Impact of delisting high-strength opioid formulations from a public drug benefit formulary on opioid utilization in Ontario, Canada.

PURPOSE: High-strength opioid formulations were delisted (removed) from Ontario's public drug formulary in January 2017, except for palliative patients. We evaluated the impact of this policy on opioid utilization and dosing. METHODS: We conducted a longitudinal study among patients receiving publicly funded, high-strength opioids from August 2016 to July 2017. The primary outcome measure was weekly median daily opioid dose (in milligrams of morphine or equivalent; MME) of (1) publicly funded and (2) all opioid prescriptions irrespective of funding source, evaluated using interrupted time series analyses and stratified by palliative care status. RESULTS: Following policy implementation, the weekly median daily dose of publicly funded opioids decreased immediately among non-palliative patients by 10 MME (95% confidence limit [CL], -16.8 to -3.1) from a pre-intervention dose of 424.5 MME (95% CL, 417.8-431.2) and fell gradually among palliative patients by 3.9 MME per week (95% CL, -5.5 to -2.3) from a pre-intervention dose of 450.1 MME (95% CL, 432.5-467.7). In contrast, among all opioid prescriptions, gradual reductions in weekly median daily doses were observed only for non-palliative patients, which decreased by 0.7 MME per week (95% CL, -1.3 to -0.2) from a pre-intervention dose of 426.2 MME (95% CL, 420.9-431.5). CONCLUSION: The delisting of publicly-funded, high-strength opioids was accompanied by changes in funding source and small reductions in the weekly median daily doses dispensed. Although observed dose reductions of less than 1 MME weekly are likely not clinically relevant, safety implications of these changes require further monitoring.

Quality of primary care among individuals receiving treatment for opioid use disorder.

OBJECTIVE: To determine if people receiving opioid agonist treatment (OAT), a long-term treatment approach, are also receiving high-quality primary care. DESIGN: Retrospective cohort study. SETTING: Ontario. PARTICIPANTS: Recipients of public drug benefits who had at least 6 months of continuous use of methadone or buprenorphine between October 1, 2012, and September 30, 2013. MAIN OUTCOME MEASURES: Rates of cancer screening and diabetes monitoring among those who had at least 6 months of continuous OAT were compared with matched controls. Conditional logistic regression models were used to assess differences after adjusting for confounders. In secondary analyses, outcomes by type of OAT and factors related to health care delivery were compared. RESULTS: A cohort of 20 406 OAT patients was identified; they had a mean (SD) of 31 (15) physician clinic visits during the 6-month study period. Compared with the control group, OAT patients were less likely to receive screening for cervical cancer (48.7% vs 62.6%; adjusted odds ratio [AOR] of 0.34, 95% CI 0.31 to 0.36), breast cancer (23.3% vs 49.1%; AOR = 0.19, 95% CI 0.16 to 0.24), and colorectal cancer (32.5% vs 49.0%; AOR = 0.34, 95% CI 0.30 to 0.38), and less likely to have monitoring for diabetes (11.7% vs 28.5%; AOR = 0.16, 95% CI 0.13 to 0.21). Patients receiving OAT who were taking buprenorphine, enrolled in a medical home, or seeing a low-volume prescriber were generally more likely to receive cancer screening and diabetes monitoring. CONCLUSION: Patients receiving OAT were less likely to receive chronic disease prevention and management than matched controls were despite frequent health care visits, indicating a gap in equitable access to primary care.

Fixed-dose combination antihypertensive medications, adherence, and clinical outcomes: A population-based retrospective cohort study.

