. pneumoniae, capable of sustained transmission and high fatality.

BackgroundPediatric long COVID is associated with substantial symptom burden, yet evidence-based pharmacologic treatments remain limited. Low-dose naltrexone (LDN) has been proposed as a potential symptomatic therapy, but data in pediatric populations is lacking. MethodsWe conducted a retrospective analysis of pediatric and young adult patients ([&le;]25 years) with a clinical diagnosis of long COVID who were prescribed LDN between July 2020 and July 2025 at three multidisciplinary pediatric long COVID programs in the United States. Deidentified clinical data were extracted from medical records. Outcomes included symptom prevalence, dosing practices, treatment continuation or discontinuation, adverse effects, and available patient-reported quality-of-life measures (PedsQL and PROMIS(R)). FindingsThe study included 62 patients (mean age, 15.6 years [range, 8-23]; 53.2% male and 46.8% female). Fatigue was nearly universal (98.4%), followed by headaches (87.1%), brain fog (74.2%), dizziness/lightheadedness (67.7%), anxiety (66.1%), and post-exertional malaise (56.5%). LDN-treated patients demonstrated a higher prevalence of neurocognitive and autonomic symptoms, compared to general clinic cohorts. Most patients (71.0%) reported no adverse effects; the most common were vivid dreams (9.7%) and insomnia (9.7%). At follow-up, 66.1% of patients remained on LDN. Medication discontinuation was attributed to perceived lack of benefit (43.8%) or side effects (25.0%). Baseline quality-of-life measures at initiation showed marked impairment: PedsQL Physical Health (M=38.0, SD=20.9) and Multidimensional Fatigue (M=35.7, SD=15.8) scores were low. PROMIS scores indicated reduced physical functioning (M=36.8, SD=8.7) and cognitive functioning (M=40.8, SD=7.6), with elevated fatigue (M=68.0, SD=10.4) and pain interference (M=58.6, SD=8.2) relative to population norms. The study was not designed to assess efficacy. InterpretationLDN was primarily prescribed to patients with prominent fatigue, neurocognitive symptoms, and autonomic dysfunction, and was generally well tolerated. These findings provide descriptive evidence of real-world prescribing practices and support the need for clinical trials to systematically evaluate LDNs efficacy in pediatric long COVID.

UK-based quantitative research on the health and education outcomes of Unaccompanied Asylum-Seeking Children (UASC) remains limited, especially at national level. Linked administrative data provide an unprecedented opportunity to study these outcomes among UASC. This paper lays a foundation for further research, particularly examining the influence of socio-demographic, legal and environmental factors on UASCs health and educational outcomes. We described the UASC population with a first recorded episode of local authority care between 1st April 2005 and 31st March 2021 in ECHILD, which gathers national records for England, by age, gender, ethnicity, region, and placement type. We calculated linkage rates between the social care and educational dataset, estimating how many UASC were recorded as being enrolled in state-funded schools. We also assessed how many of those linked to the school dataset was linked to National Health Service (NHS) datasets. Finally, we explored how linkage rates between social care, education, and NHS datasets vary by socio-demographic factors and placement type. There were 37,170 UASC recorded in the ECHILD of which 32,570 (88%) were male and 24,290 (65%) aged 16 - 17 years. We found 7,740 (21%) UASC recorded as being enrolled in state funded schools, of whom 6,690 (88%) were also linked to NHS data. The linkage rate for UASC in the social care to health datasets was therefore 19%. Of those 16-17 years at entry in social care, 4% (1,060/24,290) were recorded as enrolled in school compared to 50% (6,390/12,880) under 16 years. Linkage to the school, and subsequently to the NHS dataset, wholly depends on enrolled state-funded education, excluding College and Sixth-form education. Despite this limitation, we characterised a national cohort of 6,890 UASC in England whose social care, education, and health outcomes can be examined.

