Pediatrics

Objective: To compare the characteristics, management and outcomes of neurodivergent (ND) children with neurotypical (NT) children attending a chronic pain clinic. Design: An audit of all patients attending the clinic from 2010-2025 using electronic patient records. Setting: A tertiary pain centre in Scotland. Patients: 724 patients were included in the analysis, 193 (26%) were neurodivergent. Patients were included if they had a documented referral to the pain clinic and attendance to at least one clinic appointment. Patients were excluded if no pain clinic letter could be found on their records. Results: There was a significant increase in the percentage of children with neurodiversity attending the chronic pain clinic compared to neurotypical children (p = 0.004) accounting for over a third of children last seen in the period of 2023-2025. ND children were most likely to present with musculoskeletal pain compared with NT children (p = 0.033) representing over half of all ND children's presentations with pain. ND children were more likely to report being bedbound (18% ND, 13% NT, p = 0.0352) or needing a walking aid (40% ND, 25% NT, p = 0.000) due to chronic pain and had a higher number of referrals (ND median = 18.4, 1QR, NT median = 12.44, IQR10.28 p = 0.000). ND children were more likely to live in areas of deprivation (Cochran-Armitage test, Z -2.15, p = 0.0315). Conclusions: Children with neurodiversity are overrepresented in the chronic pain clinic, and more often present to tertiary services with musculoskeletal pain. They are more likely to have multiple referrals, spend longer with the pain service and less likely to be discharged due to pain improvement. These findings highlight the need for focused strategies to address chronic pain in neurodivergent children. Services should consider how best to identify and support children with neurodiversity and chronic pain. Key Messages {middle dot} What is already known on this topic: While there has been research regarding the role of neurodiversity in pain perception, there are gaps in knowledge regarding the influence of neurodiversity on the development and persistence of chronic pain in children. {middle dot} What this study adds: A growing proportion of neurodiverse children attended the pain clinic. Neurodiverse children presented with more severely impactful pain, they spent a longer duration of time within the pain clinic and were less likely to be discharged due to pain improvement. {middle dot} How this study might affect research, practice or policy: Identifying neurodiverse children as a patient group with distinct requirements may prompt adaptations in chronic pain management practices. This audit provides an initial framework for subsequent research.

Objective: Lyme disease diagnosis in children is challenging due to atypical presentations and testing limitations. We sought to evaluate the association between Lyme disease and socio-geographic risk factors in children. Materials and methods: We enrolled children undergoing evaluation for acute Lyme disease at one of eight Pedi Lyme Net pediatric emergency departments located in high Lyme disease incidence states over a ten-year period (2015-2024). We defined a case of Lyme disease with an erythema migrans (EM) lesion or a positive two-tier serology result in a child with signs and/or symptoms of acute disease. We linked each childs primary residential county to the following factors: urban-rural residence, socioeconomic status, population-level disease incidence, wildland-urban interface, and "Lyme disease" Google searches. We performed a multi-level logistic regression analysis to evaluate associations between Lyme disease and county factors after adjusting for individual demographics. Results: Among 5,529 children enrolled, 1,396 (25.2%) had Lyme disease: 101 (7.2%) with early-localized disease, 584 (41.8%) with early-disseminated disease, and 711 (50.9%) with late-disseminated disease. Rural residence (aOR 1.9, 95% CI 1.3-2.9), higher socioeconomic advantage (aOR 1.3, 95% CI 1.1-1.4), more "Lyme disease" Google searches (aOR 1.1, 95% CI 1.0-1.2), and higher wildland urban interface (aOR 1.2, 95% CI: 1.0-1.4) were independently associated with Lyme disease. Conclusion: Incorporating socio-geographic factors alongside clinical data may augment diagnostic risk assessment in children with suspected Lyme disease. However, these factors should be incorporated carefully to ensure clinical assessments are not based on a childs geographic location alone.

