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Insufficient sleep negatively impacts scholastic performance in children and adolescents. Here we use a dose-response time in bed (TIB) restriction study to evaluate associations between sleep loss and multiple aspects of cognition. We evaluated changes in cognitive measures across ages 10 to 23 years and determined whether the effects of sleep loss changed across this age range. A younger cohort (n = 77, age range 9.9 to 16.2 years) was studied annually for 3 years. An older cohort study (n = 82, age range 15 to 22.8 years) was interrupted by the COVID pandemic with 25 participants completing multiple years. Annually participants completed each of three TIB conditions: four consecutive nights with 7, 8.5, or 10 hours in bed. A day of cognitive testing followed the fourth night. Restricting TIB to 7 hours was associated with impaired top-down attentional control and cognitive flexibility, but performance did not differ between 8.5 and 10 hours of TIB conditions. Psychomotor vigilance test performance decreased as TIB was restricted from 10 to 8.5 hours and decreased further with restriction to 7 hours. Sternberg test measures of working memory were not significantly affected by TIB restriction. The effects of sleep loss on these cognitive measures did not change significantly with age, but age-related improvement in many of the measures may compensate for some sleep loss effects. The findings here do not indicate an adolescent decrease in sleep need; however, the minimal duration of sleep needed for optimal performance appears to differ depending on the cognitive measure., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study Objectives: To use a nationally representative sample to (1) evaluate the factor structure of the patient-reported outcome measurement information system (PROMIS) parent proxy pediatric sleep scales (Spanish translation), (2) examine the invariance of these scales across sex and across different developmental periods of childhood and adolescence, (3) confirm the information and precision of the scales using item response theory (IRT), and (4) provide age-based normative information., Methods: Parents of a nationally representative sample of 5525 Spanish children and adolescents ages 5-16 years (56.1% boys) completed the Spanish translation parent proxy short versions of the sleep disturbance and sleep-related impairment scales. We conducted confirmatory factor analyses, invariance analyses, and graded-response IRT analyses., Results: CFAs conducted separately on males and females within three age groups (early childhood: ages 5-8 years; middle childhood: ages 9-12 years; adolescence: ages 13-16 years) indicated all items had a substantial loading with one exception (the sleep continuity item ["my child slept through the night"] had a substantially lower loading and was removed for subsequent analyses). The scores on the two scales demonstrated invariance across sex within each age group. Using IRT analyses, both scales showed a high degree of information and precision from slightly below the trait means to slightly above two standard deviations above the trait means., Conclusions: The strong psychometric properties of the short versions of the parent proxy PROMIS pediatric sleep disturbance and sleep-related impairment scales, coupled with age-based norms, suggest these scales are likely to be useful for research and clinical applications., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To evaluate the radiation dose of chest computed tomography (CT) examinations of pediatric patients and the extent to which volume CT dose index (CTDIvol) underestimates radiation dose in comparison to size specific dose estimates (SSDE)., Methods: Single-center, retrospective study of consecutive unenhanced pediatric (age <18 years) chest CTs between October 2015 and October 2016. Radiation dose as well as demographic and clinical data were recorded from 133 chest CTs. Patients were grouped into 4 categories based on mean effective diameter of the chest. SSDE was generated for each patient according to the water equivalent and effective diameter and compared to CTDIvol. Factors associated with higher radiation doses were assessed., Results: CTDIvol underestimated radiation dose by 54.7%, 47.6%, 40.2%, and 31.2% (P < .001) for effective diameter groups 1 to 4, respectively, when compared to SSDE (calculated according to the water equivalent). When calculated according to the effective diameter, CTDIvol underestimated radiation dose by 47.6%, 39.4%, 27%, and 12.3% (P < .001) for effective diameter groups 1 to 4, respectively, when compared to SSDE. CT dose parameters, age, weight, Dw, and mean effective diameter were variables associated with higher radiation doses., Conclusion: CTDIvol systematically underestimated radiation dose in comparison to SSDE in pediatric patients submitted to chest CT and should not be used as the primary parameter to monitor CT protocols in these patients. SSDE calculated according to effective diameter also underestimates the radiation dose compared to SSDE calculated based on water equivalent., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This study proposes a practical approach to assessing the need for and determining the transitioning parameters from age-specific to size-specific dose protocols in paediatric head computed tomography examinations. It was designed to begin with the two different age-specific protocols currently applied on paediatric patients of 1 y ≤ age ≤ 6 y (21.34 mGy) and those of age >6 y (34.73 mGy). One characteristic size (HDthreshold) was found by measuring anteroposterior head diameter on historical topograms and used with age to set 135 cases into four groups for investigation (A, ≤6y, ≤HDthreshold; B, ≤6y, >HDthreshold; C, >6y, ≤HDthreshold; and D, >6 y, >HDthreshold). The image quality was compared in both subjective and objective manners. Results suggest patients in Group C may have received a potential overdose (38%), while the exposure setting for Group D may replace that for B. The proposed strategy was sufficient to assess the necessity and determine the transitioning parameters from age- to size-specific dose protocols., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes., Methods: Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2-4 gliomas, were collected from collaborating institutions between 2013 and 2019. Patients were categorized as pediatric (<19 years), young adult (YA; 19-39 years), or older adult (≥40 years). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine the association of age and other covariates with overall (OS) and progression-free survival (PFS)., Results: We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS., Conclusions: IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approaches varied significantly by patient age and warrant further study as addressable age-associated outcome drivers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: A higher risk of secondary brain tumor, carotid stenosis, and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion, and stroke after SRS., Methods: In this multicentric retrospective study, 2254 patients with PitNET were studied, 1377 in the exposed group, and 877 in the control group., Results: There were 9840.1 patient-years at risk for the SRS and 5266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95% CI: 0.5%, 4.1%) for SRS and 3.7% (95% CI: 0%, 8.7%) for the control group (P = .6), with an incidence rate of 1.32 per 1000 and 0.95 per 1000, respectively. SRS was not associated with an increased risk of tumorigenesis when stratified by age (HR: 1.59 [95% CI: 0.57, 4.47], Pp = .38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95% CI: 0.2, 1.6) in the SRS and 2% (95% CI: 0, 4.4) in the control group (P = .8). The 15-year probability of stroke was 2.6% (95% CI: 0.6%, 4.6%) in the SRS