Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.

Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.

Predictors of Adherence to Short-Course Probiotics Among Children with Gastroenteritis who are Enrolled in a Clinical Trial.

BACKGROUND: To improve our understanding of adherence to discharge medications in the ED and within research trials, we sought to quantify medication adherence and identify predictors thereof in children with acute gastroenteritis (AGE). METHODS: We conducted a secondary analysis of a randomized trial of twice daily probiotic for 5 days. The population included previously healthy children aged 3-47 months with AGE. The primary outcome was patient-reported adherence to the treatment regimen, defined a priori as having received >70% of the prescribed doses. Secondary outcomes included predictors of treatment adherence and concordance between patient-reported adherence and the returned medication sachet counts. RESULTS: After excluding participants with missing data on adherence, 760 participants were included in this analysis: 383 in the probiotic arm (50.4%); and 377 in the placebo arm (49.6%). Self-reported adherence was similar in both groups (77.0% in probiotic versus 80.3% in placebo). There was good agreement between self-reported adherence and sachet counts (87% within limits of agreement (-2.9 to 3.5 sachets) on the Bland-Altman plots). In the multivariable regression model, covariates associated with adherence were greater number of days of diarrhea post-emergency department visit, and the study site; covariates negatively associated with adherence were age 12-23 months, severe dehydration and greater total number of vomiting and diarrhea episodes after enrolment. CONCLUSIONS: Longer duration of diarrhea and study site were associated with higher probiotic adherence. Age 12-23 months, severe dehydration and greater number of vomiting and diarrhea episodes post enrolment negatively predicted treatment adherence.

Intestinal Microbial Composition of Children in a Randomized Controlled Trial of Probiotics to Treat Acute Gastroenteritis.

Compositional analysis of the intestinal microbiome in pre-schoolers is understudied. Effects of probiotics on the gut microbiota were evaluated in children under 4-years-old presenting to an emergency department with acute gastroenteritis. Included were 70 study participants (n=32 placebo, n=38 probiotics) with stool specimens at baseline (day 0), day 5, and after a washout period (day 28). Microbiota composition and deduced functions were profiled using 16S ribosomal RNA sequencing and predictive metagenomics, respectively. Probiotics were detected at day 5 of administration but otherwise had no discernable effects, whereas detection of bacterial infection (P<0.001) and participant age (P<0.001) had the largest effects on microbiota composition, microbial diversity, and deduced bacterial functions. Participants under 1 year had lower bacterial diversity than older aged pre-schoolers; compositional changes of individual bacterial taxa were associated with maturation of the gut microbiota. Advances in age were associated with differences in gut microbiota composition and deduced microbial functions, which have the potential to impact health later in life. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01853124.

Derivation of the Pediatric Acute Gastroenteritis Risk Score to Predict Moderate-to-Severe Acute Gastroenteritis.

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.

Pathogen-Specific Effects of Probiotics in Children With Acute Gastroenteritis Seeking Emergency Care: A Randomized Trial.

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.

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.

Is early activity resumption after paediatric concussion safe and does it reduce symptom burden at 2 weeks post injury? The Pediatric Concussion Assessment of Rest and Exertion (PedCARE) multicentre randomised clinical trial.

OBJECTIVE: Investigate whether resuming physical activity (PA) at 72 hours post concussion is safe and reduces symptoms at 2 weeks, compared with resting until asymptomatic. METHODS: Real-life conditions, multicentre, single-blinded randomised clinical trial, conducted in three Canadian paediatric emergency departments (ED). Children/youth aged 10-<18 years with acute concussion were recruited between March 2017 and December 2019, and randomly assigned to a 4-week stepwise return-to-PA protocol at 72 hours post concussion even if symptomatic (experimental group (EG)) or to a return-to-PA once asymptomatic protocol (control group (CG)). The primary outcome was self-reported symptoms at 2 weeks using the Health and Behaviour Inventory. Adherence was measured using accelerometers worn 24 hours/day for 14 days post injury. Adverse events (AE) (worsening of symptoms requiring unscheduled ED or primary care visit) were monitored. Multivariable intention-to-treat (ITT) and per-protocol analyses adjusting for prognostically important covariates were examined. Missing data were imputed for the ITT analysis. RESULTS: 456 randomised participants (EG: N=227; mean (SD) age=13.3 (2.1) years; 44.5% women; CG: N=229; mean (SD) age=13.3 (2.2) years; 43.7% women) were analysed. No AE were identified. ITT analysis showed no strong evidence of a group difference at 2 weeks (adjusted mean difference=-1.3 (95% CI:-3.6 to 1.1)). In adherent participants, initiating PA 72 hours post injury significantly reduced symptoms 2 weeks post injury, compared with rest (adjusted mean difference=-4.3 (95% CI:-8.4 to -0.2)). CONCLUSION: Symptoms at 2 weeks did not differ significantly between children/youth randomised to initiate PA 72 hours post injury versus resting until asymptomatic; however, many were non-adherent to the intervention. Among adherent participants, early PA was associated with reduced symptoms at 2 weeks. Resumption of PA is safe and may be associated with milder symptoms at 2 weeks. LEVEL OF EVIDENCE: 1b. TRIAL REGISTRATION NUMBER: NCT02893969. REGISTRY NAME: Pediatric Concussion Assessment of Rest and Exertion (PedCARE).

