Search

Background: Traditional classification of children's and nonchildren's hospitals is based on physical structure and branding. We grouped hospitals with the most similar types of pediatric patients., Methods: Retrospective analysis of 2.8 million hospitalizations in 3993 hospitals for patients 0 to 20 years in the 2019 Kids' Inpatient Database. After stratifying low-volume hospitals (greater than 100 annual admissions), we grouped the remaining hospitals using K-means clustering by case-mix of neonatal services and pediatric diagnosis diversity (DD)., Results: Clustering distinguished 6 hospital groups. Group 1 (n = 1665 [1.6% of hospitalizations]) represented low pediatric volume hospitals (13 annual pediatric hospitalizations [IQR 3-82]). Group 2 (n = 118 hospitals [1.1% of hospitalizations]) provided no neonatal care, had low DD (12 [IQR 4-34]), and had a median age of 17 years. Group 3 (n = 1156 [19.7% of hospitalizations]) hospitals provided low-severity neonatal care with low DD (13 [IQR 7-19). Group 4 (n = 674 hospitals, [24.0% of hospitalizations]) provided moderate-severity neonatal care (2.2 [ IQR 2.1-2.4]) and increased DD (24 [ IQR 6-34]). Group 5 (n = 238 hospitals [20.5% of hospitalizations]) had a similar severity of neonatal care as group 4 (2.3 [IQR 2.1-2.5]), but 2.7 times greater DD (64 [IQR 55-77]). Group 6 (n = 142 hospitals [33.0% of hospitalizations]) had the highest-severity neonatal care (2.6 [IQR 2.3-3.1]) and the greatest DD (127 [113-140])., Conclusion: Children receive inpatient care across 6 groups of hospitals, distinguished by neonatal case-mix and DD. Future studies should investigate the utility of these groups for peer comparisons with health care use and outcomes., (Copyright © 2025 by the American Academy of Pediatrics.)

Objective: The accuracy of diagnosis codes to identify suicidal behaviors, including suicide ideation (SI) and self-harm (SH) events, is unknown. The objective of this study was to determine the positive predictive value (PPV) of International Classification of Disease, 10th Revision codes to identify SI/SH events that may be used in studies using administrative and claims data., Methods: We performed a secondary analysis of a cross-sectional study of children 5 to 17 years of age hospitalized at 2 US children's hospitals with a discharge diagnosis of a neuropsychiatric event, including an SI or SH event. A true International Classification of Disease, 10th Revision SI or SH diagnosis was defined as SI or SH present on admission and directly related to hospitalization as compared with physician record review. PPV with 95% confidence intervals (CIs) were calculated overall and stratified by diagnosis order and age (5 to 11 years vs 12 to 17 years)., Results: There were 376 children or adolescents with a discharge diagnosis of an SI or SH event. The median age was 14 years, and the majority of individuals were female (58%), non-Hispanic White (69%), and privately insured (57%). A total of 332 confirmed SI/SH cases were identified with a PPV of 0.88 (95% CI 0.85-0.91). PPVs were similar when stratified by diagnosis order: primary 0.94 (95% 0.88-0.97) versus secondary 0.86 (95% CI 81-90). PPVs were also similar in adolescents (0.89, CI 0.85-0.92) compared with children (0.84, 95% CI 0.74-0.91)., Conclusions: The use of these validated code sets to identify SI or SH events may minimize misclassification in future studies of suicidal and self-harm hospitalizations., (Copyright © 2023 by the American Academy of Pediatrics.)

Randomized controlled trials (RCTs) are the gold standard study design for clinical research, as prospective randomization, at least in theory, balances any differences that can exist between groups (including any differences not measured as part of the study) and isolates the studied treatment effect. Any remaining imbalances after randomization are attributable to chance. However, there are many barriers to conducting RCTs within pediatric populations, including lower disease prevalence, high costs, inadequate funding, and additional regulatory requirements. Researchers thus frequently use observational study designs to address many research questions. Observational studies, whether prospective or retrospective, do not involve randomization and thus have more potential for bias when compared with RCTs because of imbalances that can exist between comparison groups. If these imbalances are associated with both the exposure of interest and the outcome, then failure to account for these imbalances may result in a biased conclusion. Understanding and addressing differences in sociodemographic and/or clinical characteristics within observational studies are thus necessary to reduce bias. Within this Method/ology submission we describe techniques to minimize bias by controlling for important measurable covariates within observational studies and discuss the challenges and opportunities in addressing specific variables., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: To identify patterns of psychiatric comorbidity among children and adolescents with a serious self-harm event., Methods: We studied children aged 5 to 18 years hospitalized with a neuropsychiatric event at 2 children's hospitals from April 2016 to March 2020. We used Bayesian profile regression to identify distinct clinical profiles of risk for self-harm events from 32 covariates: age, sex, and 30 mental health diagnostic groups. Odds ratios (ORs) and 95% credible intervals (CIs) were calculated compared with a reference profile with the overall baseline risk of the cohort., Results: We included 1098 children hospitalized with a neuropsychiatric event (median age 14 years [interquartile range (IQR) 11-16]). Of these, 406 (37%) were diagnosed with a self-harm event. We identified 4 distinct profiles with varying risk for a self-harm diagnosis. The low-risk profile (median 0.035 [IQR 0.029-0.041]; OR 0.08, 95% CI 0.04-0.15) was composed primarily of children aged 5 to 9 years without a previous psychiatric diagnosis. The moderate-risk profile (median 0.30 [IQR 0.27-0.33]; reference profile) included psychiatric diagnoses without depressive disorders. Older female adolescents with a combination of anxiety, depression, substance, and trauma disorders characterized the high-risk profile (median 0.69 [IQR 0.67-0.70]; OR 5.09, 95% CI 3.11-8.38). Younger males with mood and developmental disorders represented the very high-risk profile (median 0.76 [IQR 0.73-0.79]; OR 7.21, 95% CI 3.69-15.20)., Conclusions: We describe 4 separate profiles of psychiatric comorbidity that can help identify children at elevated risk for a self-harm event and subsequent opportunities for intervention., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Previous interventions to reduce emergency department (ED) overutilization from non-urgent visits have shown little success. At our hospital, we created an ED to primary care clinic (PCC) transfer protocol for non-urgent ED visits of established patients. Our study analyzed the impact of this protocol on patient encounters., Methods: Chart reviews were conducted for a retrospective cohort of transfers from the ED to PCC from 9/01/17-8/31/18. Primary outcomes included length of stay (LOS), cost, and need for return to the ED. Cost savings were calculated by comparing encounters with identical primary diagnoses in the ED with internal technical and professional financial data. Secondary outcomes were final diagnoses and primary care services provided., Results: 374 patient encounters were transferred from ED to PCC. The five most common diagnoses were viral upper respiratory infection (n=80, 21.4%), dermatologic diagnoses (n=37, 9.9%), acute otitis media (n=35, 9.4%), pharyngitis (n=34, 9.1%), and influenza (n=34, 9.1%). Overall, total cost savings equaled approximately $100,000. For the top 10 diagnoses, costs were reduced from $29-$46 per $100 of ED costs and LOS was reduced by a mean of 49 min/encounter. For 9 of these 10 conditions, costs exceeded reimbursement in both settings; however, evaluation in PCC versus ED reduced the loss of revenue by 10-68%. Sixty-four encounters (17.1%) received additional primary care services. There were no safety events or inappropriate transfers., Conclusions: This protocol provided a safe, efficient method for patients to be evaluated in their medical home while reducing non-urgent emergency visits in the ED., Level of Evidence: VI., (Copyright © 2022. Published by Elsevier Inc.)

