Prescribed Drug Spending in Canada, 2019: A Focus on Public Drug Programs.

Public drug program spending accounts for 43.1% of prescribed drug spending in Canada. This report provides an in-depth look at public drug program spending in Canada, using the Canadian Institute for Health Information's (CIHI) National Prescription Drug Utilization Information System. Public drug program spending does not include spending on drugs dispensed in hospitals or on those funded through cancer agencies and other special programs.

Further exploration of the structure-activity relationship of imidazoquinolines; identification of potent C7-substituted imidazoquinolines.

Small molecule agonists of TLR7/8, such as imidazoquinolines, are validated agonists for the treatment of cancer and for use in vaccine adjuvants. Imidazoquinolines have been extensively modified to understand the structure-activity relationship (SAR) at the N1- and C2-positions resulting in the clinical drug imiquimod, resiquimod, and several other highly potent analogues. However, the SAR of the aryl ring has not been fully elucidated in the literature. This initial study examines the SAR of C7-substituted imidazoquinolines. These compounds not only demonstrated that TLR7/8 tolerate changes at the C7-position but can increase potency and change their cytokine profiles. The most notable TLR7/8 agonists developed from this study 5, 8, and 14 which are up to 4-fold and 2-fold more active than resiquimod for TLR8 and/or TLR7, respectively, and up to 100-fold more active than the FDA approved imiquimod for TLR7.

Formulation and preclinical evaluation of a toll-like receptor 7/8 agonist as an anti-tumoral immunomodulator.

The toll-like receptor 7 and 8 (TLR7/8) agonist Resiquimod (R848) has been recognized as a promising immunostimulator for the treatment of cutaneous cancers in multiple clinical trials. However, systemic administration of R848 often results in strong immune-related toxicities while having limited therapeutic effects to the tumor. In the present study, a prodrug-based nanocarrier delivery system was developed that exhibited high therapeutic efficiency. R848 was conjugated to α-tocopherol to constitute an R848-Toco prodrug, followed by formulating with a tocopherol-modified hyaluronic acid (HA-Toco) as a polymeric nano-suspension. In vitro evaluation showed that the delivery system prolonged the release kinetics while maintaining TLR agonist activities. When administered subcutaneously, the nano-suspension formed a depot at the injection site, inducing localized immune responses without systemic expansion. This formulation also suppressed tumor growth and recruited immune cells to the tumor in a murine model of head and neck cancer. In a preclinical canine study of spontaneous mast cell tumors, the treatment led to a 67% response rate (three partial remissions and one complete remission).

Comparing the contribution of prescribed opioids to opioid-related hospitalizations across Canada: A multi-jurisdictional cross-sectional study.

BACKGROUND: The Canadian opioid crisis is a complex, multifaceted problem involving prescribed, diverted and illicitly manufactured opioids. This study sought to characterize the contribution of prescribed opioids to opioid-related hospitalizations in Canada. METHODS: We conducted a cross-sectional study of all individuals who were admitted to hospital for opioid toxicity in British Columbia (BC), Manitoba and Ontario between April 2015 and March 2016. We used prescription claims to ascertain active prescription opioid use at time of hospital admission. In secondary analyses, we defined recent opioid prescriptions as those that were dispensed in the 30 and 180 days up to and including admission, and the prevalence of active co-prescription of benzodiazepines with opioids at time of overdose. RESULTS: We identified 2599 instances of opioid toxicity over the study period. In BC, 34.1% of hospital visits for overdose occurred in people with an active opioid prescription, compared to 52.2% (47 of 90) in Manitoba and 52.8% (804 of 1524) in Ontario. However, active opioid prescriptions prior to overdose varied significantly by age and sex. Co-prescription of opioids and benzodiazepines prior to overdose ranged from 17.1% in BC to 35.6% in Manitoba. CONCLUSIONS: There remains an important ongoing contribution of prescribed opioids to overdoses across Canada, but non-prescribed opioids play a growing role, particularly in BC. These findings underscore the importance of more judicious opioid prescribing, harm reduction programs, and improved access to addiction care for people with an opioid use disorder.

Frequency and cost of potentially inappropriate prescribing for older adults: a cross-sectional study.

BACKGROUND: Many medications pose greater health risks when prescribed for older adults, compared with available pharmacologic and nonpharmacologic alternatives. We sought to quantify the frequency and cost of potentially inappropriate prescribing for older women and men in Canada. METHODS: Using data for 2013 from the National Prescription Drug Utilization Information System database, which contains prescription claims from publicly financed drug plans in all provinces except for Quebec, we identified the frequency of prescribing and cost of potentially inappropriate medications dispensed to provincial drug plan enrollees aged 65 years or more. Potentially inappropriate prescriptions were defined with the use of the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. RESULTS: For the 6 provinces with relatively complete data coverage (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario and Prince Edward Island), 37% of older people filled 1 or more prescription meeting the Beers Criteria. A higher proportion of women (42%) than men (31%) filled potentially inappropriate prescriptions. The highest rates of prescribing of potentially inappropriate medications were among women aged 85 or more (47%). Benzodiazepines and other hypnotics were the leading contributors to the overall frequency of and sex differences in prescribing of potentially inappropriate drugs among older adults. We estimated that $75 per older Canadian, or $419 million in total, was spent on potentially inappropriate medications outside of hospital settings in 2013. INTERPRETATION: Prescribing of potentially inappropriate medications for older adults is common and costly in Canada, especially for women. Multipronged and well-coordinated strategies to reduce the use and cost of potentially inappropriate drugs would likely generate significant health system savings while simultaneously generating major benefits to patient health.

