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The objective of this study was to better understand high-risk patients' readiness to engage in bone mineral density (BMD) testing to diagnose osteoporosis. Six hundred thirty-six participants in a randomized control trial for patients at high-risk for osteoporosis were surveyed. BMD screening readiness was measured by a three-item summative index. Multivariable linear regression examined the relationship between patients' scores on the index and constructs of osteoporosis and BMD testing knowledge, concern for developing osteoporosis and self-efficacy to engage in fall prevention behaviors. Participants had a mean age of 79 years, 96% were female and 80% were white. Greater concern for developing osteoporosis and better knowledge about BMD testing were significant predictors of a higher score on the index. Improving high-risk patients' knowledge about osteoporosis and the importance of BMD testing may enhance patients' readiness to undergo BMD testing. We found several correlates of readiness to undergo BMD screening that may be used to design effective interventions. [ABSTRACT FROM AUTHOR]

Patients who adhere to preventive therapies may be more likely to engage in a broad spectrum of behaviors consistent with a healthy lifestyle. Because many of these behaviors cannot be measured easily, observational studies of outcomes associated with the long-term use of preventive therapies are subject to the so-called 'healthy user bias.' To better understand this effect, the authors examined the association between adherence to statin therapy and the use of preventive health services in a Pennsylvania cohort of 20,783 new users of statins between 1996 and 2004. After adjustment for age, gender, and various comorbid conditions, patients who filled two or more prescriptions for a statin during a 1-year ascertainment period were more likely than patients who filled only one prescription to receive prostate-specific antigen tests (hazard ratio (HR) = 1.57, 95% confidence interval (CI): 1.17, 2.19), fecal occult blood tests (HR = 1.31, 95% CI: 1.12, 1.53), screening mammograms (HR = 1.22, 95% CI: 1.09, 1.38), influenza vaccinations (HR = 1.21, 95% CI: 1.12, 1.31), and pneumococcal vaccinations (HR = 1.46, 95% CI: 1.17, 1.83) during follow-up. These results suggest that patients who adhere to chronic therapies are more likely to seek out preventive health services, such as screening tests and vaccinations. Further work is needed to identify study design and analysis methods that can be used to minimize the healthy user bias in studies of preventive therapies. [ABSTRACT FROM AUTHOR]

Background: Community pharmacies typically require patients to request medication refills. The appointment-based model (ABM) is a proactive approach that synchronizes refills and schedules patient-pharmacist appointments. These appointments provide opportunities for medication reviews, medication optimization and health promotion services. The primary aim of this study was to describe the types of patients who received an ABM service in a community pharmacy in Ontario in 2017. The secondary aim was to describe reimbursable clinical service uptake., Methods: In September 2017, the ABM was implemented across 3 Ontario community pharmacies within a Canadian pharmacy banner. Patients who filled at least 1 chronic oral medication and consented to enrolment were eligible. In December 2018, data were extracted from pharmacies using pharmacy management software. Descriptive statistics and frequencies were generated., Results: Analysis of 131 patients (51.1% female; mean ± SD age 70.8 ± 10.5 years) revealed patients were dispensed a mean ± SD of 5.1 ± 2.7 medications, and 73 (55.7%) experienced polypharmacy. Hypertension (87.8%) and dyslipidemia (68.7%) were the most common medical conditions. There were 74 (56.5%) patients who received ≥1 medication review service (MedsCheck). Of 79 unique drug therapy problems (DTPs) identified, the most common categories related to patients needing additional drug therapy and adverse drug reactions., Discussion and Conclusion: Patients enrolled in the ABM were generally older adults experiencing polypharmacy. The ABM presented opportunities for DTP identification and delivery of reimbursed services. Findings support continued exploration of the ABM to support integration of clinical services within community practice., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Timely administration of denosumab every 6 mo is critical in osteoporosis treatment to avoid multiple vertebral fracture risk upon denosumab discontinuation or delay. This study aimed to estimate the immediate and prolonged impact of the COVID-19 pandemic on the timing of denosumab doses. We identified older adults (≥66 yr) residing in the community who were due to receive denosumab between January 2016 and December 2020 using Ontario Drug Benefit data. We completed an interrupted time-series analysis to estimate the impact of the COVID-19 pandemic (March 2020) on the monthly proportion of on-time denosumab doses (183 +/-30 d). Analyses were stratified by user type: patients due for their second dose (novice users), third or fourth dose (intermediate users), or ≥5th dose (established users). In additional analyses, we considered patients living in nursing homes, switching to other osteoporosis drugs, and reported trends until February 2022. We studied 148 554 patients (90.9% female, mean [SD] age 79.6 [8.0] yr) receiving 648 221 denosumab doses. The average pre-pandemic proportion of on-time therapy was steady in the community, yet differed by user type: 64.9% novice users, 72.3% intermediate users, and 78.0% established users. We identified an immediate overall decline in the proportion of on-time doses across all user types at the start of the pandemic: -17.8% (95% CI, -19.6, -16.0). In nursing homes, the pre-pandemic proportion of on-time therapy was similar across user types (average 83.5%), with a small decline at the start of the pandemic: -3.2% (95% CI, -5.0, -1.2). On-time therapy returned to pre-pandemic levels by October 2020 and was not impacted by therapy switching. Although on-time dosing remains stable as of February 2022, approximately one-fourth of patients in the community do not receive denosumab on-time. In conclusion, although pandemic disruptions to denosumab dosing were temporary, levels of on-time therapy remain suboptimal., Competing Interests: A.M.R., S.K., T.G., and S.M.C. declare that they have no conflicts of interest. A.M.C. served as a consultant for Amgen Inc. outside of this work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Observational studies of osteoporosis medications can provide critical real-world evidence (RWE) that fills knowledge gaps left by clinical trials. However, careful consideration of study design is needed to yield reliable estimates of association. In particular, obtaining valid measurements of exposure to osteoporosis medications from real-world data (RWD) sources is complicated due to different medication classes, formulations, and routes of administration, each with different pharmacology. Extended half-lives of bisphosphonates and extended dosing of denosumab and zoledronic acid require particular attention. In addition, prescribing patterns and medication taking behavior often result in gaps in therapy, switching, and concomitant use of osteoporosis therapies. In this review, we present important considerations and provide specialized guidance for measuring osteoporosis drug exposures in RWD. First, we compare different sources of RWD used for osteoporosis drug studies and provide guidance on identifying osteoporosis medication use in these data sources. Next, we provide an overview of osteoporosis pharmacology and how it can influence decisions on exposure measurement within RWD. Finally, we present considerations for the measurement of osteoporosis medication exposure, adherence, switching, long-term exposures, and drug holidays using RWD. Ultimately, a thorough understanding of the differences in RWD sources and the pharmacology of osteoporosis medications is essential to obtain valid estimates of the relationship between osteoporosis medications and outcomes, such as fractures, but also to improve the critical appraisal of published studies., Competing Interests: KNH has received grant funding paid directly to Brown University for collaborative research from Insight Therapeutics, Sanofi, and Genentech for research on complex insulin regimens and influenza outbreak control in nursing homes. KNH has also served as a consultant for the Canadian Agency for Drugs and Technologies in Health. Other authors have no conflicts of interest to report., (© 2023 The Author(s).)