and 11.1% (95% CI: 6%, 15.9%) in the control group (P < .001). In Cox multivariate analysis stratified by age, SRS (HR 1.85 [95% CI:0.64, 5.35], P = .26) was not associated with risk of new stroke., Conclusions: No increased risk of long-term secondary brain tumor, new stenosis or occlusion, and stroke was demonstrated in the SRS group compared to the control in this study with imaging surveillance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Subarachnoid hemorrhage (SAH) is a rare but life-threatening clinical event for pediatric patients. Cerebral vasospasm is a common complication of SAH that often leads to poor outcomes. This case report describes the use of dual intraventricular (IVT) vasodilators in a pediatric patient., Summary: An 11-year-old male presented with traumatic diffuse SAH and cerebral vasospasm. Despite treatment with IVT nicardipine, intravenous (IV) milrinone by continuous infusion, enteral nimodipine, and intraarterial verapamil and milrinone given during digital subtraction angiography, transcranial Doppler (TCD) mean velocities continued to rise. IVT milrinone was then added to IVT nicardipine and IV milrinone. The combination of IVT nicardipine, IV milrinone, and rescue therapy with IVT milrinone was continued for a total of 7 days. TCD mean velocities decreased into the mild to moderate range within 2 days of the patient receiving this combined regimen and remained globally low thereafter., Conclusion: This case illustrates the potential benefit of using dual IVT vasodilators to improve outcomes for pediatric patients with refractory cerebral vasospasm., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Pediatric inflammatory bowel disease (pIBD) incidence has increased over the last 25 years. We aim to report contemporaneous trends across the South West United Kingdom., Methods: Data were provided from centers covering the South West United Kingdom (Bristol, Oxford, Cardiff, Exeter, and Southampton), with a total area at-risk population (<18 years of age) of 2 947 534. Cases were retrieved from 2013 to 2022. Incident rates were reported per 100 000 at-risk population, with temporal trends analyzed through correlation. Subgroup analysis was undertaken for age groups (0-6, 6-11, and 12-17 years of age), sex, and disease subtype. Choropleth maps were created for local districts., Results: In total, 2497 pIBD cases were diagnosed between 2013 and 2022, with a mean age of 12.6 years (38.7% female). Diagnosis numbers increased from 187 to 376, with corresponding incidence rates of 6.0 per 100 000 population per year (2013) to 12.4 per 100 000 population per year (2022) (b = 0.918, P < .01). Female rates increased from 5.1 per 100 000 population per year in 2013 to 11.0 per 100 000 population per year in 2022 (b = 0.865, P = .01). Male rates increased from 5.7 per 100 000 population per year to 14.4 per 100 000 population per year (b = 0.832, P = .03). Crohn's disease incidence increased from 3.1 per 100 000 population per year to 6.3 per 100 000 population per year (b = 0.897, P < .01). Ulcerative colitis increased from 2.3 per 100 000 population per year to 4.3 per 100 000 population per year (b = 0.813, P = .04). Inflammatory bowel disease unclassified also increased, from 0.6 per 100 000 population per year to 1.8 per 100 000 population per year (b = 0.851, P = .02). Statistically significant increases were seen in those ≥12 to 17 years of age, from 11.2 per 100 000 population per year to 24.6 per 100 000 population per year (b = 0.912, P < .01), and the 7- to 11-year-old age group, with incidence rising from 4.4 per 100 000 population per year to 7.6 per 100 000 population per year (b = 0.878, P = .01). There was no statistically significant increase in very early onset inflammatory bowel disease (≤6 years of age) (b = 0.417, P = .231)., Conclusions: We demonstrate significant increases in pIBD incidence across a large geographical area including multiple referral centers. Increasing incidence has implications for service provision for services managing pIBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN., Methods: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing., Results: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae&#95;UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi., Conclusions: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression. We aimed to evaluate PGx variation in genes supported by clinical guidelines that inform dosing of thiopurines and characterize differences in the distribution of actionable PGx variation among diverse ancestral groups., Methods: Pharmacogenetic variation in TPMT and NUDT15 was captured by genome-wide genotyping of 1083 pediatric IBD patients from a diverse Canadian cohort. Genetic ancestry was inferred using principal component analysis. The proportion of PGx variation and associated metabolizer status phenotypes was compared across 5 genetic ancestral groups within the cohort (Admixed American, African, East Asian, European, and South Asian) and to prior global estimates from corresponding populations., Results: Collectively, 11% of the cohort was categorized as intermediate or poor metabolizers of thiopurines, which would warrant a significant dose reduction or selection of alternate therapy. Clinically actionable variation in TPMT was more prevalent in participants of European and Admixed American/Latino ancestry (8.7% and 7.5%, respectively), whereas variation in NUDT15 was more prevalent in participants of East Asian and Admixed American/Latino ancestry (16% and 15% respectively)., Conclusions: These findings demonstrate the considerable interpopulation variability in PGx variation underlying thiopurine metabolism, which should be factored into testing diverse patient populations., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Patterns of health services utilization among children with inflammatory bowel disease (IBD) are important to understand as the number of children with IBD continues to increase. We compared health services utilization and surgery among children diagnosed <10 years of age (Paris classification: A1a) and between 10 and <16 years of age (A1b)., Methods: Incident cases of IBD diagnosed <16 years of age were identified using validated algorithms from deterministically linked health administrative data in 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec) to conduct a retrospective cohort study. We compared the frequency of IBD-specific outpatient visits, emergency department visits, and hospitalizations across age groups (A1a vs A1b [reference]) using negative binomial regression. The risk of surgery was compared across age groups using Cox proportional hazards models. Models were adjusted for sex, rural/urban residence location, and mean neighborhood income quintile. Province-specific estimates were pooled using random-effects meta-analysis., Results: Among the 1165 (65.7% Crohn's) children with IBD included in our study, there were no age differences in the frequency of hospitalizations (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.06) or outpatient visits (RR, 0.95; 95% CI, 0.78-1.16). A1a children had fewer emergency department visits (RR, 0.70; 95% CI, 0.50-0.97) and were less likely to require a Crohn's-related surgery (hazard ratio, 0.49; 95% CI, 0.26-0.92). The risk of colectomy was similar among children with ulcerative colitis in both age groups (hazard ratio, 0.71; 95% CI, 0.49-1.01)., Conclusions: Patterns of health services utilization are generally similar when comparing children diagnosed across age groups., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1 manifestations (eg, neurocognitive function, growth reduction, and café-au-lait spots) are unknown., Methods: This open-label, phase II trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hours for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated., Results: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22 ± 5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P < .05). Prepubertal patients showed increases in height score and growth velocity (P < .05). Café-au-lait spot intensity decreased significantly (P < .05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation., Conclusions: Selumetinib decreases PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in nonmalignant diverse NF1 manifestations., Trial Registration: Cris.nih.go.kr Identifier (KCT0003700)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Since data on predictors of complicated Crohn's disease (CD) from unselected populations are scarce, we aimed to utilize a large nationwide cohort, the epi-IIRN, to explore predictors of disease course in children and adults with CD., Methods: Data of patients with CD were retrieved from Israel's 4 health maintenance organizations, whose records cover 98% of the population (2005-2020). Time-to-event modeled a complicated disease course, defined as CD-related surgery, steroid-dependency, or the need for >1 class of biologics. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results., Results: A total of 16 659 patients (2999 [18%] pediatric-onset) with 121 695 person-years of follow-up were included; 3761 (23%) had a complicated course (750 [4.5%] switched to a second biologic class, 1547 [9.3%] steroid-dependency, 1463 [8.8%] CD-related surgery). Complicated disease was more common in pediatric- than adult-onset disease (26% vs 22%, odds ratio, 1.3; 95% confidence interval [CI], 1.2-1.4). In a Cox multivariate model, complicated disease was predicted by induction therapy with biologics (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6) and severity of laboratory tests at diagnosis (HR, 1.7; 95% CI, 1.2-2.2), while high socioeconomic status was protective (HR, 0.94; 95% CI, 0.91-0.96). In children, laboratory tests predicted disease course (HR, 1.8; 95% CI, 1.2-2.5), as well as malnutrition (median BMI Z score -0.41; 95% CI, -1.42 to 0.43 in complicated disease vs -0.24; 95% CI, -1.23 to 0.63] in favorable disease; P < .001)., Conclusions: In this nationwide cohort, CD course was complicated in one-fourth of patients, predicted by laboratory tests, type of induction therapy, socioeconomic status, in addition to malnutrition in children., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To develop a reproducible, reliable clinical index of alveolar bone grafting (ABG) outcome based on the eruption position of the cleft canine tooth and determine the association between eruption position and radiographic outcome at 6 months post-grafting., Methods: Children with complete, non-syndromic, unilateral/bilateral cleft lip and palate in the West of Scotland were identified. Post-ABG radiographic outcome (Kindelan index) and canine eruption position in children with a cleft of the alveolus who had undergone ABG were documented. A Kindelan score was assigned to the 6-month post-bone-graft radiograph. Following canine tooth eruption, four-point clinical index scale (CIS) scores were assigned to maxillary occlusal images taken prior to commencement of definitive orthodontics; 1-canine eruption in alveolar crest, 2-canine eruption buccal to alveolar crest, 3-canine eruption palatal to alveolar crest, and 4-canine impaction. Intra and inter-rater reliability was assessed using Cohen and Fleiss kappa's, respectively. Duration of orthodontics treatment, number of orthodontic clinic visits, and clinical management of the cleft site space were noted., Results: Eighty-three patients representing 98 bone graft sites were identified. CIS scoring intra- and inter-rater reliability was 0.69-0.99 and 0.63-0.75, respectively. CIS score was associated with reduced visits (P = .015), months in orthodontics (P = .009), and likelihood of space closure (P = .006)., Limitations: This is a retrospective study with small numbers but is comparative to other similar studies in the literature., Conclusions: The CIS presented appears to be a reliable index of ABG outcome. It also demonstrates an association with the burden of orthodontic care post-cleft alveolar bone graft., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Parental supply of alcohol to adolescents is associated with increased risk of subsequent adolescent alcohol use and harms, so identifying factors associated with parents' decision-making is critical. This study examined how parental supply is associated with attitudes toward adolescent alcohol use, perceived norms of parental supply, perceived behavioural control and perceived acceptable age to drink alcohol. A total of 1197 Australian parents with children aged 12-17 years completed an online cross-sectional survey assessing their parental supply behaviours, attitudes and perceptions in April 2022. Logistic regression was used to explore associations between attitudes, perceptions and parental supply of alcohol to their child. Forty-three percent of respondents nominated an acceptable age to drink a full drink of alcohol below 18 years, and 23% reported supplying a full drink of alcohol to their adolescent. Parents were more likely to report supplying a full drink of alcohol if they nominated an acceptable drinking age below 18 years (<16: adjusted odds ratio [AOR] = 14.75, 95% confidence interval [CI] = 8.23-26.42; 16-17: AOR = 5.68, 95% CI = 3.69-8.73), appraised alcohol as more beneficial (AOR = 1.31, 95% CI = 1.02-1.69) and less harmful (AOR = 0.49, 95% CI = 0.36-0.68) for adolescents, and perceived that parent friends (AOR = 2.91, 95% CI = 1.80-4.70) and other parents (AOR = 2.23, 95% CI = 1.37-3.62) supplied alcohol in unsupervised contexts. Perceived behavioural control was not associated with parental supply. These findings suggest there may be value in trialling interventions that target parents' perceptions about the acceptable age to drink a full drink of alcohol, attitudes toward adolescent alcohol consumption, and perceived norms of parental supply to influence parents' supply intentions., (© The Author(s) 2024. Published by Oxford University Press.)

Cigarettes, alcohol, vaping and gambling products can cause significant harm to children and young people. The industries that make these products employ a range of tactics that aim to normalize their products and resist policy and regulatory reform. This includes 'responsibility' framing, in which parents are often held responsible for educating their children about the risks of these products. However, there has been very little research, which has investigated parents' perceptions of these industries. A qualitatively led online panel survey was conducted with n = 455 Australian parents who had at least one child aged between 11 and 17 years. Participants were asked questions relating to concerns about harmful products; what they talked about with their children; other potential sources of risk information; and who were responsible for protecting young people from these industries. Four themes were constructed. (i) Parents identified that parental influence, peer pressure, social media and advertising influenced children's attitudes towards these products. (ii) They had concerns about the short- and long-term consequences of these products. (iii) Parents actively engaged in educating their children about these products but recognized that it was difficult to counter industry messages. (iv) Parents emphasized the need for a collective approach, advocating for increased information and government regulations, particularly relating to marketing. This study demonstrates that parents are concerned about these industries and do their best to protect their children from harm but recognize that they need more support. Evidence-based education and comprehensive regulations particularly around marketing are needed to de-normalize products and protect young people., (© The Author(s) 2024. Published by Oxford University Press.)