Provider- and claims-focused administrative databases are powerful tools for conducting health services research, and these studies often have good generalizability owing to diversity of hospitals from which samples are derived. In this research methods article, we describe administrative data and how available provider- and claims-focused administrative databases can be used to conduct health services research. We describe common observational study designs using administrative data and provide real-world examples. We highlight the strengths and weaknesses of studies conducted using administrative data and describe methodological considerations to reduce bias and improve the rigor of observational studies using administrative data. Finally, we provide guidance on the types of study questions suitable for observational study designs using administrative data., Competing Interests: POTENTIAL CONFLICT OF INTEREST:Troy Richardson and Matt Hall are employed by Children’s Hospital Association, the proprietor of the Pediatric Health Information System database., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: Despite extensive efforts, overall readmission rates at US children's hospitals have not materially declined over the past decade, raising questions about how to direct future efforts. Using measures of prevalence and performance variation we describe readmission rates by condition and identify priority conditions for future intervention., Methods: Retrospective cohort study of 49 US children's hospitals in the Pediatric Health Information System in 2017. Conditions were classified using All Patients Refined Diagnosis Related Groups. 30-day unadjusted and risk-adjusted readmission rates were calculated for each hospital/condition using the Pediatric All Cause Readmission measure. We ranked the highest volume conditions by rate variation (RV, interquartile range divided by the median) for each condition across hospitals., Results: The sample included 811,434 index hospitalizations with 50,196 (6.2%) 30-day readmissions. The RV across hospitals/conditions was between 0 and 2.8 (median = 0.7). Common reasons for admission had low RVs across hospitals, for example, bronchiolitis (readmission rate = 5.6%, RV = 0.4), seizure (readmission rate = 6.6%, RV = 0.3), and asthma (readmission rate = 3.1%, RV = 0.4). We identified 33 conditions with high variation in readmission rates across hospitals, which accounted for 18% of all discharges and 11% of all pediatric readmissions. These conditions may serve as candidates for future readmission reduction activities., Conclusions: Many common childhood conditions have little variation in readmission rates across children's hospitals, suggesting limited future improvement opportunities. Conditions with high rate variation may provide opportunities for quality improvement; however, these conditions account for a relatively small share of total discharges suggesting modest potential impacts on national rates., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: Reutilization following discharge is costly to families and the health care system. Singular measures of the social determinants of health (SDOH) have been shown to impact utilization; however, the SDOH are multifactorial. The Childhood Opportunity Index (COI) is a validated approach for comprehensive estimation of the SDOH. Using the COI, we aimed to describe the association between SDOH and 30-day revisit rates., Methods: This retrospective study included children 0 to 17 years within 48 children's hospitals using the Pediatric Health Information System from 1/1/2019 to 12/31/2019. The main exposure was a child's ZIP code level COI. The primary outcome was unplanned readmissions and emergency department (ED) revisits within 30 days of discharge. Primary outcomes were summarized by COI category and compared using chi-square or Kruskal-Wallis tests. Adjusted analysis used generalized linear mixed effects models with adjustments for demographics, clinical characteristics, and hospital clustering., Results: Of 728,997 hospitalizations meeting inclusion criteria, 30-day unplanned returns occurred for 96,007 children (13.2%). After adjustment, the patterns of returns were significantly associated with COI. For example, 30-day returns occurred for 19.1% (95% confidence interval [CI]: 18.2, 20.0) of children living within very low opportunity areas, with a gradient-like decrease as opportunity increased (15.5%, 95% CI: 14.5, 16.5 for very high). The relative decrease in utilization as COI increased was more pronounced for ED revisits., Conclusions: Children living in low opportunity areas had greater 30-day readmissions and ED revisits. Our results suggest that a broader approach, including policy and system-level change, is needed to effectively reduce readmissions and ED revisits., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to develop and validate an approach to accurately identify incident pediatric neuropsychiatric events (NPEs) requiring hospitalization by using administrative data., Methods: We performed a cross-sectional, multicenter study of children 5 to 18 years of age hospitalized at two US children's hospitals with an NPE. We developed and evaluated 3 NPE identification algorithms: (1) primary or secondary NPE International Classification of Diseases, 10th Revision diagnosis alone, (2) NPE diagnosis, the NPE was present on admission, and the primary diagnosis was not malignancy- or surgery-related, and (3) identical to algorithm 2 but without requiring the NPE be present on admission. The positive predictive value (PPV) of each algorithm was calculated overall and by diagnosis field (primary or secondary), clinical significance, and NPE subtype., Results: There were 1098 NPE hospitalizations included in the study. A total of 857 confirmed NPEs were identified for algorithm 1, yielding a PPV of 0.78 (95% confidence interval [CI] 0.76-0.80). Algorithm 2 (n = 846) had an overall PPV of 0.89 (95% CI 0.87-0.91). For algorithm 3 (n = 938), the overall PPV was 0.86 (95% CI 0.83-0.88). PPVs varied by diagnosis order, NPE clinical significance, and subtype. The PPV for critical clinical significance was 0.99 (0.97-0.99) for all 3 algorithms., Conclusions: We identified a highly accurate method to identify neuropsychiatric adverse events in children and adolescents. The use of these approaches will improve the rigor of future studies of NPE, including the necessary evaluations of medication adverse events, infections, and chronic conditions., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Disproportionately high acute care utilization among children with medical complexity (CMC) is influenced by patient-level social complexity., Objective: The objective of this study was to determine associations between ZIP code-level opportunity and acute care utilization among CMC., Design, Setting, and Participants: This cross-sectional, multicenter study used the Pediatric Health Information Systems database, identifying encounters between 2016-2019. CMC aged 28 days to <16 years with an initial emergency department (ED) encounter or inpatient/observation admission in 2016 were included in primary analyses., Main Outcome and Measures: We assessed associations between the nationally-normed, multi-dimensional, ZIP code-level Child Opportunity Index 2.0 (COI) (high COI = greater opportunity), and total utilization days (hospital bed-days + ED discharge encounters). Analyses were conducted using negative binomial generalized estimating equations, adjusting for age and distance from hospital and clustered by hospital. Secondary outcomes included intensive care unit (ICU) days and cost of care., Results: A total of 23,197 CMC were included in primary analyses. In unadjusted analyses, utilization days decreased in a stepwise fashion from 47.1 (95% confidence interval: 45.5, 48.7) days in the lowest COI quintile to 38.6 (36.9, 40.4) days in the highest quintile (p < .001). The same trend was present across all outcome measures, though was not significant for ICU days. In adjusted analyses, patients from the lowest COI quintile utilized care at 1.22-times the rate of those from the highest COI quintile (1.17, 1.27)., Conclusions: CMC from low opportunity ZIP codes utilize more acute care. They may benefit from hospital and community-based interventions aimed at equitably improving child health outcomes., (© 2022 Society of Hospital Medicine.)

