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Background Elevated rates of eczema and skin infections in Canadian First Nation (FN) communities are of concern to families, community leaders and healthcare professionals. Aim To determine whether skin morbidity was associated with indoor environmental quality factors in Canadian FN children living in remote communities. Methods We quantified indoor environmental quality (IEQ) in the homes of FN children aged < 4 years of age living in four remote communities in the Sioux Lookout region of Northwestern Ontario, Canada. We conducted a quantitative housing inspection, including measuring surface area of mould (SAM), and monitored air quality for 5 days in each home, including carbon dioxide and relative humidity and quantified endotoxin in settled floor dust. We reviewed the medical charts of participating children for skin conditions and administered a health questionnaire. Relationships between IEQ and skin infections or eczema were evaluated using multivariable regression. Results In total, 98 children were included in the descriptive analyses, of whom 86 had complete data and were evaluated in multivariate analyses for dermatological outcomes (mean age 1.6 years). Of these 86 children, 55% had made ≥ 1 visits to the local health centre (HC) for skin and soft tissue infections and 25.5% for eczema. Unexpectedly, annualized eczema visits were inversely associated with SAM (RR = 0.14; 95% CI 0.01–0.93). There was a trend suggesting an inverse relationship between endotoxin and HC encounters for eczema and skin and soft tissue infections. Conclusion Skin infections were common in this population of FN children. IEQ did not appear to be associated with skin infections or eczema. Mould exposure appeared to be inversely associated with HC encounters for eczema, possibly related to complex microorganism–host interactions occurring early in life. [ABSTRACT FROM AUTHOR]

Background: Accurate and reliable evaluation of cardiac index (CI) in critically ill pediatric patients can optimize their management. Although validated, noninvasive ultrasound measurement techniques have been previously shown to be unreliable because of observer variability. Objective: To confirm intra- and inter-observer reliability when using the noninvasive USCOM [ABSTRACT FROM AUTHOR]

Background: Inuit children from Nunavut have been observed to have high rates of macrocephaly, which sometimes leads to burdensome travel for medical evaluation, often with no pathology identified upon assessment. Given reports that World Health Organization (WHO) growth charts may not reflect all populations, we sought to compare head circumference measurements in a cohort of Inuit children with the WHO charts. Methods: We extracted head circumference data from a previous retrospective cohort study where, with Inuit partnership, we reviewed medical records of Inuit children (from birth to age 5 yr) born between Jan. 1, 2010, and Dec. 31, 2013, and residing in Nunavut. To create a cohort of Inuit children similar to the cohorts used in the development of the WHO growth charts, we excluded children with preterm birth, documented neurologic or genetic disease, and most congenital anomalies. We compared head circumference values with the 2007 WHO charts using centiles estimated with a generalized additive model. Results: We analyzed records of 1960 Inuit children (8866 data points), of whom 993 (50.8%) were female. Most data were from ages 0 to 36 months. At all age points, we found that the study cohort had statistically significantly larger head circumferences than WHO medians, with most z scores for head circumference measurements among Inuit children falling 0.5–1 standard deviations above the WHO reference (p < 0.001). At age 12 months, median head circumferences were 1.3 cm and 1.5 cm larger for male and female Inuit children, respectively. Using WHO growth curves, macrocephaly was significantly overdiagnosed and microcephaly was underdiagnosed (p < 0.001). Interpretation: Our results support the observation that Inuit children from Nunavut have larger head circumferences than other populations, and use of the WHO charts may thus lead to overdiagnosis of macrocephaly and underdiagnosis of microcephaly. Population-specific growth curves for Inuit children should be considered to provide timely and appropriate diagnoses of microcephaly and avoid overinvestigation of macrocephaly. [ABSTRACT FROM AUTHOR]

Summary: The Kids ITP Tools (KIT) is a health‐related quality of life (HRQoL) questionnaire that evaluates quality of life in children with immune thrombocytopenia (ITP). There are three formats: Child Self‐Report, Parent Proxy‐Report and Parent Impact‐Report. This study aimed to develop a domain structure by grouping‐related questions from the questionnaire into domains that independently reflect various aspects of HRQoL. The study was conducted in two phases. Phase 1 involved an online survey distributed to experts to identify conceptual domains for the KIT. Phase 2 utilized a statistical approach to analyse responses from patients with ITP and their families. A revised KIT 2.0 was ultimately developed to aid in treatment decision‐making and monitoring of ITP. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectiveMethodsResultsDiscussionSelf-management education is integral for proper asthma management. However, there is an accessibility gap to self-management education following asthma hospitalizations. Most pediatric patients and their families receive suboptimal or no education.To implement a comprehensive pediatric asthma education program and evaluate subsequent self-management knowledge in patients as well as behavior change outcomes reflected in the frequency of asthma related repeat emergency department visits and hospitalization. The program implementation was informed by the Knowledge to Translation Action Framework and the i-PARIHS model for quality improvement and involved several iterative stages.We implemented a comprehensive asthma education program for the families of all children 0-18 years old who had been admitted for an asthma exacerbation to the Children’s Hospital of Eastern Ontario (CHEO), beginning on April 1, 2018. The program was adapted to the stages of the Knowledge Translation to Action Framework including undertaking an environmental scan, expert stakeholder feedback, reviews, addressing barriers, and tailoring the intervention, along with evaluating knowledge and health outcomes. Education was delivered over 1-2 h in personalized individual or small group settings, within 4 wk of hospital discharge. All education was provided by registered nurses or respiratory therapists who were also certified asthma educators. The EPIC electronic medical record was used to facilitate referral and scheduling of asthma education sessions, and to track subsequent acute asthma visits. We compared the frequency of a repeat asthma emergency department (ED) visit or hospitalization within 1-year following an initial asthma hospitalization for children who would have received comprehensive asthma education, to a historical cohort of children who were hospitalized between April 9, 2017 – Apr 8, 2018, and did not receive asthma education.The program had a high enrollment, capturing nearly 75% of the target population. Most families found the program to be acceptable and reported increased knowledge of how to manage asthma. We identified a crude overall 54% reduction in repeat hospitalizations among children 1 year after implementation of the asthma education program (i.e. 10.2% (23/225) repeat hospitalization rate pre- implementation versus 4.8% (11/227) post-implementation). In adjusted time-to event analysis, this reduction was prominent at 3 months among those who received comprehensive asthma education, relative to those who did not, but this improvement was not sustained by 1 year (HR =1.1, 95% CI =0.55- 2.05; p-value = 0.6).Although we did not find long-term improvements in ED visits, or hospitalizations, in children of caregivers who participated in comprehensive asthma education, the asthma education program holds potential given that most patients found it to be acceptable and that it increased asthma management knowledge. A future asthma education program should include multiple sessions to ensure that the knowledge and behavior change will be sustained, leading ultimately to long-term reductions in repeat ED visits and hospitalizations. [ABSTRACT FROM AUTHOR]