BACKGROUND: The majority of people with hypertension require more than one medication to achieve blood pressure control. Many patients are prescribed multipill antihypertensive regimens rather than single-pill fixed-dose combination (FDC) treatment. Although FDC use may improve medication adherence, the impact on patient outcomes is unclear. We compared clinical outcomes and medication adherence with FDC therapy versus multipill combination therapy in a real-world setting using linked clinical and administrative databases. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study of 13,350 individuals 66 years and older in Ontario, Canada with up to 5 years of follow-up. We included individuals who were newly initiated on one angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II-receptor blocker (ARB) plus one thiazide diuretic. High-dimensional propensity score matching was used to compare individuals receiving FDC versus multipill therapy. The primary outcome was a composite of death or hospitalization for acute myocardial infarction (AMI), heart failure, or stroke. We conducted 2 analyses to examine the association between adherence and patient outcomes. First, we performed an on-treatment analysis to determine whether outcomes differed between groups while patients were on treatment, censoring patients when they first discontinued treatment, defined as not receiving medications within 150% of the previous days' supply. Second, we conducted an intention-to-treat analysis that followed individuals allowing for breaks in treatment to quantify the difference in drug adherence between groups and assess its impact on clinical outcomes. As expected, there was no significant difference in the primary outcome between groups in the on-treatment analysis (HR 1.06, 95% CI 0.86-1.31, P = 0.60). In the intention-to-treat analysis, the proportion of total follow-up days covered with medications was significantly greater in the FDC group (70%; IQR 19-98) than in the multipill group (42%, IQR 11-91, P < 0.01), and the primary outcome was less frequent in FDC recipients (3.4 versus 3.9 events per 100 person-years; HR 0.89, 95% CI 0.81-0.97, P < 0.01). The main limitations of this study were the lack of data regarding cause of death and blood pressure measurements and the possibility of residual confounding. CONCLUSIONS: Among older adults initiating combination antihypertensive treatment, FDC therapy was associated with a significantly lower risk of composite clinical outcomes, which may be related to better medication adherence.

Real-world health care utilization and effectiveness of omalizumab for the treatment of severe asthma.

BACKGROUND: Omalizumab is indicated for the treatment of moderate to severe asthma. There is limited observational evidence on the costs and effectiveness of omalizumab. OBJECTIVE: To examine the costs and effectiveness of omalizumab for treatment of severe asthma relative to nonusers. METHODS: We conducted a within-person repeated-measures matched cohort study in Ontario, Canada from April 1, 2012 to March 31, 2014. Continuous users of omalizumab were matched with up to 4 nonusers according to age, sex, recent specialist visits, oral corticosteroid use, asthma severity, and Charlson comorbidity score. The primary outcome was direct health care costs. Secondary outcomes were asthma-related hospitalizations or emergency department visits and oral corticosteroid use. The association between omalizumab use and each outcome was assessed using mixed-effects models adjusting for confounders. RESULTS: Ninety-five omalizumab users and 352 nonusers were matched. Among users, there was a significant increase in health care costs of $1,796 per person owing to the cost of the medication at treatment initiation (P < .0001). Costs did not change significantly among nonusers ($85 increase in average monthly costs per person; P = .59). We found no significant changes in the rates of asthma-related hospitalizations or emergency department visits among omalizumab users (P = .44) or nonusers (P = .99) between pre- and postintervention periods. CONCLUSION: The use of omalizumab was associated with increased costs but no evidence of lower rates of clinically important outcomes. These results suggest omalizumab had limited effectiveness in our study population. Future studies should further explore subsets of patients most likely to benefit from omalizumab therapy.

Antipsychotic Use With and Without Comorbid Psychiatric Diagnosis Among Adults with Intellectual and Developmental Disabilities.

