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Background: Caustic ingestions are relatively uncommon, but remain a significant source of morbidity. Patients with caustic injury often undergo an urgent EGD, although it is not clear if an EGD is routinely needed in an asymptomatic patient. The study has two primary objectives; 1) to determine the utility of routine EGD in asymptomatic suicidal caustic ingestions; 2) to determine if asymptomatic unintentional acidic ingestions can be managed with observation alone, similar to basic ingestions., Methods: This retrospective study, which took place at 14 hospitals in three countries evaluated all patients who presented with a caustic ingestion between 2014-2020. The presence of symptoms and esophageal injury, demographic information, pH of ingested substance, reason for the ingestion, and outcome were recorded., Results: 409 patients were identified; 203 (46.9%) were male. The median (IQR) age was 18 (4-31) years; overall range 10 months to 78 years. Suicidal ingestions accounted for 155 (37.9%) of cases. Dysphagia or dysphonia were more likely in those with significant esophageal injury compared to those without (59.3% vs. 12.6% respectively; OR 10.1; 95% CI 4.43-23.1). Among 27 patients with significant esophageal injury, 48% were found in suicidal patients, compared with 51.9% in non-suicidal patients (p = NS). On multivariate regression, there was no difference in the rate of significant esophageal injury among suicidal vs. non suicidal patients (aOR 1.55; p = 0.45, 95% CI 0.45-5.33). Most ingestions involved basic substances (332/409; 81.2%). Unknown or mixed ingestions accounted for 25 (6.11%) of the ingestions. Significant esophageal burns were found in 6/52 (11.5%) of acid ingestions, compared with 21/332 (6.3%) of basic ingestions. Of the 42 cases of acidic ingestions without dysphagia or odynophagia, 2 (4.8%; 0.58-16.1%) had significant esophageal burns, compared with 9 (3.2%; 95% CI 1.4-5.9%) of the 284 basic ingestions; p = 0.64). On multivariate logistic regression, patients with acidic ingestions were not more likely to experience a significant burn (aOR 1.7; p = 0.11, 95% CI 0.9-3.1) compared to those with basic ingestions. No patient with significant esophageal burns was asymptomatic., Conclusion: In this study, there was no statistical differences in the rates of significant burns between acidic and basic caustic ingestions. There were no significant esophageal injuries noted among asymptomatic patients., (© 2024. American College of Medical Toxicology.)

Background: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described., Methods: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up., Results: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC., Conclusions: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC., Competing Interests: Potential conflicts of interest . A. F. reports grants from the University of Calgary Eyes High Postdoctoral Fellowship and Canadian Institutes of Health Research Banting Postdoctoral Fellowship, and support for meetings and/or travel from a Trainee Travel Grant (Pediatric Academic Societies and Trainee travel grant), Alberta Children's Hospital Association, University of Calgary. L. A. reports grants from Pfizer. M. W. reports support for meetings and/or travel from US Acute Care Solutions (USACS), stock and a board of directors position for EM Device Lab. N. K. reports a leadership or fiduciary role for the Pediatric Emergency Care Applied Research, Pediatric Emergency Research Network; research funding from the National Institutes of Health (NIH), Health Resources and Services Administration (HRSA), and Patient-Centered Outcomes Research Institute (PCORI). R. M. reports royalties or licenses for Affinivax; consulting fees from GSK, Affinivax, and Merck; payment for lectures and support for meetings and/or travel from GSK; patents planned, issued, or pending for Boston Children's Hospital; being a member of the Affinivax board of directors; and stock options for Affinivax and Corner Therapeutics. S. M. M. reports grants from Sanofi, Merck, Pfizer National Minority Quality Forum (US); support for meetings and/or travel from Sanofi, Merck, GSK, Pfizer, CSL, Biosciences Association of Manitoba (BAM), and the National Minority Quality Forum (US); and participation on a Data and Safety Monitoring Board or Advisory board for Sanofi. T. A. F. reports grants from the National Heart, Lung, and Blood Institute (NHLBI) and leadership or fiduciary roles for the Society of Pediatric Research and the Pediatric Academic Societies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract: Open-heart surgery with cardiopulmonary bypass often leads to complications including pain, systemic inflammation, and organ damage. Traditionally managed with opioids, these pain relief methods bring potential long-term risks, prompting the exploration of alternative treatments. The legalization of cannabis in various regions has reignited interest in cannabinoids, such as cannabidiol, known for their anti-inflammatory, analgesic, and neuroprotective properties. Historical and ongoing research acknowledges the endocannabinoid system's crucial role in managing physiological processes, suggesting that cannabinoids could offer therapeutic benefits in postsurgical recovery. Specifically, cannabidiol has shown promise in managing pain, moderating immune responses, and mitigating ischemia/reperfusion injury, underscoring its potential in postoperative care. However, the translation of these findings into clinical practice faces challenges, highlighting the need for extensive research to establish effective, safe cannabinoid-based therapies for patients undergoing open-heart surgery. This narrative review advocates for a balanced approach, considering both the therapeutic potential of cannabinoids and the complexities of their integration into clinical settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

