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Background: Attention-deficit/hyperactivity disorder (ADHD) has been shown to pose considerable clinical and economic burden; however, research quantifying the excess burden attributable to common psychiatric comorbidities of ADHD among pediatric patients is scarce. This study assessed the impact of anxiety and depression on healthcare resource utilization (HRU) and healthcare costs in pediatric patients with ADHD in the United States. Methods: Patients with ADHD aged 6–17 years were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was the date of initiation of a randomly selected ADHD treatment. Patients with ≥ 1 diagnosis for anxiety and/or depression during both the baseline (6 months pre-index) and study period (12 months post-index) were classified in the ADHD+anxiety/depression cohort; those without diagnoses for anxiety nor depression during both periods were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts. All-cause HRU and healthcare costs during the study period were compared using regression analyses. Cost analyses were also performed in subgroups by comorbid conditions. Results: The reweighted ADHD-only cohort (N = 204,723) and ADHD+anxiety/depression cohort (N = 66,231) had similar characteristics (mean age: 11.9 years; 72.8% male; 56.2% had combined inattentive and hyperactive ADHD type). The ADHD+anxiety/depression cohort had higher HRU than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 10.3; emergency room visits: 1.6; outpatient visits: 2.3; specialist visits: 5.3; and psychotherapy visits: 6.1; all p < 0.001). The higher HRU translated to greater all-cause healthcare costs; the mean per-patient-per-year (PPPY) costs in the ADHD-only cohort vs. ADHD+anxiety/depression cohort was $3,988 vs. $8,682 (p < 0.001). All-cause healthcare costs were highest when both comorbidities were present; among patients with ADHD who had only anxiety, only depression, and both anxiety and depression, the mean all-cause healthcare costs were $7,309, $9,901, and $13,785 PPPY, respectively (all p < 0.001). Conclusions: Comorbid anxiety and depression was associated with significantly increased risk of HRU and higher healthcare costs among pediatric patients with ADHD; the presence of both comorbid conditions resulted in 3.5 times higher costs relative to ADHD alone. These findings underscore the need to co-manage ADHD and psychiatric comorbidities to help mitigate the substantial burden borne by patients and the healthcare system. [ABSTRACT FROM AUTHOR]

Background. A−β+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved β-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A−β+ KPD within this cohort. Methods. We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A−β+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results. Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A−β+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions. In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A−β+ KPD. They manifest the key characteristics of obesity, preserved β-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A−β+ KPD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ambient air pollution may be a developmental endocrine disruptor. In animal models, gestational and perinatal exposure to diesel exhaust and concentrated particulate matter alters anogenital distance (AGD), a marker of prenatal androgen activity, in both sexes. Little is known in humans. OBJECTIVES: We examined exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in relation to human AGD at birth and at 1 year of age, focusing on exposures during critical windows of reproductive development: the male programming window (MPW; gestational weeks 8–14) and mini-puberty (postnatal months 1–3). METHODS: The Infant Development and Environment Study (TIDES) recruited first trimester pregnant women (β = 687) at four U.S. sites (Minneapolis, Minnesota; Rochester, New York; San Francisco, California; and Seattle, Washington) from 2010 to 2012. We measured anus to clitoris (AGD-AC) and anus to fourchette (AGD-AF) in female infants at birth; in males, we measured anus to penis (AGD-AP), anus to scrotum (AGDAS), and penile width at birth and at 1 year of age. Using advanced spatiotemporal models, we estimated maternal exposure to PM2.5 and NO2 in the MPW and mini-puberty. Covariate-adjusted, sex-stratified linear regression models examined associations between PM2.5 and NO2 and AGD. RESULTS: In males, a 1-μg/m³ increase in PM2.5 exposure during the MPW was associated with shorter AGD at birth, but a longer AGD at 1 year of age (e.g., birth AGD-AP: β = -0.35 mm; 95% CI: -0.62, -0.07; AGD-AS: β = 0.37 mm; 95% CI: 0.02, 0.73). Mini-pubertal PM2.5 exposure was also associated with shorter male AGD-AP (β = -0.50 mm; 95% CI: -0.89, -0.11) at 1 year of age. Although not associated with male AGD measures, 1-ppb increases in NO2 exposure during the MPW (β = -0.07 mm; 95% CI: -0.02, -0.12) and mini-puberty (β = -0.04 mm; 95% CI: -0.08, 0.01) were both associated with smaller penile width at 1 year of age. Results were similar in multipollutant models, where we also observed that in females AGD-AC was inversely associated with PM2.5 exposure, but positively associated with NO2 exposure. DISCUSSION: PM2.5 and NO2 exposures during critical pre- and postnatal windows may disrupt reproductive development. More work is needed to confirm these novel results and clarify mechanisms. [ABSTRACT FROM AUTHOR]