OBJECTIVE: Antipsychotic use is controversial in the management of adults with intellectual and developmental disabilities (IDD) because of inconclusive evidence for efficacy in the absence of a comorbid psychiatric condition, and substantial concerns about adverse effects. We aimed to characterize antipsychotic use among Ontario adults with IDD and compare profiles of those with and without a documented psychiatric diagnosis. METHOD: This population-based study included 51,881 adults with IDD under 65 y as of April 2010 receiving provincial drug benefits in Ontario who were followed until March 2016 to identify those dispensed at least one antipsychotic medication. Profiles of those with and without a psychiatric diagnosis were compared. RESULTS: Overall, 39.2% of adults ( n = 20,316) were dispensed an antipsychotic medication, which increased to 56.4% in a subcohort residing in group homes. Almost one-third (28.91%) of people prescribed an antipsychotic medication did not have a documented psychiatric diagnosis. Those without a psychiatric diagnosis differed considerably from those with a diagnosis. In particular, those without a psychiatric diagnosis were older, less likely to have used antidepressants or benzodiazepines in the year before, and less likely to have used ambulatory and acute care. CONCLUSIONS: Antipsychotic use in IDD is common, and occurs frequently without a psychiatric diagnosis. Attention toward how antipsychotics are prescribed and monitored for people with IDD in Canada is warranted to ensure appropriate prescribing.

Regional variation in healthcare spending and mortality among senior high-cost healthcare users in Ontario, Canada: a retrospective matched cohort study.

BACKGROUND: Senior high cost health care users (HCU) are a priority for many governments. Little research has addressed regional variation of HCU incidence and outcomes, especially among incident HCU. This study describes the regional variation in healthcare costs and mortality across Ontario's health planning districts [Local Health Integration Networks (LHIN)] among senior incident HCU and non-HCU and explores the relationship between healthcare spending and mortality. METHODS: We conducted a retrospective population-based matched cohort study of incident senior HCU defined as Ontarians aged ≥66 years in the top 5% most costly healthcare users in fiscal year (FY) 2013. We matched HCU to non-HCU (1:3) based on age, sex and LHIN. Primary outcomes were LHIN-based variation in costs (total and 12 cost components) and mortality during FY2013 as measured by variance estimates derived from multi-level models. Outcomes were risk-adjusted for age, sex, ADGs, and low-income status. In a cost-mortality analysis by LHIN, risk-adjusted random effects for total costs and mortality were graphically presented together in a cost-mortality plane to identify low and high performers. RESULTS: We studied 175,847 incident HCU and 527,541 matched non-HCU. On average, 94 out of 1000 seniors per LHIN were HCU (CV = 4.6%). The mean total costs for HCU in FY2013 were 12 times higher that of non-HCU ($29,779 vs. $2472 respectively), whereas all-cause mortality was 13.6 times greater (103.9 vs. 7.5 per 1000 seniors). Regional variation in costs and mortality was lower in senior HCU compared with non-HCU. We identified greater variability in accessing the healthcare system, but, once the patient entered the system, variation in costs was low. The traditional drivers of costs and mortality that we adjusted for played little role in driving the observed variation in HCUs' outcomes. We identified LHINs that had high mortality rates despite elevated healthcare expenditures and those that achieved lower mortality at lower costs. Some LHINs achieved low mortality at excessively high costs. CONCLUSIONS: Risk-adjusted allocation of healthcare resources to seniors in Ontario is overall similar across health districts, more so for HCU than non-HCU. Identified important variation in the cost-mortality relationship across LHINs needs to be further explored.

Impact of Unrestricted Access to Pregabalin on the Use of Opioids and Other CNS-Active Medications: A Cross-Sectional Time Series Analysis.

Objective: Access to pregabalin via Ontario's public drug insurance program was expanded to an unrestricted model on April 1, 2013, from a prior authorization model. This study aims to identify the effect of expanded access on the rate of pregabalin use by publicly insured persons and to assess the characteristics of new patients initiating pregabalin following this expanded access. Methods: We conducted a cross-sectional time series analysis using the linked health administrative records of residents of Ontario, Canada, with public drug coverage who were dispensed a prescription for pregabalin between April 1, 2006, and December 31, 2014. Results: A total of 108,047 publicly insured persons were dispensed pregabalin over the study period. The overall rate of pregabalin use increased from 1.0 per 1,000 individuals in Q1 of 2013 to 22.0 per 1,000 individuals in Q4 of 2014. Musculoskeletal (81.6%) and neurological (68.1%) conditions were the most prevalent diagnoses in patients who initiated pregabalin following the expansion of access. Past and concomitant use of opioids, nonsteroidal anti-inflammatory drugs, and antidepressants was also common in this population. Conclusions: Formulary changes in Ontario have led to expanded access to pregabalin, which may have led to an increase in off-label use of these products and potential patient risk associated with concomitant use of pregabalin with central nervous system-depressing drugs.

