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Importance: Hospitalizations for eating disorders rose dramatically during the COVID-19 pandemic. Public health restrictions, or stringency, are believed to have played a role in exacerbating eating disorders. Few studies of eating disorders during the pandemic have extended to the period when public health stringency restrictions were lifted., Objective: To assess the association between hospitalization rates for eating disorders and public health stringency during the COVID-19 pandemic and after the easing of public health restrictions., Design, Setting, and Participants: This Canadian population-based cross-sectional study was performed from April 1, 2016, to March 31, 2023, and was divided into pre-COVID-19 and COVID-19-prevalent periods. Data were provided by the Canadian Institute for Health Information and the Institut National d'Excellence en Santé et Services Sociaux for all Canadian provinces and territories. Participants included all children and adolescents aged 6 to 20 years., Exposure: The exposure was public health stringency, as measured by the Bank of Canada stringency index., Main Outcomes and Measures: The primary outcome was hospitalizations for a primary diagnosis of eating disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code F50), stratified by region, age group, and sex. Interrupted time series analyses based on Poisson regression were used to estimate the association between the stringency index and the rate of hospitalizations for eating disorders., Results: During the study period, there were 11 289 hospitalizations for eating disorders across Canada, of which 8726 hospitalizations (77%) were for females aged 12 to 17 years. Due to low case counts in other age-sex strata, the time series analysis was limited to females within the 12- to 17-year age range. Among females aged 12 to 17 years, a 10% increase in stringency was associated with a significant increase in hospitalization rates in Quebec (adjusted rate ratio [ARR], 1.05; 95% CI, 1.01-1.07), Ontario (ARR, 1.05; 95% CI, 1.03-1.07), the Prairies (ARR, 1.08; 95% CI, 1.03-1.13), and British Columbia (ARR, 1.11; 95% CI, 1.05-1.16). The excess COVID-19-prevalent period hospitalizations were highest at the 1-year mark, with increases in all regions: Quebec (RR, 2.17), Ontario (RR, 2.44), the Prairies (RR, 2.39), and British Columbia (RR, 2.02)., Conclusion and Relevance: In this cross-sectional study of hospitalizations for eating disorders across Canada, hospitalization rates for eating disorders in females aged 12 to 17 years were associated with public health measure stringency. The findings suggest that future pandemic preparedness should consider implications for youths at risk for eating disorders and their resource and support needs.

Background: Mycobacterium abscessus complex (MABC), an opportunistic nontuberculous mycobacteria (NTM), can lead to poor clinical outcomes in pulmonary infections. Conflicting data exist on person-to-person transmission of MABC within and across healthcare facilities. To investigate further, a comprehensive retrospective study across five healthcare institutions on the Island of Montréal was undertaken., Methods: We analyzed the genomes of 221 MABC isolates obtained from 115 individuals (2010-2018) to identify possible links. Genetic similarity, defined as ≤25 single-nucleotide polymorphisms (SNPs), was investigated through a blinded epidemiological inquiry., Results: Bioinformatics analyses identified 28 sequence types (STs), including globally observed dominant circulating clones (DCCs). Further analysis revealed 210 isolate pairs within the SNP threshold. Among these pairs, there was one possible lab contamination where isolates from different patients processed in the same lab differed by only 2 SNPs. There were 37 isolate pairs from patients who had provided specimens from the same hospital; however, epidemiological analysis found no evidence of healthcare-associated person-to-person transmission between these patients. Additionally, pan-genome analysis showed higher discriminatory power than core genome analysis for examining genomic similarity., Conclusions: Genomics alone is insufficient to establish MABC transmission, particularly considering the genetic similarity and wide distribution of DCCs, although pan-genome analysis has the potential to add further insight. Our findings indicate that MABC infections in Montréal are unlikely attributable to healthcare-associated person-to-person transmission., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To assess the seroprevalence of infection-acquired SARS-CoV-2 and the mental health of school/daycare staff in the months after reopening of schools in Montreal, Quebec (Canada) in the Fall of 2020 and whether these varied by school and participant characteristics., Design: A cross-sectional design based on a convenience sample of schools/daycares and staff was used as the originally planned longitudinal design was no longer feasible due to obstacles in recruitment, for example, teacher's strike., Setting: Forty-nine schools/daycares in four Montreal neighbourhoods from March to October 2021., Participants: Three-hundred and sixty-two participants completed both questionnaires and serology tests., Primary and Secondary Outcome Measures: SARS-CoV-2 seroprevalence and prevalence of anxiety, depression, resilience and burnout/emotional exhaustion., Results: The seroprevalence estimate made representative to the Quebec population of educators was 8.6% (95% CI 5.2 to 13.0). The adjusted seroprevalence in high school was 20% that of elementary school (aRR=0.20, 95% CI 0.07 to 0.58). Thirty per cent of seropositive staff were exposed to a household member with confirmed COVID-19. Prevalence of high emotional exhaustion/burnout was 35%, 44% and 53% in daycare, elementary school and high school staff, respectively. However, moderate/severe anxiety and depression and low resilience did not exceed 18%. After adjusting for confounders, being very afraid of catching COVID-19 at school was associated with moderate-severe anxiety, moderate-severe depression and high emotional exhaustion (aRR=4.4, 95% CI 2.2 to 8.9; aRR=2.8, 95% CI 1.5 to 5.4; aRR=2.2, 95% CI 1.6 to 3.0, respectively)., Conclusion: The seroprevalence, anxiety and depression among school/daycare staff were comparable to the reported levels in the adult population of Quebec. The prevalence of emotional exhaustion/burnout was high across all school levels and exceeding the average across all occupations in the USA and in teachers in Germany., Competing Interests: Competing interests: JP reports grants from MedImmune, grants and personal fees from Merck and AbbVie, and personal fees from AstraZeneca, all outside the submitted work. All other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Given the potential consequences associated with urinary tract infections (UTI), it has become standard practice to use continuous antibiotic prophylaxis (CAP) in children, even if controversial. We reviewed the effectiveness of CAP on recurrent UTI in a pediatric population to determine if equipoise remains and allow for a placebo control group to study the effectiveness of the vaccine MV140., Method: We completed a rapid review. We searched Medline, Embase and the Cochrane Library and data extraction was completed by a single reviewer. Our search criteria were 2005-2022, English and French language, randomized controlled trials (RCTs) and systematic reviews only. The population was 19 years and younger, including: vesicoureteral reflux (VUR), congenital anomalies of the kidneys and urinary tracts (CAKUT), and bladder and bowel dysfunction (BBD)., Results: Three RCTs and three systematic reviews found a benefit for CAP, mostly for a population with VUR, and those with severe VUR have more benefit. Most studies were not able to show a difference in the rate of UTIs or new renal scars (NRS). Three RCTs found a deleterious effect with CAP. Other studies were able to prove a benefit for patients with dilatation of the urinary tract without obstruction and high-grade VUR combined with BBD. The major adverse event found was antimicrobial resistance., Conclusions: High-risk patients benefit from CAP. The potential consequences of UTIs makes it unethical to use a placebo-only control group for them; however, CAP use seems difficult to justify in a low-risk population.

