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Purpose of Review: This review aims to summarize the latest publications on vitamin D focused on critically ill patients., Recent Findings: Vitamin D deficiency is common in critically ill patients (children and adults) and associated with a higher risk for mortality and morbidity as well as sepsis, acute respiratory failure, acute renal failure and prolonged ICU stay. As it is an inexpensive substance with a wide safety margin, acute treatment in form of a loading dose in addition to ongoing maintenance therapy is an interesting option in the ICU. The potential benefit of acute native (biologically inactive) vitamin D treatment has not fully been answered but even a small survival benefit demonstrable in very large analyses could be relevant to critical care. To date, less than 5000 patients cumulative have been enrolled in randomized controlled trials concerning vitamin D, with substantial heterogeneity in trial design regarding population (with or without deficiency, coronavirus disease 2019, different age groups, underlying illnesses), metabolite, dosing, outcome, and more., Summary: More research is needed, but vitamin D supplementation represents a simple intervention with an excellent safety profile. As adequate vitamin D is essential to the health of multiple organ systems, rapid normalization of deficiency states could translate to benefits across the wide range of diagnoses and organ dysfunctions experienced in the ICU setting. As a minimum, we recommend administering the standard daily dose of vitamin D3 in the critically ill patient., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited., Methods: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders., Results: Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%-74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%-80%]; third, 63% [95% CI, 46%-74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%-75%]; 2 to <6 months, 64% [95% CI, 36%-79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%-75%]; < 37 weeks, 61% [95% CI, 4%-86%]). VE against influenza hospitalization was 67% (95% CI, 50%-78%)., Conclusions: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available., Competing Interests: Potential conflicts of interest . During the conduct of this work, D. B. F. worked for the University of Ottawa and had academic appointments at the Children's Hospital of Eastern Ontario Research Institute and ICES; she is currently employed by Pfizer. K. W. is a cofounder and Chief Scientific Officer of CANImmunize, Inc; he served on the Independent Data Monitoring Committee for Medicago; and is a member of the Moderna Global Advisory Core Consultancy Group. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aOR per 28 days  = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aOR per 28 days  = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Background: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk., Methods: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status., Results: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users., Conclusions: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding., Competing Interests: Potential conflicts of interest. H. C., M. A. C., S. A. B., T. K., K. L. S., and J. C. K. report support from the Canadian Institutes of Health Research (CIHR; grant PJT 159516, paid to the institution). J. B. G. has received research grants from GSK and Hoffmann-LaRoche for antiviral resistance studies and from Pfizer to conduct microbiological surveillance of Streptococcus pneumoniae. J. B. G. also reports consulting fees from GIDEON Informatics, as a scientific editor, unrelated to the current work. A. J. M. reports research funds from GSK; grants or contracts from Sanofi, Merck, and Pfizer (paid to the institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Merck, Biogen, and Moderna; and participation on a data safety monitoring board or advisory board for Pfizer, GlaxoSmithKline, Moderna, Medicago, Janssen, AstraZeneca, Novavax, and Sanofi. D. C. R. reports participation on a data safety monitoring board or advisory board for GlaxoSmithKline (advisory board meeting on monoclonal antibodies for coronavirus disease 2019 [COVID-19]). M. S. reports grants or contracts from CIHR, Air Canada (staff and reagent costs for the COVID in International Travelers Study), the Ontario Research Fund (equipment costs for COVID-19 automation), and the Juravinski Research Fund (staff and equipment for COVID-19 diagnostic testing). G. Z. reports support from CIHR (paid to grant administered by J. C. K.) and grants from Genome Atlantic and PHAC. Roche and Abbott contribute unrestricted educational funding to the Eastern Health Regional Health Authority for employees, which include G. Z., to attend virtual meetings and, in specific restricted circumstances, travel to educational, technical, and research meetings. G. Z. is also the previous president of the National Molecular Users Group. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Children with chronic critical illness (CCI) are hypothesized to be a high-risk patient population with persistent multiple organ dysfunction and functional morbidities resulting in recurrent or prolonged critical care; however, it is unclear how CCI should be defined. The aim of this scoping review was to evaluate the existing literature for case definitions of pediatric CCI and case definitions of prolonged PICU admission and to explore the methodologies used to derive these definitions., Data Sources: Four electronic databases (Ovid Medline, Embase, CINAHL, and Web of Science) from inception to March 3, 2021., Study Selection: We included studies that provided a specific case definition for CCI or prolonged PICU admission. Crowdsourcing was used to screen citations independently and in duplicate. A machine-learning algorithm was developed and validated using 6,284 citations assessed in duplicate by trained crowd reviewers. A hybrid of crowdsourcing and machine-learning methods was used to complete the remaining citation screening., Data Extraction: We extracted details of case definitions, study demographics, participant characteristics, and outcomes assessed., Data Synthesis: Sixty-seven studies were included. Twelve studies (18%) provided a definition for CCI that included concepts of PICU length of stay (n = 12), medical complexity or chronic conditions (n = 9), recurrent admissions (n = 9), technology dependence (n = 5), and uncertain prognosis (n = 1). Definitions were commonly referenced from another source (n = 6) or opinion-based (n = 5). The remaining 55 studies (82%) provided a definition for prolonged PICU admission, most frequently greater than or equal to 14 (n = 11) or greater than or equal to 28 days (n = 10). Most of these definitions were derived by investigator opinion (n = 24) or statistical method (n = 18)., Conclusions: Pediatric CCI has been variably defined with regard to the concepts of patient complexity and chronicity of critical illness. A consensus definition is needed to advance this emerging and important area of pediatric critical care research., Competing Interests: Dr. Zorko was supported by a Canadian Institutes of Health Research Canada Graduate Scholarship—Master’s Award. Dr. McNally disclosed that the code for the website used to crowdsource the systematic review is owned by a company called insightscope and that he worked with Algonquin College to develop the code and is the president of insightscope. Dr. Perry’s institution received funding from the National Institutes of Health and the American Association of Critical Care Nurses. Dr. Choong’s institution received funding from Alternative Funding Plan Innovation Fund Research Grant; she received funding from McMaster University. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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., (Copyright © 2022 by the American Academy of Pediatrics.)

