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BACKGROUND: There is limited evidence from which to derive guidelines for the management of febrile infants aged 29 to 60 days with urinary tract infections (UTIs). Most such infants are hospitalized for ≥48 hours. Our objective was to derive clinical prediction models to identify febrile infants with UTIs at very low risk of adverse events and bacteremia in a large sample of patients. METHODS: This study was a 20-center retrospective review of infants aged 29 to 60 days with temperatures of ≥38°C and culture-proven UTIs. We defined UTI by growth of ≥50 000 colony-forming units (CFW/mL of a single pathogen or ≥10 000 CFU/mL in association with positive urinalyses. We defined adverse events as death, shock, bacterial meningitis, ICU admission need for ventilator support, or other substantial complications. We performed binary recursive partitioning analyses to derive prediction models. RESULTS: We analyzed 1895 patients. Adverse events occurred in 51 of 1842 (2.8% [95% confidence interval (CD: 2.1%-3.6%)] and bacteremia in 123 of 1877 (6.5% [95% Cl: 5.5%-7.7%]). Patients were at very low risk for adverse events if not clinically ill on emergency department (ED) examination and did not have a high-risk past medical history (prediction model sensitivity: 98.0% [95% Cl: 88.2%-99.9%]). Patients were at lower risk for bacteremia if they were not clinically ill on ED examination, did not have a high-risk past medical history, had a peripheral band count of <1250 cells per μL, and had a peripheral absolute neutrophil count of ≥1500 cells per μL (sensitivity 77.2% [95% Cl: 68.6%-84.1%]). CONCLUSION: Brief hospitalization or outpatient management with close follow-up may be considered for infants with UTIs at very low risk of adverse events. [ABSTRACT FROM AUTHOR]

Aim: Explore caregiver (i.e., person who provides direct care for a child and was present at the time of their medical visit) perspectives and preferences regarding timely access to unscheduled acute care as well as barriers and facilitators of the use of an online appointment tool (i.e., Save My Spot) in a satellite children's hospital five urgent care centers in the United States., Design: A descriptive qualitative interview study., Methods: We conducted semi-structured interviews with 49 caregivers in a private room, in person and in conjunction with medical visits from June 2023 to the end of August 2023 after obtaining institutional ethical approvals. We employed deductive and inductive content analysis and used the MAXQDA data analysis tool., Results: Average caregiver age was 37 years. Most of the caregivers were female, white, and non-Hispanic and had low income. We identified three categories: (a) Caregiver preferences for using the Save My Spot online appointment tool and their reasons for buy-in, (b) ways of promoting the Save My Spot tool and (c) enhancing the accessibility of the Save My Spot tool., Conclusion: The findings of this study suggest that when introduced successfully, caregivers adopt an online appointment tool and find it efficient in minimising wait times. Various approaches (e.g., social media, billboards) can be used to promote the tool to increase timely access to care., Impact: This study provides valuable insights into the utilisation of an online appointment tool in the two hospital-based and three stand-alone neighbourhood urgent care centers of a large urban children's hospital. Future studies capturing different tools and populations are recommended to gain diverse understanding., Reporting Methods: The study was reported following the Standards for Reporting Qualitative Research., Patient or Public Contribution: Caregivers provided their perspectives and the Paediatric Emergency Medicine Disparities Working Group contributed to the interpretation of the study findings., (© 2024 John Wiley & Sons Ltd.)

Background and Objective: Serum procalcitonin (PCT) is a highly accurate biomarker for stratifying the risk of invasive bacterial infections (IBIs) in febrile infants ≤60 days old. However, PCT is unavailable in some settings. We explored the association of leukopenia and neutropenia with IBIs in non-critically ill febrile infants ≤60 days old, with and without PCT., Methods: We conducted a secondary analysis of a prospective observational cohort consisting of 7407 non-critically ill infants ≤60 days old with temperatures ≥38°C. We focused on the risk of IBIs in patients with leukopenia (white blood cell [WBC] count <5000 cells/μL) or neutropenia (absolute neutrophil count [ANC] <1000 cells/μL), categorized to extremes of lower values, and the impact of PCT on these associations. Multiple logistic regression was used to identify independent predictors of IBIs., Results: Final analysis included 6865 infants with complete data; 45% (3098) had PCT data available. Of the 6865, a total of 111 (1.6%) had bacteremia without bacterial meningitis, 18 (0.3%) had bacterial meningitis without bacteremia, and 19 (0.3%) had both bacteremia and bacterial meningitis. IBI was present in four of 20 (20%) infants with WBC counts ≤2500 cells/μL and four of 311 (1.3%) with ANC ≤1000 cells/μL. In multivariable logistic regression analysis not including PCT, a WBC count ≤2500 cells/μL was significantly associated with IBI (OR 13.48, 95% CI 2.92-45.35). However, no patients with leukopenia or neutropenia and PCT ≤0.5 ng/mL had IBIs., Conclusions: Leukopenia ≤2500 cells/μL in febrile infants ≤60 days old is associated with IBIs. However, in the presence of normal PCT levels, no patients with leukopenia had IBIs. While this suggests leukopenia ≤2500 cells/μL is a risk factor for IBIs in non-critically ill young febrile infants only when PCT is unavailable or elevated, the overall low frequency of leukopenia in this cohort warrants caution in interpretation, with future validation required., (© 2024 Society for Academic Emergency Medicine.)

Objective: The lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants., Study Design: Secondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as 'no', 'possible' or 'definite' pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias., Results: Of 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias., Conclusions: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias., Competing Interests: Competing interests: OR reports personal fees from Sanofi-Pasteur, Merck and Pfizer, and grants from Janssen and the Bill & Melinda Gates Foundation. These fees and grants are not related to this study. No other disclosures were reported., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Health care disparities are well-documented among children based on race, ethnicity, and language for care. An agenda that outlines research priorities for disparities in pediatric emergency care (PEC) is lacking., Objective: To investigate research priorities for disparities in PEC among medical personnel, researchers, and health care-affiliated community organizations., Design, Setting, and Participants: In this survey study, a modified Delphi approach was used to investigate research priorities for disparities in PEC. An initial list of research priorities was developed by a group of experienced PEC investigators in 2021. Partners iteratively assessed the list through 2 rounds of electronic surveys using Likert-type responses in late 2021 and early 2022. Priorities were defined as achieving consensus if they received a score of highest priority or priority by at least 60% of respondents. Asynchronous engagement of participants via online web-conferencing platforms and email correspondence with electronic survey administration was used. Partners were individuals and groups involved in PEC. Participants represented interest groups, research and medical personnel organizations, health care partners, and laypersons with roles in community and family hospital advisory councils. Participants were largely from the US, with input from international PEC research networks., Outcome: Consensus agenda of research priorities to identify and address health care disparities in PEC., Results: PEC investigators generated an initial list of 27 potential priorities. Surveys were completed by 38 of 47 partners (80.6%) and 30 of 38 partners (81.1%) in rounds 1 and 2, respectively. Among 30 respondents who completed both rounds, there were 7 family or community partners and 23 medical or research partners, including 4 international PEC research networks. A total of 12 research priorities achieved the predetermined consensus threshold: (1) systematic efforts to reduce disparities; (2) race, ethnicity, and language data collection and reporting; (3) recognizing and mitigating clinician implicit bias; (4) mental health disparities; (5) social determinants of health; (6) language and literacy; (7) acute pain-management disparities; (8) quality of care equity metrics; (9) shared decision-making; (10) patient experience; (11) triage and acuity score assignment; and (12) inclusive research participation., Conclusions and Relevance: These results suggest a research priority agenda that may be used as a guide for investigators, research networks, organizations, and funding agencies to engage in and support high-priority disparities research topics in PEC.