L'intérêt envers l'utilisation des produits du cannabis à des fins médicales chez les enfants de moins de 18 ans augmente. De nombreux produits du cannabis à des fins médicales contiennent du cannabidiol, du delta-9-tétrahydrocannabinol ou ces deux produits. Malgré les nombreuses prétentions thérapeutiques, peu d'études rigoureuses guident la posologie, l'innocuité et l'efficacité du cannabis à des fins médicales en pédiatrie clinique. Le présent document de principes passe en revue les données probantes à jour et expose les recommandations sur l'utilisation du cannabis à des fins médicales chez les enfants. Les rapports à plus long terme (deux ans) souscrivent à la tolérabilité et à l'efficacité soutenues d'un traitement au cannabidiol chez les patients ayant le syndrome de Lennox-Gastaut ou le syndrome de Dravet. Les extraits de cannabis enrichis de cannabidiol qui renferment de petites quantités de delta-9-tétrahydrocannabinol ont été évalués auprès d'un petit nombre de patients d'âge pédiatrique, et d'autres recherches devront être réalisées pour éclairer les guides de pratique clinique. Étant donné l'utilisation répandue du cannabis à des fins médicales au Canada, les pédiatres devraient être prêts à participer à des échanges ouverts et continus avec les familles au sujet de ses avantages potentiels et de ses risques, ainsi qu'à préparer des plans individuels en vue d'en surveiller l'efficacité, de réduire les méfaits et de limiter les interactions médicamenteuses., (© Société canadienne de pédiatrie 2024. Publié par Oxford University Press pour le compte de la Société canadienne de pédiatrie. Tous droits réservés. Pour obtenir une autorisation, écrivez à journals.permissions@oup.com.)

Interest in using cannabis products for a medical purpose in children under the age of 18 years is increasing. There are many medical cannabis products available that can include cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC), or both. Despite many therapeutic claims, there are few rigorous studies to inform the dosing, safety, and efficacy of medical cannabis in paediatric clinical practice. This statement reviews the current evidence and provides recommendations for using medical cannabis in children. Longer-term (2-year) reports support the sustained tolerability and efficacy of cannabidiol therapy for patients with Lennox-Gastaut and Dravet syndromes. CBD-enriched cannabis extracts containing small amounts of THC have been evaluated in a small number of paediatric patients, and further research is needed to inform clinical practice guidelines. Given the widespread use of medical cannabis in Canada, paediatricians should be prepared to engage in open, ongoing discussions with families about its potential benefits and risks, and develop individualized plans that monitor efficacy, reduce harms, and mitigate drug-drug interactions., Competing Interests: All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© Canadian Paediatric Society 2024. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The impact of coronavirus disease 2019 (COVID-19) on unintentional pediatric poisonings is unclear. We examined changes in emergency department (ED) visits and hospitalizations for poisonings before and during the COVID-19 pandemic. We compared changes in cannabis vs non-cannabis poisoning events given the recent legalization of cannabis in October 2018 and cannabis edibles in January 2020., Study Design: Interrupted time-series (ITS) analyses of changes in population-level ED visits and hospitalizations for poisonings in children aged 0-9 years in Ontario, Canada (annual population of 1.4 million children), over two time periods: pre-pandemic (January 2010-March 2020) and pandemic (April 2020-December 2021)., Results: Overall, there were 28,292 ED visits and 2641 hospitalizations for unintentional poisonings. During the pandemic, poisonings per 100,000 person-years decreased by 14.6% for ED visits (40.15 pre- vs. 34.29 during) and increased by 35.9% for hospitalizations (3.48 pre- vs. 4.73 during). ED visits dropped immediately (Incidence Rate Ratio [IRR], 0.76; 95% CI, 0.70-0.82) at the onset of the pandemic, followed by a gradual return to baseline (quarterly change, IRR 1.04, 95%CI 1.03-1.06), while hospitalizations had an immediate increase (IRR 1.34; 95% CI, 1.08-1.66) and no gradual change. The only increase in poisonings was for cannabis which had a 10.7-fold for ED visits (0.45 to 4.83 per 100,000 person-years) and a 12.1-fold increase for hospitalizations (0.16 to 1.91 per 100,000 person-years). Excluding cannabis, there was no overall increase in poisoning hospitalizations., Conclusions: The COVID-19 pandemic was not associated with increases in any type of unintentional pediatric poisonings, with the exception of cannabis poisonings. Increased cannabis poisonings may be explained by the legalization of non-medical cannabis edibles in Canada in January 2020., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel T. Myran, MD reports financial support was provided by Canadian Institutes of Health Research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Episodes of substance-induced psychosis are associated with increased risk of developing a schizophrenia spectrum disorder. However, there are limited data on the transition risk for substance use without psychosis., Objectives: To quantify the risk of transition to schizophrenia spectrum disorder following an incident emergency department (ED) visit for (1) substance-induced psychosis and (2) substance use without psychosis and to explore factors associated with transition., Design, Settings, and Participants: A population-based retrospective cohort study (January 2008 to March 2022) of all individuals, aged 14 to 65 years, in Ontario, Canada, with no history of a psychotic disorder. Individuals with incident ED visits for substance use with and without psychosis were compared with members of the general population., Main Outcomes and Measures: Transition to schizophrenia spectrum disorder using a chart-validated algorithm. Associations between ED visits for substance use and subsequent transition were estimated using cause-specific hazard models., Results: The study included 9 844 497 individuals, aged 14 to 65 years (mean [SD] age, 40.2 [14.7] years; 50.2% female) without a history of psychosis. There were 407 737 individuals with an incident ED visit for substance use, of which 13 784 (3.4%) ED visits were for substance-induced psychosis. Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio [aHR], 163.2; 95% CI, 156.1-170.5) increased risk of transitioning, relative to the general population (3-year risk, 18.5% vs 0.1%). Individuals with an ED visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%), but incurred more than 3 times the absolute number of transitions (9969 vs 3029). Cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2). Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger compared with older individuals, particularly for cannabis use., Conclusions and Relevance: The findings of this cohort study suggest that ED visits for substance use were associated with an increased risk of developing a schizophrenia spectrum disorder. Although substance-induced psychoses had a greater relative transition risk, substance use without psychosis was far more prevalent and resulted in a greater absolute number of transitions. Several factors were associated with higher transition risk, with implications for counseling and early intervention.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations., Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations., Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 10 9 /L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 10 9 /L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts., Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Although nasal suctioning is the most frequently used supportive management for bronchiolitis, its benefit remains unknown., Objective: To evaluate the effectiveness of enhanced vs minimal nasal suctioning in treating infants with bronchiolitis after discharge from the emergency department (ED)., Design, Setting, and Participants: This single-blind, parallel-group, randomized clinical trial was conducted from March 6, 2020, to December 15, 2022, at 4 tertiary-care Canadian pediatric EDs. Participants included otherwise healthy infants aged 1 to 11 months with a diagnosis of bronchiolitis who were discharged home from the ED., Interventions: Participants were randomized to minimal suctioning via bulb or enhanced suctioning via a battery-operated device before feeding for 72 hours., Main Outcomes and Measures: The primary outcome was additional resource use, a composite of unscheduled revisits for bronchiolitis or use of additional suctioning devices for feeding and/or breathing concerns. Secondary outcomes included health care utilization, feeding and sleeping adequacy, and satisfaction., Results: Of 884 screened patients, 352 were excluded for criteria, 79 declined participation, 81 were otherwise excluded, 372 were randomized (185 to the minimal suction group and 187 to the enhanced suction group), and 367 (median [IQR] age, 4 [2-6] months; 221 boys [60.2%]) completed the trial (184 in the minimal suction and 183 in the enhanced suction group). Additional resource use occurred for 68 of 184 minimal suction participants (37.0%) vs 48 of 183 enhanced suction participants (26.2%) (absolute risk difference, 0.11; 95% CI, 0.01 to 0.20; P = .03). Unscheduled revisits occurred for 47 of 184 minimal suction participants (25.5%) vs 40 of 183 enhanced suction participants (21.9%) (absolute risk difference, 0.04; 95% CI, -0.05 to 0.12; P = .46). A total of 33 of 184 parents in the minimal suction group (17.9%) used additional suctioning devices vs 11 of 183 parents in the enhanced suction group (6.0%) (absolute risk difference, 0.12; 95% CI, 0.05 to 0.19; P < .001). No significant between-group differences were observed for all bronchiolitis revisits (absolute risk difference, 0.07; 95% CI, -0.02 to 0.16; P = .15), ED revisits (absolute risk difference, 0.04; 95% CI, -0.03 to 0.12; P = .30), parental care satisfaction (absolute risk difference, -0.02; 95% CI, -0.10 to 0.06; P = .70), and changes from baseline to 72 hours in normal feeding (difference in differences, 0.03; 95% CI, -0.10 to 0.17; P = .62), normal sleeping (difference in differences, 0.05; 95% CI, -0.08 to 0.18; P = .47), or normal parental sleeping (difference in differences, 0.10; 95% CI, -0.02 to 0.23; P = .09). Parents in the minimal suction group were less satisfied with the assigned device (62 of 184 [33.7%]) than parents in the enhanced suction group (145 of 183 [79.2%]) (risk difference, 0.45; 95% CI, 0.36 to 0.54; P < .001)., Conclusions and Relevance: Compared with minimal suctioning, enhanced suctioning after ED discharge with bronchiolitis did not alter the disease course because there were no group differences in revisits or feeding and sleeping adequacy. Minimal suctioning resulted in higher use of nonassigned suctioning devices and lower parental satisfaction with the assigned device., Trial Registration: ClinicalTrials.gov Identifier: NCT03361371.

