The association between recreational cannabis legalization, commercialization and cannabis-attributable emergency department visits in Ontario, Canada: an interrupted time-series analysis.

BACKGROUND AND AIMS: Recreational cannabis was legalized in Canada in October 2018. Initially, the Government of Ontario (Canada's largest province) placed strict limits on the number of cannabis retail stores before later removing these limits. This study measured changes in cannabis-attributable emergency department (ED) visits over time, corresponding to different regulatory periods. DESIGN: Interrupted time-series design using population-level data. Two policy periods were considered; recreational cannabis legalization with strict store restrictions (RCL, 17 months) and legalization with no store restrictions [recreational cannabis commercialization (RCC), 15 months] which coincided with the COVID-19 pandemic. Segmented Poisson regression models were used to examine immediate and gradual effects in each policy period. SETTING: Ontario, Canada. PARTICIPANTS: All individuals aged 15-105 years (n = 13.8 million) between January 2016 and May 2021. MEASUREMENTS: Monthly counts of cannabis-attributable ED visits per capita and per all-cause ED visits in individuals aged 15+ (adults) and 15-24 (young adults) years. FINDINGS: We observed a significant trend of increasing cannabis-attributable ED visits pre-legalization. RCL was associated with a significant immediate increase of 12% [incident rate ratio (IRR) = 1.12, 95% confidence interval (CI) = 1.02-1.23] in rates of cannabis-attributable ED visits followed by significant attenuation of the pre-legalization slope (monthly slope change IRR = 0.98, 95% CI = 0.97-0.99). RCC and COVID-19 were associated with immediate significant increases of 22% (IRR = 1.22, 95% CI = 1.09-1.37) and 17% (IRR = 1.17, 95% CI = 1.00-1.37) in rates of cannabis-attributable visits and the proportion of all-cause ED visits attributable to cannabis, respectively, with insignificant increases in monthly slopes. Similar patterns were observed in young adults. CONCLUSIONS: In Ontario, Canada, cannabis-attributable emergency department visits stopped increasing over time following recreational cannabis legalization with strict retail controls but then increased during a period coinciding with cannabis commercialization and the COVID-19 pandemic.

Physician Health Care Visits for Mental Health and Substance Use During the COVID-19 Pandemic in Ontario, Canada.

Importance: Physicians self-report high levels of symptoms of anxiety and depression, and surveys suggest these symptoms have been exacerbated by the COVID-19 pandemic. However, it is not known whether pandemic-related stressors have led to increases in health care visits related to mental health or substance use among physicians. Objective: To evaluate the association between the COVID-19 pandemic and changes in outpatient health care visits by physicians related to mental health and substance use and explore differences across physician subgroups of interest. Design, Setting, and Participants: A population-based cohort study was conducted using health administrative data collected from the universal health system (Ontario Health Insurance Plan) of Ontario, Canada, from March 1, 2017, to March 10, 2021. Participants included 34 055 physicians, residents, and fellows who registered with the College of Physicians and Surgeons of Ontario between 1990 and 2018 and were eligible for the Ontario Health Insurance Plan during the study period. Autoregressive integrated moving average models and generalized estimating equations were used in analyses. Exposures: The period during the COVID-19 pandemic (March 11, 2020, to March 10, 2021) compared with the period before the pandemic. Main Outcomes and Measures: The primary outcome was in-person, telemedicine, and virtual care outpatient visits to a psychiatrist or family medicine and general practice clinicians related to mental health and substance use. Results: In the 34 055 practicing physicians (mean [SD] age, 41.7 [10.0] years, 17 918 [52.6%] male), the annual crude number of visits per 1000 physicians increased by 27%, from 816.8 before the COVID-19 pandemic to 1037.5 during the pandemic (adjusted incident rate ratio per physician, 1.13; 95% CI, 1.07-1.19). The absolute proportion of physicians with 1 or more mental health and substance use visits within a year increased from 12.3% before to 13.4% during the pandemic (adjusted odds ratio, 1.08; 95% CI, 1.03-1.14). The relative increase was significantly greater in physicians without a prior mental health and substance use history (adjusted incident rate ratio, 1.72; 95% CI, 1.60-1.85) than in physicians with a prior mental health and substance use history. Conclusions and Relevance: In this study, the COVID-19 pandemic was associated with a substantial increase in mental health and substance use visits among physicians. Physician mental health may have worsened during the pandemic, highlighting a potential greater requirement for access to mental health services and system level change.

Predicting COVID-19 cases in diverse population groups using SARS-CoV-2 wastewater monitoring across Oklahoma City.

SARS-CoV-2 was discovered among humans in late 2019 and rapidly spread across the world. Although the virus is transmitted by respiratory droplets, most infected persons also excrete viral particles in their feces. This fact prompted a range of studies assessing the usefulness of wastewater surveillance to determine levels of infection and transmission and produce early warnings of outbreaks in local communities, independently of human testing. In this study, we collected samples of wastewater from 13 locations across Oklahoma City, representing different population types, twice per week from November 2020 to end of March 2021. Wastewater samples were collected and analyzed for the presence and concentration of SARS-CoV-2 RNA using RT-qPCR. The concentration of SARS-CoV-2 in the wastewater showed notable peaks, preceding the number of reported COVID-19 cases by an average of one week (ranging between 4 and 10 days). The early warning lead-time for an outbreak or increase in cases was significantly higher in areas with larger Hispanic populations and lower in areas with a higher household income or higher proportion of persons aged 65 years or older. Using this relationship, we predicted the number of cases with an accuracy of 81-92% compared to reported cases. These results confirm the validity and timeliness of using wastewater surveillance for monitoring local disease transmission and highlight the importance of differences in population structures when interpreting surveillance outputs and planning preventive action.

One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening.

The potential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) escape mutants is a threat to the efficacy of existing vaccines and neutralizing antibody (nAb) therapies. An understanding of the antibody/S escape mutation landscape is urgently needed to preemptively address this threat. Here we describe a rapid method to identify escape mutants for nAbs targeting the S receptor binding site. We identified escape mutants for five nAbs, including three from the public germline class VH3-53 elicited by natural coronavirus disease 2019 (COVID-19) infection. Escape mutations predominantly mapped to the periphery of the angiotensin-converting enzyme 2 (ACE2) recognition site on the RBD with K417, D420, Y421, F486, and Q493 as notable hotspots. We provide libraries, methods, and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2.