Health utilities in adults with hemophilia A: A retrospective cohort study.

INTRODUCTION: Haemophilia A negatively affects a patient's quality of life. There is a limited amount of health utility data (a measure of health-related quality of life) available for patients with haemophilia A. This information is crucial for cost-effectiveness analysis for haemophilia A treatment. OBJECTIVES: The goal of this project is to elicit the health utilities and factors impacting utility values for haemophilia A patients in Canada. METHODS: This is a population-based, cross-sectional, retrospective study of health utilities in patients with haemophilia A using Patient Report Outcomes Burdens and Experiences (PROBE) components from the Canadian Bleeding Disorders Registry (CBDR). A review of the mean utilities for three severity states, defined by clotting factor VIII level, was completed. A multiple linear regression analysis was completed to examine the determinants of health utilities including age, treatment type, chronic pain status, number of limited joints, and bleed rate. RESULTS: The average utility values (and standard deviations) for patients with haemophilia A in Canada are .79(.17), .76(.20), and .77(.19) for patients with severe, moderate, and mild haemophilia. The regression showed chronic pain status and the number of additional comorbidities as major significant factors (p-value < .001) in haemophilia A utility. Haemophilia severity was shown to be a major factor with smaller p-value (p-value < .05). CONCLUSIONS: Haemophilia A patients have lower utility than the general population. Chronic pain was shown to be a significant, major factor in health-related quality of life. Our study is essential for valuing health outcomes in haemophilia A-related cost-effectiveness analysis.

Post-initiation predictors of discontinuation of the sodium-glucose cotransporter-2 inhibitors: A comparative cohort study from the United Kingdom.

AIMS: To assess post-initiation predictors of discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl-peptidase-4 (DPP-4) inhibitors in the United Kingdom. MATERIALS AND METHODS: We conducted a comparative population-based retrospective cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) with linked data to hospital and death records. We included new metformin users who initiated either SGLT2 inhibitors or DPP-4 inhibitors between January 2013 and October 2019. The main outcome was treatment discontinuation, defined as the first 90-day gap after the estimated treatment end date. We used a series of extended Cox models to assess which time-dependent predictors were associated with treatment discontinuation. To test if the hazard ratio of discontinuation for each predictor was statistically different between SGLT2 and DPP-4 inhibitors, an exposure-predictor interaction term was added to each model. RESULTS: There were 2550 new users of SGLT2 inhibitors and 8195 new users of DPP-4 inhibitors. Approximately 69% of SGLT2 inhibitor and 74% of DPP-4 inhibitor users had discontinued treatment by the end of follow-up. Occurrence of fractures after treatment initiation was a significant predictor of discontinuation of SGLT2 inhibitors (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.12-8.06) but not DPP-4 inhibitors (HR 0.93, 95% CI 0.79-1.11). The rate of treatment discontinuation was significantly higher for those with low estimated glomerular filtration rate and minimal contact with the healthcare system. Efficacy endpoints, such as heart failure and glycated haemoglobin level, were not associated with treatment discontinuation. CONCLUSIONS: Our findings reflect some discrepancy between the available evidence and prescribing behaviour for SGLT2 inhibitors.

Herpes zoster and human papillomavirus vaccination opportunities identified using electronic prompts at the time of scheduling influenza or COVID-19 vaccines.

Background: Due to workload and competing priorities, vaccination-related interactions in community pharmacies tend to be more reactive than proactive. The aim of this study is to determine the proportion of users of a web-based scheduling system for influenza and COVID-19 vaccines who may be eligible for herpes zoster or human papillomavirus (HPV) vaccination and interested in discussing these vaccines with a pharmacist. Methods: Individuals scheduling an influenza or COVID-19 vaccine at a pharmacy using the MedEssist platform between October 2021 and March 2022 were asked about their vaccination status against HPV (if aged 9-45) or herpes zoster (if aged ≥50). Those who were unvaccinated or unsure were asked to indicate their willingness to discuss this with a pharmacist. Logistic regression was performed to identify patient characteristics associated with responses to these screening questions. Results: Among 36,659 bookings by those aged 9 to 45 and 55,728 by those aged ≥50 that included responses to screening questions, 70.1% and 55.5% were potentially unvaccinated against HPV and herpes zoster, respectively, with approximately 1 in 5 also indicating willingness to have a discussion with the pharmacist. Those scheduling appointments for COVID-19 vaccines were significantly less likely to be vaccinated against HPV or herpes zoster and less willing to discuss this with a pharmacist than those seeking influenza vaccination. Discussion: Automated prompts while booking influenza or COVID-19 vaccinations have the potential to identify vaccine-willing individuals who may benefit from further discussion on their vaccination needs. Conclusion: Community pharmacies can leverage available technology to support the efficient and effective identification of individuals eligible for vaccination.

