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Background: Direct oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting. Methods: We conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009–2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses. Results: We included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85). Interpretation: In this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation. Trial registration: ClinicalTrials.gov, no. NCT03596502 [ABSTRACT FROM AUTHOR]

Background: The College of Physicians and Surgeons of British Columbia introduced opioid prescribing standards and guidelines in mid-2016 in British Columbia. We evaluated impacts of the standards and guidelines on health outcomes. Methods: We conducted a longitudinal study with repeated measures using administrative data from December 2013 to March 2017. The study included BC patients with long-term use of prescription opioids. Those with a history of long-term care, palliative care or cancer were excluded. Patients were followed for a 12-month prepolicy period and 10-month postpolicy period and compared with historical controls. We estimated changes in level (sudden changes) and monthly trend (gradual changes) of rates of opioid overdose hospital admission, and secondary outcomes of all-cause hospital admission, all-cause emergency department visits, opioid overdose mortality and all-cause mortality. Results: The study included 68 113 patients in the main cohort and 68 429 historical controls. We did not find significant changes to opioid overdose hospital admissions in level (adjusted rate ratio [RR] 0.83, 95% confidence interval [CI] 0.45–1.54) or in trend (adjusted RR 1.00, 95% CI 0.91–1.10). All-cause hospital admissions declined in level but may have increased in trend, suggesting that a temporary decrease in hospital admissions may have occurred. We found no significant changes in all-cause emergency department visits, opioid overdose mortality or all-cause mortality. Interpretation: Among patients with a history of long-term prescription opioid use, the regulatory prescribing standards and guidelines were not associated with changes in opioid overdose hospital admissions, all-cause emergency department visits, opioid overdose mortality or all-cause mortality, or with a sustained reduction in all-cause hospital admissions, over a 10-month period after they were introduced. Future research should investigate whether opioid prescribing standards or guidelines are associated with use of nonopioid analgesic medications or nonpharmacologic treatments. [ABSTRACT FROM AUTHOR]

Background: In mid-2016, the College of Physicians and Surgeons of British Columbia (CPSBC) issued prescribing standards and guidelines relating to opioid drugs. We evaluated the impact of these regulatory standards and guidelines on prescription drug use among patients in the province with long-term opioid use. Methods: We conducted a cohort study with monthly repeated measures using administrative health data in British Columbia. Patients with long-term prescription opioid use were followed for a 12-month prepolicy period and 10-month postpolicy period, and were compared with a historical control cohort. We excluded patients with a history of long-term care, palliative care or cancer. We estimated changes in use of opioids, high-dose opioids (> 90 mg of morphine equivalents/d), opioids with sedatives/hypnotics, and opioid discontinuation. Results: The study population included 68 113 patients in the policy cohort and 68 429 patients in the historical control cohort. Following the introduction of the standards and guidelines, the average monthly use of opioids declined (adjusted difference −57 mg of morphine equivalents, 95% confidence interval [CI] −74 to −39) and discontinuation of opioids increased (odds ratio [OR] 1.24, 95% CI 1.16 to 1.32). Among patients prescribed high-dose opioids, switching to lower-dose opioids increased (OR 1.88, 95% CI 1.63 to 2.17), but discontinuation did not change significantly (OR 1.21, 95% CI 0.91 to 1.59). Interpretation: The CPSBC's regulatory standards and guidelines were associated with modestly reduced opioid use and increased switching from high-dose to lower-dose opioids among patients with long-term use of prescribed opioids. Assessment of the potential impacts on health outcomes will be necessary for understanding the implications of the standards and guidelines. [ABSTRACT FROM AUTHOR]

Background: Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario.Methods: Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12-48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations.Results: A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011.Interpretation: Adherence to the isotretinoin pregnancy prevention program in Canada was poor during the 15-year period of this study. [ABSTRACT FROM AUTHOR]

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