Competing Interests: Intérêts concurrents : Lora Giangregorio déclare avoir reçu des honoraires d’Amgen Inc. pour une conférence donnée sur l’exercice physique, hors du cadre du présent manuscrit, sans mention de médicaments. La Dre Giangregorio est également membre du conseil consultatif scientifique d’Ostéoporose Canada et coresponsable du Groupe d’intérêt spécial sur la fracture vertébrale du Fragility Fracture Network. Sandra Kim déclare qu’Ostéoporose Canada lui a offert le soutien d’une personne spécialiste de la méthodologie GRADE (Grading of Recommendations, Assessment, Development and Evaluations) à l’Université McMaster au cours de l’étude. De 2017 à 2020, la Dre Kim a aussi été membre bénévole du conseil d’administration d’Ostéoporose Canada. Nancy Santesso déclare avoir reçu une rémunération versée à son établissement (Université McMaster) afin d’apporter son expertise de l’outil GRADE à l’élaboration des lignes directrices et à la préparation de contenus au cours de l’étude. La Dre Santesso a aussi reçu du soutien d’Ostéoporose Canada pour se rendre aux réunions sur les lignes directrices. Heather McDonald-Blumer déclare avoir reçu des honoraires de consultation d’Eli Lilly et de Novartis pour sa présence à des conseils consultatifs, sans lien avec les présents travaux. Rowena Ridout est membre du conseil d’administration d’Ostéoporose Canada depuis 2020 (aucune rémunération perçue). Neil Binkley déclare avoir reçu une subvention de recherche (versée à son établissement) de Radius, ainsi que des frais de consultation et des honoraires d’Amgen. Angela Cheung a reçu des honoraires d’Amgen et des Laboratoires Paladin à titre de consultante. La Dre Cheung a aussi été membre du comité des lignes directrices cliniques de l’Endocrine Society, coprésidente du programme de santé postménopause de l’American College of Obstetrics and Gynecology et vice-présidente et coresponsable de la Conférence de prise de position 2023 de la Société internationale de densitométrie clinique. Robert Josse déclare avoir reçu des frais de consultation d’Amgen Canada, des Laboratoires Paladin et d’Alexion, ainsi que des honoraires d’Amgen et d’Alexion. Le Dr Josse a aussi participé à des comités consultatifs pour Amgen, Paladin, Alexion et Ultragenyx. Aliya Khan a reçu des subventions de recherche d’Alexion, d’Amgen Canada, de Takeda, d’Ascendis, de Chugai, de Radius, d’Amolyt et d’Ultragenyx, ainsi que des honoraires de conférencière d’Amgen, d’Alexion, d’Ascendis, de Takeda et d’Ultragenyx. La Dre Khan a également participé à des comités consultatifs pour Amgen Canada, Alexion, Amolyt, Ascendis et Takeda. E. Lynn Izumi Nash déclare que le Collège des médecins de famille de l’Ontario lui a versé des honoraires pour la conception d’ateliers de formation médicale continue sur l’ostéoporose. La Dre Nash est aussi membre du conseil consultatif scientifique d’Ostéoporose Canada (à titre bénévole). Zahra Bardai déclare avoir reçu des honoraires en tant que membre du comité de planification scientifique de Pri-Med Canada depuis 2011 et en tant que créatrice du Programme d’apprentissage basé sur la pratique en petit groupe de la Fondation pour l’éducation médicale continue, à l’Université McMaster. La Dre Bardai est aussi membre bénévole du conseil consultatif scientifique d’Ostéoporose Canada. Suzanne Cadarette déclare avoir reçu des subventions de recherche (versées à son établissement) en tant que cochercheuse principale pour des projets financés par les Instituts de recherche en santé du Canada et les National Institutes of Health. Heather Frame a siégé au conseil d’administration d’Ostéoporose Canada jusqu’en novembre 2020. Kaleen Hayes déclare avoir reçu des subventions de recherche à l’initiative des chercheurs du National Institute on Aging, d’Insight Therapeutics, de Genentech et de Sanofi (versées directement à son établissement), et des honoraires de consultation de l’Agence canadienne des médicaments et des technologies de la santé. Alexandra Papaioannou a fait partie d’un comité consultatif et de services de conférenciers et conférencières et a reçu des honoraires d’Amgen Canada. Christine Thomas a été membre du conseil d’administration d’Ostéoporose Canada à différentes périodes.