Five comparative cohorts to assess the risk of genital tract infections associated with sodium-glucose cotransporter-2 inhibitors initiation in type 2 diabetes mellitus.

AIM: To assess the association between SGLT-2 inhibitors initiation and genital tract infections (GTIs) among patients with type 2 diabetes. METHODS: A population-based cohort study using administrative healthcare data from Alberta, Canada, and primary care data from the UK's Clinical Practice Research Datalink (CPRD). Among new metformin users, we identified new users of SGLT-2 inhibitors and five active comparator cohorts (new users of dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas (SU), glucagon-like peptide-1 receptor agonists (GLP-1 RA), thiazolidinediones (TZD) and insulin). The outcome of interest was a composite GTI outcome. In each cohort, we used high-dimensional propensity score matching to adjust for confounding and conditional Cox proportional hazards regression to estimate the hazard ratios (HR). We used random-effects meta-analysis to combine aggregate data across databases. RESULTS: The risk of GTI was higher for SGLT-2 inhibitors users compared with DPP4inhibitor users (pooled HR 2.68, 95% CI 2.19 3.28), SU users (3.29, 2.62-4.13), GLP1-RA users (2.51, 1.90-3.31), TZD users (4.17, 2.46-7.08) and insulin users (1.86, 1.27-2.73). CONCLUSION: In five comparative cohorts, SGLT-2 inhibitors initiation is associated with a higher risk of GTIs. These findings from real-world data are consistent with placebo-controlled randomized controlled trials.

Pharmacists as immunizers, their pharmacies and immunization services: A survey of Ontario community pharmacists.

BACKGROUND: To improve patient access to the influenza vaccine in Ontario, pharmacists have been authorized to administer the vaccine since 2012. A survey was conducted to describe pharmacist immunizers, their pharmacies and immunization services. METHODS: Ontario community pharmacists completed an anonymous online survey regarding influenza immunization. Descriptive, comparative and multivariate statistics were used to analyze data on pharmacists' personal demographics, current workplace characteristics, immunization certification status and past and anticipated experience vaccinating. RESULTS: Of the 4307 community pharmacists contacted, 18.4% (n = 780) completed the survey. Most (81.3%, n = 603) were certified to administer vaccines, with those practising in urban pharmacies twice as likely to be certified compared to pharmacists practising in rural pharmacies (odds ratio = 2.04; 95% confidence interval, 1.04 to 4.01, p = 0.04). In the past influenza season, 70% of pharmacists had administered over 50 vaccines and 37% worked at pharmacies that had administered more than 300 vaccines. Respondent-provided profiles of immunization services described partnerships with public health, a variety of approaches for in-pharmacy and external advertising and patient vaccine access mainly through walk-in. DISCUSSION: Ontario community pharmacists demonstrate strong engagement with this expanded scope and there is further capacity for immunization service provision through engaging rural pharmacies, addition of other vaccines and leveraging the positive relationship with public health. Patients and the public benefit from easy access to the service and the additional in-store and external promotion of influenza vaccination that is provided by pharmacists and pharmacies. CONCLUSION: These provincial benchmarking data provide direction for maintaining and expanding community pharmacist-provided influenza immunization.

Does the association between adherence to statin medications and mortality depend on measurement approach? A retrospective cohort study.

