Oral Ondansetron Administration in Children Seeking Emergency Department Care for Acute Gastroenteritis: A Patient-Level Propensity-Matched Analysis.

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.

Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children.

BACKGROUND: Acute 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. METHODS: We 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). RESULTS: Among 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). CONCLUSIONS: Among 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 .).

Association Between Diarrhea Duration and Severity and Probiotic Efficacy in Children With Acute Gastroenteritis.

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.

Association between Age, Weight, and Dose and Clinical Response to Probiotics in Children with Acute Gastroenteritis.

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.

Factors Associated With Nonadherence in an Emergency Department-based Multicenter Randomized Clinical Trial of a Probiotic in Children With Acute Gastroenteritis.

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.

Do Adolescents With Higher Knowledge of HIV Have Lower Sexual Risk Behaviors?

OBJECTIVES: Human immunodeficiency virus (HIV) remains a leading cause of morbidity and mortality in the United States, and adolescents account for a disproportionate number of new cases. We aimed to assess knowledge of HIV in relation to sexual risk behaviors among adolescents seeking care in our pediatric emergency department and to assess sources of HIV knowledge among this population. METHODS: Adolescents aged 14 to 21 years who presented to the pediatric emergency department participated in a questionnaire assessing HIV knowledge, sexual risk behaviors, and sources of HIV knowledge. For purposes of statistical analysis, patients were divided into a high-score (greater than or equal to the median score) or low-score (less than the median score) group based on the HIV-Knowledge Questionnaire 18 portion of the survey. RESULTS: A total of 240 adolescents were enrolled. Of those, 112 patients scored higher than or equal to the median HIV-Knowledge Questionnaire 18 score of 11. High-scoring knowledge was independently associated with patients 18 years or older (P = 0.001), any lifetime sexual activity (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.30-3.67; P = 0.003), previous testing for HIV (OR, 2.40; 95% CI, 1.40-4.11; P = 0.002), and an "expert" source (school-based or medical professionals) as their primary source of knowledge (OR, 1.88; 95% CI, 1.05-3.41; P = 0.034). Age of first sexual encounter, number of partners, and condom use were not significantly associated with knowledge score. CONCLUSIONS: Education from "expert" sources is important in providing adolescents with accurate information. However, education alone is unlikely to change sexual practices. A more comprehensive approach to HIV prevention is needed to decrease HIV transmission among this patient population.

Implementation of Targeted Point of Care HIV Testing in a Pediatric Emergency Department.

HIV infection rates are increasing among adolescents. Despite guidelines recommending annual HIV screening among sexually active adolescents, 3.6% of adolescents tested for other sexually transmitted infections (STI) in a pediatric emergency department (PED) were screened for HIV. The aim was to increase HIV screening to 90%. METHODS: Interventions were designed to address 4 key drivers thought to be critical in reliably offering HIV testing. The primary outcome measure was the proportion of adolescents offered HIV testing among those being tested for common STIs. Statistical process control charts were used to measure performance over time and differentiate common versus special cause variation. RESULTS: We instituted point of care (POC) HIV testing in the PED in January 2012. The proportion of STI tested patients offered HIV testing was increased to >87% and sustained this performance. Implementation of a clinical decision support tool had the highest impact. The majority offered testing agreed, and the most common reason for refusal was a recent negative test. We identified eleven HIV positive patients over 5 years. Eight were newly diagnosed, and 3 had prior positive tests but were not connected to care. All 11 were successfully connected to providers with HIV care expertise. CONCLUSIONS: POC HIV testing is feasible, acceptable, and sustainable in a PED setting. The implementation of targeted HIV POC testing in the PED increased the number of HIV tests being offered, the number of high-risk patients being screened, and the number diagnosed and connected to care.

Randomised controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol.

INTRODUCTION: Acute 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 ANALYSIS: The 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 DISSEMINATION: Institutional 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 NUMBER: NCT01773967.