Palladium Catalysis Enables Benzylation of α,α-Difluoroketone Enolates.

A palladium-catalyzed decarboxylative benzylation reaction of α,α-difluoroketone enolates is reported, in which the key C(α)-C(sp(3) ) bond is generated by reductive elimination from a palladium intermediate. The transformation provides convergent access to α-benzyl-α,α-difluoroketone-based products, and should be useful for accessing biological probes.

The Canadian National System for Incident Reporting in Radiation Treatment (NSIR-RT) Taxonomy.

PURPOSE: Incident investigation, reporting, and learning are core elements of quality improvement in radiation treatment. This report describes the development of a Canadian National System for Incident Reporting in Radiation Treatment (NSIR-RT), focusing especially on the taxonomy. METHODS AND MATERIALS: The NSIR-RT was developed to provide a framework in Canada for reporting and analyzing radiation treatment incidents. A key objective was to assure compatibility with other international reporting systems to facilitate future information exchange. The Canadian community was engaged at every step of the development process through Delphi consensus building and inter-user agreement testing to promote awareness of the system and motivate broad-based utilization across the country. RESULTS: The final taxonomy was comprised of 6 data groups (impact, discovery, patient, details, treatment delivery, and investigation) and 33 data categories with predefined menu options. There was a high level agreement within the Canadian community about the final suite of data categories, and broad alignment of these categories with the World Health Organization and other American and European radiation treatment incident classifications. CONCLUSIONS: The Canadian NSIR-RT taxonomy will be implemented as an online, web-based reporting and analysis system. It is expected that the taxonomy will evolve and mature over time to meet the changing needs of the Canadian radiation treatment community and support radiation treatment incident learning on a global scale.

Drug Use among Seniors on Public Drug Programs in Canada, 2012.

Seniors take more drugs than younger Canadians because, on average, they have a higher number of chronic conditions. Although taking multiple medications may be necessary to manage these conditions, it is important to consider the benefits and risks of each medication and the therapeutic goals of the patient. This article provides an in-depth look at the number and types of drugs used by seniors using drug claims data from the CIHI's National Prescription Drug Utilization Information System Database, representing approximately 70% of seniors in Canada. In 2012, almost two-thirds (65.9%) of seniors on public drug programs had claims for five or more drug classes, while 27.2% had claims for 10 or more, and 8.6% had claims for 15 or more. The most commonly used drug class was statins, used by nearly half (46.6%) of seniors. Nearly two-thirds (60.9%) of seniors living in long-term care (LTC) facilities had claims for 10 or more drug classes. Proton pump inhibitors were the most commonly used drug class among seniors living in LTC facilities (used by 37.0% of seniors in LTC facilities), while statins ranked seventh (29.8%).

Public Drug Coverage and Its Impact on Triptan Use Across Canada: A Population-Based Study.

BACKGROUND: Public drug coverage for triptan medications varies across jurisdictions in Canada, which may lead to differences in usage patterns and patient risk for medication overuse headache. METHODS: We conducted a population-based, cross-sectional analysis of publicly funded triptan use in seven provinces across Canada from January 1, 2012 to December 31, 2012. All patients who had filled at least one prescription for a triptan during the study period were included. We defined quantity limits of 6, 12, and 18 triptan units per month to assess the prevalence of high volumes of triptan use, which may place patients at risk for medication overuse headaches, and compared this prevalence between provinces with different funding restrictions. RESULTS: We identified 14,085 publicly funded users of triptans in 2012 in the seven provinces studied, 82.5% of whom were aged less than 65 years (N = 11,631). The prevalence of triptan use ranged substantially by province, from 0.04% in Ontario to a maximum of 1.0% in Manitoba (P < .001). Furthermore, the percentage of patients in each province using more than 6, 12, or 18 units per month differed significantly between provinces (P < .001). In particular, the percentage of patients treated with more than 6 units per month ranged from as low as 2.1% in Saskatchewan to 43.8% in Ontario. CONCLUSIONS: Differing public drug reimbursement criteria for triptans may be one contributing factor that has led to our observation of considerable variation in both prevalence of triptan prescribing and potential overuse of these medications. We offer that monthly quantity limits may be considered as a tool to decrease risks for medication overuse headache.

Medication use among Canadian seniors.

As they age, many seniors develop a progressively more complex mix of health conditions. Multiple prescription medications are often required to help manage these conditions and control symptoms, with the goal of maintaining seniors' health for as long as possible. This article explores trends in the number and types of medications used by seniors on public drug programs in Canada. Our findings suggest that a high proportion of Canadian seniors are taking several medications, highlighting the need for medication management systems focusing on this population.