Introduction: Early exposure to otolaryngology (ENT) procedural skills in undergraduate medical education is limited by patient safety concerns, restricted clinical opportunities, and the cost of commercial simulators. As a result, essential ENT skills are often underrepresented in structured, hands-on curricula for medical students. Methods: We developed a low-cost, multistation ENT simulation curriculum consisting of five reproducible task trainers: ear examination and otologic procedures, mirror laryngoscopy, rigid and flexible endoscopic navigation, introductory mastoid drilling, and emergency cricothyrotomy. The curriculum was delivered as a 2-hour, faculty-led workshop during a third-year medical student otolaryngology rotation. Learners rotated through stations in small groups. Pre- and post-workshop surveys assessed self-reported anatomical familiarity, procedural confidence, and educational value using a 5-point Likert scale, with additional qualitative feedback collected. Results: All participants completed pre- and post-workshop evaluations. Learners demonstrated increased confidence across all assessed anatomical and procedural domains, including otoscopy, endoscopy, mirror laryngoscopy, mastoid drilling orientation, and cricothyroid membrane identification. Educational value ratings were high across all stations, with mean scores ranging from 4.33 to 5.00. Qualitative feedback emphasized the realism, accessibility, and benefit of hands-on practice in a low-stakes learning environment. Conclusion: This low-cost, multistation ENT simulation curriculum provides a feasible and reproducible approach for introducing foundational otolaryngology skills to medical students. The structured format and affordable models support early procedural exposure and may enhance learner preparedness prior to supervised clinical encounters, particularly in settings with limited simulation resources.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition associated with pediatric SARS-CoV-2 infection. While COVID-19 vaccines prevent infection and reduce severity, less conclusive evidence exists regarding their role in preventing MIS-C during breakthrough infections. This systematic review assessed the impact of SARS-CoV-2 vaccination on MIS-C risk during breakthrough infection. Cross-sectional studies, surveillance studies, and cohort studies were included. Of the 944 studies identified, 6 were included. A significant protective effect was seen in patients who received two doses of SARS-CoV-2 vaccination after exclusion of a biased sample (d= 0.71 [95% CI 0.07 to 1.35; p=0.03]). A trend towards a protective effect was seen after one dose of vaccination, but this effect was not statistically significant. Current literature supports a protective effect of two doses of SARS-CoV-2 vaccination against development of MIS-C in breakthrough COVID-19. The evidence supports clinician advocacy for continued vaccination of children against SARS-CoV-2.

Objective: Upper respiratory infections (URI) are the major trigger of asthma exacerbations in children with asthma and are more likely to be reported by Black and Mexican American children compared to White children in the US. We aimed to evaluate the extent to which obesity, nicotine exposure, household size, and socioeconomic status (SES) explained this excess URI risk among all children and among children with asthma. Study Design: Data collected on children aged 6-17 years from the National Health and Nutritional Examination Survey (2007-2012) were analyzed using survey weights and a mediation approach. Household SES was analyzed as a cumulative score reflecting income poverty ratio, education, and rental housing. URI was defined as cough, cold, phlegm, runny nose, or other respiratory illness (excluding hay fever and allergies) in the past 7 days. Results: Obesity and serum cotinine, a marker of nicotine exposure, explained little to none of the excess risk of URI while SES explained 36.4% (95% CI=34.1, 38.6) in Black and 28.5% (95% CI=26.7, 30.5) in Mexican American children. Living in rental housing and income poverty ratio<2, explained half (49.6%, 95% CI=46.9-52.3) and 20% (19.7%, 95% CI=18.9-20.5) of the excess URI risk among Black children, respectively. In Mexican American children, rental housing and low educational attainment each explained approximately 15-17% of the excess URI risk. Results were comparable among children with asthma. Conclusions: Markers of poverty, such as rental housing, contributed substantially to the excess risk of URI among Black and Mexican American children, including among those with asthma.

