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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.)

Objective: To assess cognitive, behavioral, and adaptive functions in children and young adults with hemophilia treated according to contemporary standards of care., Study Design: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK) is a US-based, prospective, cross-sectional, observational study (September 2018 through October 2019). Males (aged 1-21 years) with hemophilia A or B of any severity, with or without inhibitors, were eligible. Participants underwent neurologic examinations and age-appropriate neuropsychological assessments, including standardized tests/ratings scales of early development, cognition, emotional/behavioral adjustment, and adaptive skills., Results: Five hundred and fifty-one males with hemophilia A (n = 433) or B (n = 101) were enrolled. Performance on cognitive tests was largely comparable with that of age-matched US population norms, although participants in certain age groups (4-5 and 10-21 years) performed worse on measures of attention and processing speed. Furthermore, adolescents and young adults and those with comorbid attention-deficit/hyperactivity disorder (ADHD; n = 64) reported more adaptive and executive function problems in daily life. Incidence of ADHD in adolescents (21%) was higher than expected in the general population., Conclusions: In general, males with hemophilia demonstrated age-appropriate intellectual, behavioral, and adaptive development. However, specific patient/age groups showed poorer attention performance and concerns for executive and adaptive development. This study established a normative data set for monitoring neurodevelopment in individuals with hemophilia and highlight the importance of screening and intervention for challenges with cognitive and adaptive skills in this population., Clinical Trial Registration: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK); NCT03660774; https://clinicaltrials.gov/ct2/show/NCT03660774., Competing Interests: Declaration of Competing Interest CM is a consultant for Novo Nordisk, coauthor of the eTHINK and paradigm study protocols, and site co-PI of the eTHINK study and has served as a speaker for Otsuka Pharmaceutical. KSW is a consultant for Novo Nordisk, coauthor of the eTHINK and paradigm study protocols, a site PI of the eTHINK study, and a consultant for AstraZeneca, Alexion, SpringWorks, and DayOne Biopharmaceuticals. CBB was a site PI of the eTHINK study and has received consultant fees from Novo Nordisk. SEC is a site PI of the eTHINK study and a consultant for Bayer, CSL Behring, Genentech, Octapharma, and Shire and has received research funding from Genentech, Pfizer, Novo Nordisk, Spark Therapeutics, and ATHN/Hemophilia of Georgia Research. AM and MG are full-time employees of Novo Nordisk. CH is a consultant for Novo Nordisk and participated in the eTHINK study. MR has received research grants from Pfizer, Bristol-Myers Squibb, and Novo Nordisk (for clinical studies) and is a consultant for Novo Nordisk. KAS has received fees as a consultant for Novo Nordisk. GNW has received fees as a consultant for Novo Nordisk. PV is a full-time employee of Cogstate. DLC was an employee of Novo Nordisk at the time of the conception of the eTHINK study and data collections. The eTHINK study was funded by Novo Nordisk A/S, Bagsværd, Denmark., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To identify factors associated with overtreatment of presumed urinary tract infection (UTI) among children with spina bifida using such criteria., Study Design: A retrospective review of children with spina bifida (age <21 years) evaluated in the Emergency Department (ED) at a single institution was performed. Patients with a urinalysis (UA) performed who were reliant on assisted bladder emptying were included. The primary outcome was overtreatment, defined as receiving antibiotics for presumed UTI but ultimately not meeting spina bifida UTI criteria (≥2 urologic symptoms plus pyuria and urine culture growing >100k CFU/mL). The primary exposure was whether the components of the criteria available at the time of the ED visit (≥2 urologic symptoms plus pyuria) were met when antibiotics were initiated., Results: Among 236 ED encounters, overtreatment occurred in 80% of cases in which antibiotics were initiated (47% of the entire cohort). Pyuria with <2 urologic symptoms was the most important factor associated with overtreatment (OR 9.6). Non-Hispanic White race was associated with decreased odds of overtreatment (OR 0.3)., Conclusions: Overtreatment of presumed UTI among patients with spina bifida was common. Pyuria, which is not specific to UTI in this population, was the main driver of overtreatment. Symptoms are a cornerstone of UTI diagnosis among children with spina bifida, should be collected in a standardized manner, and considered in a decision to treat., 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.)

