Pandemic Stringency Measures and Hospital Admissions for Eating Disorders.

Importance: Hospitalizations for eating disorders rose dramatically during the COVID-19 pandemic. Public health restrictions, or stringency, are believed to have played a role in exacerbating eating disorders. Few studies of eating disorders during the pandemic have extended to the period when public health stringency restrictions were lifted. Objective: To assess the association between hospitalization rates for eating disorders and public health stringency during the COVID-19 pandemic and after the easing of public health restrictions. Design, Setting, and Participants: This Canadian population-based cross-sectional study was performed from April 1, 2016, to March 31, 2023, and was divided into pre-COVID-19 and COVID-19-prevalent periods. Data were provided by the Canadian Institute for Health Information and the Institut National d'Excellence en Santé et Services Sociaux for all Canadian provinces and territories. Participants included all children and adolescents aged 6 to 20 years. Exposure: The exposure was public health stringency, as measured by the Bank of Canada stringency index. Main Outcomes and Measures: The primary outcome was hospitalizations for a primary diagnosis of eating disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code F50), stratified by region, age group, and sex. Interrupted time series analyses based on Poisson regression were used to estimate the association between the stringency index and the rate of hospitalizations for eating disorders. Results: During the study period, there were 11 289 hospitalizations for eating disorders across Canada, of which 8726 hospitalizations (77%) were for females aged 12 to 17 years. Due to low case counts in other age-sex strata, the time series analysis was limited to females within the 12- to 17-year age range. Among females aged 12 to 17 years, a 10% increase in stringency was associated with a significant increase in hospitalization rates in Quebec (adjusted rate ratio [ARR], 1.05; 95% CI, 1.01-1.07), Ontario (ARR, 1.05; 95% CI, 1.03-1.07), the Prairies (ARR, 1.08; 95% CI, 1.03-1.13), and British Columbia (ARR, 1.11; 95% CI, 1.05-1.16). The excess COVID-19-prevalent period hospitalizations were highest at the 1-year mark, with increases in all regions: Quebec (RR, 2.17), Ontario (RR, 2.44), the Prairies (RR, 2.39), and British Columbia (RR, 2.02). Conclusion and Relevance: In this cross-sectional study of hospitalizations for eating disorders across Canada, hospitalization rates for eating disorders in females aged 12 to 17 years were associated with public health measure stringency. The findings suggest that future pandemic preparedness should consider implications for youths at risk for eating disorders and their resource and support needs.

Mental Health Hospitalizations in Canadian Children, Adolescents, and Young Adults Over the COVID-19 Pandemic.

Importance: The COVID-19 pandemic resulted in multiple socially restrictive public health measures and reported negative mental health impacts in youths. Few studies have evaluated incidence rates by sex, region, and social determinants across an entire population. Objective: To estimate the incidence of hospitalizations for mental health conditions, stratified by sex, region, and social determinants, in children and adolescents (hereinafter referred to as youths) and young adults comparing the prepandemic and pandemic-prevalent periods. Design, Setting, and Participants: This Canadian population-based repeated ecological cross-sectional study used health administrative data, extending from April 1, 2016, to March 31, 2023. All youths and young adults from 6 to 20 years of age in each of the Canadian provinces and territories were included. Data were provided by the Canadian Institute for Health Information for all provinces except Quebec; the Institut National d'Excellence en Santé et en Services Sociaux provided aggregate data for Quebec. Exposures: The COVID-19-prevalent period, defined as April 1, 2020, to March 31, 2023. Main Outcomes and Measures: The main outcome measures were the prepandemic and COVID-19-prevalent incidence rates of hospitalizations for anxiety, mood disorders, eating disorders, schizophrenia or psychosis, personality disorders, substance-related disorders, and self-harm. Secondary measures included hospitalization differences by sex, age group, and deprivation as well as emergency department visits for the same mental health conditions. Results: Among Canadian youths and young adults during the study period, there were 218 101 hospitalizations for mental health conditions (ages 6 to 11 years: 5.8%, 12 to 17 years: 66.9%, and 18 to 20 years: 27.3%; 66.0% female). The rate of mental health hospitalizations decreased from 51.6 to 47.9 per 10 000 person-years between the prepandemic and COVID-19-prevalent years. However, the pandemic was associated with a rise in hospitalizations for anxiety (incidence rate ratio [IRR], 1.11; 95% CI, 1.08-1.14), personality disorders (IRR, 1.21; 95% CI, 1.16-1.25), suicide and self-harm (IRR, 1.10; 95% CI, 1.07-1.13), and eating disorders (IRR, 1.66; 95% CI, 1.60-1.73) in females and for eating disorders (IRR, 1.47; 95% CI, 1.31-1.67) in males. In both sexes, there was a decrease in hospitalizations for mood disorders (IRR, 0.84; 95% CI, 0.83-0.86), substance-related disorders (IRR, 0.83; 95% CI, 0.81-0.86), and other mental health disorders (IRR, 0.78; 95% CI, 0.76-0.79). Conclusions and Relevance: This cross-sectional study of Canadian youths and young adults found a rise in anxiety, personality disorders, and suicidality in females and a rise in eating disorders in both sexes in the COVID-19-prevalent period. These results suggest that in future pandemics, policymakers should support youths and young adults who are particularly vulnerable to deterioration in mental health conditions during public health restrictions, including eating disorders, anxiety, and suicidality.

