Pediatrics

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 ([≤]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.

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.

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.

IntroductionPediatric acute appendicitis (PAA) remains challenging to diagnose despite existing diagnostic scores. The BIDIAP index is a three-item diagnostic tool with very high discriminative performance in a derivation cohort. This study aimed to prospectively and externally validate the BIDIAP index in a multicenter pediatric population. Material and MethodsWe conducted a prospective, multicenter observational study across four tertiary pediatric centers, enrolling children presenting with suspected PAA. Two groups were analyzed: patients with histopathologically confirmed PAA and patients in whom appendicitis was confidently excluded after diagnostic work-up, classified as non-surgical abdominal pain (NSAP). The BIDIAP index was applied using a predefined cutoff ([&ge;] 4 points), and diagnostic performance was assessed using ROC analysis, calibration metrics, and decision curve analysis (DCA). ResultsA total of 644 patients meeting the prespecified analytical criteria were included in the primary analysis. The BIDIAP index demonstrated excellent diagnostic performance, with an area under the ROC curve of 0.93 (95% CI, 0.92-0.95). The calibration slope was 1.00, and the intercept was close to zero, indicating close agreement between predicted and observed risks. At the prespecified cutoff value of [&ge;] 4 points, the BIDIAP index achieved a sensitivity of 90.5% and a specificity of 81.6%. DCA showed a positive net clinical benefit of the BIDIAP index over treat-all and treat-none strategies across the full range of clinically relevant threshold probabilities. ConclusionsThe BIDIAP index demonstrated excellent diagnostic performance for PAA. Its simplicity, based on only three items, and its potential applicability even when the appendix is not visualized on ultrasonography make the BIDIAP index a promising tool for supporting clinical decision-making in routine pediatric emergency practice.

BackgroundPediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt-onset neuropsychiatric symptoms, often infection- or immune-triggered. Intravenous immunoglobulin (IVIG) is recommended by expert guidelines for select cases, yet insurance denials and high out-of-pocket costs have been major barriers to access. MethodsWe surveyed 60 caregivers and/or adult PANS patients who pursued IVIG therapy, collecting data on insurance experiences, treatment protocols, financial strategies, and patient/caregiver quality of life (QoL) before and after treatment. ResultsMost patients (88%) eventually received IVIG; 10% were still in pursuit, and 2% discontinued trying. Insurance approval without appeal occurred in only 18%, while many families faced multiple denials and appeals. Insurance approvals were more expeditious for patients with comorbidities for which IVIG is typically covered; among those receiving IVIG for PANS alone, only 5% were treated within a month of the doctors order (compared to 38% of those receiving IVIG for comorbidities as well as PANS) and 14% waited [&ge;]9 months before treatment began. Financial strain was routine: one-third of families without substantial coverage (i.e., insurance that covered >=70% of expenses) reported extreme stress (10/10), 58% borrowed money, and 21% sold major assets. Even families with substantial insurance coverage commonly depleted savings or took on additional work. Prior to IVIG, patient Quality of Life (QoL) ratings were poor (means 2.1-2.8 across domains), with over one-third selecting the lowest possible ratings. During the six months following IVIG initiation, mean scores rose to 6.2-6.8, with over 60% reporting "good" to "exceedingly good" outcomes. Caregivers reported parallel gains, with family QoL ratings rising from 2.4-4.0 pre-treatment to 5.7-6.6 post-treatment. ConclusionsFamilies pursuing IVIG for PANS faced prolonged delays, repeated denials, and extreme financial strain, often resorting to loans, asset sales, and additional work. Despite these burdens, IVIG was associated with marked improvements in quality of life for both patients and caregivers, underscoring the treatments potential benefits and the urgent need for more equitable access.

