Pediatrics

In this large multi-center cohort of children evaluated for Lyme disease in a Lyme-endemic emergency department, we assessed the diagnostic accuracy of clinician suspicion and subsequent clinical decision-making for children presenting with monoarthritis. Among 1,582 children with monoarthritis evaluated for Lyme disease, 623 (39%) had Lyme arthritis and 32 (2%) had septic arthritis. Overall, 313 (20%) had an invasive joint procedure (arthrocentesis or arthroscopy), 194 (12%) received parenteral antibiotics, and 376 (24%) were hospitalized. Clinician suspicion had moderate discriminative ability for Lyme disease (area under the receiver operating characteristics curve: 0.75, 95% confidence interval: 0.72-0.77). Children with higher clinician suspicion were less likely to receive parenteral antibiotics or to be hospitalized, although invasive procedure rates were similar. Our findings highlight the challenge of clinically distinguishing Lyme from septic arthritis. Better diagnostic tools are needed to improve timely diagnosis and minimize invasive testing among children with monoarthritis in Lyme-endemic regions.

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.

ObjectivesAcute 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. MethodsWe 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). ResultsRecruitment 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. ConclusionIn 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.

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.

ObjectiveCerebral palsy (CP) affects approximately 1 million Americans and 18 million individuals worldwide, yet contemporary US epidemiologic data remains limited. We aimed to use Cerebral Palsy Research Network (CPRN) clinical registry to describe demographics and clinical characteristics of individuals with CP across the US and determine associations with gross motor function and genetic etiology. MethodsRegistry subjects were included if they had clinician-confirmed CP and prospectively entered data for Gross Motor Function Classification System (GMFCS) Level, gestational age, genetic etiology, CP distribution, and tone/movement types. Logistic regression was used to determine which of these variables plus race, sex, ethnicity, and age were associated with GMFCS level and genetic etiology. ResultsA total of 9,756 children and adults with CP from 22 CPRN sites met inclusion criteria. Participants were predominantly White (73.0%), male (57.3%), non-Hispanic (87.8%), and younger than 18 years (73.7%). Most were classified as GMFCS levels I-III (55.6%), born preterm (52.8%), had spasticity (83.8%), and had quadriplegia (41.9%); 12.2% were identified as having a genetic etiology. Tone/movement types, CP distribution, and gestational age were significantly associated with both GMFCS level and genetic etiology (p<0.001). Compared to White individuals, Black individuals were more likely to have greater gross motor impairment (p<0.001). ConclusionIn this large US cohort, clinical and demographic factors, including race, were associated with gross motor function and genetic etiology in CP. These findings highlight persistent disparities and demonstrate the value of a national clinical registry for informing prognostication, quality improvement efforts, and targeted genetic testing strategies.

Objective To evaluate physician knowledge, attitudes, and practices regarding viral exanthem diagnosis and mandatory reporting requirements among practicing physicians in major metropolitan regions of Florida. Study Design An IRB-exempt cross-sectional survey was distributed via REDCap to licensed physicians and residents in family medicine, internal medicine, pediatrics, and infectious disease across Florida. The 19-question survey assessed demographic characteristics, knowledge of viral exanthem diagnosis (measles, rubella, roseola), reporting requirements, physician attitudes, and clinical practices. Knowledge scores were compared by specialty using ANOVA with Tukey post-hoc analysis. Multivariate analysis and linear regression assessed associations between physician confidence and knowledge scores. Results A total of 162 physicians responded, with 146 complete responses included in analysis. Participants included pediatrics (n=74), family medicine (n=48), and internal medicine (n=24). The overall mean knowledge score was 78.5% (SD 20.5). Pediatricians demonstrated the highest scores (82.7%) compared with internal medicine (76.4%) and family medicine (73.3%), with pediatricians scoring significantly higher than family physicians (p=0.04). Differences in vignette-based diagnostic knowledge and mandatory reporting knowledge were not statistically significant across specialties. Roseola was the most commonly diagnosed viral exanthem (66%), followed by measles (30%) and rubella (17%). Most physicians (91.4%) expressed interest in additional training. Conclusions Although overall physician knowledge of viral exanthem diagnosis and reporting was high, clinically meaningful gaps remain, particularly in differentiating similar rash presentations. Pediatricians demonstrated higher knowledge scores than family physicians. Enhanced physician education may improve diagnostic accuracy and public health reporting as vaccination rates decline and outbreaks of vaccine-preventable viral exanthems increase.