Flag football is promoted as a safer alternative to tackle football. This may be 1 reason why participation rates have risen by 39% over the past 3 years. Despite rising participation, epidemiologic research on sport-specific injuries and associated relative risk is lacking. To prospectively document the epidemiology of injuries in youth flag football. Descriptive epidemiology study. Regional and national youth flag football tournaments. Athletes (N = 1939; 1744 boys and 195 girls), ages 6 to 12 years. An athletic trainer prospectively monitored the athletes for sport-related injury and exposures. Athlete risks of injury and injury rates were calculated overall and by sex. Injury characteristics were reported for the total population and by sex. Forty-seven injuries to unique individuals were recorded in 1939 athletes with a total of 9228 athlete-exposures (AEs). The overall risk of injury was 2.4% (95% CI = 1.79%, 3.21%), with an overall injury rate of 5.1 per 1000 AEs (95% CI = 3.75, 6.77). Of the 47 injuries, 36 occurred in boys (8365 AEs), and 11 occurred in girls (863 AEs). A higher risk in girls was evidenced by both the injury risk ratio (2.73; 95% CI = 1.41, 5.30) and injury rate ratio of 2.96 (95% CI = 1.51, 5.82). The most common injury sites were the head/face/neck (n = 15, 31.9%), followed by the ankle/foot (n = 9, 19.1%). The most frequent types of injury were contusion (55.3%), sprain/subluxation (14.9%), and general trauma (10.6%); 74.5% of all injuries resulted from direct impact. Although the competition injury rate for youth flag football was lower than the values from studies reporting comparable tackle football data, the frequencies by body part, type, and mechanism were similar. Given that most injuries were related to some form of impact and predominantly contusions, adopting minimal protective equipment or padding may reduce the numbers of these injuries. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gestational phthalate and phenol exposure disrupts adipogenesis, contributing to obesity in mice. Whether gestational phthalate or phenol exposure is associated with infant body composition has not been investigated in humans. OBJECTIVE: We examined associations between biomarkers of phthalate and phenol exposure in midpregnancy and infant size and body composition at birth and at 5 months of age. METHODS: Analyses were conducted among 438 infants from the Healthy Start prospective pregnancy cohort. Sixteen phthalate and phenol biomarkers were quantified in spot urine samples collected at 24–28 wk of gestation. Infant outcomes measured at birth and at 5 months of age included size [weight (in grams)] and body composition [fat and lean masses (in grams); percentage fat mass]. Single- (linear) and multipollutant (quantile g-computation) models were used to estimate associations of phthalate and phenol biomarkers with infant outcomes at birth and at 5 months of age. Models were adjusted for sociodemographics, sample collection timing, and lifestyle factors and used to examine for effect modification by infant sex. RESULTS: In single-pollutant models, mono-benzyl phthalate and di-n-butyl phthalate were inversely associated with percentage fat mass [ß: -0.49 (95% CI: -0:91, -0:08) and -0:51 (95% CI: -1.02, 0.01), respectively] in male but not female infants at birth. Similar, but less precise, associations were observed at 5 months of age. In multipollutant models, a 1-quartile increase in the phthalate and phenol biomarker mixture was inversely associated with percentage fat mass at birth [-1.06 (95% CI: -2.21, 0.1)] and at 5 months of age [-2.14 (95% CI: -3.88, -0.39)] among males, but associations were null among females [0.48 (95% CI: -0.78, 1.75) and -0.64 (95% CI: -2.68, 1.41), respectively]. Similar associations were observed with infant weight. CONCLUSION: In this U.S.-based prospective cohort, gestational phthalate and phenol biomarkers were inversely associated with infant weight and fat mass, particularly in males. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse intrinsic pontine gliomas in children are rare, highly malignant infiltrating tumors in a location precluding surgical resection. The absence of non-invasive correlates of response and disease progression in these tumors invites the exploration of imaging biomarkers. Magnetic resonance spectroscopy is an advanced imaging technique for measuring cell metabolites. This study evaluated whether measurements of in vivo cell metabolites using magnetic resonance spectroscopy may serve as biomarkers of response to therapy, including progression. Single-voxel magnetic resonance spectra were serially acquired in two cohorts of patients with these tumors treated with radiation therapy with or without concurrent chemotherapy and prior to progression: 14 participants were enrolled in a clinical trial of adjuvant glioma-associated antigen peptide vaccines and 32 patients were enrolled who did not receive adjuvant vaccine therapy. In the vaccine cohort, an