Background: 48,XXYY syndrome is a rare sex chromosome aneuploidy (SCA) characterized by neurodevelopmental deficits and medical comorbidities. The limited information available in the literature is almost exclusively limited to postnatally diagnosed cases. This study aims to describe the early medical and developmental features of prenatally identified 48,XXYY infants, with comparisons to 47,XYY, 47,XXY cohorts, and typical populations, as well as previously reported postnatally diagnosed 48,XXYY cases. Methods: The eXtraordinarY Babies Study prospectively follows children prenatally identified to be at high risk for SCA with annual medical and neurodevelopmental evaluations. Data presented herein include the prevalence of medical conditions, developmental milestones, developmental and adaptive functioning assessment scores, and therapy utilization in participants confirmed to have 48,XXYY. Comparisons were made between this cohort and the typical population, infants with 47,XYY and 47,XXY also enrolled in the eXtraordinarY Babies Study, and a 2008 cohort of individuals postnatally identified 48,XXYY. Results: Infants with 48,XXYY exhibited a range of early medical features, including high rates of feeding and GI disorders (breastfeeding difficulties, gastroesophageal reflux, and eosinophilic esophagitis), allergic disorders (food allergies and environmental allergies), and hypotonia. Developmental and adaptive functioning scores indicated delays in motor, communication, and social domains, with nearly all infants receiving speech therapy, physical and/or occupational therapy. Comparisons with the 47,XYY and 47,XXY cohorts revealed more medical and developmental challenges in the 48,XXYY group, however there was variability and some overlap with both the general population and sex chromosome trisomy conditions. Additionally, comparison to the 2008 postnatally identified 48,XXYY cohort indicated that while prenatal diagnosis allowed for earlier intervention, developmental outcomes in the first years of life were similar between the two groups. Conclusions: 48,XXYY diagnosed prenatally facilitates early monitoring, anticipatory guidance, and proactive referrals for medical evaluations and intervention, given developmental delays and medical challenges are more common in infancy and early childhood compared to the general population and trisomy SCAs. These findings provide valuable insights for genetic counselors and healthcare providers, emphasizing the spectrum of medical and developmental findings and importance of early and proactive care to support individual outcomes. Prospective study of this prenatally identified cohort will provide important natural history and phenotypic variability in XXYY, as well as identification of predictors of health and developmental outcomes.

Background Appendicitis is a readily treatable surgical emergency, yet it remains a cause of preventable death among children in resource-limited settings. While recent studies have documented the global burden of pediatric appendicitis, none have systematically examined its geographic clustering or spatial spillover effects. Understanding whether high-mortality countries cluster geographically, and whether neighboring countries influence each other's outcomes, is essential for designing regional surgical capacity strategies. Methods We conducted a spatial analysis of pediatric appendicitis case fatality rates in children aged 0-14 years across 169 countries from 2000 to 2019. Data were obtained from the Global Burden of Disease Study 2023 and World Bank databases. We calculated global Moran's I to assess spatial autocorrelation, used Getis-Ord Gi* to identify local hotspots, and fitted spatial lag and spatial error regression models to quantify spatial spillovers while adjusting for GDP per capita, physician density, and basic sanitation access. Results Global Moran's I was 0.621 in 2000 (p < 0.001), 0.621 in 2010 (p < 0.001), and 0.592 in 2019 (p < 0.001), indicating strong and persistent spatial clustering. Hotspots at 99% confidence were consistently concentrated in sub-Saharan Africa and parts of South Asia, with little change in geographic distribution over two decades. The spatial error model provided the best fit (AIC = 212.6), with a spatial error coefficient ({lambda}) of 0.663 (p < 0.001), suggesting that approximately 66% of residual variation was explained by unobserved regional factors. In the final model, higher GDP per capita ({beta} = -0.497, p < 0.001) and higher physician density ({beta} = -0.568, p < 0.001) were independently associated with lower case fatality, while basic sanitation access showed no significant association (p = 0.284). Conclusions Pediatric appendicitis case fatality exhibits strong and persistent geographic clustering. The substantial spatial spillover effect suggests that regional coordination of surgical capacity building may be more effective than country-by-country investments. Priority should be given to hotspot countries in sub-Saharan Africa and South Asia, with emphasis on surgical workforce expansion rather than broad economic development alone.

