Browsing by Author "Tsang, Jennifer L. Y."
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- Community versus academic hospital community-acquired pneumonia patients: a nested cohort studyPublication . Tsang, Jennifer L. Y.; Rego, Kian; Binnie, Alexandra; Binnie, Alexandra; Lee, Terry; Mccarthy, Anne; Cowan, Juthaporn; Archambault, Patrick; Lellouche, Francois; Turgeon, Alexis F.; Yoon, Jennifer; Lamontagne, Francois; Mcgeer, Allison; Douglas, Josh; Daley, Peter; Fowler, Robert; Maslove, David M.; Winston, Brent W.; Lee, Todd C.; Tran, Karen C.; Cheng, Matthew P.; Vinh, Donald C.; Boyd, John H.; Walley, Keith R.; Singer, Joel; Marshall, John C.; Haljan, Gregory; Jain, Fagun; Russell, James A.Background: Most Canadians receive their care in community hospitals, yet most clinical research is conducted in academic hospitals. This study aims to compare patients with community acquired pneumonia (CAP) treated in academic and community hospitals with respect to their demographics, clinical characteristics, treatments and outcomes. Methods This nested observational cohort substudy of the Community Acquired Pneumonia: Toward InnoVAtive Treatment (CAPTIVATE) trial included 1,329 hospitalized adults with CAP recruited between March 1st, 2018 and September 31st, 2023 from 15 Canadian hospitals. Unadjusted and adjusted analyses for age, sex and co-morbidities using logistic, Cox and censored quantile regressions were conducted. Results Patients in community hospitals were older (mean [SD] 75.0 [15.7] years vs. 68.3 [16.2] years; p < 0.001), were more likely to be female (49.7% vs. 41.0%, p = 0.002), and had more comorbidities (75.9% vs. 64.8%, p < 0.001). More patients in community hospitals received corticosteroids (49.2% vs. 37.4%, p < 0.001). Community hospital patients had a higher likelihood of developing acute respiratory distress syndrome (OR 3.13, 95% CI: 1.87, 5.24, p = < 0.001), and acute cardiac injury (OR 2.53, 95% CI: 1.33, 4.83, p = 0.005). In unadjusted and adjusted analyses, 28-day mortality difference did not meet statistical significance (OR 1.43, 95% CI: 0.98, 20.7, p = 0.062 and OR 1.23, 95% CI: 0.81, 1.87, p = 0.332, respective). Conclusion Patients with CAP in Canadian community and academic hospitals differed with respect to their age, clinical characteristics, treatments and outcomes, emphasizing the importance of including more community hospitals in clinical research studies to ensure the generalizability of results.
- Epigenetic profiling in severe sepsis: a pilot study of DNA methylation profiles in critical illnessPublication . Binnie, Alexandra; Walsh, Christopher J.; Hu, Pingzhao; Dwivedi, Dhruva J.; Fox-Robichaud, Alison; Liaw, Patricia C.; Tsang, Jennifer L. Y.; Batt, Jane; Carrasqueiro, Gabriela; Gupta, Sahil; Marshall, John C.; Castelo-Branco, Pedro; dos Santos, Claudia C.Objectives: Epigenetic alterations are an important regulator of gene expression in health and disease; however, epigenetic data in sepsis are lacking. To demonstrate proof of concept and estimate effect size, we performed the first epigenome-wide methylation analysis of whole blood DNA samples from a cohort of septic and nonseptic critically ill patients. Design: A nested case-control study using genomic DNA isolated from whole blood from septic (n = 66) and nonseptic (n = 68) critically ill patients on "Day 1" of ICU admission. Methylation patterns were identified using Illumina 450K arrays with percent methylation expressed as beta values. After quality control, 134 participants and 414,818 autosomal cytosine-phosphate-guanine sites were used for epigenome-wide methylation analyses. Setting: Tertiary care hospitals. Subjects: Critically ill septic and nonseptic patients. Interventions: Observational study. Measurements and Main Results: A total of 668 differentially methylated regions corresponding to 443 genes were identified. Known sepsis-associated genes included complement component 3; angiopoietin 2; myeloperoxidase; lactoperoxidase; major histocompatibility complex, class I, A; major histocompatibility complex, class II, isotype DR beta I; major histocompatibility complex, class I, C; and major histocompatibility complex, class II, isotype DQ beta I. When compared with whole blood gene expression data from seven external datasets containing septic and nonseptic patients, 81% of the differentially methylated region-associated genes were differentially expressed in one or more datasets and 31% in three or more datasets. Functional analysis showed enrichment for antigen processing and presentation, methyltransferase activity, cell adhesion, and cell junctions. Analysis by weighted gene coexpression network analysis revealed DNA comethylation modules that were associated with clinical traits including severity of illness, need for vasopressors, and length of stay. Conclusions: DNA methylation marks may provide important causal and potentially biomarker information in critically ill patients with sepsis.