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., Competing Interests: Dr. Lacroix’s institution received funding as a principal applicant for a Canadian Institutes of Health Research grant. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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., Competing Interests: Dr. Papenburg’s institution received funding from MedImmune; he received funding from AbbVie, Cepheid, BD Diagnostics, MedImmune, Sanofi Pasteur, Seegene, and Janssen Pharmaceutical. Dr. Quach’s institution received funding from the McGill University Health Centre, Research Institute. Dr. Jouvet received funding from the Mallinckrodt. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Respiratory syncytial virus (RSV) infection poses a substantial clinical burden among infants and young children. We sought to determine the health care costs of hospitalizations attributable to RSV in Ontario, Canada, from the health care payer perspective., Methods: For this population-based matched cohort study, we identified children younger than 24 months who were or were not hospitalized with RSV infections in 2006-2016. We performed a cost-of-illness analysis using linked administrative health data, with subjects stratified by gestational age and congenital heart disease, and propensity score-matched on established risk factors. The primary outcome was attributable health care costs per patient, reflecting the difference in direct medical costs between the groups, calculated to 12 months postdischarge in 2020 Canadian dollars., Results: We identified 14 608 RSV-infected children, matched to 72 040 controls. The adjusted attributable cost of hospitalized RSV was $134 931 900 over 10 years, or $9240 per patient (95% confidence interval [CI] $8790-$9690). Health care costs escalated 3 days before hospitalization, and persisted up to 12 months after discharge. Increased costs were associated with major comorbidities, but not extreme premature birth. The highest mean attributable cost per patient was in the presence of hemodynamically significant heart disease ($60 110, 95% CI $26 700-$93 060). Infants born at 36-43 weeks' gestation constituted the greatest overall cost burden at $117 886 720., Interpretation: Although the greatest direct medical costs per patient hospitalized with RSV infection are among children with cardiac disease, the greatest overall cost burden is from children born at or near term, who are not targeted by current prophylaxis strategies. The substantial attributable health care costs of RSV can inform cost-effectiveness analyses of novel RSV vaccines and prioritization of health care resources., Competing Interests: Competing interests: Krista Lanctot reports grants from AbbVie Canada and stock from Highmark Interactive, outside the submitted work. J. Dayre McNally reports funding from the Canadian Institutes of Health Research, outside the submitted work. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Improvements in the delivery of intensive care have increased survival among even the most critically ill children, thereby leading to a growing number of children with chronic complex medical conditions in the pediatric intensive care unit (PICU). Some of these children are at a significant risk of recurrent and prolonged critical illness, with higher morbidity and mortality, making them a unique population described as having chronic critical illness (CCI). To date, pediatric CCI has been understudied and lacks an accepted consensus case definition., Objective: This study aims to describe the protocol and methodology used to perform a scoping review that will describe how pediatric CCI has been defined in the literature, including the concept of prolonged PICU admission and the methodologies used to develop any existing definitions. It also aims to describe patient characteristics and outcomes evaluated in the included studies., Methods: We will search four electronic databases for studies that evaluated children admitted to any PICU identified with CCI. We will also search for studies describing prolonged PICU admission, as this concept is related to pediatric CCI. Furthermore, we will develop a hybrid crowdsourcing and machine learning (ML) methodology to complete citation screening. Screening and data abstraction will be performed by 2 reviewers independently and in duplicate. Data abstraction will include the details of population definitions, demographic and clinical characteristics of children with CCI, and evaluated outcomes., Results: The database search, crowd reviewer recruitment, and ML algorithm development began in March 2021. Citation screening and data abstraction were completed in April 2021. Final data verification is ongoing, with analysis and results anticipated to be completed by fall 2021., Conclusions: This scoping review will describe the existing or suggested definitions of pediatric CCI and important demographic and clinical characteristics of patients to whom these definitions have been applied. This review's results will help inform the development of a consensus case definition for pediatric CCI and set a priority agenda for future research. We will use and demonstrate the validity of crowdsourcing and ML methodologies for improving the efficiency of large scoping reviews., International Registered Report Identifier (irrid): DERR1-10.2196/30582., (©David Zorko, James Dayre McNally, Bram Rochwerg, Neethi Pinto, Rachel Couban, Katie O’Hearn, Karen Choong. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 01.10.2021.)

Background: Older adults are at increased risk of mortality from influenza infections. We estimated influenza vaccine effectiveness (VE) against mortality following laboratory-confirmed influenza., Methods: Using a test-negative design study and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against all-cause mortality following laboratory-confirmed influenza for community-dwelling adults aged >65 years during the 2010-2011 to 2015-2016 influenza seasons., Results: Among 54 116 older adults tested for influenza across the 6 seasons, 6837 died within 30 days of specimen collection. Thirteen percent (925 individuals) tested positive for influenza, and 50.6% were considered vaccinated for that season. Only 23.2% of influenza test-positive cases had influenza recorded as their underlying cause of death. Before and after multivariable adjustment, we estimated VE against all-cause mortality following laboratory-confirmed influenza to be 20% (95% confidence interval [CI], 8%-30%) and 20% (95% CI, 7%-30%), respectively. This estimate increased to 34% after correcting for influenza vaccination exposure misclassification. We observed significant VE against deaths following influenza confirmation during 2014-2015 (VE = 26% [95% CI, 5%-42%]). We also observed significant VE against deaths following confirmation of influenza A/H1N1 and A/H3N2, and against deaths with COPD as the underlying cause., Conclusions: These results support the importance of influenza vaccination in older adults, who account for most influenza-associated deaths annually., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Standard practice for conducting systematic reviews (SRs) is time consuming and involves the study team screening hundreds or thousands of citations. As the volume of medical literature grows, the citation set sizes and corresponding screening efforts increase. While larger team size and alternate screening methods have the potential to reduce workload and decrease SR completion times, it is unknown whether investigators adapt team size or methods in response to citation set sizes. Using a cross-sectional design, we sought to understand how citation set size impacts (1) the total number of authors or individuals contributing to screening and (2) screening methods., Methods: MEDLINE was searched in April 2019 for SRs on any health topic. A total of 1880 unique publications were identified and sorted into five citation set size categories (after deduplication): < 1,000, 1,001-2,500, 2,501-5,000, 5,001-10,000, and > 10,000. A random sample of 259 SRs were selected (~ 50 per category) for data extraction and analysis., Results: With the exception of the pairwise t test comparing the under 1000 and over 10,000 categories (median 5 vs. 6, p = 0.049) no statistically significant relationship was evident between author number and citation set size. While visual inspection was suggestive, statistical testing did not consistently identify a relationship between citation set size and number of screeners (title-abstract, full text) or data extractors. However, logistic regression identified investigators were significantly more likely to deviate from gold-standard screening methods (i.e. independent duplicate screening) with larger citation sets. For every doubling of citation size, the odds of using gold-standard screening decreased by 15 and 20% at title-abstract and full text review, respectively. Finally, few SRs reported using crowdsourcing (n = 2) or computer-assisted screening (n = 1)., Conclusions: Large citation set sizes present a challenge to SR teams, especially when faced with time-sensitive health policy questions. Our study suggests that with increasing citation set size, authors are less likely to adhere to gold-standard screening methods. It is possible that adjunct screening methods, such as crowdsourcing (large team) and computer-assisted technologies, may provide a viable solution for authors to complete their SRs in a timely manner.