Background: Diarrheal illness in children leads to 3.5 million care visits and 200,000 hospitalizations annually in the US. Viruses are responsible for most pediatric diarrheal cases, yet limited guidance on distinguishing viral from bacterial etiologies complicates clinical decision-making, especially regarding empiric antibiotic use. Methods: We used clinical and qualitative molecular etiologic data from the Implementation of Molecular Diagnostics for Pediatric Acute Gastroenteritis (IMPACT) study to develop prediction models for viral etiology of diarrhea. We used conditional random forests to identify informative clinical and environmental predictors and evaluated model performance using logistic regression and random forests within a 5-fold cross-validation framework. We conducted external validation using the Alberta Provincial Pediatric Enteric Infection Team (APPETITE) dataset. Results: Variables predictive of viral etiology included younger age, non-bloody diarrhea, winter season, and presence of vomiting. External validation showed that an AUC of 0.82 can be achieved with a parsimonious 5-variable model, yielding a sensitivity of 0.92 and specificity of 0.55 Conclusion: Our results suggest that in North American healthcare settings, clinical prediction models can inform decision-making by identifying children with a high probability of viral diarrhea, improving diagnostic clarity, and reducing unnecessary testing and treatment.

Abstract Background: Pediatric respiratory infections are a leading cause of morbidity and mortality globally, representing a major health challenge in children. Research Gap: Despite extensive studies on epidemiology, clinical management, and specific pathogens, no bibliometric analysis has systematically evaluated the most influential research in this field. Objectives: This study aimed to evaluate the characteristics of the top 50 most-cited articles on pediatric respiratory infections and to identify emerging research trends. Methods: The Web of Science database was searched without publication year restrictions. Independent reviewers screened studies based on predefined inclusion and exclusion criteria. Data were extracted using a standardized form, including study details. Results: The 50 most-cited articles ranged from 34 to 384 citations and showed a right-skewed distribution with a sharp drop after the top ten. Publication years ranged from 1978 to 2021, with over half published in the 2010s. Articles appeared in 31 journals, with Pediatrics contributing five. Leading countries were the United States (18%), China (12%), and Canada (10%), with research largely concentrated in high-income regions and limited multicenter collaboration. Cohort studies dominated (66%), while randomized trials (12%) and reviews/meta-analyses (16%) were less common. Research clustered around three themes: clinical outcomes (e.g., pneumonia, bronchiolitis); viral etiology/diagnostics (e.g., RSV, SARS-CoV-2); and antimicrobial stewardship. Conclusion: Over the past decades, pediatric respiratory infection research has developed but remains unbalanced, relying heavily on observational evidence from high-income countries, with limited randomized trials, systematic reviews, multicenter collaborations, and LMIC-led studies. These findings provide insights that may direct researchers to identify potential focal points and guide future research in the field.

Background and Objectives: SARS-CoV-2 (COVID-19) continues to mutate, circulate, and adversely impact health and quality of life. While COVID-19 vaccines remain safe and effective, uptake remains low, especially among children, the youngest of whom were not vaccine-eligible until after Omicron and are underrepresented in published research. This study estimated vaccine effectiveness (VE) among under-5-year-olds. Methods: We used Virginia Department of Health surveillance data from June 2022 through October 2022 to conduct a test negative case-control study. We estimated VE derived from odds ratios (ORs) of reported infections using logistic regression among children aged 6-months to 5-years. Results: Using the earliest positive (cases) or negative (controls) post-vaccine-eligible test results, the VE associated with two doses of a COVID-19 vaccine was 78% (95% CI=45%, 93%; p=0.004) in unadjusted analyses and 70% (95% CI=25%, 91%, p=0.023) when adjusting for age, sex, prior testing behavior, and prior reported infections. The adjusted VE was 74% (95% CI=28%, 94%; p=0.025) among those with no prior positives reported and 45% (95% CI=-302%, 97%; p=0.569) among those with a prior positive reported. Conclusions: These results show that even though the vaccine was not closely matched to the dominant variants circulating during the time period analyzed, it was effective at reducing the risk of reported infections. This study adds to the body of knowledge on pediatric COVID-19 VE in an underrepresented age-group and in a rural region, illustrates the utility of surveillance data for evaluation, and can inform vaccine decisions to improve vaccine uptake for young children.