ObjectiveTo evaluate whether new tuberculosis (TB) tools in the electronic health record (EHR) can support latent TB infection (LTBI) screening, testing and treatment among children and adolescents in a primary care setting. Study DesignThis retrospective cohort study included children and adolescents between the ages 1-25 years who had a well-child or well-adolescent visit at a Federally Qualified Health Center in Oakland, California, from December 2021 to December 2022. Four new EHR tools were introduced for the completion and documentation of TB risk factor screening, testing and treatment. Data were extracted from the EHR to identify gaps in these steps, and logistic regression was used to examine factors associated with completion of TB infection screening and testing. Acceptability was evaluated using provider satisfaction surveys before and after the implementation of TB EHR tools. ResultsOf 5,879 individuals (median age of 9 years at first visit, interquartile range (IQR) 4-13 years), 94% completed TB risk factor screening. Among those with a new risk factor, 59% had a TB infection test ordered and 96% completed testing. Ten participants (3%) tested positive, all initiated LTBI treatment, and most (n=7, 70%) completed treatment. Overall, 5,162 (88%) individuals completed their LTBI care cascade. Younger children ages 1-4 years were more likely to be screened for TB risk factors, but were less likely to be tested. Provider satisfaction increased from 40% to 71% for risk factor screening, and 36% to 77% for test ordering. ConclusionEHR tools supported completion of the pediatric LTBI care cascade, while also increasing provider satisfaction. EHR-based solutions show promise as part of multi-component strategies to address gaps in LTBI care for children and adolescents.

ImportanceGuideline-concordant care for young children with attention-deficit/hyperactivity disorder (ADHD) includes recommending parent training in behavior management (PTBM) as first-line treatment. However, assessing guideline adherence through manual chart review is time-consuming and costly, limiting scalable and timely quality-of-care measurement. ObjectiveTo evaluate the accuracy and explainability of large language models (LLMs) in identifying PTBM recommendations in pediatric electronic health record (EHR) notes as a scalable alternative to manual chart review. Design, Setting, and ParticipantsThis retrospective cohort study was conducted in a community-based pediatric healthcare network in California consisting of 27 primary care clinics. The study cohort included children aged 4-6 years with [&ge;] 2 primary care visits between 2020-2024 and ICD-10 diagnoses of ADHD or ADHD symptoms (n=542 patients). Clinical notes from the first ADHD-related visit were included. A stratified subset of 122 notes, including all cases with model disagreement, was manually annotated to assess model performance in identifying PTBM recommendations and rank model explanations. ExposuresAssessment and plan sections of clinical notes were analyzed using three generative large language models (Claude-3.5, GPT-4o, and LLaMA-3.3-70B) to identify the presence of PTBM recommendations and generate explanatory rationales and documentation evidence. Main Outcomes and MeasuresModel performance in identifying PTBM recommendations (measured by sensitivity, positive predictive value (PPV), and F1-score) and qualitative explainability ratings of model-generated rationales (based on the QUEST framework). ResultsAll three models demonstrated high performance compared to expert chart review. Claude-3.5 showed balanced performance (sensitivity=0.89, PPV=0.95, and F1-score=0.92) and ranked highest in explainability. LLaMA3.3-70B achieved sensitivity=0.91, PPV=0.89, and F1-score=0.90, ranking second for explainability. GPT-4o had the highest PPV [0.97] but lowest sensitivity [0.82], with an F1-score of 0.89 and the lowest explainability ranking. Based on classifications from the best-performing model, Claude-3.5, 26.4% (143/542) of patients had documented PTBM recommendations at their first ADHD-related visit. Conclusions and RelevanceLLMs can accurately extract guideline-concordant clinician recommendations for non-pharmacological ADHD treatment from unstructured clinical notes while providing clear explanations and supporting evidence. Evaluating model explainability as part of LLM implementation for medical chart review tasks can promote transparent and scalable solutions for quality-of-care measurement.