Probiotic stool secretory immunoglobulin A modulation in children with gastroenteritis: a randomized clinical trial.

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 [ß: -0.24 (-0.65, 0.18); P = 0.26] or interaction between treatment and specimen collection day [ß: -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.

Comparing Pediatric Gastroenteritis Emergency Department Care in Canada and the United States.

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.

Variables Associated With Intravenous Rehydration and Hospitalization in Children With Acute Gastroenteritis: A Secondary Analysis of 2 Randomized Clinical Trials.

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).

A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis.

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.

Simulation-Based Event Analysis Improves Error Discovery and Generates Improved Strategies for Error Prevention.

INTRODUCTION: An adverse event (AE) is a negative consequence of health care that results in unintended injury or illness. The study investigates whether simulation-based event analysis is different from traditional event analysis in uncovering root causes and generating recommendations when analyzing AEs in hospitalized children. METHODS: Two simulation scenarios were created based on real-life AEs identified through the hospital's Safety Reporting System. Scenario A involved an error of commission (inpatient drug error) and scenario B involved detecting an error that already occurred (drug infusion error). Each scenario was repeated 5 times with different, voluntary clinicians. Content analysis, using deductive and inductive approaches to coding, was used to analyze debriefing data. Causes and recommendations were compiled and compared with the traditional event analysis. RESULTS: Errors were reproduced in 60% (3/5) of scenario A. In scenario B, participants identified the error in 100% (5/5) of simulations (average time to error detection = 15 minutes). Debriefings identified reasons for errors including product labeling, memory aid interpretation, and lack of standard work for patient handover. To prevent error, participants suggested improved drug labeling, specialized drug kits, alert signs, and handoff checklists. Compared with traditional event analysis, simulation-based event analysis revealed unique causes for error and new recommendations. CONCLUSIONS: Using simulation to analyze AEs increased unique error discovery and generated new recommendations. This method is different from traditional event analysis because of the immediate clinician debriefings in the clinical environment. Hospitals should consider simulation-based event analysis as an important addition to the traditional process.

Derivation and Initial Validation of Clinical Phenotypes of Children Presenting with Concussion Acutely in the Emergency Department: Latent Class Analysis of a Multi-Center, Prospective Cohort, Observational Study.

The identification of clinical phenotypes may help parse the substantial heterogeneity that characterizes children with concussion. This study used latent class analysis (LCA) to identify discernible phenotypes among children with acute concussion and examine the association between phenotypes and persistent post-concussive symptoms (PPCS) at 4 and 12 weeks post-injury. We conducted LCA of variables representing pre-injury history, clinical presentation, and parent symptom ratings, derived from a prospective cohort, observational study that recruited participants from August 2013 until June 2015 at nine pediatric emergency departments within the Pediatric Emergency Research Canada network. This substudy included 2323 children from the original cohort ages 8.00-17.99 years who had data for at least 80% of all variables included in each LCA. Concussion was defined according to Zurich consensus statement diagnostic criteria. The primary outcome was PPCS at 4 and 12 weeks after enrollment. Participants were 39.5% female and had a mean age of 12.8 years (standard deviation = 2.6). Follow-up was completed by 1980 (85%) at 4 weeks and 1744 (75%) at 12 weeks. LCA identified four groups with discrete pre-injury histories, four groups with discrete clinical presentations, and seven groups with discrete profiles of acute symptoms. Clinical phenotypes based on the profile of group membership across the three LCAs varied significantly in their predicted probability of PPCS at 4 and 12 weeks. The results indicate that children with concussion can be grouped into distinct clinical phenotypes, based on pre-injury history, clinical presentation, and acute symptoms, with markedly different risks of PPCS. With further validation, clinical phenotypes may provide a useful heuristic for clinical assessment and management.

