Sylvain A. Lother

Background: Blastomycosis is a rare but potentially life-threatening infection caused by Blastomyces spp that is endemic in the Canadian provinces of Manitoba and northwestern Ontario. Given evolving epidemiology of endemic mycoses, we sought to evaluate the provincial experience managing inpatients with blastomycosis over time. The objectives were to describe the risk factors and predictors of poor outcomes among patients hospitalized with blastomycosis throughout Manitoba. Methods: We performed a provincial retrospective cohort study by identifying all culture-positive clinical specimens yielding Blastomyces spp within Manitoba, using the Provincial Lab Information System. We included all adult patients who required admission to hospital for infectious manifestations of microbiologically confirmed blastomycosis since 2006. We used a multivariate regression model to predict associations with mortality. Results: Of 317 patients with culture-positive Blastomyces spp, we included 141 hospitalized patients across 7 hospitals. Overall, in-hospital mortality was 24%. The presence of chest pain at presentation to hospital (odds ratio, 3.24 [95% confidence interval, 1.26–8.83]) was associated with mortality. Hospital admissions, intensive care unit admissions, and mortality have a positive temporal trend over the study period. Conclusions: Blastomycosis is associated with significant morbidity and mortality, both of which is increased over time. Further studies are needed to evaluate effective diagnostic and treatment strategies to improve outcomes.

Purpose. The global health emergency caused by the COVID-19 pandemic exposed critical gaps in emergency medicine research infrastructure, particularly the absence of resources to support rapid, coordinated clinical trials during crises. We summarized key discussions from a 2025 international summit of EM trialists and researchers and present recommendations to strengthen global preparedness for future pandemics and health emergencies. Methods. An international pre-conference summit was held during the 24th International Conference on Emergency Medicine in Montreal, Canada, in May 2025. Eighteen invited speakers and four panel discussions examined the structure, operations, barriers, and facilitators of national and international EM research networks. All presentations and discussions were audio-recorded, transcribed, and manually verified. Transcripts were summarized and thematically analyzed using an iterative qualitative approach. Summit participants were invited to contribute to the development of recommendations. Results. Five interrelated themes emerged: (1) building learning health systems, (2) sustainable funding and infrastructure, (3) citizen and community partnership, (4) collaboration at and with the front line, and (5) timely data access and linkages. These themes informed ten recommendations to improve trial readiness, including expanding research capacity in community emergency departments, harmonizing data and regulatory processes, embedding research in routine care, supporting innovative trial designs, and strengthening international collaboration. Conclusion. Strengthening emergency medicine research preparedness requires sustained investment in integrated networks, interoperable data infrastructure, and trial-ready platforms that are embedded within clinical care. Centering patient and community engagement and fostering international collaboration are essential to enabling timely, high-quality evidence generation during future crises.

Legionella is an underdiagnosed and underreported etiology of pneumonia. Legionella pneumophila serogroup 1 (LpSG1) is thought to be the most common pathogenic subgroup. This assumption is based on the frequent use of a urinary antigen test (UAT), only capable of diagnosing LpSG1. We aimed to explore the frequency of Legionella infections in individuals diagnosed with pneumonia and the performance of diagnostic methods for detecting Legionella infections. We conducted a scoping review to answer the following questions: (1) “Does nucleic acid testing (NAT) increase the detection of non-pneumophila serogroup 1 Legionella compared to non-NAT?”; and (2) “Does being immunocompromised increase the frequency of pneumonia caused by non-pneumophila serogroup 1 Legionella compared to non-immunocompromised individuals with Legionnaires’ disease (LD)?”. Articles reporting various diagnostic methods (both NAT and non-NAT) for pneumonia were extracted from several databases. Of the 3449 articles obtained, 31 were included in our review. The most common species were found to be L. pneumophila, L. longbeachae, and unidentified Legionella species appearing in 1.4%, 0.9%, and 0.6% of pneumonia cases. Nearly 50% of cases were caused by unspecified species or serogroups not detected by the standard UAT. NAT-based techniques were more likely to detect Legionella than non-NAT-based techniques. The identification and detection of Legionella and serogroups other than serogroup 1 is hampered by a lack of application of broader pan-Legionella or pan-serogroup diagnostics.

Background: Community acquired pneumonia (CAP) is a common cause of morbidity and mortality globally. Poor outcomes are driven by maladaptive inflammatory and thrombotic host responses. Effective therapies that modulate host responses are lacking. Anti-platelet medications modulate thrombotic and inflammatory pathways and improve long term outcomes in COVID-19 pneumonia, however, the role of anti-platelets in other etiologies of CAP remains uncertain. Methods: We will conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies including adult patients hospitalized for non-COVID-19 community acquired pneumonia (CAP) investigating the effect of anti-platelets (ASA or P2Y12 inhibitors) vs. control on all-cause mortality. We will search electronic databases including MEDLINE® (Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), clinical trial registries (clinicaltrials.gov, International Clinical Trials Registry Platform) and conference abstracts from inception to August 2023. Two blinded reviewers will extract data in parallel from included studies after title and abstract screening and application of eligibility criteria. We will use the Cochrane Risk of Bias tool and Newcastle Ottawa Scale to assess risk of bias and study quality from included studies. The primary meta-analysis will be conducted separately for RCTs and observational studies using Random effect inverse variance model. For observational studies, adjusted mortality estimates will be presented as hazard ratios (HR) or adjusted odds ratios (OR) whenever possible. Heterogeneity will be expressed using the I ² statistic. The evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Discussion: The overall treatment effect and safety of anti-platelets in non-COVID-19 CAP will be summarized. The findings may be used to inform the relevance and potential study design of a future RCT evaluating anti-platelets in CAP. If anti-platelets are shown to be safe and effective, this research is expected to contribute to a new standard of treatment for CAP, and a paradigm shift towards targeting host responses in serious infections. Systematic Review Registration: This protocol is reported in accordance with the guidelines produced by PRISMA-P. The protocol was registered with Open Science Framework on January 30, 2024 (DOI https://doi.org/10.17605/OSF.IO/H2G7C )

There is no known effective oral therapy for early COVID-19. This randomized trial evaluated effects of oral hydroxychloroquine on symptoms and disease severity in adult outpatients with early COVI... Visual Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 There is no known effective oral therapy for early COVID-19. This randomized, double-blind, placebo-controlled trial... Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients....

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease (COVID-19) pandemic. Currently, there is a lack of evidence-based therapies to prevent COVID-19 following exposure to the virus, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis (PEP) and pre-emptive therapy (PET) for COVID-19. Methods We will conduct two nested multicentre international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) PEP of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) PET for symptomatic outpatients with COVID-19 showing symptoms for less than four days. We will recruit 1,500 patients each for the PEP and PET trials. Participants will be randomized 1:1 to receive five days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized, hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow-up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. Discussion These complementary randomized-controlled trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce virus transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. Trials registration clinicaltrials.gov (NCT04308668); registered 16 March, 2020.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease 2019 (COVID-19) pandemic. Currently, there are a lack of evidence-based therapies to prevent COVID-19 following exposure, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis and pre-emptive therapy for COVID-19. Methods: We will conduct two nested multicenter international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) post-exposure prophylaxis (PEP) of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) pre-emptive therapy (PET) for symptomatic outpatients with COVID-19 with a total symptom duration of less than 4 days. We will recruit 1500 patients for each the PEP and PET trials. Participants will be randomized 1:1 to receive 5 days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19 disease. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized; hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. Discussion: These complementary randomized control trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted in order to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. Trials Registration: clinicaltrials.gov ( NCT04308668 ); 16 March 2020.