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Objective: Polypharmacy increases the risk of drug-drug interactions and adverse drug events. As obesity and rates of obesity-associated comorbid chronic conditions continue to rise, an improved understanding of whether children with obesity experience higher risk of polypharmacy is needed. This study aimed to compare chronic medication polypharmacy prevalence among children with and without a diagnosis of obesity., Methods: We performed a cross-sectional examination of prescription data for children aged 2-18 years prescribed ≥1 chronic medication using the 2019 Marketscan Medicaid database. Children with documented obesity were identified using medical visit diagnosis codes. Chronic medications included any ≥30-day prescription with ≥2 dispensed refills. Polypharmacy was defined as the prescription of ≥2 chronic medications for ≥1 overlapping days. Chi-squared tests compared polypharmacy prevalence and the distribution of chronic medication classes between children with and without obesity. Logistic regression determined the adjusted odds ratio (aOR) of polypharmacy for children with obesity, adjusting for relevant demographic and clinical differences., Results: Of 634,671 included children, 12.2% had documented obesity. More than one-half (52.7%) of children with obesity experienced polypharmacy compared with 47.6% of children without obesity (aOR 1.06 [95% confidence interval 1.04-1.08]). Chronic medication prescriptions, particularly for psychiatric and asthma medications, were more commonly prescribed among children with obesity than those without obesity., Conclusions: Children with documented obesity have higher polypharmacy prevalence than children without obesity. Clinicians must be aware of this risk and minimize inappropriate polypharmacy whenever possible. Future work should examine the consequences of polypharmacy, including drug-drug interactions and adverse drug events in children with obesity., (© 2022 Pharmacotherapy Publications, Inc.)

Chemical solution deposition (CSD) methods involving the thermal decomposition of 5.0 M Er(NO 3 ) 3 ·5H 2 O and Y(NO 3 ) 3 ·6H 2 O precursor solutions were employed to fabricate protective erbia and yttria coatings onto stainless steel (SS304/SS316) coupons. The two techniques tested were dip and spray coating, which were then compared to a commercial yttria spray (ZYP Coatings). It was determined that solution concentration, solvent choice, injection of Er 2 O 3 and Y 2 O 3 micropowder, and the annealing temperature/ramp profile were critical to the coatings' physical properties. For dip coatings, thicknesses were 1-20 μm after two dipping/annealing cycles, and adhesion strength was ∼1000 psi, increasing up to ∼1300 psi if the SS coupons had preliminary sandblasting. Spray coatings from precursor solutions were reported to have thicknesses of 20-80 μm and adhesion strength less than 500 psi (regardless of the coupon surface finish). Cross-sectional views of the coatings confirmed subsurface porosity, and XRD results indicated that the coatings were polycrystalline, with patterns typical to that of cubic Er 2 O 3 and Y 2 O 3 .

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: Electronic health record-based clinical decision support (CDS) is a promising antibiotic stewardship strategy. Few studies have evaluated the effectiveness of antibiotic CDS in the pediatric emergency department (ED)., Objective: To compare the effectiveness of antibiotic CDS vs. usual care for promoting guideline-concordant antibiotic prescribing for pneumonia in the pediatric ED., Design: Pragmatic randomized clinical trial., Setting and Participants: Encounters for children (6 months-18 years) with pneumonia presenting to two tertiary care children s hospital EDs in the United States., Intervention: CDS or usual care was randomly assigned during 4-week periods within each site. The CDS intervention provided antibiotic recommendations tailored to each encounter and in accordance with national guidelines., Main Outcome and Measures: The primary outcome was exclusive guideline-concordant antibiotic prescribing within the first 24 h of care. Safety outcomes included time to first antibiotic order, encounter length of stay, delayed intensive care, and 3- and 7-day revisits., Results: 1027 encounters were included, encompassing 478 randomized to usual care and 549 to CDS. Exclusive guideline-concordant prescribing did not differ at 24 h (CDS, 51.7% vs. usual care, 53.3%; odds ratio [OR] 0.94 [95% confidence interval [CI]: 0.73, 1.20]). In pre-specified stratified analyses, CDS was associated with guideline-concordant prescribing among encounters discharged from the ED (74.9% vs. 66.0%; OR 1.53 [95% CI: 1.01, 2.33]), but not among hospitalized encounters. Mean time to first antibiotic was shorter in the CDS group (3.0 vs 3.4 h; p = .024). There were no differences in safety outcomes., Conclusions: Effectiveness of ED-based antibiotic CDS was greatest among those discharged from the ED. Longitudinal interventions designed to target both ED and inpatient clinicians and to address common implementation challenges may enhance the effectiveness of CDS as a stewardship tool., (© 2023 Society of Hospital Medicine.)

De novo mutations in GNB1 , encoding the G β 1 subunit of G proteins, cause a neurodevelopmental disorder with global developmental delay and epilepsy, GNB1 encephalopathy. Here, we show that mice carrying a pathogenic mutation, K78R, recapitulate aspects of the disorder, including developmental delay and generalized seizures. Cultured mutant cortical neurons also display aberrant bursting activity on multi-electrode arrays. Strikingly, the antiepileptic drug ethosuximide (ETX) restores normal neuronal network behavior in vitro and suppresses spike-and-wave discharges (SWD) in vivo . ETX is a known blocker of T-type voltage-gated Ca 2+ channels and G protein-coupled potassium (GIRK) channels. Accordingly, we present evidence that K78R results in a gain-of-function (GoF) effect by increasing the activation of GIRK channels in cultured neurons and a heterologous model ( Xenopus oocytes)-an effect we show can be potently inhibited by ETX. This work implicates a GoF mechanism for GIRK channels in epilepsy, identifies a new mechanism of action for ETX in preventing seizures, and establishes this mouse model as a pre-clinical tool for translational research with predicative value for GNB1 encephalopathy., Competing Interests: DG is a founder of Actio Biosciences, a founder of and holds equity in Praxis, serves as a consultant to AstraZeneca, and has received research support from Janssen, Gilead, Biogen, AstraZeneca and UCB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Colombo, Reddy, Petri, Williams, Shalomov, Dhindsa, Gelfman, Krizay, Bera, Yang, Peng, Makinson, Boland, Frankel, Goldstein and Dascal.)