Multicentre, randomised clinical trial of paediatric concussion assessment of rest and exertion (PedCARE): a study to determine when to resume physical activities following concussion in children.

INTRODUCTION: Rest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol. METHODS AND ANALYSIS: This study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total of 350 participants, aged 10-17.99 years, who present within 48 hours of an acute concussion, will be recruited and randomly assigned to either the study intervention protocol (resumption of physical activity 72 hours postconcussion even if experiencing symptoms) or physical rest until fully asymptomatic. Participants will document their daily physical and cognitive activities. Follow-up questionnaires will be completed at 1, 2 and 4 weeks postinjury. Compliance with the intervention will be measured using an accelerometer (24 hours/day for 14 days). Symptoms will be measured using the validated Health and Behaviour Inventory. A linear multivariable model, adjusting for site and prognostically important covariates, will be tested to determine differences between groups. The proposed protocol adheres to the RCT-CONSORT guidelines. DISCUSSION: This trial will determine if early resumption of non-contact physical activity following concussion reduces the burden of concussion and will provide healthcare professionals with the evidence by which to recommend the best timing of reintroducing physical activities. TRIAL REGISTRATION NUMBER: Trial identifier (Clinicaltrials.gov) NCT02893969.

Multicenter Trial of a Combination Probiotic for Children with Gastroenteritis.

BACKGROUND: Gastroenteritis accounts for approximately 1.7 million visits to the emergency department (ED) by children in the United States every year. Data to determine whether the use of probiotics improves outcomes in these children are lacking. METHODS: We conducted a randomized, double-blind trial involving 886 children 3 to 48 months of age with gastroenteritis who presented to six pediatric EDs in Canada. Participants received a 5-day course of a combination probiotic product containing Lactobacillus rhamnosus R0011 and L. helveticus R0052, at a dose of 4.0×109 colony-forming units twice daily or placebo. The primary outcome was moderate-to-severe gastroenteritis, which was defined according to a post-enrollment modified Vesikari scale symptom score of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease). Secondary outcomes included the duration of diarrhea and vomiting, the percentage of children who had unscheduled physician visits, and the presence or absence of adverse events. RESULTS: Moderate-to-severe gastroenteritis within 14 days after enrollment occurred in 108 of 414 participants (26.1%) who were assigned to probiotics and 102 of 413 participants (24.7%) who were assigned to placebo (odds ratio, 1.06; 95% confidence interval [CI], 0.77 to 1.46; P=0.72). After adjustment for trial site, age, detection of rotavirus in stool, and frequency of diarrhea and vomiting before enrollment, trial-group assignment did not predict moderate-to-severe gastroenteritis (odds ratio, 1.06; 95% CI, 0.76 to 1.49; P=0.74). There were no significant differences between the probiotic group and the placebo group in the median duration of diarrhea (52.5 hours [interquartile range, 18.3 to 95.8] and 55.5 hours [interquartile range, 20.2 to 102.3], respectively; P=0.31) or vomiting (17.7 hours [interquartile range, 0 to 58.6] and 18.7 hours [interquartile range, 0 to 51.6], P=0.18), the percentages of participants with unscheduled visits to a health care provider (30.2% and 26.6%; odds ratio, 1.19; 95% CI, 0.87 to 1.62; P=0.27), and the percentage of participants who reported an adverse event (34.8% and 38.7%; odds ratio, 0.83; 95% CI, 0.62 to 1.11; P=0.21). CONCLUSIONS: In children who presented to the emergency department with gastroenteritis, twice-daily administration of a combined L. rhamnosus-L. helveticus probiotic did not prevent the development of moderate-to-severe gastroenteritis within 14 days after enrollment. (Funded by the Canadian Institutes of Health Research and others; PROGUT ClinicalTrials.gov number, NCT01853124 .).

Association of Preprocedural Fasting With Outcomes of Emergency Department Sedation in Children.