(1) Background: Pediatric emergency department (PED) settings are opportune venues in which to recruit parental smokers into tobacco cessation interventions. However, the barriers associated with parents' participation in PED-based cessation trials are unknown. The objective was to explore parents' reasons for non-participation in a PED-based tobacco cessation trial. (2) Methods: We employed the framework method and conducted a qualitative data analysis of parental smokers who were eligible to participate in a PED-based tobacco cessation trial and did not choose to participate (n = 371). (3) Results: Two main themes emerged about reasons for non-participation: (a) Not interested in participating in a research study, and (b) concerns specific to the study. Parents had various reasons for not participating in the cessation trial including not being interested in quitting, parents' health and well-being, parents' beliefs about research, and time required for the study and follow-up visits. (4) Conclusion: General disinterest and specific study-related concerns were touted as reasons for non-participation in a PED-based tobacco cessation trial. Given the potential reductions in tobacco-related morbidity to both parents and children that tobacco control interventions can facilitate, future tobacco interventions should consider alterations in study design and recruitment strategies to encourage all eligible parental smokers to participate.

Importance: Bacteremia is a major cause of morbidity and mortality in children and young adults with sickle cell disease (SCD), but among those presenting to the emergency department (ED) with fever, the absolute risk of, risk factors associated with, and outcomes of bacteremia are poorly defined., Objective: To obtain contemporary data on the absolute risk of, risk factors associated with, and outcomes associated with bacteremia in children and young adults with SCD presenting to the ED with fever., Design, Setting, and Participants: A multicenter retrospective cohort study was conducted of individuals with SCD younger than 22 years (young adults) presenting to EDs within the Pediatric Health Information Systems database from January 1, 2016, to December 31, 2021, with fever (identified by diagnostic codes for fever or the collection of blood samples for cultures and intravenous antibiotic administration). Data analysis was performed from May 17 to December 15, 2022., Main Outcomes and Measures: The risk of bacteremia (defined by diagnostic coding) was identified in these children and young adults, and univariate analyses and multivariable regression were used to examine patient-level factors and bacteremia., Results: A total of 35 548 encounters representing 11 181 individual patients from 36 hospitals were evaluated. The median age of the cohort was 6.17 (IQR, 2.36-12.11) years and 52.9% were male. Bacteremia was present in 405 encounters (1.1%, 95% CI, 1.05%-1.26%). A history of bacteremia, osteomyelitis, stroke, central line-associated bloodstream infection (CLABSI), central venous catheter, or apheresis was associated with the diagnosis of bacteremia, while age, sex, hemoglobin SC genotype, and race and ethnicity were not. In the multivariable analysis, individuals with a history of bacteremia (odds ratio [OR], 1.36; 95% CI, 1.01-1.83), CLABSI (OR, 6.39; 95% CI, 3.02-13.52), and apheresis (OR, 1.77; 95% CI, 1.22-2.55) had higher odds of bacteremia., Conclusions and Relevance: The findings of this large cohort study suggest that bacteremia in children and young adults with SCD presenting with fever is rare. A history of invasive bacterial infection, CLABSI, or a central line appears to be associated with bacteremia, while age and SCD genotype are not.

Background: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis., Methods: We will conduct a pragmatic, embedded, cluster-randomized, crossover trial in 26 pediatric institutions to determine if hyperhydration, compared to conservative fluid management, improves outcomes in 1040 children with high-risk STEC infections. The primary outcome is major adverse kidney events within 30 days (MAKE30), a composite measure that includes death, initiation of new renal replacement therapy, or persistent kidney dysfunction. Secondary outcomes include life-threatening, extrarenal complications, and development of HUS. Pathway eligible children will be treated per institutional allocation to each pathway. In the hyperhydration pathway, all eligible children are hospitalized and administered 200% maintenance balanced crystalloid fluids up to targets of 10% weight gain and 20% reduction in hematocrit. Sites in the conservative fluid management pathway manage children as in- or outpatients, based on clinician preference, with the pathway focused on close laboratory monitoring, and maintenance of euvolemia. Based on historical data, we estimate that 10% of children in our conservative fluid management pathway will experience the primary outcome. With 26 clusters enrolling a mean of 40 patients each with an intraclass correlation coefficient of 0.11, we will have 90% power to detect a 5% absolute risk reduction., Discussion: HUS is a devastating illness with no treatment options. This pragmatic study will determine if hyperhydration can reduce morbidity associated with HUS in children with high-risk STEC infection., Trial Registration: ClinicalTrials.gov NCT05219110 . Registered on February 1, 2022., (© 2023. The Author(s).)