Background and ObjectivesPatient portals allow adolescents and caregivers of pediatric patients to better engage with health care, improving their medication adherence, health knowledge, self-efficacy, and receipt of preventive care. However, disparities in access to and comfort with using these portals persist. Hospitalization represents a promising opportunity to address these disparities among a high-risk population. Design/MethodsWe conducted a cross-sectional analysis to identify disparities in portal enrollment and use (logins, messaging, or telehealth use) among patients admitted to two pediatric hospitals within a single health system from 2022-2024. We calculated unadjusted rates of portal enrollment and use before, during, and after hospitalization, stratified by patient-level factors (age, race/ethnicity, insurance coverage, medical complexity), household-level factors (preferred language), and population-level factors (neighborhood opportunity). We then used multivariable logistic regression to identify associations between these factors and portal enrollment and use. ResultsAmong 40,371 hospitalized patients, 93% had enrolled in our patient portal. Patients who identified as Non-Hispanic Black, were publicly insured, had a household language other than English, and lived in lower opportunity neighborhoods had significantly decreased odds of portal enrollment and use before, during, and after hospitalization. ConclusionsDespite high overall rates of portal enrollment among our patient population, we observed persistent disparities in portal enrollment and use. Efforts to promote equitable portal usage among hospitalized children may be most effective when focused on families who are publicly insured, prefer languages other than English, or live in lower opportunity neighborhoods.

BackgroundChildren with tracheostomies experience frequent and recurrent acute respiratory infections (ARIs). While cultured respiratory pathogens can inform ARI diagnosis, it is unknown if their presence in the airway affects future ARI risk. ObjectiveTo identify predictors of frequent (3+) ARIs within 36 months of tracheostomy. MethodsWe conducted a single-center, retrospective cohort study of children with tracheostomies placed between 2010-2016. Medical records were reviewed for each encounter in which a respiratory culture was obtained over the 3 years post-tracheostomy. ARIs were defined using encounter ICD-9/10 codes. Logistic and Poisson regression were used to model the association between clinical and microbiologic predictor variables with having frequent (3+) ARIs and the total number of ARIs per child. Mediation analysis using stepwise regression models further evaluated the role of P. aeruginosa. ResultsAmong 436 children, 631 diagnosed ARIs occurred within 36 months of tracheostomy; 20.2% of children had 3+ ARIs. Pseudomonas aeruginosa was isolated in 25% of children and was more common among those with 3+ ARIs compared with 0-2 ARIs (56.8% vs 20.7%, p<0.001). Those with early P. aeruginosa isolation were more likely to have 3+ ARIs (aOR 3.38, 95% CI 1.97-5.81), and this relationship persisted when analyzing ARIs and P. aeruginosa counts. Identification of P. aeruginosa partially mediated the relationship of ventilator dependence with ARI frequency. ConclusionIsolation of P. aeruginosa, particularly early and repeated isolation, is associated with frequent ARIs in the 3 years after tracheostomy and is an important partial mediator. Findings may inform risk stratification and targeted treatment strategies.

IntroductionCentral line-associated bloodstream-infection (CLA-BSI) and catheter-related bloodstream infections (CR-BSI) remain a significant concern in pediatric inpatient units. ObjectiveTo analyze a case series of CLA-BSI and CR-BSI in hospitalized pediatric patients in hospitals with rigorous infection prevention measures. Materials and MethodsThis was an analytical, descriptive, and retrospective study conducted in patients aged 0 to 18 years, admitted between August 2023 and March 2025, with a diagnosis of CLA-BSI or CR-BSI in two pediatric hospitals in Rio de Janeiro, Brazil. Variables potentially associated with the occurrence of infection were analyzed. ResultsA total of 86 infections were evaluated, comprising 66 CLA-BSI and 20 CR-BSI. Sixty patients (69.8%) were male, with a mean age of 71.8 months. Sixty-five (83.7%) had previous comorbidities, 63 (73.2%) had a prior hospitalization, and 27 (31.4%) had another invasive device. The mean time from catheter insertion to infection diagnosis was 32.1 days, and the mean time from hospital admission to infection onset was 18.45 days. Gram-negative bacteria were isolated in 40/86 (46.5%) cases. At 30 days post-infection, 61/86 (70.9%) had been discharged, 20/86 (23.3%) remained hospitalized, and 5/86 (5.8%) had died. There was no correlation between the bacterial group and the type of catheter used (p=0.068), nor between infection type (CLA-BSI vs. CR-BSI) and mortality outcome (p=1). ConclusionsCLA-BSI and CR-BSI occurred predominantly in patients with prolonged hospital stays and underlying comorbidities, and were mainly caused by Gram-negative bacteria.