ObjectivesAcademic medical institutions are the gatekeepers of the physician workforce and shape the future of medicine by regulating medical school admissions as well as residency training. Although broadly the field of medicine is seeing more representation from traditionally underrepresented groups, the critical decision-making platform of academic medicine continues to be uncharacteristically homogeneous, represented mainly by white males. This is even more pronounced in surgical subspecialties, such as academic neurosurgery. This study aims to quantify this phenomenon, uncover its driving factors, and define opportunities for improvement. MethodsUsing a mixed research methodology, academic neurosurgical faculty in the U.S were identified, and their demographic data was collected. An internet search using Google Scholar and Scopus was conducted to determine scholarly activity using number of publications and h-index. ResultsWe found a significant increase in female faculty in academic neurosurgery within the last decade. Comparing the faculty rank amongst male and female faculty, we found that the majority of female faculty are at the assistant professor level (n=36/79; 45.6%) while male faculty are more at the full professor rank (n=265/582; 45.5%). A similar trend was seen for under-represented minority neurosurgery faculty. Strong scholarly activity corelated with a departmental chair position for male faculty, however, this trend was not true for female faculty. There was a significant difference in the number of publications and h-index in female vs male faculty, but only when including male faculty outliers at the full professor level. ConclusionSlowly but steadily, academic neurosurgery is making progress towards a more diverse and representative workforce in the U.S that better reflects the patient population. Facilitating timely progression of females and URM neurosurgeons into senior professorship and academic leadership roles will further advance this essential progress.

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 To examine ethnic differences in the incidence and age-related trajectories of childhood health conditions from birth to adolescence within a UK birth cohort. Design Longitudinal population-based birth cohort with linkage to primary care electronic health records. Setting Born in Bradford (BiB), a multi-ethnic birth cohort in Bradford, UK. Participants 13,282 children (36% White British, 44% Pakistani British, 20% other ethnicity) born 2007 to 2011 with linked primary care records and over 1 year follow-up. Main outcome measures Incident diagnoses of atopic conditions (asthma, eczema, allergic rhinoconjunctivitis), overweight/obesity, common mental health disorders (anxiety, depression), and neurodevelopmental disorders (including ADHD and autism). Incidence rates, Kaplan-Meier cumulative incidence, and Cox regression hazards ratios (HRs) were estimated. Results Atopic conditions emerged early (median onset 5 to 6 years) and were more common among Pakistani British children, with higher hazards of eczema (HR 2.29, 95% CI 2.01 to 2.61), allergic rhinoconjunctivitis (HR 2.27, 2.00 to 2.58), and asthma (HR 1.35, 1.22 to 1.50). Overweight/ obesity developed later (median 9 to 10 years) and were also more frequent in Pakistani British children (HR 1.25, 1.16 to 1.35). In contrast, common mental health disorders emerged predominantly in early adolescence (median around 13 years), and both mental health and neurodevelopmental diagnoses were more frequently recorded among White British children; Pakistani British children had lower hazards of neurodevelopmental diagnoses (HR 0.28, 0.23 to 0.35) and mental health disorders (HR 0.53, 0.41 to 0.70). Conclusions Ethnic differences in childhood health are condition-specific and vary by age of onset, emerging at distinct stages. These findings inform the timing of prevention, service planning, and research into underlying mechanism.

ObjectiveTo describe the clinical characteristics of term neonates with neonatal bacterial meningitis (NBM) and explore the association between different pathogens and imaging complications, providing clinical evidence for early identification and individualized management. MethodsA retrospective study was conducted on 531 term neonates diagnosed with NBM admitted to the Capital Institute of Pediatrics from 2013 to 2025. Demographics, clinical manifestations, laboratory parameters, etiological results, imaging complications and treatment measures were collected. Patients were divided into favorable/adverse discharge outcome groups and pathogen-positive/negative groups. Statistical analyses were performed using appropriate tests, and Cramers V coefficient was used to analyze the association between pathogens and imaging complications. ResultsO_LIThe most common clinical manifestations were abnormal body temperature (79.85%), altered consciousness (55.18%) and jaundice (46.52%). CSF/blood culture was positive in 133 cases (25.05%), with Escherichia coli (27.07%), group B streptococcus (17.29%) and Staphylococcus species (16.54%) as predominant pathogens. The overall incidence of imaging complications was 22.22%, mainly hydrocephalus (5.84%), subdural effusion (4.90%) and encephalomalacia (2.64%). C_LIO_LIAdverse discharge outcomes occurred in 107 cases (20.15%). Compared with the favorable group, the adverse group had higher incidences of convulsions, altered consciousness, anterior fontanelle bulging, abnormal muscle tone and primitive reflexes (all P<0.001), more obvious laboratory abnormalities (higher CRP, CSF leukocytes and protein, lower CSF glucose, all P<0.05), higher culture positive rates and greater need for adjuvant therapy (all P<0.001). C_LIO_LIPathogen-positive patients had higher imaging complication rates. Gram-negative infections were associated with higher hydrocephalus and subdural effusion rates, while Gram-positive infections had higher brain abscess risk. Specifically, Escherichia coli correlated with hydrocephalus and subdural effusion; group B streptococcus with cerebral infarction and encephalomalacia; LMs with intracranial hemorrhage and brain abscess; negative cultures correlated with no imaging complications (all P<0.05). C_LI ConclusionTerm NBM neonates have non-specific manifestations, mainly abnormal body temperature and altered consciousness. Predominant pathogens areEscherichia coli, group B streptococcus and Staphylococcus species, with hydrocephalus and subdural effusion as common imaging complications. Adverse outcomes are associated with severe symptoms, obvious laboratory abnormalities and higher pathogen positivity. Specific pathogens correlate with distinct imaging complications.