Background: Variation in the use of treatments and hospitalization for anaphylaxis would suggest a lack of consensus in therapeutic approach., Objective: To evaluate trends and practice variation in the emergency department (ED) care of children with anaphylaxis in a large US cohort., Methods: We conducted a 48-site retrospective cohort study using the Pediatric Health Information System from January 2016 through September 2022. Children younger than 18 years with a primary diagnosis of anaphylaxis were included. Care trends were assessed using negative binomial regression modeling. Rates of medication use, hospitalizations, and revisits were reported as medians with interquartile ranges (IQRs)., Results: There were 42,909 ED visits for anaphylaxis, with a 4.2% per-year increase in visit incidence (95% CI, 1.8-6.7) during the study period. The median hospitalization rate was 3.5% (IQR, 2.2-6.0), and the 3-day ED revisit rate was 0.6% (IQR, 0.4-0.9). The hospital-level median use of therapies included intramuscular epinephrine (55.3%; IQR, 50.1-59.9), systemic steroids (73.8%; IQR, 63.9-81.4), antihistamines (59.9%; IQR, 53.5-65.5), H2-receptor antagonists (56.8%; IQR, 42.3-66.2), bronchodilators (15.1%; IQR, 12.5-17.0), inhaled epinephrine (1.1%; IQR, 0.6-1.9), and fluid boluses (19.8%; IQR, 11.3-29.3). Severe reactions requiring intensive care unit admission (1.5%; IQR, 0.8-2.2), vasopressors (0.3%; IQR, 0.0-0.6), and intubation (0.2%; IQR, 0.0-0.3) were rare., Conclusions: ED visits for anaphylaxis increased during the study period, but hospitalization rates were low. Substantial variation exists between EDs regarding the use of anaphylaxis therapies, supporting the need for future research to evaluate the efficacy of these medications., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to evaluate the international variation in the use of evidence-based management (EBM) in bronchiolitis. We hypothesised that management consistent with full-EBM practices is associated with the research network of care, adjusted for patient-level characteristics. Secondary objectives were to determine the association between full-EBM and (1) hospitalisation and (2) emergency department (ED) revisits resulting in hospitalisation within 21 days., Design: A secondary analysis of a retrospective cohort study., Setting: 38 paediatric EDs belonging to the Paediatric Emergency Research Network in Canada, USA, Australia/New Zealand UK/Ireland and Spain/Portugal., Patients: Otherwise healthy infants 2-11 months old diagnosed with bronchiolitis between 1 January 2013 and 31 December, 2013., Outcome Measures: Primary outcome was management consistent with full-EBM, that is, no bronchodilators/corticosteroids/antibiotics, no chest radiography or laboratory testing. Secondary outcomes included hospitalisations during the index and subsequent ED visits., Results: 1137/2356 (48.3%) infants received full-EBM (ranging from 13.2% in Spain/Portugal to 72.3% in UK/Ireland). Compared with the UK/Ireland, the adjusted ORs (aOR) of full-EBM receipt were lower in Spain/Portugal (aOR 0.08, 95% CI 0.02 to 0.29), Canada (aOR 0.13 (95% CI 0.06 to 0.31) and USA (aOR 0.16 (95% CI 0.07 to 0.35). EBM was less likely in infants with dehydration (aOR 0.49 (95% CI 0.33 to 0.71)), chest retractions (aOR 0.69 (95% CI 0.52 to 0.91)) and nasal flaring (aOR 0.69 (95% CI 0.52 to 0.92)). EBM was associated with reduced odds of hospitalisation at the index visit (aOR 0.77 (95% CI 0.60 to 0.98)) but not at revisits (aOR 1.17 (95% CI 0.74 to 1.85))., Conclusions: Infants with bronchiolitis frequently do not receive full-EBM ED management, particularly those outside of the UK/Ireland. Furthermore, there is marked variation in full-EBM between paediatric emergency networks, and full-EBM delivery is associated with lower likelihood of hospitalisation. Given the global bronchiolitis burden, international ED-focused deimplementation of non-indicated interventions to enhance EBM is needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Oseltamivir is recommended for all children hospitalized with influenza, despite limited evidence supporting its use in the inpatient setting., Objective: To determine whether early oseltamivir use is associated with improved outcomes in children hospitalized with influenza., Design, Setting, and Participants: This multicenter retrospective study included 55 799 children younger than 18 years who were hospitalized with influenza from October 1, 2007, to March 31, 2020, in 36 tertiary care pediatric hospitals who participate in the Pediatric Health Information System database. Data were analyzed from January 2021 to March 2022., Exposures: Early oseltamivir treatment, defined as use of oseltamivir on hospital day 0 or 1., Main Outcomes and Measures: The primary outcome was hospital length of stay (LOS) in calendar days. Secondary outcomes included 7-day hospital readmission, late (hospital day 2 or later) intensive care unit (ICU) transfer, and a composite outcome of in-hospital death or use of extracorporeal membrane oxygenation (ECMO). Inverse probability treatment weighting (IPTW) based on propensity scoring was used to address confounding by indication. Mixed-effects models were used to compare outcomes between children who did and did not receive early oseltamivir treatment. Outcomes were also compared within high-risk subgroups based on age, presence of a complex chronic condition, early critical illness, and history of asthma., Results: The analysis included 55 799 encounters from 36 hospitals. The median (IQR) age of the cohort was 3.61 years (1.03-8.27); 56% were male, and 44% were female. A total of 33 207 patients (59.5%) received early oseltamivir. In propensity score-weighted models, we found that children treated with early oseltamivir had shorter LOS (median 3 vs 4 days; IPTW model ratio, 0.52; 95% CI, 0.52-0.53) and lower odds of all-cause 7-day hospital readmission (3.5% vs 4.8%; adjusted odds ratio [aOR], 0.72; 95% CI, 0.66-0.77), late ICU transfer (2.4% vs 5.5%; aOR, 0.41; 95% CI, 0.37-0.46), and the composite outcome of death or ECMO use (0.9% vs 1.4%; aOR, 0.63; 95% CI, 0.54-0.73)., Conclusions and Relevance: Early use of oseltamivir in hospitalized children was associated with shorter hospital stay and lower odds of 7-day readmission, ICU transfer, ECMO use, and death. These findings support the current recommendations for oseltamivir use in children hospitalized with influenza.

It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis., Objective: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results., Methods: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results., Results: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL., Conclusions: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making., (Copyright © 2022 by the American Academy of Pediatrics.)