Clinical Outcomes of Rapid Respiratory Virus Testing in Emergency Departments: A Systematic Review and Meta-Analysis.

Importance: Rapid tests for respiratory viruses, including multiplex panels, are increasingly available in emergency departments (EDs). Their association with patient outcomes remains unclear. Objective: To determine if ED rapid respiratory virus testing in patients with suspected acute respiratory infection (ARI) was associated with decreased antibiotic use, ancillary tests, ED length of stay, and ED return visits and hospitalization and increased influenza antiviral treatment. Data Sources: Ovid MEDLINE, Embase (Ovid), Scopus, and Web of Science from 1985 to November 14, 2022. Study Selection: Randomized clinical trials of patients of any age with ARI in an ED. The primary intervention was rapid viral testing. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Two independent reviewers (T.S. and K.W.) extracted data and assessed risk of bias using the Cochrane Risk of Bias, version 2.0. Estimates were pooled using random-effects models. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Main Outcomes and Measures: Antibiotic use and secondary outcomes were pooled separately as risk ratios (RRs) and risk difference estimates with 95% CIs. Results: Of 7157 studies identified, 11 (0.2%; n = 6068 patients) were included in pooled analyses. Routine rapid viral testing was not associated with antibiotic use (RR, 0.99; 95% CI, 0.93-1.05; high certainty) but was associated with higher use of influenza antivirals (RR, 1.33; 95% CI, 1.02-1.75; moderate certainty) and lower use of chest radiography (RR, 0.88; 95% CI, 0.79-0.98; moderate certainty) and blood tests (RR, 0.81; 95% CI, 0.69-0.97; moderate certainty). There was no association with urine testing (RR, 0.95; 95% CI, 0.77-1.17; low certainty), ED length of stay (0 hours; 95% CI, -0.17 to 0.16; moderate certainty), return visits (RR, 0.93; 95%, CI 0.79-1.08; moderate certainty) or hospitalization (RR, 1.01; 95% CI, 0.95-1.08; high certainty). Adults represented 963 participants (16%). There was no association of viral testing with antibiotic use in any prespecified subgroup by age, test method, publication date, number of viral targets, risk of bias, or industry funding. Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that there are limited benefits of routine viral testing in EDs for patients with ARI. Further studies in adults, especially those with high-risk conditions, are warranted.

Association of delayed adequate antimicrobial treatment and organ dysfunction in pediatric bloodstream infections.

BACKGROUND: Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores. METHODS: We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment. RESULTS: Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88). CONCLUSIONS: We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment. IMPACT: In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research.

Perspectives of Pediatric Nephrologists, Intensivists and Nurses Regarding AKI Management and Expected Outcomes.

Background: Acute kidney injury (AKI) in critically ill children is associated with increased risk for short- and long-term adverse outcomes. Currently, there is no systematic follow-up for children who develop AKI in intensive care unit (ICU). Objective: This study aimed to assess variation regarding management, perceived importance, and follow-up of AKI in the ICU setting within and between healthcare professional (HCP) groups. Design: Anonymous, cross-sectional, web-based surveys were administered nationally to Canadian pediatric nephrologists, pediatric intensive care unit (PICU) physicians, and PICU nurses, via professional listservs. Setting: All Canadian pediatric nephrologists, PICU physicians, and nurses treating children in the ICU were eligible for the survey. Patients: N/A. Measurements: Surveys included multiple choice and Likert scale questions on current practice related to AKI management and long-term follow-up, including institutional and personal practice approaches, and perceived importance of AKI severity with different outcomes. Methods: Descriptive statistics were performed. Categorical responses were compared using Chi-square or Fisher's exact tests; Likert scale results were compared using Mann-Whitney and Kruskal-Wallis tests. Results: Surveys were completed by 34/64 (53%) pediatric nephrologists, 46/113 (41%) PICU physicians, and 82 PICU nurses (response rate unknown). Over 65% of providers reported hemodialysis to be prescribed by nephrology; a mix of nephrology, ICU, or a shared nephrology-ICU model was reported responsible for peritoneal dialysis and continuous renal replacement therapy (CRRT). Severe hyperkalemia was the most important renal replacement therapy (RRT) indication for both nephrologists and PICU physicians (Likert scale from 0 [not important] to 10 [most important]; median = 10, 10, respectively). Nephrologists reported a lower threshold of AKI for increased mortality risk; 38% believed stage 2 AKI was the minimum compared to 17% of PICU physicians and 14% of nurses. Nephrologists were more likely than PICU physicians and nurses to recommend long-term follow-up for patients who develop any AKI during ICU stay (Likert scale from 0 [none] to 10 [all patients]; mean=6.0, 3.8, 3.7, respectively) (P < .05). Limitations: Responses from all eligible HCPs in the country could not obtained. There may be differences in opinions between HCPs that completed the survey compared to those that did not. Additionally, the cross-sectional design of our study may not adequately reflect changes in guidelines and knowledge since survey completion, although no specific guidelines have been released in Canada since survey dissemination. Conclusions: Canadian HCP groups have variable perspectives on pediatric AKI management and follow-up. Understanding practice patterns and perspectives will help optimize pediatric AKI follow-up guideline implementation.