Background: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older., Methods: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework., Recommendations: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized., Interpretation: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life., Competing Interests: Competing interests: Lora Giangregorio reports receiving an honorarium from Amgen Inc. for a lecture on exercise with no mention of medications, outside the current manuscript. Dr. Giangregorio is also a member of the Scientific Advisory Council of Osteoporosis Canada and co-lead of the Vertebral Fracture Special Interest Group, Fragility Fracture Network. Sandra Kim reports receiving support from Osteoporosis Canada for a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodologist at McMaster University, during the conduct of the study. Dr. Kim was also a volunteer member of the Osteoporosis Canada Board of Directors from 2017 to 2020. Nancy Santesso reports receiving payment to provide GRADE expertise for guideline development and preparation of materials paid to institution (McMaster University), during the conduct of the study. Dr. Santesso has also received support from Osteoporosis Canada for travel to guideline-related meetings. Heather McDonald-Blumer reports receiving consulting fees from Eli Lilly and Novartis, for attendance on advisory boards, outside the submitted work. Rowena Ridout has been a member of the Osteoporosis Canada Board of Directors since 2020 (no payment received). Neil Binkley reports receiving a research grant (paid to institution) from Radius, and consulting fees and honoraria from Amgen. Angela Cheung has received honoraria for consultancy work from Amgen and Paladin Laboratories. Dr. Cheung has also held the following roles: member of the Clinical Guidelines Committee of the Endocrine Society; co-chair of the postmenopausal health pathway, American College of Obstetrics and Gynecology; and vice-president and co-chair of the 2023 Position Development Conference, International Society for Clinical Densitometry. Robert Josse reports receiving consulting fees from Amgen Canada, Paladin Laboratories and Alexion, and honoraria from Amgen and Alexion. Dr. Josse has also participated on advisory boards for Amgen, Paladin, Alexion and Ultragenyx. Aliya Khan has received research grants from Alexion, Amgen Canada, Takeda, Ascendis, Chugai, Radius, Amolyt and Ultragenyx, and speaker honoraria from Amgen, Alexion, Ascendis, Takeda and Ultragenyx. Dr. Khan has also participated on advisory boards for Amgen Canada, Alexion, Amolyt, Ascendis and Takeda. E. Lynn Izumi Nash reports receivin an honorarium from the Ontario College of Family Physicians for designing continuing medical education workshops on osteoporosis. Dr. Nash is also a member of the Scientific Advisory Council for Osteoporosis Canada (voluntary unpaid position). Zahra Bardai reports receiving honoraria as a member of the Pri-Med Canada Scientific Planning Committee (2011–present) and as an author of the Foundation for Medical Practice Education Small Group Practice–Based Learning Program, at McMaster University. Dr. Bardai is also a volunteer member of the Osteoporosis Canada Scientific Advisory Council. Suzanne Cadarette reports receiving research funds (paid to institution) as co–principal investigator on Canadian Institutes of Health Research and National Institutes of Health project grants. Heather Frame is a former member of the Osteoporosis Canada Board of Directors (term ended November 2020). Kaleen Hayes reports receiving researcher-initiated grants from the National Institute on Aging, Insight Therapeutics, Genentech and Sanofi (all paid directly to institution), and consulting fees from the Canadian Agency for Drugs and Technologies in Health. Alexandra Papaioannou has participated on an advisory board and in speakers’ bureaus and received honoraria from Amgen Canada. Christine Thomas has been a member of the Osteoporosis Canada Board of Directors at various time points. Conflict-of-Interest Oversight Committee: Heather McDonald-Blumer (Chair), Larry Funnell, Rowena Ridout., (© 2023 CMA Impact Inc. or its licensors.)

