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.

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.

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.

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.

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.

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.

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.

Evaluation of antibiotic treatment decisions in pediatric intensive care units in Saudi Arabia: A national survey.

OBJECTIVE: To describe variables used by Saudi pediatric intensivists to make antibiotic-related decisions for children with suspected severe bacterial infections. METHODS: We conducted a cross-sectional survey, which was developed using a multi-step methodological approach. The survey included 4 clinical scenarios of the most relevant bacterial infections in pediatric critical care (pneumonia, sepsis, meningitis and intra-abdominal infection). The potential determinants of antibiotic treatment duration addressed in all scenarios included clinical variables (patient characteristics, disease severity), laboratory infection markers, radiologic findings, and pathogens. RESULTS: The response rate was 65% (55/85). Eight variables (immunodeficiency, 3 months of age, 2 or more organ dysfunctions, Pediatric Risk of Mortality III score >10, leukocytosis, elevated C-reactive protein [CRP], elevated erythrocyte sedimentation rate [ESR], and elevated procalcitonin [PCT]) were associated with prolonging antibiotic treatment duration for all 4 clinical scenarios, with a median increase ranging from 3.0 days (95% confidence interval [CI] 0.5, 3.5, leukocytosis) to 8.8 days (95% CI 5.5, 10.5, immunodeficiency). There were no variables that were consistently associated with shortening antibiotic duration across all scenarios. Lastly, the proportion of physicians who would continue antibiotics for ≥5 days despite a positive viral polymerase chain reaction test result was 67% for pneumonia, 85% for sepsis, 63% for meningitis, and 95% for intra-abdominal infections. CONCLUSION: Antibiotic-related decisions for critically ill patients are complex and depend on several factors. Saudi pediatric intensivists will use prolonged courses of antibiotics for younger patients, patients with severe clinical picture, and patients with persistently elevated laboratory markers and hospital acquired infections, even when current literature and guidelines do not suggest such practices. Antimicrobial stewardship programs should include interventions to address these misconceptions to ensure the rational use of antibiotics in pediatric intensive care units.

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.

Prevalence of Acute Rehabilitation for Kids in the PICU: A Canadian Multicenter Point Prevalence Study.

OBJECTIVES: To evaluate mobilization practices, barriers, and mobility-related adverse events in Canadian PICUs. DESIGN: National 2-day point prevalence study. SETTING: Thirteen PICUs across Canada. PATIENTS: Children with a minimum 72-hour PICU length of stay on the allocated study day. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes of interest were the prevalence and nature of mobilization activities, rehabilitation resources, adverse events, and factors associated with out-of-bed mobility and therapist-provided mobility. Two PICUs (15%) had early mobilization practice guidelines, and one PICU (8%) reported a formal process for engaging families in the mobilization of patients. The prevalence of mobilization was 110 of 137 patient-days (80%). The commonest activity was out-of-bed mobility (87/137; 64% patient-days); there was no active mobilization on 46 patient-days (34%). Therapists provided mobility on 33% of patient-days. Mobility was most commonly facilitated by nurses (74% events) and family (49% events). Family participation was strongly associated with out-of-bed mobility (odds ratio 6.4; p = 0.001). Intubated, mechanically ventilated patients were mobilized out-of-bed on 18 of 50 patient-days (36%). However, the presence of an endotracheal tube, vasoactive infusions, and age greater than or equal to 3 years were independently associated with not being mobilized out-of-bed. Barriers were reported on 58 of 137 patient-days (42%), and adverse events occurred in 22 of 387 mobility events (6%). CONCLUSIONS: Mobilization is common and safe, and the majority of children in Canadian PICUs are being mobilized out-of-bed, even when mechanically ventilated. Family engagement in PICU-based rehabilitation is increasing. This study provides encouraging evidence that common barriers can be overcome in order to safely mobilize children in PICUs.

International Survey on Determinants of Antibiotic Duration and Discontinuation in Pediatric Critically Ill Patients.

OBJECTIVES: We hypothesized that antibiotic use in PICUs is based on criteria not always supported by evidence. We aimed to describe determinants of empiric antibiotic use in PICUs in eight different countries. DESIGN: Cross-sectional survey. SETTING: PICUs in Canada, the United States, France, Italy, Saudi Arabia, Japan, Thailand, and Brazil. SUBJECTS: Pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used literature review and focus groups to develop the survey and its clinical scenarios (pneumonia, septic shock, meningitis, and intra-abdominal infections) in which cultures were unreliable due to antibiotic pretreatment. Data analyses included descriptive statistics and linear regression with bootstrapped SEs. Overall response rate was 39% (482/1,251), with individual country response rates ranging from 25% to 76%. Respondents in all countries prolonged antibiotic duration based on patient characteristics, disease severity, pathogens, and radiologic findings (from a median increase of 1.8 d [95% CI, 0.5-4.0 d] to 9.5 d [95% CI, 8.5-10.5 d]). Younger age, severe disease, and ventilator-associated pneumonia prolonged antibiotic treatment duration despite a lack of evidence for such practices. No variables were reported to shorten treatment duration for all countries. Importantly, more than 39% of respondents would use greater than or equal to 7 days of antibiotics for patients with a positive viral polymerase chain reaction test in all scenarios, except in France for pneumonia (29%), septic shock (13%), and meningitis (6%). The use of elevated levels of inflammatory markers to prolong antibiotic treatment duration varied among different countries. CONCLUSIONS: Antibiotic-related decisions are complex and may be influenced by cultural and contextual factors. Evidence-based criteria are necessary to guide antibiotic duration and ensure the rational use of antibiotics in PICUs.