Background: Accepted systematic review (SR) methodology requires citation screening by two reviewers to maximise retrieval of eligible studies. We hypothesized that records could be excluded by a single reviewer without loss of sensitivity in two conditions; the record was ineligible for multiple reasons, or the record was ineligible for one or more specific reasons that could be reliably assessed., Methods: Twenty-four SRs performed at CHEO, a pediatric health care and research centre in Ottawa, Canada, were divided into derivation and validation sets. Exclusion criteria during abstract screening were sorted into 11 specific categories, with loss in sensitivity determined by individual category and by number of exclusion criteria endorsed. Five single reviewer algorithms that combined individual categories and multiple exclusion criteria were then tested on the derivation and validation sets, with success defined a priori as less than 5% loss of sensitivity., Results: The 24 SRs included 930 eligible and 27390 ineligible citations. The reviews were mostly focused on pediatrics (70.8%, N=17/24), but covered various specialties. Using a single reviewer to exclude any citation led to an average loss of sensitivity of 8.6% (95%CI, 6.0-12.1%). Excluding citations with ≥2 exclusion criteria led to 1.2% average loss of sensitivity (95%CI, 0.5-3.1%). Five specific exclusion criteria performed with perfect sensitivity: conference abstract, ineligible age group, case report/series, not human research, and review article. In the derivation set, the five algorithms achieved a loss of sensitivity ranging from 0.0 to 1.9% and work-saved ranging from 14.8 to 39.1%. In the validation set, the loss of sensitivity for all 5 algorithms remained below 2.6%, with work-saved between 10.5% and 48.2%., Conclusions: Findings suggest that targeted application of single-reviewer screening, considering both type and number of exclusion criteria, could retain sensitivity and significantly decrease workload. Further research is required to investigate the potential for combining this approach with crowdsourcing or machine learning methodologies.

Background and Objectives: Most infants hospitalized with respiratory syncytial virus (RSV) do not meet common "high-risk" criteria and are otherwise healthy. The objective of this study was to quantify the risks and relative importance of socioeconomic factors for severe, early-life RSV-related illness. We hypothesized several of these factors, particularly those indicating severe social vulnerability, would have statistically significant associations with increased RSV hospitalization rates and may offer impactful targets for population-based RSV prevention strategies, such as prophylaxis programs., Methods: We used linked health, laboratory, and sociodemographic administrative data for all children born in Ontario (2012-2018) to identify all RSV-related hospitalizations occurring before the third birthday or end of follow-up (March 31, 2019). We estimated rate ratios and population attributable fractions using a fully adjusted model., Results: A total of 11 782 RSV-related hospitalizations were identified among 789 484 children. Multiple socioeconomic factors were independently associated with increased RSV-related admissions, including young maternal age, maternal criminal involvement, and maternal history of serious mental health and/or addiction concerns. For example, an estimated 4.1% (95% confidence interval: 2.2 to 5.9) of RSV-related admissions could be prevented by eliminating the increased admissions risks among children whose mothers used welfare-based drug insurance. Notably, 41.6% (95% confidence interval: 39.6 to 43.5) of admissions may be prevented by targeting older siblings (eg, through vaccination)., Conclusions: Many social factors were independently associated with early-life RSV-related hospitalization. Existing RSV prophylaxis and emerging vaccination programs should consider the importance of both clinical and social risk factors when determining eligibility and promoting compliance., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To evaluate the effectiveness of two palivizumab programmes targeting high-risk infants, defined by prematurity, diagnosis of comorbidities and geography, and assess potential disparities by neighbourhood income., Design: Controlled, interrupted time series., Setting: Ontario, Canada., Patients: We used linked health and demographic administrative databases to identify all children born in hospitals 1 January 1993 through 31 December 2016. Follow-up ended at the earliest of second birthday or 30 June 2017., Intervention: Palivizumab-eligibility: child was born very preterm and ≤6 months old during respiratory syncytial virus (RSV) season; <24 months old with significant chronic lung or congenital heart disease; or ≤6 months, born preterm or residents of remote regions., Main Outcome: Severe RSV-related illness, defined as hospitalisation or death with a diagnosis of bronchiolitis, RSV pneumonia or RSV., Results: 3 million births and 87 000 RSV-related events were identified. Over the study period, rates of severe RSV-related illness declined 65.4% among the highest risk group, eligible infants <6 months (230.6 to 79.8 admissions per 1000 child-years). Relative to changes among ineligible infants <6 months, rates dropped 10.4% (95% CI -18.6% to 39.4%) among eligible infants immediately following introduction of a national palivizumab programme in 1998. Initially, rates were considerably higher among infants from low-income neighbourhoods, but income-specific rates converged over time among eligible infants <6 months; such convergence was not seen among other children., Conclusions: Incidence of severe RSV-related illness declined over the study period. While we cannot attribute causality, the timing and magnitude of these declines suggest impact of palivizumab in reducing RSV burden and diminishing social inequities among palivizumab-eligible infants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Solutions like crowd screening and machine learning can assist systematic reviewers with heavy screening burdens but require training sets containing a mix of eligible and ineligible studies. This study explores using PubMed's Best Match algorithm to create small training sets containing at least five relevant studies., Methods: Six systematic reviews were examined retrospectively. MEDLINE searches were converted and run in PubMed. The ranking of included studies was studied under both Best Match and Most Recent sort conditions., Results: Retrieval sizes for the systematic reviews ranged from 151 to 5,406 records and the numbers of relevant records ranged from 8 to 763. The median ranking of relevant records was higher in Best Match for all six reviews, when compared with Most Recent sort. Best Match placed a total of thirty relevant records in the first fifty, at least one for each systematic review. Most Recent sorting placed only ten relevant records in the first fifty. Best Match sorting outperformed Most Recent in all cases and placed five or more relevant records in the first fifty in three of six cases., Discussion: Using a predetermined set size such as fifty may not provide enough true positives for an effective systematic review training set. However, screening PubMed records ranked by Best Match and continuing until the desired number of true positives are identified is efficient and effective., Conclusions: The Best Match sort in PubMed improves the ranking and increases the proportion of relevant records in the first fifty records relative to sorting by recency.