BACKGROUND: The aim of this study was to examine the relationship between mortality and statin adherence using two different approaches to adherence measurement (summary versus repeated-measures). METHODS: A retrospective cohort study was conducted using administrative data from Saskatchewan, Canada between 1994 and 2008. Eligible individuals received a prescription for a statin following hospitalization for acute coronary syndrome (ACS). Adherence was measured using proportion of days covered (PDC) expressed either as: 1) a fixed summary measure, or 2) as a repeatedly measured covariate. Multivariable Cox-proportional hazards models were used to estimate the association between adherence and mortality. RESULTS: Among 9,051 individuals, optimal adherence (≥80%) modeled with a fixed summary measure was not associated with mortality benefits (adjusted HR 0.97, 95% CI 0.86 to 1.09, p = 0.60). In contrast, repeated-measures approach resulted in a significant 25% reduction in the risk of death (adjusted HR 0.75, 95% CI 0.67 to 0.85, p < 0.01). CONCLUSIONS: Unlike the summary measure, the repeated measures approach produces a significant reduction of all-cause mortality with optimal adherence. This effect may be a result of the repeated measures approach being more sensitive, or more prone to survival bias. Our findings clearly demonstrate the need to undertake (and report) multiple approaches when assessing the benefits of medication adherence.

Multiple-domain Versus Single-domain Measurements of Socioeconomic Status (SES) for Predicting Nonadherence to Statin Medications: An Observational Population-based Cohort Study.

INTRODUCTION: Low socioeconomic status (SES) should be a robust predictor of medication nonadherence because it shares key features with the theoretical origins of this phenomenon. However, population-based studies have demonstrated weak associations overall, possibly because SES is inadequately represented. We compared the performance of multiple versus single-domain measures of SES as predictors of statin adherence. METHODS: This retrospective cohort study used population-based administrative data mapped to area-level census information of individuals who received a statin medication following a hospitalization for coronary heart disease. One-year adherence was calculated by dividing the sum of all tablets dispensed by the total number of days in the observation period (365 d following the first statin dispensation). Logistic regression models were constructed and the relative impact of each SES measure was assessed by its adjusted odds ratio (OR) and improvement over the predictive accuracy of a reference model that included non-SES factors only. RESULTS: More than two thirds (ie, 68.8%; 6517/9478) of eligible individuals exhibited optimal adherence (ie, ≥80%). The estimated impact of SES on optimal adherence differed depending on the SES measure tested. The highest performing single-domain measure, household income (OR=0.75; 95% confidence interval, 0.63-0.90; model c-statistic improvement 0.5%, P=0.04) generated a similar result to the multiple-domain measure (adjusted OR=0.74; 95% confidence interval, 0.62-0.88; model c-statistic improvement 0.7%, P=0.01). CONCLUSION: Multidomain measurements of SES using administrative databases mapped to census data are not associated with better performance in predicting statin medication adherence compared with single-domain measures such as household income.

Association Between Opioid-Related Mortality and History of Surgical Procedure: A Population-Based Case-Control Study.

Objective: This study examined whether there is an association between opioid-related mortality and surgical procedures. Methods: A case-control study design using deceased controls compared individuals with and without opioid death and their exposure to common surgeries in the preceding 4 years. This population-based study used linked death and hospitalization databases in Canada (excluding Quebec) from January 01, 2008 to December 31, 2017. Cases of opioid death were identified and matched to 5 controls who died of other causes by age (±4 years), sex, province of death, and date of death (±1 year). Patients with HIV infection and alcohol-related deaths were excluded from the control group. Logistic regression was used to determine if there was an association between having surgery and death from an opioid-related cause by estimating the crude and adjusted odds ratios (ORs) with the corresponding 95% confidence interval (CI). Covariates included sociodemographic characteristics, comorbidities, and the number of days of hospitalization in the previous 4 years. Results: We identified 11,865 cases and matched them with 59,345 controls. About 11.2% of cases and 12.5% of controls had surgery in the 4 years before their death, corresponding to a crude OR of 0.89 (95% CI: 0.83-0.94). After adjustment, opioid mortality was associated with surgical procedure with OR of 1.26 (95% CI: 1.17-1.36). Conclusions: After adjusting for comorbidities, patients with opioid mortality were more likely to undergo surgical intervention within 4 years before their death. Clinicians should enhance screening for opioid use and risk factors when considering postoperative opioid prescribing.

Association between Pharmacists' Country of Qualifying Education and Practising in a Hospital Setting: A Cross-Sectional Ontario Study.