There is increasing recognition of the public health importance of snakebite envenoming. Worldwide annual incidence is likely to be 5 million bites, with mortality exceeding 150 000 deaths, and the resulting physical and psychological morbidity leads to substantial social and economic repercussions. Prevention through community education by trained health workers is the most effective and economically viable strategy for reducing risk of bites and envenoming. Clinical challenges to effective treatment are most substantial in rural areas of low-resource settings, where snakebites are most common. Classic skills of history taking, physical examination, and use of affordable point-of-care tests should be followed by monitoring of evolving local and systemic envenoming. Despite the profusion of new ideas for interventions, hyperimmune equine or ovine plasma-derived antivenoms remain the only specific treatment for snakebite envenoming. The enormous interspecies and intraspecies complexity and diversity of snake venoms, revealed by modern venomics, demands a radical redesign of many current antivenoms., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Children are at increased risk for medication errors and the transition from hospital-to-home is a vulnerable time for errors to occur. This study aimed to explore the perspectives of multidisciplinary clinicians and caregivers regarding discharge medication counseling and to develop a conceptual model to inform intervention efforts to reduce discharge medication dosing errors., Methods: We conducted semistructured interviews with clinicians and caregivers of children <4 years old discharged from the hospital on a liquid medication. A hierarchical coding system was developed using the interview guide and several transcripts. Qualitative analysis employed an iterative inductive-deductive approach to identify domains and subthemes and inform a conceptual framework., Results: We conducted focus groups and individual interviews with 17 caregivers and 16 clinicians. Using the Donabedian structure-process-outcomes model of quality evaluation, domains and subthemes included: (1) infrastructure of healthcare delivery, including supplies for counseling, content and organization of discharge instructions, clinician training and education, roles and responsibilities of team members, and hospital pharmacy delivery and counseling program; (2) processes of healthcare delivery, including medication reconciliation, counseling content, counseling techniques, and language barriers and health literacy; and (3) measurable outcomes, including medication dosing accuracy and caregiver understanding and adherence to discharge instructions., Conclusions: The conceptual model resulting from this analysis can be applied to the development and evaluation of interventions to reduce discharge medication dosing errors following a hospitalization. Interventions should use a health literacy universal precautions approach-written materials with plain language and pictures and verbal counseling with teach-back and show-back., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Penicillin (PCN) allergy labels are widely recognized to be highly inaccurate. Little is known about parental perceptions of the PCN allergy evaluation and removal process, especially in the hospital setting., Methods: Focus groups were held with parents of children and adolescents with a PCN allergy label discharged from a large academic children's hospital between January 1, 2019, and April 15, 2020. The open-ended, semistructured moderator guide included questions about PCN allergy testing and evaluation, accuracy of the PCN allergy diagnosis, amoxicillin oral challenges, delabeling process, and preferred setting for PCN allergy delabeling evaluation (outpatient clinic, hospital, etc). Study investigators coded the transcripts and identified underlying themes using inductive and deductive thematic analysis., Results: A total of 21 parents and 2 adolescents participated across 4 focus groups. We developed a theoretical framework depicting key elements of parents' and adolescents' experiences with PCN allergies, consisting of 4 major interconnected themes: (1) family context; (2) the invitation to delabel; (3) decision context; and (4) the PCN delabeling outcome. PCN allergies remained a concern for families even if their children passed an oral challenge. Some parents preferred testing to be performed in the hospital and felt this was a safer location for the procedure., Conclusions: Parents are amenable to hospital based PCN allergy evaluation and delabeling. Further studies should incorporate parental and patient preferences to implement safe and effective PCN allergy delabeling processes in the hospital setting., (Copyright © 2023 by the American Academy of Pediatrics.)

A two-dimensional (2D) mixture in the form of a self-assembled monolayer composed of two distinct organothiol compounds was created by sequentially depositing 1-naphthalenethiol (1NT) and octanethiol (OT) on a gold surface. By varying the sequence of deposition, two mixed surface systems were created. The surface structure of the resulting mixed monolayer was characterized with Scanning Tunneling Microscopy (STM) and showed surface disorder across all investigated domains. Elemental analysis was carried out with X-ray Photoelectron Spectroscopy (XPS) and indicated that the 1NT monolayer was prone to significant oxidation. Reductive desorption (RD) was used to characterize the binding strength and electrochemical environments of the molecular components in the mixture, and confirmed disordered molecular layers. Due to the presence of oxidized species in the 1NT monolayer, 1NT was displaced by OT resulting in a novel surface structure composed of either OT or 1NT. Monolayers of OT that were exposed to a solution of 1NT resulted in disordered surface structures with a significant amount of gold vacancy islands. To date, there is no experimental phase diagram explaining the chemical behavior of two-dimensional mixtures. This study addresses the need for an experimental understanding of the phase behavior of mixed organothiol self-assembled monolayers (SAMs)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: National guidelines recommend antiviral treatment for children with influenza at high risk for complications regardless of symptom duration. Little is known about concordance of clinical practice with this recommendation., Methods: We performed a cross-sectional study of outpatient children (aged 1-18 years) at high risk for complications who were diagnosed with influenza during the 2016-2019 influenza seasons. High-risk status was determined using an existing definition that includes age, comorbidities, and residence in a long-term care facility. The primary outcome was influenza antiviral dispensing within 2 days of influenza diagnosis. We determined patient- and provider-level factors associated with guideline-concordant treatment using multivariable logistic regression., Results: Of the 274 213 children with influenza at high risk for influenza complications, 159 350 (58.1%) received antiviral treatment. Antiviral treatment was associated with the presence of asthma (aOR, 1.13; 95% confidence interval [CI], 1.11-1.16), immunosuppression (aOR, 1.10; 95% CI, 1.05-1.16), complex chronic conditions (aOR, 1.04; 95% CI, 1.01-1.07), and index encounter in the urgent care setting (aOR, 1.3; 95% CI, 1.26-1.34). Factors associated with decreased odds of antiviral treatment include age 2-5 years compared with 6-17 years (aOR, 0.95; 95% CI, .93-.97), residing in a chronic care facility (aOR, .61; 95% CI, .46-.81), and index encounter in an emergency department (aOR, 0.66; 95% CI, .63-.71)., Conclusions: Among children with influenza at high risk for complications, 42% did not receive guideline-concordant antiviral treatment. Further study is needed to elucidate barriers to appropriate use of antivirals in this vulnerable population., Competing Interests: Potential conflicts of interest . C. G. G. has received consulting fees from Pfizer, Sanofi, and Merck and grants or contracts paid to their institution from Campbell Alliance/Syneos Health, Sanofi, the Centers for Disease Control and Prevention (CDC), Agency for Healthcare Research and Quality (AHRQ), NIH, and US Food and Drug Administration. D. J. W. has received in-kind research support from bioMérieux and reports grants or contracts paid to their institution from NIAID, CDC, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and National Heart, Lung, and Blood Institute (NHLBI); served as division chief of the Division of Hospital Medicine, Vanderbilt University Medical Center; and served on the Executive Committee–Pediatric Research in Inpatient Setting. J. W. A. reports grants or contracts unrelated to this work from a Turner Hazinski Research Award–Vanderbilt University Medical Center, Young Investigator Award–Academic Pediatric Association, Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub Pilot Funding–NIH NICHD, and an NIH NHLBI K12 award, all paid to their institution; and payment to author for expert testimony from Lewis Rice, LLC, unrelated to this work. J. L. G. reports grants or contracts from the NICDH and the National Institute of General Medical Sciences unrelated to this work and paid to their institution and payment or honoraria paid to author from the American Academy of Pediatrics (presentation) and the Missouri Association of School Nurses (honoraria). S. T. G. reports a Gerber Foundation Novice Research Award and Eunice Kennedy Shriver National Institute of Child Health and Human Development award unrelated to this work; participation on a University of Cincinnati data and safety monitoring board for an NICHD R01-funded protocol; and serving as a member of the American Society of Clinical Pharmacology & Therapeutics (ASCPT) By Laws Committee, ASCPT Scientific Programming Committee, and ASCPT Career Development. S. S. S. reports grant funding from the Children’s Hospital Association to their institution to develop a quality dashboard and grant funding to institution from Patient-Centered Outcomes Research Institute and AHRQ. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Children in mental health crises are increasingly admitted to children's hospitals awaiting inpatient psychiatric placement. During hospitalization, patients may exhibit acute agitation prompting pharmacologic restraint use., Objective: To determine hospital-level incidence and variation of pharmacologic restraint use among children admitted for mental health conditions in children's hospitals., Design, Setting, and Participants: We examined data for children (5 to ≤18 years) admitted to children's hospitals with a primary mental health condition from 2018 to 2020 using the Pediatric Health Information System database. Hospital rates of parenteral pharmacologic restraint use per 1000 mental health bed days were determined and compared after adjusting for patient-level and demographic factors. Cluster analysis (k-means) was used to group hospitals based on overall restraint use (rate quartiles) and drug class. Hospital-level factors for pharmacologic restraint use were compared., Results: Of 29,834 included encounters, 3747 (12.6%) had pharmacologic restraint use. Adjusted hospital rates ranged from 35 to 389 pharmacologic restraint use days per 1000 mental health bed days with a mean of 175 (standard deviation: 72). Cluster analysis revealed three hospitals were high utilizers of all drug classes. No significant differences in pharmacologic restraint use were found in the hospital-level analysis., Conclusions: Children's hospitals demonstrate wide variation in pharmacologic restraint rates for mental health hospitalizations, with a 10-fold difference in adjusted rates between highest and lowest utilizers, and high overall utilizers order medications across all drug classes., (© 2022 Society of Hospital Medicine.)