Despite clear testing recommendations for herpes simplex virus (HSV) infection in infants, few data exist on the comprehensiveness of HSV testing in practice. In a 23-center study of 112 infants with confirmed HSV disease, less than one-fifth had all recommended testing performed, highlighting the need for increased awareness of and adherence to testing recommendations for this vulnerable population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Oseltamivir therapy is recommended for all pediatric inpatients with influenza, particularly those with high-risk conditions, although data regarding its uptake and benefits are limited., Objective: To describe temporal patterns and independent patient factors associated with the use of oseltamivir and explore patterns in resource use and patient outcomes among children hospitalized with influenza., Design, Setting, and Participants: This multicenter retrospective cross-sectional study was conducted at 36 tertiary pediatric hospitals participating in the Pediatric Health Information System in the US. A total of 70 473 children younger than 18 years who were hospitalized with influenza between October 1, 2007, and March 31, 2020, were included., Exposures: Hospitalization with a diagnosis of influenza., Main Outcomes and Measures: The primary outcome was the use of oseltamivir, which was described by influenza season and by hospital. Patient factors associated with oseltamivir use were assessed using multivariable mixed-effects logistic regression models. Secondary outcomes were resource use (including antibiotic medications, chest radiography, supplemental oxygen, positive pressure ventilation, central venous catheter, and intensive care unit [ICU]) and patient outcomes (length of stay, late ICU transfer, 7-day hospital readmission, use of extracorporeal membrane oxygenation, and in-hospital mortality), which were described as percentages per influenza season., Results: Among 70 473 children hospitalized with influenza, the median (IQR) age was 3.65 (1.05-8.26) years; 30 750 patients (43.6%) were female, and 39 715 (56.4%) were male. Overall, 16 559 patients (23.5%) were Black, 36 184 (51.3%) were White, 14 133 (20.1%) were of other races (including 694 American Indian or Alaska Native [1.0%], 2216 Asian [3.0%], 372 Native Hawaiian or Pacific Islander [0.5%], and 10 850 other races [15.4%]), and 3597 (5.1%) were of unknown race. A total of 47 071 patients (66.8%) received oseltamivir, increasing from a low of 20.2% in the 2007-2008 influenza season to a high of 77.9% in the 2017-2018 season. Use by hospital ranged from 43.2% to 79.7% over the entire study period and from 56.5% to 90.1% in final influenza season studied (2019-2020). Factors associated with increased oseltamivir use included the presence of a complex chronic condition (odds ratio [OR], 1.42; 95% CI, 1.36-1.47), a history of asthma (OR, 1.31; 95% CI, 1.23-1.38), and early severe illness (OR, 1.19; 95% CI, 1.13-1.25). Children younger than 2 years (OR, 0.81; 95% CI, 0.77-0.85) and children aged 2 to 5 years (OR, 0.83; 95% CI, 0.79-0.88) had lower odds of receiving oseltamivir. From the beginning (2007-2008) to the end (2019-2020) of the study period, the use of antibiotic medications (from 74.4% to 60.1%) and chest radiography (from 59.2% to 51.7%) decreased, whereas the use of oxygen (from 33.6% to 29.3%), positive pressure ventilation (from 10.8% to 7.9%), and central venous catheters (from 2.5% to 1.0%) did not meaningfully change. Patient outcomes, including length of stay (median [IQR], 3 [2-5] days for all seasons), readmissions within 7 days (from 4.0% to 3.4%), use of extracorporeal membrane oxygenation (from 0.5% to 0.5%), and in-hospital mortality (from 1.1% to 0.8%), were stable from the beginning to the end of the study period., Conclusions and Relevance: In this cross-sectional study of children hospitalized with influenza, the use of oseltamivir increased over time, particularly among patients with high-risk conditions, but with wide institutional variation. Patient outcomes remained largely unchanged. Further work is needed to evaluate the impact of oseltamivir therapy in this population.

Background: It is unknown if probiotics exert pathogen-specific effects in children with diarrhea secondary to acute gastroenteritis., Methods: Analysis of patient-level data from 2 multicenter randomized, placebo controlled trials conducted in pediatric emergency departments in Canada and the United States. Participants were 3-48 months with >3 diarrheal episodes in the preceding 24 hours and were symptomatic for <72 hours and <7 days in the Canadian and US studies, respectively. Participants received either placebo or a probiotic preparation (Canada-Lactobacillus rhamnosus R0011/Lactobacillus helveticus R0052; US-L. rhamnosus GG). The primary outcome was post-intervention moderate-to-severe disease (ie, ≥9 on the Modified Vesikari Scale [MVS] score)., Results: Pathogens were identified in specimens from 59.3% of children (928/1565). No pathogen groups were less likely to experience an MVS score ≥9 based on treatment allocation (test for interaction = 0.35). No differences between groups were identified for adenovirus (adjusted relative risk [aRR]: 1.42; 95% confidence interval [CI]: .62, 3.23), norovirus (aRR: 0.98; 95% CI: .56, 1.74), rotavirus (aRR: 0.86; 95% CI: .43, 1.71) or bacteria (aRR: 1.19; 95% CI: .41, 3.43). At pathogen-group and among individual pathogens there were no differences in diarrhea duration or the total number of diarrheal stools between treatment groups, regardless of intervention allocation or among probiotic sub-groups. Among adenovirus-infected children, those administered the L. rhamnosus R0011/L. helveticus R0052 product experienced fewer diarrheal episodes (aRR: 0.65; 95% CI: .47, .90)., Conclusions: Neither probiotic product resulted in less severe disease compared to placebo across a range of the most common etiologic pathogens. The preponderance of evidence does not support the notion that there are pathogen specific benefits associated with probiotic use in children with acute gastroenteritis., Clinical Trials Registration: NCT01773967 and NCT01853124., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: Children with medical complexity (CMC) compose 1% of the pediatric population but account for 20% of pediatric emergency department (ED) visits. Previous descriptions of challenges and interventions to ensure quality of care are limited. Our objective was to elicit pediatric emergency medicine (PEM) physicians' perspectives on challenges and opportunities for improvement of emergency care of CMC, with a focus on emergency information forms (EIFs)., Methods: We conducted a web-based survey of PEM physicians participating the American Academy of Pediatrics Section on Emergency Medicine Survey listserv. The survey was designed using an expert panel, and subsequently piloted and revised to an 18-item survey. Data were analyzed with descriptive statistics., Results: One hundred fifty-one of 495 respondents (30%) completed the survey. Most respondents (62.9%) reported caring for >10 CMC per month. Whereas overall medical fragility and time constraints were major contributors to the challenges of caring for CMC in the ED, communication with known providers and shared care plans were identified as particularly helpful. Most respondents did not report routine use of EIFs. Anticipated emergencies/action plan was deemed the most important component of EIFs., Conclusions: Most PEM physicians view the care for CMC in the ED as challenging despite practicing in high-resource environments. Further research is needed to develop and implement strategies to improve care of CMC in the ED. Understanding experiences of providers in general ED settings is also an important next step given that 80% of CMC present for emergency care outside of major children's hospitals., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Describe the clinical presentation, prevalence of concurrent serious bacterial infection (SBI), and outcomes among infants with omphalitis., Methods: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants ≤90 days of age with omphalitis seen in the emergency department from January 1, 2008, to December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized., Results: Among 566 infants (median age 16 days), 537 (95%) were well-appearing, 64 (11%) had fever at home or in the emergency department, and 143 (25%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 472 (83%), 326 (58%), and 222 (39%) infants, respectively. Pathogens grew in 1.1% (95% confidence interval [CI], 0.3%-2.5%) of blood, 0.9% (95% CI, 0.2%-2.7%) of urine, and 0.9% (95% CI, 0.1%-3.2%) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 320 (57%) infants, with 85% (95% CI, 80%-88%) growing a pathogen, most commonly methicillin-sensitive Staphylococcus aureus (62%), followed by methicillin-resistant Staphylococcus aureus (11%) and Escherichia coli (10%). Four hundred ninety-eight (88%) were hospitalized, 81 (16%) to an ICU. Twelve (2.1% [95% CI, 1.1%-3.7%]) had sepsis or shock, and 2 (0.4% [95% CI, 0.0%-1.3%]) had severe cellulitis or necrotizing soft tissue infection. There was 1 death. Serious complications occurred only in infants aged <28 days., Conclusions: In this multicenter cohort, mild, localized disease was typical of omphalitis. SBI and adverse outcomes were uncommon. Depending on age, routine testing for SBI is likely unnecessary in most afebrile, well-appearing infants with omphalitis., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: To determine if low household income is associated with disease severity following emergency department (ED) discharge in children with acute gastroenteritis (AGE)., Methods: We conducted a secondary analysis employing data collected in 10 US-based tertiary-care, pediatric EDs between 2014 and 2017. Participants were