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Objective: To describe the safety and effectiveness of treating pediatric patients who have pulmonary arterial hypertension (PAH) with selexipag in a real-world, multicenter cohort, given that data supporting its use in pediatric PAH are sparse., Study Design: We report a multicenter, retrospective, cohort study of children with PAH treated with selexipag. Demographic and clinical variables were extracted from the medical records. Clinical parameters were analyzed at 3 timepoints: before selexipag, 3-12 months after selexipag, and >12 months follow-up., Results: Eighty-seven patients were included, 32 received selexipag as add-on to background therapy, and 55 transitioned from another prostanoid. The median starting and final doses were 4.7 and 28.5 μg/kg/dose twice daily, respectively. Add-on patients demonstrated improved indexed pulmonary to systemic vascular resistance ratio after selexipag initiation (PVRi/SVRi, 0.62v0.53; P = .034) with a lower average mean pulmonary artery pressure (46 vs 39 mm Hg; P = NS), and oxygen consumption (maximal oxygen consumption during cardiopulmonary exercise testing [VO 2 max] 27.8 mL/kg/min vs 30.9 mL/kg/min; P = NS). Transition patients demonstrated stable mean pulmonary artery pressure (47 mm Hg vs 45 mm Hg; P = NS) and a lower mean indexed pulmonary vascular resistance (10.9 Wood units∗m 2 vs 8.2 Wood units∗m 2 ; P = NS) but late functional worsening in some with VO 2 max decreased at follow-up (26.0 mL/kg/min vs 19.5 mL/kg/min). Side effects were noted in 40% of the cohort, but prompted discontinuation in only 2%., Conclusions: In a large, multicenter cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth., Study Design: This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17 years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2 years was calculated as (weight [kg] at 2 years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2 years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent., Results: Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with β-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P < .0001). Adjusted for birth weight z score and gestational age, CUG in the first 2 years after birth was not significantly associated with FSIQ (β-coefficient 0.108 [95% CI -1.373 to 1.590], P = .886)., Conclusions: Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development., Competing Interests: Declaration of Competing Interest This research was funded by The Dutch Heart Foundation (2017T075). The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This retrospective study analyzed 230 pediatric opioid exposures from a statewide poison control center over a 5-year period. Most exposures involved pharmaceutical opioids and children below 2-years-old. Narrative details were reviewed to identify uncommon sources of opioids involved in poisoning and highlight the need for tailored prevention strategies and guidance., Competing Interests: Declaration of Competing Interest No funding was secured for this study. The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the performance of childhood obesity prediction models in four independent cohorts in the United States, using previously validated variables obtained easily from medical records as measured in different clinical settings., Study Design: Data from four prospective cohorts, Latinx, Eating, and Diabetes; Stress in Pregnancy Study; Project Viva; and Center for the Health Assessment of Mothers and Children of Salinas were used to test childhood obesity risk models and predict childhood obesity by ages 4 through 6, using five clinical variables (maternal age, maternal prepregnancy body mass index, birth weight Z-score, weight-for-age Z-score change, and breastfeeding), derived from a previously validated risk model and as measured in each cohort's clinical setting. Multivariable logistic regression was performed within each cohort, and performance of each model was assessed based on discrimination and predictive accuracy., Results: The risk models performed well across all four cohorts, achieving excellent discrimination. The area under the receiver operator curve was 0.79 for Center for the Health Assessment of Mothers and Children of Salinas and Project Viva, 0.83 for Stress in Pregnancy Study, and 0.86 for Latinx, Eating, and Diabetes. At a 50th percentile threshold, the sensitivity of the models ranged from 12% to 53%, and specificity was ≥ 90%. The negative predictive values were ≥ 80% for all cohorts, and the positive predictive values ranged from 62% to 86%., Conclusion: All four risk models performed well in each independent and demographically diverse cohort, demonstrating the utility of these five variables for identifying children at high risk for developing early childhood obesity in the United States., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. Project Viva was funded by grants RO1HD034568, UH3OD023286, and R24ES030894 from the National Institutes of Health, United States to Dr. Oken. SIPS was supported by grants R01MH1316328 and R01DA057310 from the National Institutes of Health, United States to Dr. Nomura. CHAMACOS was funded by grants R82670901 and RD83171 from the Environmental Protection Agency, United States and PO1ES009605, PO1ES00960, U24ES028529, and R24ES028529 from the National Institutes of Health, United States to Dr. Eskenazi. LEAD was supported by grants NIDDK 080825 and NIDDK 097458 from the National Institutes of Health, United States, as well as the Hellman Family Foundation, United States, Allen Foundation, United States, and Marc and Lynn Benioff to Dr. Wojcicki. The funders had no role in the study design, the collection, analysis, and interpretation of the data, the writing of the report, or the decision to submit for publication., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To study school achievement in grade 9 of compulsory school in children with congenital hypothyroidism (CH), both those detected by the national screening program and those with a normal screening result and thus diagnosed later., Study Design: Nationwide study of children in the Swedish Medical Birth Register (n = 1 547 927) from 1982 through 1997, linked to the neonatal screening CH cohort and the National School Register. Dried blood spot (DBS) samples are collected from all newborn infants, according to the neonatal screening program. Thyroid-stimulating hormone was used for CH screening. CH was defined as either having an abnormal screening result (DBS+) and treatment with levothyroxine (LT4+) or having a normal screening result but a CH diagnosis in the National Patient Register and treatment with LT4 (DBS-/ICD+/LT4+). Regression models were used to study school performance, which as measured as grade point sum and national test results. Sibling analysis also was performed to account for unmeasured familial factors., Results: There were 448 children who were DBS+/LT4+ and 475 children who were DBS-/ICD+/LT4+. Children with CH had lower grade point sum, adjusted β = - 6.34 (95% CI -11.7 to -1.01) and adjusted β = -10.3 (95% CI -15.5 to -5.20) for those with abnormal (DBS+/LT4+) and normal screening (DBS-/ICD+/LT4+) results, respectively. CH also was associated with lower result on the national tests, especially in