- Epigenetics of sepsisPublication . Binnie, Alexandra; Tsang, Jennifer L. Y.; Hu, Pingzhao; Carrasqueiro, Gabriela; Castelo-Branco, Pedro; dos Santos, Claudia C.Recent evidence from the fields of microbiology and immunology, as well as a small number of human sepsis studies, suggest that epigenetic regulation may play a central role in the pathogenesis of sepsis. The term "epigenetics" refers to regulatory mechanisms that control gene expression but are not related to changes in DNA sequence. These include DNA methylation, histone modifications, and regulation of transcription via non-coding RNAs. Epigenetic modifications, occurring in response to external stressors, lead to changes in gene expression, and thus lie at the intersection between genetics and the environment. In this review, we examine data from in vitro studies, animal studies, and the existing human sepsis studies in epigenetics to demonstrate that epigenetic mechanisms are likely central to the pathogenesis of sepsis and that epigenetic therapies may have potential in the treatment of sepsis and its associated organ failures.
- Factors influencing community intensive care unit research participation: a qualitative descriptive studyPublication . Gehrke, Paige; Rego, Kian; Orlando, Elaina; Jack, Susan; Law, Madelyn; Cook, Deborah; Marticorena, Rosa M.; Binnie, Alexandra; Tsang, Jennifer L. Y.Purpose Community hospitals account for 90% of hospitals in Canada, but clinical research is mainly conducted in academic hospitals. Increasing community hospital research participation can improve generalizability of study results, while also accelerating study recruitment and increasing staff engagement. We aimed to identify and describe the factors that influence community intensive care unit (ICU) research participation and the development, implementation, and sustainability of a community ICU research program.MethodsWe conducted a qualitative descriptive study using semistructured interviews. Between April 2022 and May 2023, we interviewed a purposeful sample of individuals interested or involved in community hospital research in Canadian community ICUs. We analyzed qualitative data using both conventional content analysis and rapid qualitative analysis. Findings were deductively mapped out using the Ecological Model of Health Behavior. Quantitative survey data were analyzed using descriptive statistics.ResultsParticipants included 23 health care workers, ten research staff, and five hospital administrators (n = 38) from 20 community hospitals across six provinces in Canada. The main factors associated with community ICU research participation were 1) infrastructure, 2) personnel characteristics, 3) key relationships and connections, and 4) the COVID-19 pandemic.ConclusionIn this qualitative descriptive study, participants identified the physical resources, skills, and relationships required to start and sustain a clinical research program in a Canadian community ICU. Our findings suggest that all levels of the Canadian health care system need to invest in strengthening community hospital research capacity to increase research participation.
- Twenty articles that critical care clinicians should read about COVID-19Publication . Tsang, Jennifer L. Y.; Binnie, Alexandra; Fowler, Robert A.Infection with the severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) was first identified in December 2019 and has since become a worldwide pandemic, challenging and sometimes overwhelming healthcare systems as well as causing more than a million deaths thus far. In just 10 months, over 80,000 indexed publications have appeared that reference SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19). In this article, we highlight 20 papers that are of particular relevance to the critical care clinician. The papers are divided into four broad topics: manifestations of severe COVID- 19 disease, pharmacological therapy for COVID-19, ventilatory support for COVID-19 acute respiratory distress syndrome (ARDS), and healthcare system and worker stress. This list is not designed to be comprehensive but rather to give the reader an overview of important early papers and their findings.