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Introduction: Knowledge translation (KT) initiatives have the potential to improve prescribing quality and produce savings that exceed the cost of the KT program itself, including the cost of evaluation using pragmatic study methods. Our objective was to measure the impact and estimated savings resulting from the distribution of individualized physician portraits of statin prescribing along with therapeutic recommendations in British Columbia, Canada. Methods: A paired community design was used to study 2 725 family physicians in British Columbia. Communities were paired according to number of physicians and geographic location, with one community of each pair randomly assigned to an early (n = 1 349) or delayed (n = 1 376) intervention group. The intervention was a personalized prescribing portrait on statins that included therapeutic recommendations. The primary outcome was the impact on new prescribing (defined as statin naive) for primary prevention (defined as no diagnosis of cardiovascular disease) as recorded in the administrative claims databases of the BC Ministry of Health. Results: Compared to the delayed control group, the relative probability of a new statin prescription for primary prevention decreased by 6% in the 12 months after the Education for Quality Improvement in Patient Care (EQIP) portrait compared to the preceding 12 months (relative risk [RR] 0.94; 95% confidence interval [CI] 0.91-0.98). There was also a non-statistically significant decrease in new prescribing for secondary prevention in patients diagnosed with cardiovascular disease (RR 0.96; 95% CI 0.91-1.01). We estimated that 572 fewer patients started statins for primary prevention in the first year after the portrait was mailed compared to patients in the delayed practices. We estimated the statin cost for those patients as $465,000 in the first two years, while the KT program to provide statin portraits cost less than $100,000. Discussion: The individualized prescribing portrait had a significant beneficial effect on new statin prescribing for primary prevention but not secondary prevention. Provincial drug plan costs appear to have been reduced to a level that exceeded the cost of the program. (Contains 5 tables.)

Aims: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). Methods: We conducted multicentre matched cohort studies with secondary meta‐analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across 9 administrative healthcare databases. We included adults with NVAF initiating anticoagulation therapy (dabigatran, rivaroxaban or apixaban), and constructed 3 cohorts to compare DOACs pairwise. The primary outcome was pooled hazard ratio (pHR) of ischaemic stroke or systemic thromboembolism. Secondary outcomes included pHR of major bleeding, and a composite of stroke, major bleeding, or all‐cause mortality. We used proportional hazard Cox regressions models, and pooled estimates were obtained with random effect meta‐analyses. Results: The cohorts included 73 414 new users of dabigatran, 92 881 of rivaroxaban, and 61 284 of apixaban. After matching, the pHRs (95% confidence intervals) comparing rivaroxaban initiation to dabigatran were: 1.11 (0.93, 1.32) for ischaemic stroke or systemic thromboembolism, 1.26 (1.09, 1.46) for major bleeding, and 1.17 (1.05, 1.30) for the composite endpoint. For apixaban vs dabigatran, they were: 0.91 (0.74, 1.12) for ischaemic stroke or systemic thromboembolism, 0.89 (0.75, 1.05) for major bleeding, and 0.94 (0.78 to 1.14) for the composite endpoint. For apixaban vs rivaroxaban, they were: 0.85 (0.74, 0.99) for ischaemic stroke or systemic thromboembolism, 0.61 (0.53, 0.70) for major bleeding, and 0.82 (0.76, 0.88) for the composite endpoint. Conclusion: We found that apixaban use is associated with lower risks of stroke and bleeding compared with rivaroxaban, and similar risks compared with dabigatran. [ABSTRACT FROM AUTHOR]

Introduction: The British Columbia Ministry of Health launched a Smoking Cessation Program on September 30, 2011, providing financial coverage for smoking cessation pharmacotherapies. Although pharmacotherapies have been shown to have a moderate short-term benefit as a quitting aid, substantial cardiovascular and neuropsychiatric safety concerns have been identified in adverse-reporting databases, leading to prescription label warnings by Health Canada and the U.S. Food and Drug Administration. However, recent studies indicate these warnings may be without merit. This study examined the comparative safety of medications commonly used to aid smoking cessation.Aims and Methods: Population-based retrospective cohort study using B.C. administrative data to assess the relative safety between varenicline, bupropion, and