Contexte: L'insuffisance rénale aiguë (IRA) chez les enfants gravement malades est associée à un risque accru d'issues défavorables à court et à long terme. En ce moment, il n'existe aucun suivi systématique pour les enfants qui développent une IRA pendant un séjour à l'unité des soins intensifs (USI). Objectif: Cette étude visait à évaluer les variations dans la prise en charge de l'IRA, de son importance perçue et de son suivi, tant au sein des groupes de professionnels de la santé (PS) qu'entre les différents groupes de PS. Conception: Des sondages transversaux à remplir de façon anonyme en ligne ont été menés à l'échelle nationale auprès de néphrologues pédiatriques canadiens, de médecins des unités de soins intensifs pédiatriques (USIP) et de membres du personnel infirmier des USIP ayant été répertoriés à partir de listes professionnelles. Cadre: Tous les néphrologues pédiatriques canadiens, médecins et membres du personnel infirmier qui traitent des enfants en USI étaient admissibles à répondre au sondage. Patients: S/O. Mesures: Les sondages comportaient des questions à choix multiples et des questions de type échelle de Likert qui portaient sur les pratiques actuelles de la gestion et de suivi à long terme de l'IRA, notamment sur les approches institutionnelles et personnelles de pratique et sur l'importance perçue de la gravité de l'IRA avec différents résultats. Méthodologie: Des statistiques descriptives ont été réalisées. Les réponses catégorielles ont été comparées à l'aide du chi-carré ou de tests exacts de probabilité de Fisher; les résultats des échelles de Likert ont été comparés à l'aide de tests de Mann-Whitney et de Kruskal-Wallis. Résultats: Les sondages ont été complétés par 53 % des néphrologues pédiatriques (34/64), 41 % des médecins d'USIP (46/113) et par 82 membres du personnel infirmier d'USIP (taux de réponse inconnu). Plus de 65 % des prestataires de soins ont déclaré que l'hémodialyse était prescrite par le service de néphrologie, alors que la dialyze péritonéale et la thérapie de remplacement rénal continu (TRRC) étaient confiées à la fois à la néphrologie, à l'USI ou à un modèle partagé néphrologie-USI. L'hyperkaliémie grave était l'indication la plus importante de la TRR pour les néphrologues et les médecins en USIP (échelle de Likert de 0 [pas important] à 10 [le plus important]; médiane = 10, 10, respectivement). Les néphrologues ont signalé un seuil inférieur d'IRA pour l'augmentation du risque de mortalité; 38 % d'entre eux estimaient que l'IRA de stade 2 était le seuil minimum, contre 17 % des médecins en USI et 14 % du personnel infirmier. Les néphrologues étaient plus susceptibles que les médecins et le personnel infirmier des USIP de recommander un suivi à long terme pour les patients qui développent une IRA pendant leur séjour en USI (échelle Likert de 0 [aucun] à 10 [tous les patients]; moyennes respectives = 6,0; 3,8 et 3,7 [p < 0,05]). Limites: Il n'a pas été possible d'obtenir les réponses de tous les PS admissibles au pays. Des différences d'opinions sont possibles entre les PS qui ont répondu au sondage et ceux qui ne l'ont pas fait. De plus, la conception transversale de notre étude pourrait ne pas refléter adéquatement les changements apportés aux lignes directrices et aux connaissances depuis la fin de cette enquête, bien qu'aucune ligne directrice particulière n'ait été publiée au Canada depuis la diffusion du sondage. Conclusion: Les divers groupes de professionnels de la santé canadiens ont des points de vue différents en ce qui concerne la prise en charge et le suivi de l'IRA chez les enfants. La compréhension des modèles de pratique et des perspectives permettra d'optimiser la mise en œuvre de directives de suivi de l'IRA pédiatrique.

Designing a national pediatric critical care database: a Delphi consensus study.