BackgroundParticipating in research during medical school is supported by institutional programs and may influence subsequent professional development. ObjectiveWe aimed to describe the current status and heterogeneity of scholarly research programs for medical students in the United States, including expectations, support, and key structural features. MethodsWe conducted a cross-sectional web audit of official webpages for all accredited US MD- and DO-granting medical schools (search performed September 2024 to January 2025). Extracted variables included participation requirements, mentorship, timing and duration (overall and dedicated research time), expected scholarly outputs, funding sources, stipend information, and stated program goals. We compared Carnegie tier R1 (Very high research activity) versus other institutions, QS Top-50 versus other institutions, and MD versus DO schools using {chi}2/Fisher exact tests for 2x2 tables and exact trend or Freeman-Halton tests for multicategory variables. ResultsPrograms were identified for all 202 institutions. Funding was explicitly mentioned by 61.9% (125/202) of programs, 27.0% (51/189) were compulsory, 98.9% (188/190) reported faculty mentorship, and 91.0% (171/188) were exclusive for medical students. Program duration, dedicated time, expected outcomes, stipend reporting, funding sources, and stated goals varied widely. Carnegie R1 institutions had longer duration (P=.002) and tended to report external funding more often than other institutions (25/104, 24.0% vs 9/98, 9.2%; OR 3.13, 95% CI 1.38-7.10; P=.008). QS Top-50 institutions were more likely to require compulsory participation than other institutions (11/19, 57.9% vs 40/170, 23.5%; OR 4.47, 95% CI 1.68-11.87; P=.003). No significant differences were observed between MD and DO programs across most measured characteristics. ConclusionsScholarly research programs for medical students are ubiquitous across US medical schools but heterogeneous in structure, expectations, and support. Research-intensive and top-ranked institutions may have more external funding and sometimes may put together longer and compulsory programs Further evaluation of student experiences and outcomes is warranted.

Patient portals are designed to enhance patient and caregiver engagement by providing access to health information, communication with care teams, and telehealth services, yet their impact on health care utilization among hospitalized children is not well understood. In this cross-sectional study, we examined associations between patient portal enrollment and use and hospitalization outcomes among 40,377 children admitted to an urban quaternary or suburban tertiary pediatric hospital between 2022 and 2024. Portal activity was defined by enrollment and any use (login, messaging, or telehealth) within specified periods before or during hospitalization. Using multivariable regression models adjusted for sociodemographic factors, neighborhood opportunity, insurance type, language, medical complexity, hospital site, and year, we evaluated associations with critical care admission, hospital length of stay (LOS), and 30-day readmissions. Portal enrollment and use in the year prior to hospitalization were associated with significantly lower odds of critical care admission and shorter LOS, with average reductions of 1.56 days for enrollment and 1.21 days for use. Neither portal enrollment nor use was significantly associated with 30-day readmissions. Future research should explore any potential mechanisms facilitating lower acuity at admission and shorter hospitalizations for those engaged with digital health.