Cardiac disease in children is associated with significant morbidity and mortality as well as increased health resource utilisation. There is a perception that there is a paucity of high-quality studies, particularly randomized controlled trials (RCTs), in the field of pediatric cardiology. We sought to identify, examine, and map the range of RCTs conducted in children with cardiac conditions, including the development of a searchable open-access database. A literature search was conducted encompassing MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to 2018. All English-language RCTs enrolling children (age 0-21 years) with cardiac conditions were included. Data extraction and risk of bias assessments were performed in duplicate via crowdsourcing for each eligible study and entered into an online database. A total of 933 RCTs met eligibility criteria. Median trial recruitment was 49 patients (interquartile range 30-86) with 18.9% of studies (n = 176) including > 100 patients. A wide variety of populations and interventions were encompassed with congenital heart disease (79.8% of RCTs) and medications (63.3% of RCTs) often studied. Just over one-half of the trials (53.4%) clearly identified a primary outcome, and fewer than half (46.6%) fully documented a robust randomization process. Trials were summarised in a searchable online database (https://pediatrics.knack.com/cardiology-rct-database#cardiology-rcts/). Contrary to a commonly held perception, there are nearly 1,000 published RCTs in pediatric cardiology. The open-access database created as part of this project provides a resource that facilitates an efficient comprehensive review of the literature for clinicians and researchers caring for children with cardiac issues., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: In pandemics such as COVID-19, shortages of personal protective equipment are common. One solution may be to decontaminate equipment such as facemasks for reuse., Aim: To collect and synthesize existing information on decontamination of N95 filtering facepiece respirators (FFRs) using microwave and heat-based treatments, with special attention to impacts on mask function (aerosol penetration, airflow resistance), fit, and physical traits., Methods: A systematic review (PROSPERO CRD42020177036) of literature available from Medline, Embase, Global Health, and other sources was conducted. Records were screened independently by two reviewers, and data was extracted from studies that reported on effects of microwave- or heat-based decontamination on N95 FFR performance, fit, physical traits, and/or reductions in microbial load., Findings: Thirteen studies were included that used dry/moist microwave irradiation, heat, or autoclaving. All treatment types reduced pathogen load by a log 10 reduction factor of at least three when applied for sufficient duration (>30 s microwave, >60 min dry heat), with most studies assessing viral pathogens. Mask function (aerosol penetration <5% and airflow resistance <25 mmH 2 O) was preserved after all treatments except autoclaving. Fit was maintained for most N95 models, though all treatment types caused observable physical damage to at least one model., Conclusions: Microwave irradiation and heat may be safe and effective viral decontamination options for N95 FFR reuse during critical shortages. The evidence does not support autoclaving or high-heat (>90°C) approaches. Physical degradation may be an issue for certain mask models, and more real-world evidence on fit is needed., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Decontaminating and reusing filtering facepiece respirators (FFRs) for healthcare workers is a potential solution to address inadequate FFR supply during a global pandemic., Aim: The objective of this review was to synthesize existing data on the effectiveness and safety of using chemical disinfectants to decontaminate N95 FFRs., Methods: A systematic review was conducted on disinfectants to decontaminate N95 FFRs using Embase, Medline, Global Health, Google Scholar, WHO feed, and MedRxiv. Two reviewers independently determined study eligibility and extracted predefined data fields. Original research reporting on N95 FFR function, decontamination, safety, or FFR fit following decontamination with a disinfectant was included., Findings and Conclusion: A single cycle of vaporized hydrogen peroxide (H 2 O 2 ) successfully removes viral pathogens without affecting airflow resistance or fit, and maintains an initial filter penetration of <5%, with little change in FFR appearance. Residual hydrogen peroxide levels following decontamination were within safe limits. More than one decontamination cycle of vaporized H 2 O 2 may be possible but further information is required on how multiple cycles would affect FFR fit in a real-world setting before the upper limit can be established. Although immersion in liquid H 2 O 2 does not appear to adversely affect FFR function, there is no available data on its ability to remove infectious pathogens from FFRs or its impact on FFR fit. Sodium hypochlorite, ethanol, isopropyl alcohol, and ethylene oxide are not recommended due to safety concerns or negative effects on FFR function., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: The vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population., Methods: We conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence., Results: Forty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3-43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5-29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11-0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial., Conclusions: Pre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose., Trial Registration: ClinicalTrials.gov, NCT01838447. Registered on April 24, 2013., Competing Interests: Competing interestsDr. Khamessan is employed by Euro-Pharm International Canada Inc. Dr. Khamessan and Euro-Pharm International Canada Inc., at the request of the investigative team, developed and prepared the concentrated vitamin D solution used in the study., (© The Author(s) 2020.)

Background: The high demand for personal protective equipment during the novel coronavirus outbreak has prompted the need to develop strategies to conserve supply. Little is known regarding decontamination interventions to allow for surgical mask reuse., Aim: To identify and synthesize data from original research evaluating interventions to decontaminate surgical masks for the purpose of reuse., Methods: MEDLINE, Embase, CENTRAL, Global Health, the WHO COVID-19 database, Google Scholar, DisasterLit, preprint servers, and prominent journals from inception to April 8 th , 2020, were searched for prospective original research on decontamination interventions for surgical masks. Citation screening was conducted independently in duplicate. Study characteristics, interventions, and outcomes were extracted from included studies by two independent reviewers. Outcomes of interest included impact of decontamination interventions on surgical mask performance and germicidal effects., Findings: Seven studies met eligibility criteria: one evaluated the effects of heat and chemical interventions applied after mask use on mask performance, and six evaluated interventions applied prior to mask use to enhance antimicrobial properties and/or mask performance. Mask performance and germicidal effects were evaluated with heterogeneous test conditions. Safety outcomes were infrequently evaluated. Mask performance was best preserved with dry heat decontamination. Good germicidal effects were observed in salt-, N-halamine-, and nanoparticle-coated masks., Conclusion: There is limited evidence on the safety or efficacy of surgical mask decontamination. Given the heterogeneous methods used in studies to date, we are unable to draw conclusions on the most efficacious and safe intervention for decontaminating surgical masks., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

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.