PURPOSE: We sought to describe the processes undertaken for the systematic selection and consensus determination of the common data elements for inclusion in a national pediatric critical care database in Canada. METHODS: We conducted a multicentre Delphi consensus study of Canadian pediatric intensive care units (PICUs) participating in the creation of a national database. Participants were PICU health care professionals, allied health professionals, caregivers, and other stakeholders. A dedicated panel group created a baseline survey of data elements based on literature, current PICU databases, and expertise in the field. The survey was then used for a Delphi iterative consensus process over three rounds, conducted from March to June 2021. RESULTS: Of 86 invited participants, 68 (79%) engaged and agreed to participate as part of an expert panel. Panel participants were sent three rounds of the survey with response rates of 62 (91%), 61 (90%) and 55 (81%), respectively. After three rounds, 72 data elements were included from six domains, mostly reflecting clinical status and complex medical interventions received in the PICU. While race, gender, and home region were included by consensus, variables such as minority status, indigenous status, primary language, and ethnicity were not. CONCLUSION: We present the methodological framework used to select data elements by consensus for a national pediatric critical care database, with participation from a diverse stakeholder group of experts and caregivers from all PICUs in Canada. The selected core data elements will provide standardized and synthesized data for research, benchmarking, and quality improvement initiatives of critically ill children.

RéSUMé: OBJECTIF: Nous avons cherché à décrire les processus entrepris pour la sélection systématique et la détermination consensuelle des éléments de données communs à inclure dans une base de données nationale sur les soins intensifs pédiatriques au Canada. MéTHODE: Nous avons mené une étude multicentrique de consensus selon la méthode Delphi sur les unités de soins intensifs pédiatriques (USIP) canadiennes participant à la création d'une base de données nationale. Les personnes participant à l'étude étaient des professionnel·les de la santé de l'USIP, du personnel paramédical, des soignant·es et d'autres intervenant·es. Un groupe de travail spécialisé a créé une enquête de base des éléments de données sur la littérature, les bases de données actuelles portant sur les USIP et l'expertise dans le domaine. L'enquête a ensuite été utilisée pour créer un processus de consensus itératif Delphi sur trois cycles, mené de mars à juin 2021. RéSULTATS: Sur les 86 personnes invitées à participer, 68 (79 %) se sont engagées et ont accepté de participer à un groupe d'experts. Les membres du panel ont reçu trois rondes du sondage, avec des taux de réponse de 62 (91 %), 61 (90 %) et 55 (81 %), respectivement. Après trois cycles, 72 éléments de données provenant de six domaines ont été inclus, reflétant principalement l'état clinique et les interventions médicales complexes reçues à l'USIP. Alors que la race, le genre et la région d'origine ont été inclus par consensus, des variables telles que le statut de minorité, le statut d'autochtone, la langue principale parlée et l'origine ethnique ne l'ont pas été. CONCLUSION: Nous présentons le cadre méthodologique utilisé pour sélectionner des éléments de données consensuels destinés à une base de données nationale sur les soins intensifs pédiatriques, avec la participation d'un groupe diversifié d'expert·es et de soignant·es de toutes les USIP au Canada. Les éléments de données de base sélectionnés fourniront des données normalisées et synthétisées pour la recherche, l'analyse comparative et les initiatives d'amélioration de la qualité pour les enfants gravement malades.

"We Aren't Meant to Go Through the Hardest Parts of Our Lives Alone": Family Experience With Restricted PICU Presence During the COVID-19 Pandemic.

CONTEXT: PICUs across Canada restricted family presence (RFP) in response to the COVID-19 pandemic from allowing two or more family members to often only one family member at the bedside. The objective of this study was to describe the experiences and impact of RFP on families of critically ill children to inform future policy and practice. HYPOTHESIS: RFP policies negatively impacted families of PICU patients and caused moral distress. METHODS AND MODELS: National, cross-sectional, online, self-administered survey. Family members of children admitted to a Canadian PICU between March 2020 and February 2021 were invited to complete the survey. RFP-attributable distress was measured with a modified distress thermometer (0-10). Closed-ended questions were reported with descriptive statistics and multivariable linear regression assessed factors associated with RFP-attributable distress. Open-ended questions were analyzed using inductive content analysis. RESULTS: Of 250 respondents who experienced RFP, 124 (49.6%) were restricted to one family member at the bedside. The median amount of distress that families attributed to RFP policies was 6 (range: 0-10). Families described isolation, removal of supports, and perception of trauma related to RFP. Most families (183, 73.2%) felt that policies were enforced in a way that made them feel valued by PICU clinicians, which was associated with less RFP-attributable distress. Differential impact was seen where families with lower household income indicated higher RFP-attributable distress score (2.35; 95% CI, 0.53-4.17; p = 0.03). Most respondents suggested that future policies should allow at least two family members at the bedside. INTERPRETATIONS AND CONCLUSIONS: Families of children admitted to PICUs during the COVID-19 pandemic described increased distress, trauma, and removal of supports due to RFP policies. Vulnerable families showed an increased odds of higher distress. Healthcare professionals played an important role in mitigating distress. Allowance of at least two family members at the bedside should be considered for future policy.

Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

Antibiotic treatment duration for bloodstream infections in critically ill children-A survey of pediatric infectious diseases and critical care clinicians for clinical equipoise.

OBJECTIVE: To describe antibiotic treatment durations that pediatric infectious diseases (ID) and critical care clinicians usually recommend for bloodstream infections in critically ill children. DESIGN: Anonymous, online practice survey using five common pediatric-based case scenarios of bloodstream infections. SETTING: Pediatric intensive care units in Canada, Australia and New Zealand. PARTICIPANTS: Pediatric intensivists, nurse practitioners, ID physicians and pharmacists. MAIN OUTCOME MEASURES: Recommended treatment durations for common infectious syndromes associated with bloodstream infections and willingness to enrol patients into a trial to study treatment duration. RESULTS: Among 136 survey respondents, most recommended at least 10 days antibiotics for bloodstream infections associated with: pneumonia (65%), skin/soft tissue (74%), urinary tract (64%) and intra-abdominal infections (drained: 90%; undrained: 99%). For central vascular catheter-associated infections without catheter removal, over 90% clinicians recommended at least 10 days antibiotics, except for infections caused by coagulase negative staphylococci (79%). Recommendations for at least 10 days antibiotics were less common with catheter removal. In multivariable linear regression analyses, lack of source control was significantly associated with longer treatment durations (+5.2 days [95% CI: 4.4-6.1 days] for intra-abdominal infections and +4.1 days [95% CI: 3.8-4.4 days] for central vascular catheter-associated infections). Most clinicians (73-95%, depending on the source of bloodstream infection) would be willing to enrol patients into a trial of shorter versus longer antibiotic treatment duration. CONCLUSIONS: The majority of clinicians currently recommend at least 10 days of antibiotics for most scenarios of bloodstream infections in critically ill children. There is practice heterogeneity in self-reported treatment duration recommendations among clinicians. Treatment durations were similar across different infectious syndromes. Under appropriate clinical conditions, most clinicians would be willing to enrol patients into a trial of shorter versus longer treatment for common syndromes associated with bloodstream infections.

Continuous clonidine infusion: an alternative for children on mechanical ventilation.

OBJECTIVE: This study aimed to assess the clonidine infusion rate in the first 6 h, as maintenance dose (first 24 h), and in the pre-extubation period (last 24 h), as well as the cumulative dose of other sedatives and the hemodynamic response. METHODS: This is a retrospective cohort study. RESULTS: Children up to the age of 2 years who were admitted to the pediatric intensive care unit of a tertiary referral hospital in the south region of Brazil, between January 2017 and December 2018, were submitted to mechanical ventilation, and received continuous clonidine infusions were included in the study. The initial, maintenance, and pre-extubation doses of clonidine; the vasoactive-inotropic score; heart rate; and systolic and diastolic blood pressure of the study participants were assessed. A total of 66 patients with a median age of 4 months who were receiving clonidine infusions were included. The main indications for mechanical ventilation were acute viral bronchiolitis (56%) and pneumonia associated with acute respiratory distress syndrome (15%). The median of clonidine infusion in the first 6 h (66 patients) was 0.53 µg/kg/h (IQR 0.49-0.88), followed by 0.85 µg/kg/h (IQR 0.53-1.03) during maintenance (57 patients) and 0.63 µg/kg/h (IQR 0.54-1.01) during extubation period (42 patients) (p=0.03). No differences were observed in the doses regarding the indication for mechanical ventilation. Clonidine infusion was not associated with hemodynamic changes and showed no differences when associated with adjuvants. CONCLUSION: Clonidine demonstrated to be a well-tolerated sedation option in pediatric patients submitted to mechanical ventilation, without relevant influence in hemodynamic variables.

Continuous clonidine infusion: an alternative for children on mechanical ventilation

SUMMARY OBJECTIVE: This study aimed to assess the clonidine infusion rate in the first 6 h, as maintenance dose (first 24 h), and in the pre-extubation period (last 24 h), as well as the cumulative dose of other sedatives and the hemodynamic response. METHODS: This is a retrospective cohort study. RESULTS: Children up to the age of 2 years who were admitted to the pediatric intensive care unit of a tertiary referral hospital in the south region of Brazil, between January 2017 and December 2018, were submitted to mechanical ventilation, and received continuous clonidine infusions were included in the study. The initial, maintenance, and pre-extubation doses of clonidine; the vasoactive-inotropic score; heart rate; and systolic and diastolic blood pressure of the study participants were assessed. A total of 66 patients with a median age of 4 months who were receiving clonidine infusions were included. The main indications for mechanical ventilation were acute viral bronchiolitis (56%) and pneumonia associated with acute respiratory distress syndrome (15%). The median of clonidine infusion in the first 6 h (66 patients) was 0.53 μg/kg/h (IQR 0.49-0.88), followed by 0.85 μg/kg/h (IQR 0.53-1.03) during maintenance (57 patients) and 0.63 μg/kg/h (IQR 0.54-1.01) during extubation period (42 patients) (p=0.03). No differences were observed in the doses regarding the indication for mechanical ventilation. Clonidine infusion was not associated with hemodynamic changes and showed no differences when associated with adjuvants. CONCLUSION: Clonidine demonstrated to be a well-tolerated sedation option in pediatric patients submitted to mechanical ventilation, without relevant influence in hemodynamic variables.