Introduction: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication., Methods: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics., Results: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P  < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P  = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P  < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7)., Conclusions: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

Background: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity., Methods: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration., Results: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis ( P  = 0.89) or polynomial model ( P  = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration., Conclusion: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Background: Children managed for asthma in an emergency department (ED) may be less likely to be hospitalized if they receive intravenous magnesium sulfate (IVMg). Asthma guidelines recommend IVMg for severely sick children but note a lack of evidence to support this recommendation. All previous trials of IVMg in children with asthma have been too small to answer whether IVMg is effective and safe. A few major questions remain about IVMg. First, it has not been tested early in the course of ED treatment, when the impact on hospitalization would be greatest. Second, the clinical impact of hypotension, a known adverse effect of IVMg, has not been well characterized in previous research. Third, no trials have compared different IVMg doses or serial serum magnesium (total and ionized) concentrations to optimize dosing, so the most effective dose is unknown. A large, conclusive, randomized, placebo-controlled clinical trial of IVMg might be challenging due to the need to enroll and complete study procedures quickly, a lack of understanding of blood pressure changes after IVMg, and a lack of pharmacologic information to guide the optimal doses of IVMg to be tested. Therefore, a pilot study to inform the above gaps is warranted before conducting a definitive trial., Objective: The objectives of this study are to (1) demonstrate the feasibility of enrolling children with severe acute asthma in the ED in a multicenter, randomized controlled trial of a placebo, low-dose IVMg, or high-dose IVMg; (2) demonstrate the feasibility of timely delivery of study medication, assessment of blood pressure, and evaluation of adverse events in a standardized protocol; and (3) externally validate a previously constructed pharmacokinetic model and develop a combined pharmacokinetic/pharmacodynamic model for IVMg using magnesium (total and ionized) serum concentrations and their correlation with measures of efficacy and safety., Methods: This pilot trial tests procedures and gathers information to plan a definitive trial. The pilot trial will enroll as many as 90 children across 3 sites, randomize each child to 1 of 3 study arms, measure blood pressure frequently, and collect 3 blood samples from each participant with corresponding clinical asthma scores., Results: The project was funded by the National Heart, Lung, and Blood Institute (1 R34HL152047-2) in March 2022. Enrollment began in September 2022, and 43 children have been enrolled as of April 2023. We will submit the results for publication in late 2023., Conclusions: The results of this study will guide the planning of a large, definitive, multicenter trial powered to evaluate if IVMg reduces hospitalization. Blood pressure measurements will inform a monitoring plan for the larger trial, and blood samples and asthma scores will be used to validate pharmacologic models to select the optimal dose of IVMg to be evaluated in the definitive trial., Trial Registration: ClinicalTrials.gov NCT05166811; https://clinicaltrials.gov/ct2/show/NCT05166811., International Registered Report Identifier (irrid): DERR1-10.2196/48302., (©Michael D Johnson, Bradley J Barney, Joseph E Rower, Yaron Finkelstein, Joseph J Zorc. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 17.07.2023.)