mathematics. These associations remained in the sibling analyses., Conclusions: Youth with CH had slightly lower school achievements compared with those without CH and compared with their siblings. CH children with a normal screening result, and thus diagnosed later, presented the lowest results on grade point sum and national tests., Competing Interests: Declaration of Competing Interest A.G. was supported by Region Stockholm (clinical post doctorial appointment). Financial support also was provided from the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM) framework grant no 340-2013-5867,Sällskapet Barnavård, Karolinska Institutetand The Samariten Foundation for paediatric research. The authors declare they have no actual or potential competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess changes in health-related quality of life (HRQOL) across a 12-month period following pediatric concussion and to explore whether psychological factors (ie, preinjury mental health history, current symptoms of anxiety and depression, sleep disturbance, or grit) were associated with HRQOL., Study Design: Prospective cohort study design using data collected from patients presenting to a specialty care concussion program, with each patient followed for 12 months after initial presentation. Comparison data were collected from nonconcussed controls recruited from the community. A total of 49 concussed patients (median = 15.4 years of age) completed the Pediatric Quality of Life Inventory, Patient-Reported Outcome Measure Information Systems Anxiety and Depressive Symptoms short forms, Pediatric Sleep Disturbance forms, and a Short Grit Scale. Mixed effects models explored change in HRQOL across time., Results: Total HRQOL at initial clinic presentation was significantly lower for concussed adolescents (Pediatric Quality of Life Inventory total score mean = 72 [SD = 16]) compared with nonconcussed controls (mean = 88 [SD = 11], P < .001). HRQOL improved in the patients with concussion over a 6-month period after initial assessment with no significant changes thereafter. Preinjury history of anxiety (coefficient = -11.388, CI = -18.49 to -4.28, P < .001), current depressive symptoms (coefficient = -0.317, CI = -0.62 to -0.01, P < .01), and sleep disturbance (coefficient = -0.336, CI = -0.71 to 0.04, P < .05) all predicted lower HRQOL., Conclusions: HRQOL is significantly lower in the acute phase of pediatric concussion and steadily improves over the following 6 months. Psychological factors are linked to lower HRQOL and may serve as important indicators of risk for poor outcome., Competing Interests: Declaration of Competing Interest This work was funded by the Pennsylvania Department of Health, NIHR01NS097549, and the Frontier Program at the Children's Hospital of Philadelphia. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare the number and incidence of Kawasaki disease (KD) patients in years 2 through 4 of the coronavirus disease 2019 pandemic, and determine the impact of 3 years of implementation of infection control measures and their subsequent relaxation on the epidemiology of KD in Japan., Study Design: We conducted a population-based, cohort study including consecutive KD patients in Kobe City between 2021 and 2023. We compared the incidence of KD cases, in relation to timing of infection control measures, as well as infectious disease cases based on a regional surveillance system. Data from a previous 2016 through 2020 study were used for comparison., Results: A total of 566 children with KD were identified during the study period. During the infection control period in 2021 to 2022, the incidence of KD remained low compared with the prepandemic level (281.3 and 327.5/100 000 children aged 0-4 years in 2021 to 2022 and 2016 through 2019, respectively), but a recovery trend began in the 0-1-year age group. During the relaxation period in 2023, the incidence of KD increased across a wide-age range, reaching the highest recorded in Japan (426.7/100 000 children aged 0-4 years), and the median age of onset increased to age 30 months. The resurgence of KD coincided with the epidemic patterns for multiple infectious diseases in 2023. The seasonality of KD observed before the pandemic was altered., Conclusions: KD resurged in 2023 after relaxation of the prolonged coronavirus disease 2019 pandemic restrictions in Japan. This phenomenon coincided with the rise of multiple infectious diseases, and supports the pathogenesis of KD being triggered by infectious agents., Competing Interests: Declaration of Competing Interest The authors declare that no financial support was received for the research or publication of this article. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine the clinical benefit of drugs that earned or redeemed rare pediatric disease priority review vouchers (PRVs) from 2017 through 2023, and the revenues generated by such drugs., Study Design: In this cohort study, Federal Register documents, publicly available health technology agency (HTA) assessments, and financial filings were used to identify drugs that were issued or redeemed using a rare pediatric disease PRV from 2017 through 2023, and to assess their added therapeutic benefit and drug-specific global revenues., Results: Among the 36 drugs whose approval resulted in issuance of a rare pediatric PRV, therapeutic benefit ratings were available for 17 (47%), with 9 (53%) rated as high by at least 1 organization. Mean annual global revenues were $363 million (year 1), $621 million (year 2), and $850 million (year 3). The median annual list price for drugs issued a voucher was $788,705. Vouchers were then redeemed for 15 different drugs; out of 13 drugs with therapeutic benefit ratings, 4 (31%) were high value., Conclusions: Drugs that treat rare pediatric diseases generate similar revenues compared with other brand drugs, and drugs with high therapeutic benefit tend to generate more revenue than those with low therapeutic benefit. Drugs that earned the rare pediatric disease PRV for their manufacturer generate significant revenues and the voucher may not be necessary to incentivize drug development in the rare pediatric disease space., Competing Interests: Declaration of Competing Interest This study received funding from Arnold Ventures. A.K. reports serving as an expert witness on behalf of a class of individual plaintiffs against Gilead related to its tenofovir-containing products, and having served as an expert with the FTC in the Amgen-Horizon merger case (now settled). The other author declares no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition after admission. Admissions included feeding and medication titration, interdisciplinary care, and a home parenteral nutrition team consultation., Competing Interests: Declaration of Competing Interest C.D. was supported in part by 2P30 DK040561. M.P. is a consultant for Fresenius Kabi and receive royalties for Omegaven. A.C. is an investigator on the Pediatric Teduglutide Registry sponsored by Takeda. A.C. is an investigator on a 90 day, Phase 3, Open Labeled Exploratory Study of RELiZORB to Evaluate Safety, Tolerability, and Nutrient Absorption in Children with Short Bowel Syndrome who are Dependent on Parenteral Nutrition sponsored by Alcresta., (Copyright © 2024 Elsevier Inc. All rights reserved.)