Importance: It is not clear whether adherence to preprocedural fasting guidelines prevent pulmonary aspiration and associated adverse outcomes during emergency department (ED) sedation of children. Objective: To examine the association between preprocedural fasting duration and the incidence of sedation-related adverse outcomes in a large sample of children. Design, Setting, and Participants: We conducted a planned secondary analysis of a multicenter prospective cohort study of children aged 0 to 18 years who received procedural sedation for a painful procedure in 6 Canadian pediatric EDs from July 2010 to February 2015. The primary risk factor was preprocedural fasting duration. Secondary risk factors were age, sex, American Society of Anesthesiologists classification, preprocedural and sedation medications, and procedure type. Main Outcomes and Measures: Four outcomes were examined: (1) pulmonary aspiration, (2) the occurrence of any adverse event, (3) serious adverse events, and (4) vomiting. Results: A total of 6183 children with a median age of 8.0 years (interquartile range, 4.0-12.0 years), of whom 6166 (99.7%) had healthy or mild systemic disease (American Society of Anesthesiologists levels I or II), were included in the analysis. Of these, 2974 (48.1%) and 310 (5.0%) children did not meet American Society of Anesthesiologists fasting guidelines for solids and liquids, respectively. There were no cases of pulmonary aspiration. There were 717 adverse events (11.6%; 95% CI, 10.8%-12.4%), of which 68 (1.1%; 95% CI, 0.9%-1.3%) were serious adverse events and 315 (5.1%; 95% CI, 4.6%-5.7%) were vomiting. The odds ratio (OR) of occurrence of any adverse event, serious adverse events, and vomiting did not change significantly with each additional hour of fasting duration for both solids (any adverse event: OR, 1.00; 95% CI, 0.98 to 1.02; serious adverse events, OR, 1.01; 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.97-1.03) and liquids (any adverse event: OR, 1.00; 95% CI, 0.98-1.02; serious adverse events: 1.01, 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.96-1.03). Conclusions and Relevance: In this study, there was no association between fasting duration and any type of adverse event. These findings do not support delaying sedation to meet established fasting guidelines.

Barriers and enablers to a physician-delivered educational initiative to reduce low-acuity visits to the pediatric emergency department.

BACKGROUND: Use of the pediatric emergency department (PED) for low-acuity health issues is a growing problem, contributing to overcrowding, longer waits and higher health system costs. This study examines an educational initiative aimed at reducing low-acuity PED visits. The initiative, implemented at an academic pediatric hospital, saw PED physicians share a pamphlet with caregivers to educate them about appropriate PED use and alternatives. Despite early impacts, the initiative was not sustained. This study analyzes the barriers and enablers to physician participation in the initiative, and offers strategies to improve implementation and sustainability of similar future initiatives. METHODS: Forty-two PED physicians were invited to participate in a semi-structured individual interview assessing their views about low-acuity visits, their pamphlet use, barriers and enablers to pamphlet use, and the initiative's potential for reducing low-acuity visits. Suggestions were solicited for improving the initiative and reducing low-acuity visits. Constant comparative method was used during analysis. Codes were developed inductively and iteratively, then grouped according to the Theoretical Domains Framework (TDF). Efforts to ensure study credibility included seeking participant feedback on the findings. RESULTS: Twenty-three PED physicians were interviewed (55%). Barriers and enablers for pamphlet use were identified and grouped according to five of the 14 TDF domains: social/professional role and identity; beliefs about consequences; environmental context and resources; social influences; and emotions. CONCLUSIONS: The TDF provided an effective approach to identify the key elements influencing physician participation in the educational initiative. This information will help inform behavior change interventions to improve the implementation of similar future initiatives that involve physicians as the primary educators of caregivers.

Risk Factors for Adverse Events in Emergency Department Procedural Sedation for Children.

Importance: Procedural sedation for children undergoing painful procedures is standard practice in emergency departments worldwide. Previous studies of emergency department sedation are limited by their single-center design and are underpowered to identify risk factors for serious adverse events (SAEs), thereby limiting their influence on sedation practice and patient outcomes. Objective: To examine the incidence and risk factors associated with sedation-related SAEs. Design, Setting, and Participants: This prospective, multicenter, observational cohort study was conducted in 6 pediatric emergency departments in Canada between July 10, 2010, and February 28, 2015. Children 18 years or younger who received sedation for a painful emergency department procedure were enrolled in the study. Of the 9657 patients eligible for inclusion, 6760 (70.0%) were enrolled and 6295 (65.1%) were included in the final analysis. Exposures: The primary risk factor was receipt of sedation medication. The secondary risk factors were demographic characteristics, preprocedural medications and fasting status, current or underlying health risks, and procedure type. Main Outcomes and Measures: Four outcomes were examined: SAEs, significant interventions performed in response to an adverse event, oxygen desaturation, and vomiting. Results: Of the 6295 children included in this study, 4190 (66.6%) were male and the mean (SD) age was 8.0 (4.6) years. Adverse events occurred in 736 patients (11.7%; 95% CI, 6.4%-16.9%). Oxygen desaturation (353 patients [5.6%]) and vomiting (328 [5.2%]) were the most common of these adverse events. There were 69 SAEs (1.1%; 95% CI, 0.5%-1.7%), and 86 patients (1.4%; 95% CI, 0.7%-2.1%) had a significant intervention. Use of ketamine hydrochloride alone resulted in the lowest incidence of SAEs (17 [0.4%]) and significant interventions (37 [0.9%]). The incidence of adverse sedation outcomes varied significantly with the type of sedation medication. Compared with ketamine alone, propofol alone (3.7%; odds ratio [OR], 5.6; 95% CI, 2.3-13.1) and the combinations of ketamine and fentanyl citrate (3.2%; OR, 6.5; 95% CI, 2.5-15.2) and ketamine and propofol (2.1%; OR, 4.4; 95% CI, 2.3-8.7) had the highest incidence of SAEs. The combinations of ketamine and fentanyl (4.1%; OR, 4.0; 95% CI, 1.8-8.1) and ketamine and propofol (2.5%; OR, 2.2; 95% CI, 1.2-3.8) had the highest incidence of significant interventions. Conclusions and Relevance: The incidence of adverse sedation outcomes varied significantly with type of sedation medication. Use of ketamine only was associated with the best outcomes, resulting in significantly fewer SAEs and interventions than ketamine combined with propofol or fentanyl.

