ABSTRACT
BackgroundThe epidemiology of COVID-19 in retirement homes (also known as assisted living facilities) is largely unknown. We examined the association between retirement home and community level characteristics and the risk of COVID-19 outbreaks in retirement homes during the first wave of the COVID-19 epidemic. MethodsWe conducted a population-based retrospective cohort study of licensed retirement homes in Ontario, Canada, from March 1st - September 24th, 2020. Our primary outcome was a COVID-19 outbreak ([≥]1 resident or staff confirmed case by validated nucleic acid amplification assay). We used time-dependent proportional hazards methods to model the associations between retirement home and community level characteristics and COVID-19 outbreaks. ResultsOur cohort included all 770 licensed retirement homes in Ontario, which housed 56,491 residents. There were 172 (22.3%) COVID-19 retirement home outbreaks involving 1,045 (1.9%) residents and 548 staff (1.5%). COVID-19 cases were distributed unevenly across retirement homes, with 1,593 (92.2%) resident and staff cases occurring in 77 (10%) of homes. The adjusted hazard of a COVID-19 outbreak in a retirement home was positively associated with homes that had a large resident capacity, homes that were co-located with a long-term care facility, large corporate owned chains, homes that offered many services onsite, increases in regional COVID-19 incidence, and a higher community-level ethnic concentration. InterpretationReadily identifiable retirement home-level characteristics are independently associated with COVID-19 outbreaks and may support risk identification. A higher ethnic concentration of the community surrounding a retirement home is associated COVID-19 outbreaks, with an uncertain mechanism.
ABSTRACT
<p><b>INTRODUCTION</b>Efavirenz is an inducer of drug metabolism enzymes. We studied the effect of efavirenz and ritonavir-boosted darunavir on serum unconjugated and conjugated bilirubin, as probes for UGT1A1 and bile transporters.</p><p><b>MATERIALS AND METHODS</b>Healthy volunteers were enrolled in a clinical trial. There were 3 periods: Period 1, 10 days of darunavir 900 mg with ritonavir 100 mg once daily; Period 2, 14 days of efavirenz 600 mg with darunavir/ritonavir once daily; and Period 3, 14 days of efavirenz 600 mg once daily. Serum bilirubin (conjugated and unconjugated) concentrations were obtained at baseline, at the end of each phase and at exit.</p><p><b>RESULTS</b>We recruited 7 males and 5 females. One subject developed grade 3 hepatitis on efavirenz and was excluded. Mean serum unconjugated bilirubin concentrations were 6.09 μmol/L (95% confidence interval [CI], 4.99 to 7.19) at baseline, 5.82 (95% CI, 4.88 to 6.76) after darunavir/ritonavir, 4.00 (95% CI, 2.92 to 5.08) after darunavir/ritonavir with efavirenz, 3.55 (95% CI, 2.58 to 4.51) after efavirenz alone and 5.27 (95% CI, 3.10 to 7.44) at exit (P <0.01 for the efavirenz phases). Mean serum conjugated bilirubin concentrations were 3.55 μmol/L (95% CI, 2.73 to 4.36) at baseline, 3.73 (95% CI, 2.77 to 4.68) after darunavir/ritonavir, 2.91 (95% CI, 2.04 to 3.78) after darunavir/ritonavir with efavirenz, 2.64 (95% CI, 1.95 to 3.33) after efavirenz alone and 3.55 (95% CI, 2.19 to 4.90) at exit (P <0.05 for the efavirenz phases).</p><p><b>CONCLUSION</b>Efavirenz decreased unconjugated bilirubin by 42%, suggesting UGT1A1 induction. Efavirenz also decreased conjugated bilirubin by 26%, suggesting induction of bile efflux transporters. Ritonavir-boosted darunavir had no effect on bilirubin concentrations. These results indicate that efavirenz may reduce concentrations of drugs or endogenous substances metabolized by UGT1A1 or excreted by bile efflux transporters.</p>