Children's exposure to outlets selling, and outdoor advertisements marketing, unhealthy foods is an important risk factor for obesity. Yet few policies address the food retail and/or outdoor advertising environment, and research about children's perceptions is limited, especially in low- and middle-income countries. We used a participatory, multimodal visual/verbal approach to explore urban-dwelling South African primary school students' perceptions of unhealthy food outlets and outdoor advertisements they encountered on their journeys to school. Forty-one grade 7 students aged 11-14 years participated in drawing and/or photography activities and elicitation discussions. A mixed-methods, triangulated analysis involving the content analysis and extraction of data from research artefacts (33 journey to school drawings and 10 food advertisement photo collages) and thematic analysis of discussion transcripts was conducted. Drawings depicted 175 food outlets, two-thirds (64%) of which sold only unhealthy foods and 125 advertisements, most of which marketed unhealthy food. Unbranded, deep-fried foods prepared and sold by informal traders and independent shops were prominent. Informal and independent traders also sold unhealthy branded foods. Advertisements were primarily for unhealthy foods, especially branded, sugar-sweetened beverages. Participants thought extensive advertising bans, regulation of the sale of unhealthy food to children and other measures were needed to promote children's health in urban contexts. The results point to the need for food system-wide approaches that address multiple commercial determinants of health, including 'big food' advertising, unhealthy food sales by informal and independent traders and programs to address socio-economic influences such as poverty, unemployment and parents' poor work conditions., (© The Author(s) 2024. Published by Oxford University Press.)

This study, guided by the theory of planned behavior (TPB), aimed to investigate whether attitude, subjective norms, and perceived behavioral control can predict parents' intentions to reduce or stop adding sugar to their child's beverages, such as tea or milk. The research also seeks to determine the predictive power of the TPB on the actual behavior of parents in reducing or halting sugar intake in their children's drinks. A questionnaire was developed to assess sweetening beverage behavior variables by mothers of children aged 3-7 years attending Lebanese public schools, with 184 responses retained with no missing values for analysis. Regression analysis was utilized to examine determinants of self-reported practice and intentions regarding sweetening beverages. Results showed that attitude and perceived behavioral control were significant predictors of intention to reduce or stop adding sugar to a child's beverages. The perception of behavioral control was found to predict the behavior of adding sugar to a child's beverages, even though the intention to reduce or stop did not. The study findings suggest that individuals with low perceived behavioral control and strong habits would be more likely to be actual performers of the adding sugar behavior regardless of their intention level. When adding sugar to a child's beverages is a common parental habit in low-income Lebanese families, our findings offer valuable insights for developing culturally and socially tailored health promotion strategies to reduce or stop adding sugar to children's beverages and raise parental awareness about the health risks associated with excessive sugar consumption in children., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Early onset of alcohol consumption among Colombian adolescents highlights the need for effective and accessible preventive interventions. This project aimed to conduct formative work to inform the adaptation of an effective eHealth alcohol use prevention program originally developed in Australia, the OurFutures Alcohol Module, to the Bogotá context. Twenty-six adolescents and 10 teachers in Bogotá participated in the study. We used a mixed-methods approach comprising interviews, surveys and semi-structured discussions to evaluate the acceptability of OurFutures. Study materials were translated into Spanish before conducting three 1.5-hour focus groups with adolescents (aged 11-15; n = 26), and 1-hour interviews or online surveys with teachers to assess attitudes towards alcohol use and the acceptability of one lesson from the OurFutures Alcohol Module in the Bogotá context. Qualitative data were analysed thematically, and descriptive analyses of quantitative data reported percentage agreement for survey questions. Overall, 96% of students and 89% of teachers expressed strong satisfaction with the OurFutures Alcohol Module lesson. Most students (96%) liked its storyline and character portrayal, and most teachers (80%) said they would use OurFutures with their students. Participants provided feedback for improving program relatability, including adapting scenarios, character names, clothing and language to align with the Bogotá context and resonate with Colombian adolescents. This study marks the first step in informing the adaptation of the OurFutures Alcohol Module to the Bogotá context and highlights key considerations for cultural adaptations of other substance use prevention interventions. This research underscores the importance of place-based end-user involvement in co-designing adolescent prevention interventions., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The clinical protocol and effectiveness of dental expansion with Clear Aligner Therapy (CAT), especially among adults is still unclear. There is a need to map and explore knowledge gaps of dental expansion with CAT among children and adults., Objective: This scoping review explores the extent and depth of the available literature regarding the effectiveness and predictability of CAT in performing orthodontic expansion in both children and adults., Methods: The following databases were consulted as sources of information: PubMed, MEDLINE, Embase, Web of Science, Scopus, LILACS, COCHRANE Library, and ProQuest Dissertations & Thesis, in which the search was limited to studies on children or adults requiring transverse arch expansion and using clear orthodontic aligners. Two independent reviewers assessed the citations and extracted data, which was then synthesized in a narrative format., Results: Over all, 698 citations were retrieved, and 33 were included. Among these, 3 were systematic reviews, 4 were cohort studies, 2 were case-control studies, and 24 were case series. Eighty-five percent of the included studies were published in the last 5 years. Despite different protocols and measurement methods, aligners were effective for arch expansion in adults and children, and the expansion predictability was greater for the lower arch than for the upper arch. The evidence suggests that arch width increment is more predictable in the premolar region and less predictable in the canine and second molar areas, with high variability across studies., Conclusions: Orthodontic aligners have demonstrated effectiveness in expanding arches in both adults and children. However, the literature suggests a decrease in arch width toward the posterior region, and there is no evidence of skeletal gains. To provide more conclusive evidence, randomized controlled clinical studies are warranted., Registration: This review was registered in the Open Science Framework database (DOI: https://doi.org/10.17605/OSF.IO/6EG8F)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Seventeen percent of people living in the UK are migrants. In high-income countries, migrants have been shown to have better all-cause mortality but worse mortality for some specific causes such as infectious diseases. This observational study aims to quantify the extent to which mortality from coronavirus disease 2019 (COVID-19) differed between migrants and non-migrants for the population of England and Wales, 2020-2021. We use Official National Statistics data to compare mortality from COVID-19 in 2020 and 2021 by country/region of birth, expressed as the standardized mortality ratio with those born in England and Wales as the reference population. Migrants from 17 of 19 countries/regions examined had higher mortality from COVID-19 than non-migrants. The highest mortality was those born in Bangladesh (females SMR = 3.39, 95% CIs 3.09-3.71; males 4.41, 95% CIs 4.09-4.75); Pakistan (females 2.73, 95% CIs 2.59-2.89; males 3.02, 95% CIs 2.89-3.14); and the Caribbean (females 2.03, 95% CIs 1.87-2.20; males 2.48, 95% CIs 2.37-2.60). Migrants born in Antarctica and Oceania (females 0.54, 95% CI 0.42-0.40; males 0.71, 95% CI 0.51-0.88), and North and Central America (females 0.95, 95% CI 0.80-1.11; males 0.85, 95% CI 0.72-0.99) had lower mortality than non-migrants. Most migrant populations had higher mortality from COVID-19 than non-migrants in England and Wales. Policy-makers must work to integrate migration status into routine data collection to inform future research and understand the causes of the inequalities seen., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Objective: To evaluate the long-term status of incisors with canine-induced root resorption (CIRR)., Materials and Methods: Subjects with impacted maxillary canines (IMC) and persisting incisors with CIRR examined with cone beam computed tomography (CBCT), diagnosed ≥ 5 years earlier, were recalled. The resorption grade in the horizontal and vertical plane was assessed on CBCT images at baseline (T0) and follow-up (T1). Clinical examination was done at T1 which included probing depth, gingival retraction, mobility, ankylosis, discoloration and vitality test. In addition, patients completed a questionnaire regarding symptoms from the incisors., Results: Forty subjects (mean age 13.7 ± 2.1 years) with 43 IMC and 47 incisors with CIRR were recruited. The IMC either spontaneously erupted, were surgically exposed or surgically removed. Thirty-four of the patients were treated with a fixed appliance and six had no orthodontic treatment. The follow-up range was 5.5-14.6 years. None of the incisors were lost or endodontically treated at T1. The horizontal resorption grade was unchanged in 38, improved in 7, and worsened in 2 teeth. The corresponding results for the vertical resorption grade were unchanged in 20 and worsened in 27 teeth. Three incisors with severe horizontal resorption at T0 were significantly more obliterated at T1 (P = .01). No significant differences were found in clinical parameters or patient-reported outcomes between incisors with CIRR and non-resorbed contralateral incisors at T1., Limitations: The extent of root resorption during active orthodontic treatment was not possible to assess as only CBCT images from T0 and T1 were available., Conclusion: Incisors with CIRR caused by IMC have a high survival rate in a long-term perspective and do not cause more symptoms or exhibit more signs of pathology than non-resorbed contralateral incisors. Extraction of asymptomatic incisors based solely on root resorption should not be performed routinely., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Orthodontic Society.)