Education in the Waiting Room: Description of a Pediatric Emergency Department Educational Initiative.

OBJECTIVE: The aim of this study was to understand parents' awareness of and reactions to a slide presentation based waiting-room educational initiative. METHODS: This was a prospective observational study at a Canadian tertiary-care pediatric emergency department (ED) with an annual census of 68,000 visits. An anonymous parental survey was developed de novo, and parents were asked to complete the survey during their low-acuity ED visit over a 2-week study period. Descriptive statistics were used to describe responses and themes. RESULTS: Parents completed 520 surveys (733 approached, 70.9% response rate). Eighty-three percent of respondents had previously sought care in the ED. Most parents (68.9%) were aware of the slide presentation, but only 33.7% were able to watch it in its entirety (20 minutes' duration). Of those who watched the whole presentation, 62.9% understood that lower-acuity cases are assessed in the ambulatory zone of the ED, and sicker children are assessed in the acute zone (89.4%), 79.9% felt the presentation helped them to understand how the ambulatory zone functions, and 83.2% appreciated the current wait-time information. General questions about common health concerns were answered correctly in 58.3% (fever), 56.0% (gastroenteritis), 50.5% (abdominal pain/constipation), 35.7% (earache), and 17.0% (head injury). CONCLUSIONS: The majority of parents were aware of this waiting-room educational initiative, but there was variable uptake of information. Parents watching the entire presentation appreciated the information provided, especially wait-time information, and felt it improved their experience. Knowledge of common health conditions was low; novel methods of knowledge transfer must be utilized and evaluated.

A nurse-initiated jaundice management protocol improves quality of care in the paediatric emergency department.

BACKGROUND: Hyperbilirubinemia is a common neonatal condition requiring timely management to prevent acute bilirubin encephalopathy. Management protocols allow nonphysicians to initiate designated actions prior to physician assessment. OBJECTIVE: To assess the effectiveness of a nurse-initiated neonatal jaundice management protocol for serum bilirubin sampling and phototherapy for neonates presenting with hyperbilirubinemia to the Paediatric Emergency Department (PED). METHODS: A health records review was performed for jaundiced neonates 12 months prior to the introduction of the management protocol (control period) and 12 months after (intervention period). Randomly selected charts were evaluated for time to serum bilirubin sampling, phototherapy initiation, ED length of stay, admission rate, completion of direct antiglobulin test and nursing documentation. RESULTS: Two hundred and sixty-six neonates (131 control and 135 intervention) were included. Median time to serum bilirubin sampling was reduced by 22% (36 min versus 28 min; P<0.001) with 34 min difference at the 90th percentile (94 min [95% confidence interval (CI) 63.7 to 116.9] versus 60 min [95% CI 49.0 to 78.2]). Statistically significant improvements were found in time to phototherapy initiation (127 min [95% CI 72.0 to 160.7] versus 65 min [95% CI 50.0 to 72.4] at 90th percentile), ED length of stay (267 min [95% CI 180.9 to 292.9] versus 216 min [95% CI 171.1 to 247.4] at 90th percentile) and hospital admissions (36% versus 17%; P<0.001). Improvements were also observed in direct antiglobulin test measurement (P<0.001) and nursing documentation (P=0.017). CONCLUSIONS: Implementation of a PED neonatal jaundice management protocol was associated with improved timeliness and standardization of care for this common and important condition.