Background Post-acute sequelae are well described following COVID-19 but may also occur after other respiratory infections and Aedes-borne infections. Evidence remains fragmented due to heterogeneity in study design, populations, and exposure, outcome, and follow-up definitions. Methods We synthesized and compared post-acute sequelae across influenza, RSV-ARI, dengue fever, chikungunya, Zika, and yellow fever. We searched five databases from inception to 25-08-2025 for articles quantifying risk, incidence, or rates of post-acute sequelae following these diseases. Eligible non-randomized observational studies assessed post-acute neurological, psychiatric, gastrointestinal, cardiovascular, respiratory, renal, musculoskeletal, autoimmune, or endocrine outcomes after confirmed infection. Risk of bias was assessed using ROBINS-E. Random-effects meta-analyses with restricted maximum likelihood estimation were conducted when comparable effect estimates were available (PROSPERO #CRD420251124994). Findings 51 studies were included, predominantly from high-income regions. Most were retrospective cohorts using ICD-coded diagnoses; prospective studies used laboratory-confirmed infections. Data sources, comparator groups, exposure definitions, outcome ascertainment, and follow-up periods varied substantially. Meta-analyses were feasible for RSV, influenza, and dengue fever. All RSV-ARI studies were pediatric and assessed infections during infancy, which were associated with higher pooled odds of physician-diagnosed asthma (OR:2.93 [95%CI: 2.12-4.06]). Influenza studies used COVID-19-positive comparators; pooled estimates showed lower risk for neurological (HR:0.82 [0.76-0.89]) and composite outcomes (RR:0.88 [0.82-0.95]), with other organ systems non-significant. Dengue fever studies spanned all ages and showed increased risks of anxiety (HR:1.34 [1.01-1.78]), dementia (HR:1.61 [1.10-2.35]), autoimmune (RR:1.39 [1.17-1.67]), cardiovascular (HR:1.51 [1.27-1.80]), psychiatric (HR:1.17 [1.07-1.28]), and any sequelae (HR:1.19 [1.13-1.25]) versus those without prior infection. Interpretations Post-acute sequelae contribute to overall disease burden following RSV-ARI and dengue fever. The evidence remains limited by heterogeneity in study design, exposure and outcome definitions, comparator selection, and follow-up duration. Greater standardization in study design and reporting is needed to improve comparability and strengthen causal inference.

Objectives: Electronic Health Records (EHRs) impose a significant time burden on physicians, often requiring work to be completed outside of scheduled hours. While this burden is well-documented, how it evolves throughout emergency medicine (EM) residency remains poorly understood. This study aimed to quantify EHR usage patterns, analyze the composition of after-shift work, and characterize the development of EHR efficiency across EM training. Methods: We conducted a retrospective cohort study of EM residents (postgraduate year [PGY] 1-4) using 5.5 years of EHR audit log data (2020-2025) at a single academic institution. We analyzed EHR time per new patient encounter, stratified by postgraduate year, and categorized activities into domains such as documentation, chart review, and orders. EHR work was measured both during and after scheduled shifts. Results: The analysis included 144 unique residents and 167,010 new patient encounters across 15,386 shifts. Encounter-attributed EHR time per encounter decreased by 52% from PGY-1 to PGY-4 (median 19.9 to 9.6 minutes, p<0.001), despite an 86% increase in patient volume per shift (median 7 to 13 encounters). This efficiency gain was driven primarily by a 69% reduction in documentation time (9.3 to 2.9 minutes), accompanied by shorter notes. After-shift work (EHR activity after the 9-hour clinical shift) was present in 89.9-94.4% of encounters. At the shift level, combined after-shift EHR time (encounter-attributed plus tracking board) was a median of 64.2 minutes per shift for PGY-1 and 104.2 minutes for PGY-4. Shift-level tracking board activity dominated the after-shift burden and increased with training (median 40.2 to 79.0 minutes per shift from PGY-1 to PGY-4). Conclusions: EM residents achieve substantial gains in on-shift EHR efficiency, with the largest reductions observed in documentation time, accompanied by shorter notes and faster input speed. However, a persistent after-hours workload, dominated by administrative and patient flow tasks, suggests that (at least at this single institution) system-level factors--not just individual skill--may contribute to this pattern. Monitoring these objective EHR metrics may help programs identify struggling learners and evaluate the impact of interventions aimed at improving resident well-being and workflow efficiency.