Background: Extraction of the permanent first molars is sometimes necessitated in children and adolescents due to deep carious lesions or developmental defects., Objective: To estimate the prevalence of spontaneous space closure after extraction of permanent first molars and identify factors associated with it., Search Methods: Unrestricted searches in five databases for human studies until February 2024., Selection Criteria: Longitudinal before-and-after (cohort) human studies assessing eruption of the permanent second molars and spontaneous space closure after extraction of the permanent first molar., Data Collection and Analysis: Study selection, data extraction, and risk of bias assessment were performed in duplicate. Random-effects meta-analyses of average spontaneous space closure prevalences and odds ratios (OR) with their 95% confidence intervals (CI) were performed, followed by meta-regression/sensitivity/reporting biases' analyses and evaluation of our confidence in effect estimates., Results: Sixteen reports pertaining to 15 studies (1 prospective /14 retrospective) were included covering 1159 patients (ages 5.5-15.0 years [mean 10.0 years]; 45% male on average) and 2310 permanent second molars. The prevalence of spontaneous space closure was higher in the maxilla (nine studies; 85.3%; 95% CI = 73.7%-92.3%) than the mandible (11 studies; 48.1%; 95% CI = 34.5%-62.0%) to a significant extent (nine studies; OR = 7.77; 95% CI = 4.99-12.11; P < 0.001). For both maxillary/mandibular second molars, Demirjian category E was associated with increased space closure odds than earlier/later stages (P < 0.05). Spontaneous space closure in the mandible was seen more often for patients ages 8-10 years (compared with older patients; three studies; OR = 3.32; 95% CI = 1.73-6.36; P < 0.001) and when the mandibular permanent third molar was present (four studies; OR = 2.28; 95% CI = 1.67-3.09; P = 0.003). Additional analyses failed to find any significant modifying factors., Limitations: The quality of evidence was very low in all instances due to the inclusion of retrospective studies with methodological issues., Conclusions: Existing evidence indicates that spontaneous space closure in children and adolescents after extraction of the permanent first molar is seen more often in the maxilla than the mandible. Extraction of the permanent first molar at the Demirjian stage E of the second molar and presence of the lower permanent third molar is associated with increased odds of space closure, but uncertainty persists, due to methodological issues of existing studies., Registration: PROSPERO (CRD42023395371)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Orthodontic Society.)

Background/objectives: It is unclear whether palatal canine impaction is related to genetic or local/environmental factors. If a genetic origin is assumed, then it could be expected that palatal canine impaction is associated with overall craniofacial development. Within this context, the aim of this study was to evaluate the craniofacial morphology of individuals with palatal canine impaction and compare it to a matched group of normal controls., Materials/methods: The sample for this investigation comprised 404 individuals (232 females and 172 males). Half of these individuals presented with unilateral or bilateral palatal canine impaction confirmed clinically and radiographically. The other half were matched for sex and age with the first half and comprised individuals without tooth impaction, apart from third molars. The shape of the craniofacial structures was outlined on calibrated cephalometric images through 15 curves and 127 landmarks (11 fixed and 116 semi-landmarks). Shape configurations were superimposed using Procrustes Superimposition and the resulting shape coordinates were reduced into principal components for all subsequent analyses. The effect of palatal canine impaction on craniofacial shape was assessed with regression models, separately in females and males. All statistical tests were performed assuming a type-1 error of 5%., Results: Individuals with palatally impacted canines appear to have a less convex face, a more brachyfacial skeletal pattern, and a sagittally extended premaxilla. In females effect sizes ranged between η2 = 0.136-0.397 (P < 0.05) and in males between η2 = 0.125-0.396 (P < 0.05, apart from the entire craniofacial configuration: P = 0.259)., Limitations: Palatal canine impaction was not confirmed through cone beam computer tomography images in all patients, however, in those cases, the treatment history confirmed the diagnosis., Conclusions/implications: Palatal canine impaction is related to a distinct craniofacial shape in females and males. These findings allow for speculation that palatal canine impaction is affected by genetic pathways involved in overall craniofacial development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To propose a histological-grades-based Osseous Tumor Radiological and Interpretation and Management System (OT-RIMS) that would simplify the radiological evaluation of bone tumours, categorize key radiological features into severity levels, and inform corresponding patient management actions., Methods: This retrospective study between January 2015 and August 2022 evaluated patients with solitary bone tumours confirmed by pathology and imaging follow-up received 2 or 3 imaging modalities of radiographs, CT, or MRI. Three radiologists independently assessed radiological features, categorized bone lesions based on OT-RIMS criteria, and reached a consensus. Kappa statistics and observed agreement were calculated., Results: A total of 341 patients (mean age, 26.0 years; 159 women) were included, with 102 malignant, 177 benign, and 62 intermediate or low-grade malignant bone lesions. Sensitivity and specificity of readers 1, 2, and 3, respectively, in the identification of malignant tumours into OT-RIMS 4 were 93.1% (95 of 102) and 93.3% (223 of 239), 96.1% (98 of 102) and 91.6% (219 of 239), 92.2% (94 of 102) and 89.5% (214 of 239). Inter-reader agreement of OT-RIMS category for 3 readers was considered excellent (Kendall's W = 0.924, P < .001) with a kappa value of reproducibility in categories 1&2, 3, and 4 of 0.764, 0.528, and 0.930, respectively., Conclusions: The OT-RIMS category demonstrated excellent reproducibility despite the reader's expertise level in categorizing the risk stratification of bone tumours and informing patient management, with histological grades used as the reference standard., Advances in Knowledge: The OT-RIMS category reliably stratifies bone tumours into 4 categories corresponding to histological grades and standardized patient management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