Background: Observation status (OBS) stays incur similar costs to low-acuity, short-stay inpatient (IP) hospitalizations. Despite this, payment for OBS is likely less and may represent a financial liability for children's hospitals. Thus, we described the financial outcomes associated with OBS stays compared to similar IP stays by hospital and payer., Methods: We conducted a retrospective cohort study of clinically similar pediatric OBS and IP encounters at 15 hospitals contributing to the revenue management program in 2017. Clinical and demographic characteristics were described. For each hospitalization, the cost coverage ratio (CCR) was calculated by dividing revenue by estimated cost of hospitalization. Differences in CCR were evaluated using Wilcoxon rank sum tests and results were stratified by billing designation and payer. CCR for OBS and IP stays were compared by institution, and the estimated increase in revenue by billing OBS stays as IP was calculated., Results: OBS was assigned to 70 981 (56.9%) of 124 789 hospitalizations. Use of OBS varied across hospitals (8%-86%). For included hospitalizations, OBS stays were more likely than IP stays to result in financial loss (57.0% vs 35.7%). OBS stays paid by public payer had the lowest median CCR (0.6; interquartile range [IQR], 0.2-0.9). Paying OBS stays at the median IP rates would have increased revenue by $167 million across the 15 hospitals., Conclusions: OBS stays were significantly more likely to result in poor financial outcomes than similar IP stays. Costs of hospitalization and billing designations are poorly aligned and represent an opportunity for children's hospitals and payers to restructure payment models., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

In 2020, the American Society of Hematology published evidence-based guidelines for cerebrovascular disease in individuals with sickle cell anemia (SCA). Although the guidelines were based on National Institutes of Health-sponsored randomized controlled trials, no cost-effectiveness analysis was completed for children with SCA and silent cerebral infarcts. We conducted a cost-effectiveness analysis comparing regular blood transfusion vs standard care using SIT (Silent Cerebral Infarct Transfusion) Trial participants. This analysis included a modified societal perspective with direct costs (hospitalization, emergency department visit, transfusion, outpatient care, and iron chelation) and indirect costs (special education). Direct medical costs were estimated from hospitalizations from SIT hospitals and unlinked aggregated hospital and outpatient costs from SIT sites by using the Pediatric Health Information System. Indirect costs were estimated from published literature. Effectiveness was prevention of infarct recurrence. An incremental cost-effectiveness ratio using a 3-year time horizon (mean SIT Trial participant follow-up) compared transfusion vs standard care. A total of 196 participants received transfusions (n = 90) or standard care (n = 106), with a mean age of 10.0 years. Annual hospitalization costs were reduced by 54% for transfusions vs standard care ($4929 vs $10 802), but transfusion group outpatient costs added $22 454 to $137 022 per year. Special education cost savings were $2634 over 3 years for every infarct prevented. Transfusion therapy had an incremental cost-effectiveness ratio of $22 025 per infarct prevented. Children with preexisting silent cerebral infarcts receiving blood transfusions had lower hospitalization costs but higher outpatient costs, primarily associated with the oral iron chelator deferasirox. Regular blood transfusion therapy is cost-effective for infarct recurrence in children with SCA. This trial is registered at www.clinicaltrials.gov as #NCT00072761., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Elbow fractures are the most common pediatric fractures requiring operative treatment. To date, few studies have examined what annual factors drive pediatric elbow fracture incidence and no studies have examined which annual factors drive elbow fracture severity or resource utilization. The goal of this study was to not only document the annual patterns of pediatric elbow fracture incidence and severity but also the impact of these patterns on resource utilization in the emergency department, emergency medical service transportation, and the operating room (OR)., Methods: Retrospective cohort study of 4414 pediatric elbow fractures from a single tertiary hospital (2007 to 2017). Exclusion criteria included outside treatment or lack of diagnosis by an orthopaedist. Presentation information, injury patterns, transport, and treatment requirements were collected. Pearson correlations were used to analyze factors influencing fracture incidence, severity, and resource utilization., Results: Pediatric elbow fracture incidence positively correlated with monthly daylight hours, but significantly fewer elbow fractures occurred during summer vacation from school compared with surrounding in school months. While fewer overall fractures occurred during summer break, the fractures sustained were greater in severity, conferring higher rates of displacement, higher risk of neurovascular injury, and greater needs for emergency transportation and operative treatment. Yearly, elbow fractures required 320.6 OR hours (7.7% of all pediatric orthopaedic OR time and 12.3% of all pediatric orthopaedic operative procedures), 203.4 hospital admissions, and a total of 4753.7 miles traveled by emergency medical service transportation to manage. All-cause emergency department visits were negatively correlated with daylight hours, inversing the pattern seen in elbow fractures., Conclusion: Increased daylight, while school was in session, was a major driver of the incidence of pediatric elbow fractures. While summer vacation conferred fewer fractures, these were of higher severity. As such, increased daylight correlated strongly with monthly resource utilization, including the need for emergency transportation and operative treatment. This study provides objective data by which providers and administrators can more accurately allocate resources., Level of Evidence: Level III-Retrospective comparative study., Competing Interests: J.G.S. is a member of the education advisory board at OrthoPediatrics, receives research funding from OrthoPediatrics, serves as a board member of Pediatric Society of North America (POSNA) and research support from IONIS Pharmaceuticals. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The ATPase Family, AAA domain-containing protein 2 (ATAD2) bromodomain (BRD) has a canonical bromodomain structure consisting of four α-helices. ATAD2 functions as a co-activator of the androgen and estrogen receptors as well as the MYC and E2F transcription factors. ATAD2 also functions during DNA replication, recognizing newly synthesized histones. In addition, ATAD2 is shown to be up-regulated in multiple forms of cancer including breast, lung, gastric, endometrial, renal, and prostate. Furthermore, up-regulation of ATAD2 is strongly correlated with poor prognosis in many types of cancer, making the ATAD2 bromodomain an innovative target for cancer therapeutics. In this study, we describe the recognition of histone acetyllysine modifications by the ATAD2 bromodomain. Residue-specific information on the complex formed between the histone tail and the ATAD2 bromodomain, obtained through nuclear magnetic resonance spectroscopy (NMR) and X-ray crystallography, illustrates key residues lining the binding pocket, which are involved in coordination of di-acetylated histone tails. Analytical ultracentrifugation, NMR relaxation data, and isothermal titration calorimetry further confirm the monomeric state of the functionally active ATAD2 bromodomain in complex with di-acetylated histone ligands. Overall, we describe histone tail recognition by ATAD2 BRD and illustrate that one acetyllysine group is primarily engaged by the conserved asparagine (N1064), the "RVF" shelf residues, and the flexible ZA loop. Coordination of a second acetyllysine group also occurs within the same binding pocket but is essentially governed by unique hydrophobic and electrostatic interactions making the di-acetyllysine histone coordination more specific than previously presumed.

