Omphalitis and Concurrent Serious Bacterial Infection.

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.

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.

Lack of Association of Household Income and Acute Gastroenteritis Disease Severity in Young Children: A Cohort Study.

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.

Adolescent alcohol use predicts cannabis use over a three year follow-up period.

Background: Alcohol and cannabis use frequently co-occur, which can result in problems from social and academic impairment to dependence (i.e., alcohol use disorder [AUD] and/or cannabis use disorder [CUD]). The Emergency Department (ED) is an excellent site to identify adolescents with alcohol misuse, conduct a brief intervention, and refer to treatment; however, given time constraints, alcohol use may be the only substance assessed due to its common role in unintentional injury. The current study, a secondary data analysis, assessed the relationship between adolescent alcohol and cannabis use by examining the National Institute of Alcohol Abuse and Alcoholism (NIAAA) two question screen's (2QS) ability to predict future CUD at one, two, and three years post-ED visit. Methods: At baseline, data was collected via tablet self-report surveys from medically and behaviorally stable adolescents 12-17 years old (n = 1,689) treated in 16 pediatric EDs for non-life-threatening injury, illness, or mental health condition. Follow-up surveys were completed via telephone or web-based survey. Logistic regression compared CUD diagnosis odds at one, two, or three-year follow-up between levels constituting a single-level change in baseline risk categorization on the NIAAA 2QS (nondrinker versus low-risk, low- versus moderate-risk, moderate- versus high-risk). Receiver operating characteristic curve methods examined the predictive ability of the baseline NIAAA 2QS cut points for CUD at one, two, or three-year follow-up. Results: Adolescents with low alcohol risk had significantly higher rates of CUD versus nondrinkers (OR range: 1.94-2.76, p < .0001). For low and moderate alcohol risk, there was no difference in CUD rates (OR range: 1.00-1.08). CUD rates were higher in adolescents with high alcohol risk versus moderate risk (OR range: 2.39-4.81, p < .05). Conclusions: Even low levels of baseline alcohol use are associated with risk for a later CUD. The NIAAA 2QS is an appropriate assessment measure to gauge risk for future cannabis use.

Neonatal Mastitis and Concurrent Serious Bacterial Infection.

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.

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.

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).

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.

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.

Predictive Validity of a 2-Question Alcohol Screen at 1-, 2-, and 3-Year Follow-up.

BACKGROUND: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) 2-question screen is a valid adolescent alcohol screening tool. No studies have examined if this tool predicts future alcohol problems. We conducted a study at 16 pediatric emergency departments to determine the tool's predictive validity for alcohol misuse and alcohol use disorders (AUDs). METHODS: Participants (N = 4834) completed a baseline assessment battery. A subsample of participants completed the battery at 1, 2, and 3 years follow up. RESULTS: Of the 2209 participants assigned to follow-up, 1611 (73%) completed a 1-year follow-up, 1591 (72%) completed a 2-year follow-up, and 1377 (62%) completed a 3-year follow-up. The differences in AUDs between baseline NIAAA screen nondrinkers and lower-risk drinkers were statistically significant at 1 year (P = .0002), 2 years (P <.0001), and 3 years (P = .0005), as were the differences between moderate- and highest-risk drinkers at 1 and 2 years (P < .0001 and P = .0088, respectively) but not at 3 years (P = .0758). The best combined score for sensitivity (86.2% at 1 year, 75.6% at 2 years, and 60.0% at 3 years) and specificity (78.1% at 1 year, 79.2% at 2 years, and 80.0% at 3 years) was achieved by using "lower risk" and higher as a cutoff for the prediction of a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis. CONCLUSIONS: The NIAAA 2-question screen can accurately characterize adolescent risk for future AUDs. Future studies are needed to determine optimaluse of the screen.

Screening for Adolescent Alcohol Use in the Emergency Department: What Does It Tell Us About Cannabis, Tobacco, and Other Drug Use?

BACKGROUND: The pediatric emergency department (PED) represents an opportune time for alcohol and drug screening. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) recommends a two-question alcohol screen for adolescents as a predictor of alcohol and drug misuse. OBJECTIVE: A multi-site PED study was conducted to determine the association between the NIAAA two-question alcohol screen and adolescent cannabis use disorders (CUD), cigarette smoking, and lifetime use of other drugs. METHODS: Participants included 12-17-year olds (n = 4834) treated in one of 16 participating PEDs. An assessment battery, including the NIAAA two-question screen and other measures of alcohol, tobacco and drug use, was self-administered on a tablet computer. RESULTS: A diagnosis of CUD, lifetime tobacco use or lifetime drug use was predicted by any self-reported alcohol use in the past year, which indicates a classification of moderate risk for middle school ages and low risk for high school ages on the NIAAA two-question screen. Drinking was most strongly predictive of a CUD, somewhat weaker for lifetime tobacco use, and weakest for lifetime drug use. This same pattern held for high school and middle school students and was stronger for high school students over middle school students for all three categories. This association was also found across gender, ethnicity and race. The association was strongest for CUD for high school students, sensitivity 81.7% (95% CI, 77.0, 86.5) and specificity 70.4% (95% CI, 68.6, 72.1). Conclusions/Importance: A single question about past year alcohol use can provide valuable information about other substance use, particularly marijuana.

Methodology and Demographics of a Brief Adolescent Alcohol Screen Validation Study.

