Association between opioid use disorder and palliative care: a cohort study using linked health administrative data in Ontario, Canada.

BACKGROUND: People with opioid use disorder (OUD) are at risk of premature death and can benefit from palliative care. We sought to compare palliative care provision for decedents with and without OUD. METHODS: We conducted a cohort study using health administrative databases in Ontario, Canada, to identify people who died between July 1, 2015, and Dec. 31, 2021. The exposure was OUD, defined as having emergency department visits, hospital admissions, or pharmacologic treatments suggestive of OUD within 3 years of death. Our primary outcome was receipt of 1 or more palliative care services during the last 90 days before death. Secondary outcomes included setting, initiation, and intensity of palliative care. We conducted a secondary analysis excluding sudden deaths (e.g., opioid toxicity, injury). RESULTS: Of 679 840 decedents, 11 200 (1.6%) had OUD. Compared with people without OUD, those with OUD died at a younger age and were more likely to live in neighbourhoods with high marginalization indices. We found people with OUD were less likely to receive palliative care at the end of their lives (adjusted relative risk [RR] 0.84, 95% confidence interval [CI] 0.82-0.86), but this difference did not exist after excluding people who died suddenly (adjusted RR 0.99, 95% CI 0.96-1.01). People with OUD were less likely to receive palliative care in clinics and their homes regardless of cause of death. INTERPRETATION: Opioid use disorder can be a chronic, life-limiting illness, and people with OUD are less likely to receive palliative care in communities during the 90 days before death. Health care providers should receive training in palliative care and addiction medicine to support people with OUD.

The impact of expanded access to direct acting antivirals for Hepatitis C virus on patient outcomes in Canada.

BACKGROUND: Hepatitis C virus (HCV) has high global prevalence and can lead to liver complications and death. Access to direct-acting antivirals (DAAs) in Canada increased following several policy changes, however the real-world impact of expanded DAA access and increased use of these drugs is unknown. OBJECTIVE: We aimed to determine the early change in rates of HCV-related hospitalizations overall and HCV-related hospitalizations with hepatocellular carcinoma (HCC) after expanded DAA access. METHODS: We conducted a population-based time series analysis using national administrative health databases in Canada. Rates of HCV-related hospitalizations and HCV-related hospitalizations with HCC were enumerated monthly between April 2006 and March 2020. We used Autoregressive Integrated Moving Average (ARIMA) models with ramp functions in October 2014 and January 2017 to evaluate the impact of policies to expand DAA access on hospitalization outcomes. RESULTS: Rates of HCV-related hospitalizations in Canada increased between 2006 and 2014, and gradually declined thereafter. The decrease after October 2014, or the first policy change, was significant (p = 0.0355), but no further change was found after the second policy change in 2017 (p = 0.2567). HCV-related hospitalizations with HCC increased until end of 2013, followed by a plateau, before declining in 2016. No significant shifts were found after the first policy change in 2014 (p = 0.1291) nor the second policy change in 2017 (p = 0.6324). Subgroup analyses revealed that those aged 50-64 and males had observable declines in rates of HCV-related hospitalizations in the year prior to the first policy change. CONCLUSIONS: Expanding DAA access was associated with a drop in HCV-related hospitalizations in the overall Canadian population coinciding with the 2014 policy change. In light of the time required for HCV-related complications to manifest, continued ongoing research examining the real-world effectiveness of DAAs is required.

Anticoagulant use and associated outcomes in older patients receiving home palliative care: a retrospective cohort study.