Background CLN2 disease, Neuronal Ceroid Lipofuscinosis (NCL) type 2, is a rare, genetic neurodegenerative condition predominantly affecting children. CLN2 disease is characterized by seizures, language and motor decline, vision loss, and premature death. Currently, the only regulatory-approved therapy is the enzyme replacement therapy (ERT) Cerliponase alfa, administered fortnightly via intracerebroventricular infusion as a lifelong treatment. While ERT has been shown to slow motor and language decline, it is not curative and does not fully address disease progression, including retinal degeneration. To better understand the lived experience of affected families, and perspectives on current and emerging treatments, we conducted a community survey of parents and caregivers of individuals with CLN2 disease. Methods A 25-question anonymous, voluntary survey was distributed through the BDSRA Foundation and international partner patient advocacy organisations via email and social media. Eligible participants included current and bereaved parents or primary caregivers of individuals with CLN2 disease, regardless of treatment history. The survey explored treatment experiences, unmet needs, and knowledge of and attitudes toward emerging therapeutic approaches, particularly gene-based therapies. Results Ninety-eight respondents from 19 countries completed the survey. Fifty-seven respondents reported current or prior use of ERT, with 94.7% (n=54/57) actively receiving treatment at the time of survey. ERT was perceived to provide greatest benefit for motor function and seizure control; however, respondents reported substantial treatment burden (mean burden score 4.8/7, n=66). Despite treatment availability, 94.9% of respondents (n=75/79) indicated a need for alternative therapeutic options and 94.8% (73/77) expressed interest in learning more about gene therapy. Overall, 72.4% (n=55/76) reported they were likely or very likely to consider participation in an investigational gene therapy trial. Key factors influencing decision-making included potential safety risks (57.9%, n=44/76), preclinical safety and efficacy evidence (54.0%, n=41/76), and whether ERT discontinuation would be required to participate (54.0%, n=44/76). Conclusion While ERT has altered the treatment landscape for CLN2 disease, this survey highlights the ongoing disease burden and treatment challenges experienced by families. Findings demonstrate strong community interest in next-generation therapies that may reduce treatment burden and provide more comprehensive disease modification, including effects on both central nervous system (CNS) and ocular manifestations.

Background Diarrhea remains a leading cause of child morbidity and mortality worldwide. Improved and ongoing estimates of the etiologies of severe diarrhea, particularly in low- and middle-income countries (LMICs), are crucial to inform the use of current vaccines and other interventions and to help prioritize the development of new vaccines. Producing rigorous longitudinal data on the global burden and etiology of pediatric diarrhea requires a geographically broad surveillance network with standardized epidemiologic, laboratory, and analytic protocols. Methods We describe the rationale and methods of the Global Pediatric Diarrhea Surveillance (GPDS) network, a World Health Organization (WHO)-coordinated public health surveillance network investigating the etiology of hospitalized diarrhea among children aged <5 years in LMICs. The GPDS network enrolls children hospitalized with diarrhea at 38 sentinel surveillance sites in 31 LMICs across all 6 WHO Regions. Randomly selected stool specimens were tested by TaqMan Array Card quantitative polymerase chain reaction for 16 enteric pathogens previously associated with pediatric diarrhea. GPDS produces estimates of pathogen-specific attributable fractions and incidence of diarrheal hospitalizations at the global, regional, and country levels. Conclusions As a WHO-coordinated global surveillance network, GPDS evaluates pathogens associated with hospitalized pediatric diarrhea. The network monitors the changing burden of pathogens over time, monitors circulating strains, and generates data to inform decision-making around public health interventions. GPDS also improves global, regional, and country diarrheal disease burden estimates, informs new enteric vaccine development, and potentially provides a platform for future enteric vaccine evaluation.