It is unclear how much costs economic difficulties in families with children incur to the health and social care sector. We examined the health and social service costs after families entered into, and transitioned out of, social assistance used as a proxy measure for economic difficulties. We analyzed register data on all Finnish children born in 1997 and used the non-randomized target trial framework. The two target trials of entry to economic difficulties (social assistance) and continued economic difficulties included 697 680 and 71 131 children-year observations, respectively, in total. Inverse probability treatment weighting techniques were used to make the comparison group similar to the treatment group in terms of health, socioeconomic and demographic-related pretreatment variables. Entry to social assistance use was associated with some 1511-2619€ (50% compared to the control group) higher cumulative health and social care costs of the children three years after their families transitioned to social assistance, compared to the group that did not enter to social assistance system. This difference was primarily attributed to higher social care costs. Continued social assistance use was associated with some 1007-2709€ (31%) higher costs compared to the comparison group that exited social assistance. These findings support an economic argument to prevent families from entering economic difficulties and to help those in such situations to transition out., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Objectives: To investigate the bone age (BA) characteristics of children living in high-altitude regions and determine the impact of altitude on the development of BA., Methods: From June 2014 to July 2022, 1318 children with left-hand-wrist radiographs were retrospectively enrolled from 3 different geographical altitudes (Beijing 43.5 m above sea level [asl], Lhasa 3650 m asl, and Nagqu 4500 m asl). The predicted age difference (PAD), defined as the difference between BA and chronologic age (CA), was considered the indicator for delayed or advanced growth. The PAD of children from the 3 regions in total and according to different age groups, genders, and ethnicities were compared. The linear regression model was used to assess the effect of altitude on PAD., Results: A total of 1284 children (CA: 12.00 [6.45-15.72] years; male: 837/1284, 65.2%) were included in the study with 407 from Beijing, 491 from Lhasa, and 386 from Nagqu. The PAD for Beijing, Lhasa, and Nagqu were 0.1 [-0.30 to 0.65], -0.40 [-1.20 to 0.27], and -1.42 [-2.32 to -0.51] years, respectively. A linear regression analysis showed that altitude significantly contributed to PAD (compared to Beijing, Lhasa coefficient = -0.57, P < .001; Nagqu coefficient = -1.55, P < .001)., Conclusions: High altitude might be an independent contributor to the delayed BA development of children., Advances in Knowledge: The impact of altitude on BA development was revealed for the first time, highlighting the necessity of considering the altitude of the area when evaluating BA development for children residing in high-altitude regions.ke., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study evaluates the diagnostic utility of OLIG2 immunohistochemistry for distinguishing between pediatric high-grade gliomas (pHGG) and embryonal tumors (ETs) of the CNS. Utilizing a retrospective pediatric cohort (1990-2021) of 56 CNS tumors, classified initially as primitive neuroectodermal tumors or CNS ET, we reclassified the cases based on WHO CNS5 criteria after comprehensive review and additional molecular testing that included next-generation sequencing and DNA methylation profiling. Our results indicate that OLIG2 immunopositivity was negative or minimal in a significant subset of pHGG cases (6 out of 11). At the same time, it showed diffuse expression in all cases of CNS neuroblastomas with FOXR2 activation (5/5), demonstrating its limited specificity in differentiating between pHGG and ET. Variable OLIG2 expression in other ETs, ATRT, and ETMR suggests the broader diagnostic implications of the marker. Furthermore, incidental findings of OLIG2 positivity in cases traditionally expected to be negative, such as medulloblastoma and ependymoma, introduce an additional layer of complexity. Together, these findings highlight the challenges of relying solely on OLIG2 immunostaining for accurate tumor classification in pediatric CNS neoplasms and underscore the importance of an integrated diagnostic approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Advertising for unhealthy foods adversely affects children's food preferences and intake. The German government published plans to restrict such advertising in February 2023 and has revised them several times since. We assess the reach of the current draft from June 2023, and discuss its public health implications. We show that across 22 product categories covered by the current draft law, the median share of products permitted for marketing to children stands at 55%, with an interquartile range of 11-73%. Resistance from industry groups and from within government poses hurdles and leaves the prospects of the legislation uncertain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Pleomorphic xanthoastrocytomas (PXAs) harbor CDKN2A homozygous deletion in >90% of cases, resulting in loss of p16 expression by immunohistochemistry. Considering the proximity of MTAP to CDKN2A and their frequent concurrent deletions, loss of MTAP expression may be a surrogate for CDKN2A homozygous deletion. We evaluated p16 and MTAP expression in 38 patient PXAs (CNS WHO grade 2: n = 23, 60.5%; grade 3: n = 15, 39.5%) with available chromosomal microarray data to determine whether MTAP can be utilized independently or in combination with p16 to predict CDKN2A status. CDKN2A, CDKN2B, and MTAP homozygous deletion were present in 37 (97.4%), 36 (94.7%), and 25 (65.8%) cases, respectively. Expression of p16 was lost in 35 (92.1%) cases, equivocal in one (2.6%), and failed in 2 (5.3%), while MTAP expression was lost in 27 (71.1%) cases, retained in 10 (26.3%), and equivocal in one (2.6%). This yielded a sensitivity of 94.6% for p16 and 73.0% for MTAP in detecting CDKN2A homozygous deletion through immunohistochemistry. MTAP expression was lost in the 2 cases with failed p16 staining (combined sensitivity of 100%). Our findings demonstrate that combined p16 and MTAP immunostains correctly detect CDKN2A homozygous deletion in PXA, while MTAP expression alone shows reduced sensitivity., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.)