nicotine replacement therapies (NRTs). The primary outcome was a composite of cardiovascular hospitalizations. Secondary outcomes included mortality, a composite of neuropsychiatric hospitalizations, and individual components of the primary outcome. Statistical analysis used propensity score-adjusted log-binomial regression models. A sensitivity analysis excluded patients with a history of cardiovascular disease.Results: The study included 116 442 participants. Compared with NRT, varenicline was associated with a 10% 1-year relative risk decrease of cardiovascular hospitalization (adjusted risk ratio [RR] = 0.90, 95% confidence interval (CI): 0.82 to 1.00), a 20% 1-year relative risk decrease of neuropsychiatric hospitalization (RR: 0.80, CI: 0.7 to 0.89), and a 19% 1-year relative risk decrease of mortality (RR: 0.81, CI: 0.71 to 0.93). We found no significant association between NRT and bupropion for cardiovascular hospitalizations, neuropsychiatric hospitalizations, or mortality.Conclusions: Compared with NRT, varenicline is associated with fewer serious adverse events and bupropion the same number of serious adverse events.Implications: This study addresses the need for comparative safety evidence in a real-world setting of varenicline and bupropion against an active comparator. Compared with NRT, varenicline was associated with a decreased risk of mortality, serious cardiovascular events, and neuropsychiatric events during the treatment, or shortly after the treatment, in the general population of adults seeking pharmacotherapy to aid smoking cessation. These results provide support for the removal of the varenicline boxed warning for neuropsychiatric events and add substantively to the cardiovascular safety findings of previous observational studies and randomized clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To describe and implement a novel method of measuring comparative effectiveness using sequential episodes of pharmacotherapy as a proxy for treatment failure. Methods: Retrospective cohort study using linked deidentified data from the British Columbia Ministry of Health during a government‐sponsored smoking cessation reimbursement program.Three study cohorts were created based on first use of varenicline, bupropion, or nicotine replacement therapy (NRT), for adults aged 18 or older, in the period September 30th, 2011 to March 31st, 2013. The study cohorts were analyzed for sequential episodes of pharmacotherapy, defined as re‐initiating a smoking cessation pharmacotherapy after an initial episode of treatment and washout period. The statistical analysis used propensity score adjusted log‐binomial regression models with one‐year and two‐year fixed follow‐up after a 12‐week washout period. A sensitivity analysis excluded the washout period. A secondary analysis investigated predictors of receiving a sequential episode of smoking cessation pharmacotherapy Results: 116,442 participants of the B.C. Smoking Cessation Program were analyzed. Compared to NRT, varenicline users were 13% less likely, and bupropion users were 18% less likely, to re‐start smoking cessation therapy within 1‐year after an initial course of treatment. Conclusions Sequential episodes of pharmacotherapy identified treatment failures to smoking cessation therapy. Based on sequential episodes of pharmacotherapy during a drug benefit policy of smoking cessation medications, varenicline and bupropion were more effective aids to smoking cessation than NRT. The method was also used to identify patient characteristics associated with treatment effectiveness [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of a personalised audit and feedback prescribing report (AF) and brief educational summary (ES) on empiric treatment of uncomplicated lower urinary tract infections (UTIs) by family physicians (FPs)., Design: Cluster randomised control trial., Setting: The intervention was conducted in British Columbia, Canada between 23 September 2021 and 28 March 2022., Participants: We randomised 5073 FPs into a standard AF and ES intervention arm (n=1691), an ES-only arm (n=1691) and a control arm (n=1691)., Interventions: The AF contained personalised and peer-comparison data on first-line antibiotic prescriptions for women with uncomplicated lower UTI and key therapeutic recommendations. The ES contained detailed, evidence-based UTI management recommendations, incorporated regional antibiotic resistance data and recommended nitrofurantoin as a first-line treatment., Main Outcome Measures: Nitrofurantoin as first-line pharmacological treatment for uncomplicated lower UTI, analysed using an intention-to-treat approach., Results: We identified 21 307 cases of uncomplicated lower UTI among the three trial arms during the study period. The impact