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.

Introduction: There are limited options for pain and distress management in children undergoing minor procedures, without the burden of an intravenous line insertion. Prior to this study, we conducted a dose-escalation study and identified 6 mg/kg as a potentially optimal initial dose of intranasal ketamine., Objective: To assess the efficacy and safety of intranasal ketamine at a dose of 6 mg/kg for procedural sedation to repair lacerations with sutures in children in the emergency department., Methods: We conducted a single-arm, open-label multicenter clinical trial for intranasal ketamine for laceration repair with sutures in children aged 1 to 12 years. A convenience sample of 30 patients received 6 mg/kg of intranasal ketamine for their procedural sedation. The primary outcome was the proportion (95% CI) of patients who achieved an effective procedural sedation., Results: We recruited 30 patients from April 2018 to December 2019 in two pediatric emergency departments in Canada. Lacerations repaired were mostly facial in 21(70%) patients and longer than 2 cm in 20 (67%) patients. Sedation was effective in 18/30 (60% [95% CI 45, 80]) children and was suboptimal in 5 (17%) patients but procedure was completed in them with minimal difficulties. Sedation was poor in the remaining 7 (23%) patients, with 3 (10%) of them required additional sedative agents. No serious adverse events were reported., Conclusions: Using a single dose of 6 mg/kg of intranasal Ketamine for laceration repair led to successful sedation in 60% of patients according to our a priori definition. An additional 17% of patients were considered suboptimal, but their procedure was still completed with minimal difficulty., Clinical Trial Registration: ClinicalTrials.gov (NCT03053947)., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children., Competing Interests: RJH and LEK served on Health Canada’s Scientific Advisory Committee on Health Products Containing Cannabis whose views are not reflected in this manuscript. RJH received a grant from the Jim Pattison Children’s Hospital Foundation for a study on medical cannabis in childhood refractory epilepsy and was Co-Chair, Health Canada Scientific Advisory Committee on Health Products Containing Cannabis (an unpaid position). EL received speaking fees from Spectrum Therapeutics and holds leadership positions in the following groups: Jamaican Medical Cannabis Corporation (unpaid position), Medical Cannabis Clinicians Society (UK), Canadian Collaborative for Childhood Cannabinoid Therapeutics, MedCan Support and Canadian Patient Advocacy & Support Services. CM-H is the controlling shareholder of a small publicly traded company that made an incremental $1.7M investment in a biotechnology company involved in medical research related to minor cannabinoids. JA has participated in an advisory board for Zyus Life Science. REB is a member of the Advisory Council, Drug-Free Kids Canada, and was Co-Chair of the Cannabis Project Advisory Group, Canadian Paediatric Society (both unpaid positions). SC holds a leadership position on the Network of Networks (N2) Board of Directors. AG reports that this article was researched and written prior to her employment at Health Canada and any views, opinions, and recommendations expressed within are those of the authors and do not reflect the position of Health Canada and/or the Government of Canada. JJ received grants from NSERC, CIHR, AMA Pediatrics, and Alberta Children’s Hospital Foundation, consulting fees from EISAI, UCB, and PENDOPHARM, payment/honoraria from EISAI, UCB, PENDOPHARM, and SUNOVION, and travel reimbursement from Neurocrine. JJ also holds leadership positions in the American Epilepsy Society, the Canadian League Against Epilepsy, and Hope for Hypothalamic Hamartomas. MJR is a member of the Paediatrics & Child Health editorial board. Another editor was responsible for overseeing the peer review of this manuscript. AS is the founder of Shackelford Pharma., an emerging medical cannabis company. There is also a provisional patent application filed, but not yet issued, on behalf of Shackelford Pharma, Inc. RV was director of the Department of Pediatric Pharmacy, Children’s Hospital of Eastern Ontario when this manuscript was written and submitted for publication but is now Vice President of Pharmacy Affairs for BCE Pharma. He has received consulting fees from Harvest Medicine Clinic and recently concluded an 8-year term as a Director of the International Pharmaceutical Federation Foundation. LEK holds a Board of Directors position at the Canadian Consortium for the Investigation of Cannabinoids and holds funding from the Canadian Institutes of Health Research, the Canadian Cancer Society, and the SickKids Foundation for C4T. She holds a Mitacs Accelerate grant for a separate project in partnership with Canopy Growth. There are no other disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Paediatric Society.)

Competing Interests: Competing interests: None declared.