Pressure versus Sudden Wean from Nasal Continuous Positive Airway Pressure in Preterm Infants: A Systematic Review and Meta-Analysis.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is a well-studied treatment for respiratory problems in preterm infants. However, the best strategy for NCPAP weaning is unknown. OBJECTIVE: We aimed to compare the success of progressive pressure wean versus sudden wean for discontinuation of NCPAP in preterm infants. METHODS: We conducted a systematic review and meta-analysis of publications identified by searching MEDLINE, Embase, -CINAHL, and CENTRAL. Randomized controlled trials comparing pressure wean to sudden wean for NCPAP in preterm infants were included. Primary outcomes were postmenstrual age (PMA) at successful weaning and weight gain. Secondary outcomes were total duration of ventilation, success of weaning strategy on first attempt, length of stay (LOS), and bronchopulmonary dysplasia (BPD). RESULTS: Two trials (422 infants) were eligible for inclusion. Pressure wean was associated with a higher PMA at weaning (33.9 ± 2.1 vs. 32.1 ± 2.0 weeks, mean difference [MD] 0.88, 95% CI 0.40 to 1.35, low quality evidence). Daily weight gain was only reported in 1 trial. Total duration of ventilation was not reported. Pressure wean was associated with higher probability of successful weaning at first attempt (risk ratio [RR] 1.25, 95% CI 1.03-1.53). However, it was not associated with LOS (MD -2.5 days, 95% CI -7.3 to 2.4) or BPD (RR 0.92, 95% CI 0.52-1.63). CONCLUSION: Sudden wean of NCPAP was associated with a lower PMA at successful wean compared to pressure wean but also with a lower rate of successful wean at first attempt, most likely because of the developmental stage at which weaning is possible.

Early fluid overload was associated with prolonged mechanical ventilation and more aggressive parameters in critically ill paediatric patients.

AIM: We evaluated the influence of early fluid overload on critically ill children admitted to a paediatric intensive care unit by examining mechanical ventilation (MV), mortality, length of stay and renal replacement therapy. METHODS: This retrospective cohort study covered January 2015 to December 2016 and focused on all episodes of MV support that exceeded 24 hours. The fluid overload percentage (FO%) was calculated daily for the first 72 hours and we estimated its effect on outcomes. RESULTS: We included 186 MV episodes in 154 patients. The median age was 13.8 months, with an interquartile range (IQR) of 3.8-34.0 months, and the mortality rate was 12.4%. The median FO% in the first 72 hours was 8.0% (IQR 3.6%-11.2%). An FO% of ≥10% was associated with higher ventilatory parameters, namely peak inspiratory pressure (P = .023) and positive end expiratory pressure (P = .003), and renal replacement therapy (P = .02) and higher mortality (8.8% vs 19.7%). In a multivariate Cox regression model, FO ≥ 10% at 72 hours was independently associated with longer MV support, but not mortality (P = .001). CONCLUSION: In a heterogeneous paediatric population given MV, an early cumulative FO of ≥10% was associated with more aggressive ventilatory parameters and prolonged length of MV, but not mortality.

The Clinical Utility of Respiratory Viral Testing in Hospitalized Children: A Meta-analysis.

CONTEXT: Respiratory virus (RV) detection tests are commonly used in hospitalized children to diagnose viral acute respiratory infection (ARI), but their clinical utility is uncertain. OBJECTIVES: To systematically review and meta-analyze the impact of RV test results on antibiotic consumption, ancillary testing, hospital length of stay, and antiviral use in children hospitalized with severe ARI. DATA SOURCES: Seven medical literature databases from 1985 through January 2018 were analyzed. STUDY SELECTION: Studies in children <18 years old hospitalized for severe ARI in which the clinical impact of a positive versus negative RV test result or RV testing versus no testing are compared. DATA EXTRACTION: Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed study quality. RESULTS: We included 23 studies. High heterogeneity did not permit an overall meta-analysis. Subgroup analyses by age, RV test type, and viral target showed no difference in the proportion of patients receiving antibiotics between those with positive versus negative test results. Stratification by study design revealed that RV testing decreased antibiotic use in prospective cohort studies (odds ratio = 0.58; 95% confidence interval: 0.45-0.75). Pooled results revealed no conclusive impact on chest radiograph use (odds ratio = 0.71; 95% confidence interval: 0.48-1.04). Results of most studies found that positive RV test results did not impact median hospital length of stay, but they may decrease antibiotic duration. Nineteen (83%) studies were at serious risk of bias. LIMITATIONS: Low-quality studies and high clinical and statistical heterogeneity were among the limitations. CONCLUSIONS: Higher-quality prospective studies are needed to determine the impact of RV testing on antibiotic use in children hospitalized with severe ARI.

