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Opioid-related policies and guidelines increased the prevalence of rapid opioid dose tapering between 2016 and 2017 in Ontario, Canada, but instances were temporary and short-lived., 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.

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.

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.

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.

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 $lt; 0,01) pour l’hydromorphone, de 40 644 190 à 33 555 480 mg (p $lt; 0,03) pour la morphine et de 9 604 913 à 5 842 405 mcg/h (p $lt; 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.

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.

Background Despite concerns surrounding high patient volumes in methadone clinics, little is known about the practice patterns of opioid maintenance therapy (OMT) providers in Ontario. We examined the distribution of these services and how physician characteristics differ based on prescribing volume. Methods We conducted a cross-sectional study among prescribers of methadone or buprenorphine to Ontario public drug beneficiaries in 2014 by stratifying physicians into low- (lower 50%), moderate- (51–89%) and high-volume (top 10%) prescribers. We summarized the distribution of OMT prescription days dispensed and urine drug screens (UDS) ordered using Lorenz curves and examined physician characteristics using descriptive statistics. Results We identified 893 OMT prescribers in 2014. Physicians were mostly male (67.5%; N = 603), and middle-aged (median was 50). High-volume methadone providers (N = 57) prescribed approximately 56% (N = 4,115,322) of the total days of methadone (Gini coefficient = 0.76, 95% CI 0.74–0.79) while high-volume buprenorphine providers (N = 64) prescribed 61% (N = 589,463) of the total days of buprenorphine (Gini coefficient = 0.78, 95% CI 0.75–0.80). On average, each high-volume methadone prescriber treated 435 OMT patients and billed 43 UDS per patient, while each high-volume buprenorphine prescriber treated 64 OMT patients and billed 22 UDS per patient. Daily OMT patient volume was on average 74 for high-volume methadone prescribers and 6 for high-volume buprenorphine prescribers. Conclusions OMT services are highly concentrated among a small portion of OMT providers who carry high daily patient volumes. Future research should examine the quality of primary care received by their patients to better elucidate the possible consequences of this highly unequal distribution of services.

Background Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in Methods Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. Results Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). Conclusions In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents.

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.

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.

IntroductionReview of post-mortem toxicological results is the gold standard for identifying whether a death is opioid-related. The Drug and Drug/Alcohol Related Death (DDARD) database contains abstracted information from the Office of the Chief Coroner of Ontario, for all opioid-related deaths that occurred in Ontario, Canada between 1991 and 2016. Objectives and ApproachThe DDARD, which contains manner of death and drug concentrations from post-mortem toxicology results for opioids-related deaths in Ontario, was linked to the data repository housed at ICES. The objective of this project was to examine demographic characteristics and the type of opioid contributing to opioid-related deaths in FY2015/16. Individuals identified within DDARD who died from an opioid-related cause were linked to demographic, hospitalization and prescription drug databases to report on age, gender, neighbourhood income quintile, past health services utilization for opioid-toxicity, alcohol use disorders (AUD), mental health emergency department (ED) visits, and opioid(s) present at time of death. ResultsWe identified 737 opioid-related deaths in FY2015/16, the majority of which involved men (n=497; 67.4%), those living in lower socioeconomic status areas (n=395; 53.6%), and those residing in urban regions (n=655; 88.9%). Nearly half (n=325; 44.1%) of opioid-related deaths occurred among those aged 45 to 65 years. We found 9.5% (n=70) of individuals had a previous hospital visit for opioid toxicity, 25.4% (n=187) had previously diagnosed AUD, and 42.5% (n=313) had a previous mental health ED visit. Overall, 250 (33.9%) individuals had an active opioid prescription at time of death with oxycodone (n=92; 36.8%) the most commonly dispensed. Among those who didn’t have an active opioid prescription at time of death (n=484; 66%), fentanyl (n=184; 37.8%) was the most commonly found opioid on post-mortem toxicology. Conclusion/ImplicationsThis project demonstrates how data obtained through chart abstractions can be used to enhance existing administrative health datasets. Given the concern around the safety of opioids, it is important to examine the characteristics and type of opioid(s) involved at time of opioid-related death in order to develop targeted preventative strategies.

IntroductionSupporting standardized approaches to common tasks is an important component of quality research using linked administrative data. Standard concept definitions and classifications are vital for ensuring accuracy and consistency in definitions between projects, and improving efficiency and quality. Other leading organizations have published online standard definitions of concepts and classifications. Objectives and ApproachWe developed a comprehensive concept dictionary using a standardized definition template of key components including data sources, codes, scale or range of values, validation details, limitations, SAS code and formats, related concepts, and MeSH terms. A web-based application (built on the Microsoft SharePoint platform) was developed to offer the latest web content authoring capabilities, and advanced search mechanisms enabling the user to search concepts by MeSH terms and key words. It also allowed for navigating concepts through category navigation including clickable categories and sub-categories. Entries will be reviewed annually to ensure the content remains up-to-date. ResultsTo date, ten concepts, with accompanying codes, have been published on the concept dictionary with another ten currently undergoing editorial review. These concepts span a variety of topics such as injuries, mental health and addictions-related outpatient services, and annual physical exams. New concepts written by content experts and reviewed by an editorial committee will be added on an on-going basis; thirty concepts are currently under development. Conclusion/ImplicationsDevelopment of a concept dictionary provides standardized definitions, algorithms and codes to ensure consistency and quality of research and analysis across multiple projects. Future aims include expansion of the internal organizational site to an external site through collaboration with key stakeholders.