PurposeWe evaluated healthcare resource utilization (HCRU) and costs in patients with eosinophilic granulomatosis with polyangiitis (EGPA). MethodsPatients with newly diagnosed EGPA (2017-2021), [&ge;]12 months pre-diagnosis health plan enrollment, and [&ge;]1 inpatient or [&ge;]2 outpatient claims with an EGPA diagnosis were included. Follow-up was from EGPA diagnosis until disenrollment or database end. HCRU and health insurer payment costs during follow-up were compared with those for matched cohorts of general insured patients without EGPA (comparison A) and without EGPA but with severe uncontrolled asthma (SUA; comparison B). ResultsIn comparison A, all-cause HCRU was higher in the EGPA cohort (n = 213) versus matched patients (n = 779) for all clinical encounters/pharmacy claim types; annualized, mean total all-cause costs were 16-fold higher ($117,563/patient) versus matched patients ($7,520/patient). In comparison B, all-cause HCRU was higher for the EGPA cohort (n = 182) versus the matched SUA cohort (n = 640) for all clinical encounters/pharmacy claim types, with 5-fold higher mean total all-cause costs ($118,127/patient vs $22,286/patient). In both EGPA cohorts, HCRU and associated costs increased between the baseline and follow-up periods. ConclusionsThese findings highlight the need for more effective treatments to reduce the clinical and economic burden of EGPA.

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.

BackgroundGroup A streptococcus (GAS) infections have been associated with neuropsychiatric disorders in epidemiologic studies and animal models, but data in US health care populations are limited. GAS is also associated with autoimmune sequelae, including acute rheumatic fever (ARF)/Sydenham chorea (SC), poststreptococcal reactive arthritis (PSRA), poststreptococcal glomerulonephritis (PSGN), and guttate psoriasis (GP). Epstein-Barr virus (EBV) has been linked to systemic lupus erythematosus (SLE) and multiple sclerosis (MS) and the complexity of these associations parallels that of GAS-associated conditions, providing a useful comparison. Objectives1) Assess the association between a positive GAS test and incident neuropsychiatric diagnoses within 1 year in a large US health care database. 2) Assess the validity of the same database in detecting well-established disease associations while avoiding false associations. Design, Setting, ParticipantsRetrospective cohort study using TriNetX data from US health care organizations. Patients with positive or negative tests were propensity score-matched (GAS cohort n=178,301; EBV cohort n=64,854). Patients with documented neuropsychiatric diagnoses prior to testing were excluded. To approximate a primary care population, inclusion required at least one well-visit. ExposuresPositive vs negative GAS test; positive vs negative EBV test (separate cohorts). Main Outcomes and ValidationsMain outcome: incident neuropsychiatric diagnoses within 1 year of GAS testing. Positive control outcomes: ARF/SC, PSRA, PSGN, and GP (for GAS cohort); SLE and MS (for EBV cohort). Negative control outcomes: conditions without known association with GAS. ResultsAfter matching, a positive GAS test was associated with attention-deficit/hyperactivity disorder (ADHD) (RR: 1.09; 95% CI: 1.03-1.15). Among established poststreptococcal conditions, only GP was associated with prior GAS (RR: 1.75; 95% CI: 1.06-2.89). Case counts were insufficient to evaluate ARF/SC, PSRA, and PSGN. Negative control outcomes showed no association. In the EBV cohort, no association was observed with SLE, and MS showed a decreased risk. Conclusions and RelevanceA positive GAS test was associated with ADHD but not with other neuropsychiatric disorders. The database detected poststreptococcal GP but did not identify most established postinfectious autoimmune associations, likely reflecting rarity, heterogeneity, and diagnostic complexity. These findings begin to describe the range of real-world health care databases to evaluate postinfectious neuropsychiatric risk.