Importance: Canada legalized cannabis in October 2018 but initially prohibited the sale of edibles (eg, prepackaged candies). Starting in January 2020, some provinces permitted the sale of commercial cannabis edibles. The association of legalizing cannabis edibles with unintentional pediatric poisonings is uncertain., Objective: To evaluate changes in proportions of all-cause hospitalizations for poisoning due to cannabis in children during 3 legalization policy periods in Canada's 4 most populous provinces (including 3.4 million children aged 0-9 years)., Design, Setting, and Participants: This repeated cross-sectional study included all hospitalizations in children aged 0 to 9 years in Ontario, Alberta, British Columbia, and Quebec between January 1, 2015, and September 30, 2021., Exposures: Prelegalization (January 2015 to September 2018); period 1, in which dried flower only was legalized in all provinces (October 2018 to December 2019); and period 2, in which edibles were legalized in 3 provinces (exposed provinces) and restricted in 1 province (control province) (January 2020 to September 2021)., Main Outcomes and Measures: The primary outcome was the proportion of hospitalizations due to cannabis poisoning out of all-cause poisoning hospitalizations. Data analysis was performed using descriptive statistics and Poisson regression models., Results: During the 7-year study period, there were 581 pediatric hospitalizations for cannabis poisoning (313 [53.9%] boys; 268 [46.1%] girls; mean [SD] age, 3.6 [2.5] years) and 4406 hospitalizations for all-cause poisonings. Of all-cause poisoning hospitalizations, the rate per 1000 due to cannabis poisoning before legalization was 57.42 in the exposed provinces and 38.50 in the control province. During period 1, the rate per 1000 poisoning hospitalizations increased to 149.71 in the exposed provinces (incidence rate ratio [IRR], 2.55; 95% CI, 1.88-3.46) and to 117.52 in the control province (IRR, 3.05; 95% CI, 1.82-5.11). During period 2, the rate per 1000 poisoning hospitalizations due to cannabis more than doubled to 318.04 in the exposed provinces (IRR, 2.16; 95% CI, 1.68-2.80) but remained similar at 137.93 in the control province (IRR, 1.18; 95% CI, 0.71-1.97)., Conclusions and Relevance: This cross-sectional study found that following cannabis legalization, provinces that permitted edible cannabis sales experienced much larger increases in hospitalizations for unintentional pediatric poisonings than the province that prohibited cannabis edibles. In provinces with legal edibles, approximately one-third of pediatric hospitalizations for poisonings were due to cannabis. These findings suggest that restricting the sale of legal commercial edibles may be key to preventing pediatric poisonings after recreational cannabis legalization.

Objectives: We aimed to evaluate the international variation in the use of evidence-based management (EBM) in bronchiolitis. We hypothesised that management consistent with full-EBM practices is associated with the research network of care, adjusted for patient-level characteristics. Secondary objectives were to determine the association between full-EBM and (1) hospitalisation and (2) emergency department (ED) revisits resulting in hospitalisation within 21 days., Design: A secondary analysis of a retrospective cohort study., Setting: 38 paediatric EDs belonging to the Paediatric Emergency Research Network in Canada, USA, Australia/New Zealand UK/Ireland and Spain/Portugal., Patients: Otherwise healthy infants 2-11 months old diagnosed with bronchiolitis between 1 January 2013 and 31 December, 2013., Outcome Measures: Primary outcome was management consistent with full-EBM, that is, no bronchodilators/corticosteroids/antibiotics, no chest radiography or laboratory testing. Secondary outcomes included hospitalisations during the index and subsequent ED visits., Results: 1137/2356 (48.3%) infants received full-EBM (ranging from 13.2% in Spain/Portugal to 72.3% in UK/Ireland). Compared with the UK/Ireland, the adjusted ORs (aOR) of full-EBM receipt were lower in Spain/Portugal (aOR 0.08, 95% CI 0.02 to 0.29), Canada (aOR 0.13 (95% CI 0.06 to 0.31) and USA (aOR 0.16 (95% CI 0.07 to 0.35). EBM was less likely in infants with dehydration (aOR 0.49 (95% CI 0.33 to 0.71)), chest retractions (aOR 0.69 (95% CI 0.52 to 0.91)) and nasal flaring (aOR 0.69 (95% CI 0.52 to 0.92)). EBM was associated with reduced odds of hospitalisation at the index visit (aOR 0.77 (95% CI 0.60 to 0.98)) but not at revisits (aOR 1.17 (95% CI 0.74 to 1.85))., Conclusions: Infants with bronchiolitis frequently do not receive full-EBM ED management, particularly those outside of the UK/Ireland. Furthermore, there is marked variation in full-EBM between paediatric emergency networks, and full-EBM delivery is associated with lower likelihood of hospitalisation. Given the global bronchiolitis burden, international ED-focused deimplementation of non-indicated interventions to enhance EBM is needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is limited ability to predict the severity of allergic reactions in children. Data derived predominantly from adults have implicated the platelet-activating factor pathway as a potential contributor to severe anaphylaxis. In this study, we sought to prospectively assess involvement of key components of the platelet-activating factor pathway in pediatric patients with anaphylaxis., Methods: Forty-six pediatric patients (<18 years) presenting with acute anaphylaxis were assessed. Anaphylaxis severity was graded and serum anaphylaxis markers were measured acutely and in 36 children who returned for follow-up >4 weeks after their acute presentation. These markers were compared with pediatric laboratory reference sera., Results: Severe anaphylaxis was experienced by 12/46 (26%) and mild-moderate anaphylaxis in 34/46 (74%) children. Platelet-activating factor acetylhydrolase (PAF-AH) activity was inversely associated with severe anaphylaxis: 9/12 children with severe anaphylaxis had reduced PAF-AH activity as compared with 14/34 with mild-moderate anaphylaxis (p < .05). Furthermore, 3/3 children who required intensive care had markedly reduced mean PAF-AH (nmol/ml/min) (13.73, 95%CI: 7.42-20.03) versus 20/23 who required ward/emergency department care (17.81, 95%CI: 16.80-18.83; p < .05). In children with anaphylaxis, PAF-AH during acute anaphylaxis was unchanged relative to the child's basal levels (mean, 17.26, 95%CI: 16.10-18.42 vs 17.50, 95%CI: 16.21-18.78, p = .63) and was lower than healthy pediatric controls (mean 19.21; 95%CI:18.21-20.21; p < .05)., Conclusion: Decreased serum PAF-AH activity is a biomarker of severe anaphylaxis. Levels of this enzyme do not change from basal levels during acute anaphylaxis. Our results show that PAF-AH is a biomarker of anaphylaxis severity in children. This key regulatory enzyme may modulate susceptibility to severe anaphylaxis., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: We sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children., Methods: We collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were <18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed. To determine if SARS-CoV-2 test status was independently associated with corticosteroid administration, we used a multivariable conditional logistic regression model matched by study site to compare treatments administered based on SARS-CoV-2 test and disposition status. This analysis was repeated for the subgroup of study participants who were hospitalized., Results: 30.3% (3,121/10,315) of participants were SARS-CoV-2-positive. Although remdesivir was more commonly administered to SARS-CoV-2-positive children, use was infrequent (25/3120 [0.8%] vs 1/7188 [0.01%]; P = .001). Corticosteroid use was less common among SARS-CoV-2-positive children (219/3120 [7.0%] vs 759/7190 [10.6%]; P < .001). Among hospitalized children, there were no differences in provision of inotropes, respiratory support, chest drainage or extracorporeal membrane oxygenation between groups. Corticosteroid administration was associated with age, history of asthma, wheezing, study month, hospitalization and intensive care unit admission; it was not associated with a positive SARS-CoV-2 test result overall (aOR: 0.91; 95%CI: 0.74, 1.12) or among the subgroup of those hospitalized (aOR: 1.04; 95%CI: 0.75, 1.44)., Conclusions: Few disease-specific treatments are provided to SARS-CoV-2-positive children; clinical trials evaluating therapies in children are urgently needed., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children., Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs., Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls., Exposure: SARS-CoV-2 detected via nucleic acid testing., Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey., Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00])., Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