of receiving both the AF and ES increased the relative probability of prescribing nitrofurantoin as first-line treatment for uncomplicated lower UTI by 28% (OR 1.28; 95% CI 1.07 to 1.52), relative to the delay arm. This translates to additional prescribing of nitrofurantoin as first-line treatment, instead of alternates, in an additional 8.7 cases of uncomplicated UTI per 100 FPs during the 6-month study period., Conclusion: AF prescribing data with educational materials can improve primary care prescribing of antibiotics for uncomplicated lower UTI., Trial Registration Number: NCT05817253., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Orally administered bisphosphonate drugs (i.e., alendronate, etidronate, risedronate) can reduce the risk of vertebral fracture. However, only alendronate and risedronate have proven efficacy in reducing the risk of hip fracture. We sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults., Methods: We identified new users of orally administered bisphosphonate drugs in British Columbia and Ontario between 2001 and 2008. We used province- and sex-specific propensity score-matching strategies to maximize comparability between exposure groups. We used Cox proportional hazards models to compare time-to-hip fracture within 1 year of treatment between exposures by sex in each province. Our secondary analyses considered hip fracture rates within 2 and 3 years' follow-up. We used alendronate as the reference for all comparisons and pooled provincial estimates using random effects variance-weighted meta-analysis., Results: We identified 321 755 patients who were eligible for inclusion in the study. We found little difference in fracture rates between men (pooled hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74-1.14) or women (pooled HR 1.15, 95% CI 0.73-1.56) taking risedronate and those taking alendronate. We similarly identified little difference in fracture rates between women taking etidronate and those taking alendronate (pooled HR 1.00, 95% CI 0.82-1.18). However, we identified lower rates of hip fracture among men taking etidronate relative to alendronate (pooled HR 0.77, 95% CI 0.60-0.94). Results extended to 2 and 3 years' follow-up were similar. However, with 3 years' follow-up, rates of hip fracture were lower among women in British Columbia who had taken alendronate., Interpretation: We identified little overall difference between alendronate and risedronate in reducing the risk of hip fracture in men or women. Our finding that etidronate is associated with lower fracture risk among men is likely due to selection bias. The long-term comparative effects of orally administered bisphosphonate drugs warrant further study.

Objective: Concerns persist about a possible association between tumor necrosis factor alpha (TNFalpha) antagonist treatment and development of cancers in patients with rheumatoid arthritis (RA). This study was undertaken to estimate the association between treatment with biologic disease-modifying antirheumatic drugs (DMARDs) and development of cancer in patients with RA., Methods: We conducted a cohort study pooling administrative databases from 2 US states and 1 Canadian province. A cohort of patients who had received a diagnosis of RA on > or =1 occasion and had been prescribed DMARDs was identified. We categorized patients with a prescription for a biologic DMARD as biologic DMARD users, and those with a prescription for methotrexate (MTX) but no biologic DMARD as MTX users. We used time-varying propensity scores to adjust for the large number of possible confounders and stratified proportional hazards regression to estimate the effects of biologic DMARDs on cancer. The primary end points were hematologic malignancies (lymphoma, multiple myeloma, and leukemia) and common solid tumors (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary tract/bladder, and melanoma)., Results: The pooled cohort included 1,152 biologic DMARD users and 7,306 MTX users. We identified 11 hematologic malignancies and 46 solid tumors during 2,940 person-years of biologic DMARD use, and 88 hematologic malignancies and 558 solid tumors during 30,300 person-years of MTX use. Comparing biologic DMARD users with MTX users, the propensity score-adjusted pooled hazard ratio was 1.37 (95% confidence interval 0.71-2.65) for hematologic malignancies and 0.91 (95% confidence interval 0.65-1.26) for solid tumors., Conclusion: Our results indicate that users of biologic agents are unlikely to have a substantial increase in the risk of hematologic malignancies and solid tumors as compared with MTX users. Despite the use of large combined data sets, studying the effect of an infrequent exposure (biologic DMARDs) on rare diseases (hematologic malignancies) remains a challenge.