Background: Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients where edema does not improve with prednisone therapy, the most common supportive medications are diuretics and albumin. However, due to the complex pathophysiology of edema formation in NS patients resulting in intravascular normovolemia or hypovolemia, optimal therapy for edema is still debated. We conducted a systematic review with the objective of evaluating the change in urine volume and urine sodium excretion after treatment with furosemide only versus furosemide with albumin in edematous patients with NS. Objectives: (1) To evaluate efficacy of furosemide alone versus furosemide with albumin in the treatment of nephrotic edema in adults and children. (2) To compare the harms and benefits of different doses of furosemide for treating nephrotic edema. Search methods: The search included all randomized or quasi-randomized controlled trials in English and French using MEDLINE, Embase, and CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface. ClinicalTrials.gov and the International Clinical Trials Registry Platform were also searched. Selection criteria: We included all RCTs and randomized cross-over studies in which furosemide and furosemide plus albumin are used in the treatment of children or adults with nephrotic edema. We excluded patients with hypoalbuminemia of non-renal origin and severe chronic kidney disease (CKD) with a glomerular filtration rate below 30 ml/min/1.74 m2 and patients with congenital NS. Data collection and analysis: All abstracts were independently assessed by at least two authors to determine which studies met the inclusion criteria. Information on study design, methodology, and outcome data (urine volume, urine sodium excretion, adverse effects) from each identified study was entered into a separate data sheet. The differences in outcomes between the types of therapy were expressed as standardized mean difference (SMD) with 95% confidence intervals (CI). Results: The search yielded 525 records, and after screening, five studies were included in the systematic review and four of those studies in the meta-analysis. One study had high risk of bias and the remaining three studies were deemed to have some concerns. Urine excretion was greater after treatment with furosemide and albumin versus furosemide (SMD 0.85, 95% CI = 0.33 to 1.38). Results for sodium excretion were inconclusive (SMD 0.37, 95%CI = − 0.28 to 1.02). Authors' conclusions: The current evidence is not sufficient to make definitive conclusions about the role of albumin in treating nephrotic edema. High-quality randomized studies with adequate samples sizes are needed. Including an assessment of intravascular volume status may be helpful. Trial registration: Prospero: CRD4201808979. https://www.crd.york.ac.uk/PROSPERO A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP), a marker for inflammation, was evaluated with other routine blood tests in children with newly diagnosed inflammatory bowel disease. Evaluation of CRP level helped identify additional patients found to have inflammatory bowel disease at endoscopy, although a sizeable number of patients with mild ulcerative colitis had a normal CRP level. [Copyright &y& Elsevier]

The immune response to coronavirus disease 2019 (COVID-19) vaccination is stronger among adults with prior infection (hybrid immunity). It is important to understand if children demonstrate a similar response to better inform vaccination strategies. Our study investigated the humoral response after BNT162b2 COVID-19 vaccine doses in SARS-CoV-2 naïve and recovered children (5–11 years). A multi-institutional, longitudinal, prospective cohort study was conducted. Children were enrolled in a case-ascertained antibody surveillance study in Ottawa, Ontario from September/2020-March/2021; at least one household member was severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive on RT-PCR. In November 2021, BNT162b2 COVID-19 vaccine was authorized for children aged 5–11 in Canada. Children enrolled in the surveillance study intending to receive two vaccine doses were invited to participate in this study from November 2021-April 2022. Main exposure was prior SARS-CoV-2 infection, defined by positive RT-PCR or SARS-CoV-2 anti-N IgG antibody presence. Primary outcome was spike IgG antibody levels measured following the first vaccine dose (2–3 weeks) and second vaccine dose (3–4 weeks). Of the 153 eligible children, 75 participants (median age 8.9 IQR (7.4, 10.2) years; 38 (50.7 %) female; 59 (78.7 %) Caucasian) had complete follow-up. Fifty-four (72 %) children had prior SARS-COV-2 infection. Spike IgG antibody levels are significantly higher in SARS-CoV-2 recovered participants after receiving the first dose (p < 0.001) and the second (p = 0.01) compared to infection naïve children. SARS-CoV-2 recovered children (5–11 years) demonstrated higher antibody levels following first BNT162b2 vaccine dose compared with naïve children. Most reached antibody saturation two to three weeks after the first dose; a second dose didn't change the saturation level. A single vaccine dose in SARS-CoV-2 recovered children may be equivalent or superior to a 2-dose primary series in naïve children. Further research is needed on the durability and quality of a single vaccine dose in this population. [ABSTRACT FROM AUTHOR]