Helminth infections of cattle place significant burdens on livestock production and farm economic efficiency. Heavy infections are relatively easy to detect and treat with anthelmintics. However, subclinical infections have major but often hidden impacts on animals, necessitating more refined diagnostics to detect them and ideally inform farmers about the likely impact of anthelmintic treatment on animal and herd performance. Here, we review recent advances in diagnosing three major cattle helminth infections - gastrointestinal nematodes (GINs), liver flukes, and lungworms - and the search for subclinical infection thresholds to guide treatment decisions. Combining refined diagnostic thresholds with farm-specific information on grazing systems and animal history enables farmers to tailor helminth treatments to specific epidemiological circumstances, thereby limiting anthelmintic resistance (AR) and boosting agricultural efficiency and food security., Competing Interests: Declaration of interests J.C. and E.C. are involved in a license agreement between Ghent University and INDICAL Bioscience GmbH for commercialization of SVANOVIR® O. ostertagi-Ab and F. hepatica-Ab ELISA. The authors declare no other known conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to its unique physical and chemical properties, bismuth is an attractive candidate for a wide range of applications such as battery anodes, radiation shielding, and semiconductors, to name a few. This work presents the electrodeposition of mechanically stable and homogenous bismuth films at micron-scale thicknesses. A simple one-step electrodeposition process using either a pulse/reverse or direct current source yielded thick, homogenous, and mechanically stable bismuth films. Morphology, electrochemical behavior, adhesion, and mechanical stability of bismuth coatings plated with varying parameters were characterized via optical profilometry, cyclic voltammetry, electron microscopy, and tribology. Scratch testing on thick electroplated coatings (> 100 µm) revealed similar wear resistance properties between the pulse/reverse plated and direct current electroplated films. This study presents a versatile bismuth electroplating process with the possibility to replace lead in radiation shields with an inexpensive, non-toxic metal, or to make industrially relevant electrocatalytic devices., (© 2023. The Author(s).)

Background: Older people experience greater morbidity with a corresponding increase in medication use resulting in a potentially higher risk of adverse drug reactions (ADRs). Objectives: The aim of this study was to; 1) determine the prevalence and characteristics of ADR-related hospital admissions among older patients (≥65 years) in Ireland; and 2) identify the risk factors associated with ADR-related hospital admissions. Methods: A cross-sectional study of ADR prevalence in patients aged ≥65 years admitted acutely to hospital in Ireland over a 8 month period (November 2016- June 2017). A multifaceted review of each hospital admission was undertaken to assess the likelihood of an ADR being a reason for admission (cause of admission or contributing to admission) in the context of the patient's medication, clinical conditions, comorbidities and investigations. A number of decision aids were applied by two independent reviewers to assess ADR causality, avoidability and severity. A random sample of patients, determined not to have a suspected ADR on screening, were assigned to a non-ADR control group. Multivariable logistic regression was used to assess the association between potential risk factors for ADR-related admissions compared with non-ADR-related admissions. Results: In total, 3,760 hospital admission episodes (in 3,091 patients) were screened and 377 admissions were considered ADR-related (10.0%, 95% CI 9.1%, 11.0%). 219 (58.1%) ADR-related admissions were caused by an ADR, while ADRs contributed to 158 (41.9%) admissions. 268 (71.1%) of all ADR-related admissions were deemed definitely or possibly preventable/avoidable. 350 (92.8%) ADRs were classified as being of moderate severity, with 27 (7.2%) classified as severe. Antithrombotic agents, mainly aspirin and warfarin, were the drugs most frequently associated with ADR-related admissions (gastrointestinal and vascular haemorrhagic disorders). In multivariable analysis, immobility, frailty, having delirium or ulcer disease and taking anticoagulant and antiplatelet medication on admission were significantly associated with an ADR-related hospital admission. Conclusion: One in ten hospital admissions, among those aged 65 + years, were considered ADR-related, with approximately 70% potentially avoidable. Reliable and validated ADR detection and prediction tools are needed to develop prevention strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cahir, Curran, Walsh, Hickey, Brannigan, Kirke, Williams and Bennett.)

Background: The number of youth presenting to hospitals with suicidality and/or self-harm has increased substantially in recent years. We implemented a multihospital quality improvement (QI) collaborative from February 1, 2018 to January 31, 2019, aiming for an absolute increase in hospitals' mean rate of caregiver lethal means counseling (LMC) of 10 percentage points (from a baseline mean performance of 68% to 78%) by the end of the collaborative, and to evaluate the effectiveness of the collaborative on LMC, adjusting for secular trends., Methods: This 8 hospital collaborative used a structured process of alternating learning sessions and action periods to improve LMC across hospitals. Electronic medical record documentation of caregiver LMC was evaluated during 3 phases: precollaborative, active QI collaborative, and postcollaborative. We used statistical process control to evaluate changes in LMC monthly. Following collaborative completion, interrupted time series analyses were used to evaluate changes in the level and trend and slope of LMC, adjusting for covariates., Results: In the study, 4208 children and adolescents were included-1314 (31.2%) precollaborative, 1335 (31.7%) during the active QI collaborative, and 1559 (37.0%) postcollaborative. Statistical process control analyses demonstrated that LMC increased from a hospital-level mean of 68% precollaborative to 75% (February 2018) and then 86% (October 2018) during the collaborative. In interrupted time series analyses, there were no significant differences in LMC during and following the collaborative beyond those expected based on pre-collaborative trends., Conclusions: LMC increased during the collaborative, but the increase did not exceed expected trends. Interventions developed by participating hospitals may be beneficial to others aiming to improve LMC for caregivers of hospitalized youth with suicidality., (Copyright © 2022 by the American Academy of Pediatrics.)

The field of kink (or BDSM) studies has grown significantly in recent years, with several areas of study being initiated. This paper summarizes the current state of kink research, including prevalence rates; marginalization and stigma; key biological, psychological, and social research findings; clinical issues; and recommendations for further research. Theoretical frameworks, such as minority stress, serious leisure, sexual orientation, personal growth, and sensation-seeking theories appear to be useful frameworks outside of approaches that assume psychopathology as an etiological factor. Studies find the following results: higher levels of sensation-seeking; kink activities generating states of flow and transient hypofrontality; notable levels of gender, sexual orientation, and relationship style diversity in kink samples; and higher levels of minority stress-related suicidality., Competing Interests: Conflict of interest statement The authors declare no conflicts of interest associated with this paper., (Published by Elsevier Ltd.)