Over the past decade, visits to American and Canadian emergency departments (EDs) for child and youth mental health care have increased substantially. 1,2 Acute mental health crises can occur as a result of a variety of concerns, including those that are life threatening (eg, suicide attempts), pose safety concerns (eg, suicidal intentions, aggressive behaviors, alcohol and other drug use), and are physically distressing to the child or youth (eg, panic attacks). ED health care providers play a vital role in assessing the safety and well-being of the child or youth and referring them to services for ongoing care. 3,4 During the ED visit, assessment and care should pinpoint risks, inform treatment, and consider family needs and preferences as part of a patient-centered approach. Yet, this approach to care is not widely adopted in EDs. Most EDs do not require the use of pediatric-specific mental health tools to guide assessments or have patient-centered procedures in place to guide the care of patients with mental health emergencies. 5-7 Our team believes these limitations have led to the provision of acute mental health care that can lack sufficient quality and efficiency. This study protocol describes a trial designed to evaluate if a novel mental health care bundle that was co-designed with parents and youth results in greater improvements in the well-being of children and youth 30 days after seeking ED care for mental health and/or substance misuse concerns compared with existing care protocols. We hypothesize that the bundle will positively impact child and youth well-being, while also providing cost-effective health care system benefits., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Patient engagement in healthcare research is a necessity to ensure that research objectives align with priorities, outcomes and needs of the population under study, and to facilitate ease of implementation and adoption of findings. In clinical trials, there is an increasing focus on patient engagement during the planning and conduct of clinical trials due to the potential for ethical and methodological benefits. As patient engagement in clinical trials increases, there is a need to evaluate the approaches of these activities to contribute evidence on what is most appropriate and successful. The purpose of this study is to evaluate patient engagement processes and the activities of patient partners during and after a paediatric mental healthcare trial., Methods and Analysis: Using a mixed-methods study design, we will evaluate patient partners' engagement activities across set time-points during the trial and after trial completion. In this study, the term 'patient partner' is inclusive of two groups of people with lived experience: (1) caregivers (parents, formal/informal caregivers and family), and (2) youth (aged 15-24 years). Engagement will be evaluated using the participant and project questionnaires of the Public and Patient Engagement Evaluation Tool (PPEET), followed sequentially by semi-structured interviews. Quantitative data from the PPEET questionnaire will be analysed and reported using descriptive statistics. Data from open-ended questions from the PPEET questionnaires and semi-structured interviews will be analysed using thematic analysis., Ethics and Dissemination: Approval from Athabasca University Research Ethics Board will be obtained for this project. Findings will be disseminated at both academic and public venues whether in-person or online, and using platforms that are caregiver and youth friendly., Trial Registration Number: NCT04902391., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: SF is supported by the Alberta Children’s Hospital Professorship in Child Health and Wellness. MS is the recipient of a Canadian Research Chair in Interdisciplinary Microbiome Research. YF is the recipient of the Canada Research Chair in Pediatric Drug Safety and Efficacy. PS is the recipient of a Canadian Research Chair in Gastrointestinal Disease and research funded by the Canadian Institutes of Health Research (MOP-89894 and IOP-92890) and received honoraria from Abbott Nutrition, Mead Johnson Nutritionals and Nestlé Nutrition. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Horne, Freedman, Johnson-Henry, Pang, Lee, Farion, Gouin, Schuh, Poonai, Hurley, Finkelstein, Xie, Williamson-Urquhart, Chui, Rossi, Surette and Sherman.)