aged 3 to 48 months and presented for care due to AGE. Income status was defined based on 1) home ZIP Code median annual home income and 2) percentage of home ZIP Code households below the poverty threshold. The primary outcome was moderate-to-severe AGE, defined by a post-ED visit Modified Vesikari Scale (MVS) score ≥9. Secondary outcomes included in-person revisits, revisits with intravenous rehydration, hospitalization, and etiologic pathogens., Results: About 943 (97%) participants with a median age of 17 months (interquartile range 10, 28) completed follow-up. Post-ED visit MVS scores were lower for the lowest household income group (adjusted: -0.60; 95% confidence interval [CI]: -1.13, -0.07). Odds of experiencing an MVS score ≥9 did not differ between groups (adjusted odds ratio: 0.91; 95% CI: 0.54, 1.52). No difference in the post-ED visit MVS score or the proportion of participants with scores ≥9 was observed using the national poverty threshold definition. For both income definitions, there were no differences in terms of revisits following discharge, hospitalizations, and intravenous rehydration. Bacterial enteropathogens were more commonly identified in the lowest socioeconomic group using both definitions., Conclusions: Lower household income was not associated with increased disease severity or resource use. Economic disparities do not appear to result in differences in the disease course of children with AGE seeking ED care., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Although most acute gastroenteritis (AGE) episodes in children rapidly self-resolve, some children go on to experience more significant and prolonged illness. We sought to develop a prognostic score to identify children at risk of experiencing moderate-to-severe disease after an index emergency department (ED) visit., Methods: Data were collected from a cohort of children 3 to 48 months of age diagnosed with AGE in 16 North American pediatric EDs. Moderate-to-severe AGE was defined as a Modified Vesikari Scale (MVS) score ≥9 during the 14-day post-ED visit. A clinical prognostic model was derived using multivariable logistic regression and converted into a simple risk score. The model's accuracy was assessed for moderate-to-severe AGE and several secondary outcomes., Results: After their index ED visit, 19% (336/1770) of participants developed moderate-to-severe AGE. Patient age, number of vomiting episodes, dehydration status, prior ED visits, and intravenous rehydration were associated with MVS ≥9 in multivariable regression. Calibration of the prognostic model was strong with a P value of 0.77 by the Hosmer-Lemenshow goodness-of-fit test, and discrimination was moderate with an area under the receiver operator characteristic curve of 0.68 (95% confidence interval [CI] 0.65-0.72). Similarly, the model was shown to have good calibration when fit to the secondary outcomes of subsequent ED revisit, intravenous rehydration, or hospitalization within 72 hours after the index visit., Conclusions: After external validation, this new risk score may provide clinicians with accurate prognostic insight into the likely disease course of children with AGE, informing disposition decisions, anticipatory guidance, and follow-up care., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively., Objective: We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility., Methods: We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale., Results: The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices., Conclusions: We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The use of free open-access medical education (FOAM) and other online knowledge dissemination methods has increased over the past decade. However, the role and impact of these tools in the knowledge translation continuum are poorly understood, potentially limiting the ability of knowledge generators to fully harness and exploit their potential. Here, we aim to comprehensively map and synthesize the literature describing the use of online tools for the dissemination of emergency medicine research., Methods: Using scoping review methodology, we searched the traditional literature via PubMed, CINAHL, EMBASE, ERIC, SCOPUS, and the gray literature for publications exploring online methods to disseminate new research findings. We synthesized the results and constructed a conceptual model of current research dissemination methods., Results: We included 79 out of 655 unique abstracts and articles identified in our search, 62 of which were from the traditional literature. We describe six primary domains: integration with traditional literature, measurement of dissemination, online organizations and communities of practice, professional development, quality assurance tools and techniques, and advantages and disadvantages of FOAM. For each domain we present an exemplar article and prevailing gaps in knowledge. Finally, we propose a current conceptual framework for dissemination of new research findings that describes both traditional and novel methods of dissemination., Conclusions: This comprehensive review of the literature and current dissemination framework will empower researchers, research networks, and granting organizations to maximize their use of FOAM and other online methods to disseminate new knowledge as well as provide clinicians a better understanding of the tools and methods by which to access and implement new research findings., Competing Interests: The authors have no potential conflicts to disclose., (© 2022 by the Society for Academic Emergency Medicine.)

Study Objective: This study aimed to explore oral ondansetron usage and impact on outcomes in clinical practice., Methods: This observational study was a planned secondary analysis of 2 trials conducted in 10 US and 6 Canadian institutions between 2014 and 2017. Children 3 to 48 months old with gastroenteritis and ≥3 episodes of vomiting in the 24 hours preceding emergency department (ED) presentation were included. Oral ondansetron was administered at the discretion of the provider. The principal outcomes were intravenous fluid administration and hospitalization at the index visit and during the subsequent 72 hours and diarrhea and vomiting frequency during the 24 hours following the ED visit., Results: In total, 794 children were included. The median age was 16.0 months (interquartile range 10.0 to 26.0), and 50.1% (398/794) received oral ondansetron. In propensity-adjusted analysis (n=528), children administered oral ondansetron were less likely to receive intravenous fluids at the index visit (adjusted odds ratio [aOR] 0.50; 95% confidence interval [CI] 0.29 to 0.88). There were no differences in the frequencies of intravenous fluid administration within the first 72 hours (aOR 0.65; 95% CI 0.39 to 1.10) or hospitalization at the index visit (aOR 0.31; 95% CI 0.09 to 1.10) or the subsequent 72 hours (aOR 0.52; 95% CI 0.21 to 1.28). Episodes of vomiting (aRR 0.86; 95% CI 0.63 to 1.19) and diarrhea (aRR 1.11; 95% CI 0.93 to 1.32) during the 24 hours following ED discharge also did not differ., Conclusion: Among preschool-aged children with gastroenteritis seeking ED care, oral ondansetron administration was associated with a reduction in index ED visit intravenous fluid administration; it was not associated with intravenous fluids administered within 72 hours, hospitalization, or vomiting and diarrhea in the 24 hours following discharge., (Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection., Methods: In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively., Results: Of all infants included, 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] <14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with >28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43)., Conclusions: A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Andrea Cruz is an associate editor for Pediatrics. The other authors have no relevant conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Introduction: It is unclear whether the alleged efficacy of probiotics in childhood acute gastroenteritis depends on the duration and severity of symptoms before treatment., Methods: Preplanned secondary analysis of 2 randomized placebo-controlled trials in children 3-48 months of age was conducted in 16 emergency departments in North America evaluating the efficacy of 2 probiotic products (Lactobacillus rhamnosus GG and a combination probiotic: L. rhamnosus and L. helveticus). Participants were categorized in severity groups according to the duration (<24, 24-<72, and ≥72 hours) and the frequency of diarrhea episodes in the 24 hours (≤3, 4-5, and ≥6) before presentation. We used regression models to assess the interaction between pretreatment diarrhea severity groups and treatment arm (probiotic or placebo) in the presence of moderate-to-severe gastroenteritis (Modified Vesikari Scale score ≥9). Secondary outcomes included diarrhea frequency and duration, unscheduled healthcare provider visits, and hospitalization., Results: A total of 1,770 children were included, and 882 (50%) received a probiotic. The development of moderate-to-severe gastroenteritis symptoms after the initiation of treatment did not differ between groups (probiotic-18.4% [162/882] vs placebo-18.3% [162/888]; risk ratio 1.00; 95% confidence interval 0.87, 1.16; P = 0.95). There was no evidence of interaction between baseline severity and treatment (P = 0.61) for the primary or any of the secondary outcomes: diarrhea duration (P = 0.88), maximum diarrheal episodes in a 24-hour period (P = 0.87), unscheduled healthcare visits (P = 0.21), and hospitalization (P = 0.87)., Discussion: In children 3-48 months with acute gastroenteritis, the lack of effect of probiotics is not explained by the duration of symptoms or frequency of diarrheal episodes before presentation., (Copyright © 2021 by The American College of Gastroenterology.)