Inappropriate Antibiotic Prescribing for Acute Bronchiolitis in US Emergency Departments, 2007-2015.

One-fourth of patients with bronchiolitis seen in US emergency departments between 2007 and 2015 received antibiotics; 70% of them had no documented bacterial coinfection. Macrolides were prescribed in 38% of the cases. Antibiotic use did not decrease after national recommendations against routine prescribing. Efforts are needed to reduce unnecessary and inappropriate antibiotic use for bronchiolitis.

Molecular and epidemiologic investigation of a rhinovirus outbreak in a neonatal intensive care unit.

We performed a molecular and epidemiologic study of a healthcare-associated rhinovirus outbreak to better understand transmission in neonatal intensive care settings. Sequencing of the 7 outbreak strains revealed 4 distinct clades, indicating multiple sources. A single clade infected 3 patients in adjacent rooms, suggesting horizontal transmission. We observed 1 rhinovirus-associated death.

Use of C-reactive protein to tailor antibiotic use: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: C-reactive protein (CRP) has been proposed to guide the use of antibiotics. However, study results are controversial regarding the benefits of such a strategy. We synthesised the evidence of CRP-based algorithms on antibiotic treatment initiation and on antibiotic treatment duration in adults, children and neonates, as well as their safety profile. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, CENTRAL and CINAHL from inception to 20 July 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised controlled trials (RCTs), non-RCTs and cohort studies (prospective or retrospective) investigating CRP-guided antibiotic use in adults, children and neonates with bacterial infection. DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened all identified studies and retrieved the data. Outcomes were duration of antibiotic use, antibiotic initiation, mortality, infection relapse and hospitalisation. We assessed the quality of the included studies using the Cochrane Collaboration's tool (RCTs), and A Cochrane Risk Of Bias Assessment Tool: for Non-Randomized Studies of Interventions and the Newcastle-Ottawa scale (non-RCTs). We analysed our results using descriptive statistics and random effects models. RESULTS: Of 11 165 studies screened, 15 were included. In five RCTs in adult outpatients, the risk difference for antibiotic treatment initiation in the CRP group was -7% (95% CI: -10% to -4%), with no difference in hospitalisation rate. In neonates, CRP-based algorithms shortened antibiotic treatment duration by -1.45 days (95% CI -2.61 to -0.28) in two RCTs, and by -1.15 days (95% CI -2.06 to -0.24) in two cohort studies, with no differences in mortality or infection relapse. CONCLUSION: The use of CRP-based algorithms seems to reduce antibiotic treatment duration in neonates, as well as to decrease antibiotic treatment initiation in adult outpatients. However, further high-quality studies are still needed to assess safety, particularly in children outside the neonatal period. PROSPERO REGISTRATION NUMBER: CRD42016038622.

Can biomarkers improve the rational use of antibiotics?

PURPOSE OF REVIEW: We aim to review recent literature about the use of biomarkers to guide the initiation and duration of antibiotic treatments for suspected bacterial infections. RECENT FINDINGS: Several good quality meta-analyses show that procalcitonin can be safely used to guide antibiotic-related decisions, especially for respiratory infections, thereby decreasing unnecessary antibiotic exposure. Furthermore, the use of CRP-based algorithms to guide antibiotic initiation in primary care patients with acute respiratory infections is associated with a reduction in antibiotic use without an increase in adverse events. Regarding neutrophil CD64 and serum amyloid A, more good-quality evidence is needed to assess their utility as biomarkers to tailor antibiotic use. Finally, transcriptomics, metabolomics and proteomics are promising tools for the development of tests to differentiate specific host responses to viral, bacterial and noninfectious stimuli, but such tests still need further validation. SUMMARY: Evidence shows that the use of biomarkers, procalcitonin and CRP, can safely reduce unnecessary antibiotic prescriptions in certain infectious syndromes. The clinical utility of host-based strategies such as transcriptomics, metabolomics and proteomics for the diagnosis of infectious diseases has yet to be evaluated, as well as considerations such as costs, technical complexity and result turnaround time.