Background: Young children treated for central nervous system (CNS) malignancies are at high risk for difficulties with academic functioning due to increased vulnerability of the developing brain and missed early developmental opportunities. Extant literature examining academics in this population is limited. We investigated academic readiness, its clinical and demographic predictors, and its relationship with distal academic outcomes among patients treated for CNS tumors during early childhood., Methods: Seventy patients with newly diagnosed CNS tumors were treated on a prospective, longitudinal, multisite study with chemotherapy, with or without photon or proton irradiation. Patients underwent assessments of academic skills at baseline, 6 months, 1 year, and then annually for 5 years. Assessments measured academic readiness and academic achievement in reading and math., Results: Mixed linear models revealed slowed development of academic readiness skills over time. Socioeconomic status (SES) was predictive of academic readiness at all time points. Other demographic (eg, age at treatment) and clinical (eg, shunt status, treatment exposure) variables were not predictive of academic readiness. Distal reading difficulties were proportionally greater than normative expectations while math difficulties did not differ. Academic readiness was predictive of distal academic outcomes in reading and math., Conclusions: Treatment for CNS malignancies in early childhood appears to slow development of academic readiness skills, with SES predictive of risk. Academic readiness skills were predictive of subsequent academic achievement. A disproportionate number of long-term survivors performed below age-based expectations in reading. These findings suggest the need for monitoring and interventions targeting early academic skills in this population., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: Children with cancer are at risk of poor nutritional status during treatment and into survivorship. Objectively measured taste perception and self-reported food hedonics are 2 factors that may influence food intake., Objective: This 2-armed systematic review examined whether chemotherapy and radiotherapy affect (1) taste perception and (2) hedonic experiences of children and survivors of childhood cancer., Data Source: A 2-armed systematic literature search was conducted in the Medline, CINAHL, Embase, and PsychInfo database until June 2022. The effects of cancer treatment on objective taste perception or food hedonics (ie, food liking or aversion and appetite) were examined., Data Extraction: Peer-reviewed articles published in English of studies that included children (aged <18 years) or survivors of childhood cancer (any age) were reviewed. Risk of bias was determined using the Evidence Analysis Library by the Academy of Nutrition and Dietetics., Data Analysis: A total of 1417 articles in the taste search arm and 3862 articles in the hedonics search arm were identified. Of these, 9 and 4 articles were eligible for review, respectively. Cancer treatment had highly variable effects on taste perception during treatment and into survivorship. Learned food aversions were experienced by children receiving chemotherapy treatment and liking of meats and salty foods by children with cancer was affected. The impact of treatment on appetite varied., Conclusions: Cancer treatment did not uniformly affect taste perception. Food liking may be negatively affected, and learned food aversions may develop during cancer treatment. To establish the clinical relevance of childhood cancer treatment on taste perception and food hedonics, more research is required., Systematic Review Registration: PROSPERO registration no.CRD42020207127., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Primary spinal cord gliomas are rare and are associated with high mortality. Unlike brain tumors, the clinicopathological features of spinal cord gliomas are not well defined. We analyzed clinical, histopathology, and immunohistochemical features and overall survival (OS) of 25 patients with primary spinal cord gliomas treated between 1994 and 2023 at 4 institutions. IDH1 R132H, H3K27M, and p53 were assessed by immunohistochemistry (IHC). Four (16%), 5 (20%), 2 (8%), and 13 (52%) patients were diagnosed as having grades 1, 2, 3, and 4 gliomas according to the World Health Organization (WHO) 2021 classification, respectively. One case (4%), with a circumscribed diffuse midline glioma, H3K27-altered, had a rare molecular profile and could not be graded. IHC demonstrated H3K27M positivity, indicative of H3F3A K27M or HIST1H3B K27M mutation, in 9 (36%) patients. H3K27me3-loss was evident in 13 (52%) patients. In one patient with a grade 1 tumor that showed negative staining for H3K27M and H3K27me3 loss, numbers of EZHIP-positive cells were increased, suggesting diffuse midline glioma, H3K27-altered (WHO grade 4). H3K27me3 loss, frequency of p53 positive cells (≥10%), MIB-1 index (≥10%), and high histopathological grades significantly correlated with poor OS. These results indicate the pathological and immunohistochemical characteristics of primary spinal cord gliomas that impact prognosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The appropriate antithrombotic regimen after a Fontan operation is yet to be elucidated. Hence, this study aimed to compare the incidence of thromboembolic events in patients with and without receiving warfarin for thromboprophylaxis in a large post-Fontan population., Methods: This retrospective cohort study used data from the Diagnosis Procedure Combination database in Japan between April 2011 and March 2022. We identified all patients who underwent a Fontan operation and excluded those who were born before 2010, died during the hospitalization or received mechanical heart replacement. Propensity score overlap weighting was performed between patients discharged with warfarin (with or without aspirin) and the control group (only aspirin or neither aspirin nor warfarin). Cox and Fine-Gray hazards models compared thromboembolic and bleeding events., Results: We identified 2007 eligible patients, including 1670 warfarin users and 337 non-users. The mean follow-up duration was 2.1 years. The crude proportions of thromboembolic events were 3.0% and 3.0% and those of bleeding events were 0.4% and 0.3% in the warfarin and control groups, respectively. There was no significant difference in thromboembolic events between the groups (sub-distribution hazard ratio: 0.77; 95% confidence interval 0.39-1.51; P = 0.45) or bleeding events (sub-distribution hazard ratio: 0.78; 95% confidence interval 0.09-7.03; P = 0.83)., Conclusions: Warfarin use at discharge after a Fontan operation may not be necessary for thromboembolism prophylaxis in paediatric patients, based on large-scale real-world data, with a mean postoperative follow-up duration of 2.1 years. There is room for further studies to reconsider routine warfarin use in patients post-Fontan operation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objective: Outcomes are poor for patients with congenital adrenal hyperplasia (CAH), in part due to the supraphysiological glucocorticoid doses required to control adrenal androgen excess. Hydrocortisone (ie, cortisol) is the recommended glucocorticoid for treatment of CAH. However, the other endogenous glucocorticoid in humans, corticosterone, is actively transported out of metabolic tissues such as adipose tissue and muscle, so we hypothesized that corticosterone could control adrenal androgens while causing fewer metabolic adverse effects than hydrocortisone., Methods: Thirteen patients (8 female, 5 male) with CAH due to 21-hydroxylase deficiency completed a randomized placebo-controlled crossover study comparing 5 h intravenous infusions of either hydrocortisone, corticosterone or placebo. 6-6[2H]2-glucose and 1,1,2,3,3-[2H]5-glycerol were infused to measure glucose and glycerol kinetics, and blood samples were collected throughout. Subcutaneous abdominal adipose tissue biopsies were obtained at the end of each infusion., Results: During the infusion, corticosterone and hydrocortisone similarly reduced ACTH, 17α-hydroxyprogesterone, androstenedione, and testosterone (in females only) compared with placebo. Despite achieving circulating corticosterone concentrations ∼2.5-fold higher than hydrocortisone, by T + 300 min hydrocortisone but not corticosterone increased glucose and insulin concentrations and reduced 6-6-[2H]2-glucose clearance compared with placebo. Hydrocortisone increased mRNA levels of the glucocorticoid regulated transcript PER1 in adipose to a greater extent than corticosterone., Conclusions: Corticosterone acutely controls biochemical markers of androgen excess similarly to hydrocortisone but without inducing markers of glucocorticoid "toxicity" in CAH. These data demonstrate proof of concept that corticosterone may be a safer glucocorticoid replacement than current medications, although further research is required to assess the longer-term effects of corticosterone replacement., Competing Interests: Conflict of interest: None of the authors have any conflicts to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

To determine if healthcare-associated (HA)-respiratory syncytial virus (RSV) is associated with worse outcomes, this multicenter cohort study studied 26 children with HA-RSV and 78 matched non-HA-RSV patients of whom 58% and 55%, respectively, had ≥2 comorbidities. Overall, 39% of HA-RSV versus 18% of non-HA-RSV patients required respiratory support escalation (adjusted odds ratio (aOR) 5.1, CI95 1.4, 19.1)., (© The Journal of the Pediatric Infectious Diseases Society 2024.)