Inadequate supply of filtering facepiece respirators (FFRs) for healthcare workers during a pandemic such as the novel coronavirus outbreak (SARS-CoV-2) is a serious public health issue. The aim of this study was to synthesize existing data on the effectiveness of ultraviolet germicidal irradiation (UVGI) for N95 FFR decontamination. A systematic review (PROSPERO CRD42020176156) was conducted on UVGI in N95 FFRs using Embase, Medline, Global Health, Google Scholar, WHO feed, and MedRxiv. Two reviewers independently determined eligibility and extracted predefined variables. Original research reporting on function, decontamination, or mask fit following UVGI were included. Thirteen studies were identified, comprising 54 UVGI intervention arms and 58 N95 models. FFRs consistently maintained certification standards following UVGI. Aerosol penetration averaged 1.19% (0.70-2.48%) and 1.14% (0.57-2.63%) for control and UVGI arms, respectively. Airflow resistance for the control arms averaged 9.79 mm H 2 O (7.97-11.70 mm H 2 O) vs 9.85 mm H 2 O (8.33-11.44 mm H 2 O) for UVGI arms. UVGI protocols employing a cumulative dose >20,000 J/m 2 resulted in a 2-log reduction in viral load. A >3-log reduction was observed in seven UVGI arms using >40,000 J/m 2 . Impact of UVGI on fit was evaluated in two studies (16,200; 32,400 J/m 2 ) and no evidence of compromise was found. Our findings suggest that further work in this area (or translation to a clinical setting) should use a cumulative UV-C dose of 40,000 J/m 2 or greater, and confirm appropriate mask fit following decontamination., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: The requirement for a tracheostomy in children is associated with significant morbidity, mortality, and healthcare utilization. Easy identification of children with tracheostomies would facilitate important research on this population and provide quality improvement initiatives., Aim: The purpose of this study is to determine whether an algorithm of diagnostic and procedural codes can accurately identify children hospitalized with a tracheostomy using routinely collected health data., Methods: Chart reviews were performed at the Children's Hospital of Eastern Ontario (CHEO) and the London Health Sciences Center (LHSC) to establish a true positive cohort of pediatric patients with tracheostomies admitted between 2008 and 2016. A multidisciplinary team developed algorithms of diagnostic and procedural codes contained within the Canadian Institute for Health Information Discharge Abstract Database. Algorithms were tested and refined against the true-positive and true-negative cohort. The accuracy of the diagnostic codes related to tracheostomy complications was also evaluated., Results: A chart review identified 158 unique children with tracheostomies (77 at CHEO, 81 at LHSC) with 901 individual admissions (401 at CHEO, 507 at LHSC). The best algorithms for identifying children with a tracheostomy had a sensitivity and specificity of more than 99%, a positive predictive value (PPV) of 94.0% and negative predictive value (NPV) of 100%. The algorithm for the identification of tracheostomy-related complications had a sensitivity of 76.7%, a specificity of 65%, PPV of 52.3%, and an NPV of 84.7%., Conclusions: This study provides an algorithm for the accurate identification of children hospitalized in Canada with a tracheostomy, facilitating population-level epidemiological research and quality improvement initiatives., (© 2020 Wiley Periodicals, Inc.)

Pediatric in-patients with tracheostomy (PIT) are at high risk for clinical deterioration. Medical emergency teams (MET) have been developed to identify high-risk patients. This study compared MET activation rates between PITs and the general ward population. This was a retrospective cohort study conducted at a tertiary pediatric hospital. The primary outcome (MET activation) was obtained from a database. Between 2008 and 2014, the MET activation rate was significantly higher in the PIT group than the general ward population (14 vs. 2.9 per 100 admissions, p  < 0.001). PITs are at significantly higher risk for MET activation. Strategies should be developed to reduce their risk on the wards., Competing Interests: Conflict of Interest None declared., (© Thieme Medical Publishers.)

Background: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in young children in Canada, despite routine immunoprophylaxis in those with medical risk factors. We aimed to determine if cold temperatures are associated with RSV hospitalization., Methods: We conducted a population-based nested case-control study of children in Ontario, Canada, using health administrative data. We compared children hospitalized for RSV between September 1, 2011 and August 31, 2012 to age and sex matched controls. We used multivariable logistic regression to identify associations between minimum daily temperature and RSV hospitalizations with adjustment for sociodemographic and environmental factors., Results: We identified 1670 children with RSV hospitalizations during the study period and 6680 matched controls. Warmer temperatures (OR = 0.94, 95%CI: 0.93, 0.95) were associated with lower odds of RSV hospitalization. Southern ecozone (OR = 1.6, 95%CI: 1.2, 2.1), increased ozone concentration (OR = 1.03, 95%CI: 1.01, 1.06) and living in a lower income neighbourhood (OR = 1.3, 95%CI: 1.1, 1.5) significantly increased the odds of RSV hospitalization, as did living in a household with a larger number of siblings in a sub-cohort of children (OR = 1.34, 95%CI: 1.26, 1.41)., Conclusions: In Ontario, the likelihood of having an RSV hospitalization is associated with colder temperature exposures and socioeconomic factors.

Background: Annual influenza immunization is recommended for people with chronic obstructive pulmonary disease (COPD) by all major COPD clinical practice guidelines. We sought to determine the seasonal influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations among older adults with COPD., Methods: We conducted a test-negative study of influenza VE in community-dwelling older adults with COPD in Ontario, Canada using health administrative data and respiratory specimens collected from patients tested for influenza during the 2010-11 to 2015-16 influenza seasons. Influenza vaccination was ascertained from physician and pharmacist billing claims. Multivariable logistic regression was used to estimate the adjusted odds ratio of influenza vaccination in people with, compared to those without, laboratory-confirmed influenza., Results: Receipt of seasonal influenza vaccine was associated with an adjusted 22% (95% confidence interval [CI], 15%-27%) reduction in laboratory-confirmed influenza-associated hospitalization. Adjustment for potential misclassification of vaccination status increased this to 43% (95% CI, 35%-52%). Vaccine effectiveness was not found to vary by patient- or influenza-related variables., Conclusions: During the studied influenza seasons, influenza vaccination was at least modestly effective in reducing laboratory-confirmed influenza-associated hospitalizations in people with COPD. The imperfect effectiveness emphasizes the need for better influenza vaccines and other preventive strategies., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

IntroductionAnnual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive.AimWe investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults.MethodsWe conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history.ResultsWe included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1-3 (26%; 95%CI: 13 to 37%), 4-6 (24%; 95%CI: 15 to 33%), 7-8 (13%; 95%CI: 2 to 22%), or 9-10 (7%; 95%CI: -4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously.ConclusionsAlthough VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.

Purpose: Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer., Patients and Methods: We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time., Results: We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, -5% to 19%) for patients with hematologic malignancies ( P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer., Conclusion: Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.

