Post-COVID-19 Condition in Children 6 and 12 Months After Infection.

Importance: There is a need to understand the long-term outcomes among children infected with SARS-CoV-2. Objective: To quantify the prevalence of post-COVID-19 condition (PCC) among children tested for SARS-CoV-2 infection in pediatric emergency departments (EDs). Design, Setting, and Participants: Multicenter, prospective cohort study at 14 Canadian tertiary pediatric EDs that are members of the Pediatric Emergency Research Canada network with 90-day, 6-month, and 12-month follow-up. Participants were children younger than 18 years who were tested for SARS-CoV-2 infection between August 2020 and February 2022. Data were analyzed from May to November 2023. Exposure: The presence of SARS-CoV-2 infection at or within 14 days of the index ED visit. Main Outcomes and Measures: Presence of symptoms and QoL reductions that meet the PCC definition. This includes any symptom with onset within 3 months of infection that is ongoing at the time of follow-up and affects everyday functioning. The outcome was quantified at 6 and 12 months following the index ED visit. Results: Among the 5147 children at 6 months (1152 with SARS-CoV-2 positive tests and 3995 with negative tests) and 5563 children at 12 months (1192 with SARS-CoV-2 positive tests and 4371 with negative tests) who had sufficient data regarding the primary outcome to enable PCC classification, the median (IQR) age was 2.0 (0.9-5.0) years, and 2956 of 5563 (53.1%) were male. At 6-month follow-up, symptoms and QoL changes consistent with the PCC definition were present in 6 of 1152 children with positive SARS-CoV-2 tests (0.52%) and 4 of 3995 children with negative SARS-CoV-2 tests (0.10%; absolute risk difference, 0.42%; 95% CI, 0.02% to 0.94%). The PCC definition was met at 12 months by 8 of 1192 children with positive SARS-CoV-2 tests (0.67%) and 7 of 4371 children with negative SARS-CoV-2 tests (0.16%; absolute risk difference, 0.51%; 95% CI, 0.06 to 1.08%). At 12 months, the median (IQR) PedsQL Generic Core Scale scores were 98.4 (90.0-100) among children with positive SARS-CoV-2 tests and 98.8 (91.7-100) among children with negative SARS-CoV-2 tests (difference, -0.3; 95% CI, -1.5 to 0.8; P = .56). Among the 8 children with SARS-CoV-2 positive tests and PCC at 12-month follow-up, children reported respiratory (7 of 8 patients [88%]), systemic (3 of 8 patients [38%]), and neurologic (1 of 8 patients [13%]) symptoms. Conclusions and Relevance: In this cohort study of children tested for SARS-CoV-2 infection in Canadian pediatric EDs, although children infected with SARS-CoV-2 reported increased chronic symptoms, few of these children developed PCC, and overall QoL did not differ from children with negative SARS-CoV-2 tests.

Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada.