elevated myo-inositol/choline ratio after 2–3 doses was associated with longer survival. Scans performed up to 6 months before death showed a terminal decline in the myo-inositol/choline ratio. Higher myo-inositol/choline ratios following radiation therapy, consistent with less proliferate tumors and decreased cell turnover, were associated with longer survival, suggesting that this ratio can serve as a biomarker of prognosis following radiation therapy. Purpose: Diffuse intrinsic pontine gliomas (DIPG) are highly aggressive tumors with no currently available curative therapy. This study evaluated whether measurements of in vivo cell metabolites using magnetic resonance spectroscopy (MRS) may serve as biomarkers of response to therapy, including progression. Methods: Single-voxel MR spectra were serially acquired in two cohorts of patients with DIPG treated with radiation therapy (RT) with or without concurrent chemotherapy and prior to progression: 14 participants were enrolled in a clinical trial of adjuvant glioma-associated antigen peptide vaccines and 32 patients were enrolled who did not receive adjuvant vaccine therapy. Spearman correlations measured overall survival associations with absolute metabolite concentrations of myo-inositol (mI), creatine (Cr), and n-acetyl-aspartate (NAA) and their ratios relative to choline (Cho) during three specified time periods following completion of RT. Linear mixed-effects regression models evaluated the longitudinal associations between metabolite ratios and time from death (terminal decline). Results: Overall survival was not associated with metabolite ratios obtained shortly after RT (1.9–3.8 months post-diagnosis) in either cohort. In the vaccine cohort, an elevated mI/Cho ratio after 2–3 doses (3.9–5.2 months post-diagnosis) was associated with longer survival (rho = 0.92, 95% CI 0.67–0.98). Scans performed up to 6 months before death showed a terminal decline in the mI/Cho ratio, with an average of 0.37 ratio/month in vaccine patients (95% CI 0.11–0.63) and 0.26 (0.04–0.48) in the non-vaccine cohort. Conclusion: Higher mI/Cho ratios following RT, consistent with less proliferate tumors and decreased cell turnover, were associated with longer survival, suggesting that this ratio can serve as a biomarker of prognosis following RT. This finding was seen in both cohorts, although the association with OS was detected earlier in the vaccine cohort. Increased mI/Cho (possibly reflecting immune-effector cell influx into the tumor as a mechanism of tumor response) requires further study. [ABSTRACT FROM AUTHOR]

This study examines the risk-related factors during the pandemic and protective factors that might reduce its effects on family functioning in a sample of 161 low-income Hispanic parents in the United States, recruited from an ongoing longitudinal intervention study. They were surveyed about family functioning six months into the pandemic. We focused on the associations between social (e.g., exposure to the virus) and economic (e.g., job loss) pandemic-related risks on parental stress, parenting, and children's socioemotional problems and skills, as well as the degree to which coparenting support, parents' positivity, economic support, and access to services and information mitigated (protected) the negative effects of these stressors on family functioning. We found that increases in economic risk were associated with more child competence skills, whereas increases in social risk were associated with less parental engagement. Positivity and economic support moderated the effects of economic risk on parental stress and engagement. These findings show that to intervene effectively with low-income Hispanic families, we need to strengthen and support the resources for coping with adversity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure. OBJECTIVE: We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3–6 years of age). METHODS: Within The Infant Development and the Environment Study (TIDES), a prospective pregnancy cohort, we analyzed a panel of phthalate metabolites in urine collected at two visits from early and late gestation (푁 = 780). We estimated average phthalate metabolite associations with child weight 푧-scores from ~20 wk gestation (estimated by ultrasound), birth, and 1, 3, 4, and 6 years of age using linear mixed-effects (LME) models. We also modeled associations with adiposity 푧-scores from birth (weight for length) and 1, 3, 4, and 6 years of age [body mass index (BMI)] using LME models. RESULTS: For weight, we observed inverse associations between several phthalate metabolites and birth weight 푧-scores, but no associations were observed with postnatal weight 푧-scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length 푧-scores at birth, but positive associations were observed with BMI 푧-scores at 3–4 years of age in LME models. For example, mono-ethyl phthalate was associated with a 0.17-unit decrease in birth weight-for-length 푧-score [95% confidence interval (CI): –0:29, –0:05] and a 0.18-unit increase in 4-years-of-age BMI 푧-score (95% CI: 0.04, 0.32). DISCUSSION: We observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3–4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. [ABSTRACT FROM AUTHOR]