The safety of casirivimab + imdevimab (CAS + IMD) (anti-severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] monoclonal antibodies [mAbs]) in pediatric outpatients with coronavirus disease 2019 (COVID-19) was evaluated in a randomized phase 1/2/3 trial. Consistent with adults, CAS + IMD was generally well tolerated with low drug-induced immunogenicity rates. The findings support the development of next-generation anti-SARS-CoV-2 mAbs for at-risk pediatric patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

The Pediatric Surviving Sepsis Campaign Guidelines recommend delivery of antibiotics within 1 hour for children with septic shock and, for those without shock but with sepsis-related organ dysfunction, as soon as feasible within 3 hours. In this review, we summarize the available adult and pediatric literature supporting these recommendations. We also explore the implications of implementing time-to-antibiotic goals at the point of antibiotic initiation in clinical practice, as well as the potential downstream impacts of these goals on antibiotic de-escalation., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Pediatric hospitals are uniquely positioned to be impacted by antimicrobial waste. To explore this issue, we reviewed the current literature to identify the reasons, costs, and potential solutions to waste. Identified reasons for waste included weight-based dosing, medication order changes due to changing patient status, loss or expiration of doses, and medication errors. The cost of waste included financial costs, promotion of antimicrobial resistance, and generation of greenhouse gases. Proposed interventions to reduce waste included an early switch from intravenous to oral administration, required stop dates, standardized dosing times, and optimization of the pharmacy batching process. However, additional studies are needed to assess the potential correlation between these proposed interventions and waste reduction. Antimicrobial stewardship programs have been identified as a group that can play a crucial role in partnering to implement these interventions to potentially reduce antimicrobial waste and promote better healthcare sustainability., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Intraepithelial mast cells (MCs) are increased in eosinophilic esophagitis (EoE) and reduced with elimination of dietary antigens. Single food reintroduction can identify triggers of eosinophilia; however, the extent to which specific foods trigger intraepithelial mastocytosis remains unknown. We hypothesized that specific foods drive different degrees of MC inflammation. We previously reported a prospective pediatric EoE cohort treated with a 4-food elimination diet (4FED) with removal of soy, egg, wheat, and milk. We retrieved unstained slides in which baseline, 4FED, and post-4FED diet reintroduction time points were available. Slides were stained with tryptase, and intraepithelial MCs were counted. Comparisons were made by stratifying patients by eosinophilia, basal cell hyperplasia (BCH), endoscopic abnormalities, and symptoms. Pearson correlation was assessed for MCs with eosinophilic, endoscopic, and BCH severity; symptoms; and a novel mucosal activity score combining endoscopic and histologic structural severity. Slides were available from 37 patients with at least 1 food reintroduced. MCs were significantly reduced with 4FED. Wheat led to increased intraepithelial MCs in the upper esophagus and with food-induced eosinophilia, while milk led to significantly increased MCs in the upper and lower esophagus and was significantly associated with patients with food-triggered eosinophilia, endoscopic abnormalities, BCH, and symptoms. MCs best correlated with the mucosal activity score during milk reintroduction. In children with EoE, MCs are reduced with 4FED. During milk reintroduction, significant increases in MCs were observed with all metrics of inflammation along with moderate correlation with structural mucosal activity that was not seen with other foods. This suggests that milk exerts unique effects either directly or indirectly on MCs in the esophagus in EoE patients., Competing Interests: Conflict of interest statement. J.B.W. has served as a consultant for Allakos, Ellodi, Regeneron, Sanofi/Genzyme, Bristol-Myers Squibb, Invea Therapeutics, CellDex, and AstraZeneca; and has received clinical trial/research funding from Allakos and Sanofi-Regeneron., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cardiovascular magnetic resonance (CMR) imaging is recommended in patients with congenital heart disease (CHD) in clinical practice guidelines as the imaging standard for a large variety of diseases. As CMR is evolving, novel techniques are becoming available. Some of them are already used clinically, whereas others still need further evaluation. In this statement, the authors give an overview of relevant new CMR techniques for the assessment of CHD. Studies with reference values for these new techniques are listed in the Supplementary data online, supplement., Competing Interests: Conflict of interest: The authors have nothing to Disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Implementation science research identifies clinical champions as instrumental in aligning healthcare professionals' (HCPs) behavior with practice guidelines for delivering health services, including vaccinations. However, we know relatively little about identifying or supporting champions. To characterize who vaccine champions are, what they do, and how to support their work in pediatric primary care. In 2022, we interviewed a purposive sample of peer-nominated or self-identified vaccine champions (n=20) and HCPs who worked with vaccine champions (n=4). We thematically analyzed qualitative data. Vaccine champions' defining characteristics were firsthand primary care experience, whether as providers or nursing staff, and a strong belief in vaccinations as uniquely effective tools for primary prevention. Participants noted these beliefs were "part of the DNA" of specialties like pediatrics and infectious disease, where they perceived champions as especially common. Being "insatiable in their quest for knowledge," champions primarily conceptualized their role as understanding and sharing complex information and performance metric data related to vaccine administration. Champions' role in leading other implementation strategies, such as communication training, was more peripheral. Champions reported that dedicated time and staff support helped them "go above and beyond" to improve vaccination rates. Our findings suggest that vaccine champions can be found among providers and nursing staff with deep clinical experience and commitment to primary prevention through vaccination, including through providing vaccine education to colleagues. Healthcare systems can allocate resources to support champions as educators, while exploring opportunities to extend their role in other implementation strategies to improve vaccination rates., (© Society of Behavioral Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)