Prevention of COVID-19 with oral vitamin D supplemental therapy in essential healthcare teams (PROTECT): protocol for a multicentre, triple-blind, randomised, placebo-controlled trial.

INTRODUCTION: In the COVID-19 pandemic, healthcare workers (HCWs) were at high risk of infection due to their exposure to COVID infections. HCWs were the backbone of our healthcare response to this pandemic; every HCW withdrawn or lost due to infection had a substantial impact on our capacity to deliver care. Primary prevention was a key approach to reduce infection. Vitamin D insufficiency is highly prevalent in Canadians and worldwide. Vitamin D supplementation has been shown to significantly decrease the risk of respiratory infections. Whether this risk reduction would apply to COVID-19 infections remained to be determined. This study aimed to determine the impact of high-dose vitamin D supplementation on incidence of laboratory-confirmed COVID-19 infection rate and severity in HCWs working in high COVID incidence areas. METHODS AND ANALYSIS: PROTECT was a triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D supplementation in HCWs. Participants were randomly allocated in a 1:1 ratio in variable block size to intervention (one oral loading dose of 100 000 IU vitamin D3+10 000 IU weekly vitamin D3) or control (identical placebo loading dose+weekly placebo). The primary outcome was the incidence of laboratory-confirmed COVID-19 infection, documented by RT-qPCR on salivary (or nasopharyngeal) specimens obtained for screening or diagnostic purposes, as well as self-obtained salivary specimens and COVID-19 seroconversion at endpoint. Secondary outcomes included disease severity; duration of COVID-19-related symptoms; COVID-19 seroconversion documented at endpoint; duration of work absenteeism; duration of unemployment support; and adverse health events. The trial was terminated prematurely, due to recruitment difficulty. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Research Ethics Board (REB) of the Centre hospitalier universitaire (CHU) Sainte-Justine serving as central committee for participating institutions (#MP-21-2021-3044). Participants provided written informed consent to participate in the study before taking part. Results are being disseminated to the medical community via national/international conferences and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/NCT04483635.

Oscillometry to support clinical assessment in asthmatic preschoolers: Real-life impact.

In preschoolers, asthma control is assessed clinically using history and physical examination. In certain centres, oscillometry is used to support clinical assessment; yet its clinical utility for asthma management remains to be quantified. The objectives were to determine if oscillometry, as adjunct to clinical assessment, influences asthma assessment, management and control, compared to clinical assessment alone in preschoolers. We conducted a cross-sectional study in children aged 3-5 years with a confirmed asthma diagnosis. Oscillometry-tested preschoolers were matched by propensity score to untested children. The co-primary outcomes, the likelihood of a persistent asthma phenotype and a maintenance therapy prescription at the index visit, were examined by multivariable logistic regression. Asthma control over the next year was examined by cumulative logistic regression in the nested retrospective cohort with available drug claim data. The cohort comprised 726 (249 oscillometry-tested; 477 untested) children with 57.4% male (median age: 4.6 years). Propensity score matching resulted in comparable groups. Compared to controls, oscillometry-tested children were more frequently labelled with a persistent phenotype (67% vs. 50%; adjusted OR [95% CI]: 2.34 [1.66-3.34]) with no significant difference in maintenance therapy prescription (65% vs. 58%; 1.37 [0.98-1.92]); but experienced a lower likelihood of poor control over the next year (adjusted OR [95% CI]: 0.24 [0.08-0.74]). The association between the addition of oscillometry to clinical assessment with more persistent phenotype labelling and better asthma control supports its clinical utility; no significant impact on maintenance therapy prescription was observed at the index visit.

Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank.

INTRODUCTION: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted. METHODS AND ANALYSIS: Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank. PROSPERO REGISTRATION NUMBERS: CRD42020132990, CRD42020171624.

Impact of two oral doses of 100,000 IU of vitamin D3 in preschoolers with viral-induced asthma: a pilot randomised controlled trial.