Objective: To determine the relationship between transient neonatal hypoglycemia in at-risk infants and neurocognitive function at 6-7 years of corrected age., Study Design: The pre-hPOD Study involved children born with at least 1 risk factor for neonatal hypoglycemia. Hypoglycemia was defined as ≥1 consecutive blood glucose concentrations <47 mg/dl (2.6 mmol/L), severe as <36 mg/dl (2.0 mmol/L), mild as 36 to <47 mg/dL (2.0 to <2.6 mmol/L), brief as 1-2 episodes, and recurrent as ≥3 episodes. At 6-7 years children were assessed for cognitive and motor function (NIH-Toolbox), learning, visual perception and behavior. The primary outcome was neurocognitive impairment, defined as >1 SD below the normative mean in ≥1 Toolbox tests. The 8 secondary outcomes covered children's cognitive, motor, language, emotional-behavioral, and visual perceptual development. Primary and secondary outcomes were compared between children who did and did not experience neonatal hypoglycemia, adjusting for potential confounding by gestation, birthweight, sex and receipt of prophylactic dextrose gel (pre-hPOD intervention). Secondary analysis included assessment by severity and frequency of hypoglycemia., Results: Of 392 eligible children, 315 (80%) were assessed at school age (primary outcome, n = 308); 47% experienced hypoglycemia. Neurocognitive impairment was similar between exposure groups (hypoglycemia 51% vs 50% no hypoglycemia; aRD -4%, 95% CI -15%, 7%). Children with severe or recurrent hypoglycemia had worse visual motion perception and increased risk of emotional-behavioral difficulty., Conclusion: Exposure to neonatal hypoglycemia was not associated with risk of neurocognitive impairment at school-age in at-risk infants, but severe and recurrent episodes may have adverse impacts., Trial Registration: Hypoglycemia Prevention in Newborns with Oral Dextrose: the Dosage Trial (pre-hPOD Study): ACTRN12613000322730., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose. The pre-hPOD Study was funded by Lottery Health Research (241266), Cure Kids (3561), philanthropic donations to the University of Auckland Foundation (F-ILG- LRSR), Health Research Council of New Zealand (15-216), Gravida, National Centre for Growth and Development (SCH-14-14), Auckland Medical Research Foundation (1113012), A+ Trust (5696) and Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (R01HD091075). The pre-hPOD Early School-age Outcomes Study was funded by the Health Research Council of New Zealand (19/960) and the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (R01HD091075). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the prevalence, trends, and factors associated with psychotropic medication use and polypharmacy among children and adolescents initiating intensive behavioral therapy for severe challenging behavior over a 10-year period., Study Design: In this retrospective observational study, we examined data from caregiver interviews and patient medical records on the number and types of psychotropic medications prescribed to patients initiating intensive behavioral therapy between January 1, 2013, and December 31, 2022. Trends in medication use and polypharmacy across the 10-year period were analyzed using regression analysis, while differences in demographics and clinical factors for patients with use and polypharmacy were analyzed using nonparametric statistical analysis with odds ratios presented for significant factors., Results: Data from all 302 pediatric patients initiating intensive behavioral therapy across the 10-year period were analyzed. Among all patients and all years, 83.8% were taking at least 1 psychotropic medication and 68.2% experienced polypharmacy. There were no changes in the prevalence of use, mean number of medications taken, or polypharmacy across the 10-year period. Patients diagnosed with attention-deficit/hyperactivity disorder or anxiety disorder, as well as those exhibiting self-injurious behavior had higher use of psychotropic medication and polypharmacy and were taking more medications overall., Conclusions: Psychotropic medication use and polypharmacy were extremely high for children and adolescents with severe challenging behavior, but use and polypharmacy did not change over the 10-year period of data collection. Further research is needed to establish the generality of these findings to other regions of the US., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To identify clinical characteristics that distinguish cannabinoid hyperemesis syndrome (CHS) from cyclic vomiting syndrome (CVS), 2 conditions marked by episodes of nausea, vomiting, and abdominal