Background: Traditionally, much of community pharmacy practice relies on patients to request their own medication refills. These refills are often not aligned, which has been shown to decrease adherence and workflow efficiencies. The appointment-based model (ABM) is designed to proactively synchronize refills and schedule patient-pharmacist appointments., Objectives: To describe the characteristics of patients enrolled in the ABM; and to compare the number of distinct refill dates, number of refills, and adherence for antihypertensives, oral antihyperglycemics, and statins 6-months and 12-months pre-post ABM implementation., Methods: In September 2017, the ABM was implemented across independent community pharmacies within a pharmacy banner in Ontario, Canada. In December 2018, a convenience sample of three pharmacies was extracted. Demographic and clinical characteristics were collected on program enrollment (index) date for individual patients and their medication fill histories were used to investigate adherence measures including distinct number of refill dates, number of refills, and proportion of days covered. Descriptive statistics were analyzed using StataCorp., Results: Analysis of 131 patients (48.9% male; mean age 70.8 years ± 10.5 SD) filled on average 5.1 ± 2.7 medications with 73 (55.7%) experiencing polypharmacy. Patients had a significant reduction in mean number of refill dates (6.8 ± 3.8 SD six-months pre-enrollment, 4.9 ± 3.1 SD six-months post-enrollment, p < 0.0001). Adherence to chronic medications remained high (PDC ≥95%)., Conclusion: The ABM was implemented for a cohort of established users, already highly adherent to their chronic medications. Results demonstrate reduced filling complexity and fewer refill dates while also sustaining the high baseline adherence across all chronic medications studied. Future studies should investigate patient perspectives and potential clinical benefits of the ABM., Competing Interests: Declaration of competing interest All authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Inc.)

We identified inconsistency in fracture definitions in a prior review of studies that utilized claims data. Here, we aimed to compare fracture rates estimated using thirteen hip and seven radius/ulna fracture definitions. Our primary analysis compared results in a cohort of 120,363 older adults treated with oral bisphosphonates for ≥3 years. The most inclusive definition (hip: inpatient or emergency diagnosis; radius/ulna: inpatient, emergency, or outpatient diagnosis) served as a referent to compare the number and proportion of fractures captured. In sensitivity analyses, we considered a 180-day washout, excluded fractures associated with trauma; and hip only, excluded: (1) subtrochanteric fractures, and (2) hip replacement procedures. Hip fractures varied by definition in number (52-8058) and incidence (0.7-111.8/10,000 person-years). The second most inclusive definition required one inpatient diagnosis and identified 8% fewer hip fractures than the referent. Excluding hip replacements missed 33% of hip fractures relative to the primary analysis. Radius/ulna fractures also ranged in number (1589-6797) and incidence (22.0-94.3/10,000 person-years). Outpatient data were important, when restricted to inpatient or emergency data, only 78% of radius/ulna fractures were identified. Other than hip replacement procedures, sensitivity analyses had minimal impact on fracture identification. Analyses were replicated in a cohort of patients treated with long-term glucocorticoids. This study highlights the importance and impact of coding decisions on fracture outcome definitions. Further research is warranted to inform best practice in fracture outcome identification.

Healthcare administrative (claims) data are commonly utilized to estimate drug effects. We identified considerable heterogeneity in fracture outcome definitions in a scoping review of 57 studies that estimated osteoporosis drug effects on fracture risk. Better understanding of the impact of different fracture definitions on study results is needed., Purpose: Healthcare administrative (claims) data are frequently used to estimate the real-world effects of drugs. Fracture incidence is a common outcome of osteoporosis drug studies. We aimed to describe how fractures are defined in studies that use claims data., Methods: We searched MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and gray literature for studies published in English between 2000 and 2020 that estimated fracture effectiveness (hip, humerus, radius/ulna, vertebra) or safety (atypical fracture of the femur, AFF) of osteoporosis drugs using claims data in Canada and the USA. Literature searches, screening and data abstraction were completed independently by two reviewers., Results: We identified 57 eligible studies (52 effectiveness, 3 safety, 2 both). Hip fracture was the most common fracture site studied (93%), followed by humerus (66%), radius/ulna (59%), vertebra (61%), and AFF (9%). Half (n = 29) of the studies did not indicate specific data sources, codes, or cite a validation paper. Of the papers with sufficient detail, heterogeneity in fracture definitions was common. The most common definition within each fracture site was used by less than half of the studies that examined effectiveness (12 definitions in 29 hip fracture papers, 8 definitions in 17 humerus papers, 8 definitions in 13 radius/ulna papers, 9 definitions in 15 vertebra papers), and 3 definitions among 4 AFF papers., Conclusion: There is ambiguity and heterogeneity in fracture outcome definitions in studies that leverage claims data. Better transparency in outcome reporting is needed. Future exploration of how fracture definitions impact study results is warranted., (© 2022. The Author(s).)

Competing Interests: Conflict of Interest Statement: The authors report no conflicts of interest.