Importance: Clinical manifestations of SARS-CoV-2 variants have not been systematically compared in children. Objective: To compare symptoms, emergency department (ED) chest radiography, treatments, and outcomes among children with different SARS-CoV-2 variants. Design, Setting, and Participants: This multicenter cohort study was performed at 14 Canadian pediatric EDs. Participants included children and adolescents younger than 18 years (hereinafter referred to as children) tested for SARS-CoV-2 infection in an ED between August 4, 2020, and February 22, 2022, with 14 days of follow-up. Exposure(s): SARS-CoV-2 variants detected on a specimen collected from the nasopharynx, nares, or throat. Main Outcomes and Measures: The primary outcome was presence and number of presenting symptoms. The secondary outcomes were presence of core COVID-19 symptoms, chest radiography findings, treatments, and 14-day outcomes. Results: Among 7272 participants presenting to an ED, 1440 (19.8%) had test results positive for SARS-CoV-2 infection. Of these, 801 (55.6%) were boys, with a median age of 2.0 (IQR, 0.6-7.0) years. Children with the Alpha variant reported the fewest core COVID-19 symptoms (195 of 237 [82.3%]), which were most often reported by participants with Omicron variant infection (434 of 468 [92.7%]; difference, 10.5% [95% CI, 5.1%-15.9%]). In a multivariable model with the original type as the referent, the Omicron and Delta variants were associated with fever (odds ratios [ORs], 2.00 [95% CI, 1.43-2.80] and 1.93 [95% CI, 1.33-2.78], respectively) and cough (ORs, 1.42 [95% CI, 1.06-1.91] and 1.57 [95% CI, 1.13-2.17], respectively). Upper respiratory tract symptoms were associated with Delta infection (OR, 1.96 [95% CI, 1.38-2.79]); lower respiratory tract and systemic symptoms were associated with Omicron variant infection (ORs, 1.42 [95% CI, 1.04-1.92] and 1.77 [95% CI, 1.24-2.52], respectively). Children with Omicron infection most often had chest radiography performed and received treatments; compared with those who had Delta infection, they were more likely to have chest radiography performed (difference, 9.7% [95% CI, 4.7%-14.8%]), to receive intravenous fluids (difference, 5.6% [95% CI, 1.0%-10.2%]) and corticosteroids (difference, 7.9% [95% CI, 3.2%-12.7%]), and to have an ED revisit (difference, 8.8% [95% CI, 3.5%-14.1%]). The proportions of children admitted to the hospital and intensive care unit did not differ between variants. Conclusions and Relevance: The findings of this cohort study of SARS-CoV-2 variants suggest that the Omicron and Delta variants were more strongly associated with fever and cough than the original-type virus and the Alpha variant. Children with Omicron variant infection were more likely to report lower respiratory tract symptoms and systemic manifestations, undergo chest radiography, and receive interventions. No differences were found in undesirable outcomes (ie, hospitalization, intensive care unit admission) across variants.

Association Between Early Return to School Following Acute Concussion and Symptom Burden at 2 Weeks Postinjury.

Importance: Determining how the timing of return to school is related to later symptom burden is important for early postinjury management recommendations. Objective: To examine the typical time to return to school after a concussion and evaluate whether an earlier return to school is associated with symptom burden 14 days postinjury. Design, Setting, and Participants: Planned secondary analysis of a prospective, multicenter observational cohort study from August 2013 to September 2014. Participants aged 5 to 18 years with an acute (<48 hours) concussion were recruited from 9 Canadian pediatric emergency departments in the Pediatric Emergency Research Canada Network. Exposure: The independent variable was the number of days of school missed. Missing fewer than 3 days after concussion was defined as an early return to school. Main Outcomes and Measures: The primary outcome was symptom burden at 14 days, measured with the Post-Concussion Symptom Inventory (PCSI). Symptom burden was defined as symptoms status at 14 days minus preinjury symptoms. Propensity score analyses applying inverse probability of treatment weighting were performed to estimate the relationship between the timing of return to school and symptom burden. Results: This cohort study examined data for 1630 children (mean age [SD] 11.8 [3.4]; 624 [38%] female). Of these children, 875 (53.7%) were classified as having an early return to school. The mean (SD) number of days missed increased across age groups (5-7 years, 2.61 [5.2]; 8-12 years, 3.26 [4.9]; 13-18 years, 4.71 [6.1]). An early return to school was associated with a lower symptom burden 14 days postinjury in the 8 to 12-year and 13 to 18-year age groups, but not in the 5 to 7-year age group. The association between early return and lower symptom burden was stronger in individuals with a higher symptom burden at the time of injury, except those aged 5 to 7 years. Conclusions and Relevance: In this cohort study of youth aged 5 to 18 years, these results supported the growing belief that prolonged absences from school and other life activities after a concussion may be detrimental to recovery. An early return to school may be associated with a lower symptom burden and, ultimately, faster recovery.

Evaluation of baseline pediatric readiness of emergency departments in Manitoba, Canada.