Introduction : Interventions designed to improve safety culture in hospitals foster organisational environments that prevent patient safety events and support organisational and staff learning when events do occur. A safety culture supports the required health workforce behaviours and norms that enable safe patient care, and the well-being of patients and staff. The impact of safety culture interventions on staff perceptions of safety culture and patient outcomes has been established. To-date, however, there is no common understanding of what staff outcomes are associated with interventions to improve safety culture and what staff outcomes should be measured. Objectives : The study seeks to examine the effect of safety culture interventions on staff in hospital settings, globally. Methods and Analysis : A mixed methods systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches will be conducted using the electronic databases of MEDLINE, EMBASE, CINAHL, Health Business Elite, and Scopus. Returns will be screened in Covidence according to inclusion and exclusion criteria. The mixed-methods appraisal tool (MMAT) will be used as a quality assessment tool. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials and non-randomised studies of interventions will be employed to verify bias. Synthesis will follow the Joanna Briggs Institute methodological guidance for mixed methods reviews, which recommends a convergent approach to synthesis and integration. Discussion : This systematic review will contribute to the international evidence on how interventions to improve safety culture may support staff outcomes and how such interventions may be appropriately designed and implemented., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Finn M et al.)

Objective: Neighborhood conditions influence child health outcomes, but data examining association between local factors and hospital utilization are lacking. We determined if hospitals' mix of patients by neighborhood opportunity correlates with rehospitalization for common diagnoses at US children's hospitals., Methods: We analyzed all discharges in 2018 for children ≤18 years at 47 children's hospitals for 14 common diagnoses. The exposure was hospital-level mean neighborhood opportunity - measured by Child Opportunity Index (COI) - for each diagnosis. The outcome was same-cause rehospitalization within 365 days. We measured association via Pearson correlation coefficient. For diagnoses with significant associations, we also examined shorter rehospitalization time windows and compared unadjusted and COI-adjusted rehospitalization rates., Results: There were 256,871 discharges included. Hospital-level COI ranged from 17th to 70th percentile nationally. Hospitals serving lower COI neighborhoods had more frequent rehospitalization for asthma (ρ -0.34 [95% confidence interval -0.57, -0.06]) and diabetes (ρ -0.33 [-0.56, -0.04]), but fewer primary mental health rehospitalizations (ρ 0.47 [0.21, 0.67]). There was no association for 11 other diagnoses. Secondary timepoint analysis revealed increasing correlation over time, with differences by diagnosis. Adjustment for hospital-level COI resulted in 26%, 32%, and 45% of hospitals changing >1 decile in rehospitalization rank order for diabetes, asthma, and mental health diagnoses, respectively., Conclusions: Children's hospitals vary widely in their mix of neighborhoods served. Asthma, diabetes, and mental health rehospitalization rates correlate with COI, suggesting that neighborhood factors may influence outcome disparities for these conditions. Hospital outcomes may be affected by neighborhood opportunity, which has implications for benchmarking., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the epidemiology and outcomes of neurologic complications associated with coronavirus disease 2019 (COVID-19) in children., Methods: We performed a cross-sectional study of children 2 months to &lt;18 years of age with COVID-19 discharged from 52 children's hospitals from March 2020 to March 2022. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye's syndrome, and cerebral infarction. We assessed length of stay (LOS), ICU admission, 30 day readmissions, deaths, and hospital costs. We used multivariable logistic regression to identify factors associated with neurologic complications., Results: Of 15 137 children hospitalized with COVID-19, 1060 (7.0%) had a concurrent diagnosis of a neurologic complication. The most frequent neurologic complications were febrile seizures (3.9%), nonfebrile seizures (2.3%), and encephalopathy (2.2%). Hospital LOS, ICU admission, ICU LOS, 30 day readmissions, deaths, and hospital costs were higher in children with neurologic complications compared with those without complications. Factors associated with lower odds of neurologic complications included: younger age (adjusted odds ratio [aOR]: 0.97; 95% confidence interval [CI]: 0.96-0.98), occurrence during delta variant predominant time period (aOR: 0.71; 95% CI: 0.57-0.87), presence of a nonneurologic complex chronic condition (aOR: 0.80; 95% CI: 0.69-0.94). The presence of a neurologic complex chronic condition was associated with higher odds of neurologic complication (aOR 4.14, 95% CI 3.48-4.92)., Conclusions: Neurologic complications are common in children hospitalized with COVID-19 and are associated with worse hospital outcomes. Our findings emphasize the importance of COVID-19 immunization in children, especially in high-risk populations, such as those with neurologic comorbidity., (Copyright © 2022 by the American Academy of Pediatrics.)

The authors argue that their target is orthogonal to the realism and instrumentalist debate. I argue that it is born directly from it. While the distinction is helpful in illuminating how some ontological commitments demand a theory of implementation, it's less clear whether different views cleanly map onto the epistemic and metaphysical uses defined in the paper.

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotics. We examined the gastrointestinal microbiota in children treated with β-lactams for community-acquired pneumonia. Data were from 66 children (n = 198 samples), aged 6-71 months, enrolled in the SCOUT-CAP trial (NCT02891915). AAD was defined as ≥1 day of diarrhea. Stool samples were collected on study days 1, 6-10, and 19-25. Samples were analyzed using 16S ribosomal RNA gene sequencing to identify associations between patient characteristics, microbiota characteristics, and AAD (yes/no). Nineteen (29%) children developed AAD. Microbiota compositional profiles differed between AAD groups (permutational multivariate analysis of variance, P < .03) and across visits (P < .001). Children with higher baseline relative abundances of 2 Bacteroides species were less likely to experience AAD. Higher baseline abundance of Lachnospiraceae and amino acid biosynthesis pathways were associated with AAD. Children in the AAD group experienced prolonged dysbiosis (P < .05). Specific gastrointestinal microbiota profiles are associated with AAD in children., Competing Interests: Potential conflicts of interest. V. G. F. reports personal consultancy fees from Novartis, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, The Medicines Co, Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Basilea, Affinergy, Janssen, xBiotech, Contrafect, Regeneron, Basilea, Destiny, Amphliphi Biosciences. Integrated Biotherapeutics; C3J, Armata, Valanbio, Akagera, and Aridis; reports grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Basilea, and Janssen; has received royalties from UpToDate and stock options from Valanbio; has a patent pending in sepsis diagnostics; has received educational fees from Green Cross, Cubist, Cerexa, Durata, Theravance, and Debiopharm; and has received an editor’s stipend from the Infectious Diseases Society of America. C. B. C. reports personal consultancy fees from Astellas, Vir Biotechnology, Horizon Therapeutics, Altimmune, and Premier Healthcare; grants from Merck and GSK; and royalties from UpToDate. J. M. reports grants from the NIH and Merck and consultancy fees from Merck. W. C. H. is a member of the Endpoint Adjudication Committee for Pfizer and an advisory board member for ADMA Biologics and has stock in Pfizer, Bristol-Meyers Squibb, and Zimmer Biomet. E. B. W. has received research support from Pfizer and Moderna and has served on the scientific advisory board for Vaxcyte. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Pathological low birth weight due to fetal growth restriction (FGR) is an important predictor of adverse obstetric and neonatal outcomes. It is more common amongst native lowlanders when gestating in the hypoxic environment of high altitude, whilst populations who have resided at high altitude for many generations are relatively protected. Genetic study of pregnant populations at high altitude permits exploration of the role of hypoxia in FGR pathogenesis, and perhaps of FGR pathogenesis more broadly. We studied the umbilical cord blood DNA of 316 neonates born to pregnant women managed at the Sonam Norboo Memorial Hospital, Ladakh (altitude 3540m) between February 2017 and January 2019. Principal component, admixture and genome wide association studies (GWAS) were applied to dense single nucleotide polymorphism (SNP) genetic data, to explore ancestry and genetic predictors of low birth weight. Our findings support Tibetan ancestry in the Ladakhi population, with subsequent admixture with neighboring Indo-Aryan populations. Fetal growth protection was evident in Ladakhi neonates. Although no variants achieved genome wide significance, we observed nominal association of seven variants across genes (ZBTB38, ZFP36L2, HMGA2, CDKAL1, PLCG1) previously associated with birthweight., Competing Interests: The authors have declared that no competing interests exist.