Noninferiority Margin Size and Acceptance of Trial Results: Contingent Valuation Survey of Clinician Preferences for Noninferior Mortality.

OBJECTIVES: We used modified contingent valuation methodology to determine how noninferiority margin sizes influence clinicians' willingness to accept clinical trial results that compare mortality in critically ill children. METHODS: We surveyed pediatric infectious diseases and critical care clinicians in Canada, Australia, and New Zealand and randomized respondents to review 1 of 9 mock abstracts describing a noninferiority trial of bacteremic critically ill children assigned to 7 or 14 d of antibiotics. Each scenario showed higher mortality in the 7-d group but met noninferiority criterion. We explored how noninferiority margins and baseline mortality rates influenced respondent acceptance of results. RESULTS: There were 106 survey respondents: 65 (61%) critical care clinicians, 28 (26%) infectious diseases physicians, and 13 (12%) pharmacists. When noninferiority margins were 5% and 10%, 73% (24/33) and 79% (27/33) respondents would accept shorter treatment, compared with 44% (17/39) when the margin was 20% (P = 0.003). Logistic regression adjusted for baseline mortality showed 5% and 10% noninferiority margins were more likely to be associated with acceptance of shorter treatment compared with 20% margins (odds ratio [OR] 3.5, 95% confidence interval [CI]: 1.3-9.6, P = 0.013; OR 5.1, 95% CI: 1.8-14.6, P = 0.002). Baseline mortality was not a significant predictor of acceptance of shorter treatment. CONCLUSIONS: Clinicians are more likely to accept shorter treatment when noninferiority margins are ≤10%. However, nearly half of respondents who reviewed abstracts with 20% margins were still willing to accept shorter treatment. This is a novel application of contingent valuation methodology to elicit acceptance of research results among end users of the medical literature. HIGHLIGHTS: Clinicians are more likely to accept shorter treatment durations based on noninferior mortality results when the noninferiority margin is 5% or 10% than if the margin is 20%.However, nearly half of clinicians would still accept shorter-duration treatment as noninferior with margins of 20%.Baseline mortality does not independently predict acceptance of shorter-duration treatment.Contingent valuation is a novel approach to elicit the acceptance of research design parameters from the perspective of endusers of the medical literature.

Antimicrobial treatment duration for uncomplicated bloodstream infections in critically ill children: a multicentre observational study.

BACKGROUND: Bloodstream infections (BSIs) cause significant morbidity and mortality in critically ill children but treatment duration is understudied. We describe the durations of antimicrobial treatment that critically ill children receive and explore factors associated with treatment duration. METHODS: We conducted a retrospective observational cohort study in six pediatric intensive care units (PICUs) across Canada. Associations between treatment duration and patient-, infection- and pathogen-related characteristics were explored using multivariable regression analyses. RESULTS: Among 187 critically ill children with BSIs, the median duration of antimicrobial treatment was 15 (IQR 11-25) days. Median treatment durations were longer than two weeks for all subjects with known sources of infection: catheter-related 16 (IQR 11-24), respiratory 15 (IQR 11-26), intra-abdominal 20 (IQR 14-26), skin/soft tissue 17 (IQR 15-33), urinary 17 (IQR 15-35), central nervous system 33 (IQR 15-46) and other sources 29.5 (IQR 15-55) days. When sources of infection were unclear, the median duration was 13 (IQR 10-16) days. Treatment durations varied widely within and across PICUs. In multivariable linear regression, longer treatment durations were associated with severity of illness (+ 0.4 days longer [95% confidence interval (CI), 0.1 to 0.7, p = 0.007] per unit increase in PRISM-IV) and central nervous system infection (+ 17 days [95% CI, 6.7 to 27.4], p = 0.001). Age and pathogen type were not associated with treatment duration. CONCLUSIONS: Most critically ill children with BSIs received at least two weeks of antimicrobial treatment. Further study is needed to determine whether shorter duration therapy would be effective for selected critically ill children.

Bronchiolitis Management and Unnecessary Antibiotic Use Across 3 Canadian PICUs.

