Search

ObjectivesWe 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.DesignA secondary analysis of a retrospective cohort study.Setting38 paediatric EDs belonging to the Paediatric Emergency Research Network in Canada, USA, Australia/New Zealand UK/Ireland and Spain/Portugal.PatientsOtherwise healthy infants 2-11 months old diagnosed with bronchiolitis between 1 January 2013 and 31 December, 2013.Outcome measuresPrimary 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.Results1137/2356 (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)).ConclusionsInfants 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.

UNLABELLED: 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

BackgroundIt is unknown if probiotics exert pathogen-specific effects in children with diarrhea secondary to acute gastroenteritis.MethodsAnalysis 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

ObjectiveTo determine if low household income is associated with disease severity following emergency department (ED) discharge in children with acute gastroenteritis (AGE).MethodsWe 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.ResultsAbout 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.ConclusionsLower 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.

ObjectivesAlthough 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.MethodsData 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.ResultsAfter 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.ConclusionsAfter 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.

Study objectiveThis study aimed to explore oral ondansetron usage and impact on outcomes in clinical practice.MethodsThis 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.ResultsIn 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.ConclusionAmong 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.

IntroductionIt is unclear whether the alleged efficacy of probiotics in childhood acute gastroenteritis depends on the duration and severity of symptoms before treatment.MethodsPreplanned 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 (

BackgroundBetween-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.MethodsWe conducted a preplanned analysis employing patient-level emergency department (ED) data from children enrolled in 2 previously conducted clinical trials. Participants aged 3 to

AbstractNonadherence 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.

BackgroundGastroenteritis 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.ObjectivesWe 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.MethodsThis 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.ResultsA 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).ConclusionsLGG 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.

BackgroundAcute gastroenteritis develops in millions of children in the United States every year, and treatment with probiotics is common. However, data to support the use of probiotics in this population are limited.MethodsWe conducted a prospective, randomized, double-blind trial involving children 3 months to 4 years of age with acute gastroenteritis who presented to one of 10 U.S. pediatric emergency departments. Participants received a 5-day course of Lactobacillus rhamnosus GG at a dose of 1×1010 colony-forming units twice daily or matching placebo. Follow-up surveys were conducted daily for 5 days and again 14 days after enrollment and 1 month after enrollment. The primary outcome was moderate-to-severe gastroenteritis, which was defined as an illness episode with a total score on the modified Vesikari scale of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease), within 14 days after enrollment. Secondary outcomes included the duration and frequency of diarrhea and vomiting, the duration of day-care absenteeism, and the rate of household transmission (defined as the development of symptoms of gastroenteritis in previously asymptomatic household contacts).ResultsAmong the 971 participants, 943 (97.1%) completed the trial. The median age was 1.4 years (interquartile range, 0.9 to 2.3), and 513 participants (52.9%) were male. The modified Vesikari scale score for the 14-day period after enrollment was 9 or higher in 55 of 468 participants (11.8%) in the L. rhamnosus GG group and in 60 of 475 participants (12.6%) in the placebo group (relative risk, 0.96; 95% confidence interval, 0.68 to 1.35; P=0.83). There were no significant differences between the L. rhamnosus GG group and the placebo group in the duration of diarrhea (median, 49.7 hours in the L. rhamnosus GG group and 50.9 hours in the placebo group; P=0.26), duration of vomiting (median, 0 hours in both groups; P=0.17), or day-care absenteeism (median, 2 days in both groups; P=0.67) or in the rate of household transmission (10.6% and 14.1% in the two groups, respectively; P=0.16).ConclusionsAmong preschool children with acute gastroenteritis, those who received a 5-day course of L. rhamnosus GG did not have better outcomes than those who received placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01773967 .).

BACKGROUND:Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed. METHODS:We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns. RESULTS:Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%-0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9-24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4-6.2). Sixty-eight (0.26%, 95% CI: 0.21%-0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%-72%) and to whom acyclovir was administered (23%; range 4%-53%) varied widely across sites. CONCLUSIONS:An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.

IntroductionAcute gastroenteritis (AGE) is a common and burdensome condition that affects millions of children worldwide each year. Currently available strategies are limited to symptomatic management, treatment and prevention of dehydration and infection control; no disease-modifying interventions exist. Probiotics, defined as live microorganisms beneficial to the host, have shown promise in improving AGE outcomes, but existing studies have sufficient limitations such that the use of probiotics cannot currently be recommended with confidence. Here we present the methods of a large, rigorous, randomised, double-blind placebo-controlled study to assess the effectiveness and side effect profile of Lactobacillus rhamnosus GG (LGG) (ATCC 53103) in children with AGE.Methods and analysisThe study is being conducted in 10 US paediatric emergency departments (EDs) within the federally funded Pediatric Emergency Care Applied Research Network, in accordance with current SPIRIT and CONSORT statement recommendations. We will randomise 970 children presenting to participating EDs with AGE to either 5 days of treatment with LGG (1010colony-forming unit twice a day) or placebo between July 2014 to December 2017. The main outcome is the occurrence of moderate-to-severe disease over time, as defined by the Modified Vesikari Scale. We also record adverse events and side effects related to the intervention. We will conduct intention-to-treat analyses and use an enrichment design to restore the statistical power in case the presence of a subpopulation with a substantially low treatment effect is identified.Ethics and disseminationInstitutional review board approval has been obtained at all sites, and data and material use agreements have been established between the participating sites. The results of the trial will be published in peer-reviewed journals. A deidentified public data set will be made available after the completion of all study procedures.Trial registration numberNCT01773967.

ObjectiveTo determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection.Study designWe performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005-2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result.ResultsOf 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0-0.4).ConclusionsAlthough enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one-third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

The authors consider the case of a pragmatic clinical trial that raises important questions between informed consent and the risks associated with complex interventions and high stakes outcomes. Topics discussed include an approach to the ethical questions that arose in this trial and the need for more empirical research to guide the approach to future pragmatic trials.