Background: Platinum-based chemotherapy is known to cause severe and debilitating hearing loss, but unlike cisplatin, the true incidence of carboplatin-induced hearing loss remains unclear. We evaluated functional hearing outcomes in children receiving carboplatin to determine the incidence and severity of ototoxicity. Procedure: We identified a large cohort of children with cancer treated with carboplatin and graded their audiograms using the SIOP ototoxicity scale. Patients with inadequate audiological follow-up, prior hearing loss, or exposure to cisplatin were excluded. Fishers exact test, logistic regression, and ROC analyses were performed to investigate associations of demographic, treatment, and exposure-related risk factors with incidence of hearing loss. Results: 200 patients were included, all of whom had been treated with carboplatin. Only nine (4.5%) patients developed clinically significant hearing loss (SIOP grade [&ge;]2). Younger age at first exposure to carboplatin was the only significant predictor of hearing loss (OR = 0.7888, p=0.0241). Age [&le;]28 months was significantly associated with hearing loss (OR 12.37, p=0.0042). No other risk factors or exposures were statistically significant. Conclusions: Clinically significant carboplatin-associated hearing loss was uncommon (incidence 4.5%). We show that young age is the single-most important risk factor for hearing loss; of nine children who developed hearing loss, eight were aged [&le;]28 months. Children below this age have twelve-fold higher odds of developing hearing loss compared to those above this age (OR 12.37). These findings will allow physicians to provide more appropriate counselling to families regarding ototoxic risk and support intensified hearing surveillance in young children.

We assembled a multimodal clinical dataset describing demographics, placement history, prenatal substance exposure (PSE), birth characteristics, adverse childhood experiences (ACEs), International Classification of Diseases (ICD) diagnoses, and laboratory results for 3,685+ pediatric patients evaluated between 2014 and 2024 at the University of Minnesotas Adoption Medicine Clinic (AMC). Data were curated from electronic medical records through a combined manual and automated extraction protocol using a standardized operating procedure. The resulting dataset integrates structured EMR fields including neuropsychological, laboratory, and diagnostic information with manually pulled fields of ACE scores, PSE history, and placement history. We provide an overview of the population represented and describe the datasets structure, variable definitions, and validation procedures. This resource enables investigations into how early adversity impacts medical and developmental outcomes, and provides one of the largest standardized clinical placement history, PSE, and ACE datasets in an adoption and foster care pediatric population.

Introduction: Respiratory infections are a leading cause of morbidity. Newly available vaccines to prevent respiratory syncytial virus (RSV) disease and encouraging clinical progress on vaccines for human metapneumovirus (hMPV) and parainfluenza (PIV) could reduce the disease burden beyond existing influenza and SARS-CoV-2 immunisation programs. However, evidence on the contribution of these viruses to respiratory disease burden across the lifespan remains limited. Methods: We reviewed studies from 01/2002-11/2025 reporting age-stratified, medically attended cases of influenza, and at least one of RSV, hMPV, or PIV, in high-income countries, excluding periods substantially overlapping with the COVID-19 pandemic. Using only studies that tested for all four viruses, we estimated the age-specific proportion of cases that were non-influenza (total across RSV, hMPV and PIV) compared to influenza using a mixed-effects logistic regression model. Results: Following exclusions and screening, 61 studies were included in the primary analysis comprising >500,000 detections of the four viruses. We found that a substantial proportion of medically attended respiratory illness in infants and young children was due to PIV, hMPV and RSV, rather than influenza, with a non-influenza virus proportion of 90.2% (95% CI 85.9-93.2%) in young infants aged 0-6 months. The converse was true for school-aged children, with a non-influenza virus proportion of 34.8% (95% CI 26.5-44.2%) in children aged 5-18 years. In adults aged 65+ years, non-influenza causes of medically attended disease were common at 60.2% (95% CI 50.0-69.5%). Restricting to studies reporting hospitalised cases (n=19) produced broadly similar age-specific trends in relative virus burden contributions. Discussion: We highlight the significant burden of medically attended illness due to PIV, hMPV and RSV across ages, particularly in infant and preschool-aged children and older adults, supporting the need for effective vaccines targeting this burden.