OBJECTIVE: The aim of this study was to determine the psychometric properties of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) 2-question alcohol screen within 16 Pediatric Emergency Care Applied Research Network pediatric emergency departments. This article describes the study methodology, sample characteristics, and baseline outcomes of the NIAAA 2-question screen. METHODS: Participants included 12- to 17-year-olds treated in one of the participating pediatric emergency departments across the United States. After enrollment, a criterion assessment battery including the NIAAA 2-question screen and other measures of alcohol, drug use, and risk behavior was self-administered by participants on a tablet computer. Two subsamples were derived from the sample. The first subsample was readministered the NIAAA 2-question screen 1 week after their initial visit to assess test-retest reliability. The second subsample is being reassessed at 12 and 24 months to examine predictive validity of the NIAAA 2-question screen. RESULTS: There were 4834 participants enrolled into the study who completed baseline assessments. Participants were equally distributed across sex and age. Forty-six percent of the participants identified as white, and 26% identified as black. Approximately one quarter identified as Hispanic. Using the NIAAA 2-question screen algorithm, approximately 8% were classified as low risk, 12% were classified as moderate risk, and 4% were classified as highest risk. Alcohol use was less likely to be reported by black participants, non-Hispanic participants, and those younger than 16 years. DISCUSSION: This study successfully recruited a large, demographically diverse sample to establish rates of the NIAAA screen risk categories across age, sex, ethnicity, and race within pediatric emergency departments.

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 .).

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.

Diagnostic performance of a biomarker panel as a negative predictor for acute appendicitis in adult ED patients with abdominal pain.

OBJECTIVES: Evaluate the diagnostic accuracy of the APPY1TM biomarker panel, previously described for use in pediatric patients, for identifying adult ED patients with abdominal pain who are at low risk of acute appendicitis. METHODS: This study prospectively enrolled subjects >18years of age presenting to seven U.S. emergency departments with <72hours of abdominal pain suggesting possible acute appendicitis. The APPY1 panel was performed on blood samples drawn from each patient at the time of initial evaluation and results were correlated with the final diagnosis either positive or negative for acute appendicitis. RESULTS: 431 patients were enrolled with 422 completing all aspects of the study. The APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3-99.3%), a negative predictive value of 98.4% (95% CI, 94.4-99.6%), a negative likelihood ratio of 0.07 (95% CI, 0.02-0.27), with a specificity of 36.5% (95% CI, 31.6-41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%) patients who did not have appendicitis with 2 (2.5%) false negatives. The CT utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232 were done for patients who did not have appendicitis and 79 (34%) of these patients were correctly identified as negative with "low risk" biomarker panel results, representing 26% (79/307) of all CT scans performed. CONCLUSION: This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult cohort, thereby potentially reducing the dependence on CT for the evaluation of possible acute appendicitis.

Challenges Enrolling Children Into Traumatic Brain Injury Trials: An Observational Study.

OBJECTIVES: In preparation for a clinical trial of therapeutic agents for children with moderate-to-severe blunt traumatic brain injuries (TBIs) in emergency departments (EDs), we conducted this feasibility study to (1) determine the number and clinical characteristics of eligible children, (2) determine the timing of patient and guardian arrival to the ED, and (3) describe the heterogeneity of TBIs on computed tomography (CT) scans. METHODS: We conducted a prospective observational study at 16 EDs of children ≤ 18 years of age presenting with blunt head trauma and Glasgow Coma Scale scores of 3-12. We documented the number of potentially eligible patients, timing of patient and guardian arrival, patient demographics and clinical characteristics, severity of injuries, and cranial CT findings. RESULTS: We enrolled 295 eligible children at the 16 sites over 6 consecutive months. Cardiac arrest and nonsurvivable injuries were the most common characteristics that would exclude patients from a future trial. Most children arrived within 2 hours of injury, but most guardians did not arrive until 2-3 hours after the injury. There was a substantial range in types of TBIs, with subdural hemorrhages being the most common. CONCLUSION: Enrolling children with moderate-to-severe TBI into time-sensitive clinical trials will require large numbers of sites and meticulous preparation and coordination and will prove challenging to obtain informed consent given the timing of patient and guardian arrival. The Federal Exception from Informed Consent for Emergency Research will be an important consideration for enrolling these children.

Addition of a biomarker panel to a clinical score to identify patients at low risk for appendicitis.

BACKGROUND: The diagnosis of pediatric acute appendicitis can be difficult. Although scoring systems such as the Pediatric Appendicitis Score (PAS) are helpful, they lack adequate sensitivity and specificity as standalone diagnostics. When used for risk stratification, they often result in large percentages of moderate-risk patients requiring further diagnostic evaluation. METHODS: We applied a biomarker panel (the APPY1 Test) that has high sensitivity and negative predictive value (NPV) to patients with PAS in the moderate-risk range (3-7) and reclassified those patients with a negative result to the low-risk group. We compared the specificity, sensitivity, and NPV of the original and reclassified low-risk groups at several different PAS low-risk cutoffs. RESULTS: The application of a negative biomarker panel to a group of patients with a moderate risk for appendicitis (PAS, 3-7) resulted in 4 times more patients (586 vs 145) being safely classified as low risk. Reclassification increased the overall specificity or the proportion of patients without appendicitis who were correctly identified as low risk, from 10.3% to 42.0%. The high NPV (97.2%) in the original group was preserved (97.6%) in the reclassified low-risk group, as was the sensitivity (original 99.1% vs reclassified 96.9%). CONCLUSION: The addition of negative biomarker test results to patients with a moderate risk of appendicitis based on the PAS can safely reclassify many to a low-risk group. This may allow clinicians to provide more conservative management in children with suspected appendicitis and decrease unnecessary resource utilization.