IntroductionThe Ontario Narcotics Monitoring System (NMS) captures information on all prescriptions for controlled medications dispensed from outpatient pharmacies in Ontario, Canada, regardless of payer. This system was introduced in 2012, as a strategy to promote appropriate prescribing and dispensing practices. Objectives and ApproachWe sought to explore the degree to which prescriptions in the NMS can be linked to other health claims databases, and describe the types of medications dispensed between July 2012 and December 2016. We also linked opioid prescriptions to hospitalization and mortality data to examine the relative contributions of prescribed and non-prescribed opioids to opioid toxicity events in 2016. A recent opioid prescription was defined as a prescription with a days’ supply that overlapped the opioid toxicity event. Analyses were stratified by gender and age. ResultsWe examined 1.3 million prescriptions in the NMS during the study period: 72.8% for opioids, 21% for benzodiazepines, 4.4% for stimulants and

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.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.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.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.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.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.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 (p0,01) pour l’hydromorphone, de 40 644 190 à 33 555 480 mg (p0,03) pour la morphine et de 9 604 913 à 5 842 405 mcg/h (p0,01) 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.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.

Opioid initiation for postsurgical and musculoskeletal pain is associated with the highest dose and duration at initiation, respectively, relative to other indications., 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.

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.

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.

IntroductionSenior high-cost users (HCUs) are estimated to represent 60% of all HCUs in Ontario, Canada’s most populous province. To improve our understanding of individual and health system characteristics related to senior HCUs, we will examine incident senior HCUs to determine their incremental healthcare utilisation and costs, characteristics of index hospitalisation episodes, mortality and their regional variation across Ontario.Methods and analysisA retrospective, population-based cohort study using administrative healthcare records will be used. Incident senior HCUs will be defined as Ontarians aged ≥66 years who were in the top 5% of healthcare cost users during fiscal year 2013 but not during fiscal year 2012. Each HCU will be matched to three non-HCUs by age, sex and health planning region. Incremental healthcare use and costs will be determined using the method of recycled predictions. We will apply multivariable logistic regression to determine patient and health service factors associated with index hospitalisation and inhospital mortality during the incident year. The most common causes of admission will be identified and contrasted with the most expensive hospitalised conditions. We will also calculate the ratio of inpatient costs incurred through admissions of ambulatory care sensitive conditions to the total inpatient expenditures. The magnitude of variation in costs and health service utilisation will be established by calculating the extremal quotient, the coefficient of variation and the Gini mean difference for estimates obtained through multilevel regression analyses.Ethics and disseminationThis study has been approved by Hamilton Integrated Research Ethics Board (ID#1715-C). The results of the study will be distributed through peer-reviewed journals. They also will be disseminated at research events in academic settings, national and international conferences as well as with presentations to provincial health authorities.

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.

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.

We investigated autobiographical memory in a group of passengers onboard a transatlantic flight that nearly ditched at sea. The consistency of traumatic exposure across passengers, some of whom developed posttraumatic stress disorder (PTSD), provided a unique opportunity to assess verified memory for life-threatening trauma. Using the Autobiographical Interview, which separates episodic from nonepisodic details, passengers and healthy controls (HCs) recalled three events: the airline disaster (or a highly negative event for HCs), the September 11, 2001, attacks, and a nonemotional event. All passengers showed robust mnemonic enhancement for episodic details of the airline disaster. Although neither richness nor accuracy of traumatic recollection was related to PTSD, production of nonepisodic details for traumatic and nontraumatic events was elevated in PTSD passengers. These findings indicate a robust mnemonic enhancement for trauma that is not specific to PTSD. Rather, PTSD is associated with altered cognitive control operations that affect autobiographical memory in general.

ObjectivesTo describe factors associated with initiating antipsychotics and patterns of persistence to antipsychotic therapy in a large cohort of adults with intellectual and developmental disabilities.DesignPopulation-based cohort study.SettingOntario, Canada.ParticipantsAdults with intellectual and developmental disabilities (IDD) in Ontario.Outcome measuresWe 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.ResultsAmong 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.ConclusionsFactors 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.

Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in 40% of cases, raising concerns about the generalizability of this finding.Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases.Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03).In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents.

To describe the contributions of prescribed and non-prescribed opioids to opioid related deaths.Population based cohort study.Ontario, Canada, from 1 January 2013 to 31 December 2016.All Ontarians who died of an opioid related cause.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.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 trend0.001). Similarly, 46% (124/272) of women had an active opioid prescription at time of death compared with 26.4% (154/583) of men (P0.001). 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 (P0.001).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.

