Mina Tadrous

The Burden of Opioid-Related Mortality in the United States

Key Points Question What has been the burden of opioid-related deaths in the United States over a recent 15-year period? Findings In this serial cross-sectional study, we found that the percentage of all deaths attributable to opioids increased 292% (from 0.4% to 1.5%) between 2001 and 2016, resulting in approximately 1.68 million person-years of life lost in 2016 alone (5.2 per 1000 population). The burden was particularly high among adults aged 24 to 35 years; in 2016, 20% of deaths in this age group involved opioids. Meaning Premature death from opioids imposes an enormous and growing public health burden across the United States.

Appropriate prescribing in nursing homes demonstration project (APDP) study protocol: pragmatic, cluster-randomized trial and mixed methods process evaluation of an Ontario policy-maker initiative to improve appropriate prescribing of antipsychotics

BackgroundAntipsychotic medications are routinely prescribed in nursing homes to address the behavioral and psychological symptoms of dementia. Unfortunately, inappropriate prescribing of antipsychotic medications is common and associated with increased morbidity, adverse drug events, and hospitalizations. Multifaceted interventions can achieve a 12–20xa0% reduction in antipsychotic prescribing levels in nursing homes. Effective interventions have featured educational outreach and ongoing performance feedback.Methods/DesignThis pragmatic, cluster-randomized control trial and embedded process evaluation seeks to determine the effect of adding academic detailing to audit and feedback on prescribing of antipsychotic medications in nursing homes, compared with audit and feedback alone. Nursing homes within pre-determined regions of Ontario, Canada, are eligible if they express an interest in the intervention. The academic detailing intervention will be delivered by registered health professionals following an intensive training program including relevant clinical issues and techniques to support health professional behavior change. Physicians in both groups will have the opportunity to access confidential reports summarizing their prescribing patterns for antipsychotics in comparison to the local and provincial average. Participating homes will be allocated to one of the two arms of the study (active/full intervention versus standard audit and feedback) in two waves, with a 2:1 allocation ratio. Homes will be randomized after stratifying for geography, baseline antipsychotic prescription rates, and size, to ensure a balance of characteristics. The primary outcome is antipsychotic dispensing in nursing homes, measured 6xa0months after allocation; secondary outcomes include clinical outcomes and healthcare utilization.DiscussionPolicy-makers and the public have taken note that antipsychotics are used in nursing homes in Ontario far more than other jurisdictions. Academic detailing can be an effective technique to address challenges in appropriate prescribing in nursing homes, but effect sizes vary widely. This opportunistic, policy-driven evaluation, embedded within a government-initiated demonstration project, was designed to ensure policy-makers receive the best evidence possible regarding whether and how to scale up the intervention.Trial registrationClinicalTrials.gov NLM Identifier: NCT02604056.

Publicly funded overactive bladder drug treatment patterns in Ontario over 15 years: An ecological study

INTRODUCTIONnMedication is an important option for patients with overactive bladder (OAB), with four different drugs approved over the last 10 years, including the first non-anticholinergic treatment, mirabegron. We set out to describe the number and rate of users of medication for the management of OAB over the last 15 years among residents of Ontario, Canada covered by the public drug programs.nnnMETHODSnWe conducted a population-based, repeated cross-sectional study examining quarterly publically funded prescription claims for OAB medications from January 2000 to June 2016 in Ontario, Canada.nnnRESULTSnWe report two major changes in prescription patterns for OAB. The first was the rise of newer, more selective anticholinergics (tolterodine, solifenacin, and darifenacin) replacing oxybutynin. This led to a 54.8% reduction in the rate of users of oxybutynin over the study period from 10.4 users/1000 beneficiaries in 2000 to 4.7 users/1000 beneficiaries in 2016. Recently, we saw the emergence of mirabegron as the most commonly prescribed treatment for OAB. By the final quarter of the observation period, mirabegron was the most commonly used OAB treatment with 25.0% (n=19 411) of all OAB medication users in Ontario (n=77 660).nnnCONCLUSIONSnOur findings highlight the rapid uptake of novel agents and a major shift in the treatment of OAB over the last three years.

Contributions of prescribed and non-prescribed opioids to opioid related deaths: population based cohort study in Ontario, Canada

Abstract Objective To describe the contributions of prescribed and non-prescribed opioids to opioid related deaths. Design Population based cohort study. Setting Ontario, Canada, from 1 January 2013 to 31 December 2016. Participants All Ontarians who died of an opioid related cause. Exposure Active opioid prescriptions, defined as those with a duration overlapping the date of death, and recent opioid prescriptions, defined as those dispensed in the 30 and 180 days preceding death. Postmortem toxicology results from the Drug and Drug/Alcohol Related Death database were used to characterise deaths on the basis of presence of prescribed and non-prescribed (that is, diverted or illicit) opioids, overall and stratified by year and age. Results 2833 opioid related deaths occurred. An active opioid prescription on the date of death was relatively common but declined slightly throughout the study period (38.2% (241/631) in 2013 and 32.5% (278/855) in 2016; P for trend=0.03). Older people and women were relatively more likely to have an active opioid prescription at time of death. In 2016, 46% (169/364) of people aged 45-64 had an active opioid prescription compared with only 12% (8/69) among those aged 24 or younger (P for trend<0.001). Similarly, 46% (124/272) of women had an active opioid prescription at time of death compared with 26.4% (154/583) of men (P<0.001). Among people with active opioid prescriptions at time of death, 37.8% (375/993) also had evidence of a non-prescribed opioid on postmortem toxicology. By 2016, the non-prescribed opioid most commonly identified after death was fentanyl (41%; 47 of 115 cases). Among people without an active opioid prescription at time of death, fentanyl was detected in 20% (78/390) of deaths in 2013, increasing to 47.5% (274/577) by 2016 (P<0.001). Conclusions Prescribed, diverted, and illicit opioids all play an important role in opioid related deaths. Although more than half of all opioid related deaths still involved prescription drugs (either dispensed or diverted) in 2016, the increased rate of deaths involving fentanyl between 2015 and 2016 is concerning and suggests the need for a multifactorial approach to this problem that considers both the prescribed and illicit opioid environments.