Objectives: Describe the clinical presentation, prevalence, and outcomes of concurrent serious bacterial infection (SBI) among infants with mastitis., Methods: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants aged ≤90 days with mastitis who were seen in the emergency department between January 1, 2008, and December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized., Results: Among 657 infants (median age 21 days), 641 (98%) were well appearing, 138 (21%) had history of fever at home or in the emergency department, and 63 (10%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 581 (88%), 274 (42%), and 216 (33%) infants, respectively. Pathogens grew in 0.3% (95% confidence interval [CI] 0.04-1.2) of blood, 1.1% (95% CI 0.2-3.2) of urine, and 0.4% (95% CI 0.01-2.5) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 335 (51%) infants, with 77% (95% CI 72-81) growing a pathogen, most commonly methicillin-resistant Staphylococcus aureus (54%), followed by methicillin-susceptible S aureus (29%), and unspecified S aureus (8%). A total of 591 (90%) infants were admitted to the hospital, with 22 (3.7%) admitted to an ICU. Overall, 10 (1.5% [95% CI 0.7-2.8]) had sepsis or shock, and 2 (0.3% [95% CI 0.04-1.1]) had severe cellulitis or necrotizing soft tissue infection. None received vasopressors or endotracheal intubation. There were no deaths., Conclusions: In this multicenter cohort, mild localized disease was typical of neonatal mastitis. SBI and adverse outcomes were rare. Evaluation for SBI is likely unnecessary in most afebrile, well-appearing infants with mastitis., Competing Interests: POTENTIAL CONFLICTS OF INTEREST: Dr Andrea Cruz is an associate editor of Pediatrics; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: There is no widely adopted severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions, thus limiting the ability to optimize and standardize management practices and advance research., Objective: The aim of this study was to develop a severity grading system for acute allergic reactions for use in clinical care and research., Methods: From May to September 2020, we convened a 21-member multidisciplinary panel of allergy and emergency care experts; 9 members formed a writing group to critically appraise and assess the strengths and limitations of prior severity grading systems and develop the structure and content for an optimal severity grading system. The entire study panel then revised the grading system and sought consensus by utilizing Delphi methodology., Results: The writing group recommended that an optimal grading system encompass the severity of acute allergic reactions on a continuum from mild allergic reactions to anaphylactic shock. Additionally, the severity grading system must be able to discriminate between clinically important differences in reaction severity to be relevant in research while also being intuitive and straightforward to apply in clinical care. Consensus was reached for all elements of the proposed severity grading system., Conclusion: We developed a consensus severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions. Successful international validation, refinement, dissemination, and application of the grading system will improve communication among providers and patients about the severity of allergic reactions and will help advance future research., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Between-country variation in health care resource use and its impact on outcomes in acute care settings have been challenging to disentangle from illness severity by using administrative data., Methods: We conducted a preplanned analysis employing patient-level emergency department (ED) data from children enrolled in 2 previously conducted clinical trials. Participants aged 3 to <48 months with <72 hours of gastroenteritis were recruited in pediatric EDs in the United States ( N = 10 sites; 588 participants) and Canada ( N = 6 sites; 827 participants). The primary outcome was an unscheduled health care provider visit within 7 days; the secondary outcomes were intravenous fluid administration and hospitalization at or within 7 days of the index visit., Results: In adjusted analysis, unscheduled revisits within 7 days did not differ (adjusted odds ratio [aOR]: 0.72; 95% confidence interval (CI): 0.50 to 1.02). At the index ED visit, although participants in Canada were assessed as being more dehydrated, intravenous fluids were administered more frequently in the United States (aOR: 4.6; 95% CI: 2.9 to 7.1). Intravenous fluid administration rates did not differ after enrollment (aOR: 1.4; 95% CI: 0.7 to 2.8; US cohort with Canadian as referent). Overall, intravenous rehydration was higher in the United States (aOR: 3.8; 95% CI: 2.5 to 5.7). Although hospitalization rates during the 7 days after enrollment (aOR: 1.1; 95% CI: 0.4 to 2.6) did not differ, hospitalization at the index visit was more common in the United States (3.9% vs 2.3%; aOR: 3.2; 95% CI: 1.6 to 6.8)., Conclusions: Among children with gastroenteritis and similar disease severity, revisit rates were similar in our 2 study cohorts, despite lower rates of intravenous rehydration and hospitalization in Canadian-based EDs., 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 assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting., Study Design: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness., Results: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%., Conclusions: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: We previously conducted the Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) study, which identified no improvements in children with acute gastroenteritis (AGE) administered a probiotic. However, the aforementioned study did not evaluate immunomodulatory benefits., Objectives: The object of this study was to determine if stool secretory immunoglobulin A (sIgA) concentrations in children with AGE increase more among participants administered a Lactobacillus rhamnosus/helveticus probiotic compared with those administered placebo., Methods: This a priori planned multicenter, randomized, double-blinded, placebo-controlled ancillary study enrolled children presenting for emergency care who received a 5-d probiotic or placebo course. Participants submitted stool