Overdose deaths and the COVID-19 pandemic in British Columbia, Canada.

INTRODUCTION: British Columbia (BC) declared an overdose public health emergency in 2016. Since then, BC has consistently reported the highest overdose death rates of any province in Canada. In the context of the COVID-19 pandemic, overdose deaths in BC reached a record high in 2020. This analysis reports on changes in the profile of people who have died of overdose since BC's declaration of COVID-19 as a public health emergency on 17 March 2020. METHODS: Using BC Coroners Service data, Chi-square tests and multivariable logistic regression were conducted to compare demographic, geographic and post-mortem toxicology data between people who died of overdose before (17 March-31 December 2019) and after (17 March-31 December 2020) BC's declaration of COVID-19 as a public health emergency. RESULTS: Overdose deaths observed since 17 March 2020 (n = 1516) more than doubled those observed in the same period in 2019 (n = 744). In the adjusted logistic regression model, odds of death in the post compared to pre-COVID-19 period was significantly higher among males compared to females, among all older age groups compared to people aged 30-39, and was lower in public buildings compared to private residences. DISCUSSION AND CONCLUSIONS: Alongside a significant increase in overdose deaths since BC's declaration of COVID-19 as a public health emergency, the demographic profile of people who have died of overdose has changed. Ongoing overdose prevention efforts in BC must seek to reach people who remain most isolated, including older adults, who during dual public health emergencies are facing compounded risk of preventable mortality.

Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta-analysis.

Preclinical studies suggest mesenchymal stromal cell extracellular vesicles (MSC-EVs) reduce inflammation and improve organ function in lung diseases; however, an objective analysis of all available data is needed prior to translation. Using rigorous meta-research methods, we determined the effectiveness of MSC-EVs for preclinical respiratory diseases and identified experimental conditions that may further refine this therapy. A systematic search of MEDLINE/Embase identified 1167 records. After screening, 52 articles were included for data extraction and evaluated for risk of bias and quality of reporting in study design. A random effects meta-analysis was conducted for acute lung injury (ALI; N = 23), bronchopulmonary dysplasia (BPD; N = 8) and pulmonary arterial hypertension (PAH; N = 7). Subgroup analyses identified EV methods/characteristics that may be associated with improved efficacy. Data is presented as standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CI). For ALI, MSC-EVs markedly reduced lung injury (SMD -4.33, CI -5.73 to -2.92), vascular permeability (SMD -2.43, CI -3.05 to -1.82), and mortality (RR 0.39, CI 0.22 to 0.68). Small EVs were more consistently effective than large EVs whereas no differences were observed between tissue sources, immunocompatibility or isolation techniques. For BPD, alveolarization was improved by MSC-EVs (SMD -1.45, CI -2.08 to -0.82) with small EVs more consistently beneficial then small/large EVs. In PAH, right ventricular systolic pressure (SMD -4.16, CI -5.68 to -2.64) and hypertrophy (SMD -2.80, CI -3.68 to -1.91) were significantly attenuated by EVs. In BPD and PAH, EVs isolated by ultracentrifugation demonstrated therapeutic benefit whereas tangential flow filtration (N = 2) displayed minimal efficacy. Lastly, risk of bias and quality of reporting for experimental design were consistently unclear across all studies. Our findings demonstrate clear potential of MSC-EVs to be developed as therapy for acute and chronic lung diseases. However, greater transparency in research design and direct comparisons of isolation technique and EV subtypes are needed to generate robust evidence to guide clinical translation. Protocol Registration: PROSPERO CRD42020145334.