Publicly Funded Oral Chronic Hepatitis B Treatment Patterns in Ontario over 16 Years: An Ecologic Study

BACKGROUNDnReimbursement for the use of hepatitis B virus (HBV) treatments has not been previously reported for public payers.nnnOBJECTIVEnTo describe the number of users and total cost of HBV treatments over the last 16 years among residents of Ontario, Canada, who were covered by the public drug program.nnnMETHODSnWe conducted a repeated cross-sectional study for HBV treatments reimbursed by the public drug program in Ontario from January 1, 2000, to December 31, 2015. We projected total spending to 2020 based on current utilization trends.nnnRESULTSnHBV drug users per year increased 30-fold, from 132 users in 2000 to 4,035 users in 2015. Total spending on HBV treatments increased 150-fold, from

Opioids in Ontario: The current state of affairs and a path forward

136,368 annually in 2000 to

Interprovincial Variation of Psychotropic Prescriptions Dispensed to Older Canadian Adults

21.0 million in 2015. The spending on HBV agents is projected to increase by 65%, with an estimated drug cost of

Varenicline and Risk of Self-Harm: A Nested Case-Control Study.

34.6 million by 2020.nnnCONCLUSIONSnAlthough not reimbursed as first-line therapy, tenofovir disoproxil fumarate has become the most commonly reimbursed HBV treatment and was associated with an increase in HBV treatment use and total spending. Results of this study found that rapid growth of HBV treatments led to a sustained increase in spending for public payers in Ontario.nnnDISCLOSURESnThis study was funded by grants from the Ontario Ministry of Health and Long-Term Care (MOHLTC) and Ontario Strategy for Patient-Orientated Research (SPOR) Support Unit, which is supported by the Canadian Institutes of Health Research and the Province of Ontario. This study was also supported by the Institute for Clinical Evaluative Sciences (ICES), a non-profit research institute sponsored by the Ontario MOHLTC. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, opinions and statements expressed herein are those of the authors and not necessarily those of CIHI. Mamdani has received honoraria from Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Bayer. Janssen has received research support, consulting, and/or speaking fees from Gilead, Roche, Merck, AbbVie, Bristol-Myers Squibb, Arbutus, Janssen, and MedImmune. No other authors have any conflicts of interest to declare.

Variations in costs and use of provincially-funded testosterone replacement therapy across Canada: a population-based study

The opioid crisis currently dominates news across North America, with estimates of approximately 42,000 opioidrelated deaths in the United States in 2016 and nearly 4,000 in Canada in 2017 [1,2]. This growing crisis of opioid-related harm is complex and has been attributed both to broad use of prescription opioids over the past two decades and recent changes to the potency of illicit opioids. Prescription opioids are most commonly used to treat pain, and evidence suggests that they can be used safely and effectively at low doses, and for short durations [3]. However, following the introduction and heavy marketing of new controlled-release opioid formulations in the 1990s, the use of opioids to treat chronic pain became increasingly prevalent, despite limited evidence from clinical trials to support their long-term safety and effectiveness [3,4]. Importantly, these patterns of increased prescription opioid use correlated with increased rates of opioid misuse, opioid-related morbidity and hospitalizations, opioid use disorder, and opioid-related overdose that were observed across North America [3,5]. In recent years, policy-makers have developed drug policies in response to the concerns of harm arising from inappropriate opioid prescribing. However, as rates of opioid prescribing have started to fall in the United States and Canada, there is increasing concern that this has led to significant changes in treatment patterns for patients with chronic pain, and increased demand in the illicit opioid environment, which is increasingly becoming infiltrated with potent, synthetic opioids such as illicit fentanyl and its analogs. One jurisdiction that has been heavily impacted by the crisis has been the province of Ontario, Canada.

Characteristics of Opioid-Related Deaths in Ontario, Canada: Leveraging the Drug and Drug/Alcohol Related Death (DDARD) Database

Background Utilization of psychotropic medications among the elderly has garnered attention due to concerns about safety and degree of efficacy, but may be used differently across regions. Methods We conducted a cross-sectional study of all antipsychotic, benzodiazepine, and trazodone prescriptions dispensed to seniors ( ≥ 65 years) leveraging IQVIA (Durham, NC) GPM data in 2013. We report the units dispensed (per 100 seniors) by province. Results Nationally, on average, 26,210 units of antipsychotics, 24,257 of benzodiazepines, and 7,519 of trazodone were dispensed in 2013 for every 100 seniors; reports varied across Canada. The rate of antipsychotic and benzodiazepine prescribing was highest in New Brunswick (AP: 35,375 units per 100, BZD: 43,989 units per 100), and lowest in Newfoundland & Labrador for antipsychotics (20,974 per 100) and Saskatchewan for benzodiazepines (12,692 per 100). Trazodone unit dispensation rates were highest in Nova Scotia (9,164 per 100) and lowest in Newfoundland & Labrador (2,968 per 100). Conclusions There is considerable geographic variation in the prescribing patterns of antipsychotics, benzodiazepine, and trazodone. This study serves as the first step in understanding these differences, while future work is needed to develop region-specific strategies to optimize the prescribing of psychotropic medications to older Canadian adults.