Purpose: Given that syrinx is often considered an indication of surgery in children with Chiari I malformation (CM1), understanding of the natural history of these patients is very challenging. In this study, we investigate the natural history of children with CM1 that have syrinx and/or prominence of the central canal on presentation. Methods: All pediatric Chiari I patients who had syrinx and/or prominence of the central canal who underwent MR imaging of the head and spine from 2007 to 2020 were reviewed. Patients were divided into 3 groups (early surgery, delayed surgery, and conservative management). We focused on those patients who did not initially undergo surgery and had at least 1 year of clinical follow-up. We assessed if there were any radiological features that would correlate with need for delayed surgical intervention. Results: Thirty-seven patients met the inclusion criteria. Twenty-one patients were female and 16 were male. The mean age at presentation was 8.7 (5.8 SD). Fourteen (38%) patients had early surgical intervention, with a mean of 2.5 months after initial presentation, 8 (16%) had delayed surgery due to new or progressive neurological symptoms and 46% of patients did not require intervention during follow-up. The length of tonsillar herniation and the position of the obex were associated with the need of surgery in patients who were initially treated conservatively. Conclusion: In pediatric patients with CM1 with syringomyelia and prominence of the central canal, conservative treatment is initially appropriate when symptoms are absent or mild. Close follow-up of patients with CM1 and dilatation of the central canal who have an obex position below the foramen magnum and greater tonsillar herniation is suggested, as these patients show a trend towards clinical deterioration over time and may require earlier surgical intervention. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Extravasation of iodinated contrast material during computed tomography (CT) is a rare complication. A few patients may develop severe complications such as compartment syndrome. Objective: The purpose of this study was to retrospectively assess the prevalence, severity, management, and outcome of contrast extravasations in our institution and to perform a comparison to what has been reported in the existing literature. Materials and methods: This is a research ethics board (REB)–approved retrospective study comprising 11 patients who had intravenous contrast-enhanced CT between 2019 and 2022 in a tertiary pediatric center, and experienced extravasation of iodinated contrast as a complication. Age, weight, sex, co-morbidities, angiocatheter size, venous access location, total contrast volume, flow rate, patient's symptoms, severity of injury, and management were collected. For the systematic review, PRISMA guidelines were followed. Results: Only 11 (0.3%) (0.17-0.54 (95%CI)) contrast extravasations occurred in a total of 3638 CTs performed with intravenous contrast during the same period in children. The median age (IQR) was 12.5 (10.0, 15.0) years. In our cohort, 1/11 patients developed compartment syndrome and required fasciotomy. The systematic review assessed 12 articles representing a population of 110 children with extravasations. Pooled prevalence from articles stratified by age was 0.32% (0.06-0.58% (95%CI)). Only three children experienced moderate to severe complications. Conclusions: We confirm that severe complications of contrast extravasation are rare and can occur at any age. No strong associations were seen with the need for surgical consultation (including age, sex, weight, flow rate, injection site, catheter size, and type of contrast). [ABSTRACT FROM AUTHOR]

Background/Purpose: Previous studies of uveitis in Juvenile Idiopathic Arthritis (JIA) patients have reported prevalence and not incidence. The ReACCh Out cohort, a large inception cohort of newly diagnosed JIA patients provided the opportunity to prospectively ascertain the true incidence of new onset uveitis. The objectives of this study were to determine the overall incidence rate and its trajectory over time. Methods: ReACCh Out recruited newly diagnosed JIA patients between January 2005 and December 2010, from 16 Canadian centres across the country. Prospective data was collected every 6 months for the first 2 years, then yearly. Data was collected on numerous clinical and laboratory measures including the diagnosis of uveitis and its complications, determined by an ophthalmologist. A Poisson model was used to estimate the overall incidence rate. A Kaplan-Meier plot was used to evaluate the time from diagnosis of JIA to the time of diagnosis of new onset uveitis. Results: 1104 patients with newly diagnosed (≤6 months) JIA with ≥1 follow-up visit were reviewed. Patients were predominantly female (63%), age at diagnosis was 9.3 (3.9, 13.0) years. Time from diagnosis to enrollment was 0.3 (0, 1.6) months. Follow-up to last visit or study end was 34.2 (21.5, 48) months. 23 patients whose uveitis status was not available, were excluded. 77 patients with new onset uveitis were identified during the study period. The overall incidence rate of new cases of uveitis following the diagnosis of JIA was 2.9% per year (95% confidence interval 2.3-3.6). Following the trajectory of new cases of uveitis over time, the incidence of new cases showed a slow decline over time (Figure ). Importantly, new cases of uveitis occurred as far out from diagnosis as the end of the study period. Kaplan-Meier plots were also used to evaluate age at diagnosis of new onset uveitis and gender. Results support previously identified risk factors for uveitis including younger age (<5 years) and female gender. The frequency of uveitis occurred in the JIA patients in the following distribution according to subtype: oligoarthritis (43, 56%), polyarthritis RF negative (18, 23%), polyarthritis RF positive (1, 1%), psoriatic (4, 5%), ERA (1, 1%), systemic (1, 1%) and undifferentiated (9, 12%). [ABSTRACT FROM AUTHOR]