Off-label use of inhaled tobramycin in Ontario, Canada.

Inhaled tobramycin solution is indicated for use in the management of Pseudomonas aeruginosa in patients with cystic fibrosis (CF). Concerns have been raised regarding increasing off-label use of inhaled tobramycin, particularly for the management of COPD. We conducted an 8-year repeated cross-sectional study examining the indication for prescription claims for inhaled tobramycin in Ontario paid for by the Public Drug Benefit Program, which covers all Ontario residents with financial needs or aged 65 and older. Inhaled tobramycin prescription claims increased approximately 3 times greater from 86 prescriptions in the second quarter of 2007 to 261 prescriptions in the first quarter of 2015. Approximately half of all prescriptions (range: 46-65%) per quarter were dispensed to patients with CF. A large proportion of prescriptions (range: 31-36%) were dispensed to individuals who did not have a diagnosis of CF but had a diagnosis of COPD. In 2014, there were 324 unique users of inhaled tobramycin solution in the Ontario Public Drug Program (OPDP). Only half of users (54%; n=163) had a diagnosis of CF. Our study found increasing prescriptions of inhaled tobramycin from 2007 to 2015 in the OPDP with approximately half of these claims being for off-label use, mostly among patients with COPD.

Impact of changes in opioid funding and clinical policies on rapid tapering of opioids in Ontario, Canada.

ABSTRACT: Reports have emerged of abrupt tapering among recipients of long-term prescription opioids to conform new prescribing guidelines. We conducted a population-based, repeated cross-sectional time-series study among very high-dose (≥200 MME) opioid recipients in Ontario, Canada, to examine changes in the monthly prevalence of rapid tapering from 2014 to 2018, defined as recipients experiencing either a ≥50% reduction in daily doses or abrupt discontinuation sustained for 30 days. Interventional autoregressive integrated moving average models were used to test for significant changes following key guidelines and drug policies and programs. A sensitivity analysis examined rapid tapering sustained for 90 days. The monthly prevalence of rapid tapering events was stable from January 2014 to September 2016 (average monthly prevalence: 1.4%) but increased from 1.4% in October 2016 to 1.8% in April 2017 (P = 0.001), coincident with Ontario's Fentanyl Patch-for-Patch Return Program implementation. Transient spikes in the prevalence of rapid tapering also occurred 2 months after Ontario's delisting of publicly funded high-strength opioids and the release of updated Canadian Opioid Prescribing Guideline for Chronic Pain, reaching 2.3% in March 2017 and July 2017, respectively. However, this prevalence decreased to 1.2% in December 2018 (P < 0.0001). Although the prevalence of abrupt opioid discontinuation was lower, similar trends were observed. Our sensitivity analysis examining long-lasting rapid tapering found similar trends but lower prevalence, with no changes in complete discontinuation. These temporary increases in rapid tapering events highlight the need for improved communication and evidence-based resources for prescribers to minimize negative consequences of evolving policies and guidelines.

Medication use and its impact on high-cost health care users among older adults: protocol for the population-based matched cohort HiCOSTT study.