specimens on days 0, 5, and 28. The primary endpoint was the change in stool sIgA concentrations on day 5 compared with baseline., Results: A total of 133 (n = 66 probiotic, 67 placebo) of 886 PROGUT participants (15.0%) provided all 3 specimens. Median stool sIgA concentrations did not differ between the probiotic and placebo groups at any of the study time points: day 0 median (IQR): 1999 (768, 4071) compared with 2198 (702, 5278) (P = 0.27, Cohen's d = 0.17); day 5: 2505 (1111, 5310) compared with 3207 (982, 7080) (P = 0.19, Cohen's d = 0.16); and day 28: 1377 (697, 2248) compared with 1779 (660, 3977) (P = 0.27, Cohen's d = 0.19), respectively. When comparing measured sIgA concentrations between days 0 and 5, we found no treatment allocation effects [β: -0.24 (-0.65, 0.18); P = 0.26] or interaction between treatment and specimen collection day [β: -0.003 (-0.09, 0.09); P = 0.95]. Although stool sIgA decreased between day 5 and day 28 within both groups (P < 0.001), there were no differences between the probiotic and placebo groups in the median changes in sIgA concentrations when comparing day 0 to day 5 median (IQR) [500 (-1135, 2362) compared with 362 (-1122, 4256); P = 0.77, Cohen's d = 0.075] and day 5 to day 28 [-1035 (-3130, 499) compared with -1260 (-4437, 843); P = 0.70, Cohen's d = 0.067], respectively., Conclusions: We found no effect of an L. rhamnosus/helveticus probiotic, relative to placebo, on stool IgA concentrations. This trial was registered at clinicaltrials.gov as NCT01853124., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Importance: Despite guidelines endorsing oral rehydration therapy, intravenous fluids are commonly administered to children with acute gastroenteritis in high-income countries., Objective: To identify factors associated with intravenous fluid administration and hospitalization in children with acute gastroenteritis., Design, Setting, and Participants: This study is a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) probiotic trials. Participants include children aged 3 to 48 months with 3 or more watery stools in 24 hours between November 5, 2013, and April 7, 2017, for the PERC study and July 8, 2014, and June 23, 2017, for the PECARN Study. Children were from 16 pediatric emergency departments throughout Canada (6) and the US (10). Data were analyzed from November 2, 2018, to March 16, 2021., Exposures: Sex, age, preceding health care visit, distance between home and hospital, country (US vs Canada), frequency and duration of vomiting and diarrhea, presence of fever, Clinical Dehydration Scale score, oral ondansetron followed by oral rehydration therapy, and infectious agent., Main Outcomes and Measures: Intravenous fluid administration and hospitalization., Results: This secondary analysis of 2 randomized clinical trials included 1846 children (mean [SD] age, 19.1 [11.4] months; 1007 boys [54.6%]), of whom 534 of 1846 (28.9%) received oral ondansetron, 240 of 1846 (13.0%) received intravenous rehydration, and 67 of 1846 (3.6%) were hospitalized. The following were independently associated with intravenous rehydration: higher Clinical Dehydration Scale score (mild to moderate vs none, odds ratio [OR], 8.73; 95% CI, 5.81-13.13; and severe vs none, OR, 34.15; 95% CI, 13.45-86.73); country (US vs Canada, OR, 6.76; 95% CI, 3.15-14.49); prior health care visit with intravenous fluids (OR, 4.55; 95% CI, 1.32-15.72); and frequency of vomiting (per 5 episodes, OR, 1.66; 95% CI, 1.39-1.99). The following were independently associated with hospitalization: higher Clinical Dehydration Scale score (mild to moderate vs none, OR, 11.10; 95% CI, 5.05-24.38; and severe vs none, OR, 23.55; 95% CI, 7.09-78.25) and country (US vs Canada, OR, 3.37; 95% CI, 1.36-8.40). Oral ondansetron was associated with reduced odds of intravenous rehydration (OR, 0.21; 95% CI, 0.13-0.32) and hospitalization (OR, 0.44; 95% CI, 0.21-0.89)., Conclusions and Relevance: Intravenous rehydration and hospitalization were associated with clinical evidence of dehydration and lack of an oral ondansetron-supported oral rehydration period. Strategies focusing on oral ondansetron administration followed by oral rehydration therapy in children with dehydration may reduce the reliance on intravenous rehydration and hospitalization., Trial Registration: ClinicalTrials.gov Identifiers: NCT01853124 (PERC) and NCT01773967 (PECARN).

Purpose: To identify factors associated with firearm injury (FI) and willingness to enroll in a violence intervention program amongst pediatric victims of violence., Methods: Cross-sectional study of victims of violence age 6-19 years presenting to a children's hospital emergency department from 2014 to 2017. Participants were interviewed by social workers prior to being offered enrollment in a violence intervention program. We used multivariate logistic regression analyses to identify factors associated with FI and enrollment in the violence intervention program., Results: Four hundred seven patients were analyzed, 156 (38%) of which were victims of FI and 251 (62%) were victims of non-firearm-related physical assaults (PA). Multiple factors were associated with FI including older adolescent age, male sex, separated/divorced parents, losses in family/social network due to violence, being on probation, illicit substance use, gang affiliation, and lack of school enrollment. One hundred four patients (26%) enrolled in the violence intervention program. There was no difference in enrollment between FI and PA. However, older adolescent age, illicit substance use and probation were associated with significantly decreased odds of enrolling in the program., Conclusions: Multiple identifiable and potentially actionable risk factors exist amongst pediatric victims of acute FI. More specific targeting of at-risk groups may improve enrollment in violence interventions programs., Level of Evidence: This is a prognostic study, investigating the natural history of pediatric firearm injuries, factors associated with firearm injuries as well as those associated with patient propensity to enroll in a violence intervention program. This study is observational in nature and utilizes patients with non-firearm-related physical assaults as a control group, making this study Level III evidence., (Published by Elsevier Inc.)