The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of Serratia, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of Serratia., (© 2022. The Author(s).)

Background and Objectives: No standardized risk assessment tool exists for community-acquired pneumonia (CAP) in children. This study aims to investigate the association between red blood cell distribution width (RDW) and pediatric CAP., Methods: Data prospectively collected by the Etiology of Pneumonia in the Community study (2010-2012) was used. Study population was pediatric patients admitted to tertiary care hospitals in Nashville and Memphis, Tennessee with clinically and radiographically confirmed CAP. The earliest measured RDW value on admission was used, in quintiles and also as a continuous variable. Outcomes analyzed were: severe CAP (requiring ICU, mechanical ventilation, vasopressor support, or death) or moderate CAP (hospital admission only). Analysis used multivariable logistic regression and restricted cubic splines modeling., Results: In 1459 eligible children, the median age was 29 months (interquartile range: 12-73), median RDW was 13.3% (interquartile range: 12.5-14.3), and 289 patients (19.8%) developed severe disease. In comparison with the lowest RDW quintile (Q1), the adjusted odds ratio (95% CI) for severe CAP in subsequent quintiles were, Q2: 1.20 (0.72-1.99); Q3: 1.28 (0.76-2.14); Q4: 1.69 (1.01-2.82); Q5: 1.25 (0.73-2.13). Consistently, RDW restricted cubic splines demonstrated an independent, nonlinear, positive association with CAP severity (P = .027), with rapid increases in the risk of severe CAP with RDW values up to 15%., Conclusions: Higher presenting RDW was associated with an increased risk of severe CAP in hospitalized children. Widely available and inexpensive, RDW can serve as an objective data point to help with clinical assessments., (Copyright © 2022 by the American Academy of Pediatrics.)

Mutations in HNF1A cause Maturity Onset Diabetes of the Young (HNF1A-MODY). To understand mechanisms of β-cell dysfunction, we generated stem cell-derived pancreatic endocrine cells with hypomorphic mutations in HNF1A. HNF1A-deficient β-cells display impaired basal and glucose stimulated-insulin secretion, reduced intracellular calcium levels in association with a reduction in CACNA1A expression, and accumulation of abnormal insulin granules in association with SYT13 down-regulation. Knockout of CACNA1A and SYT13 reproduce the relevant phenotypes. In HNF1A deficient β-cells, glibenclamide, a sulfonylurea drug used in the treatment of HNF1A-MODY patients, increases intracellular calcium, and restores insulin secretion. While insulin secretion defects are constitutive in β-cells null for HNF1A, β-cells heterozygous for hypomorphic HNF1A (R200Q) mutations lose the ability to secrete insulin gradually; this phenotype is prevented by correction of the mutation. Our studies illuminate the molecular basis for the efficacy of treatment of HNF1A-MODY with sulfonylureas, and suggest promise for the use of cell therapies., (© 2022. The Author(s).)

Ectodermal dysplasia (ED) involves the aberrant development of at least two ectodermal derivatives, such as skin, teeth, hair, sweat glands, and ocular tissue. The group of over 200 conditions is commonly classified into two major types: hypohidrotic/anhidrotic ED, in which sweat glands are either absent or significantly reduced, and hidrotic ED, in which sweat glands are normal. Ocular manifestations pertinent to patients undergoing corneal vision correction surgery include multifaceted dry eye syndrome, corneal pathology, such as recurrent erosions, scars, neovascularization, and limbal stem cell deficiency, and early-onset cataracts and glaucoma. In this article we discuss the current understanding of ED and offer factors to consider when these patients are seeking corneal refractive surgery., (© 2022. The Author(s).)

Objectives: Rhabdomyolysis in children is a highly variable condition with presentations ranging from myalgias to more severe complications like acute renal failure. We sought to explore demographics and incidence of pediatric rhabdomyolysis hospitalizations and rates of associated renal failure, as our current understanding is limited., Methods: This was a retrospective analysis using the Healthcare Cost and Utilization Project Kids' Inpatient Database to identify children hospitalized with a primary diagnosis of rhabdomyolysis. Data were analyzed for demographic characteristics, as well as geographic and temporal trends. Multivariable logistic regression was used to identify characteristics associated with rhabdomyolysis-associated acute renal failure., Results: From 2006 to 2016, there were 8599 hospitalized children with a primary diagnosis of rhabdomyolysis. Overall, hospitalizations for pediatric rhabdomyolysis are increasing over time, with geographic peaks in the South and Northeast regions, and seasonal peaks in March and August. Though renal morbidity was diagnosed in 8.5% of children requiring hospitalization for rhabdomyolysis, very few of these patients required renal replacement therapy (0.41%), and death was rare (0.03%). Characteristics associated with renal failure included male sex, age greater than 15 years, and non-Hispanic Black race., Conclusions: Though renal failure occurs at a significant rate in children hospitalized with rhabdomyolysis, severe complications, including death, are rare. The number of children hospitalized with rhabdomyolysis varies by geographic region and month of the year. Future studies are needed to explore etiologies of rhabdomyolysis and laboratory values that predict higher risk of morbidity and mortality in children with rhabdomyolysis., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Embedding Public and Patient Involvement (PPI) in postgraduate research has been recognized as an important component of post-graduate training, providing research scholars with an awareness and a skillset in an area which prepares them for future roles as healthcare researchers. Improving Pathways for Acute STroke And Rehabilitation (iPASTAR) is a structured PhD training program [Collaborative Doctoral Award (CDA)] which aims to design a person-centered stroke pathway throughout the trajectory of stroke care, to optimize post-stroke health and wellbeing. PPI is embedded at all stages., Purpose: The iPASTAR research programme was strongly informed by a round-table PPI consultation process with individuals who experienced stroke and who provided broad representation across ages, gender, geographical locations (urban and rural) and the PhD themed areas of acute care, early supported discharge and lifestyle-based interventions after stroke. Four PhD scholars taking part in the CDA-iPASTAR now work collaboratively with four stroke champions, supported by a wider PPI advisory panel., Methods: This study will evaluate the process and impact of embedding PPI during a PhD program. We will conduct a longitudinal mixed-methods evaluation, conducting focus groups at 24, 36, and 48 months to explore the experiences of the key stakeholders involved. The participants will include PhD scholars, PPI partners (PPI Advisory Group and PPI Champions), PhD supervisors and a PPI manager. An independent researcher will conduct the evaluation. We will include focus groups, individual interviews and participant reflections. Qualitative data will be analyzed using thematic and content analysis, quantitative data will be analyzed using descriptive statistics., Discussion: PPI and patient voice initiatives bring together researchers, family, and people with health care issues into meaningful dialogue and allow the development of a patient-voice learning network. Embedding PPI training within a PhD program can build meaningful capacity in PPI partnerships in stroke research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Horgan, Lennon, Hickey, Sorensen, Kroll, McCartan, Hall, O'Callaghan, Fitzgerald, Hickey, Fahy, Osborne, Scullion, Ní Bhroin and Williams.)