BACKGROUND: Health interventions and policies for high-cost health care users (HCUs) who are older adults need to be informed by a better understanding of their multimorbidity and medication use. This study aims to determine the financial contribution of medications to HCU expenditures and explore whether potentially inappropriate prescribing is associated with incident HCU development. METHODS: This is a protocol for a retrospective population-based matched cohort analysis of incident older adult HCUs (those with the highest 5% of costs and 66 years of age or older) in Ontario during fiscal year 2013. We will obtain person-level data for the index year and year before HCU status from health administrative databases and match each HCU to 3 non-HCUs based on age, sex and geographic location. Average annual medication costs (per patient) and the ratio of medication to total health care costs (at population level) will be examined over the HCU transition period and compared with non-HCUs. We will explore potential quality improvement areas for prescribing by analyzing chronic conditions and the use of medications with a strong evidence base for either clinical benefit or risk of harms outweighing benefits in older adults with these diagnoses. The relation between these medication classes and incident HCU status will be explored using logistic regression. INTERPRETATION: Using a matched cohort design and focusing on incident rather than prevalent HCUs, this protocol will explore our hypotheses that medications and the quality of their prescribing may be important triggers of HCU status and facilitate the identification of potential preventive clinical interventions or policies. Dissemination of results will occur via publications in peer-reviewed journals, presentations at conferences and academic settings, and knowledge translation activities with relevant health system and patient stakeholder groups. STUDY REGISTRATION: Clinicaltrials.gov, no. NCT02815930.

Antipsychotic initiation among adults with intellectual and developmental disabilities in Ontario: a population-based cohort study.

OBJECTIVES: To describe factors associated with initiating antipsychotics and patterns of persistence to antipsychotic therapy in a large cohort of adults with intellectual and developmental disabilities. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Adults with intellectual and developmental disabilities (IDD) in Ontario. OUTCOME MEASURES: We used multivariable logistic regression to investigate patient characteristics associated with antipsychotic initiation. Patient characteristics studied included sociodemographic characteristics, measures of clinical comorbidity and health service use. RESULTS: Among 39 244 individuals eligible for this study, 6924 (17.6%) initiated an antipsychotic over the accrual window, of whom 1863 (26.9%) had no psychiatric diagnosis in the prior 2 years. A number of factors were significantly associated with antipsychotic initiation, including male gender, residence in a group home, prior use of benzodiazepines, antidepressants or cognitive enhancers, a recent emergency department visit or mental health hospitalisation and a visit to a psychiatrist or family physician in the prior 90 days. In a secondary analysis, the association between antipsychotic initiation and age, prior diagnosis of diabetes or myocardial infarction and polypharmacy differed slightly on the basis of whether an individual had a previously diagnosed psychiatric disorder. CONCLUSIONS: Factors associated with the initiation of an antipsychotic differ according to the presence of a psychiatric diagnosis. Given the long duration of antipsychotic use in this population, future research is needed to understand the appropriateness of antipsychotic initiation among adults with IDD and the safety implications of long-term use of these products.

Unplanned index hospital admissions among new older high-cost health care users in Ontario: a population-based matched cohort study.

BACKGROUND: Most health care spending is concentrated within a small group of high-cost health care users. To inform health policies, we examined the characteristics of index hospital admissions and their predictors among incident older high-cost users compared to older non-high-cost users in Ontario. METHODS: Using Ontario administrative data, we identified incident high-cost users aged 66 years or more and matched them 1:3 on age, gender and Local Health Integration Network with non-high-cost users aged 66 years or more. We defined high-cost users as patients within the top 5% most costly high-cost users during fiscal year 2013/14 but not during 2012/13. An index hospital admission, the main outcome, was defined as the first unplanned hospital admission during 2013/14, with no hospital admissions in the preceding 12 months. Descriptively, we analyzed the attributes of index hospital admissions, including costs. We identified predictors of index hospital admissions using stratified logistic regression. RESULTS: Over half (95 375/175 847 [54.2%]) of all high-cost users had an unplanned index hospital admission, compared to 8838/527 541 (1.7%) of non-high-cost users. High-cost users had a poorer health status, longer acute length of stay (mean 7.5 d v. 2.9 d) and more frequent designation as alternate level of care before discharge (20.8% v. 1.7%) than did non-high-cost users. Ten diagnosis codes accounted for roughly one-third of the index hospital admission costs in both cohorts. Although many predictors were similar between the cohorts, a lower risk of an index hospital admission was associated with residence in long-term care, attachment to a primary care provider and recent consultation by a geriatrician among high-cost users. INTERPRETATION: The high prevalence of index hospital admissions and the corresponding costs are a distinctive feature of incident older high-cost users. Improved access to specialist outpatient care, home-based social care and long-term care when required are worth further investigation.