Introduction: There remain significant knowledge gaps about the management and outcomes of children with anaphylaxis. These gaps have led to practice variation regarding decisions to hospitalise children and length of observation periods following treatment with epinephrine. The objectives of this multicentre study are to (1) determine the prevalence of and risk factors for severe, persistent, refractory and biphasic anaphylaxis, as well as persistent and biphasic non-anaphylactic reactions; (2) derive and validate prediction models for emergency department (ED) discharge; and (3) determine data-driven lengths of ED and inpatient observation prior to discharge to home based on initial reaction severity., Methods and Analysis: The study is being conducted through the Pediatric Emergency Medicine Collaborative Research Committee (PEMCRC). Children 6 months to less than 18 years of age presenting to 30 participating EDs for anaphylaxis from October 2015 to December 2019 will be eligible. The primary outcomes for each objective are (1) severe, persistent, refractory or biphasic anaphylaxis, as well as persistent or biphasic non-anaphylactic reactions; (2) safe ED discharge, defined as no receipt of acute anaphylaxis medications or hypotension beyond 4 hours from first administered dose of epinephrine; and (3) time from first to last administered dose of epinephrine and vasopressor cessation. Analyses for each objective include (1) descriptive statistics to estimate prevalence and generalised estimating equations that will be used to investigate risk factors for anaphylaxis outcomes, (2) least absolute shrinkage and selection operator regression and binary recursive partitioning to derive and validate prediction models of children who may be candidates for safe ED discharge, and (3) Kaplan-Meier analyses to assess timing from first to last epinephrine doses and vasopressor cessation based on initial reaction severity., Ethics and Dissemination: All sites will obtain institutional review board approval; results will be published in peer-reviewed journals and disseminated via traditional and social media, blogs and online education platforms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gastroenteritis is a common and impactful disease in childhood. Probiotics are often used to treat acute gastroenteritis (AGE); however, in a large multicenter randomized controlled trial (RCT) in 971 children, Lactobacillus rhamnosus GG (LGG) was no better than placebo in improving patient outcomes., Objectives: We sought to determine whether the effect of LGG is associated with age, weight z score and weight percentile adjusted for age and sex, or dose per kilogram administered., Methods: This was a preplanned secondary analysis of a multicenter double-blind RCT of LGG 1 × 1010 CFU twice daily for 5 d or placebo in children 3-48 mo of age with AGE. Our primary outcome was moderate to severe gastroenteritis. Secondary outcomes included diarrhea and vomiting frequency and duration, chronic diarrhea, and side effects. We used multivariable linear and nonlinear models testing for interaction effects to assess outcomes by age, weight z score and weight percentile adjusted for age and sex, and dose per kilogram of LGG received., Results: A total of 813 children (84%) were included in the analysis; 413 received placebo and 400 LGG. Baseline characteristics were similar between treatment groups. There were no differential interaction effects across ranges of age (P-interaction = 0.32), adjusted weight z score (P-interaction = 0.43), adjusted weight percentile (P-interaction = 0.45), or dose per kilogram of LGG received (P-interaction = 0.28) for the primary outcome. Whereas we found a statistical association favoring placebo at the extremes of adjusted weight z scores for the number of vomiting episodes (P-interaction = 0.02) and vomiting duration (P-interaction = 0.0475), there were no statistically significant differences in other secondary outcome measures (all P-interactions > 0.05)., Conclusions: LGG does not improve outcomes in children with AGE regardless of the age, adjusted weight z score, and adjusted weight percentile of participants, or the probiotic dose per kilogram received. These results further strengthen the conclusions of low risk of bias clinical trials which demonstrate that LGG provides no clinical benefit in children with AGE.This trial was registered at clinicaltrials.gov as NCT01773967., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Abstract: Nonadherence in clinical trials affects safety and efficacy determinations. Predictors of nonadherence in pediatric acute illness trials are unknown. We sought to examine predictors of nonadherence in a multicenter randomized trial of 971 children with acute gastroenteritis receiving a 5-day oral course of Lactobacillus rhamnosus GG or placebo. Adherence, defined as consuming all doses of the product, was reported by the parents and recorded during daily follow-up contacts. Of 943 patients with follow-up data, 766 (81.2%) were adherent. On multivariate analysis, older age (OR 1.19; 95% CI: 1.00-1.43), increased vomiting duration (OR 1.23; 95% CI: 1.05-1.45), higher dehydration score (OR 1.23, 95% CI: 1.07-1.42), and hospitalization following ED discharge (OR 4.16, 95% CI: 1.21--14.30) were factors associated with nonadherence; however, those with highest severity scores were more likely to adhere (OR 0.87, 95% CI: 0.80-0.95). These data may inform strategies and specific targets to maximize adherence in future pediatric trials., Competing Interests: S.B.F. has received in-kind (study drug and placebo) from Institut Lallemand Inc, Novartis and GlaxoSmithKline. He provides consulting services to Takeda Pharmaceutical Company, RedHill Biopharma Ltd and Eligo Bioscience S.A.S. on childhood intestinal disorders and is supported by the Alberta Children's Hospital Foundation Professorship in Child Health and Wellness. P.I.T. is a consultant to, a holder of equity in, and a member of the Scientific Advisory Board of MediBeacon Inc, which is developing technology to test intestinal permeability in people, and is a co-inventor on a patent that might generate royalties on this technology in the future. He is also a consultant to Takeda Pharmaceuticals on childhood intestinal disorders. All other authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts., Objective: Our aim was to develop consensus definitions for clinically relevant anaphylaxis outcomes by utilizing a multidisciplinary group of clinical and research experts in anaphylaxis., Methods: Using Delphi methodology, we developed agenda topics and drafted questions to review during monthly conference calls. Through online surveys, a 19-member panel consisting of experts in allergy and/or immunology and emergency medicine rated their level of agreement with the appropriateness of statements on a scale of 1 to 9. A median value of 1.0 to 3.4 was considered inappropriate, a median value of 3.5 to 6.9 was considered uncertain, and a median value of 7.0 to 9.0 was considered appropriate. A disagreement index was then calculated, with values less than 1.0 categorized as "consensus reached." If consensus was not reached after the initial survey, subsequent surveys incorporating the aggregate de-identified responses from prior surveys were sent to panel members. This process was repeated until consensus was reached or 4 survey rounds had been completed, after which the question was categorized as "no consensus reached.", Results: The panel developed outcome definitions for persistent, refractory, and biphasic anaphylaxis, as well as for persistent and biphasic nonanaphylactic reactions. There was also consensus among panel members regarding the need to develop an anaphylaxis severity grading system., Conclusion: Dissemination and application of these definitions in clinical care and research will help standardize the terminology used to describe anaphylaxis outcomes and serve as the foundation for future research, including research aimed at development of an anaphylaxis severity grading system., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The aim of this review is to provide an update of nonantibiotic therapies for acute gastroenteritis (AGE), focusing on antiemetics and probiotics., Recent Findings: The mainstay of therapy for nonsevere AGE remains oral rehydration therapy (ORT). Recent randomized controlled trials and metaanalyses have further strengthened the evidence-base supporting single-dose ondansetron administration in emergency departments to facilitate ORT based on evidence that it safely reduces intravenous fluid administration and hospitalization rates. Intravenous ondansetron administration and multiple-dose use should be avoided. A bimodal release ondansetron formulation was shown to improve outcomes in adolescents and adults with AGE in one study, but further evidence is required to support use. Recent large trials evaluating probiotic administration demonstrated a lack of benefit and guidelines that recommend their use should reevaluate their positions in light of this evidence. Furthermore, caution should be exercised when use is considered in high-risk populations and settings., Summary: The benefits, dosing/route, and target populations most likely to benefit from ondansetron have been further clarified. Optimization of the real-life effectiveness of this therapy will require implementation strategies. Recent high-quality evidence showing a lack of efficacy and potential harm associated with probiotic use suggests that routine use for AGE should be discouraged.