Background and Objectives: Previous pediatric studies have revealed substantial variation in laboratory testing for specific conditions, but clinical outcomes associated with high- versus low-frequency testing are unclear. We hypothesized that hospitals with high- versus low-testing frequency would have worse clinical outcomes., Methods: We conducted a multicenter retrospective cohort study of patients 0 to 18 years old with low-acuity hospitalizations in the years 2018-2019 for 1 of 10 common All Patient Refined Diagnosis Related Groups. We identified hospitals with high-, moderate-, and low-frequency testing for 3 common groups of laboratory tests: complete blood cell count, basic chemistry studies, and inflammatory markers. Outcomes included length of stay, 7- and 30-day emergency department revisit and readmission rates, and hospital costs, comparing hospitals with high- versus low-frequency testing., Results: We identified 132 391 study encounters across 44 hospitals. Laboratory testing frequency varied by hospital and condition. We identified hospitals with high- (13), moderate- (20), and low-frequency (11) laboratory testing. When we compared hospitals with high- versus low-frequency testing, there were no differences in adjusted hospital costs (rate ratio 0.89; 95% confidence interval 0.71-1.12), length of stay (rate ratio 0.98; 95% confidence interval 0.91-1.06), 7-day (odds ratio 0.99; 95% confidence interval 0.81-1.21) or 30-day (odds ratio 1.01; 95% confidence interval 0.82-1.25) emergency department revisit rates, or 7-day (odds ratio 0.84; 95% confidence interval 0.65-1.25) or 30-day (odds ratio 0.91; 95% confidence interval 0.76-1.09) readmission rates., Conclusions: In a multicenter study of children hospitalized for common low-acuity conditions, laboratory testing frequency varied widely across hospitals, without substantial differences in outcomes. Our results suggest opportunities to reduce laboratory overuse across conditions and children's hospitals., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background and Objectives: Patient complexity at US children's hospitals is increasing. Hospitals experience concurrent pressure to reduce length of stay (LOS) and readmissions, yet little is known about how these common measures of resource use and quality have changed over time. Our aim was to examine temporal trends in medical complexity, hospital LOS, and readmissions across a sample of US children's hospitals., Methods: Retrospective cohort study of hospitalized patients from 42 children's hospitals in the Pediatric Health Information System from 2013 to 2017. After excluding deaths, healthy newborns, obstetric care, and low volume service lines, we analyzed trends in medical complexity, LOS, and 14-day all-cause readmissions using generalized linear mixed effects models, adjusting for changes in patient factors and case-mix., Results: Between 2013 and 2017, a total of 3 355 815 discharges were included. Over time, the mean case-mix index and the proportion of hospitalized patients with complex chronic conditions or receiving intensive care increased ( P < .001 for all). In adjusted analyses, mean LOS declined 3% (61.1 hours versus 59.3 hours from 2013 to 2017, P < .001), whereas 14-day readmissions were unchanged (7.0% vs 6.9%; P = .03). Reductions in adjusted LOS were noted in both medical and surgical service lines (3.6% and 2.0% decline, respectively; P < .001)., Conclusions: Across US children's hospitals, adjusted LOS declined whereas readmissions remained stable, suggesting that children's hospitals are providing more efficient care for an increasingly complex patient population., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: High costs associated with hospitalization have encouraged reductions in unnecessary encounters. A subset of observation status patients receive minimal interventions and incur low use costs. These patients may contain a cohort that could safely be treated outside of the hospital. Thus, we sought to describe characteristics of low resource use (LRU) observation status hospitalizations and variation in LRU stays across hospitals., Methods: We conducted a retrospective cohort study of pediatric observation encounters at 42 hospitals contributing to the Pediatric Health Information System database from January 1, 2019, to December 31, 2019. For each hospitalization, we calculated the use ratio (nonroom costs to total hospitalization cost). We grouped stays into use quartiles with the lowest labeled LRU. We described associations with LRU stays and performed classification and regression tree analyses to identify the combination of characteristics most associated with LRU. Finally, we described the proportion of LRU hospitalizations across hospitals., Results: We identified 174 315 observation encounters (44 422 LRU). Children <1 year (odds ratio [OR] 3.3; 95% confidence interval [CI] 3.1-3.4), without complex chronic conditions (OR 3.6; 95% CI 3.2-4.0), and those directly admitted (OR 4.2; 95% CI 4.1-4.4) had the greatest odds of experiencing an LRU encounter. Those children with the combination of direct admission, no medical complexity, and a respiratory diagnosis experienced an LRU stay 69.5% of the time. We observed variation in LRU encounters (1%-57% of observation encounters) across hospitals., Conclusions: LRU observation encounters are variable across children's hospitals. These stays may include a cohort of patients who could be treated outside of the hospital., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To describe the prevalence and characteristics of infection-related readmissions in children and to identify opportunities for readmission reduction and estimate associated cost savings., Study Design: Retrospective analysis of 380,067 nationally representative index hospitalizations for children using the 2014 Nationwide Readmissions Database. We compared 30-day, all-cause unplanned readmissions and costs across 22 infection categories. We used the Inpatient Essentials database to measure hospital-level readmission rates and to establish readmission benchmarks for individual infections. We then estimated the number of readmissions avoided and costs saved if hospitals achieved the 10th percentile of hospitals' readmission rates (ie, readmission benchmark). All analyses were stratified by the presence/absence of a complex chronic condition (CCC)., Results: The overall 30-day readmission rate was 4.9%. Readmission rates varied substantially across infections and by presence/absence of a CCC (CCC: range, 0%-21.6%; no CCC: range, 1.5%-8.6%). Approximately 42.6% of readmissions (n = 3,576) for children with a CCC and 54.7% of readmissions (n = 5,507) for children without a CCC could have been potentially avoided if hospitals achieved infection-specific benchmark readmission rates, which could result in an estimated savings of $70.8 million and $44.5 million, respectively. Bronchiolitis, pneumonia, and upper respiratory tract infections were among infections with the greatest number of potentially avoidable readmissions and cost savings for children with and without a CCC., Conclusion: Readmissions following hospitalizations for infection in children vary significantly by infection type. To improve hospital resource use for infections, future preventative measures may prioritize children with complex chronic conditions and those with specific diagnoses (eg, respiratory illnesses).

Background and Objectives: Hospitals treating patients with greater diagnosis diversity may have higher fixed and overhead costs. We assessed the relationship between hospitals' diagnosis diversity and cost per hospitalization for children., Methods: Retrospective analysis of 1 654 869 all-condition hospitalizations for children ages 0 to 21 years from 2816 hospitals in the Kids' Inpatient Database 2016. Mean hospital cost per hospitalization, Winsorized and log-transformed, was assessed for freestanding children's hospitals (FCHs), nonfreestanding children's hospitals (NFCHs), and nonchildren's hospitals (NCHs). Hospital diagnosis diversity index (HDDI) was calculated by using the D-measure of diversity in Shannon-Wiener entropy index from 1254 diagnosis and severity-of-illness groups distinguished with 3M Health's All Patient Refined Diagnosis Related Groups. Log-normal multivariable models were derived to regress hospital type on cost per hospitalization, adjusting for hospital-level HDDI in addition to patient-level demographic (eg, age, race and ethnicity) and clinical (eg, chronic conditions) characteristics and hospital teaching status., Results: Admission counts were 383 789 (23.2%) in FCHs, 588 463 (35.6%) in NFCHs, and 682 617 (41.2%) in NCHs. Unadjusted mean cost per hospitalization was $10 757 (95% confidence interval [CI]: $9451 to $12 243) in FCHs, $6264 (95% CI: $5830 to $6729) in NFCHs, and $4192 (95% CI: $4121 to $4265) in NCHs. HDDI was significantly ( P < .001) higher in FCHs and NFCHs (median 9.2 and 6.4 times higher, respectively) than NCHs. Across all hospitals, greater HDDI was associated ( P = .002) with increased cost. Adjusting for HDDI resulted in a nonsignificant ( P = .1) difference in cost across hospital types., Conclusions: Greater diagnosis diversity was associated with increased cost per hospitalization and should be considered when assessing associated costs of inpatient care for pediatric patients., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To identify where rural children with mental health conditions are hospitalized and to determine differences in outcomes based on location of hospitalization., Study Design: This is a retrospective cohort analysis of US rural children aged 0-18 years with a mental health hospitalization between January 1, 2014, and November 30, 2014, using the 2014 Agency for Healthcare Research and Quality's Nationwide Readmissions Database. Hospitalizations for rural children were categorized by children's hospitals, metropolitan non-children's hospitals, or rural hospitals. Associations between hospital location and outcomes were assessed with logistic (readmission) and negative binomial regression (length of stay [LOS]) models. Classification and regression trees (CART) were used to describe the characteristics of most common hospitalizations at a rural hospital., Results: Of 21 666 mental health hospitalizations of rural children, 20.6% were at rural hospitals. After adjustment for clinical and demographic characteristics, LOS was higher at metropolitan non-children's and children's hospitals compared with rural hospitals (LOS: adjusted rate ratio [aRR], 1.35 [95% CI 1.29-1.41] and 1.33 [95% CI, 1.25-1.41]; P < .01 for all). The 30-day readmission was lower at metropolitan non-children's and children's hospitals compared with rural hospitals (aOR, 0.73 [95% CI, 0.63-0.84] and 0.59 [95% CI, 0.48-0.71]; P < .001 for all). Adolescent males living in poverty with externalizing behavior disorder had the highest percentage of hospitalization at rural hospitals (69.4%)., Conclusions: Although hospitalizations at children's and metropolitan non-children's hospitals were longer, patient outcomes were more favorable., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/objective: Pediatric patients hospitalized with bacterial infections often receive intravenous (IV) antibiotics. Early transition to enteral antibiotics can reduce hospital duration, cost, and complications. We aimed to identify opportunities to transition from IV to enteral antibiotics, describe variation of transition among hospitals, and evaluate feasibility of novel stewardship metrics., Methods: This multisite retrospective cohort study used the Pediatric Health Information System to identify pediatric patients hospitalized with pneumonia, neck infection, orbital infection, urinary tract infection (UTI), osteomyelitis, septic arthritis, or skin and soft tissue infection (SSTI) between 2017 and 2018. Opportunity days were defined as days on which patients received both IV antibiotics and enteral medications, suggesting enteral tolerance. Percent opportunity was defined as opportunity days divided by days on any antibiotics. Both outcomes excluded IV antibiotics that have no alternative oral formulation. We evaluated outcomes per infection and antibiotic and assessed across-hospital variation., Results: We identified 88,522 aggregate opportunity days in 100,103 hospitalizations. On 57% of the antibiotic days, there was an opportunity to switch patients to enteral therapy, with greatest opportunity days in SSTI, neck infection, and pneumonia encounters, and with clindamycin, ceftriaxone, and ampicillin-sulbactam. Percent opportunity varied by infection (73% in septic arthritis to 40% in pneumonia). There was significant across-hospital variation in percent opportunity for all infections., Conclusion: This multicenter study demonstrated the potential opportunity to transition from IV to enteral therapy in over half of antibiotic days. Opportunity varied by infection, antibiotic, and hospital. Across-hospital variation demonstrated likely missed opportunities for earlier transition and the need to define optimal transition times. Stewardship efforts promoting earlier transition for highly bioavailable antibiotics could reduce healthcare utilization and promote high-value care. We identified feasible stewardship metrics.