Although evidence supports diverse assessment strategies, including patient/caregiver involvement in Competency-Based Medical Education (CBME), few residency programs formally include patients/caregivers in assessment. We aimed to determine the milestones for which patient/caregiver inclusion would be valuable in the Canadian Pediatric Competence By Design (CBD) curriculum. Program directors from 17 Canadian pediatric residency programs were invited to participate in a Delphi study. This Delphi included 209 milestones selected by the study team from the 320 milestones of the draft pediatric CBD curriculum available at the time of the study. In round 1, 16 participants representing 13 institutions rated the value of including patients/caregivers in the assessment of each milestone using a 4-point scale. We obtained consensus for 150 milestones, leaving 59 for re-exposure. In round 2, 14/16 participants rated remaining items without consensus. Overall, 67 milestones met consensus for 'valuable,' of which 11 met consensus for 'extremely valuable.' The majority of these milestones related to communication skills. Patient/caregiver assessment is valuable for 21% of milestones in the draft pediatric CBD curriculum, predominantly those relating to communication skills. This confirms the perceived importance of patient/caregiver assessment of trainees in CBME curricula; formal inclusion may be considered. Future directions could include exploring patients/caregivers' perspectives of their roles in assessment in CBD. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively correlate imaging findings post-sclerotherapy of low-flow vascular malformations with clinical outcome. Materials and Methods: We retrospectively evaluated 81 pediatric patients who had sclerotherapy in our department over a 14-year period. Patients with a diagnosis of low-flow vascular malformation, pre and post-treatment ultrasound (US) and clinical follow-up evaluation were included in the study. Exclusion criteria were coexisting high-flow vascular malformations, history of additional surgical or medical treatment to their malformation and large infiltrative lesions difficult to measure on US. Pre and post-treatment sonographic volumes of the malformation were assessed. Changes in volume were categorized into 6- increased volume, stable and volume decrease of 1-25%/26-50%/51-75%/75-100%. Clinical outcomes were categorized into 4 – worse, no change, improved and symptom free. In cases where pre-treatment MRI was available, the estimated malformation volumes in both modalities were correlated using Spearman's rank correlation. The change in sonographic volume was correlated with clinical outcome using Spearman's rank correlation. P -values <.05 were considered significant. Results: Twenty-nine patients were included in the study; 13 with venous malformation (VM), and 16 with lymphatic malformation (LM). Nineteen patients had both pre-treatment US and MRI, showing correlation in volume between the 2 modalities (P <.001). Post-treatment change in volume correlated with clinical outcome for combined venous and LMs (rho =.44, P =.02). No correlation was found when venous (rho =.48, P =.09) and lymphatic (rho =.33, P =.21) malformations were considered separately. Conclusion: Ultrasound can potentially be used as an objective tool in evaluating sclerotherapy treatment response of low-flow vascular malformations in the pediatric population. [ABSTRACT FROM AUTHOR]

Asthma is a leading cause of emergency department (ED) visits and hospitalizations in children, though many could be prevented. Our study objective was to identify factors from the published literature that are associated with future hospitalization for asthma beyond 30 days following an initial asthma ED visit. We searched CINAHL, CENTRAL, MEDLINE, and Embase for all studies examining factors associated with asthma-related hospitalization in children from January 1, 1992 to February 7, 2022.Selecting Studies: All citations were reviewed independently by two reviewers and studies meeting inclusion criteria were assessed for risk of bias. Data on all reported variables were extracted from full text and categorized according to identified themes. Where possible, data were pooled for meta-analysis using random effects models. Of 2262 studies, 68 met inclusion criteria. We identified 28 risk factors and categorized these into six themes. Factors independently associated with future hospitalization in meta-analysis include: exposure to environmental tobacco smoke (OR = 1.94 95%CI 0.67–5.61), pets exposure (OR = 1.67 95%CI 1.17–2.37), and previous asthma hospitalizations (OR = 3.47 95% CI 2.95–4.07). Additional related factors included previous acute care visits, comorbid health conditions (including atopy), allergen exposure, severe-persistent asthma phenotype, inhaled steroid use prior to ED visit, poor asthma control, higher severity symptoms at ED presentation, warmer season at admission, longer length of stay or ICU admission, and African-American race/ethnicity. We identified multiple factors that are consistently associated with future asthma hospitalization in children and could be used to identify those who would benefit from targeted preventative interventions. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of nocturnal hypoglycemia (NH) in pediatric type 1 diabetes, to compare the prevalence of NH detected by continuous glucose monitoring (CGM) and self-monitored blood glucose (SMBG), and to compare the prevalence of NH using different thresholds. Study design: Twenty-five patients wore a continuous glucose monitor for 3 nights and also conducted SMBG. NH was defined with three thresholds: (1) <3.9 mmol/L; (2) <3.3 mmol/L; and (3) <2.9 mmol/L. Results: The prevalence of NH with CGM was 68%, 52%, and 48% with the different thresholds. Of the 35 episodes of NH detected by CGM, 25 were not symptomatic and therefore not detected by SMBG. The mean difference in blood glucose between CGM and SMBG was -0.18 mmol/L (P = .35). Conclusions: This pilot study suggests that the prevalence of NH in pediatric patients with type 1 diabetes with conventional treatment may be as high as 68%, although this varied according to the method of detection and threshold used. Patients may benefit from CGM to detect asymptomatic NH. [Copyright &y& Elsevier]

Reports on the termination of John Hoey and Anne Marie Todkill from the "Canadian Medical Association Journal" on February 20, 2006. Implications of the termination for the journal; Contributions of Hoey and Todkill to the journal; Reaction of other editors of the journal to the termination.