ImportanceThe United States is facing a projected shortage of 40,000 primary care physicians by 2034. Student-run clinics (SRCs) are widely regarded as service-learning environments that may encourage students to enter a primary care specialty, but prior studies have yielded conflicting results and are limited to non-generalizable, single site analyses. ObjectiveTo compare likelihood of practice in a primary care specialty between students who did and did not participate in an SRC via pooled meta-analysis of U.S.-based studies. Study SelectionStudies were first identified through a comprehensive library of U.S.-based SRC literature. The inclusion criteria were publications on SRCs in the United States with MD/DO students, from all time until March 1, 2024. Exclusion criteria were: full text not available; published abstract/textbook/dissertation/thesis; not in English. Two authors independently screened the database for publications on SRC participation and practice in primary care specialties. To identify relevant literature after March 1, 2024, the authors performed iterative snowball sampling of the bibliographies of included studies and their Google Scholar "cited by" lists until saturation. Finally, we included original data from the single largest study on this topic. Data Extraction and SynthesisWe evaluated study quality using the NIH Study Quality Appraisal Tool. We used a random-effects model to account for heterogeneity. Main Outcomes and MeasuresThe primary outcome was the relative likelihood (risk ratio) of pursuing a primary care specialty among SRC volunteers versus non-volunteers. We used a funnel plot and sensitivity analysis to assess for bias. ResultsSeven studies met inclusion criteria with a cumulative sample size of 7,468 students. SRC volunteers pursued primary care at 102% to 160% the rate of non-volunteers. The pooled risk ratio was 1.25 (95% CI: 1.09-1.44). Funnel plot and multiple sensitivity analyses did not suggest publication bias or undue influence from included studies. Conclusions and RelevanceSRC participation is associated with a statistically-significant 25% increased likelihood of practicing in a primary care specialty. These findings may inform national and institutional strategies to support service-learning and address the national primary care workforce shortage. KEY POINTSO_ST_ABSQuestionC_ST_ABSIs participation in a student-run clinic during medical school associated with increased likelihood of practicing in a primary care specialty? FindingsDespite conflicting results in the literature among small and single-site studies, in this meta-analysis of 7,468 medical students, participation in a student-run clinic was associated with a statistically significant 25% increased likelihood of practicing in a primary care specialty. MeaningStudent-run clinics may be a potential strategy for strengthening the pipeline into primary care and reducing the projected shortage of 40,000 primary care physicians.

Background and ObjectivesAnnual tuberculosis (TB) screening is recommended for all children and adolescents in the United States, but gaps remain in the diagnosis and treatment of latent TB infection (LTBI). We utilized the electronic health record (EHR) to examine the pediatric LTBI care cascade and assessed if an EHR note template could increase risk factor screening. MethodsWe extracted EHR data from well-child and -adolescent visits at a federally qualified health center in Northern California from 2014-2020. We constructed the LTBI care cascade from screening through treatment and performed multivariable logistic regression to assess factors associated with completion of cascade steps. A TB risk factor question was added to the progress note template in 2014, and we measured the change in TB risk factor screening and testing over time. ResultsWe included 10,409 children from 18,681 visits, with median age of 6.9 years (IQR 2.8-12.1). Most visits (90%) had completed risk factor screening, and the note template significantly increased screening over time. However, 20% with a TB risk factor had testing ordered, though the proportion increased from 7% to 33% throughout the period. Of those tested, 4% had a positive test, and the majority completed subsequent steps. Children under 5 years old were more likely to have risk factor screening than older children but were less likely to be tested. ConclusionsLTBI risk factor screening is high, but ongoing gaps in testing could have led to underdiagnosis. Simple EHR-based solutions have the potential to improve pediatric TB care. Article SummaryWe examined the care cascade for latent tuberculosis infection (LTBI) in children and evaluated the role of the electronic health record to support LTBI care. Whats Known on This SubjectThe American Academy of Pediatrics recommends annual tuberculosis screening at well-child visits, but gaps remain in completion of the care cascade. Electronic health record (EHR) systems can be utilized to monitor and guide completion of health maintenance activities. What This Study AddsPrior efforts to characterize the latent tuberculosis infection (LTBI) care cascade for children were incomplete, with limited EHR-based interventions. This study provides a full assessment of the LTBI care cascade and examines the role of the EHR to improve screening.