BACKGROUND: Data on the readiness of the general emergency departments (EDs) in Canada to care for children requiring emergency care are limited. Recent evidence suggests an inverse association between pediatric readiness of the general ED and mortality. OBJECTIVES: To assess the baseline pediatric readiness of the general EDs in the province of Manitoba, Canada, to care for acutely ill and injured children. METHODS: This was a cross-sectional survey study conducted between 2019 and 2020. We used a validated pediatric readiness research checklist to obtain information on the six domains of the general EDs in Manitoba in the fiscal year 2019. A general ED that managed acutely ill patients (0-17th birthday), except for psychiatric cases (up to the 18th birthday), was defined as eligible. We performed a descriptive analysis using the weighted pediatric readiness score (WPRS) based on a 100-point scale. The factors associated with the total WPRS were examined in linear regression models. RESULTS: Of the 42 eligible general EDs, 34 centers participated with a participation rate of 81%. However, only 27 general EDs plus one specialized children ED (28, 67%) completed the survey. The overall median WPRS (/100) attained by the general EDs was 52.34 (interquartile range [IQR] = 10.44). The only specialized children ED in Manitoba achieved a score of 89.75. Over half (15, 55.6%) of the general EDs scored 50 or more. The mean volume of the general ED that participated was 4010.9 (± SD 2137.2) pediatric general ED visits/year. The average scores attained in the domains such as coordination of patient care, general ED staffing and training, and quality improvement were low across the five Regional Health Authorities. The general ED volume was directly associated with the total WPRS, regression coefficient, ß = 0.24 (95% CI 0.04-0.44). Neither the capacity of the general ED to receive pediatric patients from a nursing station, ß = - 0.07 (95% CI - 0.28-0.14), nor the capacity to admit pediatric patients that visited the general ED, ß = - 0.03 (- 0.23-0.17) was associated with the total WPRS. CONCLUSIONS: The pediatric readiness of the general EDs across Manitoba is comparable to other Canadian region, yet some domains need to be improved.

Paediatric post-concussive symptoms: symptom clusters and clinical phenotypes.

OBJECTIVE: To assess the co-occurrence and clustering of post-concussive symptoms in children, and to identify distinct patient phenotypes based on symptom type and severity. METHODS: We performed a secondary analysis of the prospective, multicentre Predicting and Preventing Post-concussive Problems in Pediatrics (5P) cohort study, evaluating children 5-17 years of age presenting within 48 hours of an acute concussion. Our primary outcome was the simultaneous occurrence of two or more persistent post-concussive symptoms on the Post-Concussion Symptom Inventory at 28 days post-injury. Analyses of symptom and patient clusters were performed using hierarchical cluster analyses of symptom severity ratings. RESULTS: 3063 patients from the parent 5P study were included. Median age was 12.1 years (IQR: 9.2-14.6 years), and 1857 (60.6%) were male. Fatigue was the most common persistent symptom (21.7%), with headache the most commonly reported co-occurring symptom among patients with fatigue (55%; 363/662). Headache was common in children reporting any of the 12 other symptoms (range: 54%-72%). Physical symptoms occurred in two distinct clusters: vestibular-ocular and headache. Emotional and cognitive symptoms occurred together more frequently and with higher severity than physical symptoms. Fatigue was more strongly associated with cognitive and emotional symptoms than physical symptoms. We identified five patient groups (resolved/minimal, mild, moderate, severe and profound) based on symptom type and severity. CONCLUSION: Post-concussive symptoms in children occur in distinct clusters, facilitating the identification of distinct patient phenotypes based on symptom type and severity. Care of children post-concussion must be comprehensive, with systems designed to identify and treat distinct post-concussion phenotypes.

Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial.

Importance: Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization. Objective: To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables. Design, Setting, and Participants: This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo. Exposures: Intravenous magnesium sulfate therapy (40-75 mg/kg). Main Outcomes and Measures: The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect. Results: Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001). Conclusions and Relevance: After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma. Trial registration: ClinicalTrials.gov: NCT01429415.

Symptom Burden, School Function, and Physical Activity One Year Following Pediatric Concussion.