Background: Workplace violence (WPV) is a complex global challenge in healthcare that can only be addressed through a quality improvement initiative composed of a complex intervention. However, multiple WPV-specific quality indicators are required to effectively monitor WPV and demonstrate an intervention's impact. This study aims to determine a set of quality indicators capable of effectively monitoring WPV in healthcare., Methods: This study used a modified Delphi process to systematically arrive at an expert consensus on relevant WPV quality indicators at a large, multisite academic health science centre in Toronto, Canada. The expert panel consisted of 30 stakeholders from the University Health Network (UHN) and its affiliates. Relevant literature-based quality indicators which had been identified through a rapid review were categorised according to the Donabedian model and presented to experts for two consecutive Delphi rounds., Results: 87 distinct quality indicators identified through the rapid review process were assessed by our expert panel. The surveys received an average response rate of 83.1% in the first round and 96.7% in the second round. From the initial set of 87 quality indicators, our expert panel arrived at a consensus on 17 indicators including 7 structure, 6 process and 4 outcome indicators. A WPV dashboard was created to provide real-time data on each of these indicators., Conclusions: Using a modified Delphi methodology, a set of quality indicators validated by expert opinion was identified measuring WPV specific to UHN. The indicators identified in this study were found to be operationalisable at UHN and will provide longitudinal quality monitoring. They will inform data visualisation and dissemination tools which will impact organisational decision-making in real time., Competing Interests: Competing interests: RS has received support from the Quality Improvement Physicians Grant, University Health Network. BMRL has received support from the Quality Improvement Physicians Grant, University Health Network. JG has received support from the Quality Improvement Physicians Grant, University Health Network. BS has received support from the Quality Improvement Physicians Grant, University Health Network. TH has nothing to declare. JH has nothing to declare. MT is on the board of Health Insurance Reciprocal of Canada. CS-Q has received education scholarship support from Academic Scholars Award, Department of Psychiatry, University of Toronto, and Young Leaders Program and Cancer Experience Program, Princess Margaret Cancer Center, University Health Network and the Quality Improvement Physicians Grant, University Health Network. He is on the board of directors for the Canadian Academy for Consultation and Liaison Psychiatry. He is the Provincial Quality Lead Psychiatry–Psychosocial Oncology at Ontario Health, Ontario, Canada., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The COVID-19 pandemic resulted in multiple socially restrictive public health measures and reported negative mental health impacts in youths. Few studies have evaluated incidence rates by sex, region, and social determinants across an entire population., Objective: To estimate the incidence of hospitalizations for mental health conditions, stratified by sex, region, and social determinants, in children and adolescents (hereinafter referred to as youths) and young adults comparing the prepandemic and pandemic-prevalent periods., Design, Setting, and Participants: This Canadian population-based repeated ecological cross-sectional study used health administrative data, extending from April 1, 2016, to March 31, 2023. All youths and young adults from 6 to 20 years of age in each of the Canadian provinces and territories were included. Data were provided by the Canadian Institute for Health Information for all provinces except Quebec; the Institut National d'Excellence en Santé et en Services Sociaux provided aggregate data for Quebec., Exposures: The COVID-19-prevalent period, defined as April 1, 2020, to March 31, 2023., Main Outcomes and Measures: The main outcome measures were the prepandemic and COVID-19-prevalent incidence rates of hospitalizations for anxiety, mood disorders, eating disorders, schizophrenia or psychosis, personality disorders, substance-related disorders, and self-harm. Secondary measures included hospitalization differences by sex, age group, and deprivation as well as emergency department visits for the same mental health conditions., Results: Among Canadian youths and young adults during the study period, there were 218 101 hospitalizations for mental health conditions (ages 6 to 11 years: 5.8%, 12 to 17 years: 66.9%, and 18 to 20 years: 27.3%; 66.0% female). The rate of mental health hospitalizations decreased from 51.6 to 47.9 per 10 000 person-years between the prepandemic and COVID-19-prevalent years. However, the pandemic was associated with a rise in hospitalizations for anxiety (incidence rate ratio [IRR], 1.11; 95% CI, 1.08-1.14), personality disorders (IRR, 1.21; 95% CI, 1.16-1.25), suicide and self-harm (IRR, 1.10; 95% CI, 1.07-1.13), and eating disorders (IRR, 1.66; 95% CI, 1.60-1.73) in females and for eating disorders (IRR, 1.47; 95% CI, 1.31-1.67) in males. In both sexes, there was a decrease in hospitalizations for mood disorders (IRR, 0.84; 95% CI, 0.83-0.86), substance-related disorders (IRR, 0.83; 95% CI, 0.81-0.86), and other mental health disorders (IRR, 0.78; 95% CI, 0.76-0.79)., Conclusions and Relevance: This cross-sectional study of Canadian youths and young adults found a rise in anxiety, personality disorders, and suicidality in females and a rise in eating disorders in both sexes in the COVID-19-prevalent period. These results suggest that in future pandemics, policymakers should support youths and young adults who are particularly vulnerable to deterioration in mental health conditions during public health restrictions, including eating disorders, anxiety, and suicidality.

The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been indicated for pregnant women in Quebec, Canada since 2018. Recent literature suggests maternal Tdap interferes with the pneumococcal vaccine response in children exposed in utero because of maternally transferred anti-diphtheria antibodies, a phenomenon known as blunting. Using an indirect cohort study, we investigated whether maternal Tdap vaccination could alter the protection of PCV vaccines against serotype 19A/F IPD (conjugated to diphtheria toxoid in PCV10). Thirty-seven immunized IPD cases (serotype 19A/F) and 90 immunized IPD controls (non-vaccine serotypes) were analyzed using multivariate logistic regression. Our analyses did not identify antenatal Tdap exposure as a risk factor for IPD in vaccinated children, with and odds ratio close to the null (odds ratio = 0.82, 95%CI = 0.32-2.07). As this study is the first to assess the impact of maternal immunization on pneumococcal disease risk, future investigations involving a larger number of cases should be conducted to confirm or infirm our findings.