BackgroundEvidence to guide the choice of injectable antibiotics and supportive care for children with severe pneumonia is limited and may not reflect changes in epidemiology associated with vaccination and antimicrobial resistance. MethodsIn this pragmatic, open-label, factorial, randomized trial conducted in 16 hospitals in Kenya, children aged 2-59 months with World Health Organization-defined severe pneumonia were assigned to receive one of three injectable antibiotic regimens: benzylpenicillin plus gentamicin (standard care), ceftriaxone, or amoxicillin-clavulanic acid. Eligible children were also randomly assigned to receive nasogastric tube feeding or intravenous fluids. The primary outcome was death from any cause by day 5 after enrollment. ResultsA total of 4393 children underwent randomization to the antibiotic groups, and 1064 to the supportive care groups. By day 5, deaths occurred in 87/1463 children (6.0%) receiving benzylpenicillin plus gentamicin, 82/1458 (5.6%) receiving amoxicillin-clavulanic acid (adjusted risk ratio [aRR], 0.94; 97.5% confidence interval [CI], 0.67 to 1.31), and 81/1462 (5.5%) receiving ceftriaxone (aRR vs. benzylpenicillin plus gentamicin, 0.95; 97.5% CI, 0.68 to 1.33). Death by day 5 occurred in 30/531 children (5.7%) receiving nasogastric tube feeding and 35/532 (6.7%) receiving intravenous fluids (aRR, 1.13; 97.5% CI, 0.71 to 1.79). Secondary outcomes were similar across groups. ConclusionsAmong children hospitalized with severe pneumonia, outcomes with benzylpenicillin plus gentamicin were similar to those with ceftriaxone or amoxicillin-clavulanic acid, and nasogastric tube feeding was similar to intravenous fluids with respect to mortality and safety.

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.

Objectives. To compare the efficacy and safety of invasive sacral neuromodulation (SNM) and noninvasive enteral neuromodulation (ENM) in children with refractory gastrointestinal motility disorders (GMD). Materials and Methods. This prospective interventional trial enrolled pediatric patients with GMD between 2019 and 2024 at a single tertiary referral center. Children with inflammatory bowel disease or mechanical causes of GMD were excluded. Participants received either SNM via an implanted device or ENM via surface electrodes. Stimulation was delivered at 14 Hz, 210 s pulse width, with individualized intensity (median 1.0 mA for SNM; 6.0 mA for ENM). Primary outcomes were abdominal pain, fecal incontinence, defecation frequency, and stool consistency. Treatment success was defined as clinically significant improvement in at least two of these four domains. Quality of life was assessed at baseline and 12 weeks. Safety outcomes were monitored over a 12-month follow-up. Results. Of 70 eligible patients, 48 completed the study (18 SNM; 30 ENM). Diagnoses included Hirschsprung disease, functional constipation, and congenital neuronal malformations. Severe comorbidities were more frequent in the SNM group (45%) than the ENM group (3%; P = .0018). Treatment success was observed in 80% of ENM and 83% of SNM patients (P = 1.00). No significant differences were found between groups for individual outcomes. No major complications occurred. Minor adverse events were comparable (ENM 27% vs SNM 17%; P = .50). Conclusions. Both SNM and ENM are effective and safe options for treating pediatric GMD and may be considered within a multimodal therapeutic approach.

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.

Methods: Using Global Burden of Disease (GBD) data, we analyzed prevalence, incidence, mortality, and disability-adjusted life years (DALYs) rates across global and 21 GBD regions from 1990-2023. Joinpoint regression identified temporal trends, age-period-cohort models analyzed effect contributions, Das Gupta decomposition quantified demographic and epidemiological impacts, inequality indices assessed health equity, and Bayesian models projected 2024-2038 trends. Results: In 2023, the global number of children and adolescents with asthma reached 131 million, with an age-standardized prevalence rate (ASPR) of 1,789.9 per 100,000. From 1990 to 2023, the global ASPR and age-standardized incidence rate (ASIR) of asthma in children and adolescents showed an upward trend, while the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate (ASDR) exhibited a downward trend. Among the 0-14 age group, the disease burden was greater in males than in females, whereas in the 15-19 age group, males had a lower disease burden than females. Projections indicate that over the next 15 years, the overall disease burden will continue to decline; however, female mortality rates and DALYs rates are projected to show an upward trend. Conclusions: The increasing prevalence and incidence rates, coupled with declining mortality and DALYs rates of asthma among children and adolescents globally, underscore the necessity for targeted public health interventions. These findings provide crucial insights for early diagnosis, treatment optimization, and global health policy formulation.

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.