Background: Enhanced recovery after surgery pathways confer significant perioperative benefits to patients and are currently well described for adult patients undergoing a variety of surgical procedures. Robust data to support enhanced recovery pathway use in children are relatively lacking in the medical literature, though clinical benefits are reported in targeted pediatric surgical populations. Surgery for complex hip pathology in the adolescent patient is painful, often requiring prolonged courses of opioid analgesia. Postoperative opioid-related side effects may lead to prolonged recovery periods and suboptimal postoperative physical function. Excessive opioid use in the perioperative period is also a major risk factor for the development of opioid misuse in adolescents. Perioperative opioid reduction strategies in this vulnerable population will help to mitigate this risk., Methods: A total of 85 adolescents undergoing complex hip reconstructive surgery were enrolled into an enhanced recovery after surgery pathway (October 2015 to December 2018) and were compared with 110 patients undergoing similar procedures in previous years (March 2010 to September 2015). The primary outcome was total perioperative opioid consumption. Secondary outcomes included hospital length of stay, postoperative nausea, intraoperative blood loss, and other perioperative outcomes. Total cost of care and specific charge sectors were also assessed. Segmented regression was used to assess the effects of pathway implementation on outcomes, adjusting for potential confounders, including the preimplementation trend over time., Results: Before pathway implementation, there was a significant downward trend over time in average perioperative opioid consumption (-0.10 mg total morphine equivalents/90 days; 95% confidence interval [CI], -0.20 to 0.00) and several secondary perioperative outcomes. However, there was no evidence that pathway implementation by itself significantly altered the prepathway trend in perioperative opioid consumption (ie, the preceding trend continued). For postanesthesia care unit time, the downward trend leveled off significantly (pre: -5.25 min/90 d; 95% CI, -6.13 to -4.36; post: 1.04 min/90 d; 95% CI, -0.47 to 2.56; Change: 6.29; 95% CI, 4.53-8.06). Clinical, laboratory, pharmacy, operating room, and total charges were significantly associated with pathway implementation. There was no evidence that pathway implementation significantly altered the prepathway trend in other secondary outcomes., Conclusions: The impacts of our pediatric enhanced recovery pathway for adolescents undergoing complex hip reconstruction are consistent with the ongoing improvement in perioperative metrics at our institution but are difficult to distinguish from the impacts of other initiatives and evolving practice patterns in a pragmatic setting. The ERAS pathway helped codify and organize this new pattern of care, promoting multidisciplinary evidence-based care patterns and sustaining positive preexisting trends in financial and clinical metrics.

Background and Objectives: National estimates indicate that the incidence of neonatal abstinence syndrome (NAS), a postnatal opioid withdrawal syndrome, increased more than fivefold between 2004 and 2016. There is no gold standard definition for capturing NAS across clinical, research, and public health settings. Our objective was to evaluate how different definitions of NAS modify the calculated incidence when applied to a known population of opioid-exposed infants., Methods: Data for this retrospective cohort study were obtained from opioid-exposed infants born at Vanderbilt University Medical Center in 2018. Six commonly used clinical and surveillance definitions of opioid exposure and NAS were applied to the study population and evaluated for accuracy in assessing clinical withdrawal., Results: A total of 121 opioid-exposed infants met the criteria for inclusion in our study. The proportion of infants who met criteria for NAS varied by predefined definition, ranging from 17.4% for infants who received morphine to 52.8% for infants with the diagnostic code for opioid exposure. Twenty-eight infants (23.1%) received a clinical diagnosis of NAS by a medical provider, and 38 (34.1%) received the diagnostic code for NAS at discharge., Conclusions: We found significant variability in the incidence of opioid exposure and NAS among a single-center population using 6 common definitions. Our findings suggest a need to develop a gold standard definition to be used across clinical, research, and public health surveillance settings., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

The financial impact of the rising number of pediatric mental health hospitalizations is unknown. Therefore, this study assessed costs, reimbursements, and net profits or losses for 111,705 mental health and non-mental health medical hospitalizations in children's hospitals with use of the Pediatric Health Information System and Revenue Management Program. Average financial margins were calculated as (reimbursement per day) - (cost per day), and they were lowest for mental health hospitalizations ($136/day), next lowest for suicide attempt ($518/day), and highest for other medical hospitalizations ($611/day). For 10 of 17 hospitals, margin per day for mental health hospitalizations was lower than margin per day for other medical hospitalizations. For these 10 hospitals, the total net loss for inpatient and observation status mental health hospitalizations, compared with other medical hospitalizations, was $27 million (median, $2.2 million per hospital). Financial margins were usually lower for mental health vs non-mental health medical hospitalizations.

Bromodomains exhibit preferences for specific patterns of post-translational modifications on core and variant histone proteins. We examined the ligand specificity of the ATAD2B bromodomain and compared it to its closely related paralogue in ATAD2. We show that the ATAD2B bromodomain recognizes mono- and diacetyllysine modifications on histones H4 and H2A. A structure-function approach was used to identify key residues in the acetyllysine-binding pocket that dictate the molecular recognition process, and we examined the binding of an ATAD2 bromodomain inhibitor by ATAD2B. Our analysis demonstrated that critical contacts required for bromodomain inhibitor coordination are conserved between the ATAD2/B bromodomains, with many residues playing a dual role in acetyllysine recognition. We further characterized an alternative splice variant of ATAD2B that results in a loss of function. Our results outline the structural and functional features of the ATAD2B bromodomain and identify a novel mechanism regulating the interaction of the ATAD2B protein with chromatin.