Purpose: Multiple imaging parameters have been examined to estimate the presence of syrinx and the need for surgery in Chiari I patients (CM1); however, no consistent or definitive criteria have been proposed. The objective of this study was to review existing and identify novel radiological and clinical characteristics of CM1 patients that associate syrinx development and surgical intervention. Methods: Patients with Chiari I malformation diagnosed on imaging between 0 and 18 years were retrospectively reviewed from January 1, 2007 to February 12, 2020. Participants were included if they had a baseline MRI of the head and spine prior to surgical intervention if required. Forty age-matched controls with cranial imaging were identified for comparison. Imaging parameters and clinical symptoms were recorded. Results: A total of 122 CM1 patients were included in this study. Of the 122 patients, 28 (23%) had syrinx, and 27 (22%) had surgery. The following imaging parameters associated with syrinx and surgical intervention were identified: midbrain length (P < 0.001; P = 0.032), the obex position (P = 0.002; P < 0.001) and medullary kinking (P = 0.041; P < 0.001). Among the clinical features, the presence of overall pain (P = 0.017; P = 0.042), neck pain (P = 0.005; P = 0.027), and sensory dysfunction (P < 0.001) were found to be strongly associated with syrinx and surgery. Conclusion: While further investigation is needed, these specific radiological and clinical parameters should be considered when evaluating CM1 patients and may be used to guide further management. [ABSTRACT FROM AUTHOR]

Objectives Since 2016, use of nasal continuous positive airway pressure (nCPAP) in Nunavut for air transport in select patients has become common practice. This study examines the outcomes of patients transferred by air from the Qikiqtaaluk Region during air transport. We examined intubation rates, adverse events during transfer, and respiratory parameters at departure and upon arrival. Methods This was a retrospective review from September 2016 to December 2019 including patients under 2 years of age transferred by air on nCPAP from the Qikiqtaaluk Region of Nunavut. Results Data were collected for 40 transfers involving 34 unique patients. Six transfers were from remote communities in Nunavut to Iqaluit, and 33 transfers were from Iqaluit to CHEO. The primary outcome measure was whether the patient required intubation during transport, or urgent intubation upon arrival to CHEO. The median nCPAP setting during transport was 6 cm H2O (5–7 cm H2O) and at arrival to CHEO was 6 cm H2O (6–7 cm H2O). Six of the 33 (18.2%) patients required intubation during their hospital stay and five (15.2%) in a controlled ICU setting. There were no discernible adverse events that occurred during transport for 28 patients (84.5%). Four patients (12.1%) required a brief period of bag-mask ventilation and one patient had an episode of bradycardia. Conclusions nCPAP on air transport is a safe and useful method for providing ventilatory support to infants and young children with respiratory distress. [ABSTRACT FROM AUTHOR]

Background: The incidence of hospitalizations for acute respiratory infections (ARI) among young Indigenous children from Northern Canada is consistently high. ARIs requiring urgent air transfer can be life-threatening and costly. We aimed to describe their epidemiology, estimate age-specific incidences, and explore factors associated with level of care required. Methods: We undertook a retrospective cohort study of children <5 years old from Northern Canada transferred by urgent air transport for ARI from 2005 through 2014 to 5 pediatric tertiary care centers in Vancouver, Edmonton, Winnipeg, Ottawa and Montreal. Admissions were identified via ARI-related ICD-9/10 coding and forward sortation area. Descriptive statistics and univariable analyses were performed. Results: Among 650 urgent air transfers, the majority were from Nunavut (n = 349, 53.7%) or Nunavik (n = 166, 25.5%), <6 months old (n = 372, 57.2%), and without underlying comorbidity (n = 458; 70.5%). Estimated annual tertiary care ARI admission rates in infants <1 year old from Nunavut (40.7/1000) and Nunavik (44.5/1000) were tenfold higher than in children aged 1 to 4 years. Bronchiolitis (n = 333, 51.2%) and pneumonia (n = 208, 32.0%) were the most common primary discharge diagnoses. Nearly half required critical care (n = 316, 48.6%); mechanical ventilation rates ranged from 7.2% to 55.9% across centres. The most common primary pathogen was respiratory syncytial virus (n = 196, 30.1%). Influenza A or B was identified in 35 cases (5.4%) and vaccine-preventable bacterial infections in 27 (4.1%) cases. Interpretation: Urgent air transfers for ARI from Northern Canada are associated with high acuity. Variations in levels of care were seen across referral centers, age groups and pathogens. [ABSTRACT FROM AUTHOR]

Background: Rates of lower respiratory tract infection (LRTI) among First Nations (FN) children living in Canada are elevated. We aimed to quantify indoor environmental quality (IEQ) in the homes of FN children in isolated communities and evaluate any associations with respiratory morbidity. Methods: We performed a crosssectional evaluation of 98 FN children (81 with complete data) aged 3 years or younger, living in 4 FN communities in the Sioux Lookout region of Northern Ontario. We performed medical chart reviews and administered questionnaires. We performed a housing inspection, including quantifying the interior surface area of mould (SAM). We monitored air quality for 5 days in each home and quantified the contaminant loading of settled floor dust, including endotoxin. We analyzed associations between IEQ variables and respiratory conditions using univariable and multivariable analyses. Results: Participants had a mean age of 1.6 years and 21% had been admitted to hospital for respiratory infections before age 2 years. Houses were generally crowded (mean occupancy 6.6 [standard deviation 2.6, range 3-17] people per house). Serious housing concerns were frequent, including a lack of functioning controlled ventilation. The mean SAM in the occupied space was 0.2 m2. In multivariable modelling, there was evidence of an association of LRTI with log endotoxin (p = 0.07) and age (p = 0.02), and for upper respiratory tract infections, with SAM (p = 0.07) and age (p = 0.03). Wheeze with colds was associated with log endotoxin (p = 0.03) and age (p = 0.04). Interpretation: We observed poor housing conditions and an association between endotoxin and wheezing in young FN children living in Northern Ontario. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Aminopenicillins are recommended empiric therapy for community-acquired pneumonia (CAP). The aim of the study was to assess treatment over a 5-year period after CAP guideline publication and introduction of an antimicrobial stewardship program (ASP). Methods Using ICD-10 discharge codes for pneumonia, children less than 18 years admitted to the Children's Hospital of Eastern Ontario January 1, 2012 and December 31, 2016 were identified. Children ≥ 2 months with consolidation were included. One day of therapy (DOT) was one or more doses of an antimicrobial given for 1 day. Results Of 1,707 patients identified, 713 met inclusion criteria. Eighteen (2.5%) had bacteria identified by culture and 79 of 265 (29.8%) had Mycoplasma pneumoniae detected. Mean DOT/1,000 patient days of aminopenicillins/penicillin (AAP) increased by 18.1% per year (95% confidence interval [CI] −0.2, 39.9%) and decreased by 37.6% per year (95% CI −56.1, −11.3%) for second- and third-generation cephalosporins in the post-ASP period. The duration of discharge antimicrobials decreased. Of 74 (10.4%) patients who had pleural fluid drained, 35 (47.3%) received more than 5 days of AAP and ≤ 5 days of second-/third-generation cephalosporins with no difference in median length of stay nor mean duration of antimicrobials. Conclusions Implementation of CAP management guidelines followed by prospective audit and feedback stewardship was associated with a sustained decrease in the use of broad-spectrum antibiotics in childhood CAP. Use of AAP should also be strongly considered in patients with effusions (even if no pathogen is identified), as clinical outcome appears similar to patients treated with broad-spectrum antimicrobials. [ABSTRACT FROM AUTHOR]