Background: Linking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE., Methods: We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies., Results: We included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010-11 to 2015-16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27-44%) in 2010-11 and 5% (95%CI, -2, 11%) in 2014-15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies., Conclusions: Routinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Systematic reviews (SRs) are often cited as the highest level of evidence available as they involve the identification and synthesis of published studies on a topic. Unfortunately, it is increasingly challenging for small teams to complete SR procedures in a reasonable time period, given the exponential rise in the volume of primary literature. Crowdsourcing has been postulated as a potential solution., Objective: The feasibility objective of this study was to determine whether a crowd would be willing to perform and complete abstract and full text screening. The validation objective was to assess the quality of the crowd's work, including retention of eligible citations (sensitivity) and work performed for the investigative team, defined as the percentage of citations excluded by the crowd., Methods: We performed a prospective study evaluating crowdsourcing essential components of an SR, including abstract screening, document retrieval, and full text assessment. Using CrowdScreenSR citation screening software, 2323 articles from 6 SRs were available to an online crowd. Citations excluded by less than or equal to 75% of the crowd were moved forward for full text assessment. For the validation component, performance of the crowd was compared with citation review through the accepted, gold standard, trained expert approach., Results: Of 312 potential crowd members, 117 (37.5%) commenced abstract screening and 71 (22.8%) completed the minimum requirement of 50 citation assessments. The majority of participants were undergraduate or medical students (192/312, 61.5%). The crowd screened 16,988 abstracts (median: 8 per citation; interquartile range [IQR] 7-8), and all citations achieved the minimum of 4 assessments after a median of 42 days (IQR 26-67). Crowd members retrieved 83.5% (774/927) of the articles that progressed to the full text phase. A total of 7604 full text assessments were completed (median: 7 per citation; IQR 3-11). Citations from all but 1 review achieved the minimum of 4 assessments after a median of 36 days (IQR 24-70), with 1 review remaining incomplete after 3 months. When complete crowd member agreement at both levels was required for exclusion, sensitivity was 100% (95% CI 97.9-100) and work performed was calculated at 68.3% (95% CI 66.4-70.1). Using the predefined alternative 75% exclusion threshold, sensitivity remained 100% and work performed increased to 72.9% (95% CI 71.0-74.6; P<.001). Finally, when a simple majority threshold was considered, sensitivity decreased marginally to 98.9% (95% CI 96.0-99.7; P=.25) and work performed increased substantially to 80.4% (95% CI 78.7-82.0; P<.001)., Conclusions: Crowdsourcing of citation screening for SRs is feasible and has reasonable sensitivity and specificity. By expediting the screening process, crowdsourcing could permit the investigative team to focus on more complex SR tasks. Future directions should focus on developing a user-friendly online platform that allows research teams to crowdsource their reviews., (©Nassr Nama, Margaret Sampson, Nicholas Barrowman, Ryan Sandarage, Kusum Menon, Gail Macartney, Kimmo Murto, Jean-Philippe Vaccani, Sherri Katz, Roger Zemek, Ahmed Nasr, James Dayre McNally. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 29.04.2019.)

Background: Respiratory illnesses are a major contributor to pediatric hospitalizations, with influenza and respiratory syncytial virus (RSV) causing substantial morbidity and cost each season. We compared the characteristics and outcomes of children 0-59 months of age who were hospitalized with laboratory-confirmed influenza or RSV between 2009 and 2014 in Ontario, Canada., Methods: We included hospitalized children who were tested for influenza A, influenza B and RSV and were positive for a single virus. We characterized individuals by their demographics and healthcare utilization patterns and compared their hospital outcomes, in-hospital cost and postdischarge healthcare use by virus type and by presence of underlying comorbidities., Results: We identified and analyzed 7659 hospitalizations during which a specimen tested positive for influenza or RSV. Children with RSV were the youngest whereas children with influenza B were the oldest [median ages 6 months (interquartile range: 2-17 months) and 25 months (interquartile range: 10-45 months), respectively]. Complex chronic conditions were more prevalent among children with all influenza (sub)types than RSV (31%-34% versus 20%). In-hospital outcomes were similar by virus type, but in children with comorbidities, postdischarge outcomes varied. We observed no differences in in-hospital cost between viruses or by presence of comorbidities [overall median cost: $4150 Canadian dollars (interquartile range: $3710-$4948)]., Conclusions: Influenza and RSV account for large numbers of pediatric hospitalizations. RSV and influenza were similar in terms of severity and cost in hospitalized children. Influenza vaccination should be promoted in pregnant women and young children, and a vaccine against RSV would mitigate the high burden of RSV.

Background: Consistent with accepted practice in stable ambulatory populations, the majority of ICU research has evaluated vitamin D status using a single blood 25-hydroxyvitamin D (25(OH)D) level. Only a limited number of ICU studies have measured the active hormone, 1,25-dihydroxyvitamin D (calcitriol) and none have used change in calcitriol levels to evaluate axis functioning. The objective of this study was to describe the impact of Congenital Heart Disease (CHD) surgery on calcitriol levels and evaluate the relationship between change in postoperative levels and clinical course., Methods: Secondary analysis of a prospective cohort study of 56 children undergoing surgery for CHD., Results: Mean calcitriol levels dropped from 122.3 ± 69.1 pmol/L preoperatively to 65.3 ± 36.5 pmol/L (p < 0.0001) at PICU admission. The majority (61%, n = 34) were unable to increase calcitriol levels in the 48 h immediately following surgery. Post operative trend in calcitriol was inversely related to cardiovascular dysfunction, fluid requirements, ventilatory support and PICU length of stay (p < 0.01)., Conclusion: CHD patients had significant dysfunction of the vitamin D axis immediately postoperatively, demonstrated by both a significant intraoperative decline in calcitriol and inability to increase levels. Interventional research will be required to determine whether the use of calcitriol, in addition to cholecalciferol, reduces postoperative illness severity.

Background: Vitamin D deficiency (VDD) has been hypothesized not only to be common but also to represent a potentially modifiable risk factor for greater illness severity and clinical outcome during critical illness. The objective of this systematic review was to determine the frequency of VDD in pediatric critical illness and its association with clinical outcomes., Methods: MEDLINE, Embase, and CENTRAL were searched through December 12, 2016, with no date or language restrictions. The primary objective was to estimate the prevalence of VDD in the pediatric intensive care unit (PICU) and compare vitamin D status with healthy control populations. Secondary objectives were to evaluate whether VDD is associated with mortality, increased illness severity, PICU interventions, and patient clinical course. Random effects meta-analysis was used to calculate pooled VDD event rate, compare levels with those of control subjects, and evaluate for associations between VDD and clinical outcome., Results: Among 2700 citations, 17 studies meeting study eligibility were identified. The studies reported a total of 2783 critically ill children and had a median sample size of 120 (range 12-511). The majority of studies used a 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/L to define VDD, and the pooled VDD prevalence was 54.8 (95% CI 45.4-63.9). Average 25(OH)D levels were significantly lower in PICU patients than in healthy control subjects (pooled difference -17.3 nmol/L, 95% CI -14.0 to -20.6). In a meta-analysis calculation, we found that VDD was associated with increased mortality (OR 1.62, 95% CI 1.11-2.36), illness severity, and need for PICU interventions., Conclusions: Approximately 50% of critically ill children have VDD at the time of PICU admission, defined as a blood total 25(OH)D concentration under 50 nmol/L. VDD was further determined to be associated with greater illness severity, multiple organ dysfunction, and mortality in the PICU setting. Clinical trials are required to determine if optimization of vitamin D status improves patient outcome., Trial Registration: PROSPERO, CRD42016026617 . Registered on 11 January 2016.