Background and Objectives: Length of stay (LOS) is a common benchmarking measure for hospital resource use and quality. Observation status (OBS) is considered an outpatient service despite the use of the same facilities as inpatient status (IP) in most children's hospitals, and LOS calculations often exclude OBS stays. Variability in the use of OBS by hospitals may significantly impact calculated LOS. We sought to determine the impact of including OBS in calculating LOS across children's hospitals., Methods: Retrospective cohort study of hospitalized children (age <19 years) in 2017 from the Pediatric Health Information System (Children's Hospital Association, Lenexa, KS). Normal newborns, transfers, deaths, and hospitals not reporting LOS in hours were excluded. Risk-adjusted geometric mean length of stay (RA-LOS) for IP-only and IP plus OBS was calculated and each hospital was ranked by quintile., Results: In 2017, 45 hospitals and 625 032 hospitalizations met inclusion criteria (IP = 410 731 [65.7%], OBS = 214 301 [34.3%]). Across hospitals, OBS represented 0.0% to 60.3% of total discharges. The RA-LOS (SD) in hours for IP and IP plus OBS was 75.2 (2.6) and 54.3 (2.7), respectively ( P < .001). For hospitals reporting OBS, the addition of OBS to IP RA-LOS calculations resulted in a decrease in RA-LOS compared with IP encounters alone. Three-fourths of hospitals changed ≥1 quintile in LOS ranking with the inclusion of OBS., Conclusions: Children's hospitals exhibit significant variability in the assignment of OBS to hospitalized patients and inclusion of OBS significantly impacts RA-LOS calculations. Careful consideration should be given to the inclusion of OBS when determining RA-LOS for benchmarking, quality and resource use measurements., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: In several states, payers penalize hospitals when an inpatient readmission follows an inpatient stay. Observation stays are typically excluded from readmission calculations. Previous studies suggest inconsistent use of observation designations across hospitals. We sought to describe variation in observation stays and examine the impact of inclusion of observation stays on readmission metrics., Methods: We conducted a retrospective cohort study of hospitalizations at 50 hospitals contributing to the Pediatric Health Information System database from January 1, 2018, to December 31, 2018. We examined prevalence of observation use across hospitals and described changes to inpatient readmission rates with higher observation use. We described 30-day inpatient-only readmission rates and ranked hospitals against peer institutions. Finally, we included observation encounters into the calculation of readmission rates and evaluated hospitals' change in readmission ranking., Results: Most hospitals ( n = 44; 88%) used observation status, with high variation in use across hospitals (0%-53%). Readmission rate after index inpatient stay (6.8%) was higher than readmission after an index observation stay (4.4%), and higher observation use by hospital was associated with higher inpatient-only readmission rates. When compared with peers, hospital readmission rank changed with observation inclusion (60% moving at least 1 quintile)., Conclusions: The use of observation status is variable among children's hospitals. Hospitals that more liberally apply observation status perform worse on the current inpatient-to-inpatient readmission metric, and inclusion of observation stays in the calculation of readmission rates significantly affected hospital performance compared with peer institutions. Consideration should be given to include all admission types for readmission rate calculation., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objectives: To assess hospital-level variation in laboratory testing and intravenous fluid (IVF) use and examine the association between these interventions and hospitalization outcomes among infants admitted with neonatal hyperbilirubinemia., Methods: We performed a retrospective multicenter study of infants aged 2 to 7 days hospitalized with a primary diagnosis of hyperbilirubinemia from December 1, 2016, to June 30, 2018, using the Pediatric Health Information System. Hospital-level variation in laboratory and IVF use was evaluated after adjusting for clinical and demographic factors and associated with hospital-level outcomes by using Pearson correlation., Results: We identified 4396 infants hospitalized with hyperbilirubinemia. In addition to bilirubin level, the most frequently ordered laboratories were direct antiglobulin testing (45.7%), reticulocyte count (39.7%), complete blood cell counts (43.7%), ABO blood type (33.4%), and electrolyte panels (12.9%). IVFs were given to 26.3% of children. Extensive variation in laboratory testing and IVF administration was observed across hospitals (all P < .001). Increased use of laboratory testing but not IVFs was associated with a longer length of stay ( P = .007 and .162, respectively). Neither supplementary laboratory use nor IVF use was associated with either readmissions or emergency department revisits., Conclusions: Substantial variation exists among hospitals in the management of infants with hyperbilirubinemia. With our results, we suggest that additional testing outside of bilirubin measurement may unnecessarily increase resource use for infants hospitalized with hyperbilirubinemia., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

PCE is a complication of HSCT that has previously been described in small single-center studies. This study aimed to assess the frequency of, risk factors for, and outcomes of children with a PCE following HSCT across a large multi-center cohort. All patients ≤21 years undergoing first HSCT (1/2005-9/2015) were identified from the Pediatric Health Information System. ICD-9 codes were used to identify patients with a PCE during or following the transplant encounter. Multivariable modeling assessed risk factors for developing a PCE and assessed the impact of PCE on patient outcome. Of 10 455 included patients, 739 (7.1%) developed a PCE (median 69 days post-HSCT, interquartile range 33-165 days). PCE developed more commonly in allogeneic vs autologous HSCT recipients (9.1% vs 2.9%, P < .001). Among allogeneic HSCT recipients, independent risk factors for PCE included thrombotic microangiopathy (AHR 2.94, 95% CI 2.16-4.00), heart failure (AHR 2.07, 95% CI 1.61-2.66), PCE pre-HSCT (AHR 1.92, 95% CI 1.19-3.09), arrhythmia (AHR 1.76, 95% CI 1.44-2.16), graft-versus-host disease (AHR 1.31, 95% CI 1.05-1.62), female sex (AHR 1.28, 95% CI 1.07-1.52), and malignancy (AHR 1.28, 95% CI 1.02-1.60). Allogeneic HSCT patients with PCE demonstrated worse survival than those without PCE (5-year survival 50.8% vs 76.9%, P < .001). PCE was independently associated with mortality (AHR 1.96, 95% CI 1.62-2.37) following allogeneic HSCT and was not impacted by pericardial intervention. PCE occurs more commonly in patients following allogeneic (vs autologous) HSCT and is associated with inferior outcomes., (© 2020 Wiley Periodicals LLC.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The author has indicated he has no potential conflicts of interest to disclose.