Background: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations., Methods: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied., Results: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms., Conclusions: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, and Sanofi-Pasteur; all funds have been paid to his institute, and he has not received any personal payments. VC received honoraria from Pfizer, Aralez pharmaceuticals and CSL Behring financial support for publication from CSL Behring. JEMU reports advisory board for Pfizer, clinical trials with Sanofi, and other from Novartis, all outside the current work. KZ reports honoraria from AstraZeneca and Regeneron. JMP is an investigator on projects funded by MedImmune and Merck; all funds have been paid to his institute, and he has not received any personal payments. ZA reports honoraria for speaker fees for Pfizer outside of the submitted work. AM received honoraria for presentations from Pfizer and Sanofi. ADR participated in multicentric studies with ALK for sublingual immunotherapy as investigator. AC received honoraria for presentations from Pfizer, AstraZeneca, GlaxoSmithKline and Moderna. JC received honoraria for presentations from Pfizer, AstraZeneca, and GlaxoSmithKline. KAT has received funding to her institution from the Coalition for Epidemic Preparedness Innovations for vaccine safety studies. All other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This scoping review aimed to assess the non-standardized decision-making process of National or International Immunization Technical Advisory Groups (NITAG) in developing novel off-label recommendations by examining the supportive evidence., Methods: We used the Joanna Briggs Institute framework. A search strategy was developed with a librarian to identify recommendations and evidence from peer-reviewed and gray literature until January 2022, using PubMed, Medline, EMBASE, clinicaltrials.gov, the International Clinical trials registry, governmental agency and pharmaceutical websites, the Global NITAG Network center website, and Google Scholar. Recommendations involving one of 26 pre-identified vaccine-preventable diseases, human use, and the introduction of a novel change across time and countries, were included. Evidence regarding efficacy/effectiveness, safety, or immunogenicity were included. Recommendations for fast-track approval, unlabeled or individual level off-label use, passive immunization, booster doses or provincial strategies were excluded. Only English and French documents were included. Two reviewers reviewed title/abstracts and full-text documents, and three performed data extraction. The primary outcome was the presence and elements of the evidence., Findings: Out of 4023 documents, 12 were included, and 116 were found through manual search. Over the 40-year span captured (1982-2018), most recommendations were from the last two decades and included evidence, except three from the 1990s. Most included safety (69.2%) and immunogenicity (65.4%) studies and randomized controlled trials (57.7%). Indication-based recommendations included RCTs more often (84.6%) than posology-based recommendations (30.8%). There was evidence involving populations or vaccines different from those in the recommendation., Interpretation: Critical outcomes evidence is not systematically included in off-label recommendations, nor must it involve the exact population or vaccine(s) of concern. However, in recent years, more off-label recommendations include critical outcome evidence, mainly RCTs., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Evaluate the effects of five disinfection methods on bacterial concentrations in hospital sink drains, focusing on three opportunistic pathogens (OPs): Serratia marcescens, Pseudomonas aeruginosa and Stenotrophomonas maltophilia., Design: Over two years, three sampling campaigns were conducted in a neonatal intensive care unit (NICU). Samples from 19 sink drains were taken at three time points: before, during, and after disinfection. Bacterial concentration was measured using culture-based and flow cytometry methods. High-throughput short sequence typing was performed to identify the three OPs and assess S. marcescens persistence after disinfection at the genotypic level., Setting: This study was conducted in a pediatric hospitals NICU in Montréal, Canada, which is divided in an intensive and intermediate care side, with individual rooms equipped with a sink., Interventions: Five treatments were compared: self-disinfecting drains, chlorine disinfection, boiling water disinfection, hot tap water flushing, and steam disinfection., Results: This study highlights significant differences in the effectiveness of disinfection methods. Chlorine treatment proved ineffective in reducing bacterial concentration, including the three OPs. In contrast, all other drain interventions resulted in an immediate reduction in culturable bacteria (4-8 log) and intact cells (2-3 log). Thermal methods, particularly boiling water and steam treatments, exhibited superior effectiveness in reducing bacterial loads, including OPs. However, in drains with well-established bacterial biofilms, clonal strains of S. marcescens recolonized the drains after heat treatments., Conclusions: Our study supports thermal disinfection (>80°C) for pathogen reduction in drains but highlights the need for additional trials and the implementation of specific measures to limit biofilm formation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bourdin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Group 2 innate lymphoid cells (ILC2s) rapidly induce a type 2 inflammation in the lungs in response to allergens. Here, we focused on the role of iron, a critical nutritional trace element, on ILC2 function and asthma pathogenesis. We found that transferrin receptor 1 (TfR1) is rapidly up-regulated and functional during ILC2 activation in the lungs, and blocking transferrin uptake reduces ILC2 expansion and activation. Iron deprivation reprogrammed ILC2 metabolism, inducing a HIF-1α-driven up-regulation of glycolysis and inhibition of oxidative mitochondrial activity. Consequently, we observed that in vivo iron chelation or induction of hypoferremia reduced the development of airway hyperreactivity in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s rapidly induced TfR1 during activation, whereas inhibition of iron uptake or iron deprivation reduced effector functions. Last, we found a negative relationship between circulating ILC2 TfR1 expression and airway function in cohorts of patients with asthma. Collectively, our studies define cellular iron as a critical regulator of ILC2 function.

Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here, we report that Piezo1 channels repress group 2 innate lymphoid cell (ILC2)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human-circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s, and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma., (© 2024 Hurrell et al.)

Background: Sex impacts individuals' response to vaccination. However, most vaccine studies do not report these differences disaggregated by sex. The aim of this study was to assess sex differences in the immunogenicity and efficacy of influenza vaccine., Methods: We performed a meta-analysis using phase 3 randomized controlled trial data conducted between 2010 and 2018. Using hemagglutination inhibition antibody titers for each strain, differences in geometric mean ratios (GMRs) were calculated by sex. Risk ratios (RRs) comparing seroconversion proportions were pooled for females and males using random-effects models. Vaccine efficacy (VE) was assessed. Data were analyzed by age group (18-64 vs ≥65 years)., Results: A total of 33 092 healthy adults from 19 studies were included for immunogenicity analysis, and 6740 from 1 study for VE. Whereas no sex differences in immunogenicity were found in adults <65 years old, older females had a significantly greater chance to seroconvert compared to older males for all strains: RR H1N1 = 1.17 [95% confidence interval {CI}, 1.12-1.23]; RR H3N2 = 1.09 [95% CI, 1.05-1.14]; RR Victoria = 1.23 [95% CI, 1.14-1.31]; RR Yamagata = 1.22 [95% CI, 1.14-1.30]. GMRs were also higher in older females for all strains compared to older males. VE in preventing laboratory-confirmed influenza was higher in older females compared to older males with VEs of 27.32% (95% CI, 1.15%-46.56%) and 6.06% (95% CI, -37.68% to 35.90%), respectively., Conclusions: Our results suggest a higher immunogenicity and VE in females compared to males in older adults. These differences in immunogenicity and VE support the disaggregation of vaccine data by sex in clinical trials and observational studies., Clinical Trials Registration: CRD42018112260., Competing Interests: Potential conflicts of interest. M. S. has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi Pasteur, CSL-Seqirus, Symvivo, and VBI Vaccines, all paid to institution. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two-dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show thatBT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary immunoglobulin (Ig)G and IgA levels against the Omicron spike and enhanced reactivity to the ancestral spike for the IgA isotype, which also reacted with SARS-CoV-1. Serumneutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for the development of intranasal vaccines that could emulate the enhanced mucosal and humoral immunity induced by Omicron BT without exposing individuals to the risks associated with SARS-CoV-2 infection., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period., Methods: Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466)., Findings: Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline., Conclusions: PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity., Funding: This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific., Competing Interests: Declaration of interests J.D.R. has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services, Inc. (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Center for Mental Health, Joseph M. West Family Memorial Fund, and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion, Braxia Health, Braxia Scientific Corp., and COMPASS. R.S.M. has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC), and the Milken Institute and speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. R.S.M. is a CEO of Braxia Scientific Corp. C.S.-Q. has received education scholarship support from Academic Scholars Award, Department of Psychiatry, University of Toronto, and Young Leaders Program and Cancer Experience Program, Princess Margaret Cancer Center, University Health Network. He is on the board of directors for the Canadian Academy for Consultation and Liaison Psychiatry. M.G.B. currently works as an independent contractor serving clients for psychedelic-assisted psychotherapy with Braxia Scientific Corp.; in a consulting role, he owns stake in a psychedelic technology company called Entheosense and has received speaking fees as an honorarium for providing a training lecture on psychedelic spiritual care for psychotherapists in this Braxia clinical trial. R.B.M. has received research grant support from the CIHR, the PSI Foundation, and the Baszucki Brain Research Fund and an Academic Scholars Award, Department of Psychiatry, University of Toronto. F.A.G. has received research grant support from the Brain & Behavior Research Foundation (BBRF), Southeastern Ontario Academic Medical Organization (SEAMO), and Queen’s Health Sciences and speaker/consultation fees from Lundbeck, Otsuka, and Abbvie. Z.D., RN, is a clinical project lead with Braxia Scientific Corp. J.B. was a paid co-chair of a psilocybin therapist training event with Braxia Scientific Corp., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Workplace violence (WPV) in healthcare is a growing challenge posing significant risks to patient care and employee well-being. Existing metrics to measure WPV in healthcare settings often fail to provide decision-makers with an adequate reflection of WPV due to the complexity of the issue. This increases the difficulty for decision-makers to evaluate WPV in healthcare settings and implement interventions that can produce sustained improvements., Objective: This study aims to identify and compile a list of quality indicators that have previously been utilized to measure WPV in healthcare settings. The identified quality indicators serve as tools, providing leadership with the necessary information on the state of WPV within their organization or the impact of WPV prevention interventions. This information provides leadership with a foundation for planning and decision making related to addressing WPV., Methods: Ovid databases were used to identify articles relevant to violence in healthcare settings, from which 43 publications were included for data extraction. Data extraction produced a total of 229 quality indicators that were sorted into three indicator categories using the Donabedian model: structure, process, and outcome., Results: A majority of the articles (93%) contained at least 1 quality indicator that possessed the potential to be operationalized at an organizational level. In addition, several articles (40%) contained valuable questionnaires or survey instruments for measuring WPV. In total, the rapid review process identified 84 structural quality indicators, 121 process quality indicators, 24 outcome quality indicators, 57 survey-type questions and 17 survey instruments., Conclusions: This study provides a foundation for healthcare organizations to address WPV through systematic approaches informed by quality indicators. The utilization of indicators showed promise for characterizing WPV and measuring the efficacy of interventions. Caution must be exercised to ensure indicators are not discriminatory and are suited to specific organizational needs. While the findings of this review are promising, further investigation is needed to rigorously evaluate existing literature to expand the list of quality indicators for WPV., (© 2024. The Author(s).)