Sleep problems are highly co-morbid with psychiatric disorders and are part of the complex and multiple factors contributing to symptoms and functional disability. The current study aimed to determine how sleep problems in the period preceding psychiatric admission relate to profiles of mental health needs in adolescent inpatients. This retrospective study included 424 adolescents (13–17 years) admitted over a five-year period to an acute crisis stabilization unit in a tertiary care pediatric hospital. Adolescents were divided into two age- and sex-matched groups based on the presence of moderate to severe sleep problems. Profiles of mental health needs were assessed at admission using the Child and Adolescent Needs and Strengths - Mental Health Acute (CANS-MH) and a complexity score was calculated as the total number of actionable CANS-MH items. Results showed a positive association between sleep problems and needs pertaining to eating disturbances, adjustment to trauma, and school attendance. Odds ratios for sleep problems increased progressively as the complexity scores increased, reaching a plateau at six needs beyond which odds ratios remained at their highest level. Adolescents with sleep problems were more likely to undergo medication changes during psychiatric hospitalization and were more likely to be discharged with antipsychotic medication. These findings suggest that sleep difficulties in adolescent inpatients may be associated with distinct and more complex profiles of mental health needs. The evaluation of sleep problems early in the course of psychiatric hospitalization may be an important part of the psychiatric assessment process to inform the global treatment plan. [ABSTRACT FROM AUTHOR]

Background: Self-monitoring of blood glucose (SMBG) is an essential component of type 1 diabetes (T1D) management and typically involves several daily tests. However, due to high cost, SMBG supplies are often unavailable in low-resource settings. This study assessed whether the use of two SMBG tests per day improves glycemic control, measured by a change in HbA1c, in youth with T1D followed at the DREAM Trust (DT) in Nagpur, India. Methods: Single-site prospective cohort study of youth ≤ 23 years of age with T1D ≥ 1 year followed by DT, who were provided with SMBG meters and two test strips per day. Patients received education regarding SMBG and how to respond to blood glucose values and trends. They were followed every 3 months with HbA1c and questionnaires for a total of 21 months. Results: HbA1c declined significantly from 10.2 ± 2.5% (88 ± 4 mmol/mol) at baseline to 9.5 ± 2.4% (80 ± 3 mmol/mol) at 21 months (p < 0.001). In univariable analysis, change in HbA1c was associated with adherence to insulin dosing, number of patient education sessions, household income, and holding a below the poverty line certificate. In multivariable analysis, only adherence to insulin dosing was a significant predictor for a decrease in HbA1c. There was no increase in diabetes-related acute complications. Conclusions: The use of two SMBG test strips per day for the management of T1D in a low-resource setting was safe, and over the 21 months following its introduction, there was a clinically and statistically significant decrease in HbA1c. [ABSTRACT FROM AUTHOR]

Objectives: We designed a written Canadian Anaphylaxis Action Plan for Kids (Kids' CAP) which incorporates validated pictograms with written instructions. Using a patient-centered approach, we aimed to validate the Kids' CAP and assess its impact on anaphylaxis recognition and treatment, and to determine its' perceived usefulness.Patient Involvement: Children and their parents were involved in appraising the design and written contents of the Kids' CAP.Methods: The design process consisted of a development phase and clinical validation phase. First, we assessed the readability and understandability of the Kids' CAP using validated instruments. Then, patients (12-17 years of age) and parents of patients (<12 years of age) were given the Kids' CAP during the first consultation with allergy specialists or an Emergency Department visit for anaphylaxis. Subsequently, we conducted a phone interview 2-3 weeks later to assess their comprehension of anaphylaxis management. We also used the Consumer Information Rating Form to measure the participants' perception of the design quality and usefulness of the Kids' CAP.Results: Of the 230 participants enrolled, 205 (89%) completed the follow-up interview. The written contents of the Kid's CAP were modified to match grade 7 readability level. The total mean score of the Consumer Information Rating Form for comprehensibility was 23.1 (SD 2.4), and 25.1 (SD 2.3) for design quality. The mean comprehension score was 11.3 (SD 1.8) (reference range 0-12), with no significant difference between participants with and without previous experience with anaphylaxis, or high vs. low literacy level.Conclusion: Engaging children and parents in the design and contents of written anaphylaxis action plan is an innovative approach to produce a useful document for the end-users.Practice Implications: The Kids' CAP is a valid tool that can be used in emergency departments and allergy clinics to improve patient's comprehension of anaphylaxis manifestations and treatment. [ABSTRACT FROM AUTHOR]