Objective: To examine how characteristics vary between children with any mental health (MH) diagnosis who have typical spending and the highest spending; to identify independent predictors of highest spending; and to examine drivers of spending groups., Methods: This retrospective analysis utilized 2016 Medicaid claims from 11 states and included 775,945 children ages 3 to 17 years with any MH diagnosis and at least 11 months of continuous coverage. We compared demographic characteristics and Medicaid expenditures based on total health care spending: the top 1% (highest-spending) and remaining 99% (typical-spending). We used chi-squared tests to compare the 2 groups and adjusted logistic regression to identify independent predictors of being in the top 1% highest-spending group., Results: Children with MH conditions accounted for 55% of Medicaid spending among 3- to 17-year olds. Patients in the highest-spending group were more likely to be older, have multiple MH conditions, and have complex chronic physical health conditions (P <.001). The highest-spending group had $164,003 per-member-per-year (PMPY) in total health care spending, compared to $6097 PMPY in the typical-spending group. Ambulatory MH services contributed the largest proportion (40%) of expenditures ($2455 PMPY) in the typical-spending group; general health hospitalizations contributed the largest proportion (36%) of expenditures ($58,363 PMPY) in the highest-spending group., Conclusions: Among children with MH conditions, mental and physical health comorbidities were common and spending for general health care outpaced spending for MH care. Future research and quality initiatives should focus on integrating MH and physical health care services and investigate whether current spending on MH services supports high-quality MH care., (Copyright © 2020 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: A national quality measure in the Child Core Set is used to assess whether pediatric patients hospitalized for a mental illness receive timely follow-up care. In this study, we examine the relationship between adherence to the quality measure and repeat use of the emergency department (ED) or repeat hospitalization for a primary mental health condition., Methods: We used the Truven MarketScan Medicaid Database 2015-2016, identifying hospitalizations with a primary diagnosis of depression, bipolar disorder, psychosis, or anxiety for patients aged 6 to 17 years. Primary predictors were outpatient follow-up visits within 7 and 30 days. The primary outcome was time to subsequent mental health-related ED visit or hospitalization. We conducted bivariate and multivariate analyses using Cox proportional hazard models to assess relationships between predictors and outcome., Results: Of 22 844 hospitalizations, 62.0% had 7-day follow-up, and 82.3% had 30-day follow-up. Subsequent acute use was common, with 22.4% having an ED or hospital admission within 30 days and 54.8% within 6 months. Decreased likelihood of follow-up was associated with non-Hispanic or non-Latino black race and/or ethnicity, fee-for-service insurance, having no comorbidities, discharge from a medical or surgical unit, and suicide attempt. Timely outpatient follow-up was associated with increased subsequent acute care use (hazard ratio [95% confidence interval]: 7 days: 1.20 [1.16-1.25]; 30 days: 1.31 [1.25-1.37]). These associations remained after adjusting for severity indicators., Conclusions: Although more than half of patients received follow-up within 7 days, variations across patient population suggest that care improvements are needed. The increased hazard of subsequent use indicates the complexity of treating these patients and points to potential opportunities to intervene at follow-up visits., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objectives: To identify variation in the proportion of blood cultures obtained for pediatric skin and soft tissue infections (SSTIs) among children's hospitals., Methods: We conducted a retrospective cohort study using the Pediatric Health Information System database, which we queried for emergency department (ED)-only and hospital encounters between 2012 and 2017 for children aged 2 months to 18 years with diagnosis codes for SSTI. The primary outcome was proportion of SSTI encounters during which blood cultures were obtained. Encounters with and without blood cultures were compared for length of stay, costs, and 30-day ED revisit and readmission rates, adjusted for patient factors and hospital clustering. We also identified encounters with bacteremia using billing codes for septicemia and bacteremia., Results: We identified 239 954 ED-only and 49 291 hospital SSTI encounters among 38 hospitals. Median proportions of ED-only and hospital encounters with blood cultures were 3.2% (range: 1%- 11%) and 51.6% (range: 25%-81%), respectively. Adjusted ED-only encounters with versus without blood culture had higher costs ($1266 vs $460, P < .001), higher ED revisit rates (3.6% vs 2.9%, P < .001), and higher admission rates (2.0% vs 0.9%, P < .001). Hospital encounters with blood culture had longer length of stay (2.3 vs 2.0 days, P < .001), higher costs ($5254 vs $4425, P < .001), and higher readmission rates (0.8% vs 0.7%, P = .027). The overall proportion of encounters with bacteremia was 0.6% for ED-only encounters and 1.0% for hospital encounters., Conclusions: Despite multiple studies in which low clinical value was demonstrated and current Infectious Diseases Society of America guidelines arguing against the practice, blood cultures were obtained frequently for children hospitalized with SSTIs, with substantial variation across institutions. Few bacteremic encounters were identified., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: Pediatric acute kidney injury (AKI) is common and associated with increased morbidity, mortality, and length of stay. We performed a pragmatic randomized trial testing the hypothesis that AKI risk alerts increase AKI screening., Methods: All intensive care and ward admissions of children aged 28 days through 21 years without chronic kidney disease from 12/6/2016 to 11/1/2017 were included. The intervention alert displayed if calculated AKI risk was > 50% and no serum creatinine (SCr) was ordered within 24 h. The primary outcome was SCr testing within 48 h of AKI risk > 50%., Results: Among intensive care admissions, 973/1909 (51%) were randomized to the intervention. Among those at risk, more SCr tests were ordered for the intervention group than for controls (418/606, 69% vs. 361/597, 60%, p = 0.002). AKI incidence and severity were the same in intervention and control groups. Among ward admissions, 5492/10997 (50%) were randomized to the intervention, and there were no differences between groups in SCr testing, AKI incidence, or severity of AKI., Conclusions: Alerts based on real-time prediction of AKI risk increased screening rates in intensive care but not pediatric ward settings. Pragmatic clinical trials provide the opportunity to assess clinical decision support and potentially eliminate ineffective alerts.

Many children's hospitals are actively working to reduce readmissions to improve care and avoid financial penalties. We sought to determine if pediatric readmission rates have changed over time. We used data from 66 hospitals in the Inpatient Essentials Database including index hospitalizations from January, 2010 through June, 2016. Seven-day all cause (AC) and potentially preventable readmission (PPR) rates were calculated using 3M PPR software. Total and condition-specific quarterly AC and PPR rates were generated for each hospital and in aggregate. We included 4.52 million hospitalizations across all study years. Readmission rates did not vary over the study period. The median seven-day PPR rate across all quarters was 2.5% (range 2.1%-2.5%); the median seven-day AC rate across all quarters was 5.1% (range 4.3%-5.3%). Readmission rates for individual conditions fluctuated. Despite significant national efforts to reduce pediatric readmissions, both AC and PPR readmission rates have remained unchanged over six years.

Importance: Adolescents and young adults (AYA) who have complex chronic disease (CCD) are a growing population that requires hospitalization to treat severe, acute health problems. These patients may have increased risk of readmission as demands on their self-management increase and as they transfer care from pediatric to adult health care practitioners., Objective: To assess variation across CCDs in the likelihood of readmission for AYA with increasing age., Design, Setting, and Participants: Retrospective 1-year cross-sectional study of the 2014 Agency for Healthcare Research and Quality Nationwide Readmissions Database for all US hospitals. Participants were 215 580 hospitalized individuals aged 15 to 30 years with cystic fibrosis (n = 15 213), type 1 diabetes (n = 86 853), inflammatory bowel disease (n = 48 073), spina bifida (n = 7819), and sickle cell anemia (n = 57 622) from January 1, 2014, to December 1, 2014., Exposures: Increasing age at index admission., Main Outcomes and Measures: Unplanned 30-day hospital readmission. Readmission odds were compared by patients' ages in 2-year epochs (with age 15-16 years as the reference) using logistic regression, accounting for confounding patient characteristics and data clustering by hospital., Results: Of 215 580 participants, 115 982 (53.8%) were female; the median (interquartile range) age was 24 (20-27) years. Across CCDs, multimorbidity was common; the percentages of index hospitalizations with 4 or more coexisting conditions ranged from to 33.4% for inflammatory bowel disease to 74.2% for spina bifida. Thirty-day hospital readmission rates varied significantly across CCDs: 20.2% (cystic fibrosis), 19.8% (inflammatory bowel disease), 20.4% (spina bifida), 22.5% (type 1 diabetes), and 34.6% (sickle cell anemia). As age increased from 15 to 30 years, unadjusted, 30-day, unplanned hospital readmission rates increased significantly for all 5 CCD cohorts. In multivariable analysis, age trends in the adjusted odds of readmission varied across CCDs. For example, for AYA who had cystic fibrosis, the adjusted odds of readmission increased to 1.9 (95% CI, 1.5-2.3) by age 21 years and remained elevated through age 30 years. For AYA who had type 1 diabetes, the adjusted odds of readmission peaked at ages 23 to 24 years (odds ratio, 2.3; 95% CI, 2.1-2.6) and then declined through age 30 years., Conclusions and Relevance: These findings suggest that hospitalized AYA who have CCDs have high rates of multimorbidity and 30-day readmission. The adjusted odds of readmission for AYA varied significantly across CCDs with increasing age. Further attention is needed to hospital discharge care, self-management, and prevention of readmission in AYA with CCD.