OBJECTIVES: To characterize symptom burden, school function, and physical activity in youth 1 year following acute concussion and those with subsequent repeat concussion. STUDY DESIGN: Secondary analysis of Predicting Persistent Postconcussive Problems in Pediatrics prospective, multicenter cohort study conducted in 9 Canadian emergency departments. Participants were children between ages 5 and 18 years who presented consecutively ≤48 hours of concussion and agreed to participate in a post hoc electronic survey 1 year after injury. Outcomes were assessed using a standardized 25-question symptom scale derived from the Post-Concussion Symptom Inventory-Parent; school function and physical activity outcomes were queried. The primary outcome was total symptom score 1 year following concussion, defined as the number of symptoms experienced more than before injury. RESULTS: Of 3052 youth enrolled in the Predicting Persistent Postconcussive Problems in Pediatrics study, 432 (median [IQR] age, 11.5 [9,14] years; 266 [62%] male) completed the 1-year survey; 34 respondents reported a repeat concussion. Following acute concussion, youth were more likely to be symptom-free than following repeat concussion (75% vs 50%; difference = 25% [95% CI 8-41]; P = .002) and to have recovered fully (90% vs 74%; difference = 17% [95% CI 5-34]; P = .002) after 1 year. Although physical symptoms were less 1 year after initial emergency department presentation for both groups (P < .001), youth with a repeat concussion reported greater headache persistence (26% vs 13%; difference = 13% [95% CI 1,31]; P = .024). Both groups returned to their normal school routine (100% vs 95%; difference = 5% [95% CI -5 to 8; P = .618). Youth without repeat concussion more frequently returned to normal physical activities (98% vs 85%; difference = 13% [95% CI 4-28]; P < .0001) and sport (95% vs 82%; difference = 13% [95% CI 3-29]; P = .009). CONCLUSIONS: Most youth are symptom-free and fully recovered 1 year following concussion. Some children with repeat concussion have worse outcomes and have delays in returning to normal school routines and sport.

Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex Trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: study protocol.

INTRODUCTION: Up to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is painful and can be technically difficult in children. We hypothesise that a combination of intranasal dexmedetomidine plus intranasal ketamine (Ketodex) will be non-inferior to intravenous ketamine for effective sedation in children undergoing a closed reduction. METHODS AND ANALYSIS: This is a six-centre, four-arm, adaptive, randomised, blinded, controlled, non-inferiority trial. We will include children 4-17 years with a simple upper limb fracture or dislocation that requires sedation for a closed reduction. Participants will be randomised to receive either intranasal Ketodex (one of three dexmedetomidine and ketamine combinations) or intravenous ketamine. The primary outcome is adequate sedation as measured using the Paediatric Sedation State Scale. Secondary outcomes include length of stay, time to wakening and adverse effects. The results of both per protocol and intention-to-treat analyses will be reported for the primary outcome. All inferential analyses will be undertaken using a response-adaptive Bayesian design. Logistic regression will be used to model the dose-response relationship for the combinations of intranasal Ketodex. Using the Average Length Criterion for Bayesian sample size estimation, a survey-informed non-inferiority margin of 17.8% and priors from historical data, a sample size of 410 participants will be required. Simulations estimate a type II error rate of 0.08 and a type I error rate of 0.047. ETHICS AND DISSEMINATION: Ethics approval was obtained from Clinical Trials Ontario for London Health Sciences Centre and McMaster Research Ethics Board. Other sites have yet to receive approval from their institutions. Informed consent will be obtained from guardians of all participants in addition to assent from participants. Study data will be submitted for publication regardless of results. TRIAL REGISTRATION NUMBER: NCT0419525.

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial.

Importance: While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown. Objective: To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy. Design, Setting, and Participants: A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed. Interventions: Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408). Main Outcomes and Measures: The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes. Results: Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%). Conclusions and Relevance: Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT01429415.

A pragmatic randomized controlled trial of multi-dose oral ondansetron for pediatric gastroenteritis (the DOSE-AGE study): statistical analysis plan.