Background: Ultrasonography might be an important imaging method for assessing the pediatric enthesis. To diagnose pathology, knowledge of physiological findings is essential but limited.Objective: To provide a detailed ultrasonographic assessment of four lower-extremity entheses in healthy adolescents as a reference for the correct interpretation of findings in children with rheumatic diseases.Materials and Methods: The quadriceps tendon, proximal and distal patella tendon, and Achilles enthesis were examined in B-mode, Power and color Doppler in 41 boys and girls ages 11-14 years in neutral position and 30° flexion. We assessed Doppler signals at various distances from the enthesis and analyzed the data using a marginal logistic regression model with generalized estimating equation. We assessed agreement between observers using weighted kappa and we determined agreement on repeat scans using prevalence- and bias-adjusted kappa.Results: Doppler signals were predominantly in the quadriceps and distal patella tendon with odds ratios of 50.85 and 21.35 (P<0.001) compared to the Achilles tendon. They were within 2 mm or 5 mm of the enthesis (odds ratios [ORs] of 4.58 and 4.24, P<0.001), without significant difference between flexion and neutral position and between the right and the left legs. Agreement between first and second assessment was good, with aggregate kappas from 0.79 to 0.90. The inter-reader agreement was also good, with aggregate kappas ranging from 0.75 to 0.95.Conclusion: We found a differential Doppler pattern in lower-extremity entheses, with signals present mostly in the quadriceps and distal patella entheses. [ABSTRACT FROM AUTHOR]

Abstract Objectives To evaluate immediate versus delayed surgical intervention on treatment outcomes in the management of congenital choanal atresia. Methods This study adhered to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines in reporting a systematic review of the literature. OVID Medline, EMBASE and Pubmed databases were searched using relevant key terms. Inclusion and exclusion criteria were designed to capture studies examining immediate versus delayed primary surgery for congenital choanal atresia. Timing of surgery was classified as immediate or delayed based on median age of intervention stratified by type of obstruction. Primary outcomes were primary treatment failure, respiratory function and mortality rates. Results A total of 2765 abstracts were identified and screened by 2 independent reviewers. Of the 688 articles reviewed in full text, 23 articles met the study criteria and were subjected to quality assessment. The full study assessment and quality control measures yielded 23 studies (representing 362 patients) for pooled patient-level analysis in the systematic review. Primary treatment failures occurred in 24.8% of patients that underwent immediate surgery and 42.6% of patients that underwent delayed surgery for bilateral choanal atresia (p = 0.01). There were no differences in mortality rates (5.6% vs 4.2%; p = 1.00) or qualitative measures of respiratory function. There were no difference in treatment outcomes for patients with unilateral choanal atresia (p > 0.05). Conclusions Through an analysis of pooled individual patient data, this systematic review of the literature demonstrated that there was significantly higher rates of treatment failure in patients that underwent delayed surgery for bilateral choanal atresia. Clinical trials and large prospective cohort studies investigating outcomes following immediate and delayed surgical intervention will provide further insight into treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: Sleep-disordered breathing (SDB) is highly prevalent in children with Down syndrome. Given the scarcity of resources and the presence of risk factors for SDB in this population, the objective of this study is to identify the clinical predictors of SDB, which would assist prioritization of children with Down syndrome for SDB evaluation.Methods: A retrospective cohort study was conducted on children enrolled in the Down syndrome clinic at CHEO who underwent polysomnography in 2004-2014. Total apnea-hypopnea index (AHI) or obstructive AHI (OAHI) > 5 events/hour was considered clinically significant. Associations between SDB and concurrent diagnoses, referral reasons, and sleep symptoms assessed by questionnaire were examined using Pearson's chi-square test or Fisher's exact test as appropriate. Univariate and multivariate logistic regression analyses were used to examine the predictors of SDB.Results: SDB was present in 42.9% of 119 children, with its highest prevalence at age 8 years. Symptoms were not significantly associated with AHI > 5 events/hour or OAHI > 5 events/hour. Gastroesophageal reflux was associated with lower odds of OAHI > 5 events/hour on univariate testing (odds ratio 0.16, 95% CI 0.04-0.72; p = 0.02) and multivariate analysis (odds ratio 0.05, 95% CI 0.0006-0.50; p = 0.002).Conclusions: SDB is highly prevalent at all ages in children with Down syndrome. Symptoms did not predict SDB in this population, although gastroesophageal reflux may mimic SDB, which indicates that clinicians should continue to perform ongoing surveillance for SDB throughout the lifespan of children with Down syndrome. [ABSTRACT FROM AUTHOR]