BackgroundPediatric eczema is a highly prevalent condition that often causes substantial suffering among affected children and their families. Numerous modifiable lifestyle and environmental risk factors for the condition have been identified, although these risk factors and related interventions have generally been studied in isolation. The goal of this study was to evaluate the effects of an integrative program for parents of children with eczema that simultaneously addressed multiple lifestyle and environmental risk factors. MethodsChildren with eczema diagnosis who began the online eczema program and provided outcomes data from May 2024 to May 2025 were eligible. The primary outcome was the Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), a validated measure of eczema symptoms and burden. Outcomes were assessed at baseline and at one month, two months, and six months after beginning the program. Changes in mean PO-SCORAD scores from baseline throughout the duration of the study were assessed with analysis of variance (ANOVA). Multivariate linear regression modeling of PO-SCORAD scores using population-averaged generalized estimating equations (GEE) were also constructed accounting for baseline PO-SCORAD scores and adjusting for age, sex, presence of any allergy, use of topical corticosteroids, and use of antihistamines. Results197 participants were included in the study. The mean baseline PO-SCORAD score was 51.4, which is considered severe eczema. PO-SCORAD scores improved over the course of the study (p<0.0001) and there were statistically significant and clinically meaningful improvements noted after one month (11.3 points, 22.0% improvement), two months (17.8 points, 34.6% improvement), and six months (27.2 points, 52.9% improvement) in the program (p<0.0001). After accounting for baseline PO-SCORAD scores and covariates in regression modeling, there was a 22.5-point (p<0.0001) improvement in PO-SCORAD scores from baseline to final assessment. There was a 31.4-point decrease in PO-SCORAD scores from baseline to final assessment (p<0.0001, 47.2% improvement) among the subgroup of participants with severe eczema symptoms at baseline. ConclusionsAn online program focusing on modifiable lifestyle and environmental modifications was associated with clinically meaningful symptom improvements among children with eczema. Symptoms improved relatively quickly and the greatest improvements were noted among children with severe symptoms at baseline.

Background and ObjectivesDecision-making about resuscitating a critically ill child is complex yet common. We aimed to study the survival thresholds at which physicians, compared to parents, decide to treat or withhold resuscitating a child. Moreover, we aimed to compare physicians survival estimates with those from a nationwide registry. MethodsWe conducted a cross-sectional survey-based study in the United States. Clinical vignettes based on hypothetical survival probabilities were used to study and compare the decision thresholds for parents and physicians. Vignettes developed using the Get-With-The-Guidelines-Resuscitation registry were used to explore physicians decision thresholds and compare their survival estimates with those from the data. Thresholds were determined using mixed-effect logistic regression models. ResultsWe had decisions for 501 and 257 vignettes from 167 parents and 43 physicians, respectively. The decision threshold for survival to discharge was 5.3% (95% CI: 3.7 to 7.0) for physicians and 1.2% (95% CI: -0.8 to 3.0) for parents. Whereas the decision threshold for survival to discharge with PCPC 1 or 2 was 3.5% (95% CI: 1.1 to 7.1) for physicians and 0.6% (95% CI: -1.2 to 1.8) for parents. About 58% of the physicians overestimated the likelihood of survival. ConclusionsThe study found that the decision threshold for the physicians was higher than that for the parents (5.3% vs. 1.2%). This illustrates that parents still want to attempt resuscitation at a survival probability where physicians would recommend withholding resuscitation. These findings have implications for clinical practice and counseling the parents of critically ill hospitalized children.

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; 965% 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.

Structured AbstractO_ST_ABSBackgroundC_ST_ABSHair cortisol analysis allows assessment of long-term cortisol exposure and may provide insight into chronic hypothalamic-pituitary-adrenal activation in medical residents and residency on-call responsibilities. ObjectiveTo determine the hair cortisol concentration(HCC) representing 3 months of medical residency and secondarily, its association with various on-call models (in-hospital, night float, home call and no call). DesignCross-sectional study of 66 medical residents who were recruited to provide hair samples collected after a three-month block in medical residency. SettingAcademic, tertiary health care system. ParticipantsVolunteer sample of first through third year medical and primary care residents. Exposure3 cm of hair was divided into 3 segments of 1 cm each; each segment represented 1 month of cumulative cortisol production. Main Outcome MeasureHCC results were compared to a published, cortisol assay-specific normative population reference interval. HCC results were interpreted according to a priori categorizations of moderate (+1.5SD), considerable (+2SD) or extreme (> +3SD) HCC elevations. Associations with various on-call models were an exploratory secondary outcome. ResultsThe median age was 28 (26-30) years with median sleep duration of 2 hours on in-hospital call. 40% of trainees had at least one HCC segment above the threshold deemed marked elevation. Median HCC was significantly higher for in-hospital and night float vs. no call (285 ng/g and 335 ng/g vs 78 ng/g p<0.05) and approached significance compared to home call (190 ng/g, p= 0.06). Conclusions and RelevanceWe have described chronic exposure to endogenous cortisol in medical residency. Nearly half of trainees experienced at least one month of severe hypothalamic-pituitary-adrenal axis activation in a 3-month timeframe; many had marked chronic cortisol elevations across the entire 3 month observation frame. HCC was higher in months where in-hospital on-call was required. This may have implications for long-term health of trainees and raises questions about the structure of duty hours and sequence of care acuity blocks within residency training programs.