BACKGROUND: Acute gastroenteritis is a leading cause of emergency department visits and hospitalizations among children in North America. Oral-rehydration therapy is recommended for children with mild-to-moderate dehydration, but children who present with vomiting are frequently offered intravenous rehydration in the emergency department (ED). Recent studies have demonstrated that the anti-emetic ondansetron can reduce vomiting, intravenous rehydration, and hospitalization when administered in the ED to children with dehydration. However, there is little evidence of additional benefit from prescribing ondansetron beyond the initial ED dose. Moreover, repeat dosing may increase the frequency of diarrhea. Despite the lack of evidence and potential adverse side effects, many physicians across North America provide multiple doses of ondansetron to be taken following ED disposition. Thus, the Multi-Dose Oral Ondansetron for Pediatric Gastroenteritis (DOSE-AGE) trial will evaluate the effectiveness of prescribing multiple doses of ondansetron to treat acute gastroenteritis-associated vomiting. This article specifies the statistical analysis plan (SAP) for the DOSE-AGE trial and was submitted before the outcomes of the study were available for analysis. METHODS/DESIGN: The DOSE-AGE study is a phase III, 6-center, placebo-controlled, double-blind, parallel design randomized controlled trial designed to determine whether participants who are prescribed multiple doses of oral ondansetron to administer, as needed, following their ED visit have a lower incidence of experiencing moderate-to-severe gastroenteritis, as measured by the Modified Vesikari Scale score, compared with a placebo. To assess safety, the DOSE-AGE trial will investigate the frequency and maximum number of diarrheal episodes following ED disposition, and the occurrence of palpitations, pre-syncope/syncope, chest pain, arrhythmias, and serious adverse events. For the secondary outcomes, the DOSE-AGE trial will investigate the individual elements of the Modified Vesikari Scale score and caregiver satisfaction with the therapy. DISCUSSION: The DOSE-AGE trial will provide evidence on the effectiveness of multiple doses of oral ondansetron, taken as needed, following an initial ED dose in children with acute gastroenteritis-associated vomiting. The data from the DOSE-AGE trial will be analyzed using this SAP. This will reduce the risk of producing data-driven results and bias in our reported outcomes. The DOSE-AGE study was registered on ClinicalTrials.gov on February 22, 2019. TRIAL REGISTRATION: ClinicalTrials.gov NCT03851835 . Registered on 22 February 2019.

Multi-dose Oral Ondansetron for Pediatric Gastroenteritis: study Protocol for the multi-DOSE oral ondansetron for pediatric Acute GastroEnteritis (DOSE-AGE) pragmatic randomized controlled trial.

BACKGROUND: There are limited treatment options that clinicians can provide to children presenting to emergency departments with vomiting secondary to acute gastroenteritis. Based on evidence of effectiveness and safety, clinicians now routinely administer ondansetron in the emergency department to promote oral rehydration therapy success. However, clinicians are also increasingly providing multiple doses of ondansetron for home use, creating unquantified cost and health system resource use implications without any evidence to support this expanding practice. METHODS/DESIGN: DOSE-AGE is a randomized, placebo-controlled, double-blinded, six-center, pragmatic clinical trial being conducted in six Canadian pediatric emergency departments (EDs). In September 2019 the study began recruiting children aged 6 months to 18 years with a minimum of three episodes of vomiting in the 24 h preceding enrollment, <72 h of gastroenteritis symptoms and who were administered a dose of ondansetron during their ED visit. We are recruiting 1030 children (1:1 allocation via an internet-based, third-party, randomization service) to receive a 48-h supply (i.e., six doses) of ondansetron oral solution or placebo, administered on an as-needed basis. All participants, caregivers and outcome assessors will be blinded to group assignment. Outcome data will be collected by surveys administered to caregivers 24, 48 and 168 h following enrollment. The primary outcome is the development of moderate-to-severe gastroenteritis in the 7 days following the ED visit as measured by a validated clinical score (the Modified Vesikari Scale). Secondary outcomes include duration and frequency of vomiting and diarrhea, proportions of children experiencing unscheduled health care visits and intravenous rehydration, caregiver satisfaction with treatment and safety. A preplanned economic evaluation will be conducted alongside the trial. DISCUSSION: Definitive data are lacking to guide the clinical use of post-ED visit multidose ondansetron in children with acute gastroenteritis. Usage is increasing, despite the absence of supportive evidence. The incumbent additional costs associated with use, and potential side effects such as diarrhea and repeat visits, create an urgent need to evaluate the effect and safety of multiple doses of ondansetron in children focusing on post-emergency department visit and patient-centered outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03851835. Registered on 22 February 2019.

Early versus delayed emergency department presentation following mild Traumatic Brain Injury and the presence of symptom at 1, 4 and 12 weeks in children.