While the economic burden of influenza infection is well described among adults aged 65 and older, less is known about younger adults. A systematic literature review was conducted to describe the economic burden of seasonal influenza in adults aged 18 to 64 years, to identify the main determinants of direct and indirect costs, and to highlight any gaps in the existing published evidence. MEDLINE and Embase were searched from 2007 to February 7, 2020, for studies reporting primary influenza-related cost data (direct or indirect) or absenteeism data. Of the 2613 publications screened, 51 studies were included in this review. Half of them were conducted in the United States, and 71% of them described patients with influenza-like illness rather than laboratory-confirmed disease. Only 12 studies reported cost data specifically for at-risk populations. Extracted data highlighted that within the 18- to 64-year-old group, up to 88% of the economic burden of influenza was attributable to indirect costs, and up to 75% of overall direct costs were attributable to hospitalizations. Furthermore, within the 18- to 64-year-old group, influenza-related costs increased with age and underlying medical conditions. The reported cost of influenza-related hospitalizations was found to be up to 2.5 times higher among at-risk populations compared with not-at-risk populations. This review documents the considerable economic impact of influenza among adults aged 18 to 64. In this age group, most of the influenza costs are indirect, which are generally not recognized by decision makers. Future studies should focus on at-risk subgroups, lab-confirmed cases, and European countries., (© 2022 Sanofi Pasteur. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter., Objective: To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy., Design: Population-based, matched, cohort study., Setting: Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020., Patients: Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday., Measurements: The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups., Results: A total of 25 077 propensity score-matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32])., Limitation: Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events., Conclusion: Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk., Primary Funding Source: Canadian Institutes of Health Research.

Objective: The objective of this review is to describe fracture outcome definitions in observational osteoporosis drug effects studies from Canada and the United States., Introduction: Health care administrative data are commonly utilized in pharmacoepidemiologic studies. These data are used to define outcomes, such as fractures, and are critical to determining real-world safety and effectiveness of medications. However, there is no current standard for fracture outcome definitions in observational studies. As a result, fractures are inconsistently defined. To inform future research, a synthesis of how fractures are defined in observational studies using health care administrative claims data is needed. Providing clarity on how fractures are defined will provide guidance for future research., Inclusion Criteria: We will include observational studies from the United States and Canada that consider the impact of osteoporosis pharmacotherapies on fracture risk and leverage health care administrative data., Methods: This review will follow the three-step JBI methodology for scoping reviews. We will search MEDLINE, Embase, and CINAHL for studies published in English from 2000 to the present. Following de-duplication, titles and abstracts will be screened independently by two reviewers. We will then conduct full-text screening for eligible studies. In addition, Canadian and US government pharmacovigilance websites will be searched to identify gray literature. Data extraction will be completed by two reviewers. Results will be presented in figures and in tabular format., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

Objective: The objective of this review is to summarize observational research methods employed to study fracture risk and the use of type 2 diabetes mellitus medications. The methods summary will be used as a case study to illustrate current practices in the study of medication effects on fracture risk., Introduction: Observational studies examining drug effects on fracture risk fill knowledge gaps left by clinical trials but require specific design considerations. In recent years, several pharmacoepidemiologic studies have examined fracture risk as a possible adverse effect of type 2 diabetes mellitus medications using varying methodologies; these studies can illustrate design considerations for studies of fracture risk., Inclusion Criteria: This scoping review will consider peer-reviewed observational studies that examine the effects of type 2 diabetes mellitus medications on fracture risk. Primary literature comprising empirical pharmacoepidemiologic studies, such as cohort, case-control, case-crossover, self-controlled, case series, and case-cohort designs, that evaluate fracture risk associated with at least one type 2 diabetes mellitus medication will be eligible. Studies without use of an administrative database and those with an experimental, cross-sectional, or time-series design will be excluded., Methods: This scoping review will follow JBI methodology for scoping reviews. MEDLINE (Ovid), Embase (Ovid), and CINAHL Plus with Full Text (EBSCO) will be searched from January 1, 2000 (to capture recent methodologies) to the present to identify eligible articles. After de-duplication, titles and abstracts will be screened independently by two reviewers, then full texts will be reviewed. Data on study methods will be extracted from eligible texts using a piloted form developed by the authors, and study methods will be aggregated in tabular format., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