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry , reflectometry , sounding , interferometry , plasma characterization , and ranging . Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world., Competing Interests: Competing InterestsThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2024.)

Background: We identified patient characteristics associated with an increased risk of developing MIS-C., Methods: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders., Results: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development., Conclusions: Children with pre-existing morbidity have a considerably elevated risk of MIS-C., Impact: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Molecular typing techniques are utilized to determine genetic similarities between bacterial isolates. However, the use of environmental DNA profiling to assess epidemiologic links between patients and their environment has not been fully explored. This work reports the development and validation of two high-throughput short sequence typing (HiSST) schemes targeting the opportunistic pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia , along with a modified SM2I selective medium for the specific isolation of S. maltophilia . These HiSST schemes are based on four discriminative loci for each species and demonstrate high discriminating power, comparable to pairwise whole-genome comparisons. Each scheme includes species-specific PCR primers for precise differentiation from closely related taxa, without the need for upstream culture-dependent methods. For example, the primers targeting the bvgS locus make it possible to distinguish P. aeruginosa from the very closely related Pseudomonas paraeruginosa sp. nov. The selected loci included in the schemes are adapted to massive parallel amplicon sequencing technology. An R-based script implemented in the DADA2 pipeline was assembled to facilitate HiSST analyses for efficient and accurate genotyping of P. aeruginosa and S. maltophilia . We demonstrate the performance of both schemes through in silico validations, assessments against reference culture collections, and a case study involving environmental samples.