Trends in the utilisation of COPD therapeutic regimens before and after the introduction of LAMA/LABA combination products: A population-based study.

INTRODUCTION: Long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) combination products have recently been introduced. We sought to describe the impact of these products on patterns of chronic obstructive pulmonary disease (COPD) therapy. MATERIALS AND METHODS: We used administrative healthcare data from Ontario, Canada, to identify all residents aged ≥ 65 years who were dispensed a product to treat COPD at least once between January 2010 and May 2016, and to calculate the monthly prevalence of use of 11 mutually exclusive therapeutic regimens. We also compared the characteristics of new users of LAMA/LABA and LAMA + LABA regimens. RESULTS: Overall use of any COPD regimen remained stable in the year following the formulary listing of LAMA/LABA combination products in May 2015, as did the use of LABA/ICS (most commonly-used regimen). Use of LAMA/LABA and LAMA/LABA + ICS (inhaled corticosteroid) regimens rose rapidly to 283 and 56 users per 100,000 population, respectively, while concurrent falls were seen for LAMA + LABA/ICS (2047 to 1944), LAMA + LABA + ICS (30-19), and LAMA + LABA (103-63). LAMA and LABA monotherapy use declined (1764 to 1669 and 57 to 51, respectively). New users of LAMA/LABA were more likely to be male, urban-dwelling, and to have transitioned from LABA/ICS therapy than new users of LAMA + LABA, and less likely to have transitioned from LAMA or LABA monotherapy, or LAMA + ICS. They were also more likely to have visited a respirologist, and less likely to have been hospitalised, at least once in the preceding 180 days. CONCLUSIONS: The introduction of LAMA/LABA combination products led to population-level changes in regimens used for COPD therapy, but no overall increase in long-acting therapy use. New users of LAMA/LABA and LAMA + LABA regimens transitioned to dual LAMA and LABA therapy through different treatment pathways.

Opioid prescribing and adverse events in opioid-naive patients treated by emergency physicians versus family physicians: a population-based cohort study.

BACKGROUND: Emergency physicians provide primary care to patients and often prescribe opioids for acutely painful self-limiting conditions. The objective of this study was to describe patterns of opioid prescribing by emergency physicians and family physicians and to explore the relation between setting of initiation of opioid treatment and adverse events over the subsequent 2 years. METHODS: This was a population-based cohort study using administrative data from Ontario. Opioid-naive patients aged 15-64 years who received an opioid prescription for noncancer pain from an emergency or family physician between Apr. 1, 2008, and Mar. 31, 2012 were eligible for inclusion. RESULTS: A total of 34 713 and 45 952 patients were initiated on an opioid by an emergency physicians and family physicians, respectively. Both emergency and family physicians most commonly prescribed codeine-containing products (58.9% and 79.6% of prescriptions, respectively); however, emergency physicians were twice as likely as family physicians to prescribe higher-potency opioids (morphine, oxycodone, hydromorphone, fentanyl, meperidine) (both combination and single-agent preparations) (40.6% v. 19.9%, ∆ = 20.7, 95% confidence interval [CI] 20.0-21.3). Compared to patients in the family physician group, those in the emergency physician group received significantly higher daily dosages, a higher proportion were initiated on a daily dosage of 100 mg of morphine equivalents (MEQs) or more, and had a hospital admission for opioid toxicity within 2 years (0.5% v. 0.3%, ∆ = 0.2%, 95% CI 0.1%-0.3%). A higher proportion of patients in the family physician group than in the emergency physician group had dosage escalation beyond 199 mg MEQs within 2 years (0.7% v. 0.1%, ∆ = 0.6%, 95% CI 0.5%-0.7%). INTERPRETATION: Codeine was the most common opioid prescribed by emergency and family physicians. Compared to patients prescribed opioids by family physicians, those prescribed opioids by emergency physicians received higher initial daily dosages and had an increased likelihood of opioid toxicity.