Uncertainty remains regarding the magnitude of effectiveness of influenza vaccines for preventing serious outcomes, especially among young children. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations among children aged 6-59 months. We used the test-negative design in hospitalized children in Ontario, Canada during the 2010-11 to 2013-14 influenza seasons. We used logistic regression models adjusted for age, season, and time within season to calculate VE estimates by vaccination status (full vs. partial), age group, and influenza season. We also assessed VE incorporating prior history of influenza vaccination. We included specimens from 9,982 patient hospitalization episodes over four seasons, with 12.8% testing positive for influenza. We observed variation in VE by vaccination status, age group, and influenza season. For the four seasons combined, VE was 60% (95%CI, 44%-72%) for full vaccination and 39% (95%CI, 17%-56%) for partial vaccination. VE for full vaccination was 67% (95%CI, 48%-79%) for children aged 24-59 months, 48% (95%CI, 12%-69%) for children aged 6-23 months, 77% (95%CI, 47%-90%) for 2010-11, 59% (95%CI, 13%-81%) for 2011-12, 33% (95%CI, -18% to 62%) for 2012-13, and 72% (95%CI, 42%-86%) for 2013-14. VE in children aged 24-59 months appeared similar between those vaccinated in both the current and previous seasons and those vaccinated in the current season only, with the exception of 2012-13, when VE was lower for those vaccinated in the current season only. Influenza vaccination is effective in preventing pediatric laboratory-confirmed influenza hospitalizations during most seasons.

Objectives: To describe the use of deferred and prior informed consent models in the context of a low additional risk to standard of care, placebo-controlled randomized controlled trial of corticosteroids in pediatric septic shock., Design: An observational substudy of consent processes in a randomized controlled trial of hydrocortisone versus placebo., Setting: Seven tertiary level PICUs in Canada., Patients: Children newborn to 17 years inclusive admitted to PICU with suspected septic shock between July 2014 and March 2016., Interventions: None., Measurements and Main Results: Information on the number of families approached, consent rates obtained, and spontaneously volunteered reasons for nonparticipation were collected for both deferred and informed consent. The research ethics board of five of seven centers approved a deferred consent model; however, implementation criteria for use of this model varied across sites. The consent rate using deferred versus prior informed consent was significantly higher (83%; 35/42 vs 58%; 15/26; p = 0.02). The mean times from meeting inclusion criteria to randomization (1.8 ± 1.8 vs 3.6 ± 2.1 hr; p = 0.007) and study drug administration (3.4 ± 2.7 hr vs 4.8 ± 2.1 hr; p = 0.05) were significantly shorter with the use of deferred consent versus prior informed consent. No family member or research ethics board expressed concern following use of deferred consent., Conclusions: Deferred consent was acceptable in time-sensitive critical care research to most research ethics boards, families, and healthcare providers and resulted in higher consent rates and more efficient recruitment. Larger studies on deferred consent and consistency interpreting jurisdictional guidelines are needed to advance pediatric acute care.

Objective  To develop standardized definitions for a list of indicators that represent significant events during pediatric transport, which were previously identified by a national Delphi study. Methods  We designed a three-phase consensus process that applied Delphi methodology to a combination of electronic questionnaires and a live consensus meeting. Results  Thirty-one pediatric transport experts evaluated a total of 59 indicators. Twenty-four indicators represented events or interventions that did not require definition. One indicator was removed from the list. Definitions for the remaining 34 indicators were developed. Conclusion  This standardized indicator list is intended for application to quality improvement and clinical research initiatives.

Objectives: To describe the criteria that currently guide empiric antibiotic treatment in children admitted to Canadian PICUs., Design: Cross-sectional survey., Setting: Canadian PICUs., Subjects: Pediatric intensivists and pediatric infectious diseases specialists., Interventions: None., Measurements and Main Results: We used focus groups and literature review to design the survey questions and its four clinical scenarios (sepsis, pneumonia, meningitis, and intra-abdominal infections). We analyzed our results using descriptive statistics and multivariate linear regression. Our response rate was 60% for pediatric intensivists (62/103) and 36% for pediatric infectious diseases specialists (37/103). Variables related to patient characteristics, disease severity, pathogens, and clinical, laboratory, and radiologic infection markers were associated with longer courses of antibiotics, with median increment ranging from 1.75 to 7.75 days. The presence of positive viral polymerase chain reaction result was the only variable constantly associated with a reduction in antibiotic use (median decrease from, -3.25 to -8.25 d). Importantly, 67-92% of respondents would still use a full course of antibiotics despite positive viral polymerase chain reaction result and marked clinical improvement for patients with suspected sepsis, pneumonia, and intra-abdominal infection. Clinical experience was associated with shorter courses of antibiotics for meningitis and sepsis (-1.3 d [95% CI, -2.4 to -0.2] and -1.8 d [95% CI, -2.8 to -0.7] per 10 extra years of clinical experience, respectively). Finally, site and specialty also influenced antibiotic practices., Conclusions: Decisions about antibiotic management for PICU patients are complex and involve the assessment of several different variables. With the exception of a positive viral polymerase chain reaction, our findings suggest that physicians rarely consider reducing the duration of antibiotics despite clinical improvement. In contrast, they will prolong the duration when faced with a nonreassuring characteristic. The development of objective and evidence-based criteria to guide antibiotic therapy in critically ill children is crucial to ensure the rational use of these agents in PICUs.