OBJECTIVES: We evaluated the association between timing of presentation and postconcussive symptoms (PCS) at 1, 4 and 12 weeks after injury. METHODS: This was a secondary analysis of a prospective cohort study conducted in nine Canadian paediatric EDs in 2013-2015 (5P study). Participants were children who suffered a head injury within the preceding 48 hours and met Zurich consensus concussion diagnostic criteria. The exposure was the time between head injury and ED presentation. The primary outcome was the presence of PCS at 1 week defined by the presence of at least three symptoms on the Post-Concussion Symptom Inventory (PCSI). Secondary outcomes evaluated PCS at 4 and 12 weeks. Multivariable logistic regression analyses were adjusted for ED PCSI and other potential confounders. RESULTS: There were 3041 patients with a concussion in which timing of the injury was known. 2287 (75%) participants sought care in the first 12 hours, 388 (13%) 12-24 hours after trauma and 366 (12%) between 24 and 48 hours. Compared with children who sought care >24 hours after trauma, children who sought care in the first 12 hours had a significantly lower incidence of PCS at 1 week (OR: 0.55 (95% CI 0.41 to 0.75)) and 4 weeks (OR: 0.74 (95% CI 0.56 to 0.99)) but not at 12 weeks (OR: 0.88 (95% CI 0.63 to 1.23)). CONCLUSIONS: Patients who present early after a concussion appear to have a shorter duration of PCS than those presenting more than 12 hours later. Patients/families should be informed of the higher probability of PCS in children with delayed presentation.

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged <18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/µL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count <250 × 103/µL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/µL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.

Practice Patterns in Pharmacological and Non-Pharmacological Therapies for Children with Mild Traumatic Brain Injury: A Survey of 15 Canadian and United States Centers.

Given the lack of evidence regarding effective pharmacological and non-pharmacological interventions for pediatric mild traumatic brain injury (mTBI) and the resultant lack of treatment recommendations reflected in consensus guidelines, variation in the management of pediatric mTBI is to be expected. We therefore surveyed practitioners across 15 centers in the United States and Canada who care for children with pediatric mTBI to evaluate common-practice variation in the management of pediatric mTBI. The survey, developed by a panel of pediatric mTBI experts, consisted of a 10-item survey instrument regarding providers' perception of common pediatric mTBI symptoms and mTBI interventions. Surveys were distributed electronically to a convenience sample of local experts at each center. Frequencies and percentages (with confidence intervals [CI]) were determined for survey responses. One hundred and seven respondents (71% response rate) included specialists in pediatric Emergency Medicine, Sports Medicine, Neurology, Neurosurgery, Neuropsychology, Neuropsychiatry, Physical and Occupational Therapy, Physiatry/Rehabilitation, and General Pediatrics. Respondents rated headache as the most prevalently reported symptom after pediatric mTBI, followed by cognitive problems, dizziness, and irritability. Of the 65 (61%; [95% CI: 51,70]) respondents able to prescribe medications, non-steroidal anti-inflammatory medications (55%; [95% CI: 42,68]) and acetaminophen (59%; [95% CI: 46,71]) were most commonly recommended. One in five respondents reported prescribing amitriptyline for headache management after pediatric mTBI, whereas topiramate (8%; [95% CI: 3,17]) was less commonly reported. For cognitive problems, methylphenidate (11%; [95% CI: 4,21]) was used more commonly than amantadine (2%; [95% CI: 0,8]). The most common non-pharmacological interventions were rest ("always" or "often" recommended by 83% [95% CI: 63,92] of the 107 respondents), exercise (59%; [95%CI: 49,69]), vestibular therapy (42% [95%CI: 33,53]) and cervical spine exercises (29% [95%CI: 21,39]). Self-reported utilization for common pediatric mTBI interventions varied widely across our Canadian and United States consortium. Future effectiveness studies for pediatric mTBI are urgently needed to advance the evidence-based care.

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.

The Diagnosis of Concussion in Pediatric Emergency Departments: A Prospective Multicenter Study.