Background High-risk subgroups among household contacts of persons with tuberculosis (TB) might benefit from additional interventions. However, the significance of an abnormal baseline chest radiograph (CXR) suggestive of TB, despite negative sputum microbiology, is uncertain. Methods Adults ([&ge;]18 years) with recent household TB exposure were enrolled at three South African sites (April 2021-September 2022). All participants underwent symptom screening, CXR, and sputum Xpert Ultra and MGIT culture. Pulmonary TB diagnosis was microbiologically-confirmed. Participants without prevalent TB were followed for symptomatic incident TB through 12 months. Multivariable logistic regression identified factors associated with abnormal CXR suggestive of TB. Poisson regression estimated adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95%CI). Results Baseline CXR were available for 795/846 (94.0%) participants without prevalent TB and were abnormal in 157/795 (19.7%); associated with older age (adjusted odds ratio, aOR=1.04, 95%CI 1.02-1.05); prior TB (aOR=6.39, 95%CI 4.18-9.78); and current smoking (aOR=1.61, 95%CI 1.00-2.62). Symptomatic incident TB developed in 8/795 (1.0%) participants, including 7/8 (87.5%) who were asymptomatic and 4/8 (50.0%) with abnormal CXR at baseline. TB incidence was higher in those with abnormal versus normal CXR (aIRR=4.11, 95%CI 1.29-13.09), but after median 12.1 (IQR 11.1-13.1) months follow-up, 153/157 (97.5%) had not progressed to incident TB. Conclusions Adult household contacts with CXR abnormalities, but without prevalent TB, had a four-fold higher incidence of TB within one year, compared to those with normal CXR. This additional risk warrants targeted preventive treatment and extended surveillance, but since most remained TB-free, therapeutic TB treatment is not justified.

Background: As tuberculosis (TB) incidence declines, transmission increasingly concentrates into vulnerable populations. There is an urgent need for affordable surveillance strategies to monitor trends, identify high-risk groups and target interventions. Mycobacterium tuberculosis (Mtb) immunoreactivity surveys indirectly detect transmission and therefore undiagnosed infectious disease. Methods: We conducted a cross-sectional community-based interferon-gamma release assay (IGRA) survey in children aged 1-4 years in Blantyre, Malawi. Community-representative participants were recruited using novel convenience sampling in health facilities alongside random household sampling, and tested for Mtb immunoreactivity using QFT-Plus IGRA. We constructed hierarchical Bayesian logistic regression models for IGRA positivity, with neighbourhood-level random effects. Findings: Of 1,545 participants, 102 (6.6%) had a positive IGRA: an annual risk of Mtb infection (ARTI) of 2.7% (95% CrI 2.2-3.2%). Immunoreactivity was higher in the poorest third of households (8.7% vs 4.9%; adjusted odds ratio: 1.88, 95% CrI 1.08-3.01) compared to the richest, but was not associated with HIV exposure, malnutrition or reported household TB exposure. There was substantial between-neighbourhood heterogeneity (ARTI range 1.1-4.1%). There was no association between neighbourhood-level TB case notifications and ARTI. Interpretation: An innovative convenience sampling approach identified a high burden and substantial spatial variation of recent TB transmission, which did not correspond to case notification rates. This strategy could support identification of high-risk populations, monitoring of trends and targeted public health interventions.

Background: The chromosome 1q31 Th2 pathway-associated interval has been linked to asthma, but its phenotype specificity and cross-ancestry architecture remain unclear. Methods: We analyzed African (AFR) and European (EU) ancestry datasets, including 9,965 asthma cases and 37,391 controls of AFR, and 6,074 cases and 116,255 controls of EU ancestry. Imputed dosage-based association analyses were performed for asthma, steroid-dependent asthma (SDA), and non-steroid-dependent asthma, followed by QC-filtered SDA remapping, leave-one-batch-out analysis, cross-ancestry comparison, and functional enrichment. Results: Strong regional association was observed only for SDA. After quality-control (QC) filtering, the SDA signal remained significant in both ancestries, with 2,280 genome-wide significant variants in AFR and 859 in EU. Cross-ancestry comparison identified 3,129 significant variants: 10 shared, 2,270 AFR-specific, and 849 EU-specific. Shared variants showed concordant effects, whereas 237 variants showed nominal heterogeneity. AFR-specific signals included PTPRC variants with larger effects in AFR. Functional enrichment suggested different biological emphases within the same interval: immune and contractile airway-wall biology in AFR, and additional neuroaxonal components in EU. Conclusions: The 1q31 interval is strongly associated with SDA in both AFR and EU populations, and its fine-scale architecture differs by ancestry. These findings highlight population-specific effects within a shared SDA susceptibility interval, with potential implications for population-informed precision medicine in steroid responsiveness and asthma management.