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.

High cost users (HCUs) are a small proportion of the population that use disproportionate healthcare resources. In 2011, 5% of the population in Ontario, Canada accounted for 65% ($19.8 billion) of provincial health expenditures. Understanding HCU multi-morbidity and drug use is required to target interventions to improve clinical outcomes and contain healthcare costs. This study aimed to compare senior HCUs to non-HCUs based on demographics, co-morbidities, medication use, health service utilization, clinical outcomes and costs. We conducted a retrospective population-based matched cohort analysis of incident senior HCUs defined as Ontarians age ≥ 66 years in the top 5% of total healthcare costs in FY2013. Healthcare and prescription drug utilization data were obtained from health administrative databases. The primary outcomes were annual total healthcare expenditures per patient, total drug costs per patient and drug-to-total healthcare expenditure ratio. Secondary outcomes were one-year mortality and hospitalization rate. Senior HCUs (n=176,604) accounted for $4.9 billion in total healthcare expenditures and $433 million in medication costs in FY2013. Compared to non-HCUs (n=529,812) on a per patient basis, HCUs incurred higher total healthcare costs ($27,697 vs. $2233) and higher medication costs ($2453 vs. $842). HCUs were characterized by greater polypharmacy (>5 medications, 87.7% vs. 47.6%) and multi-morbidity (median John Hopkins Expanded Diagnosis Clusters [EDCs], 14 vs. 10). HCUs had higher annual mortality (10.39% vs. 0.72%) and hospitalization rates (3.20 vs. 0.06 hospitalizations per 1000 person-years). Compared to non-HCUs, senior HCUs are frail, multi-morbid and vulnerable. The contribution of prescribing and medication utilization quality deserves further study.

Background Comorbidity can affect health-care utilization and outcomes, and the results and interpretation of risk adjustment studies that attempt to predict rehabilitation utilization and outcomes are influenced by the choice of comorbidity measurement. Although the identification of an appropriate measurement has been conducted in some populations and outcomes, this information is currently lacking for the non-traumatic brain injury (nTBI) population in inpatient rehabilitation settings. As such, this is a systematic review protocol to survey the methods used to measure comorbidities in the rehabilitation setting for patients with nTBI. Methods/design MEDLINE, MEDLINE In-Process, Embase, The Cochrane Database of Systematic Reviews, PsycINFO, and Health and Psychosocial Instruments will be systematically searched using the concepts ‘nTBI,’ ‘comorbidity,’ and ‘rehabilitation.’ Grey matters and the reference list of eligible articles will also be searched. Study selection will be performed independently by two reviewers based on predetermined eligibility criteria through two rounds of screening using, first, the title and abstract, followed by full-text. Extracted information will include study purpose, design, and setting; data source and type; outcomes variables; statistical methods; comorbidity measurement method, rationale, justification, or validation; and results involving comorbidity. The data will be tabulated and narratively synthesized. Meta-analyses will be performed if appropriate. Systematic review registration This protocol has not been registered with PROSPERO. Discussion This protocol provides a systematic method for surveying current practice as well as monitoring the progress on comorbidity measurement methodology and effects of comorbidity on rehabilitation outcomes for patients with nTBI. The selection of an appropriate comorbidity measurement method has implications for the interpretation of both descriptive and risk adjustment studies, and thus, the validity of evidence used to inform planning and delivery of services. Electronic supplementary material The online version of this article (doi:10.1186/2046-4053-4-14) contains supplementary material, which is available to authorized users.

Recollection of previously experienced events is a key element of human memory that entails recovery of spatial, perceptual, and mental state details. While deficits in this capacity in association with brain disease have serious functional consequences, little is known about individual differences in autobiographical memory (AM) in healthy individuals. Recently, healthy adults with highly superior autobiographical capacities have been identified (e.g., LePort, A.K., Mattfeld, A.T., Dickinson-Anson, H., Fallon, J.H., Stark, C.E., Kruggel, F., McGaugh, J.L., 2012. Behavioral and neuroanatomical investigation of Highly Superior Autobiographical Memory (HSAM). Neurobiol. Learn. Mem. 98(1), 78–92. doi: 10.1016/j.nlm.2012.05.002). Here we report data from three healthy, high functioning adults with the reverse pattern: lifelong severely deficient autobiographical memory (SDAM) with otherwise preserved cognitive function. Their self-reported selective inability to vividly recollect personally experienced events from a first-person perspective was corroborated by absence of functional magnetic resonance imaging (fMRI) and event-related potential (ERP) biomarkers associated with naturalistic and laboratory episodic recollection, as well as by behavioral evidence of impaired episodic retrieval, particularly for visual information. Yet learning and memory were otherwise intact, as long as these tasks could be accomplished by non-episodic processes. Thus these individuals function normally in day-to-day life, even though their past is experienced in the absence of recollection.