OBJECTIVES: To describe the patient characteristics, clinical management, and infectious etiology in critically ill children with bronchiolitis. The secondary objective was to determine the association between antibiotic use and hospital length of stay among patients without concomitant bacterial infections. METHODS: Retrospective cohort study including patients ≤2 years old with bronchiolitis admitted to 3 Canadian pediatric intensive care units between 2016 and 2018. RESULTS: We included 372 patients with a median age of 2.1 months (interquartile range 1.2-6.6) and Pediatric Risk of Mortality III score 3.0 (interquartile range 0-3.0). Initial ventilatory management included high flow nasal cannula (28.2%) and noninvasive positive pressure ventilation (53.7%), of which 41.9% and 87.5%, respectively, did not require escalation of ventilatory support. Chest radiographs (81.7%) and respiratory virus testing (95.4%) were performed in most patients; 14.0% received systemic steroids. Respiratory syncytial virus was detected in 61.3% patients, and 7.5% had a culture-positive concomitant bacterial infection. Of 258 (69.4%) patients with a viral infection, only 45.3% received antibiotics. In this group, antibiotic use beyond 72 hours was not associated with hospital length of stay (ratio 1.14, 95% confidence interval 0.97-1.34). CONCLUSIONS: High flow nasal canulae and noninvasive ventilation are commonly used in severe bronchiolitis. Despite contrary evidence, steroids and antibiotics were also frequently used. Evidence-based guidelines specific to children with severe bronchiolitis are needed to improve the care delivered to this patient population.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Clinical Reasoning Behind Antibiotic Use in PICUs: A Qualitative Study.

OBJECTIVES: To describe the reasoning processes used by pediatric intensivists to make antibiotic-related decisions. DESIGN: Grounded theory qualitative study. SETTING: Three Canadian university-affiliated tertiary medical, surgical, and cardiac PICUs. PATIENTS: Twenty-one PICU physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted field observation during morning rounds followed by semistructured interviews with participants to examine the clinical reasoning behind antibiotic-related decisions (starting/stopping antibiotics, or treatment duration) made for patients with a suspected/proven bacterial infection. We used a grounded theory approach for data collection and analysis. Thematic saturation was reached after 21 interviews. Of the 21 participants, 10 (48%) were female, 15 (71%) were PICU attending staff, and 10 (48%) had greater than 10 years in clinical practice. Initial clinical reasoning involves using an analytical approach to determine the likelihood of bacterial infection. In case of uncertainty, an assessment of patient safety is performed, which partly overlaps with the use of intuitive clinical reasoning. Finally, if uncertainty remains, physicians tend to consult infectious diseases experts. Factors that override this clinical reasoning process include disease severity, pressure from consultants, and the tendency to continue antibiotic treatment initiated by colleagues. CONCLUSIONS: Antibiotic-related decisions for critically ill children are complex, and pediatric intensivists use several clinical reasoning strategies to decrease the uncertainty around the bacterial etiology of infections. However, disease severity and patient safety concerns may overrule decisions based on clinical evidence and lead to antibiotic use. Several cognitive biases were identified in the clinical reasoning processes.

Association between leukoreduced red blood cell transfusions and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

BACKGROUND AND OBJECTIVES: Hospital-acquired infections (HAIs) are an important problem in critically ill children. Studies show associations between the transfusion of non-leukoreduced red blood cell units (RBC) and increased HAI incidence rates (IRs). We hypothesize that transfusing pre-storage leukoreduced RBC is also associated with increased HAI IR. We aim to evaluate the associations between (1) a leukoreduced RBC restrictive transfusion strategy and HAI IR, (2) leukoreduced RBC transfusions and HAI IR, and (3) the number or volume of leukoreduced RBC transfusions and HAI IR in critically ill children. MATERIALS AND METHODS: This post hoc secondary analysis of the "Transfusion Requirement in Paediatric Intensive Care Units" (TRIPICU) randomized controlled trial (637 patients) used quasi-Poisson multivariable regression models to estimate HAI incidence rate ratios (IRRs) and 95% confidence intervals (CI). RESULTS: A restrictive transfusion strategy yielded an IRR of 0.88 (95% CI 0.67, 1.16). The association between transfusing leukoreduced RBCs (IRR 1.25; 95% CI 0.73, 2.13) and HAI IR was not statistically significant. However, we observed significant associations between patients who received >20 cc/kg volume of leukoreduced RBC transfusions (IRR 2.14; 95% CI 1.15, 3.99) and ≥3 leukoreduced RBC transfusions (IRR 2.40; 95% CI 1.15, 4.99) and HAI IR. CONCLUSION: Exposing critically ill children to >20 cc/kg or ≥3 leukoreduced RBC transfusions were associated with higher HAI IR, suggesting dose-response patterns.

Antimicrobial Stewardship in Bronchiolitis: A Retrospective Cohort Study of Three PICUs in Canada.