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

INTRODUCTION: Medication 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. METHODS: We 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. RESULTS: We 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). CONCLUSIONS: Our 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.

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.

Evaluating the early impacts of delisting high-strength opioids on patterns of prescribing in Ontario. / Évaluation des premiers effets du retrait des opioïdes à forte concentration sur les schémas de prescription en Ontario.

INTRODUCTION: Ontario delisted high-strength fentanyl, hydromorphone and morphine from the public drug formulary for non-palliative care prescribers on 31 January, 2017. Our aim is to assess the early impact of this policy on prescribing patterns and to examine whether this impact varied by prescriber type, opioid type and opioid strength. METHODS: We conducted a population-based, cross-sectional study on palliative and non-palliative care patients dispensed fentanyl, hydromorphone or morphine through the Ontario public drug program between 1 January, 2014, and 31 July, 2017. For each month during the study period, we reported the total number of high-strength opioid recipients stratified by prescriber type, and the total volume of each drug dispensed, stratified by strength. We used interventional autoregressive integrated moving average (ARIMA) models to assess the policy's impact on prescribing patterns. RESULTS: We observed a 98% decrease in the total number of publicly funded recipients of high-strength opioids between December 2016 and July 2017 (5930 to 133 recipients) for all prescribers. The policy led to a significant decline in the total volume of all three opioids dispensed: hydromorphone from 20 374 621 to 16 952 097 mg (p < .01); morphine from 40 644 190 to 33 555 480 mg (p < .03); and fentanyl from 9 604 913 to 5 842 405 mcg/h (p < .01). For both fentanyl and hydromorphone, this reduction generally corresponded to an increase in the number of low-strength opioids dispensed. CONCLUSION: Delisting high-strength opioids substantially reduced the number of highstrength opioid recipients and reduced the overall volume of long-acting opioids dispensed in Ontario through the public drug program. Future studies should examine its impact on patient outcomes.

INTRODUCTION: Le 31 janvier 2017, l'Ontario a retiré le fentanyl, l'hydromorphone et la morphine à forte concentration des médicaments remboursables par les programmes publics de médicaments s'ils sont prescrits par des médecins en soins non palliatifs. Nous avons voulu évaluer les premiers effets de cette politique sur les schémas de prescription et déterminer si ces effets variaient en fonction du type de prescripteur ainsi que du type d'opioïdes et de leur concentration. MÉTHODOLOGIE: Nous avons mené une étude transversale représentative de la population auprès de patients nécessitant des soins palliatifs et des soins non palliatifs à qui du fentanyl, de l'hydromorphone ou de la morphine couverts par les programmes publics de médicaments de l'Ontario avaient été prescrits entre le 1er janvier 2014 et le 31 juillet 2017. Pour chacun des mois de la période à l'étude, nous avons calculé le nombre total de patients ayant reçu des opioïdes à forte concentration (réparti par type de prescripteurs) ainsi que le volume total de chaque médicament délivré (réparti par concentration). Nous avons utilisé des modèles autorégressifs à moyennes mobiles intégrés (ARMMI) interventionnels pour évaluer les effets des changements apportés par la politique sur les habitudes de prescription. RÉSULTATS: Entre décembre 2016 et juillet 2017, le nombre total de patients ayant reçu des opioïdes à forte concentration remboursés par le régime public a diminué de 98 % pour l'ensemble des prescripteurs, passant de 5 930 à 133. La nouvelle politique a entraîné une baisse substantielle du volume total des trois opioïdes délivrés, soit de 20 374 621 à 16 952 097 mg (p < 0,01) pour l'hydromorphone, de 40 644 190 à 33 555 480 mg (p < 0,03) pour la morphine et de 9 604 913 à 5 842 405 mcg/h (p < 0,01) pour le fentanyl. Dans le cas du fentanyl et de l'hydromorphone, cette diminution a dans l'ensemble coïncidé avec une augmentation du nombre d'opioïdes à faible concentration délivrés. CONCLUSION: Le retrait des opioïdes à forte concentration a sensiblement réduit le nombre de patients à qui ces médicaments ont été prescrits, ainsi que le volume total d'opioïdes à action prolongée délivrés en Ontario dans le cadre du régime public de médicaments. D'autres études devraient être menées pour en examiner les effets sur les patients.