pain., Study Design: We performed a retrospective chart review of patients admitted to a large children's health care system from 2015 through 2022. Patients with CHS and CVS were identified by the electronic medical record using International Classification of Diseases, Ninth and Tenth Revision codes., Results: Of 201 patients screened, 125 were included. Patients with CHS were older than those with CVS (mean [SD] 18.06 [1.41] vs 14.50 [2.91] years, P < .001). There were no significant differences in sex, race, ethnicity, or hospital length of stay between groups. Patients with CHS were more likely to have a positive urine drug screen (86% vs 2.9%, P < .001), lower mean (SD) serum potassium (3.62 [0.77] vs 3.88 [0.49], P < .001), and greater mean (SD) serum creatinine (0.83 (0.41) vs 0.63 (0.17), P < .001). The average (SD) systolic blood pressure was significantly greater in patients with CHS (systolic blood pressure 124.46 [10.66] vs 118.55 [10.99], P = .032) compared with children of comparable age range with CVS. Imaging was obtained in 36% of all patients, and only 2.4% had abnormalities., Conclusions: Clinical features including older age, greater systolic blood pressure, positive urine drug screen, and select electrolyte findings might distinguish CHS from CVS. Abdominal imaging in both conditions is of low yield. These findings may allow for early recognition and appropriate therapy in CHS patients., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood., Study Design: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model., Results: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10., Conclusion: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years., Competing Interests: Declaration of Competing Interest The authors have no financial relationships or any other conflicts of interest relevant to this article to disclose. This study was supported by the National Institute of Neurological Disorders and Stroke (grants 5U01NS040069-05 and 2R01NS040069-09) and the Office of the Director of the National Institutes of Health (1UG3OD023348-01)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine which groups of children with cancer for whom to apply the newly developed quality measures (QMs) for end-of-life (EOL) care., Study Design: In a series of nominal groups, panelists answered the question: "Which children, diagnoses, conditions, or prognoses should be included when examining the quality of EOL care for children with cancer?" In each group, individual panelists proposed answers to the question. After collating individual responses, each panelist ranked their 5 top answers and points were assigned (5 pts for the best answer, 4 pts the second best, etc.). A team of pediatric oncology and palliative care clinician-scientists developed and applied a coding structure for responses and associated themes and subthemes for responses., Results: We conducted 5 nominal groups with a total of 44 participants. Most participants identified as female (88%) and non-Hispanic White (86%). Seventy-nine percent were clinicians, mainly in pediatric palliative care, pediatric oncology, or hospice; 40% were researchers and 12% were bereaved parents. Responses fell into 5 themes: (1) poor prognosis cancer; (2) specific treatment scenarios; (3) certain populations; (4) certain symptoms; and (5) specific utilization scenarios. Poor prognosis cancer and specific treatment scenarios received the most points (320 pts [49%] and 147 pts [23%], respectively)., Conclusions: Participants developed a framework to identify which children should be included in EOL QMs for children with cancer. The deliberate identification of the denominator for pediatric QMs serves as a potent tool for enhancing quality, conducting research, and developing clinical programs., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. This work was supported by an American Cancer Society Grant (to E.E.J.) and a Doris Duke Charitable Foundation Gift to UAB with E.E.J. as a subrecipeint (via CARES Retention Program)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To characterize the evaluation and outcomes of children referred to pediatric hematology for normocytic anemia., Study Design: Retrospective cohort study of children aged 0-21 years referred to a tertiary pediatric hematology clinic for normocytic anemia from 2019 through 2021. Normocytic anemia was defined as a low hemoglobin and normal mean corpuscular volume, per the referring laboratory reference range., Results: Two-hundred seventy-one patients (48% female, median age 5.4 years) were included. The most common hematologic diagnoses included iron deficiency (n = 90, 33%), statistical anemia (n = 64, 24%), transient marrow suppression (n = 36, 13%), and transient erythroblastopenia of childhood (TEC, n = 19, 7%). There were 17 (6%) patients in whom anemia was thought to be secondary to a nonhematologic disorder and therefore were referred to another pediatric specialty. Sixteen patients (6%) had anemia which spontaneously resolved without an underlying etiology being identified. Aside from iron deficient patients, 35 (13%) had diagnoses requiring ongoing hematology care including transient erythroblastopenia of childhood, hemolytic anemia, Diamond Blackfan Anemia, and abnormal beta globin traits. Two-hundred fifty-one patients (93%) were discharged from hematology care after a median of 25 days (range 0-2124 days)., Conclusion: Pediatric patients with normocytic anemia have diverse underlying etiologies with iron deficiency being most common. These data support initial management within the primary care setting including assessment of a serum ferritin, iron panel, and reticulocyte count, with only a subset of patients requiring ongoing subspecialty care., Competing Interests: Declaration of Competing Interest Dr Powers discloses past consultancy to Pharmacosmos, LLC, which is unrelated to the content of this manuscript. Ms Kirk discloses advisory board with Sanofi and honoraria from BioMarin and X4 Pharmaceuticals which are unrelated to the content of this manuscript. Ms Equitz has no conflicts to disclose. Baylor College of Medicine, no external funding was secured for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care., Study Design: In this retrospective cohort study, we assessed all-cause health care utilization and direct health care costs associated with pediatric CP (n = 91) compared with juvenile arthritis (n = 135), inflammatory bowel disease (n = 90), type 1 diabetes (n = 475) or type 2 diabetes (n = 289), anxiety (n = 7193), and controls (n = 273) 2 and 5 years prior to patients entering subspecialty care in Manitoba, Canada. Linked data from physician encounters, emergency department visits, hospitalizations, and prescriptions were extracted from administrative databases. Differences in health care utilization and direct health care costs associated with CP vs the other conditions were tested using negative binomial and zero-inflated negative binomial regression models, respectively., Results: After adjustment for age at diagnosis, sex, location of residence, and socioeconomic status, CP continued to be associated with the highest number of consulted physicians and subspecialists and the highest number of physician billings compared with all other conditions (P < .01, respectively). CP was significantly associated with higher physician costs than juvenile arthritis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, or controls (P < .01, respectively); anxiety was associated with the highest physician and prescription costs among all cohorts (P < .01, respectively)., Conclusion: Compared with chronic inflammatory and endocrinologic conditions, pediatric CP and anxiety were associated with substantial burden on the health care system prior to subspecialty care, suggesting a need to assess gaps and resources in the management of CP and mental health conditions in the primary care setting., Competing Interests: Declaration of Competing Interest This research was funded by the Children Hospital Research Institute of Manitoba and the Children's Hospital Foundation of Manitoba. The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

We sought to determine the prevalence of sexual health counseling in patients with Duchenne muscular dystrophy in a single-institution setting. Keywords related to sexual health and development concerns were documented at least once for 75% of patients across the duration of their care. Integration of sexual health discussions was facilitated by comprehensive multidisciplinary support, particularly with the inclusion of specialists in endocrinology and adolescent medicine., Competing Interests: Declaration of Competing Interest This work was supported by the Aerosmith Endowment Fund, Boston Children's Hospital. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lung function was assessed at 8 years in 308 infants born extremely preterm between 1994 and 2013. Although lung function of those infants born at 22 through 25 weeks remained unchanged, those who were born at 26-27 weeks showed a significant improvement over the past 2 decades., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest for this study. No funding was obtained for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)