Objectives: Psychological interventions for advanced cancer patients are effective in decreasing distress but are not well integrated into cancer care. Oncology nurses are well positioned to deliver such interventions, and their participation may enhance professional satisfaction and wellbeing. Managing Cancer and Living Meaningfully (CALM) is an evidence-based psychotherapy supporting advanced cancer patients. A CALM-Nurses (CALM-N) training program was developed to teach oncology nurses the basics of CALM for use in daily practice. Feasibility and acceptability of CALM-N and its impact on professional wellbeing were assessed in this pilot study., Data Sources: Fifty-five nurses attended CALM-N in three groups. Thirty-five nurses completed the first e-learning, 29 nurses (83%) attended the first group session, and 22 (63%) attended all sessions. At baseline, 35 questionnaires were collected. Response rate at follow-up was 63% for Jefferson Scale of Empathy (n=22), 66% for self-efficacy scale (n=23), and for subscales of Professional Quality of Life Scale burnout; 51% (n=18), secondary traumatic stress; 49% (n=17), compassion satisfaction; 57% (n=20). A statistically significant increase in self-efficacy was found, but there were no significant changes in PROQOL and empathy. Focus groups suggested CALM-N helped nurses' understanding of patients and nurse-patient communication and increased reflection and perspective taking., Conclusion: CALM-N is a feasible and acceptable intervention for oncology nurses, with the potential to improve nurse-patient communication and the nurses' reflective capacities., Implications for Nursing Practice: CALM-N has the potential to improve the capacity of oncology nurses to provide psychosocial care for advanced cancer patients and its application to nursing practice merits further investigation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Froukje de Vries reports financial support was provided by University of Toronto Temerty Faculty of Medicine. Merel van Klinken was a Guest Editor for the ‘End of life care in Cancer’ Special Issue of Seminars in Oncology Nursing. As an author of this article, she did not participate in any editorial process or decision-making, which was handled by another editor., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Despite being a vaccine-preventable disease, influenza remains a major public health threat with vaccine safety concerns reducing vaccine acceptability. Immune responses to vaccines and adverse events may differ between males and females, but most studies do not report results by sex. Using data from clinical trials, we explored sex differences in adverse events following seasonal influenza vaccines., Methods: We obtained data for phase III randomised controlled trials identified through a systematic review and clinical trials registries, and performed a two-stage meta-analysis. Risk ratios (RR) and 95% confidence intervals (95% CI) comparing solicited reactions in females versus males were pooled using the Mantel-Haenszel method and a random-effects model. We used the ROBINS-I tool to assess risk of bias and the I 2 statistic for heterogeneity. Main analysis was stratified by age: 18-64 years and ≥65 years., Results: The dataset for this analysis included 34 343 adults from 18 studies (12 with individual-level data and 6 with aggregate data). There was a higher risk of injection site reactions in females compared with males for both younger and older participants, with RRs of 1.29 (95% CI 1.21 to 1.37) and 1.43 (95% CI 1.28 to 1.60), respectively. Higher risk in females was also observed for systemic reactions, with RRs of 1.25 (95% CI 1.20 to 1.31) and 1.27 (95% CI 1.20 to 1.34) for younger and older participants, respectively. We also observed elevated risks of severe reactions in females, with a higher RR in younger versus older participants for systemic reactions (RRs 2.12 and 1.48, p=0.03, I 2 =79.7%). RRs were not found to vary between quadrivalent and trivalent vaccines., Conclusion: This meta-analysis suggested a higher risk of solicited reactions following influenza vaccines for females compared with males, irrespective of age and vaccine type. Transparent communication of this risk could increase the trust in vaccines and limit vaccine hesitancy. Future studies should report results stratified by sex and explore the role of gender in the occurrence of adverse events., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments; there are no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious health problems that manifest as acute respiratory failure in response to different conditions, including viral respiratory infections. Recently, the inhibitory properties of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) were demonstrated in allergic and viral airway inflammation. In this study, we investigate the implication of LAIR-1 in ALI/ARDS and explore the underlying mechanisms. Polyinosinic:polycytidylic acid, a synthetic analog of double-stranded RNA, was used to mimic acute inflammation in viral infections. We demonstrate that LAIR-1 is predominantly expressed on macrophages and regulates their recruitment to the lungs as well as their activation in response to polyinosinic:polycytidylic acid. Interestingly, LAIR-1 deficiency increases neutrophil recruitment as well as lung resistance and permeability. In particular, we highlight the capacity of LAIR-1 to regulate the secretion of CXCL10, considered a key marker of macrophage overactivation in acute lung inflammation. We also reveal in COVID-19-induced lung inflammation that LAIR1 is upregulated on lung macrophages in correlation with relevant immune regulatory genes. Altogether, our findings demonstrate the implication of LAIR-1 in the pathogenesis of ALI/ARDS by means of the regulation of macrophages, thereby providing the basis of a novel therapeutic target., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has challenged traditional vaccine guidance infrastructure and frameworks, and added urgency and complexity to the operation of National Immunization Technical Advisory Groups (NITAGs). Canada's National Advisory Committee on Immunization (NACI) provides immunization guidance to the Public Health Agency of Canada (PHAC) who publicly shares expert and evidence-informed guidance with Canadian provinces and territories. Throughout the pandemic, NACI and PHAC implemented many adaptations to meet urgent needs for pandemic vaccine guidance. In this paper, we describe: structural adaptations in response to the accelerated pace and amount of work required to issue recommendations that were timed around product authorizations and dynamic epidemiology; technical adaptations in response to rapidly evolving evidence of variable quality which required close monitoring, and which promoted reliance on basic vaccine principles due to incomplete direct evidence; the need to provide nimble advice (e.g., off-label recommendations, preferential recommendations); communications adaptations (e.g. identify sustainable spokespeople for the committee, receive stakeholder feedback, and ensure urgent nuanced advice was communicated to a diverse audience); and research adaptations focussing on solutions to constrained supply (e.g. prioritisation, extended intervals, and heterologous schedules). The early pandemic vaccine experience has created a roadmap of lessons and adaptations that should be leveraged in future pandemic vaccine programs, and has highlighted the essential role of NITAGs to complement regulatory structures during pandemics to ensure timely, impactful, and evidence-informed public health vaccine guidance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew Tunis, Shainoor Ismail, Marina Salvadori, Bryna Warshawsky, Kelsey Young, Christine Mauviel, and Erin Henry are employed by the Public Health Agency of Canada. Shelley Deeks and Robyn Harrison are the current Chair and Vice Chair of NACI, but not compensated for these roles. Caroline Quach was a previous Chair of NACI during the COVID-19 pandemic, but not compensated for this role. All authors contributed to the conception of the study, drafting the article, and approved the submitted version., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Streptococcus pneumoniae serotype 19A is a highly diverse, often antimicrobial-resistant Gram-positive bacterium which can cause invasive pneumococcal disease (IPD). In 2021, public health authorities in the Canadian province of Québec observed an increase of serotype 19A IPD in children <5 years. The purpose of this study was to determine the clonal composition of serotype 19A isolates collected from this age group in Québec, from 2016 to 2021. Forty-one and 37 IPD isolates from children <5 years from Québec and the remainder of Canada, respectively, were sequenced using the Illumina NextSeq platform. Phylogenetic analysis using SNVPhyl identified three clusters, corresponding to three common clones of serotype 19A: CC199, CC320 and ST695. CC199, predominantly represented by ST416, accounted for similar proportions of serotype 19A isolates collected from children in Québec (19.5 %) and other Canadian jurisdictions (OCJs, 21.6 %), with significant presence of ermB (62.5 % and 60 % of ST416 isolates, respectively). CC320 was more commonly identified from OCJs in comparison to Québec (18.9 % vs. 7.3 %, respectively), but were highly antimicrobial-resistant regardless of region. ST695 was the most common clone of serotype 19A collected in Québec from children <5 years, representing 65.9 % of isolates collected over the study period (40.5 % of isolates collected in OCJs). Phylogenetic analysis identified geographical differences in ST695 across Canada; including a large clade specific to Québec (with both susceptible and macrolide-resistant [ermB] subclades), and a separate macrolide-resistant (mefA) clade associated with OCJs. The Québec-specific ermB-ST695 clone represented 48.1 % of ST695 collected from the province. Continued genomic surveillance of S. pneumoniae serotype 19A is required to: i) track the prevalence and clonal composition of serotype 19A in Québec in future years; ii) characterize the clonal distribution of serotype 19A in adult populations; and iii) monitor whether the currently geographically restricted ermB-ST695 clone observed in Québec expands to OCJs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Disparities in youth COVID-19 vaccine acceptance and uptake have been documented in several countries, yet few studies have explored the attitudes and perceptions underlying vaccine-related decision-making among adolescent populations with unique sociocultural, environmental, and/or structural contexts that may influence vaccine uptake., Methods: This study used data from surveys and semistructured interviews collected between January and March 2022 as part of an ongoing community-based research project in two ethnoculturally diverse, lower income neighborhoods of Montreal, Canada. Youth researchers designed and conducted interviews with unvaccinated adolescents, and thematic analysis was employed to explore attitudes and perceptions underlying vaccine-related decisions and opinions about vaccine passports. Survey data were used to describe sociodemographic and psychological determinants of COVID-19 vaccination., Results: Among 315 survey participants aged 14-17 years, most (74%) were fully vaccinated against COVID-19. Prevalence ranged from 57% among Black adolescents to 91% among South and/or Southeast Asian adolescents (34% difference, 95% confidence interval: 20-49). Qualitative and quantitative findings highlighted several misconceptions about the safety, effectiveness, and necessity of COVID-19 vaccines and adolescents' desire for trusted sources of information to address their concerns. Vaccine passports likely increased uptake, yet adolescents were strongly resistant to the policy, and for some, it may have fueled distrust of government and scientific institutions., Discussion: Strategies that increase the trustworthiness of institutions and foster genuine partnership with underserved youth may improve vaccine confidence and help ensure an effective, proequity recovery from COVID-19., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010-2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Potential conflicts of interest The sponsor had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, and preparation, review, and approval of the manuscript. This research received no other external financial or non-financial support. All co-authors have nothing to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe clinical disorders that mainly develop from viral respiratory infections, sepsis, and chest injury. Antigen-presenting cells play a pivotal role in propagating uncontrolled inflammation and injury through the excess secretion of pro-inflammatory cytokines and recruitment of immune cells. Autophagy, a homeostatic process that involves the degradation of cellular components, is involved in many processes including lung inflammation. Here, we use a polyinosinic-polycytidylic acid (poly(I:C))-induced lung injury mouse model to mimic viral-induced ALI/ARDS and show that disruption of autophagy in macrophages exacerbates lung inflammation and injury, whereas autophagy induction attenuates this process. Therefore, induction of autophagy in macrophages can be a promising therapeutic strategy in ALI/ARDS., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The EnCORE study is a prospective serology study of SARS-CoV-2 in a cohort of children from Montreal, Canada. Based on data from our fourth round of data collection (May-October 2022), we estimated SARS-CoV-2 seroprevalence and seroconversion. Using multivariable regression, we identified factors associated with seroconversion. Our results show that previously seronegative children were approximately 9-12 times more likely to seroconvert during the early Omicron-dominant period compared to pre-Omicron rounds. Unlike the pre-Omicron rounds, the adjusted rate of seroconversion among 2- to 4-year-olds was higher than older age groups. As seen previously, higher seroconversion rates were associated with ethnic/racial minority status., Competing Interests: JP reports grants from MedImmune, grants and personal fees from Merck and AbbVie, and personal fees from AstraZeneca, all outside the submitted work., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