Background and objectivesCeftazidime-Avibactam (CAZ-AVI) is one of the last options to treat Enterobacteriales and Pseudomonas aeruginosa carbapenem-resistant. We aim to describe the susceptibility profile of bloodstream isolates of Enterobacterales and Pseudomonas aerunosa to ceftazidime-avibactam (CAZ-AVI) among strains resistant to third- and fourth-generation cephalosporins and/or carbapenems. MethodsWe conducted a retrospective descriptive study in two pediatric hospitals of Rio de Janeiro city, Brazil, between January 2023 and February 2025. All blood samples with resistance to third/fourth cephalosporins and/or carbapenem resistance were tested to CAZ-AVI, according to the BRCast methodology. Sensibility of CAZ-AVI and clinical profile of patients and outcomes were described. ResultsWe analyzed 116 blood samples. Of these, 107/116 (92.2%) were resistant to third/fourth-generation cephalosporins with susceptibility to carbapenems, and 9/116 (7.8%) were resistant to both third/fourth-generation cephalosporins and carbapenems. Overall susceptibility to CAZ-AVI was 107/116 (92.2%). The 116 blood samples represented 73 bloodstream infections (BSI) in 66 patients, including 66 single episodes and 7 persistent BSIs. Of the 73 infections, 69(94.5%) were caused by Enterobacterales and 4 (5.5%) by Pseudomonas aeruginosa. Twenty-two (30.1%) infections were detected at hospital admission, and 51 (69.9%) were healthcare-associated infections. Death occurred in 5/73 (6.8%) patients. Length of hospital stay (p=0.01596) were statistically significantly higher in non-survivors compared to survivors. The CAZ-AVI was prescribed for four patients with Enterobacteriales or Pseudomonas aeruginosa infections with clearance from the blood. ConclusionSusceptibility of CAZ-AVI to BSI in children was higher and this antibiotic could be an option to treat carbapenem-resistant infection due to Enterobacteriales and Pseudomonas aeruginosa.

ObjectiveTo examine how sociodemographic and educational factors influence progression into early clinical academic careers among UK medical graduates, focusing on intercalation, Academic Foundation Programme (AFP) participation, and Pre-doctoral Fellowships (PFs). DesignRetrospective cohort study using linked national data from the UK Medical Education Database (UKMED). SettingAll UK medical schools with graduates entering the UK Foundation Programme between 2017 and 2022. Participants32,580 graduates (25,290 standard-entry (SE); 7,290 graduate-entry (GE)). Main outcome measuresCompletion of an intercalated degree; application to and acceptance for AFP; application to and acceptance for a PF during specialty training. ResultsAmong SE graduates, 63.9% intercalated, 21.4% applied to AFP and 7.6% were accepted. Male, minority ethnic, privately educated, and less deprived graduates were more likely to intercalate; disability and higher deprivation were associated with lower intercalation. Intercalation, publications, high Education Performance Measure (EPM) scores and attendance at six-year programmes strongly predicted AFP application and acceptance. At PF stage, minority ethnic SE doctors were significantly less likely to be accepted (OR 0.60, 95% CI 0.45 to 0.80, p < 0.001), despite similar application rates. AFP completion was the strongest predictor of PF progression (OR 7.82, 95% CI 6.68 to 9.15, p <0.001). GE graduates had similar AFP application (21.9%) and acceptance (6.3%) rates. Male, minority ethnic graduates were more likely to apply to the AFP, while low EPM scores reduced acceptance. Few sociodemographic factors predicted PF applications, although prior AFP acceptance strongly did. Interaction analyses showed GE status attenuated some disparities in AFP application, but reversed patterns observed for ethnicity in acceptance. ConclusionsEarly clinical academic progression is shaped by educational achievements and persistent sociodemographic inequalities. Equitable access to funded research opportunities during medical school is likely to strengthen and diversify the future clinical academic workforce.

