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Gastroenteritis accounts for nearly 500,000 deaths in children younger than 5 years annually. Although probiotics have been touted as having the potential to expedite diarrhea resolution, recent clinical trials question their effectiveness. A potential explanation is a shift in pathogens following the introduction of a rotavirus vaccine. Here, we report the results of a multi-center, double-blind trial of 816 children with acute gastroenteritis who completed follow-up and provided multiple stool specimens. Participants were randomized to receive a probiotic containing Lactobacillus rhamnosus and Lactobacillus helveticus or placebo. We report no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or viral nucleic acid clearance from stool specimens collected up to 28 days following enrollment. We provide pathophysiological and microbiologic evidence to support the clinical findings and conclude that our data do not support routine probiotic administration to children with acute gastroenteritis, regardless of the infecting virus. Here, the authors report the results of a randomized, placebo controlled trial of children with acute gastroenteritis who were treated with a probiotic and find no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or clearance of viral nucleic acid from stool specimens.

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.

Background Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished. Results We studied a cohort of febrile term infants < 60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E . coli . Infants with E . coli infections who were colonized by the putatively isogenic pathogen strain had significantly higher E . coli phylogroup B2 abundance in their gut, and their microbiome was more likely to contain virulence factor loci associated with adherence, exotoxin production, and nutritional/metabolic function. Conclusions The intestine plausibly serves as a reservoir for EBI pathogens in a subset of febrile term infants, prompting consideration of new opportunities for surveillance and EBI prevention among colonized, pre-symptomatic infants. FR_LxsBa6e-P_DcxZo_3p7 Video Abstract

IntroductionThere 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 analysisThe 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 disseminationAll 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.

(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.

Restoring intestinal flora may improve outcomes in children with acute gastroenteritis. In this multicenter trial, the administration of lactobacillus for 5 days in children with acute gastroenteritis was not associated with clinical benefit.

Acute gastroenteritis is a common illness, and treatment with probiotics is common. In a double-blind, placebo-controlled trial, treatment with Lactobacillus rhamnosus GG was found to afford no benefit in reducing symptoms associated with acute gastroenteritis in children.

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