Background: Underlying comorbidities are common in children with pneumonia., Objective: To determine associations between comorbidity-related functional limitations and risk for severe pneumonia outcomes., Design, Setting, and Participants: We prospectively enrolled children <18 years with and without comorbidities presenting to the emergency department with clinical and radiographic pneumonia at two institutions. Comorbidities included chronic conditions requiring daily medications, frequent healthcare visits, or which limited age-appropriate activities. Among children with comorbidities, functional limitations were defined as none or mild, moderate, and severe., Main Outcomes and Measures: Outcomes included an ordinal severity outcome, categorized as very severe (mechanical ventilation, shock, or death), severe (intensive care without very severe features), moderate (hospitalization without severe features), or mild (discharged home), and length of stay (LOS). Multivariable ordinal logistic regression was used to examine associations between comorbidity-related functional limitations and outcomes, while accounting for relevant covariates., Results: A cohort of 1116 children, including 452 (40.5%) with comorbidities; 200 (44.2%) had none or mild functional limitations, 93 (20.6%) moderate, and 159 (35.2%) had severe limitations. In multivariable analysis, comorbidity-related functional limitations were associated with the ordinal severity outcome and LOS (p < .001 for both). Children with severe functional limitations had tripling of the odds of a more severe ordinal (adjusted odds ratio [aOR]: 3.01, 95% confidence interval [2.05, 4.43]) and quadrupling of the odds for longer LOS (aOR: 4.72 [3.33, 6.70]) as compared to children without comorbidities., Conclusion: Comorbidity-related functional limitations are important predictors of disease outcomes in children with pneumonia. Consideration of functional limitations, rather than the presence of comorbidity alone, is critical when assessing risk of severe outcomes., (© 2022 Society of Hospital Medicine.)

Background: Penicillin allergy labels are often inaccurate in children and removing unnecessary labels results in improved outcomes and lower health care costs. Although the hospital setting is a frequent point of contact for children, strategies to evaluate penicillin allergies in the hospital are lacking., Methods: We performed a prospective pilot study to determine the feasibility of a centralized, pharmacy-led approach to penicillin allergy evaluation. Children with a reported history of penicillin allergy admitted to our children's hospital were risk-stratified and those stratified as low-risk underwent a single-dose oral challenge by a central pharmacist, regardless of the need for antibiotics. After the completion of each patient's delabeling process, surveys were distributed to health care personnel involved in the patient's care to collect perceptions on the acceptability, appropriateness, and feasibility of this intervention. Measures were scored by using a 5-point Likert scale., Results: Of the 23 patients who screened as low-risk, 20 underwent a penicillin allergy evaluation and an oral challenge. Of these, the penicillin allergy label was removed in 19 (95%) patients (Fig 1). The median age was 7 years (range 11 months-18 years). Participants rated the risk stratification and delabeling favorably overall, with high ratings on all 3 implementation measures: acceptability (mean 4.55, ± standard deviation [STD] 0.65), appropriateness (mean 4.58, STD ± 0.6), and feasibility (mean 4.51, STD ± 0.73). Measures of acceptability, appropriateness, and feasibility remained high when stratified by health care worker type and provider type., Conclusions: Our findings provide support for systemic implementation of penicillin allergy delabeling strategies in hospitalized children., (Copyright © 2022 by the American Academy of Pediatrics.)

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.)

Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children ( n  = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P  < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam ( r : 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC ( r : 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cornish, McDonnell and Williams.)

Objective: To determine whether empirical antibiotic initiation and selection for children with pneumonia was associated with procalcitonin (PCT) levels when results were blinded to clinicians., Methods: We enrolled children <18 years with radiographically confirmed pneumonia at 2 children's hospitals from 2014 to 2019. Blood for PCT was collected at enrollment (blinded to clinicians). We modeled associations between PCT and (1) antibiotic initiation and (2) antibiotic selection (narrow versus broad-spectrum) using multivariable logistic regression models. To quantify potential stewardship opportunities, we calculated proportions of noncritically ill children receiving antibiotics who also had a low likelihood of bacterial etiology (PCT <0.25 ng/mL) and those receiving broad-spectrum therapy, regardless of PCT level., Results: We enrolled 488 children (median PCT, 0.37 ng/mL; interquartile range [IQR], 0.11-2.38); 85 (17%) received no antibiotics (median PCT, 0.32; IQR, 0.09-1.33). Among the 403 children receiving antibiotics, 95 (24%) received narrow-spectrum therapy (median PCT, 0.24; IQR, 0.08-2.52) and 308 (76%) received broad-spectrum (median PCT, 0.46; IQR, 0.12-2.83). In adjusted analyses, PCT values were not associated with antibiotic initiation (odds ratio [OR], 1.02, 95% confidence interval [CI], 0.97%-1.06%) or empirical antibiotic selection (OR 1.07; 95% CI, 0.97%-1.17%). Of those with noncritical illness, 246 (69%) were identified as potential targets for antibiotic stewardship interventions., Conclusion: Neither antibiotic initiation nor empirical antibiotic selection were associated with PCT values. Whereas other factors may inform antibiotic treatment decisions, the observed discordance between objective likelihood of bacterial etiology and antibiotic use suggests important opportunities for stewardship., (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.)

Objective: To develop and test a new quality measure assessing timeliness of follow-up mental health care for youth presenting to the emergency department (ED) with suicidal ideation or self-harm., Methods: Based on a conceptual framework, evidence review, and a modified Delphi process, we developed a quality measure assessing whether youth 5 to 17 years old evaluated for suicidal ideation or self-harm in the ED and discharged to home had a follow-up mental health care visit within 7 days. The measure was tested in 4 geographically dispersed states (California, Pennsylvania, South Carolina, Tennessee) using Medicaid administrative data. We examined measure feasibility of implementation, variation, reliability, and validity. To test validity, adjusted regression models examined associations between quality measure scores and subsequent all-cause and same-cause hospital readmissions/ED return visits., Results: Overall, there were 16,486 eligible ED visits between September 1, 2014 and July 31, 2016; 53.5% of eligible ED visits had an associated mental health care follow-up visit within 7 days. Measure scores varied by state, ranging from 26.3% to 66.5%, and by youth characteristics: visits by youth who were non-White, male, and living in an urban area were significantly less likely to be associated with a follow-up visit within 7 days. Better quality measure performance was not associated with decreased reutilization., Conclusions: This new ED quality measure may be useful for monitoring and improving the quality of care for this vulnerable population; however, future work is needed to establish the measure's predictive validity using more prevalent outcomes such as recurrence of suicidal ideation or deliberate self-harm., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Importance: Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance., Objective: To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children., Design, Setting, and Participants: Randomized double-blind placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings in 8 US cities. A total of 380 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled from December 2, 2016, to December 16, 2019. Data were analyzed from January to September 2020., Intervention: On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic., Main Outcomes and Measures: The primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child's clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR). Within each DOOR rank, participants were further ranked by the number of antibiotic days, assuming that shorter antibiotic durations were more desirable. Using RADAR, the probability of a more desirable outcome was estimated for the short- vs standard-course strategy. In a subset of children, throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora., Results: A total of 380 children (189 randomized to short course and 191 randomized to standard course) made up the study population. The mean (SD) age was 35.7 (17.2) months, and 194 participants (51%) were male. Of the included children, 8 were Asian, 99 were Black or African American, 234 were White, 32 were multiracial, and 7 were of unknown or unreported race; 33 were Hispanic or Latino, 344 were not Hispanic or Latino, and 3 were of unknown or unreported ethnicity. There were no differences between strategies in the DOOR or its individual components. Fewer than 10% of children in either strategy had an inadequate clinical response. The short-course strategy had a 69% (95% CI, 63-75) probability of a more desirable RADAR outcome compared with the standard-course strategy. A total of 171 children were included in the resistome analysis. The median (range) number of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC (1.17 [0.35-2.43] vs 1.33 [0.46-11.08]; P = .01) and β-lactamase RGPC (0.55 [0.18-1.24] vs 0.60 [0.21-2.45]; P = .03)., Conclusions and Relevance: In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance., Trial Registration: ClinicalTrials.gov Identifier: NCT02891915.