Background: It is hypothesized that international pharmacy graduates (IPGs) are underrepresented in more clinically challenging work. Objective: To examine the association between country of qualifying education for pharmacists in Ontario and the likelihood of practising in a hospital setting. Methods: This study was based on publicly available data from the Ontario College of Pharmacists website, specifically records for all Ontario pharmacists with authorization to provide patient care and for whom country of qualifying education and an accredited pharmacy as a place of practice were reported. Pharmacists who met the inclusion criteria were categorized as Canadian graduates or IPGs. The odds ratio (OR) and 95% confidence interval (CI) for reporting hospital pharmacy as a place of practice were estimated by fitting a logistic regression, with adjustment for gender and years since graduation. Results: A total of 14 689 pharmacists were included in the study: 7403 (50.4%) Canadian graduates and 7286 (49.6%) IPGs. These pharmacists worked in a total of 5028 accredited pharmacies (243 hospital pharmacies [4.8%] and 4785 community pharmacies [95.2%]). Among Canadian graduates, 2458 (33.2%) reported at least 1 hospital pharmacy practice site, whereas the proportion was much smaller among IPGs (427, 5.9%). Canadian graduates represented 85.2% (2458/2885) of all pharmacists who reported hospital practice. The estimated crude OR for practice in a hospital pharmacy was 7.98 (95% CI 7.16-8.91), and the adjusted OR was 7.12 (95% CI 6.39-7.98). Conclusions: IPGs may face barriers impeding their ability to practise in a hospital setting. Providing opportunities such as structured clinical training and experiential placements may facilitate integration of IPGs in institutional settings.

Contexte: On émet l'hypothèse que les diplômés internationaux en pharmacie (DIP) sont sous-représentés dans des tâches plus cliniquement exigeantes. Objectif: Étudier l'association entre le pays de formation qualifiante des pharmaciens en Ontario et la probabilité de pratiquer dans un environnement hospitalier. Méthodes: Cette étude se fondait sur des données accessibles au public sur le site Web de l'Ordre des pharmaciens de l'Ontario, plus précisément les dossiers de tous les pharmaciens de l'Ontario autorisés à prodiguer des soins aux patients et pour lesquels le pays de formation qualifiante ainsi qu'une pharmacie accréditée en tant que lieu de pratique étaient signalés. Les pharmaciens répondant aux critères d'inclusion ont été catégorisés en tant que diplômés canadiens ou DIP. Le rapport de cotes (RC) et l'intervalle de confiance (IC) à 95 % pour le signalement de la pharmacie pratiquée en milieu hospitalier ont été estimés en utilisant une régression logistique, tenant compte du sexe et du nombre d'années depuis l'obtention du diplôme. Résultats: Un total de 14 689 pharmaciens ont été inclus dans l'étude : 7403 (50,4 %) diplômés canadiens et 7286 (49,6 %) DIP. Ces pharmaciens travaillaient dans 5028 pharmacies accréditées au total (243 pharmacies en milieu hospitalier [4,8 %] et 4785 pharmacies communautaires [95,2 %]). Parmi les diplômés canadiens, 2458 (33,2 %) ont signalé au moins un site de pratique en pharmacie hospitalière, tandis que la proportion était beaucoup plus faible parmi les DIP (427, 5,9 %). Les diplômés canadiens représentaient 85,2 % (2458/2885) de tous les pharmaciens ayant signalé une pratique de la pharmacie en milieu hospitalier. Le rapport de cotes (RC) brut estimé pour la pratique en pharmacie en milieu hospitalier était de 7,98 (IC à 95 % 7,16­8,91), et le RC ajusté était de 7,12 (IC à 95 % 6,39­7,98). Conclusions: Les DIP peuvent être confrontés à des obstacles qui entravent leur capacité à exercer dans un environnement hospitalier. Offrir des occasions, comme des formations cliniques structurées et des stages expérientiels, pourrait faciliter leur intégration dans des milieux institutionnels.

Trends and Determinants of Self-reported Aspirin Use Among Patients With Diabetes Stratified by Presence and Risk of Cardiovascular Diseases: A Repeated Pan-Canadian Cross-sectional Study.