Introduction: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication., Methods: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics., Results: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p  = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p  = 0.01) were independent predictors of severe outcome., Conclusions: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Objective: Trauma is the leading cause of childhood death in the United States. Our goal was to determine the effectiveness of tranexamic acid (TXA) in improving survival in pediatric trauma., Methods: MEDLINE (OVID), Embase (OVID), Cochrane Central Register databases, CINAHL (EBSCO), Web of Science (Clarivate Analytics), and grey literature sources were searched for publications reporting survival and safety outcomes in children receiving TXA in acute trauma, with no language restrictions, published until February 11, 2021. Two independent researchers assessed studies for eligibility, bias, and quality. Data on the study setting, injury type, participants, design, interventions, TXA dosing and outcomes were extracted. The primary outcome was survival in children who received TXA following trauma. Forest plots of effect estimates were constructed for each study. Heterogeneity was assessed and data were pooled by meta-analysis using a random-effects model., Results: Fourteen articles met inclusion criteria - six single-institution and eight multicentre retrospective cohort studies. Overall, TXA use was not associated with increased survival in pediatric trauma (adjusted odds ratio [aOR]: 0.61, 95% CI: 0.30-1.22) after adjustment for patient-level variables, such as injury severity. Increased survival was documented in the subset of children experiencing trauma in combat settings (aOR for mortality: 0.31, 95% CI: 0.14-0.68). There were no differences in the odds of thromboembolic events (OR 1.15, 95% CI: 0.46-2.87) in children who received TXA versus not., Conclusions: The utility of TXA in children with trauma is unclear. Guidelines supporting TXA use in pediatric trauma may not be based on the available evidence of its use in this context. Rigorous trials measuring survival and other meaningful outcomes and exploring optimal TXA dosing are urgently needed. Study Registration (PROSPERO): CRD42020157683., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study is to describe the impact of the pandemic on poisoning in children under 18 years presenting to a tertiary care paediatric emergency department (ED) in Canada., Methods: We utilized the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) surveillance data to identify children presenting to the Hospital for Sick Children for poisonings during two time periods: pre-pandemic (March 11 to December 31, 2018 and 2019) and pandemic (March 11 to December 31, 2020). Primary outcomes investigated the change in proportion for total poisonings, unintentional poisonings, recreational drug use, and intentional self-harm exposures over total ED visits. Secondarily, we examined the change in proportion of poisonings between age, sex, substance type, and admission requirement pre-pandemic versus during pandemic., Results: The proportions significantly increased for total poisonings (122.5%), unintentional poisonings (127.8%), recreational drug use (160%), and intentional self-harm poisonings (104.2%) over total ED visits. The proportions over all poisoning cases also significantly increased for cannabis (44.3%), vaping (134.6%), other recreational drugs (54.5%), multi-substance use (29.3%), and admissions due to poisonings (44.3%) during the pandemic., Conclusion: Despite an overall decrease in ED visits, there was a significant increase in poisoning presentations to our ED during the pandemic compared with pre-pandemic years. Our results will provide better insight into care delivery and public health interventions for paediatric poisonings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the effects of pre- and intraprocedural opioids on adverse events in children undergoing procedural sedation with ketamine in the emergency department (ED)., Study Design: We conducted a retrospective cohort study of all children aged 0-18 years who underwent procedural sedation with intravenous ketamine alone, or in combination with an opioid, at a tertiary-care pediatric ED between June 1, 2018, and August 31, 2020. We explored predictors of serious adverse events (SAEs), desaturation or respiratory intervention, and vomiting., Results: Of 1164 included children (694 male, 59.6%; median age 5.0 years [IQR 2.0-8.0]), 80 (6.8%) vomited, 63 (5.4%) had a desaturation or required respiratory interventions, and 6 (0.5%) had SAEs. Pre- and intraprocedural opioids were not independent predictors of sedation-related adverse events. A concurrent respiratory illness (aOR 3.73; 95% CI 1.31-10.60, P = .01), dental procedure (aOR 3.05; 95% CI 1.25-7.21, P = .01), and a greater total ketamine dose (aOR 1.75; 95% CI 1.21-2.54, P = .003) were independent predictors of desaturation or respiratory interventions. A greater total ketamine dose (aOR 1.86; 95% CI 1.16-2.98, P = .01) and older age (aOR 1.15; 95% CI 1.07-1.24, P < .001), were independent predictors of vomiting., Conclusions: Pre- and intraprocedural opioids do not increase the likelihood of sedation-related adverse events. SAEs are rare during pediatric procedural sedation with ketamine in the ED., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The proton dynamics of a 2D water monolayer confined inside a graphene slit pore is studied in Cartesian and molecular frames of reference using molecular dynamics simulations. The vibrational density of states of the proton was calculated versus temperature and was further used to deduce the mean kinetic energy of the hydrogen atoms, Ke(H), in both frames of reference. The directional components of Ke(H) are in good agreement with experimental observations for bulk as well as nanoconfined water. Nonetheless, while in the molecular frame of reference the effect of temperature on the anisotropy ratios of Ke(H) (the ratio between its directional components) are practically invariant between the 2D and 3D cases, those in the Cartesian frame of reference reveal a rather notable reduction across 200 K, indicating the occurrence of an order-disorder transition. This result is further supported by the calculated entropy and enthalpy of the confined water molecules. Overall, it is shown that Ke(H) anisotropy ratios may serve as a valuable order parameter for detecting structural transformations in hydrogen bonds containing molecular systems.

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized., Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED)., Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021., Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing., Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death., Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%)., Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.

Introduction: On April 13, 2017, a bill to legalize cannabis was introduced to the Canadian Parliament and presented to the public. On October 17, 2018, Canada legalized recreational cannabis use. We assessed intoxication severity, reflected by ICU admission rates, risk factors and other characteristics in children who presented to the emergency department (ED) with cannabis intoxication, before and after legalization., Methods: A retrospective cohort study of children 0-18 years who presented to a pediatric ED between January 1, 2008 and December 31, 2019 with cannabis intoxication. The pre-legalization period was defined from January 1, 2008 to April 12, 2017 and the peri-post legalization period from April 13, 2017 to December 31, 2019., Results: We identified 298 patients; 232 (77.8%) presented in the pre legalization period and 66 (22.1%) in the peri-post legalization period; median age: 15.9 years (range: 11 months-17.99 years). A higher proportion of children were admitted to the ICU in the peri-post legalization period (13.6% vs. 4.7%, respectively; p  = .02). While the median monthly number of cannabis-related presentations did not differ between the time periods (2.1 [IQR:1.9-2.5] in the pre legalization period vs. 1.7 [IQR:1.0-3.0] in the peri-post legalization period; p =  .69), the clinical severity did. The proportions of children with respiratory involvement (65.9% vs. 50.9%; p  = .05) and altered mental status (28.8% vs. 14.2%; p  < .01) were higher in the peri-post legalization period. The peri-post legalization period was characterized by more children younger than 12 years (12.1% vs. 3.0%; p  = .04), unintentional exposures (14.4% vs, 2.8%; p  = .002) and edibles ingestion (19.7% vs. 7.8%; p  = .01). Edible ingestion was an independent predictor of ICU admission (adjusted OR: 4.1, 95%CI: 1.2-13.7, p  = .02)., Conclusions: The recreational cannabis legalization in Canada is associated with increased rates of severe intoxications in children. Edible ingestion is a strong predictor of ICU admission in the pediatric population.