For self-controlled studies of medication-related effects, time-varying confounding by indication can occur if the indication varies over time. We describe how active comparators might mitigate such bias, using an empirical example. Approaches to using active comparators are described for case-crossover design, case-time-control design, self-controlled case-series, and sequence symmetry analyses. In the empirical example, we used Danish data from 1996-2018 to study the association between penicillin and venous thromboembolism (VTE), using roxithromycin, a macrolide antibiotic, as comparator. Upper respiratory infection is a transient risk factor for VTE, thus representing time-dependent confounding by indication. Odds ratios for case-crossover analysis were 3.35 (95% confidence interval: 3.23, 3.49) for penicillin and 3.56 (95% confidence interval: 3.30, 3.83) for roxithromycin. We used a Wald-based method or an interaction term to estimate the odds ratio for penicillin with roxithromycin as comparator. These 2 estimates were 0.94 (95% confidence interval: 0.87, 1.03) and 1.03 (95% confidence interval: 0.95, 1.13). Results were similar for the case-time-control analysis, but both the self-controlled case-series and sequence symmetry analysis suggested a weak protective effect of penicillin, seemingly explained by VTE affecting future exposure exclusively for penicillin. The strong association of antibiotics with VTE suggests presence of confounding by indication. Such confounding can be mitigated by using an active comparator., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This scoping review will aim to compare strategies for measuring prescription medication switching with pharmacy claims data, with a focus on psychotropic vs non-psychotropic medications., Introduction: Medication switching (ie, the replacement of one medication for another) is common and occurs due to several factors (such as adverse effects to a specific medication). In pharmacoepidemiology studies that use pharmacy claims data, it is important to identify and account for switches; however, due to data limitations and lack of a methodological standard, this can be challenging. The aim of this scoping review is to describe how studies have previously measured medication switching with pharmacy claims data in order to create a repository of common strategies and highlight areas for future research., Inclusion Criteria: This review will include studies that have used pharmacy claims data to measure medication switching as their primary independent or dependent variable. Studies conducted at the individual level (ie, not ecological), published between January 1, 1980, and October 31, 2020, and investigating orally administered, non-anti-infective medications will be considered. No age, population, or context restrictions are specified as inclusion criteria., Methods: JBI methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews were used for this protocol. MEDLINE (PubMed), Embase (Ovid), Central (Cochrane Library), CINAHL (EBSCO), and Google Scholar will be searched with the assistance of a health sciences research librarian. Two reviewers will independently screen titles, abstracts, and full-text articles. Strategies for measuring medication switching will be narratively described and summarized overall and by broad medication class., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

Competing Interests: Conflict of interest statement: The authors report no conflicts of interest.

Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years., Introduction: The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up., Methods: Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy., Results: We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab., Conclusions: Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.

Purpose: Consensus is needed on conceptual foundations, terminology and relationships among the various self-controlled "trigger" study designs that control for time-invariant confounding factors and target the association between transient exposures (potential triggers) and abrupt outcomes. The International Society for Pharmacoepidemiology (ISPE) funded a working group of ISPE members to develop guidance material for the application and reporting of self-controlled study designs, similar to Standards of Reporting Observational Epidemiology (STROBE). This first paper focuses on navigation between the types of self-controlled designs to permit a foundational understanding with guiding principles., Methods: We leveraged a systematic review of applications of these designs, that we term Self-controlled Crossover Observational PharmacoEpidemiologic (SCOPE) studies. Starting from first principles and using case examples, we reviewed outcome-anchored (case-crossover [CCO], case-time control [CTC], case-case-time control [CCTC]) and exposure-anchored (self-controlled case-series [SCCS]) study designs., Results: Key methodological features related to exposure, outcome and time-related concerns were clarified, and a common language and worksheet to facilitate the design of SCOPE studies is introduced., Conclusions: Consensus on conceptual foundations, terminology and relationships among SCOPE designs will facilitate understanding and critical appraisal of published studies, as well as help in the design, analysis and review of new SCOPE studies. This manuscript is endorsed by ISPE., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Competing Interests: Conflict of Interest Statement:The authors report no conflicts of interest.

Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight.

Adverse events related to long-term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long-term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as ≥12 months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120-day period preceding discontinuation or restart referent to the 120-day preceding control periods. Among 73,800 long-term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12 months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual-energy X-ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long-term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Background: Several clinical prediction rules (CPRs) for complications and mortality of Clostridioides difficile infection (CDI) have been developed but only a few have gone through external validation, and none is widely recommended in clinical practice., Methods: CPRs were identified through a systematic review. We included studies that predicted severe or complicated CDI (cCDI) and mortality, reported at least an internal validation step, and for which data were available with minimal modifications. Data from a multicenter prospective cohort of 1380 adults with confirmed CDI were used for external validation. In this cohort, cCDI occurred in 8% of the patients and 30-day all-cause mortality occurred in 12%. The performance of each tool was assessed using individual outcomes, with the same cut-offs and standard parameters., Results: Seven CPRs were assessed. Three predictive scores for cCDI showed low sensitivity (25-61%) and positive predictive value (PPV; 9-31%), but moderate specificity (54-90%) and negative predictive value (NPV; 82-95%). One model [using age, white blood cell count (WBC), narcotic use, antacids use, and creatinine ratio > 1.5× the normal level as covariates] showed a probability of 25% of cCDI at the optimal cut-off point with 36% sensitivity and 84% specificity. Two scores for mortality had low sensitivity (4-55%) and PPV (25-31%), and moderate specificity (71-78%) and NPV (87-92%). One predictive model for 30-day all-cause mortality [Charlson comorbidity index, WBC, blood urea nitrogen (BUN), diagnosis in ICU, and delirium] showed an AUC-ROC of 0.74. All other CPRs showed lower AUC values (0.63-0.69). Errors in calibration ranged from 12%- 27%., Conclusions: Included CPRs showed moderate performance for clinical use in a large validation cohort with a majority of patients infected with ribotype 027 strains and a low rate of cCDI and mortality. These data show that better CPRs need to be developed and validated., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: L.V. has served on advisory boards for Merus, Merck, Abbott, and Wyeth, and has received compensation to conduct clinical trials involving antibacterials from Wyeth, Pfizer, Optimer, Cubist, Merck and Actelion. A.E.S. served on Merck Advisory Boards and received honoraria for speaking on behalf of Merck Canada Inc. All other authors have no competing interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no restrictions on sharing of data and/or materials.