Introduction: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study., Methods: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1β, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging., Results: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1β, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003)., Conclusion: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials., (© 2021 S. Karger AG, Basel.)

Purpose: A damaged vertebral body can exhibit accelerated 'creep' under constant load, leading to progressive vertebral deformity. However, the risk of this happening is not easy to predict in clinical practice. The present cadaveric study aimed to identify morphometric measurements in a damaged vertebral body that can predict a susceptibility to accelerated creep., Methods: A total of 27 vertebral trabeculae samples cored from five cadaveric spines (3 male, 2 female, aged 36 to 73 (mean 57) years) were mechanically tested to establish the relationship between bone damage and residual strain. Compression testing of 28 human spinal motion segments (three vertebrae and intervening soft tissues) dissected from 14 cadaveric spines (10 male, 4 female, aged 67 to 92 (mean 80) years) showed how the rate of creep of a damaged vertebral body increases with increasing "damage intensity" in its trabecular bone. Damage intensity was calculated from vertebral body residual strain following initial compressive overload using the relationship established in the compression test of trabecular bone samples., Results: Calculations from trabecular bone samples showed a strong nonlinear relationship between residual strain and trabecular bone damage intensity (R 2  = 0.78, P < 0.001). In damaged vertebral bodies, damage intensity was then related to vertebral creep rate (R 2  = 0.39, P = 0.001). This procedure enabled accelerated vertebral body creep to be predicted from morphological changes (residual strains) in the damaged vertebra., Conclusion: These findings suggest that morphometric measurements obtained from fractured vertebrae can be used to quantify vertebral damage and hence to predict progressive vertebral deformity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate associations of race/ethnicity and social determinants with 90-day rehospitalization for mental health conditions to acute care nonpsychiatric children's hospitals., Study Design: We conducted a retrospective cohort analysis of mental health hospitalizations for children aged 5-18 years from 2016 to 2018 at 32 freestanding US children's hospitals using the Children's Hospital Association's Pediatric Health Information System database to assess the association of race/ethnicity and social determinants (insurance payer, neighborhood median household income, and rurality of patient home location) with 90-day rehospitalization. Risk factors for rehospitalization were modeled using mixed-effects multivariable logistic regression., Results: Among 23 556 index hospitalizations, there were 1382 mental health rehospitalizations (5.9%) within 90 days. Non-Hispanic Black children were 26% more likely to be rehospitalized than non-Hispanic White children (aOR 1.26, 95% CI 1.08-1.48). Those with government insurance were 18% more likely to be rehospitalized than those with private insurance (aOR 1.18, 95% CI 1.04-1.34). In contrast, those living in a suburban location were 22% less likely to be rehospitalized than those living in an urban location (suburban: aOR 0.78, 95% CI 0.63-0.97)., Conclusions: Non-Hispanic Black children and those with public insurance were at greatest risk for 90-day rehospitalization, and risk was lower in those residing in suburban locations. Future work should focus on upstream interventions that will best attenuate social disparities to promote equity in pediatric mental healthcare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: States which reduce foetal oxygen delivery are associated with impaired intrauterine growth. Hypoxia results when barometric pressure falls with ascent to altitude, and with it the partial pressure of inspired oxygen ('hypobaric hypoxia'). birthweight is reduced when native lowlanders gestate at such high altitude (HA)-an effect mitigated in native (millennia) HA populations. Studying HA populations offer a route to explore the mechanisms by which hypoxia impacts foetal growth., Methods: Between February 2017 and January 2019, we prospectively studied 316 pregnant women, in Leh, Ladakh (altitude 3524 m, where oxygen partial pressure is reduced by 1/3) and 101 pregnant women living in Delhi (low altitude, 216 m above sea level)., Results: Of Ladakhi HA newborns, 14% were small for gestational age (<10th birthweight centile) vs 19% of newborn at low altitude. At HA, increased maternal body mass index, age, and uterine artery (UtA) diameter were positively associated with growth >10th weight centile., Conclusions: This study showed that Ladakhi offspring birthweight is relatively spared from the expected adverse HA effects. Furthermore, maternal body composition and greater UtA size may be physiological HA adaptations and warrant further study, as they offer potential mechanisms to overcome hypoxia-related growth issues., Impact: Reduced foetal oxygen delivery seen in native lowlanders who gestate at HA causes foetal growth restriction-an effect thought to be mitigated in native HA populations. We found that greater maternal body mass and UtA diameter were associated with increased offspring birthweight in a (Ladakh) HA population. This supports a role for them as physiological mediators of adaptation and provides insights into potential mechanisms that may treat hypoxia-related growth issues., (© 2021. The Author(s).)

The Lake Michigan Ozone Study 2017 (LMOS 2017) was a collaborative multiagency field study targeting ozone chemistry, meteorology, and air quality observations in the southern Lake Michigan area. The primary objective of LMOS 2017 was to provide measurements to improve air quality modeling of the complex meteorological and chemical environment in the region. LMOS 2017 science questions included spatiotemporal assessment of nitrogen oxides (NO x = NO + NO 2 ) and volatile organic compounds (VOC) emission sources and their influence on ozone episodes; the role of lake breezes; contribution of new remote sensing tools such as GeoTASO, Pandora, and TEMPO to air quality management; and evaluation of photochemical grid models. The observing strategy included GeoTASO on board the NASA UC-12 aircraft capturing NO 2 and formaldehyde columns, an in situ profiling aircraft, two ground-based coastal enhanced monitoring locations, continuous NO 2 columns from coastal Pandora instruments, and an instrumented research vessel. Local photochemical ozone production was observed on 2 June, 9-12 June, and 14-16 June, providing insights on the processes relevant to state and federal air quality management. The LMOS 2017 aircraft mapped significant spatial and temporal variation of NO 2 emissions as well as polluted layers with rapid ozone formation occurring in a shallow layer near the Lake Michigan surface. Meteorological characteristics of the lake breeze were observed in detail and measurements of ozone, NO x , nitric acid, hydrogen peroxide, VOC, oxygenated VOC (OVOC), and fine particulate matter (PM 2.5 ) composition were conducted. This article summarizes the study design, directs readers to the campaign data repository, and presents a summary of findings.