BackgroundStudent-run clinics (SRC) serve a unique role in healthcare by addressing the needs of underserved communities while providing medical students hands-on learning experiences. The Houston Outreach Medicine Education and Social Services (HOMES) Clinic is a SRC and a program of Healthcare for the Homeless - Houston that provides medical care to individuals experiencing unstable housing in Houston, Texas. Amid a growing shortage of primary care physicians in the United States, understanding factors that influence specialty choice is critical. This study aimed to explore whether volunteering at HOMES Clinic is associated with an increased likelihood of matching into primary care specialties. MethodsThis study used a retrospective cohort design of HOMES Clinic volunteers from 2014-2025. Students who volunteered at HOMES Clinic represented the exposure group (n=1,157), while non-volunteers served as the reference group (n=3,666). The primary outcome was the association between volunteering and matching into primary care specialties. Secondary outcomes included residency program rank, in-state residency placement, and induction into the Alpha Omega Alpha and Gold Humanism Honor Societies. ResultsHOMES Clinic volunteers matched into primary care specialties at a 7.5% higher rate than non-volunteers (p=1.3x10-5; OR=1.38; 95% CI = 1.20-1.59). Conversely, HOMES volunteers showed a 5.3% lower proportion of students who matched into surgical specialties (p=8.9x10-4; OR=0.76; 95% CI = 0.65-0.89). Volunteers also showed a modest association with matching into higher-ranked residency programs (p<0.05) and had 25% higher odds of Alpha Omega Alpha induction and 41% higher odds of Gold Humanism Honor Society induction. ConclusionsVolunteering at HOMES Clinic showed a positive association with matching into primary care specialties. This trend likely reflects both self-selection of students interested in primary care and the influence of SRC experience on shaping student residency specialty choices. Our results provide insights into how medical schools and SRCs foster the development of the next generation of primary care physicians.

BackgroundIn 2024, the National Advisory Committee on Immunization recommended universal RSV immunization across Canada, prioritizing infants in remote communities. However, in the absence of population-based data, programs may not effectively narrow health gaps in remote communities. MethodsRetrospective cohort study of all births in British Columbia (BC) from April 2013 to March 2024, followed for 1 year, using health administrative data. Main outcomes were hospitalizations for all-cause and RSV-lower respiratory tract infection (LRTI). Secondary outcomes were tertiary Pediatric Intensive Care Unit (PICU) admissions, length of stay, and air transport. Main exposures were community remoteness and social determinants of health. Incidence rates and incidence rate ratios (IRR) adjusted for sex, prematurity, and chronic conditions were estimated using Poisson generalized estimating equations. ResultsAmong 472,623 infants, those living in remote communities (N=3636) had higher hospitalization risk for all-cause (IRR: 2.91, 95%CI 2.02-3.65) and RSV-LRTIs (IRR: 1.60, 95%CI 1.17-2.19) compared to metropolitan areas. Length of stay and PICU admission rates were similar by region. Almost half (48.8%) of children from remote areas hospitalized for all-cause LRTIs required air evacuation. Infants from remote communities remained at higher risk for all-cause (aIRR 2.84, 95% CI 2.22-3.63) and RSV-LRTI (aIRR 1.56, 95% CI 1.15-2.12) hospitalizations after adjusting for covariates. InterpretationInfants in remote communities experienced a disproportionately high RSV-LRTI burden, supporting prioritized RSV interventions in these regions. The residual risk after accounting for known factors highlights the need to investigate additional drivers of vulnerability in remote areas.