General pediatricians and those specialized in developmental-behavioral and neurodevelopmental disabilities support children with neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We identified substantial geographic disparities in pediatrician availability (eg, urban > rural areas), as well as regions with low pediatrician access but high ASD/ADHD prevalence estimates (eg, the US Southeast)., Competing Interests: Declaration of Competing Interest This publication was made possible in part by Grant Number T32-GM081740 from NIH-NIGMS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH. This project was supported in part by the Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services (HHS) under grant number U1CRH30539 Rural Health Research Grant Program Cooperative Agreement. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the US Government. This work was also supported by the Centers for Disease Control and Prevention (CDC), National Center on Birth Defects and Developmental Disabilities (Cooperative Agreement #5U19DD001218)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess whether beta-lactam extended or continuous beta-lactam infusions (EI/CI) improve clinical outcomes in children with proven or suspected bacterial infections., Study Design: We included observational and interventional studies that compared beta-lactam EI or CI with standard infusions in children less than 18 years old, and reported on mortality, hospital or intensive care unit length of stay, microbiological cure, and/or clinical cure. Data sources included PubMed, Medline, EBM Reviews, EMBASE, and CINAHL and were searched from January 1, 1980, to November 3, 2023. Thirteen studies (2945 patients) were included: 5 randomized control trials and 8 observational studies. Indications for antimicrobial therapies and clinical severity varied, ranging from cystic fibrosis exacerbation to critically ill children with bacteriemia., Results: EI and CI were not associated with a reduction in mortality in randomized control trials (n = 1464; RR 0.93, 95% CI 0.71, 1.21), but were in observational studies (n = 833; RR 0.43, 95% CI 0.19, 0.96). We found no difference in hospital length of stay. Results for clinical and microbiological cures were heterogeneous and reported as narrative review. The included studies were highly heterogeneous, limiting the strength of our findings. The lack of shared definitions for clinical and microbiological cure outcomes precluded analysis., Conclusions: EI and CI were not consistently associated with reduced mortality or length of stay in children. Results were conflicting regarding clinical and microbiological cures. More well-designed studies targeting high-risk populations are necessary to determine the efficacy of these alternative dosing strategies., Competing Interests: Declaration of Competing Interest Amélie Marsot receives salary subsidy as chercheur boursier Junior 1 from the Fonds de Recherche Québec Santé (FRQS). Nadia Roumeliotis receives funding support as a clinician scientist from the Fonds de Recherche Québec Santé (FRQS) and the Canadian Institute for Health Research (CIHR) for projects unrelated to this work. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the initial and long-term clinical course of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome after tonsillectomy regarding fever episodes and non-febrile PFAPA-related symptoms., Study Design: An observational cohort study with retrospective and cross-sectional data based on 86 of 101 patients who underwent tonsillectomy for PFAPA between January 2006 and March 2020 from a cohort of 336 patients diagnosed with PFAPA as children. Data were collected by structured telephone interviews and review of medical records. Parents were interviewed regarding initial response to tonsillectomy and the clinical course following tonsillectomy. Patients, if ≥18 years old, or parents, if patients were younger, were interviewed regarding symptoms present at the time of this long-term follow-up study., Results: Six months after tonsillectomy, 45 of 86 (54%) participants had no symptoms of PFAPA, 19 (22%) had only non-febrile PFAPA-related symptoms, 17 (20%) had ongoing but fewer or milder fever episodes, 1 (1%) had ongoing febrile episodes without improvement, and 4 (5%) had missing data because parents were unavailable. In 10 of 45 patients with initial remission, fever episodes reappeared 0.5-4.5 years after tonsillectomy. At long-term follow-up (median 8.8 years [range 2.8-16.1 years] after tonsillectomy), 54 of 86 (63%) had no symptoms of PFAPA, 15 (17%) had febrile episodes, generally with longer intervals between flares than before tonsillectomy, and 17 (20%) had non-febrile PFAPA-related symptoms., Conclusions: While PFAPA symptoms resolve or are milder post-tonsillectomy among most of the patients, the long-term outcomes showing residual symptoms among a substantial minority should be considered when evaluating tonsillectomy as a treatment option for PFAPA. Increased awareness of persistent symptoms after tonsillectomy may improve understanding and healthcare for these patients., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The objective of this study was to describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers., Study Design: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period., Results: Among 608 patients on ETI, 109 (17.9%) reported at least 1 AE. The majority (n = 85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA P value .026)., Conclusions: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To examine the effectiveness of an education intervention for reducing physician diagnostic error in identifying pediatric burn and bruise injuries suspicious for abuse, and to determine case-specific variables associated with an increased risk of diagnostic error., Study Design: This was a multicenter, prospective, cross-sectional study. A convenience sample of pediatricians and other front-line physicians who treat acutely injured children in the United States and Canada were eligible for participation. Using a web-based education and assessment platform, physicians deliberately practiced with a spectrum of 300 pediatric burn and bruise injury image-based cases. Participants were asked if there was a suspicion for abuse present or absent, were given corrective feedback after every case, and received summative diagnostic performance overall (accuracy), suspicion for abuse present (sensitivity), and absent (specificity)., Results: Of the 93/137 (67.9%) physicians who completed all 300 cases, there was a significant reduction in diagnostic error (initial 16.7%, final 1.6%; delta -15.1%; 95% CI -13.5, -16.7), sensitivity error (initial 11.9%, final 0.7%; delta -11.2%; 95% CI -9.8, -12.5), and specificity error (initial 23.3%, final 6.6%; delta -16.7%; 95% CI -14.8, -18.6). Based on 35 627 case interpretations, variables associated with diagnostic error included patient age, sex, skin color, mechanism of injury, and size and pattern of injury., Conclusions: The education intervention substantially reduced diagnostic error in differentiating the presence vs absence of a suspicion for abuse in children with burn and bruise injuries. Several case-based variables were associated with diagnostic error, and these data can be used to close specific skill gaps in this clinical domain., Competing Interests: Declaration of