OBJECTIVES: Our aim in this study was to quantify the prevalence over time and identify determinants of acetylsalicylic acid (ASA) use in patients with diabetes with and without cardiovascular disease (CVD) in a representative Canadian sample from 2005 to 2014, and to determine whether the use of ASA among patients with diabetes changed after the Diabetes Canada clinical practice guidelines updates. METHODS: Data from the Canadian Community Health Survey were used. Respondents who were at least 35 years of age and diagnosed with diabetes---not during pregnancy---were included and categorized into secondary prevention (previous heart disease or stroke) or primary prevention (high or low CVD risk) groups. A stratified and weighted multivariable logistic regression model was used to quantify ASA use and identify determinants of use. RESULTS: Our sample consisted of 15,100 respondents with diabetes (weighted sample of ∼2,429,900). Approximately 70% and 50% of Canadians with diabetes used ASA for secondary and primary prevention, respectively. Overall, the trend of ASA use was stable over the study period in both the secondary and the primary prevention groups. This trend did not change after the clinical practice guidelines update in 2008. Having a regular doctor and older age were associated with increased use of ASA. Other significant determinants independently associated with ASA use included income, body mass index, smoking, immigration status, gender and chronic diseases. CONCLUSIONS: Among patients with diabetes in Canada, ASA appears to be underutilized in secondary prevention and high-risk primary prevention populations. Future research should address whether regular use of ASA is associated with clinical outcomes among patients with diabetes.

Stepping up to the Canadian opioid crisis: a longitudinal analysis of the correlation between socioeconomic status and population rates of opioid-related mortality, hospitalization and emergency department visits (2000-2017). / Remédier à la crise des opioïdes au Canada : une analyse longitudinale de la corrélation entre le statut socioéconomique et les taux de décès, d'hospitalisations et de visites à l'urgence liés aux opioïdes dans la population (2000-2017).

INTRODUCTION: High levels of income inequality and increased opioid-related harm across Canada bring into question the role of socioeconomic status (SES) in the opioid epidemic. Only a few studies have examined this association, and most of those have analyzed this issue on a provincial level. This study examined the association between opioid-related health outcomes and SES, and investigated rate ratios over time. METHODS: Administrative databases were used to identify opioid-related mortality, hospitalization and emergency department visits between 2000 and 2017. Patient's postal code was linked to the quintile of median household income at the forward sortation area level. Crude rates and age- and sex-adjusted rates in each quintile were calculated, as well as the adjusted rate ratio of average annual rates between the lowest and highest quintiles. The significance of the time trend of rate ratios for all outcomes was examined using linear regression. RESULTS: A stepped gradient of opioid-related outcomes across all income quintiles emerged from these data. For mortality, hospitalization and emergency department visits, the average annual rate ratio between lowest quintile and highest quintile was 3.8, 4.3 and 4.9, respectively. These ratios were generally stable and consistent over the study period, albeit the opioid-related mortality SES gap decreased gradually (p < 0.01). CONCLUSION: Area income quintile was found to be highly associated with opioid outcomes. Psychosocial factors (stress, unemployment, housing insecurity) that are typically concentrated in low SES areas may play a significant role in the opioid epidemic. Health policies should address these factors in order to provide effective solutions.

Sodium-Glucose Cotransporter-2 Inhibitors and Urinary Tract Infections: A Propensity Score-matched Population-based Cohort Study.

OBJECTIVES: Sodium-glucose cotransporter-2 (SGLT2) inhibitor-induced glycosuria is hypothesized to increase the risk of urinary tract infections (UTIs). We assessed the risk of UTIs associated with SGLT2 inhibitor initiation in type 2 diabetes. METHODS: We conducted a population-based cohort study using primary care data from the United Kingdom's Clinical Practice Research Datalink (CPRD) and administrative health-care data from Alberta, Canada. From a base cohort of new metformin users, we constructed 5 comparative cohorts, wherein the exposure contrast was defined as new use of SGLT2 inhibitors or 1 of 5 active comparators: dipeptidylpeptidase-4 (DPP-4) inhibitors, sulfonylureas (SU), glucagon-like peptide-1 receptor agonists (GLP-1 RA), thiazolidinediones (TZD) and insulin. We defined a composite UTI outcome based on hospitalizations or physician visit records. For each comparative cohort, we used high-dimensional propensity score matching to adjust for confounding and Cox proportional hazards regression to estimate the hazard ratios (HRs) in each database. We meta-analyzed estimates using a random-effects model. RESULTS: SGLT2 inhibitor use was not associated with a higher risk of UTI compared with DPP-4 inhibitors (pooled HR, 1.08; 95% confidence interval [CI], 0.89 to 1.30), SU (pooled HR, 1.08; 95% CI, 0.90 to 1.30), GLP-1 RA (pooled HR, 0.81; 95% CI, 0.61 to 1.09) or TZD (pooled HR, 0.81; 95% CI, 0.55 to 1.19). The risk of UTI was lower compared with insulin (pooled HR, 0.74; 95% CI, 0.63 to 0.87). The risk of UTI did not differ based on the SGLT2 inhibitor agent or dose. Last, SGLT2 inhibitor initiation was not associated with an increased risk of UTI recurrence. CONCLUSION: SGLT2 inhibitor use is not associated with an increased risk of UTIs, compared with other antidiabetic agents.