The purpose of this paper is to help readers choose an appropriate observational study design for measuring an association between an exposure and disease incidence. We discuss cohort studies, sub-samples from cohorts (case-cohort and nested case-control designs), and population-based or hospital-based case-control studies. Appropriate study design is the foundation of a scientifically valid observational study. Mistakes in design are often irremediable. Key steps are understanding the scientific aims of the study and what is required to achieve them. Some designs will not yield the information required to realise the aims. The choice of design also depends on the availability of source populations and resources. Choosing an appropriate design requires balancing the pros and cons of various designs in view of study aims and practical constraints. We compare various cohort and case-control designs to estimate the effect of an exposure on disease incidence and mention how certain design features can reduce threats to study validity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered., Introduction: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time., Methods: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex., Results: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%)., Conclusions: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.

We studied 46,797 older adults who initiated denosumab in Ontario, Canada. Patient characteristics remained relatively stable over time and aligned with public reimbursement restrictions. Almost half of patients persisted with therapy for at least 3 years. Fifty-nine percent of patients who discontinued denosumab returned to treatment within 3.6 years., Introduction: The purpose of this study was to describe the characteristics of patients who initiated denosumab and estimate persistence with therapy., Methods: We identified older adults (aged ≥ 66 years) in Ontario who initiated denosumab between 2012/02 and 2015/03 and followed them to 2016/03. Patient characteristics were summarized using medical and pharmacy claims in the year before starting denosumab and osteoporosis drug use considered since 1996/10. Persistence with denosumab and return after discontinuation (> 90-day gap) were estimated using Kaplan-Meier curves. Analyses were stratified by community and long-term care (LTC) residence., Results: We identified 46,797 patients (monthly mean = 1263, SD = 187); 97% female, 13% LTC. Community-dwelling patients had a higher prevalence of bone mineral density testing (62% vs. 5%), yet were younger (mean age 78.5 vs. 86.6 years) and had lower prevalence of hip fractures (3% vs. 10%) compared to LTC patients. Eighty-two percent of patients had used osteoporosis medications in the past; 99% of whom took an oral bisphosphonate. Persistence was similar between community-dwelling and LTC patients: 59% persisted ≥ 2 years, 48% ≥ 3 years, and 38% ≥ 4 years, yet a larger proportion of LTC patients returned to denosumab after discontinuation (76% vs. 57%)., Conclusions: Denosumab utilization is increasing at a steady rate in Ontario. However, persistence remains a concern given the highly reversible pharmacokinetic profile of denosumab that results in a rapid increased fracture risk following discontinuation. Over 80% of patients had a history of oral bisphosphonate therapy, which may persist in bone despite discontinuing denosumab. Consequently, better understanding of denosumab safety and effectiveness among real-world users is important.

MedsCheck (MC) is an annual medication review service delivered by community pharmacists and funded by the government of Ontario since 2007 for residents taking three or more medications for chronic conditions. In 2010, MC was expanded to include patients with diabetes (MCD), home-bound patients (MCH), and residents of long-term care homes (MCLTC). The Ontario government introduced an abrupt policy change effective 1 October 2016 that added several components to all MC services, especially those completed in the community. We used an interrupted time series design to examine the impact of the policy change (24 months pre- and post-intervention) on the monthly number of MedsCheck services delivered. Immediate declines in all services were identified, especially in the community (47%-64% drop MC, 71%-83% drop MCD, 55% drop MCH, and 9%-14% drop MCLTC). Gradual increases were seen over 24 months post-policy change, yet remained 21%-76% lower than predicted for MedsCheck services delivered in the community, especially for MCD. In contrast, MCLTC services were similar or exceeded predicted values by September 2018 (from 5.1% decrease to 3.5% increase). A more effective implementation of health policy changes is needed to ensure the feasibility and sustainability of professional community pharmacy services., Competing Interests: The authors declare no conflict of interest.