Background and Objectives: Although potentially dangerous, little is known about outpatient opioid exposure (OE) in children and youth with special health care needs (CYSHCN). We assessed the prevalence and types of OE and the diagnoses and health care encounters proximal to OE in CYSHCN., Methods: This is a retrospective cohort study of 2 597 987 CYSHCN aged 0-to-18 years from 11 states, continuously enrolled in Medicaid in 2016, with ≥1 chronic condition. OE included any filled prescription (single or multiple) for opioids. Health care encounters were assessed within 7 days before and 7 and 30 days after OE., Results: Among CYSHCN, 7.4% had OE. CYSHCN with OE versus without OE were older (ages 10-18 years: 69.4% vs 47.7%), had more chronic conditions (≥3 conditions: 49.1% vs 30.6%), and had more polypharmacy (≥5 other medication classes: 54.7% vs 31.2%), P < .001 for all. Most (76.7%) OEs were single fills with a median duration of 4 days (interquartile range: 3-6). The most common OEs were acetaminophen-hydrocodone (47.5%), acetaminophen-codeine (21.5%), and oxycodone (9.5%). Emergency department visits preceded 28.8% of OEs, followed by outpatient surgery (28.8%) and outpatient specialty care (19.1%). Most OEs were preceded by a diagnosis of infection (25.9%) or injury (22.3%). Only 35.1% and 62.2% of OEs were associated with follow-up visits within 7 and 30 days, respectively., Conclusions: OE in CYSHCN is common, especially with multiple chronic conditions and polypharmacy. In subsequent studies, researchers should examine the appropriateness of opioid prescribing, particularly in emergency departments, as well as assess for drug interactions with chronic medications and reasons for insufficient follow-up., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

The ATPase family, AAA domain-containing protein 2 (ATAD2) has a C-terminal bromodomain, which functions as a chromatin reader domain recognizing acetylated lysine on the histone tails within the nucleosome. ATAD2 is overexpressed in many cancers and its expression is correlated with poor patient outcomes, making it an attractive therapeutic target and potential biomarker. We solved the crystal structure of the ATAD2 bromodomain and found that it contains a disulfide bridge near the base of the acetyllysine binding pocket (Cys1057-Cys1079). Site-directed mutagenesis revealed that removal of a free C-terminal cysteine (C1101) residue greatly improved the solubility of the ATAD2 bromodomain in vitro. Isothermal titration calorimetry experiments in combination with the Ellman's assay demonstrated that formation of an intramolecular disulfide bridge negatively impacts the ligand binding affinities and alters the thermodynamic parameters of the ATAD2 bromodomain interaction with a histone H4K5ac peptide as well as a small molecule bromodomain ligand. Molecular dynamics simulations indicate that the formation of the disulfide bridge in the ATAD2 bromodomain does not alter the structure of the folded state or flexibility of the acetyllysine binding pocket. However, consideration of this unique structural feature should be taken into account when examining ligand-binding affinity, or in the design of new bromodomain inhibitor compounds that interact with this acetyllysine reader module., (© 2018 Wiley Periodicals, Inc.)

Objective: To inform resource allocation toward a continuum of care for youth at risk of suicide, we examined unplanned 30-day readmissions after pediatric hospitalization for either suicide ideation (SI) or suicide attempt (SA)., Methods: We conducted a retrospective cohort study of a nationally representative sample of 133,516 hospitalizations for SI or SA among 6- to 17-year-olds to determine prevalence, risk factors, and characteristics of 30-day readmissions using the 2013 and 2014 Nationwide Readmissions Dataset (NRD). Risk factors for readmission were modeled using logistic regression., Results: We identified 95,354 hospitalizations for SI and 38,162 hospitalizations for SA. Readmission rates within 30 days were 8.5% for SI and SA hospitalizations. Among 30-day readmissions, more than one-third (34.1%) occurred within 7 days. Among patients with any 30-day readmission, 11% had more than one readmission within 30 days. The strongest risk factors for readmission were SI or SA hospitalization in the 30 days preceding the index SI/SA hospitalization (adjusted odds ratio [AOR]: 3.14, 95% CI: 2.73-3.61) and hospitalization for other indications in the previous 30 days (AOR: 3.18, 95% CI: 2.67-3.78). Among readmissions, 94.5% were for a psychiatric condition and 63.4% had a diagnosis of SI or SA., Conclusions: Quality improvement interventions to reduce unplanned 30-day readmissions among children hospitalized for SI or SA should focus on children with a recent prior hospitalization and should be targeted to the first week following hospital discharge., Funding: Dr. Zima received funding from the Behavioral Health Centers of Excellence for California (SB852)., (© 2018 Society of Hospital Medicine.)

Objective: To evaluate and compare readmission causes and timing within the first 30 days after hospitalization for 3 acute and 3 chronic common pediatric conditions., Study Design: Data from the 2013 to 2014 Nationwide Readmissions Database were used to examine the daily percentage of readmissions occurring on days 1-30 and the leading causes of readmission after hospitalization for 3 acute (appendicitis, bronchiolitis/croup, and gastroenteritis) and 3 chronic (asthma, epilepsy, and sickle cell) conditions for patients aged 1-17 years (n = 2 753 488). Data were analyzed using Cox proportional hazards regression., Results: The 30-day readmission rates ranged from 2.6% (SE, 0.1) after hospitalizations for appendectomy to 19.1% (SE, 0.5) after hospitalizations for sickle cell anemia. More than 50% of 30-day readmissions after acute conditions occurred within 15 days after discharge, whereas readmissions after chronic conditions occurred more uniformly throughout the 30 days after discharge. Higher numbers of patient comorbidities were associated with increased risk of readmission at days 1-7, 8-15, and 16-30 after discharge for all conditions examined. Most 30-day readmissions after chronic conditions were for the same diagnosis or closely related conditions as the index admission (67% for asthma, 65% for seizure disorder, and 82% for sickle cell anemia) in contrast with 50% or fewer readmissions after acute conditions (46% for appendectomy, 47% for bronchiolitis/croup, and 19% for gastroenteritis)., Conclusions: The timing and causes of pediatric readmissions vary greatly across pediatric conditions. To be effective, strategies for reducing readmissions need to account for the index diagnosis to better target the highest risk period and causes for readmission., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In the Medicare population, measures of relative severity of illness (SOI) for hospitalized patents have been used in prospective payment models. Similar measures for pediatric populations have not been fully developed., Objective: To develop hospitalization resource intensity scores for kids (H-RISK) using pediatric relative weights (RWs) for SOI and to compare hospital types on case-mix index (CMI)., Design/methods: Using the 2012 Kids' Inpatient Database (KID), we developed RWs for each All Patient Refined Diagnosis Related Group (APR-DRG) and SOI level. RW corresponded to the ratio of the adjusted mean cost for discharges in an APR-DRG SOI combination over adjusted mean cost of all discharges in the dataset. RWs were applied to every discharge from 3,117 hospitals in the database with at least 20 discharges. RWs were then averaged at the hospital level to provide each hospital's CMI. CMIs were compared by hospital type using Kruskal- Wallis tests., Results: The overall adjusted mean cost of weighted discharges in Healthcare Cost and Utilization Project KID 2012 was $6,135 per discharge. Solid organ and bone marrow transplantations represented 4 of the 10 highest procedural RWs (range: 35.5 to 91.7). Neonatal APRDRG SOIs accounted for 8 of the 10 highest medical RWs (range: 19.0 to 32.5). Free-standing children's hospitals yielded the highest median (interquartile range [IQR]) CMI (2.7 [2.2-3.1]), followed by urban teaching hospitals (1.8 [1.3-2.6]), urban nonteaching hospitals (1.1 [0.9-1.5]), and rural hospitals (0.8 [0.7-0.9]; P < .001)., Conclusions: H-RISK for populations of pediatric admissions are sensitive to detection of substantial differences in SOI by hospital type., (© 2018 Society of Hospital Medicine.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The author has indicated he has no potential conflicts of interest to disclose.