Risk of hospitalization and death associated with sodium glucose cotransporter-2 inhibitors: A comparison with five other classes of antidiabetic drugs.

AIM: We assessed the risk of all-cause hospitalization and all-cause death associated with the use of Sodium Glucose Cotransporter-2 inhibitors (SGLT2i). METHODS: Population-based propensity scores-matched cohort study of new users of metformin who subsequently initiated SGLT2i compared to those who initiated dipeptidyl peptidase-4 inhibitors (DPP4i) (primary comparison), sulfonylureas, thiazolidinediones, GLP1-Receptors agonists, and insulin, respectively. Alberta (Canada) health administrative data and United Kingdom Clinical Practice Research Datalink (CPRD) data were used to assess the study outcomes. Conditional Cox regressions were performed to assess the risk of each outcome, separately for each dataset and then results were combined using random-effects meta-analysis. RESULTS: For SGLT2i versus DPP4i, 7531 and 1647 SGLT2i-DPP4i matched pairs were analyzed in Alberta and CPRD data respectively. The mean age of patients was 56 and 57 years, and 39% and 43% were females, respectively in Alberta and CPRD cohorts. Compared with DPP-4-i, SGLT2i use was associated with a significant lower risk of all-cause hospitalization (combined hazard ratio (HR): 0.84, 95% confidence interval (95%CI): 0.75-0.95), and all-cause death (0.56, 0.38-0.83). SGLT2i use was also associated with a significant lower risk of all-cause hospitalization and all-cause death when compared to sulfonylureas (HRs: 0.80, 95%CI: 0.71-0.90 and 0.56, 95%CI: 0.38-0.82, respectively) and insulin (HRs: 0.55, 95%CI: 0.41-0.74, and 0.33, 95%CI: 0.24-0.46, respectively). CONCLUSIONS: SGLT2i initiation was associated with a decreased risk of all-cause hospitalization and all-cause death when compared to DPP4i, sulfonylureas, and insulin.

National trends in population rates of opioid-related mortality, hospitalization and emergency department visits in Canada between 2000 and 2017. A population-based study.

BACKGROUND AND AIMS: Existing assessments of the time-trends of opioid-related mortality, hospitalization and emergency department visits in Canada have relied mainly on provincial databases, while national assessments generally do not provide information before 2016. We aimed to estimate Canadian national time trends in opioid-related mortality from 2000 to 2017 and opioid-related hospitalization and emergency department visits between 2000 and 2012. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Residents of all Canadian provinces and territories for which comparable data were available from 2000 to 2017. MEASUREMENTS: We identified opioid-related mortality, hospitalization and emergency department visits using validated algorithms using ICD codes from administrative databases. We calculated crude rates and sex- and age-adjusted rates per million. For hospitalizations, we calculated case-fatality, 90-day and 365-day all-cause mortality and opioid-related re-hospitalization rates. We used Poisson regression to examine the significance of the time trend. FINDINGS: From 2000 to 2017, the adjusted opioid mortality rate in Canada (outside Quebec) increased significantly by 592.9% (from 20.0 opioid deaths per million in 2000 to 118.3 in 2017). The highest year-to-year increases were from 2015 to 2016 (31.8%) and from 2016 to 2017 (52.2%). The adjusted hospitalizations doubled significantly during the study period (an increase of 103.7%, from 159.7 opioid hospitalizations per million Canadians in 2000 to 325.3 in 2012). The adjusted rate of emergency department visits increased significantly by 188.7% (from 280.6 per million in 2000 to 810.1 in 2012). Case-fatality was 2.3% overall and was mainly constant during the study period. Both 90- and 365-day all-cause mortality increased significantly between 2000 and 2011 (from 1.7 to 3.1% and 3.9 to 7.4%, respectively), while re-hospitalization for opioid-related diagnoses was reduced (from 7.8 to 6.4% and 14.2 to 12.9%, respectively). CONCLUSIONS: Opioid-related mortality, hospitalization and emergency department visits in Canada have been increasing gradually since 2000.