The lesbian, gay, bisexual, transgender, queer/questioning and two-spirited, plus (LGBTQ2 +) community experiences cancer-related health disparities and inequities. Our objective was to assess LGBTQ2 + knowledge, attitudes, practices and education interest of healthcare professionals (HCPs), identify opportunities to improve care and inform the development of an HCP education curriculum. This was a mixed methods quality improvement study conducted within a tertiary academic cancer centre. An email was sent to all gynaecologic oncology disease site staff (n = 92) with a secure link to an online survey. We measured respondents' sociodemographic characteristics and LGBTQ2 + knowledge, attitudes, practice behaviours and education interest. Open comments explored HCP experiences and reservations caring for LGBTQ2 + patients and suggestions to improve care. Seventy-five out of ninety-two (82%) HCPs completed the survey, with 7% identifying as LGBTQ2 + . HCPs reported feeling less comfortable (88% vs. 80%, p = 0.031) and knowledgeable (44% vs. 27%, p < 0.001) caring for transgender patients compared to LGBQ2 + patients. Most (76%) were unaware whether LGBTQ2 + -specific patient educational materials existed within their institution. Almost all (92% strongly agreed/agreed) were interested in receiving LGBTQ2 + -specific education. Two themes emerged from analysis of open comments: (i) HCPs are concerned of offending LGBTQ2 + individuals because of their lack of knowledge and (ii) HCPs desire LGBTQ2 + -specific health training, specifically in asking pronouns and caring for transgender patients. HCPs report competency gaps in caring for LGBTQ2 + patients with cancer but desire education. In response, we recommend institutions develop an educational curriculum for HCPs improve communication and inclusivity in cancer care., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

In a tertiary-care, pediatric healthcare center in Québec, Canada, healthcare workers who reported a household exposure to confirmed coronavirus disease 2019 (COVID-19) cases were allowed to work. On repeated testing, 15% became severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive by reverse-transcription polymerase chain reaction (RT-PCR), with no nosocomial transmission. Being asymptomatic and receiving a booster dose >7 days prior to exposure was protective against becoming SARS-CoV-2-positive by PCR.

Objectives: To use serological testing to assess the pre-Omicron seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montréal, Canada., Design: This analysis is from a prospective cohort study of children aged 2-17 years (at baseline) that included blood spots for antibody detection. The serostatus of participants was determined by enzyme-linked immunosorbent assays using the receptor-binding domain from the spike protein and the nucleocapsid protein as antigens. We estimated seroprevalence, seroconversion rates, and the likelihood of seroreversion at 6 months and 1 year., Results: The baseline (October 2020 to April 2021) seroprevalence was 5.8% (95% confidence interval [CI] 4.8-7.1), which increased to 10.5% (May to September 2021) and 11.0% (November 2021 to March 2022) for the respective follow-ups (95% CI 8.6-12.7; 95% CI 8.8-13.5). The crude rate of seroconversion over the study period was 12.8 per 100 person-years (95% CI 11.0-14.7). The adjusted hazard rates of seroconversion by child characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes in the lowest tercile of our study population. The likelihood of remaining seropositive at 6 months was 68% (95% CI 60-77%) and dropped to 42% (95% CI 32-56%) at 1 year., Conclusion: Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels after infection., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Compelling evidence suggests a contribution of the sink environment to the transmission of opportunistic pathogens from the hospital environment to patients in neonatal intensive care units (NICU). In this study, the distribution of the opportunistic pathogen Serratia marcescens in the sink environment and newborns in a NICU was investigated. More than 500 sink drain and faucet samples were collected over the course of five sampling campaigns undertaken over 3 years. Distribution and diversity of S. marcescens were examined with a modified MacConkey medium and a high-throughput short-sequence typing (HiSST) method. Sink drains were an important reservoir of S. marcescens, with an average of 44% positive samples, whereas no faucet sample was positive. The genotypic diversity of S. marcescens was moderate, with an average of two genotypes per drain, while the spatial distribution of S. marcescens was heterogeneous. The genotypic profiles of 52 clinical isolates were highly heterogeneous, with 27 unique genotypes, of which 71% of isolates were found in more than one patient. S. marcescens acquisition during the first outbreaks was mainly caused by horizontal transmissions. HiSST analyses revealed 10 potential cases of patient-to-patient transmission of S. marcescens, five cases of patient-to-sink transmission, and one bidirectional transfer between sink and patient. Environmental and clinical isolates were found in sink drains up to 1 year after the first detection, supporting persisting drain colonization. This extensive survey suggests multiple reservoirs of S. marcescens within the NICU, including patients and sink drains, but other external sources should also be considered. IMPORTANCE The bacterium Serratia marcescens is an important opportunistic human pathogen that thrives in many environments, can become multidrug resistant, and is often involved in nosocomial outbreaks in neonatal intensive care units (NICU). We evaluated the role of sinks during five suspected S. marcescens outbreaks in a NICU. An innovative approach combining molecular and culture methods was used to maximize the detection and typing of S. marcescens in the sink environment. Our results indicate multiple reservoirs of S. marcescens within the NICU, including patients, sink drains, and external sources. These results highlight the importance of sinks as a major reservoir of S. marcescens and potential sources of future outbreaks., Competing Interests: The authors declare no conflict of interest.

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 D 3 +10 000 IU weekly vitamin D 3 ) 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cannabis use by adolescents is widespread, but its effects on the ovaries remain largely unknown. Δ9-tetrahydrocannabinol (THC) exerts its pharmacological effects by activating, and in some conditions hijacking, cannabinoid receptors (CBRs). We hypothesized that adolescent exposure to THC affects ovarian function in adulthood. Peripubertal female C57BL/6N mice were given THC (5 mg/kg) or its vehicle, once daily by intraperitoneal injection. Some mice received THC from postnatal day (PND) 30-33 and their ovaries were harvested PND34; other mice received THC from PND30-43, and their ovaries were harvested PND70. Adolescent treatment with THC depleted ovarian primordial follicle numbers by 50% at PND70, 4 weeks after the last dose. The treatment produced primordial follicle activation, which persisted until PND70. THC administration also caused DNA damage in primary follicles and increased PUMA protein expression in oocytes of primordial and primary follicles. Both CB1R and CB2R were expressed in oocytes and theca cells of ovarian follicles. Enzymes involved in the formation (N-acylphosphatidylethanolamine phospholipase D) or deactivation (fatty acid amide hydrolase) of the endocannabinoid anandamide were expressed in granulosa cells of ovarian follicles and interstitial cells. Levels of mRNA for CBR1 were significantly increased in ovaries after adolescent THC exposure, and upregulation persisted for at least 4 weeks. Our results support that adolescent exposure to THC may cause aberrant activation of the ovarian endocannabinoid system in female mice, resulting in substantial loss of ovarian reserve in adulthood. Relevance of these findings to women who frequently used cannabis during adolescence warrants investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This document is part of the "SHEA Neonatal Intensive Care Unit (NICU) White Paper Series." It is intended to provide practical, expert opinion, and/or evidence-based answers to frequently asked questions about CLABSI detection and prevention in the NICU. This document serves as a companion to the CDC Healthcare Infection Control Practices Advisory Committee (HICPAC) Guideline for Prevention of Infections in Neonatal Intensive Care Unit Patients. Central line-associated bloodstream infections (CLABSIs) are among the most frequent invasive infections among infants in the NICU and contribute to substantial morbidity and mortality. Infants who survive CLABSIs have prolonged hospitalization resulting in increased healthcare costs and suffer greater comorbidities including worse neurodevelopmental and growth outcomes. A bundled approach to central line care practices in the NICU has reduced CLABSI rates, but challenges remain. This document was authored by pediatric infectious diseases specialists, neonatologists, advanced practice nurse practitioners, infection preventionists, members of the HICPAC guideline-writing panel, and members of the SHEA Pediatric Leadership Council. For the selected topic areas, the authors provide practical approaches in question-and-answer format, with answers based on consensus expert opinion within the context of the literature search conducted for the companion HICPAC document and supplemented by other published information retrieved by the authors. Two documents in the series precede this one: "Practical approaches to Clostridioides difficile prevention" published in August 2018 and "Practical approaches to Staphylococcus aureus prevention," published in September 2020.