We examined the 5-year refracture rate of 6543 patients and found an overall rate of 9.7%. Adjusted analysis showed that presenting with multiple fractures was an indicator of a higher refracture risk; while presenting with an ankle fracture was associated with a lower refracture risk., Introduction: To examine refractures among patients screened in a province-wide fracture liaison service (FLS)., Methods: We assessed the 5-year refracture rate of fragility fracture patients aged 50+ who were screened at 37 FLS fracture clinics in Ontario, Canada. Refracture was defined as a new hip, pelvis, spine, distal radius, or proximal humerus fracture. Kaplan-Meier curves and Cox proportional hazards model adjusting for age, sex, and index fracture type were used to examine refracture rates., Results: The 5-year refracture rate of 6543 patients was 9.7%. Those presenting with multiple fractures at baseline (i.e., two or more fractures occurring simultaneously) had the highest refracture rate of 19.6%. As compared to the 50-65 age group, refracture risk increased monotonically with age group (66-70 years: HR = 1.3, CI 95%, 1.0-1.7; 71-80 years: HR = 1.7, CI 1.4-2.1; 81+ years: HR = 3.0, CI 2.4-3.7). Relative to distal radius, presenting with multiple fractures at screening was associated with a higher risk of refracture (HR = 2.3 CI 1.6-3.1), while presenting with an ankle fracture was associated with a lower risk of refracture (HR = 0.7 CI 0.6-0.9). Sex was not a statistically significant predictor of refracture risk in this cohort (HR = 1.2, CI 1.0-1.5)., Conclusions: One in ten patients in our cohort refractured within 5 years after baseline. Presenting with multiple fractures was an indicator of a higher refracture risk, while presenting with an ankle fracture was associated with a lower refracture risk. A more targeted FLS approach may be appropriate for patients at a higher refracture risk.

Background: Little is known about those vaccinated against influenza after pharmacists were added to the Ontario Universal Influenza Immunization Program, in 2012. Our aim was to identify characteristics of patients vaccinated against influenza and predictors of vaccination at a physician's office versus a community pharmacy., Methods: We conducted a cross-sectional study of Ontario residents who had a record of receipt of an influenza vaccine between October and March in the 2013/14 and 2015/16 influenza seasons in Ontario using health administrative databases. We used Poisson regression models to estimate associations between baseline characteristics and the receipt of influenza vaccination in a community pharmacy. All analyses were stratified by age group (≤ 65 yr or ≥ 66 yr)., Results: Overall, we found a 7.9% decrease in vaccinations administered in 2015/16 (2 454 178) compared to 2013/14 (2 677 278). The number of patients vaccinated in community pharmacies increased between the 2 periods (757 729 [28.3%] in 2013/14 v. 859 794 [35.0%] in 2015/16). Living in nonurban areas or higher-income neighbourhoods, not identifying as an immigrant, not having a diagnosis of diabetes or hypertension, and receiving a pharmacist service on the same day as the vaccination were predictors of being vaccinated in a pharmacy, regardless of age group. Among patients aged 66 or more, those who had a hospital admission in the previous year were more likely to be vaccinated in a pharmacy than in a physician's office (adjusted incidence rate ratio [IRR] 1.08, 95% confidence interval [CI] 1.06-1.09), whereas those with higher annual medication costs were more likely to be vaccinated in a physician's office. The location of the previous season's vaccination predicted the current season's place of vaccination (age ≥ 66 yr: physician's office: adjusted IRR 0.56 [95% CI 0.56-0.57], pharmacy: adjusted IRR 2.37 [95% CI 2.35-2.39]; age ≤ 65 yr: physician's office: adjusted IRR 0.57 [95% CI 0.57-0.57], pharmacy: adjusted IRR 2.19 [95% CI 2.18-2.20])., Interpretation: For the 2013/14 and 2015/16 influenza seasons, the influenza vaccine was administered more frequently in physician offices than in community pharmacies, but the proportion of patients vaccinated in community pharmacies increased between the 2 periods. Physicians and pharmacists can encourage patients to take advantage of the availability of influenza vaccines across various settings., Competing Interests: Competing interests: Sherilyn Houle and Nancy Waite have received educational grants from Merck and Sanofi, and Sherilyn Houle received support for a graduate student trainee from Valneva Canada. No other competing interests were declared., (Copyright 2019, Joule Inc. or its licensors.)

Objectives: To describe insulin utilization and spending across Canada and investigate how interprovincial variations in long-acting insulin uptake impact provincial spending., Methods: We conducted a cross-sectional time-series analysis of insulin products dispensed nationally from January 1, 2010, to December 31, 2015, using data from IQVIA (Durham, North Carolina, United States). Analysis was stratified according to insulin type, payer and province. We report annual numbers for national insulin dispensing and spending and provincial numbers for publicly funded long-acting insulin dispensing and spending rates that are standardized by public drug beneficiary enrolment and diabetes prevalence. We report the percent of change of an annual provincial cost-to-utilization index of total insulin spending to total insulin dispensing between 2010 and 2015., Results: Between 2010 and 2015, total insulin utilization increased 21% (4.4 million to 5.3 million prescriptions), and total insulin costs increased 54% ($345 million to $530 million) nationally. The national dispensing rate of long-acting insulin (+96%) and rapid-acting insulin (+38%) increased, while the national dispensing rate for intermediate-acting (-23%), short-acting (-37%) and premixed (-28%) insulins declined. Large interprovincial variation was observed for the rate of long-acting insulin uptake (range, Alberta, +1,505%; British Columbia, +27%) and the rate of long-acting insulin spending (Alberta, +2,177%; British Columbia, +44%) between 2010 and 2015 after standardization. Provinces with higher rates of long-acting insulin uptake experienced faster increases in their cost-to-utilization index (Alberta, +78%; British Columbia, +24%)., Conclusions: Overall, the rate of uptake of long-acting insulins has increased nationally. Uptake varies widely among provinces and is likely to be associated with differential cost increases across public payers in Canada., (Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)