Clinical indications associated with opioid initiation for pain management in Ontario, Canada: a population-based cohort study.

Concerns over prescription opioids contributing to high levels of opioid use disorder and overdose have led policymakers and clinicians to seek means to reduce inappropriate and high-dose initial prescriptions. To inform such efforts, we sought to describe the clinical indications associated with opioid initiation and the characteristics of the initial prescriptions and patients through a retrospective population-based cohort study. Our cohort included Ontarians initiating prescription opioids for pain management between April 1, 2015, and March 31, 2016. We identified the apparent clinical indication for opioid initiation by linking prescription drug claims to procedural and diagnostic information on health service records on the day of, and 5 days preceding prescription. Outcomes included initial opioid type, prescription duration, and daily dose (in milligram morphine equivalents), stratified either by indication or indication cluster. Among 653,993 individuals, we successfully classified 575,512 (88.0%) people initiating opioids into 23 clinical indications in 6 clusters: dental (23.2%); postsurgical (17.4%); musculoskeletal (12.0%); trauma (11.2%); cancer/palliative care (6.5%); and other less frequent indications (17.7%). Individuals with postsurgical pain received the highest daily doses (40.5% with greater than 50 milligram morphine equivalent), and those with musculoskeletal pain received more initial prescriptions with a duration exceeding 7 days (34.2%). Opioids are initiated for a wide range of indications with varying doses and durations; yet, those who initiated opioids for postsurgical and musculoskeletal pain received the greatest doses and durations of therapy, respectively. These findings may help tailor and prioritize efforts to promote more appropriate opioid prescribing.

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.

A Systematic Review of Comorbidity Measurement Methods for Patients With Nontraumatic Brain Injury in Inpatient Rehabilitation Settings.

This review summarizes comorbidity measurements used on patients with nontraumatic brain injury in inpatient rehabilitation and describes findings on measurement validation and comorbidity profiles. MEDLINE and MEDLINE In-Process, EMBASE, PsycINFO, the Cochrane Database of Systematic Reviews, Health, and Psychosocial Measurement Instruments were searched. Two reviewers screened results according to predefined inclusion and exclusion criteria. Population, statistical methods, comorbidity measurement, justification of its use, and results involving comorbidity were extracted using a standard table. Of 9476 articles retrieved, 16 were included. Comorbidity has been measured using various methods including the following: number and type within various classification systems, such as the International Disease Classification system, the Charlson comorbidity index, Centers for Medicare and Medicaid Services comorbidity tiers and patient comorbidity and complexity level values and subsets of diagnoses within nonadministrative data studies. No studies have assessed the predictive ability of the comorbidity measurements for inpatient rehabilitation outcomes in this population. Because comorbidities are common among the nontraumatic brain injury population, the predictive validity of comorbidity measurements should be assessed to determine the most appropriate measure to predict or risk adjust rehabilitation outcomes, which has implications for the development of clinical guidelines, and to inform health service research, planning, and delivery.