Renal effectiveness and safety of the sodium-glucose cotransporter-2 inhibitors: a population-based cohort study.

INTRODUCTION: To assess the comparative effectiveness and safety of renal-related outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2-i) initiation among patients with type 2 diabetes using real-world data. RESEARCH DESIGN AND METHODS: We conducted a population-based cohort study using administrative healthcare data from Alberta (AB), Canada and primary care data from the Clinical Practice Research Datalink (CPRD), UK. From a cohort of new metformin users, we identified initiators of a SGLT2-i or dipeptidyl peptidase-4 inhibitor (DPP4-i) between January 1, 2014 and March 30, 2018 (AB) or between January 1, 2013 and November 29, 2018 (CPRD). Initiators of an SGLT2-i or DPP4-i were followed until death, disenrolment, therapy discontinuation, or study end date. The effectiveness outcome was renal disease progression, defined as a composite of new-onset macroalbuminuria, serum creatinine doubling with estimated glomerular filtration rate of ≤45 mL/min/1.73 m2, renal replacement therapy, hospital admission or death from renal causes. The safety outcome was hospitalization due to acute kidney injury (AKI). We adjusted for confounding using high-dimensional propensity score matching and estimated HRs using Cox proportional hazards regression. Aggregate data from each database were combined by random-effects meta-analysis. RESULTS: Among the 29 465 included patients (20 564 AB, 8901 CPRD), 37.5% were new SGLT2-i users in AB and 21.3% in CPRD. Compared with DPP4 initiators, SGLT2-i initiators were associated with a reduced risk of renal disease progression (pooled HR 0.79, 95% CI 0.62 to 1.00); however, there was no significant difference in the risk of AKI (pooled HR 0.89, 95% CI 0.58 to 1.36). These findings were consistent with other exposure definitions and antidiabetic comparators. CONCLUSIONS: Our findings support a renoprotective effect of SGLT2-i without an increased risk of AKI, compared with clinically relevant active comparators.

Economic evaluation of pharmacists prescribing for minor ailments in Ontario, Canada: a cost-minimization analysis.

OBJECTIVES: The objective of this study was to use a decision-analytic model to examine the potential economic impact of establishing a remunerated programme for pharmacists prescribing for minor ailments (PPMA) in Ontario, Canada. METHODS: A novel decision tool was developed to assess the economic impact of pharmacists prescribing for upper respiratory tract infections (URTIs), contact dermatitis (CD) and conjunctivitis by performing a cost-minimization analysis from a public payer perspective. Two prescribing strategies were compared: (1) PPMA, where patients may seek care from pharmacists or physicians, and (2) the usual care model (UCM), where all patients receive care from physicians. Two remuneration models for the PPMA strategy were also compared: (1) a prescription-detached scenario (PDS), where pharmacists were remunerated CAD$18.00 for each consultation, and (2) a Prescription-Attached Scenario (PAS), where pharmacists were only remunerated if a decision to prescribe was made. KEY FINDINGS: At a service uptake rate of 38% for the PDS, the PPMA model led to savings of $7.51, $4.08 and $5.15 per patient for URTIs, CD and conjunctivitis, respectively. Per 30 000 patients, the PPMA model for these minor ailments was projected to lead to cumulative reductions in visits to the emergency department, family physician and walk-in clinics by 799, 3677 and 5090, respectively. CONCLUSIONS: The results of the study strongly suggest that enabling community pharmacists to assess and prescribe for minor ailments could potentially lead to large savings for the government in Ontario, Canada. In 100% of the PAS scenarios simulated, pharmacists as prescribers led to cost savings.