Objective: Rapid response systems using medical emergency teams reduce hospital wide cardiorespiratory arrest and mortality. While rapid response systems improve hospital-wide outcomes, children receiving medical emergency team review may still be at increased risk for morbidity and mortality. The study purpose was to compare the length of stay and mortality rate in children receiving a medical emergency team review with those of other hospitalized children., Design: Retrospective cohort study., Setting: Tertiary Pediatric Hospital, Children's Hospital of Eastern Ontario, Ottawa, Canada., Patients: Cohort of 42,308 pediatric admissions to the general inpatient ward., Interventions: Data over 7 years were obtained from a prospectively maintained rapid response systems database., Measurements and Main Results: From the cohort, 995 (2.35%) of the admissions had one and 276 (0.65%) had multiple medical emergency team activations. When compared with patients without, children having one or multiple medical emergency team reviews had 13.34 (95% CI, 5.33-33.2) and 50.10 (95% CI, 19.86-126.39) times the odds of death, respectively. Patients experiencing a medical emergency team review stayed in hospital 1.59 times (95% CI, 1.39-1.82) longer, whereas those with multiple medical emergency team reviews stayed 2.44 times (95% CI, 1.85-3.20) longer. The associations remained significant after controlling for important confounders and excluding elective admissions from the analyses. Most repeat medical emergency team reviews occurred within a day of the initial review or involved patients with multiple comorbidities., Conclusions: Our study suggests that pediatric patients reviewed by the medical emergency team are at significantly higher risk of mortality and longer length of stay than general ward inpatients. As well, patients with multiple medical emergency team reviews were at particularly high risk compared with patients with one medical emergency team review. Patients who experience medical emergency team reviews should be recognized as a high-risk group, and future studies should consider how to decrease morbidity and mortality. Based on our findings, we suggest that these patients be followed for 24-48 hours after any medical emergency team activation.

Objective: To evaluate all published pediatric randomized controlled trials of patients with septic shock from any cause to examine the outcome measures used, the strengths and limitations of these measurements and whether the trial outcomes met feasibility criteria., Data Sources: We used a previously published database of pediatric critical care randomized controlled trials (PICUtrials.net) derived from searches of MEDLINE, EMBASE, LILACS, and CENTRAL., Study Selection: We included randomized controlled trials of interventions to children admitted to a PICU with septic or dengue hemorrhagic shock which were published in English., Data Extraction: Study characteristics and outcomes were retrieved by two independent reviewers with disagreement being resolved by a third reviewer. We defined feasibility as 1) recruitment of at least 90% of the targeted sample size and agreement of the observed outcome rate in the control group with the rate used for the sample size calculation to within 10% or 2) finding of a statistically significant difference in an interim or final analysis., Data Synthesis: Nineteen of 321 identified articles were selected for review. Fourteen of 19 studies (74%) provided an a priori definition of their primary outcome measure in their "Methods section." Mortality rate was the most commonly reported primary outcome (8/14; 57%), followed by duration of shock (4/14; 29%) followed by organ failure (1/14; 7%). Only three of 19 included trials met feasibility criteria., Conclusions: Our review found that use of mortality alone as a primary outcome in pediatric septic shock trials was associated with significant limitations and that long-term patient-centered outcomes were not used in this setting. Composite outcomes incorporating mortality and long-term outcomes should be explored for use in future pediatric septic shock trials.

Background: Completing large systematic reviews and maintaining them up to date poses significant challenges. This is mainly due to the toll required of a small group of experts to screen and extract potentially eligible citations. Automated approaches have failed so far in providing an accessible and adaptable tool to the research community. Over the past decade, crowdsourcing has become attractive in the scientific field, and implementing it in citation screening could save the investigative team significant work and decrease the time to publication., Methods: Citations from the 2015 update of a pediatrics vitamin D systematic review were uploaded to an online platform designed for crowdsourcing the screening process (http://www.CHEORI.org/en/CrowdScreenOverview). Three sets of exclusion criteria were used for screening, with a review of abstracts at level one, and full-text eligibility determined through two screening stages. Two trained reviewers, who participated in the initial systematic review, established citation eligibility. In parallel, each citation received four independent assessments from an untrained crowd with a medical background. Citations were retained or excluded if they received three congruent assessments. Otherwise, they were reviewed by the principal investigator. Measured outcomes included sensitivity of the crowd to retain eligible studies, and potential work saved defined as citations sorted by the crowd (excluded or retained) without involvement of the principal investigator., Results: A total of 148 citations for screening were identified, of which 20 met eligibility criteria (true positives). The four reviewers from the crowd agreed completely on 63% (95% CI: 57-69%) of assessments, and achieved a sensitivity of 100% (95% CI: 88-100%) and a specificity of 99% (95% CI: 96-100%). Potential work saved to the research team was 84% (95% CI: 77-89%) at the abstract screening stage, and 73% (95% CI: 67-79%) through all three levels. In addition, different thresholds for citation retention and exclusion were assessed. With an algorithm favoring sensitivity (citation excluded only if all four reviewers agree), sensitivity was maintained at 100%, with a decrease of potential work saved to 66% (95% CI: 59-71%). In contrast, increasing the threshold required for retention (exclude all citations not obtaining 3/4 retain assessments) decreased sensitivity to 85% (95% CI: 65-96%), while improving potential workload saved to 92% (95% CI: 88-95%)., Conclusions: This study demonstrates the accuracy of crowdsourcing for systematic review citations screening, with retention of all eligible articles and a significant reduction in the work required from the investigative team. Together, these two findings suggest that crowdsourcing could represent a significant advancement in the area of systematic review. Future directions include further study to assess validity across medical fields and determination of the capacity of a non-medical crowd., Competing Interests: The authors have no conflicts of interest to declare.

Vitamin D deficiency (VDD) is a well-established cause of pediatric bone and muscle disease. In addition, a role has been recognized for vitamin D in the health and stress response of other organs, including the cardiovascular, immune, and respiratory systems. As these organs are central to the development of and recovery from critical illness, VDD has been hypothesized to be a modifiable risk factor for ICU outcome. Over the past 5 years, a growing number of adult and pediatric critical care studies have investigated the prevalence of VDD and its association with illness severity and outcome. The adult studies have recently been synthesized in systematic reviews, with results that convincingly suggest the need for trials to determine whether optimization of vitamin D status improves outcome. In contrast, the pediatric ICU and related literature has not been similarly synthesized. The goal of this review is to describe vitamin D metabolism, known biological mechanisms, potential role in pathophysiology, and summarize the available pediatric intensive care unit (PICU) studies reporting on prevalence of VDD deficiency and its association with outcome. The problems with currently approved supplementation approaches and alternative strategies are discussed, including evidence from available RCTs in adult ICU. Altogether the results suggest that critically ill children are at risk for VDD, and that VDD appears to be associated with a worse clinical course. Clinical trials evaluating novel approaches to testing for and supplementing vitamin D require exploration.