Vitamin D in the critically ill - update 2024.

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.

Defining Pediatric Chronic Critical Illness: A Scoping Review.

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.

Evaluating the relationship between citation set size, team size and screening methods used in systematic reviews: a cross-sectional study.

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.

Crowdsourcing the Citation Screening Process for Systematic Reviews: Validation Study.

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.

Vitamin D deficiency in critically ill children: a systematic review and meta-analysis.

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.

Increased Mortality and Length of Stay Associated With Medical Emergency Team Review in Hospitalized Pediatric Patients: A Retrospective Cohort Study.

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.

Primary Outcome Measures in Pediatric Septic Shock Trials: A Systematic Review.

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.

Determinants of Antibiotic Tailoring in Pediatric Intensive Care: A National Survey.

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.

Comparison of Consent Models in a Randomized Trial of Corticosteroids in Pediatric Septic Shock.

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.

A PICU patient safety checklist: rate of utilization and impact on patient care.

OBJECTIVE: In healthcare, checklists help to ensure patients receive evidence-based, safe care. Since 2007, we have used a bedside checklist in our PICU to facilitate daily discussion of care-related questions at each bedside. The primary objective of this study was to assess compliance with checklist use and to assess how often individual checklist elements affected patient management. A secondary objective was to determine whether patient and unit factors (severity of illness, unit census, weekday vs. weekend, admitting diagnosis group) influenced checklist use. DESIGN: This was a prospective observational study. A research assistant attended daily bedside rounds to collect data at each eligible patient encounter. SETTING: The study was conducted in the Children's Hospital of Eastern Ontario (CHEO) PICU, a 12-bed cardiac and medical-surgical unit. PARTICIPANTS: Included all patients admitted to the PICU prior to 6 am and who were not being discharged that day. INTERVENTION: A bedside rounds checklist. MAIN OUTCOME MEASURES: Included compliance and whether the checklist affected the patient's management plan. RESULTS: A total of 148 encounters were collected on 28 days between September 2013 and February 2014. Compliance with the checklist was 89.2% (132/148; 95% CI 83.2-93.2%) and was not influenced by admitting diagnosis group, patient census, severity of patient's conditions or weekday/weekend status. The checklist affected the patient management plan 52.6% of the time (69/132; 95% CI 44.2-61%). CONCLUSIONS: Our study found high rates of compliance with an established checklist that has been in use in the PICU since 2007. Checklist use frequently resulted in a change in the patient management plan.

Efficacy of high-dose vitamin D in pediatric asthma: a systematic review and meta-analysis.

CONTEXT: Observational studies have suggested a relationship between vitamin D status and asthma-related respiratory outcomes. The benefit of vitamin D supplementation for pulmonary function, symptoms and exacerbations is not well established. OBJECTIVE: To systematically review paediatric clinical trials investigating the role of vitamin D on asthma-related respiratory outcomes. DATA SOURCES: MEDLINE, EMBASE and CENTRAL were searched until January 2014. No date or language restrictions. STUDY SELECTION: Clinical trials reporting asthma-related respiratory outcomes following vitamin D administration at a dose equal or greater than 500 IU per day were included and reviewed independently by two authors for full systematic review eligibility. DATA EXTRACTION: Two reviewers independently extracted and verified pre-defined data fields. RESULTS: We identified five studies that met study eligibility and assessed final data synthesis. The median trial size was 48 participants (range 17-430) and the average daily dose of cholecalciferol ranged from 500 to 2000 IU/day. Overall study methodological quality was high, but some heterogeneity in population and vitamin D dosing regimen was evident. Meta-analysis suggested a statistically significant reduction (RR 0.41, CI 0.27-0.63) in asthma exacerbation with vitamin D therapy. LIMITATIONS: Due to variability in outcome selection and missing data, it was not possible to perform meta-analysis for pulmonary function testing and asthma symptom scores. Vitamin D-related adverse events were not considered in four of five papers. CONCLUSIONS: Available evidence from this systematic review suggests that high dose vitamin D may prevent asthma exacerbation. This should be confirmed through larger well-designed randomised controlled trials.

Routine Medical Emergency Team Assessments of Patients Discharged From the PICU: Description of a Medical Emergency Team Follow-Up Program.

OBJECTIVE: This study describes one follow-up program in the Ontario Rapid-Response System project consisting of routine medical emergency team visits of patients discharged from the PICU consisting of two planned visits within 48 hours following discharge. Study purpose was to describe interventions provided and the patient characteristics associated with medical emergency team utilization. DESIGN: Retrospective cohort study. SETTING: Tertiary Pediatric Hospital, Children's Hospital of Eastern Ontario, Ottawa, Canada. PATIENTS: Discharged pediatric patients from PICU. INTERVENTIONS: Data over 41 months were obtained from a prospectively maintained rapid-response system database. Major medical emergency team support was defined as an early unplanned visit, intervention, or readmission during the follow-up period. MEASUREMENTS AND MAIN RESULTS: Interrupted time-series analysis comparing the 2 years preceding rapid-response system implementation with the subsequent 4 years demonstrated a statistically significant immediate change in PICU readmission rate (-5.5%, p = 0.0001). There were 1,805 patients followed after PICU discharge. During the 48-hour planned follow-up period, 4% of patients received an unplanned medical emergency team visit and 13% received an active intervention. Analysis of the first medical emergency team visit identified that 10% received major medical emergency team support. After the initial visit, 6% of patients received major medical emergency team support with predictive characteristics being an unplanned first visit (odds ratio, 3.7; 95% CI, 1.6-8.5) or an intervention during the first visit (odds ratio, 3.5; 95% CI, 2.1-5.8). Multiple diseased organs were associated with major medical emergency team support after the initial visit for recent surgical patients (odds ratio, 3.0 vs 1.2; p = 0.03). CONCLUSIONS: Routine medical emergency team visits following PICU discharge reduced the risk of early readmission. Our results suggest that one in seven patients in the follow-up program receive major medical emergency team support. We suggest a follow-up program with at least one routine medical emergency team visit within the first 24 hours of discharge with a second planned visit reserved for complex postsurgical patients.

Successful incorporation of single reviewer assessments during systematic review screening: development and validation of sensitivity and work-saved of an algorithm that considers exclusion criteria and count.

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.

Pediatric Chronic Critical Illness: Protocol for a Scoping Review.

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.

Palivizumab's real-world effectiveness: a population-based study in Ontario, Canada, 1993-2017.

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.

High Rate of Medical Emergency Team Activation in Children with Tracheostomy.

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.

Prevention of post-cardiac surgery vitamin D deficiency in children with congenital heart disease: a pilot feasibility dose evaluation randomized controlled trial.

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.

A pilot validation study of crowdsourcing systematic reviews: update of a searchable database of pediatric clinical trials of high-dose vitamin D.

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.