BACKGROUND: The accurate identification of children with a concussion by emergency physicians is important to initiate appropriate anticipatory guidance and management. OBJECTIVES: We compared the frequency of persistent concussion symptoms in children who were provided the diagnosis of concussion by an emergency physician versus those who met Berlin/Zurich international criteria for this diagnosis. We also determined the clinical variables independently associated with a physician-diagnosed concussion. METHODS: This was a planned secondary analysis of a prospective, multicenter cohort study. Participants were 5-17 years of age and met the Zurich/Berlin International Consensus Statement criteria for concussion. RESULTS: There were 2946 enrolled children. In those with physician-diagnosed concussion vs. no concussion, the frequency of persistent symptoms was 62.5% vs. 38.8% (p < 0.0001) at 1 week, 46.3% vs. 25.8% (p < 0.0001) at 2 weeks, and 33.0% vs. 23.0% (p < 0.0001) at 4 weeks. Of those meeting international criteria, 2340 (79.4%) were diagnosed with a concussion by an emergency physician and 12 variables were associated with this diagnosis. Five had an odds ratio (OR) > 1.5: older age (13-17 vs. 5-7 years, OR 2.9), longer time to presentation (≥16 vs. <16 h, OR 2.1), nausea (OR 1.7), sport mechanism (OR 1.7), and amnesia (OR 1.6). CONCLUSIONS: Relative to international criteria, the more selective assignment of concussion by emergency physicians was associated with a greater frequency of persistent concussion symptoms. In addition, while most children meeting international criteria for concussion were also provided this diagnosis for concussion by an emergency physician, the presence of 5 specific variables made this diagnosis more likely.

The impact of transport of critically ill pediatric patients on rural emergency departments in Manitoba.

INTRODUCTION: Although the interfacility transport (IFT) of critically ill pediatric patients from rural to tertiary health centres may improve outcomes, the impact of IFTs on the rural referring centre is not known. The purpose of this study was to investigate how the IFT of critically ill children affects staffing and functionality of rural emergency departments (EDs) in Manitoba. METHODS: In 2015, surveys were emailed to the medical directors of all 15 regional EDs within 2 hours' travel time from a tertiary pediatric hospital. The survey consisted of 9 questions that addressed baseline characteristics of the regional EDs and duration of ED staffing changes or closures due to IFT of critically ill pediatric patients. RESULTS: Ten surveys were received (67% response rate); a regional ED catchment population of about 130 000 people was represented. Interfacility transport caused most EDs (60%, with an average catchment population of 15 000) to close or to alter their staffing to a registered nurse only. These temporary changes lasted a cumulative total of 115 hours. CONCLUSION: Interfacility transport of critically ill pediatric patients resulted in ED closures and staffing changes in rural Manitoba. These findings suggest that long-term sustainable solutions are required to improve access to emergency care.

INTRODUCTION: Même si le transfert entre établissements (TEE) des patients pédiatriques gravement malades des centres de santé ruraux vers des centres tertiaires peut améliorer les résultats, l'impact du TEE sur les centres ruraux d'origine est inconnu. Le but de cette étude était d'évaluer dans quelle mesure le TEE des enfants gravement malades affecte la dotation en personnel et la fonctionnalité des services d'urgence ruraux au Manitoba. METHODS: En 2015, des sondages ont été envoyés par courriel aux directeurs médicaux des 15 services d'urgence régionaux se trouvant à 2 heures de distance ou moins d'un hôpital pédiatrique de soins tertiaires. Le sondage comportait 9 questions qui portaient sur les caractéristiques de base des services d'urgence régionaux et la durée des changements de leur dotation en personnel ou leur fermeture en raison du TEE des patients pédiatriques gravement malades. RESULTS: Dix sondages ont été reçus (taux de réponse : 67 %); une population d'environ 130 000 personnes desservies par les services d'urgence régionaux se trouvait représentée. Le transfert entre établissements a entraîné la fermeture ou la modification de la dotation en personnel ramené à une seule infirmière dans la plupart des services d'urgence (60 %, desservant en moyenne une population de 15 000 personnes). Ces changements temporaires ont eu une durée cumulative de 115 heures. CONCLUSION: Le transfert entre établissements des patients pédiatriques gravement malades a entraîné la fermeture des services d'urgence et des modifications de leur dotation en personnel dans les régions manitobaines rurales. Ces observations donnent à penser que des solutions viables à long terme sont nécessaires pour améliorer l'accès aux soins d'urgence.

Serial optic nerve sheath diameter ultrasonography during pediatric diabetic ketoacidosis management: A pilot study.