Competing Interest Data used for this research was extracted from the ImageSim platform. Dr. Kathy Boutis is married to Dr. Martin Pecaric of Contrail Consulting Inc. Contrail Consulting Inc. provides technical support for ImageSim. This is managed under an agreement with the Hospital for Sick Children. Dr. Boutis and Dr. Pusic are unpaid co-academic directors for ImageSim. This study was funded by the Hospital for Sick Children and Physician Services Incorporated., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To determine the long-term outcomes among a cohort of patients with Kawasaki disease (KD) and a history of giant coronary artery aneurysms (CAAs) at a single US center., Study Design: Medical records for all patients with KD and giant CAAs at a pediatric academic institution were reviewed. Primary outcomes included major adverse cardiovascular events (MACE) and normalization of CA luminal diameter, using Kaplan-Meier analyses., Results: There were 60 patients with KD and giant CAAs identified between 1989 and 2023. The majority of patients were male (71.7%) with a median age at diagnosis of 0.9 years (range, 0.2-13.3 years). Patients were followed for a median of 11 years, up to 34.5 years. MACE occurred in 13 patients (21.7%) at a median of 1.4 years (range, 0.04-22.6 years) after KD diagnosis. The 10-, 20-, and 30-year MACE-free rates were 75%, 75%, and 60%. Patients with maximal CA z scores of ≥20 or bilateral CAA were more likely to have MACE. During follow-up, 26.7% of CAA regressed to a normal luminal diameter at a median of 3.6 years (range, 0.6-12.0 years). The 10-, 20- and 30-year likelihood of CA regression to normal luminal diameter was 36%, 46%, and 46%., Conclusions: Over 30 years, MACE occurred in nearly 22% of patients, more often in those with bilateral CAA or CA z scores of ≥20. Despite regression to a normal luminal diameter in >25% of CAAs, patients with a history of KD-associated giant CAA require ongoing surveillance for cardiac complications, even years after the initial disease., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess recent temporal trends in guideline-compliant pediatric lipid testing, and to examine the influence of social determinants of health (SDoH) and provider characteristics on the likelihood of testing in youth., Study Design: In this observational, multiyear cross-sectional study, we calculated lipid testing prevalence by year among 268 627 12-year olds from 2015 through 2019 who were enrolled in Florida Medicaid and eligible for universal lipid screening during age 9 to 11, and 11 437 22-year olds (2017-2019) who were eligible for screening during age 17-21. We compared trends in testing prevalence by SDoH and health risk factors at two recommended ages and modeled the associations between patient characteristics and provider type on lipid testing using generalized estimating equations., Results: Testing among 12-year olds remained low between 2015 through 2019 with the highest prevalence in 2015 (8.0%) and lowest in 2017 (6.7%). Screening compliance among 22-year olds was highest in 2017 (21.1%) and fell to 17.8% in 2019. Hispanics and non-Hispanic Blacks in both age groups had about 2%-3% lower testing prevalence than non-Hispanic Whites. Testing in 12-year olds was 12.3% vs 7.7% with and without obesity, and 14.4% vs 7.6% with and without antipsychotic use. Participants who saw providers who were more likely to prescribe lipid testing were more likely to receive testing (OR = 2.3, 95% CI 2.0-2.8, P < .001)., Conclusions: Although lipid testing prevalence was greatest among high-risk children, overall prevalence of lipid testing in youth remains very low. Provider specialty and choices by individual providers play important roles in improving guideline-compliant pediatric lipid testing., Competing Interests: Declaration of Competing Interest This work is part of the Ph.D. dissertation of T.H.. She has graduated from the University of Florida and is currently an employee of IQVIA, Inc. M.C. is an employee of WW International Inc. The other authors declare no conflicts of interest. Research reported in this publication was supported in part by the OneFlorida Clinical Data Network, funded by the Patient-Centered Outcomes Research Institute (PCORI) numbers CDRN-1501-26 ,692 and RI-CRN-2020-005; in part by the OneFlorida Cancer Control Alliance, funded by the Florida Department of Health's James and Esther King Biomedical Research Program number 4KB16; and in part by the University of Florida Clinical and Translational Science Institute and its Clinical and Translational Science Award (CTSA) hub partner, Florida State University, which are supported in part by three CTSA Program grants awarded on August 15, 2015, and renewed for 5 years on July 2, 2019, by the National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR001427, KL2TR001429 and TL1TR001428]. This work was also supported by the National Institute of Diabetes and Digestive and Kidney Diseases [K01DK115632]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate characteristics of sport-related concussion (SRC), recreation-related concussion (RRC), and nonsport or recreation-related concussion (non-SRRC) in patients 5 through 12 years old, an understudied population in youth concussion., Study Design: This observational study included patients aged 5 through 12 years presenting to a specialty care concussion setting at ≤28 days postinjury from 2018 through 2022. The following characteristics were assessed: demographics, injury mechanism (SRC, RRC, or SRRC), point of healthcare entry, and clinical signs and symptoms. Kruskal-Wallis and chi-square tests were used to assess group differences. Posthoc pairwise comparisons were employed for all analyses (α = 0.017)., Results: One thousand one hundred forty-one patients reported at ≤28 days of injury (female = 42.9%, median age = 11, interquartile range (IQR) = 9-12) with the most common mechanism being RRC (37.3%), followed by non-SRRC (31.9%). More non-SRRCs (39.6%) and RRC (35.7%) were first seen in the emergency department (P < .001) compared with SRC (27.9%). Patients with RRC and non-SRRC were first evaluated at specialists 2 and 3 days later than SRC (P < .001). Patients with non-SRRC reported with higher symptom burden, more frequent visio-vestibular abnormalities, and more changes to sleep and daily habits (P < .001) compared with RRC and SRC (P < .001)., Conclusions: In concussion patients 5 through 12 years, RRCs and non-SRRC were more prevalent than SRC, presenting first more commonly to the emergency department and taking longer to present to specialists. Non-SRRC had more severe clinical features. RRC and non-SRRC are distinct from SRC in potential for less supervision at time of injury and less direct access to established concussion health care following injury., Competing Interests: Declaration of Competing Interest This study was funded by the National Institute of Neurologic Disorders and Stroke of the National Institutes of Health under award numbers R01NS097549 (Christina Master and Kristy Arbogast) and T32NS043126 (Patricia Roby) and the Pennsylvania Department of Health. The authors declare no conflicts of interest. The funder/sponsor did not participate in the work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the extent of extraskeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI)., Study Design: This cross-sectional study utilized the Kids' Inpatient Database as a part of the Healthcare Cost and Utilization Project to investigate inpatient hospital outcomes and management in patients with OI from 1997 through 2016. Data regarding hospital characteristics, cost of treatment, inpatient outcomes, and procedures were collected and analyzed., Results: There were 7291 admissions that listed OI as a diagnosis in the Kids' Inpatient Database from 1997 through 2016. Unexpectedly, more than one-third of all admissions in these children with OI presented with an extraskeletal manifestation. The rate of major complications was 3.85%. The rate of minor complications was 19.4%, most commonly respiratory problems. The mortality rate was 18.2% in the neonatal period and 1.0% in all other admissions. Total charges of hospital stay increased over the years., Conclusions: We identified a striking prevalence of extraskeletal manifestations in OI along with inpatient outcomes and complications associated with OI, of which respiratory complications were predominant. We observed a significant financial burden for patients with OI and identified additional risks for financial crisis, in addition to disparities in care identified among socioeconomic groups. These data contribute to a more holistic understanding of OI from diagnosis to management., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children., Study Design: This retrospective, case-control study included all children ≤21 years undergoing COVID-19 polymerase chain reaction testing at a tertiary children's hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes., Results: 116 209 patients age 8.5 ± 6.2 years underwent 234 867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI nonuse [RR 0.85 (95% CI 0.76, 0.94), P = .002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P = .77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P = .26]., Conclusions: We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children., Competing Interests: Declaration of Competing Interest This study was supported by NIHK23DK137036-01(Hirsch), NIHR01 DK097112-01 (Rosen), and an American Neurogastroenterology and Motility Society (ANMS) Discovery Grant (Hirsch). R.R. serves as a consultant to Reckitt Benckiser and NeurAxis. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Discordance in perception of disease activity between adolescent patients with lupus and their providers may influence disease outcomes. We found that patients endorsed higher perceptions of disease activity than providers. Discordance was present at all levels of disease activity, particularly in patients with high activity, nephritis, and/or taking corticosteroids or mycophenolate mofetil., Competing Interests: Declaration of Competing Interest K.K.R., K.R., and S.B. are the recipients of grant funding (#2019-10021) from the National Institute on Disability, Independent Living and Rehabilitation Research (NIDILRR). T.B.R. is supported by the Childhood Arthritis and Rheumatology Research Alliance/Arthritis Foundation Career Development Award and the National Institute of Arthritis and Musculoskeletal Skin Diseases (NIAMS) (K23AR080803). The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess if ventricular size before shunting is correlated with neurodevelopmental outcomes in children with postnatal myelomeningocele closure., Study Design: This retrospective review included children with postnatal surgical closure of myelomeningocele and neuropsychological testing between 2018 and 2023 at the University of California, San Francisco. Frontal-occipital horn ratio (FOHR) was measured immediately before shunt placement or on the first study that reported ventricular stability for nonshunted patients. The primary outcome was full scale IQ (FSIQ) on the Weschler Intelligence Scale. Secondary outcomes included indices of the Weschler scale, the Global Executive Composite from the Behavior Rating Inventory of Executive Function, and the general adaptive composite from the Adaptive Behavior Assessment Scale. Univariable and multivariable regression was used to determine if FOHR was correlated with neuropsychological scores., Results: Forty patients met the inclusion criteria; 26 (65%) had shunted hydrocephalus. Age at neuropsychological testing was 10.9 ± 0.6 years. FOHR was greater in the shunted group (0.64 vs 0.51; P < .001). There were no differences in neuropsychological results between shunted and nonshunted groups. On univariable analysis, greater FOHR was associated with lower FSIQ (P = .025) and lower Visual Spatial Index scores (P = .013), which remained significant on multivariable analysis after adjusting for gestational age at birth, lesion level, shunt status, and shunt revision status (P = .049 and P = .006, respectively). Separate analyses by shunt status revealed that these effects were driven by the shunted group., Conclusions: Greater FOHR before shunting was correlated with lower FSIQ and the Visual Spatial Index scores on the Weschler Intelligence Scales. Larger studies are needed to explore further the relationship between ventricle size, hydrocephalus, and neurodevelopmental outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. Funding: There was no funding for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to classify it by molecular genetics., Study Design: We categorized 186 retrospective cases of LO diagnosed between 2003 and 2023 into suspected Beckwith-Wiedemann spectrum, PIK3CA-related overgrowth spectrum (PROS), vascular overgrowth, or isolated LO, based on initial clinical assessments, to determine the appropriate first-tier molecular tests and tissue for analysis. Patients underwent testing for 11p15 epigenetic abnormalities or somatic variants in genes related to PI3K/AKT/mTOR, vascular proliferation, and RAS-MAPK cascades using blood or skin DNA. For cases with negative initial tests, a sequential cascade molecular approach was employed to improve diagnostic yield., Results: This approach led to a molecular diagnosis in 54% of cases, 89% of cases consistent with initial clinical suspicions, and 11% reclassified. Beckwith-Wiedemann spectrum was the most common cause, with 43% of cases exhibiting 11p15 abnormalities. PIK3CA-related overgrowth spectrum had the highest confirmation rate, with 74% of clinically diagnosed patients showing a PIK3CA variant. Vascular overgrowth demonstrated significant clinical overlap with other syndromes. A molecular diagnosis of isolated LO proved challenging, with only 21% of cases classifiable into a specific condition., Conclusions: LO is underdiagnosed from a molecular viewpoint and to date has had no diagnostic guidelines, which is crucial for addressing potential cancer predisposition, enabling precision medicine treatments, and guiding management. This study sheds light on the molecular etiology of LO, highlighting the importance of a tailored diagnostic approach and of selecting appropriate testing to achieve the highest diagnostic yield., Competing Interests: Declaration of Competing Interest No funding was required for this work. The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To describe for intervertebral spondylodiscitis (IS) its clinical characteristics, treatment approaches with intravenous (IV) antibiotics, and clinical implications of changes in treatment approach., Study Design: This retrospective study included all children aged 0-18 years diagnosed with imaging-confirmed thoracic and lumbar IS from 2000 to 2022 at a tertiary pediatric hospital. Patients with longer IV treatment regimen were compared with those with a shorter clinically directed IV to oral regimen., Results: In all, 124 cases were included with median age 14.9 months (IQR, 12.7-19.4 months) at diagnosis. Irritability and pain while changing diapers were common symptoms (52.4% and 49.2%, respectively). Elevated erythrocyte sedimentation rate (ESR) was the most common laboratory finding (95%; median, 50 mm/h [IQR 34-64 mm/h]). Elevated erythrocyte sedimentation rate was found in higher proportions (95%) compared with elevated C-reactive protein (76%; median, 1.8 mg/dL; P < .001). Since implementing the shorter clinically directed IV treatment duration for patients with thoracic and lumbar IS, hospitalization duration was decreased from a median of 12 to 8 days (P = .008) and IV treatment duration by a median of 14 to 8 days (P < .001). Only 1 patient (1.6%) in the clinically directed treatment group required rehospitalization owing to failure of therapy. Conversely, 9 of 124 children in the cohort suffered from IV treatment-related complications; all had been treated IV for prolonged periods., Conclusions: Early transition to oral treatment in pediatric spondylodiscitis seems to be appropriate clinically and shortens hospital stay and IV treatment duration without major negative clinical impact., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory director, a Clinical Laboratory Improvement Amendments certificate of waiver, as well as training of school personnel., Study Design: Descriptive report of a point-of-care, school-based antigen testing program in California from August 1st, 2021 through May 30, 2022, in which participants grades K-12 self-swabbed and school personnel performed testing. Participants included 944 009 students, personnel, and community members from 4022 California kindergarten through high schools. Outcomes measured include sensitivity and specificity (with polymerase chain reaction [PCR] as comparator) of the Abbott BinaxNOW antigen test, number of tests performed, and active infections identified., Results: Of 102 022 paired PCR/antigen tests, the overall sensitivity and specificity for the antigen test was 81.2% (95% CI: 80.5%-81.8%) and 99.6% (95% CI: 99.5%-99.6%), respectively, using cycle threshold values <30. During January through March 2022, the highest prevalence period, the positive predictive value of antigen testing was 94.7% and the negative predictive value was 94.2%. Overall, 4022 school sites were enrolled and 3 987 840 million antigen tests were performed on 944 009 individuals. A total of 162 927 positive antigen tests were reported in 135 163 individuals (14.3% of persons tested)., Conclusions: Rapidly implementing a school-based testing program in thousands of schools is feasible. Self-swabbing and testing by school personnel can yield accurate results. On-site COVID-19 testing is no longer necessary in schools, but this model provides a framework for future infectious disease threats., Competing Interests: Declaration of Competing Interest Funding for the pilot program was provided through the Public Health Institute with support from the California Endowment and the Chan-Zuckerberg Initiative (grant 2021-232540). Funding for the statewide antigen testing program was through support from a CDC Epidemiology and Laboratory Capacity grant (NU50CK000539-02-09)(43) CDPH statewide antigen testing program included all California counties except LA county who received their own ELC funding grant. The other authors declare no conflicts of interest., (Published by Elsevier Inc.)

Objectives: To assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program., Study Design: In this prospective cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound examination and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4-6 months, anthropometric measurements, serum biochemical analysis, ultrasound examination, and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration, and hepatic IR by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), respectively., Results: Of 200 patients with obesity, 56% had evidence of steatosis on ultrasound examination and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already increased in patients with only mild steatosis (P = .0403). Patients with more insulin-sensitive adipose tissue exhibited a lower liver fat content (P < .05) and serum alanine transaminase levels (P = .001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (P < .001), but not with total body fat percentage (P = .263). After 4-6 months of lifestyle management, both MASLD and Adipo-IR improved., Conclusions: Our data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis., Competing Interests: Declaration of Competing Interest Work in the lab of A.G. and S.L. has received funding from Inventiva. The other authors declare not conflicts of interest. Supported by a grant from the Ghent University Hospital (FIKO19-TYPE2-006). S.L. is supported by a grant from the Research Foundation – Flanders (FWO) (1227824N). H.V., A.G., and R.B. are senior clinical investigators of the FWO (1801721N, 1805718N and 1843824N). These funding agencies were not involved in study design, analysis or reporting., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD)., Study Design: A single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression., Results: Among 151 patients, 17.2% (n = 26) developed unprovoked seizures (Sz group), while 82.8% (n = 125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs 20.0%, P = .01). The Sz group also exhibited a greater frequency of slowing (42.3% vs 13.6%, P < .01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, P = .01) or any slowing (HR 2.78, 95% CI 1.02-7.58, P = .046 significantly increased the risk of developing unprovoked seizures., Conclusion: Long-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention., Competing Interests: Declaration of Competing Interest A.D. is supported by Uehara Memorial Foundation, and SENSHIN Medical Research Foundation to research abroad. H.N. is supported by the National Institute of Neurological Disorders and Stroke (NINDS) K23NS128318, the Sudha Neelakantan & Venky Harinarayan Charitable Fund, the Elsie and Isaac Fogelman Endowment, and the UCLA Children's Discovery and Innovation Institute (CDI) Junior Faculty Career Development Grant (#CDI-TTCF-07012021). R.S. serves on scientific advisory boards and speakers bureaus and has received honoraria and funding for travel from Eisai, Greenwich Biosciences, UCB Pharma, Sunovion, Supernus, Lundbeck Pharma, Liva Nova, West Therapeutics (advisory only); receives royalties from the publication of Pellock's Pediatric Neurology (Demos Publishing, 2016) and Epilepsy: Mechanisms, Models, and Translational Perspectives (CRC Press, 2011). S.H. has received research support from the John C. Hench Foundation, the CJDA Foundation, the Mohammed F. Alibrahim Endowment, the Elsie and Isaac Fogelman Endowment, the Epilepsy Therapy Project, the Milken Family Foundation, Paul Hughes Family Foundation, the Pediatric Epilepsy Research Foundation, Eisai, Bio-Pharm, Lundbeck, Insys, GW Pharmaceuticals, UCB Biopharma, Zogenix, Marinus, and the NIH. He has received compensation for service as a consultant to Amzell, Aquestive Therapeutics, Equilibre Biopharmaceuticals, Insys, GW Pharmaceuticals, Mallinckrodt, Marinus, MGC Pharmaceuticals, Radius, Shennox, UCB Biopharma, Upsher-Smith Laboratories, West Therapeutic Development, and Zogenix. The other authors declare no conflicts of interest. The funder/sponsor did not participate in the work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Two of 11 children with acute hepatitis of unknown origin were found to have rat hepatitis E virus infection. This infection should be considered in the differential diagnosis of children with acute hepatitis of unknown origin., Competing Interests: Declaration of Competing Interest This work was supported by the Andalusian General Secretariat for Research, Development, and Innovation in Health (PI-0287-2019), the Spanish Ministry of Health (RD12/0017/0012), co-financed by European Regional Development Fund (ERDF), and the Carlos III Health Institute (Research Project grant numbers: PI21/00  793 and PI22/01  098). Projects “PI21/00  793” and “PI22/01  098” were funded by Carlos III Health Institute (ISCIII) and co-funded by the European Union. LRM is the recipient of a “INVESTIGO” research program grant funded by the European Union NextGenerationEU Plan. MCJ is the recipient of a PFIS predoctoral grant (FI22/00  180) from the Carlos III Health Institute and co-funded by the European Union. ARJ is supported by a contract from the Spanish Junta de Andalucía (Nicolas Monardes program: C1-0001-2023). JCG is supported by the CIBERINFEC (CB21/13/00  083), Carlos III Health Institute, Spanish Ministry of Science, and NextGenerationEU. The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: We sought to determine the effect of secondary management strategies in addition to urotherapy on bowel bladder dysfunction outcomes., Study Design: The review protocol was prospectively registered (CRD42023422168). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus (database initiation until June 2023) were searched. Comparative studies of secondary management strategies vs conventional urotherapy alone were included. Two authors independently screened titles, abstracts, and reviewed full-text articles. Two authors extracted data related to study characteristics, methodology, subjects, and results., Results: In this systematic review and meta-analysis of 18 studies and 1228 children, secondary management strategies (home-based education, biofeedback, and physical therapy) were associated with reduced symptom burden, fewer recurrent urinary tract infections, and improved uroflowmetry findings than children treated solely with urotherapy for conservative management., Conclusions: Although there is significant reporting heterogeneity, secondary conservative management strategies such as home education, biofeedback or cognitive behavioral therapy, and physiotherapy-based education are associated with less urinary incontinence, fewer infections, and fewer abnormal uroflowmetry findings., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest.

Objective: To evaluate the effectiveness of patient education, physician counseling, and point-of-care (POC) testing on improving adherence to lipid screening national guidelines in a general pediatric cardiology practice (2017-2023)., Study Design: Regional primary care providers were surveyed regarding lipid screening practices. Key drivers were categorized (physician, patient, and system) with corresponding interventions. Pediatric cardiologists started offering lipid screening during regular visits by providing families with preventive cardiovascular education materials and lab phlebotomy testing. System redesign included educational posters, clinical intake protocol, physician counseling, electronic health record integration, and POC testing. Run charts and statistical process control charts measured screening rates and key processes., Results: The primary care survey response rate was 32% (95/294); 97% supported pediatric cardiologists conducting routine lipid screening. Pediatric cardiology mean baseline lipid screening rate was 0%, increased to 7% with patient education, and to 61% after system redesign including POC testing. Screening rates among 1467 patients were similar across age groups (P = .98). More patients received lipid screening by POC (91.7%) compared with phlebotomy (8.3%). Lipid abnormalities detected did not differ by screening methodology (P = .49)., Conclusion: Patient education, counseling, and POC testing improved adherence to national lipid screening guidelines, providing a possible model for primary care implementation., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest. Funding/Support: Children's Miracle Network., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

Objective: To assess health-related quality of life (HRQOL) and global quality of life (QOL) in children and adolescents with Fontan physiology and identify key predictors influencing these outcomes., Study Design: Cross-sectional analysis of 73 children and adolescents enrolled in the Australia and New Zealand Fontan Registry aged 6-17 years, at least 12 months post-Fontan operation. Assessments included the Pediatric Quality of Life Inventory (PedsQL) for HRQOL and a developmentally-tailored visual analogue scale (0-10) for global QOL, along with validated sociodemographic, clinical, psychological, relational, and parental measures. Clinical data were provided by the Australia and New Zealand Fontan Registry., Results: Participants (mean age: 11.5 ± 2.6 years, 62% male) reported lower overall HRQOL (P < .001), and lower scores across all HRQOL domains (all P < .0001), compared with normative data. Median global QOL score was 7.0 (IQR 5.8-8.0), with most participants (79%) rating their global QOL ≥6. Anxiety and depressive symptoms requiring clinical assessment were reported by 21% and 26% of participants, respectively. Age, sex, and perceived seriousness of congenital heart disease explained 15% of the variation in HRQOL scores, while depressive symptoms and treatment-related anxiety explained an additional 37% (final model: 52% of variance explained). For global QOL, sociodemographic and clinical factors explained 13% of the variance in scores, while depressive symptoms explained a further 25% (final model: 38% of variance explained). Parental factors were not associated with child QOL outcomes., Conclusions: Children and adolescents with Fontan physiology experience lower HRQOL than community-based norms, despite reporting fair overall QOL. Psychological factors predominantly influenced QOL outcomes, indicating strategies to bolster psychological health could improve QOL in this population., Competing Interests: Declaration of Competing Interest This work was supported by HeartKids Australia and Australian National Health and Medical Research Council (NHMRC) Project (APP1065794) and Partnership (APP1076849) Grants. The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The author declares no conflicts of interest. Funded by the Intramural Research Program at the NIH Clinical Center. However, the opinions expressed are the author's own. They do not represent the position or policy of the National Institutes of Health, US Department of Health and Human Services, or the US government. The NIH had no role in the study design, the collection, analysis, and interpretation of data, the writing of the report, or the decision to submit the manuscript for publication.

Objective: To investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations, utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations., Study Design: We analyzed data from 2 multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam, and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (forced expiratory volume in the first second (FEV1) z-score ≤ -1.645) as per 2022 American Thoracic Society (ATS) guidelines., Results: Compared with the race-specific GLI, the race-neutral equation yielded increases in the median forced expiratory volume in the first second and forced vital capacity (FVC) percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21%, and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; P < .001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; P = .001). Results were similar across both cohorts., Conclusions: As there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children., Competing Interests: Declaration of Competing Interest The study was supported by NIH grants U01 AI087881, R01 AI114552, R01 AI127507, and UH3 OD023253. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest Drs. Chen and Anderson were supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award from National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest.

Competing Interests: Declaration of Competing Interest S.C. and M.P.A. were supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award from National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest.

Intensive multidisciplinary intervention is increasingly recognized as the standard of care for children with complex feeding problems. Much, however, remains unknown about this treatment model. This current qualitative, prospective study sought to identify intensive multidisciplinary day hospital programs operating in the US, describe the treatment approach, and summarize current capacity., Competing Interests: Declaration of Competing Interest Funding for this study was provided by The Marcus Foundation. The authors have no financial relationships relevant to this article to disclose. No authors have potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To analyze the real-life health care costs of home parenteral nutrition (HPN) in children with short bowel syndrome with intestinal failure (SBS-IF) before and after treatment with teduglutide, and to compare those with costs of children with SBS-IF not treated with teduglutide., Study Design: All consecutive children with SBS-IF on HPN treated with subcutaneous teduglutide starting from 2018 through 2020 in a tertiary French referral center were retrospectively included. These patients were matched to children with SBS-IF on HPN followed during the same 3-year period who were eligible for the teduglutide but were not treated. HPN direct medical costs included home-care charges, HPN bags, hospital admissions, and teduglutide. A comparison of costs before/after treatment and between patients treated/not treated was performed., Results: Sixty children were included: 30 (50%) were treated with teduglutide and 30 (50%) were untreated. In the treated group, the median total costs of HPN significantly decreased after 1 (P < .001) and 2 years of treatment (P < .001) from 59 454 euros/year/patient to 43 885 euros/year/patient and 34 973 euros/year/patient, respectively. When we compared patients treated and not treated, the total HPN costs/year/patient were similar at baseline (P = .6) but were significantly lower in the teduglutide-treated group after 1 (P = .006) and 2 years of treatment (P < .001). When we added the cost of teduglutide into the analysis, the total cost increased significantly in the treated group and remained much greater even after modeling a reduction in the cost of the drug to one-third the present cost and PN weaning (P < .001)., Conclusions: Treatment with teduglutide is associated with a significant reduction in the annual costs of HPN but still remains expensive because of the drug itself. Finding cost-saving strategies is essential., Competing Interests: Declaration of Competing Interest C.L. received honoraria from Shire-Takeda as consultant for teaching and staff training. C.L. did not receive honoraria in direct relation with this study. All other authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence., Study Design: Project Viva is a prospective prebirth cohort (n = 2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n = 1107), early adolescence (n = 1027), and mid-adolescence (n = 693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI)., Results: In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n = 27) had a higher BMI z-score (β; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI., Conclusion: Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities., Competing Interests: Declaration of Competing Interest Authors have no conflict of interest to disclose. SC was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (T32, DK007028-46). SHL was supported by the American Diabetes Association (7-23-PDFT2DY-3) and Thomas O. Pyle Fellowship Award (Harvard Medical School Department of Population of Medicine). IA was supported by the American Heart Association (23CDA1050962); and the National Institutes of Health (5U54 AG062322-04, 1UG3 OD035533-01, 2R01 ES013744-16A1). This work was supported by the National Institutes of Health (R01HD034568)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

Objective: To increase the percentage of patients who undergo rapid magnetic resonance imaging (rMRI) rather than computed tomography (CT) for evaluation of mild traumatic brain injury (TBI) from 45% in 2020 to 80% by December 2021., Study Design: This was a quality improvement initiative targeted to patients presenting to the pediatric emergency department presenting with mild TBI, with baseline data collected from January 2020 to December 2020. From January 2021 to August 2021, we implemented a series of improvement interventions and tracked the percentage of patients undergoing neuroimaging who received rMRI as their initial study. Balancing measures included proportion of all patients with mild TBI who underwent neuroimaging of any kind, proportion of patients requiring sedation, emergency department length of stay, and percentage with clinically important TBI., Results: The utilization of rMRI increased from a baseline of 45% to a mean of 92% in the intervention period. Overall neuroimaging rates did not change significantly after the intervention (19.8 vs 23.2%, P = .24). There was no difference in need for anxiolysis (12 vs 7%, P = .30) though emergency department length of stay was marginally increased (1.4 vs 1.7 hours, P = < 0.01)., Conclusion: In this quality improvement initiative, transition to rMRI as the primary imaging modality for the evaluation of minor TBI was achieved at a level 1 pediatric trauma center with no significant increase in overall use of neuroimaging., Competing Interests: Declaration of Competing Interest No funding was secured for this study. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)