Competing Interests: Intérêts concurrents: Richard Huntsman et Lauren Kelly sont coprésidents du Comité consultatif scientifique sur les produits de santé contenant du cannabis de Santé Canada; l’opinion du Comité n’est ni reflétée ni garantie dans cet article. Lauren Kelly détient une bourse Mitacs Accélération en partenariat avec Canopy Growth, sans lien avec le présent manuscrit. Juan Pablo Appendino déclare avoir reçu des honoraires de Pendopharm, Sunovion et UCB; il est également membre de comités ou de conseils de la Canadian League Against Epilepsy, de la Société canadienne de neurophysiologie clinique, de la Fédération des sciences neurologiques du Canada et de l’Académie ibéro-américaine de neurologie pédiatrique. Richard Bélanger fait partie du comité sur le cannabis de la Société canadienne de pédiatrie. Bruce Crooks indique avoir participé au comité de surveillance de la sécurité des données pour l’étude ReRAD et il est membre du comité consultatif pour la Nouvelle-Écosse et du comité consultatif médical de la fondation Rêves d’enfants Canada. Evan Lewis est conseiller médical bénévole auprès de JMCC Canada Corp. et déclare avoir reçu des honoraires de Spectrum Therapeutics. Alexander Repetski a occupé un poste de consultant bénévole auprès de Strainprint. Michael Rieder est membre du comité de surveillance de l’innocuité des médicaments pour une étude sur l’utilisation du cannabis médical pour traiter la céphalée chez l’enfant, et il est l’auteur principal du document de principes de la Société canadienne de pédiatrie sur le cannabis médical chez les enfants. Régis Vaillancourt déclare avoir reçu des honoraires de consultation de Harvest Medicine. Aucun financement n’a été versé pour la rédaction de ce manuscrit. Aucun autre intérêt n’a été déclaré.

Objective: To determine 1-year attributable healthcare costs of bronchiolitis., Methods: Using a population-based matched cohort and incidence-based cost analysis approach, we identified infants <12 months old diagnosed in an emergency department (ED) or hospitalized with bronchiolitis between April 1, 2003 and March 31, 2014. We propensity-score matched infants with and without bronchiolitis on sex, age, income quintile, rurality, co-morbidities, gestational weeks, small-for-gestational-age status and pre-index healthcare cost deciles. We calculated mean attributable 1-year costs using a generalized estimating equation model and stratified costs by age, sex, income quintile, rurality, co-morbidities and prematurity., Results: We identified 58,375 infants with bronchiolitis (mean age 154±95 days, 61.3% males, 4.2% with comorbidities). Total 1-year mean bronchiolitis-attributable costs were $4,313 per patient (95%CI: $4,148-4,477), with $2,847 (95%CI: $2,712-2,982) spent on hospitalizations, $610 (95%CI: $594-627) on physician services, $562 (95%CI: $556-567)] on ED visits, $259 (95%CI: $222-297) on other healthcare costs and $35 ($27-42) on drugs. Attributable bronchiolitis costs were $2,765 (95%CI: $2735-2,794) vs $111 (95%CI: $102-121) in the initial 10 days post index date, $4,695 (95%CI: $4,589-4,800) vs $910 (95%CI: $847-973) in the initial 180 days and $1,158 (95%CI: $1,104-1213) vs $639 (95%CI: $599-679) during days 181-360. Mean 1-year bronchiolitis costs were higher in infants <3 months old [$5,536 (95%CI: $5,216-5,856)], those with co-morbidities [$17,530 (95%CI: $14,683-20,377)] and with low birthweight [$5,509 (95%CI: $4,927-6,091)]., Conclusions: Compared to no bronchiolitis, bronchiolitis incurs five-time and two-time higher healthcare costs within the initial and subsequent six-months, respectively. Most expenses occur in the initial 10 days and relate to hospitalization., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: Richard Huntsman and Lauren Kelly are co-chairs of the Health Canada scientific advisory committee on health products containing cannabis, whose opinion is not reflected or guaranteed within. Lauren Kelly holds a Mitacs Accelerate award in partnership with Canopy Growth, unrelated to this manuscript. Juan Pablo Appendino reports honoraria from Pendopharm, Sunovion and UCB, as well as board or committee membership with the Canadian League Against Epilepsy, the Canadian Society of Clinical Neurophysiologists, the Canadian Neurological Sciences Federation and the Iberoamerican Academy of Pediatric Neurology. Richard Bélanger is on the cannabis committee of the Canadian Paediatric Society. Bruce Crooks reports participation on the data safety monitoring board of the ReRAD study, as well as membership with the Nova Scotia chapter advisory board and medical advisory committee of Make a Wish Foundation Canada. Evan Lewis has an unpaid position as medical advisor to the JMCC Canada Corp., and also reports honoraria from Spectrum Therapeutics. Alexander Repetski has an unpaid advisory position with Strainprint. Michael Rieder is a member of the drug safety monitoring board for a study exploring the use of medical cannabis for headache in children and is the principal author of the Canadian Paediatric Society’s statement on medical cannabis for children. Regis Vaillancourt reports consulting fees from Harvest Medicine. No funding was received to author this manuscript. No other competing interests were declared.