OBJECTIVE: Intracranial hypertension is an infrequent but serious acute complication of pediatric diabetic ketoacidosis (DKA). Subclinical elevations of intracranial pressures however, may be more common, and can be indirectly evaluated with ultrasonography of the optic nerve sheath diameter (ONSD). In this pilot study, we report serial data on ONSD trajectories from five pediatric patients with DKA to generate hypotheses for future studies. METHODS: Five pediatric patients with type 1 diabetes presented to our emergency department with DKA and enrolled in our study <3h after initiation of treatment. Ultrasonographic evaluation of the ONSD was conducted at presentation, every three hours until resolution of acidosis, and finally 24h post presentation. Following each interval evaluation, a clinical bedside neurologic tool developed for detecting cerebral edema in DKA was utilized. RESULTS: Four of the five patients exhibited a similar "bell" shaped trajectory - an increase of ONSD after initiation of treatment followed by a return to admission baseline. Patients demonstrated peak ONSDs nine and twelve hours after DKA therapy was initiated, at resolution of acidosis, and at admission. No children exhibited clinical signs suggestive of cerebral edema. CONCLUSIONS: Peak ONSDs cannot be reliability determined in children with DKA unless serial investigations are conducted. Practices to mitigate risks for intracranial hypertension may require constant surveillance during DKA management.

Magnesium nebulization utilization in management of pediatric asthma (MagNUM PA) trial: study protocol for a randomized controlled trial.

BACKGROUND: Up to 30 % of children with acute asthma are refractory to initial therapy, and 84 % of this subpopulation needs hospitalization. Finding safe, noninvasive, and effective strategies to treat this high-risk group would substantially decrease hospitalizations, healthcare costs, and the psycho-social burden of the disease. Whereas intravenous magnesium (Mg) is effective in severe refractory asthma, its use is sporadic due to safety concerns, with the main treatment goal being to prevent intensive care unit admission. In contrast, nebulized Mg is noninvasive, allows higher pulmonary drug concentrations, and has a much higher safety potential due to the lower rate of systemic delivery. Previous studies of inhaled Mg show disparate results due to the use of unknown/inefficient delivery methods and other methodological flaws. METHODS/DESIGN: The study is a randomized double-blind controlled trial in seven Canadian pediatric Emergency Departments (two-center pilot 2011 to 2014, Canada-wide November 2014 to December 2017). The trial will include 816 otherwise healthy children who are 2 to 17 years old, having had at least one previous wheezing episode, have received systemic corticosteroids, and have a Pediatric Respiratory Assessment Measure (PRAM) ≥ 5 points after three salbutamol and ipratropium treatments for a current acute asthma exacerbation. Eligible consenting children will receive three experimental treatments of nebulized salbutamol with either 600 mg of Mg sulfate or placebo 20 min apart, using an Aeroneb Go nebulizer, which has been shown to maximize pulmonary delivery while maintaining safety. The primary outcome is hospitalization within 24 h of the start of the experimental therapy for persistent respiratory distress or supplemental oxygen. Secondary outcomes include all-cause hospitalization within 24 h, PRAM, vital signs, number of bronchodilator treatments by 240 min, and the association between the difference in the primary outcome between the groups, age, gender, baseline PRAM, atopy, and "viral induced wheeze" phenotype (Fig. 1). DISCUSSION: If effective, inhaled Mg may represent an effective strategy to minimize morbidity in pediatric refractory acute asthma. Unlike previous works, this trial targets nonresponders to optimized initial therapy who are the most likely to benefit from inhaled Mg. Future dissemination of results will include knowledge translation, incorporation into a Cochrane Review, presentation at scientific meetings, and a peer-reviewed publication. TRIAL REGISTRATION: NCTO1429415 , registered 2 September 2011.

Clinical Risk Score for Persistent Postconcussion Symptoms Among Children With Acute Concussion in the ED.

IMPORTANCE: Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. OBJECTIVE: To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-<18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. EXPOSURES: All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. MAIN OUTCOMES AND MEASURES: The primary outcome was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. RESULTS: In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95% CI, 0.69-0.74) for the derivation cohort and 0.68 (95% CI, 0.65-0.72) for the validation cohort. CONCLUSIONS AND RELEVANCE: A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility.