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.

BackgroundIn order to address the opioid crisis in North America, many regions have adopted preventative strategies, such as prescription drug monitoring programs (PDMPs). PDMPs aim to increase patient safety by certifying that opioids are prescribed in appropriate quantities. We aimed to synthesize the literature on changes in opioid-related harms and consequences, an important measure of PDMP effectiveness.MethodsWe completed a systematic review. We conducted a narrative synthesis of opioid-related harms and consequences from PDMP implementation. Outcomes were grouped into categories by theme: opioid dependence, opioid-related care outcomes, opioid-related adverse events, and opioid-related legal and crime outcomes.ResultsWe included a total of 22 studies (49 PDMPs) in our review. Two studies reported on illicit and problematic use but found no significant associations with PDMP status. Eight studies examined the association between PDMP status and opioid-related care outcomes, of which two found that treatment admissions for prescriptions opioids were lower in states with PDMP programs (p < 0.05). Of the thirteen studies that reported on opioid-related adverse events, two found significant (p < 0.001 and p < 0.05) but conflicting results with one finding a decrease in opioid-related overdose deaths after PDMP implementation and the other an increase. Lastly, two studies found no statistically significant association between PDMP status and opioid-related legal and crime outcomes (crime rates, identification of potential dealers, and diversion).ConclusionOur study found limited evidence to support overall associations between PDMPs and reductions in opioid-related consequences. However, this should not detract from the value of PDMPs’ larger role of improving opioid prescribing.

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 PARTICIPANTSA population-based cohort study was conducted using health administrative data collected from the universal health system (Ontario Health Insurance

Background and objectiveThe optimal ambulatory management of renin-angiotensin-aldosterone system inhibitor (RAASi)–related hyperkalemia to reduce the risk of recurrence is unknown. We examined the risk of hyperkalemia recurrence on the basis of outpatient pharmacologic changes following an episode of RAASi-related hyperkalemia.DesignWe performed a population-based, retrospective cohort study of older adults (n=49,571; mean age 79 years) who developed hyperkalemia (potassium ≥5.3 mEq/L) while on a RAASi and were grouped as follows: no intervention, RAASi discontinuation, RAASi dose decrease, new diuretic, diuretic dose increase, or sodium polystyrene sulfonate within 30 days. The primary outcome was hyperkalemia recurrence, with secondary outcomes of cardiovascular events and all-cause mortality within 1 year.ResultsAmong patients who received a pharmacologic intervention (23% of the cohort), RAASi discontinuation was the most commonly prescribed strategy (74%), followed by RAASi decrease (15%), diuretic increase (7%), new diuretic (3%), and sodium polystyrene sulfonate (1%). A total of 16,977 (34%) recurrent hyperkalemia events occurred within 1 year. Compared with no intervention (35%, referent), the cumulative incidence of recurrent hyperkalemia was lower with RAASi discontinuation (29%; hazard ratio, 0.82; 95% confidence interval, 0.78 to 0.85), whereas there was no difference with RAASi dose decrease (36%; hazard ratio, 0.94; 95% confidence interval, 0.86 to 1.02), new diuretic (32%; hazard ratio, 0.95; 95% confidence interval, 0.78 to 1.17), or diuretic increase (38%; hazard ratio, 0.99; 95% confidence interval, 0.87 to 1.12) and a higher incidence with sodium polystyrene sulfonate (55%; hazard ratio, 1.30; 95% confidence interval, 1.04 to 1.63). RAASi discontinuation was not associated with a higher risk of 1-year cardiovascular events (hazard ratio, 0.96; 95% confidence interval, 0.91 to 1.02) or all-cause mortality (hazard ratio, 1.05; 95% confidence interval, 0.96 to 1.15) compared with no intervention.ConclusionsAmong older adults with RAASi-related hyperkalemia, RAASi discontinuation is associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in short-term risks for cardiovascular events or all-cause mortality.

nticoagulant-associated hemorrhage is one of the most common adverse drug reactions requiring hospitalization among individuals of advanced age, with a 2-fold increase among those older than 75 years. 1 Identification and avoidance of dangerous drug-drug interactions are associated with a significant reduction in adverse events and improvement in evidence-based prescription patterns.During the last decade, direct oral anticoagulants (DO-ACs) have supplanted traditional vitamin K antagonists as the anticoagulation drugs of choice. 2 Large phase 3 trials have demonstrated noninferiority or superiority of DOACs relative to traditional anticoagulants (warfarin) for effectiveness in stroke prevention for those who have atrial fibrillation and for pre-vention and treatment of venous thromboembolism. [3][4][5][6][7][8][9][10][11] Patient preferences for DOACs are based on their simplicity of use, with no need for routine bloodwork monitoring. 12 As such, recent guidelines recommend DOACs as the first-line agents for the prevention of stroke in patients with nonvalvular atrial fibrillation (strong recommendation; high-quality evidence) and the treatment of venous thromboembolism. 13,14 Direct oral anticoagulants have 2 predominant mechanisms of metabolism: P-glycoprotein (Pgp) cell transporters, which are involved in transcellular transportation, and the cytochrome P450 enzyme CYP3A4, which is involved in the metabolism in the human liver. 15 Dabigatran etexilate mesylate requires efflux transportation by the Pgp system but is independent of the cytochrome P450 enzyme system. 16 Apixaban and rivar-IMPORTANCE Clarithromycin is a commonly prescribed antibiotic associated with higher levels of direct oral anticoagulants (DOACs) in the blood, with the potential to increase the risk of hemorrhage.OBJECTIVE To assess the 30-day risk of a hospital admission with hemorrhage after coprescription of clarithromycin compared with azithromycin among older adults taking a DOAC. DESIGN, SETTING, AND PARTICIPANTSThis population-based, retrospective cohort study was conducted among adults of advanced age (mean [SD] age, 77.6 [7.2] years) who were newly coprescribed clarithromycin (n = 6592) vs azithromycin (n = 18 351) while taking a DOAC (dabigatran, apixaban, or rivaroxaban) in Ontario, Canada, from June 23, 2009, to December 31, 2016. Cox proportional hazards regression was used to examine the association between hemorrhage and antibiotic use (clarithromycin vs azithromycin). Statistical analysis was performed from December 23, 2019, to March 25, 2020. MAIN OUTCOMES AND MEASURES Hospital admission with major hemorrhage (upper or lower gastrointestinal tract or intracranial). Outcomes were assessed within 30 days of a coprescription. RESULTS Among the 24 943 patients (12 493 women; mean [SD] age, 77.6 [7.2] years) in the study, rivaroxaban was the most commonly prescribed DOAC (9972 patients [40.0%]), followed by apixaban (7953 [31.9%]) and dabigatran (7018 [28.1%]). Coprescribing clarithromycin vs azithromycin with a DOAC was associa...