OBJECTIVES: To determine the association between the implementation of an antimicrobial stewardship program at a local PICU and to determine the association between the presence of an antimicrobial stewardship programs and antimicrobial use across three Canadian PICUs, among critically ill children with bronchiolitis. DESIGN: A multicenter retrospective cohort study. SETTING: Three Canadian PICUs over two winter seasons. INTERVENTIONS: An antimicrobial stewardship program was implemented at PICU 1 at the end of season 1. PATIENTS: Patients less than or equal to 2 years old admitted with bronchiolitis. MEASUREMENTS AND MAIN RESULTS: We used regression models with an interaction term between site (PICU 1 and PICU 2) and season (1 and 2) as the primary analysis to determine the association between implementation of an antimicrobial stewardship program at PICU 1 and 1) the proportion of antimicrobials discontinued 72 hours after hospital admission (logistic regression), 2) antimicrobial treatment duration (negative binomial regression), and 3) antimicrobial prescriptions within 48 hours of hospital admission (logistic regression). As a secondary analysis, we determined the association between having an antimicrobial stewardship program present and the aforementioned outcomes across the three PICUs. A total of 372 patients were included. During seasons 1 and 2, median age was 2.2 months (interquartile range, 1.2-6.2 mo) and 2.1 months (interquartile range, 1.3-6.8 mo), respectively. Among patients with viral bronchiolitis, implementation of an antimicrobial stewardship program at PICU 1 was associated with increased odds of discontinuing antimicrobials (odds ratio, 25.63; 95% CI, 2.86-326.29), but not with antimicrobial duration (odds ratio, 0.56; 95% CI, 0.31-1.02) or antimicrobial prescriptions (odds ratio, 0.33; 95% CI, 0.10-1.04). The presence of an antimicrobial stewardship program was similarly associated with antimicrobial discontinuation among patients with viral bronchiolitis (odds ratio, 20.79; 95% CI, 2.46-244.92), but not with antimicrobial duration (odds ratio, 0.57; 95% CI, 0.32-1.03) or antimicrobial prescriptions (odds ratio, 0.37; 95% CI, 0.12-1.11). CONCLUSIONS: Antimicrobial stewardship programs were associated with increased likelihood of discontinuing antimicrobial treatments in the PICU patients with viral bronchiolitis. However, larger studies are needed to further determine the role of an antimicrobial stewardship programs in reducing unnecessary antimicrobial use in this patient population.

TOwards enhancing Paediatric Intensive Care for Children with Medical Complexity (ToPIC CMC): a mixed-methods study protocol using Experience-based Co-design.

INTRODUCTION: Advances in medical technology and postoperative care have led to increased survival of children with medical complexity (CMC). Parents of CMC develop substantial caregiver expertise and familiarity with paediatric intensive care unit (PICU) staff and treatment procedures which may give rise to tensions regarding respective roles, caretaking preferences, treatment goals and expected outcomes. A therapeutic alliance built through strong partnerships constitutes the foundation of patient and family-centred care (PFCC), contributing to improvements in experiences and outcomes. Yet acute care settings continue to struggle with integrating PFCC into practice. This study aims to enhance PFCC for CMC in the PICU using an innovative approach to integrated knowledge translation. METHODS: A mixed-method concurrent triangulation design will be used to develop, implement and evaluate PFCC practice changes for CMC in the PICU. Qualitative data will be collected using an Experience-based Co-design (EBCD) approach. Parents, CMC and staff will reflect on their PICU care experiences (stages 1 and 2), identify priorities for improvement (stage 3), devise strategies to implement changes (stage 4), evaluate practice changes and study process, and disseminate findings (stage 5). The quantitative arm will consist of a prepractice and postpractice change evaluation, compared with a control site. Analysis of qualitative and quantitative data will provide insights regarding the impact of PICU practice changes on PFCC. ETHICS AND DISSEMINATION: The McGill University Health Centre Research Ethics Board (Ref. #2019-5021) and the Hospital for Sick Children Research Ethics Board (Ref. #1000063801) approved the study. Knowledge users and researchers will be engaged as partners throughout the study as per our participatory approach. Knowledge products will include a short film featuring themes and video/audio clips from the interviews, recommendations for improvements in care, and presentations for healthcare leaders and clinical teams, in addition to traditional academic outputs such as conference presentations and publications.

Association between the length of storage of transfused leukoreduced red blood cell units and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

OBJECTIVE: Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital-acquired infection (HAI) incidence rate in critically ill children. BACKGROUND: RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion-related immunomodulation due to bioactive substances' release as transfused blood ages. METHODS: In this secondary analysis of the 'Transfusion Requirement in Paediatric Intensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre-storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21-34 days), and 3) transfusion of 'long-stored' RBCs (≥35 days). All were compared to a 'golden' period (11-20 days), representing the time between 'fresh' and 'stored'. We used quasi-Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI). RESULTS: We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'long-stored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). CONCLUSION: Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children.