Severe antisocial behavior in girls, best exemplified by conduct disorder (CD), is a serious clinical and public health problem. Treatment is difficult, particularly in girls with comorbid internalizing disorders. Identifying biological correlates may help to develop new treatments or diagnostic, prognostic, or treatment response biomarkers. Based on our earlier work and research from others occurring primarily in boys with severe antisocial behavior, it is possible that abnormalities in the hypothalamic pituitary adrenal (HPA) axis circadian cortisol cycle may be associated with female CD. Additionally, research suggests that the presence of comorbid internalizing disorders may be related to differences in cortisol secretion, compared to subjects who only have CD. Our study aimed: 1) to compare the circadian cortisol cycle in 98 girls with CD, 15–16 years of age to 47 girls without any psychiatric disorder (ND) and 2) to compare the cycle in girls with CD and comorbid internalizing disorders (CD + INT) to those without such comorbidity (CD Only). Salivary cortisol was collected over 24 h during weekdays at scheduled times, with protocol adherence measures in place. Unstructured covariance pattern modeling, controlling for effects of age, social class, IQ, and awakening time was used to analyze cortisol data. CD was associated with overall lower cortisol secretion (p = 0.03), but this difference was due to a lower volume of cortisol secreted 30 min after awakening (area under the curve with respect to ground, p = 0.01). Circadian cortisol secretion was no different in the CD+INT group compared to the CD Only group (p = 0.52). Our findings need to be replicated using current consensus guidelines for the assessment of the CAR. We also suggest two new avenues of research in this field. • Research on circadian cortisol secretion in adolescent girls with conduct disorder is lacking. • Girls with conduct disorder showed lower cortisol secretion in the morning after awakening compared to girls with no disorder. • There were no differences in cortisol levels between girls with and without conduct disorder at any other timepoint. • Cortisol levels did not differ at any timepoint between conduct disordered-girls with or without anxiety or depressive disorders. • Effects of neuropsychological function or comorbid oppositional defiant disorder are important topics for future research. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To establish reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) at 3–6weeks of age in very low birth weight (VLBW) infants with the Beckman Coulter Unicel DxI 800 by gender, birth weight (BW) and gestational age (GA) subgroups. Design and methods: A 4year retrospective cohort of 308 VLBW infants (GA=27.9weeks, BW=992.3g) was studied. All blood samples for TSH and FT4 were analyzed using the modified fTSH2 (TSH) and two-step competitive enzyme immunoassay (FT4). Reference intervals were evaluated according to the most recent Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: The study provides non-parametric 95% reference intervals with associated 90% confidence intervals for FT4 and TSH derived from 308 infants screened at a median of 31days. The reference intervals for this population are TSH=1.14–11.04mIU/L and FT4=10.9–21.4pmol/L. TSH statistically differed according to birth weight (<1000g vs 1000–1499g) while FT4 differed according to gender and gestational age at time of testing (<32weeks vs ≥32weeks); however, these differences were not clinically significant and a single reference interval for each analyte is reported. Conclusion: The results of this study highlight the importance and complexity of establishing appropriate reference intervals for thyroid function testing for the preterm population. [Copyright &y& Elsevier]

Background : Point of Care Ultrasound (POCUS) is an important tool in pediatric emergency medicine. In neonatal intensive care medicine ultrasound is often used to evaluate the brains of sick neonates. In theory, POCUS could be used in the ED in young children to evaluate the brain for abnormal pathology. Objectives : To examine the ability of PEM faculty to use brain POCUS to identify clinically significant brain injuries in children with head injuries and/or abnormal neurological exams, and generate sensitivity and specificity of brain POCUS in assessing such findings. Methods : This study used a convenience sample of patients seen in a tertiary care pediatric centre who required a CT head. A team of physicians who were trained at a workshop for brain POCUS were on call to perform the POCUS while being blinded to the results of the CT. Results: 21 children were enrolled in the study. Five (24%) of the patients had a CT that was positive for intracranial bleeds. Of the 5 patients with a positive CT, 3 had a brain POCUS scan that was also positive. The two false negative brain POCUS scans were on patients with small bleeds (no surgical intervention required) on CT, as reported by radiology. The sensitivity of brain POCUS was 60% (CI 15% - 95%) with a specificity of 94% (CI 70%-100%). The diagnostic accuracy of brain POCUS was 86% (CI 64% - 97%). Conclusion: This small proof of concept study shows that brain POCUS is an imaging modality with reasonable sensitivity and specificity in identifying intracranial pathologies that are present on CT. Its use may be most beneficial to expedite definitive imaging and subspeciality involvement., Competing Interests: The authors have no conflicts of interest to disclose. All funding was awarded through the Research Institute at the Children’s Hospital of Eastern Ontario, Fellow Research Grant., (Copyright (c) 2023 Stephanie Davenport, Nadya Ben Fadel , Jorge Davila, Nick Barrowman, Vid Bijelic , Allan Shefrin.)

Purpose: Pain catastrophizing (PC) is the tendency to magnify the threat value of pain sensations and is associated with greater postsurgical pain intensity, functional disability, and pain chronicity. Higher parental PC predicts higher chronic postsurgical pain in youth. Treating PC in caregivers and youth prior to surgery may improve recovery and surgical outcomes. We developed and evaluated a psychoeducational workshop addressing PC for presurgical youth and their parents/caregivers. We hypothesized that parent/caregiver and youth PC scores would decrease over time. We also explored preintervention levels of youth anxiety and depression as moderators of outcome., Methods: Youth (n = 43) and caregivers (n = 41) attended a virtual, group-based single-session intervention (SSI). Single-session intervention content addressed pain neuroscience, PC, and adaptive coping strategies for managing pain and PC drawn from cognitive-behavioural, acceptance and commitment, and dialectical behaviour therapy approaches. Participants completed questionnaires assessing PC at preintervention, postintervention, and two weeks postsurgery. Youth mood and anxiety were assessed at preintervention., Results: Caregiver PC scores decreased from pre- to postintervention (P = 0.006), and this was maintained at postsurgery (P = 0.002). Youth PC scores decreased from preintervention to postsurgery, but only for those with higher preintervention anxiety (P = 0.01)., Conclusion: Our results provide proof-of-concept support for a virtual SSI targeting caregivers and youth PC during the perioperative period. The present findings highlight the possible need to screen presurgical candidates for symptoms of anxiety. Replication with larger and more diverse samples, and a more robust design are warranted., (© 2023. Canadian Anesthesiologists' Society.)

Background: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU., Methods: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial., Results: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%)., Conclusions: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up., Clinicaltrials: gov NCT02452762 Registered 25/05/2015., (© 2023. BioMed Central Ltd., part of Springer Nature.)