BACKGROUND: New evidence supports the use of supplemental vitamin D in the prevention of exacerbation of asthma; however, the optimal posology to sufficiently raise serum levels while maximising adherence is unclear. The objective was to ascertain the efficacy of high-dose vitamin D3 in increasing serum vitamin D in preschoolers with asthma and provide preliminary data on safety and efficacy outcomes. METHODS: We conducted a 7-month, triple-blind, randomised, placebo-controlled, pilot trial of children aged 1-5 years with viral-induced asthma. Participants were allocated to receive two oral doses of 100,000 IU vitamin D3 (intervention) or identical placebo (control) 3.5 months apart, once in the fall and once in the winter. Serum 25-hydroxyvitamin D (25OHD) was measured by tandem mass spectrometry at baseline, 10 days, 3.5 months, 3.5 months + 10 days, and 7 months. The main outcome was the change in serum 25OHD from baseline (Δ25OHD) over time and at 3.5 and 7 months; other outcomes included the proportion of children with 25OHD ≥ 75 nmol/L, safety, and adverse event rates. RESULTS: Children (N = 47) were randomised (intervention, 23; control, 24) in the fall. There was a significant adjusted group difference in the Δ25OHD (95% confidence interval) of 57.8 (47.3, 68.4) nmol/L, p < 0.0001), with a time (p < 0.0001) and group*time interaction effect (p < 0.0001), in favour of the intervention. A significant group difference in the Δ25OHD was observed 10 days after the first (119.3 [105.8, 132.9] nmol/L) and second (100.1 [85.7, 114.6] nmol/L) bolus; it did not reach statistical significance at 3.5 and 7 months. At 3.5 and 7 months, respectively, 63% and 56% of the intervention group were vitamin D sufficient (≥ 75 nmol/L) compared to 39% and 36% of the control group. Hypercalciuria, all without hypercalcaemia, was observed in 8.7% of intervention and 10.3% of control samples at any time point. Exacerbations requiring rescue oral corticosteroids, which appear as a promising primary outcome, occurred at a rate of 0.87/child. CONCLUSION: Two oral boluses of 100,000 IU vitamin D3,once in the fall and once in the winter, rapidly, safely, and significantly raises overall serum vitamin D metabolites. However, it is sufficient to maintain 25OHD ≥ 75 nmol/L throughout 7 months in only slightly more than half of participants. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02197702 (23 072014). Registered on 23 July 2014.

Focusing the focus group: impact of the awareness of major factors contributing to non-adherence to acute paediatric asthma guidelines.

RATIONALE: The administration of oral corticosteroids within the first hour in the emergency department is associated with reduced hospitalization rates in children with moderate and severe asthma, yet less than half of patients benefit from this recommendation. To ensure patients receive recommended treatment, a clear understanding of what is causing suboptimal care management is needed. The assessment of barriers and solutions to optimal care is often done without a thorough examination of the factors associated with non-adherence. OBJECTIVE: To evaluate whether knowledge of factors associated with delayed administration of systemic corticosteroids modifies the focus and prioritization of barriers and solutions identified by focus groups. METHODS: We conducted two parallel focus groups of emergency health care professionals - one group informed and the other non-informed of key factors. Both groups received a presentation on the acute asthma guidelines, the evidence supporting its recommendations, and current practice. In addition, the informed group was provided with the factors associated and not associated with delayed administration. The groups were given 20 minutes to discuss barriers and solutions, with 5 minutes each for voting for the main barriers and solutions. Group difference in the misdirection of discussion was measured as time spent discussing barriers that were shown not to be associated with systemic corticosteroids. Prioritization of barriers and solutions was based on group endorsement. RESULTS: The non-informed group spent more time discussing barriers not associated with delayed administration (15 vs. 2 minutes, P = 0.05). Although the non-informed group proposed more solutions, most were to overcome barriers not associated with delayed administration. Of the main barriers and solutions identified by each group, only one barrier and solution were similar between the two groups: emergency department overcrowding and administrating corticosteroids at triage. CONCLUSION: The awareness of objective factors of non-adherence enabled a more directed discussion on relevant barriers and solutions, affecting prioritization of each. The administration of oral corticosteroids at triage appears to be the best solution to overcome delayed administration.