Background: Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia., Methods: We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in 8 US hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression., Results: PIV was more commonly detected in children (155/2354; 6.6%) than in adults (66/2297; 2.9%) (P < .001). Other pathogens were commonly co-detected among PIV cases (110/221; 50%). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 1.88-37.80). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens., Conclusions: Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community-acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Purpose: Cognitive impairment no dementia (CIND) and dementia are common stroke outcomes, with significant health and societal implications for aging populations. These outcomes are not included in current epidemiological models. We aimed to develop an epidemiological model to project incidence and prevalence of stroke, poststroke CIND and dementia, and life expectancy, in Ireland to 2035, informing policy and service planning., Methods: We developed a probabilistic Markov model (the StrokeCog model) applied to the Irish population aged 40 to 89 years to 2035. Data sources included official population and hospital-episode statistics, longitudinal cohort studies, and published estimates. Key assumptions were varied in sensitivity analysis. Results were externally validated against independent sources. The model tracks poststroke progression into health states characterized by no cognitive impairment, CIND, dementia, disability, stroke recurrence, and death., Results: We projected 69 051 people with prevalent stroke in Ireland in 2035 (22.0 per 1000 population [95% CI, 20.8-23.1]), with 25 274 (8.0 per 1000 population [95% CI, 7.1-9.0]) of those projected to have poststroke CIND, and 12 442 having poststroke dementia (4.0 per 1000 population [95% CI, 3.2-4.8]). We projected 8725 annual incident strokes in 2035 (2.8 per 1000 population [95% CI, 2.7-2.9]), with 3832 of these having CIND (1.2 per 1000 population [95% CI, 1.1-1.3]), and 1715 with dementia (0.5 per 1000 population [95% CI, 0.5-0.6]). Life expectancy for stroke survivors at age 50 was 23.4 years (95% CI, 22.3-24.5) for women and 20.7 (95% CI, 19.5-21.9) for men., Conclusions: This novel epidemiological model of stroke, poststroke CIND, and dementia draws on the best available evidence. Sensitivity analysis indicated that findings were robust to assumptions, and where there was uncertainty a conservative approach was taken. The StrokeCog model is a useful tool for service planning and cost-effectiveness analysis and is available for adaptation to other national contexts.

Objective: To determine the frequency of neurologic complications associated with influenza in hospitalized children., Stud Design: We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression., Results: Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2)., Conclusions: Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: After Action Review is a form of facilitated team learning and review of events. The methodology originated in the United States Army and forms part of the Incident Management Framework in the Irish Health Services. After Action Review has been hypothesized to improve safety culture and the effect of patient safety events on staff (second victim experience) in health care settings. Yet little direct evidence exists to support this and its implementation has not been studied., Aim: To investigate the effect of After Action Review on safety culture and second victim experience and to examine After Action Review implementation in a hospital setting., Methods: A mixed methods study will be conducted at an Irish hospital. To assess the effect on safety culture and second victim experience, hospital staff will complete surveys before and twelve months after the introduction of After Action Review to the hospital (Hospital Survey on Safety Culture 2.0 and Second Victim Experience and Support Tool). Approximately one in twelve staff will be trained as After Action Review Facilitators using a simulation based training programme. Six months after the After Action Review training, focus groups will be conducted with a stratified random sample of the trained facilitators. These will explore enablers and barriers to implementation using the Theoretical Domains Framework. At twelve months, information will be collected from the trained facilitators and the hospital to establish the quality and resource implications of implementing After Action Review., Discussion: The results of the study will directly inform local hospital decision-making and national and international approaches to incorporating After Action Review in hospitals and other healthcare settings., Competing Interests: The authors have declared that no competing interests exist.

Access to safe, effective, quality-assured antivenom products that are tailored to endemic venomous snake species is a crucial component of recent coordinated efforts to reduce the global burden of snakebite envenoming. Multiple access barriers may affect the journey of antivenoms from manufacturers to the bedsides of patients. Our review describes the antivenom ecosystem at different levels and identifies solutions to overcome these challenges. At the global level, there is insufficient manufacturing output to meet clinical needs, notably for antivenoms intended for use in regions with a scarcity of producers. At national level, variable funding and deficient regulation of certain antivenom markets can lead to the procurement of substandard antivenom. This is particularly true when producers fail to seek registration of their products in the countries where they should be used, or where weak assessment frameworks allow registration without local clinical evaluation. Out-of-pocket expenses by snakebite victims are often the main source of financing antivenoms, which results in the underuse or under-dosing of antivenoms, and a preference for low-cost products regardless of efficacy. In resource-constrained rural areas, where the majority of victims are bitten, supply of antivenom in peripheral health facilities is often unreliable. Misconceptions about treatment of snakebite envenoming are common, further reducing demand for antivenom and exacerbating delays in reaching facilities equipped for antivenom use. Multifaceted interventions are needed to improve antivenom access in resource-limited settings. Particular attention should be paid to the comprehensive list of actions proposed within the WHO Strategy for Prevention and Control of Snakebite Envenoming., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Ltd.)

Procalcitonin (PCT) is a useful, albeit imperfect, diagnostic aid that can help clinicians make more informed decisions around antibiotic use in children with lower respiratory tract infections (LRTI), including community-acquired pneumonia (CAP). Recent data suggest that a very low PCT concentration has a high negative predictive value to identify a population of children at low risk of typical bacterial infections. Although the preponderance of data on the clinical utility of PCT in LRTI come from adult studies, the potential for benefit is likely greatest in paediatric CAP and other LRTIs where viral aetiologies predominate, yet antibiotics are frequently prescribed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Little is known about the clinical factors associated with COVID-19 disease severity in children and adolescents., Methods: We conducted a retrospective cohort study across 45 US children's hospitals between April 2020 to September 2020 of pediatric patients discharged with a primary diagnosis of COVID-19. We assessed factors associated with hospitalization and factors associated with clinical severity (eg, admission to inpatient floor, admission to intensive care unit [ICU], admission to ICU with mechanical ventilation, shock, death) among those hospitalized., Results: Among 19,976 COVID-19 encounters, 15,913 (79.7%) patients were discharged from the emergency department (ED) and 4063 (20.3%) were hospitalized. The clinical severity distribution among those hospitalized was moderate (3222, 79.3%), severe (431, 11.3%), and very severe (380, 9.4%). Factors associated with hospitalization vs discharge from the ED included private payor insurance (adjusted odds ratio [aOR],1.16; 95% CI, 1.1-1.3), obesity/type 2 diabetes mellitus (type 2 DM) (aOR, 10.4; 95% CI, 8.9-13.3), asthma (aOR, 1.4; 95% CI, 1.3-1.6), cardiovascular disease, (aOR, 5.0; 95% CI, 4.3- 5.8), immunocompromised condition (aOR, 5.9; 95% CI, 5.0-6.7), pulmonary disease (aOR, 5.3; 95% CI, 3.4-8.2), and neurologic disease (aOR, 3.2; 95% CI, 2.7-5.8). Among children and adolescents hospitalized with COVID-19, greater disease severity was associated with Black or other non-White race; age greater than 4 years; and obesity/type 2 DM, cardiovascular, neuromuscular, and pulmonary conditions., Conclusions: Among children and adolescents presenting to US children's hospital EDs with COVID-19, 20% were hospitalized; of these, 21% received care in the ICU. Older children and adolescents had a lower risk for hospitalization but more severe illness when hospitalized. There were differences in disease severity by race and ethnicity and the presence of selected comorbidities. These factors should be taken into consideration when prioritizing mitigation and vaccination strategies.