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias - A narrative review.

Donepezil, galantamine, and rivastigmine are the three acetylcholinesterase inhibitors (AChEIs), out of a total of only four medications prescribed in the treatment of Alzheimer's Disease (AD) and related dementias. These medications are known to be associated with bradycardia given their mechanism of action of increasing acetylcholine (ACh). However, in March 2015, donepezil was added to the CredibleMeds "known-risk" category, a list where medications have a documented risk for acquired long-QT syndrome (ALQTS) and torsades de pointes (TdP) - a malignant ventricular arrhythmia that is a different adverse event than bradycardia (and is not necessarily associated with ACh action). The purpose of this article is to review the three AChEIs, especially with regards to mechanistic differences that may explain why only donepezil poses this risk; several pharmacological mechanisms may explain why. However, from an empirical point-of-view, aside from some case-reports, only a limited number of studies have generated relevant information regarding AChEIs' and electrocardiogram findings; none have specifically compared donepezil against galantamine or rivastigmine for malignant arrhythmias such as TdP. Currently, the choice of one of the three AChEIs for treatment of AD symptoms is primarily dependent upon clinician and patient preference. However, clinicians should be aware of the potential increased risk associated with donepezil. There is a need to examine the comparative risk of malignant arrhythmias among AChEIs users in real-world practice; this may have important implications with regards to changes in AChEI prescribing patterns.

Estimates of population-based incidence of malignant arrhythmias associated with medication use-a narrative review.

Certain medications are reported to be associated with acquired long-QT syndrome (ALQTS), which can degenerate into a potentially severe 'malignant' arrhythmia known as torsades de pointes (TdP). However, population-based estimations of the incidence of medication-associated malignant arrhythmia are limited. The purpose of this article is to review the clinical symptoms, cellular mechanism, categorization, and risk factors of these malignant arrhythmias, as well as illustrate results and methodological limitations of epidemiological literature which have previously estimated population-based incidence of ALQTS and malignant arrhythmia. Administrative databases in universal healthcare systems (such as Canada) can be used to provide a robust estimate of this incidence. We present a valid operational definition of medication-associated malignant arrhythmia, using Canadian hospital administrative data linked to prescription databases that can be used to estimate the population-based incidence. An estimation of incidence may have important implications with regard to understanding the potential widespread distribution of this adverse effect-which may influence medication prescribing patterns.

The availability of pharmacists with Additional Prescribing Authorization in relation to the distribution of vulnerable populations - A cross-sectional study.

BACKGROUND: For vulnerable patients- such as immigrants or those with low income- to benefit from pharmacists' advanced services, such as independent prescribing, pharmacists must be accessible to these populations. OBJECTIVES: This research examines the geographical relationship between Alberta pharmacists with Additional Prescribing Authorization (APA) and a neighbourhood's proportion of vulnerable populations. METHODS: Publicly available data were extracted from the Alberta College of Pharmacy website for active registered pharmacists' primary location of practice and APA status. Pharmacists with APA were grouped depending on the postal codes of their main self-reported place of practice. These postal codes were converted to geospatial locations and then linked to aggregated dissemination area's (ADA's) income and immigrant quintiles. The mean number of APA pharmacists per ADA was compared using analysis of variance (ANOVA) between income and immigrant quintiles. The number of APA pharmacists per ADA in the highest and lowest income and immigrant quintiles was compared using negative binomial regression model. RESULTS: The records of 3,742 pharmacists with 1,054 unique postal codes of practice sites were included in the study and were linked to unique ADAs (N = 527). Almost one half of all ADAs in Alberta (47.6%, n = 251) had no APA pharmacist. Income quintiles of ADAs were associated with the mean number of APA pharmacists (p < 0.001), with high income areas estimated to have 0.44 more APA pharmacists (p = 0.01). Similarly, areas with the highest quintile of recent immigrants were estimated to have 0.66 more APA pharmacists than other ADAs (p < 0.01). CONCLUSIONS: A sizable proportion of the Alberta population still does not have access to a pharmacist with APA, and those with APA seem to concentrate in areas with higher income and higher proportions of the population who are immigrants. Future research should examine the utilization of expanded scope of practice in relation to the distribution of vulnerable populations.