Purpose of the Review: Sexual and gender diverse (SGD) cancer patients possess unique identities and needs that must be considered during their cancer care. This narrative review explores the current literature on sexual and gender diversity in cancer care and survivorship, in addition to providing recommendations encouraged by the current literature., Recent Findings: We performed a literature search for articles published in English between January 2021 and June 2022 in Medline ALL and Embase. Fifty-two studies were included in this review. The many identities encapsulated in 2SLGBTQIA+ (2 Spirited, Lesbian, Gay, Bisexual, Transgender, Queer, Intersexual, Asexual, Agender, Aromantic and all gender identities and sexual orientations that are not listed) communities each have their own unique backgrounds, needs and disparities in cancer care and survivorship. However, we also identified specific protective factors in the cancer experience of SGD patients such as reports of higher resiliency and stronger support networks. Much of the recent research features recommendations on improving cancer care by creating inclusive patient questionnaires, improving in-person and online resources, and educating healthcare providers and patient-facing staff on inclusive care., Summary: SGD patients have their own specific challenges during and following their cancer care. As the research continues to grow, we gain a better understanding of the needs of these patients and future steps to take to improve SGD patients' cancer experience., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections., Methods: We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated., Findings: A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics., Interpretation: These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions targeting RSV, such as vaccines, for IPD prevention should be considered., Funding: The study was supported by a grant from the Quebec Ministry of Health and Social Services (' ministère de la Santé et des Services sociaux du Québec' ). Publication was supported by a grant from "Fondation de l'Assistance Publique - Hôpitaux de Paris et de l'Alliance « Tous Unis contre le Virus » (Fondation de France/Institut Pasteur/APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award., Competing Interests: N.O. reports travel grants from Pfizer, Sanofi, and GSK, outside the present work. B.L. received research grants from Pfizer. All other authors report no potential conflicts., (© 2023 The Authors.)

Background: The prevalence of multiple sclerosis (MS) in older people is increasing due to population aging and availability of effective disease-modifying therapies (DMTs). Treating older people with MS is complicated by age-related and MS-related comorbidities, immunologic effects of prior DMTs, and immunosenescence. Teriflunomide is a once-daily oral immunomodulator that has demonstrated efficacy and acceptable safety in clinical trials of adults with relapsing forms of MS (RMS). However, there are limited clinical trial and real-world data regarding teriflunomide use in people with MS aged >55 years. We analyzed real-world data to assess the effectiveness and safety of teriflunomide in older people with RMS who had switched to this agent from other DMTs., Methods: People with RMS (relapsing remitting and active secondary progressive MS) aged ≥55 years who had switched from other DMTs to teriflunomide (7 mg or 14 mg) for ≥1 year were identified retrospectively by chart review at four sites in the United States. Data were extracted from medical records from 1 year pre-index to 2 years post-index (index defined as the teriflunomide start date). Assessments of effectiveness included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging (MRI) outcomes. Assessments of safety included lymphocyte counts, infections, and malignancies. We examined the effectiveness outcomes and lymphocyte counts within sub-groups defined by age (55-64, ≥65 years), sex, MS type, and prior route of DMT administration (oral, injectable, infusible)., Results: In total, 182 patients with RMS aged ≥55 years who switched from other DMTs to teriflunomide were identified (mean [SD] age: 62.5 [5.4] years). Mean ARR decreased from the start of teriflunomide treatment (mean [SD]: 0.43 [0.61]) to year 1 post-index (0.13 [0.65]) and year 2 post-index (0.05 [0.28]). Mean EDSS score remained unchanged from index (mean [SD]: 4.5 [1.8]) to 1 year post-treatment (4.5 [1.8]) and increased slightly at 2 years post-treatment (4.7 [1.7]). MRI scans from index and years 1 and 2 post-index compared with scans from the previous year indicated that most patients had stable or improved MRI outcomes at index (87.7%) and remained stable or improved at years 1 (96.0%) and 2 (93.6%). Lymphopenia decreased at years 1 (21.4%) and 2 post-index (14.8%, compared to index (23.5%). By 1 year post-index, fewer patients had grade 3 or 4 lymphopenia, and at 2 years post-index, there were no patients with grade 3 or 4 lymphopenia. Infection incidence was low (n = 40, 22.0%) and none were related to teriflunomide. The decreases in lymphopenia were driven by decreases among people who switched from a prior oral DMT; there were no notable differences in lymphopenia across the other sub-groups examined. ARR, EDSS score, and MRI outcomes across all sub-groups were similar to the results of the overall population., Conclusion: Our multicenter, longitudinal, retrospective study demonstrated that patients with RMS aged 55 or older switching to teriflunomide from other DMTs had significantly improved ARR, stable disability, and stable or improved MRI over up to 2 years' follow up. Safety results were acceptable with fewer patients exhibiting lymphopenia at years 1 and 2 post-index., (Copyright © 2022. Published by Elsevier B.V.)

Aims: We assessed the impact of Covid-19 on gestational diabetes rates in Quebec, the pandemic epicenter of Canada., Methods: We conducted a population-based study of 569,686 deliveries in Quebec between 2014 and 2021. We measured gestational diabetes rates in wave 1 (March 1, 2020-August 22, 2020) and wave 2 (August 23, 2020-March 31, 2021), compared with the prepandemic period. We used interrupted time series regression to assess changes in gestational diabetes rates during each wave, and log-binomial regression models to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of the pandemic with gestational diabetes. We identified the types of patients that contributed to the change in gestational diabetes rates using Kitagawa's decomposition., Results: Gestational diabetes rates were higher during the first (13.2 per 100 deliveries) and second waves (14.3 per 100 deliveries) than during the prepandemic period (12.4 per 100 deliveries). Risk of gestational diabetes increased both in wave 1 (RR 1.05, 95% CI 1.02-1.09) and wave 2 (RR 1.14, 95% CI 1.10-1.18), compared with the prepandemic period. However, most of the increase in gestational diabetes rates was driven by low-risk women without Covid-19 infections who were socioeconomically advantaged, had no comorbidity, and were 25-34 years of age., Conclusions: Gestational diabetes rates increased during the pandemic, mainly among women traditionally at low risk of hyperglycemia who did not have Covid-19 infections. Sudden widespread changes in screening or lifestyle can have a large impact on gestational diabetes rates in a population., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Neutrophilic asthma is associated with disease severity and corticosteroid insensitivity. Novel therapies are required to manage this life-threatening asthma phenotype. Programmed cell death protein-1 (PD-1) is a key homeostatic modulator of the immune response for T-cell effector functions., Objective: We sought to investigate the role of PD-1 in the regulation of acute neutrophilic inflammation in a murine model of airway hyperreactivity (AHR)., Methods: House dust mite was used to induce and compare neutrophilic AHR in wild-type and PD-1 knockout mice. Then, the therapeutic potential of a human PD-1 agonist was tested in a humanized mouse model in which the PD-1 extracellular domain is entirely humanized. Single-cell RNA sequencing and flow cytometry were mainly used to investigate molecular and cellular mechanisms., Results: PD-1 was highly induced on pulmonary T cells in our inflammatory model. PD-1 deficiency was associated with an increased neutrophilic AHR and high recruitment of inflammatory cells to the lungs. Consistently, PD-1 agonist treatment dampened AHR, decreased neutrophil recruitment, and modulated cytokine production in a humanized PD-1 mouse model. Mechanistically, we demonstrated at the transcriptional and protein levels that the inhibitory effect of PD-1 agonist is associated with the reprogramming of pulmonary effector T cells that showed decreased number and activation., Conclusions: PD-1 agonist treatment is efficient in dampening neutrophilic AHR and lung inflammation in a preclinical humanized mouse model., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Antidepressants require several weeks for the onset of action, a lag time that may exceed life expectancy in palliative care. Ketamine has demonstrated rapid antidepressant effects, but has been minimally studied in cancer and palliative care populations. Herein, the objective was to determine the feasibility, safety, tolerability and preliminary efficacy of intranasal racemic ketamine for major depressive disorder (MDD) in patients with advanced cancer. We conducted a single-arm, open-label phase II trial at the Princess Margaret Cancer Centre in Toronto, ON, Canada. Participants with advanced cancer with moderate to severe MDD received three flexible doses of intranasal (IN) ketamine (50−150 mg) over a one-week period. The primary efficacy outcome was an antidepressant response and remission rates as determined by the Montgomery−Åsberg Depression Rating Scale (MADRS) from baseline to the Day 8 primary endpoint. Twenty participants were enrolled in the trial, receiving at least one dose of IN ketamine, with fifteen participants receiving all three doses. The Day 8 antidepressant response (MADRS decreased by >50%) and remission (MADRS < 10 on Day 8) rates were high at 70% and 45%, respectively. Mean MADRS scores decreased significantly from baseline (mean MADRS of 31, standard deviation 7.6) to Day 8 (11 +/− 7.4) with an overall decrease of 20 points (p < 0.001). Antidepressant effects were partially sustained in the second week in the absence of additional ketamine doses, with a Day 14 mean MADRS score of 14 +/− 9.9. Common adverse effects included fatigue, dissociation, nausea, dysgeusia and headaches; almost all adverse effects were mild and transient, resolving within 2 h of each ketamine dose with one dropout related to adverse effects (negative dissociative episode). Given these promising findings, larger, controlled trials are merited.

Objective: Throughout the COVID-19 pandemic, there have been concerns about the mental health of health care workers (HCW). Although numerous studies have investigated the level of distress among HCW, few studies have explored programs to improve their mental well-being. In this paper, we describe the implementation and evaluation of a program to support the mental health of HCW at University Health Network (UHN), Canada's largest healthcare network., Methods: Using a quality improvement approach, we conducted a needs assessment and then created and evaluated a modified stepped-care model to address HCW mental health during the pandemic. This included: online resources focused on psychoeducation and self-management, access to online support and psychotherapeutic groups, and self-referral for individual care from a psychologist or psychiatrist. We used ongoing mixed-methods evaluation, combining quantitative and qualitative analysis, to improve program quality., Results: The program is ongoing, running continuously throughout the pandemic. We present data up to November 30, 2021. There were over 12,000 hits to the UHN's COVID mental health intranet web page, which included self-management resources and information on group support. One hundred and sixty-six people self-referred for individual psychological or psychiatric care. The mean wait time from referral to initial appointment was 5.4 days, with an average of seven appointments for each service user. The majority had moderate to severe symptoms of depression and anxiety at referral, with over 20% expressing thoughts of self-harm or suicide. Post-care user feedback, collected through self-report surveys and semistructured interviews, indicated that the program is effective and valued., Conclusions: Development of a high-quality internal mental health support for HCW program is feasible, effective, and highly valued. By using early and frequent feedback from multiple perspectives and stakeholders to address demand and implement changes responsively, the program was adjusted to meet HCW mental health needs as the pandemic evolved.

Background: The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial., Methods: In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vitamin D 3 or placebo. The co-primary outcomes were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75 nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented., Results: Thirty-four (19 intervention, 15 control) subjects were randomized, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95% CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95% CI:1.6, 22.9). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported., Conclusion: The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation., Trial Registration: This trial was registered at https://clinicaltrials.gov on July 23, 2020 (# NCT04483635 )., (© 2022. The Author(s).)

Background: SARS-CoV-2 transmission has an impact on education. In this study, we assessed the performance of rapid antigen detection tests (RADTs) versus polymerase chain reaction (PCR) for the diagnosis of SARS-CoV-2 infection in school settings, and RADT use for monitoring exposed contacts., Methods: In this real-world, prospective observational cohort study, high-school students and staff were recruited from 2 high schools in Montréal, Canada, and followed from Jan. 25 to June 10, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared with those of other high schools in the same area., Results: Overall, 2099 students and 286 school staff members consented to participate. The overall specificity of RADTs varied from 99.8% to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR result on days 6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 51 (72.5%) were secondary to household transmission, 13 (25.5%) to intraschool transmission, and 1 to community contacts between students in the same school., Interpretation: Rapid antigen detection tests did not perform well compared with PCR in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADTs on the spot may avoid subsequent substantial exposures in class. Preprint: medRxiv - doi.org/10.1101/2021.10.13.21264960., Competing Interests: Competing interests: Ana Blanchard reports project grants from Réseau de recherche en Santé Respiratoire du Québec and Cystic Fibrosis Foundation (payments to Centre Hospitalier Universitaire Sainte-Justine). Annie-Claude Labbé reports honoraria for a lecture from Hologic, speakers honoraria from Merck and Pfizer, and provision of reagents for SARS-CoV-2 testing from Seegene, DiaSorin and Roche Diagnostics, as part of another study. Kate Zinszer reports grant funding from the Public Health Agency of Canada, Canadian Institutes of Health Research and Fonds de Recherche du Québec — Santé. Caroline Quach reports a project grant from Ministère de la Santé et des Services sociaux — Québec (payments to Centre Hospitalier Universitaire Sainte-Justine). No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Canadian long-term care facility (LTCF) residents experienced higher death rates compared to other countries during the first wave of the COVID-19 pandemic. This cohort study analyzes the individual, therapeutic, and institutional factors associated with death in LTCFs., Methods: Institutional data for 17 LTCFs in Montreal, Canada were obtained from local administrative registries. Individual data for 1197 residents infected by SARS-CoV-2 between February 23 and July 11, 2020 were obtained through chart reviews. A multivariable modified Poisson regression model, which accounted for LTCF clustering, was used to identify resident and facility covariates associated with 30-day mortality after COVID-19 diagnosis., Results: Severe shortage of licensed practical nurses (RR 2.60 95% CI 1.20-5.61) and medium-sized facilities compared to smaller-sized facilities (RR 2.73 95% CI 1.23-6.07) were associated with 30-day mortality. Later COVID-19 diagnosis (RR 0.98 95% CI 0.97-0.99 per additional day) was associated with survival. Individual risk factors for death included age (RR 1.33 95% CI 1.23-1.45 per additional 10 years), male sex (RR 1.46 95% CI 1.24-1.71), functional impairment (RR 1.08 95% CI 1.04-1.12 per unit increase of SMAF), as well as a diagnosis of congestive heart failure (RR 1.31 95% CI 1.04-1.66) and neurocognitive disorder (RR 1.31 95% CI 1.01-1.70). Among severe cases, anticoagulation was associated with survival (RR 0.70 95% CI 0.51-0.96)., Conclusions: This study identified practical nurse shortages and facility size as institutional risk factors for COVID-19 death. Anticoagulation was associated with survival among severe cases., (© 2022 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)