BACKGROUND: The benefits and harms of anticoagulants for people near the end of life are not well understood, nor is it known what proportion of patients discontinue these medications. We aimed to characterize anticoagulant use in older recipients of home palliative care and describe patient and provider characteristics, as well as outcomes associated with anticoagulant discontinuation in this group. METHODS: Using linked administrative health databases, we conducted a population-based cohort study of patients aged 66 years and older who initiated home palliative care in Ontario from 2010 to 2018. We calculated the prevalence of anticoagulant use. We used multilevel logistic regression models to assess patient (e.g., sociodemographic, comorbidities) and physician (e.g., demographic, training, practice) factors associated with anticoagulant discontinuation after initiation of home palliative care. We defined discontinuation as either primary (no anticoagulant claim within 1.5 times the days' supply of the previous prescription) or secondary (no subsequent anticoagulant claim at any time after the index date). In secondary analyses, we used cause-specific hazards regression to explore subsequent thrombotic and bleeding events associated with anticoagulant discontinuation, and multivariable logistic regression for location of death. RESULTS: We identified 98 089 recipients of home palliative care, of whom 15.5% were taking anticoagulants at the time of the first palliative care visit. Depending on the definition of discontinuation, 18.0% to 24.4% of patients discontinued anticoagulants after the first home palliative care visit. Compared with warfarin, use of a direct oral anticoagulant (adjusted odds ratio [OR] 0.49, 95% confidence interval [CI] 0.43-0.56) and low-molecular-weight heparin (adjusted OR 0.56, 95% CI 0.47-0.66) were associated with a lower likelihood of discontinuation. Few patient or physician characteristics - and no comorbidities or indications for therapeutic anticoagulation - were associated with discontinuation. Anticoagulant discontinuation after beginning home palliative care was associated with similar rates of thrombosis (adjusted hazard ratio [HR] 1.06, 95% CI 0.81-1.39), lower rates of bleeding (adjusted HR 0.75, 95% CI 0.62-0.90) and a higher likelihood of a home death (adjusted OR 1.22, 95% CI 1.09-1.36) compared with continuing anticoagulation. INTERPRETATION: Among recipients of home palliative care in Ontario, anticoagulant use is common, and discontinuation is not influenced by comorbidities or indication for anticoagulation. Physician preference may play an important role; patients should be made aware of their options toward the end of life and supported in shared decision-making.

Correlates of Opioid Use Among Ontario Long-Term Care Residents and Variation by Pain Frequency and Intensity: A Cross-sectional Analysis.

BACKGROUND: Chronic non-cancer pain is common among older residents of long-term care (LTC) homes and often poorly recognized and treated. With heightened concerns regarding opioid prescribing in recent years, it is important to examine the current prevalence of opioid use and its association with resident characteristics to help identify those potentially at risk of medication harms as well as suboptimal pain management. OBJECTIVES: The aims were to estimate the prevalence and correlates of opioid use among non-palliative LTC residents and explore variation in opioid prevalence and correlates across strata defined by pain frequency and intensity. METHODS: We conducted a population-based cross-sectional study of all older (aged > 65 years) LTC residents (excluding those with cancer or receiving palliative care) in Ontario, Canada during 2018-2019. Health administrative databases were linked with standardized clinical assessment data to ascertain residents' health and pain characteristics and their opioid and other medication use. Modified Poisson regression models estimated unadjusted and adjusted associations between residents' characteristics and opioid use, overall and across strata capturing pain frequency and intensity. RESULTS: Among 75,020 eligible residents (mean age 85.1 years; 70% female), the prevalence of opioid use was 18.5% and pain was 29.4%. Opioid use ranged from 12.2% for residents with no current pain to 55.7% for those with severe pain. In adjusted models, residents newly admitted to LTC (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI] 0.57-0.62) and with moderate to severe cognitive impairment (aRR = 0.69, 95% CI 0.66-0.72) or dementia (aRR = 0.76, 95% CI 0.74-0.79) were significantly less likely to receive an opioid, whereas residents with select conditions (e.g., arthritis, aRR = 1.37, 95% CI 1.32-1.41) and concurrently using gabapentinoids (aRR = 1.80, 95% CI 1.74-1.86), benzodiazepines (aRR = 1.33, 95% CI 1.28-1.38), or antidepressants (aRR = 1.31, 95% CI 1.27-1.35) were significantly more likely to receive an opioid. The associations observed for residents newly admitted, with dementia, and concurrently using gabapentinoids, benzodiazepines, or antidepressants were largely consistent across all pain strata. CONCLUSIONS: Our findings describe resident sub-groups at potentially higher risk of adverse health outcomes in relation to both opioid use and non-use. LTC clinical and policy changes informed by research are required to ensure the appropriate recognition and management of non-cancer pain in this setting.

Opioid prescribing practices in chronic kidney disease: a population-based cohort study.

BACKGROUND: Chronic pain is common, and its management is complex in patients with chronic kidney disease (CKD), but limited data are available on opioid prescribing. We examined opioid prescribing for non-cancer and non-end-of-life care in patients with CKD. METHODS: This was a population-based retrospective cohort study using administrative databases in Ontario, Canada which included adults with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 from 1 November 2012 to 31 December 2018 and estimated the proportion of opioid prescriptions (type, duration, dose, potentially inappropriate prescribing, etc.) within 1 year of cohort entry. Prescriptions had to precede dialysis, kidney transplant or death. RESULTS: We included 680 445 adults with CKD, and 198 063 (29.1%) were prescribed opioids. Codeine (14.9%) and hydromorphone (7.2%) were the most common opioids. Among opioid users, 24.3% had repeated or long-term use, 26.1% were prescribed high doses and 56.8% were new users. Opioid users were more likely to be female, had cardiac disease or a mental health diagnosis, and had more healthcare visits. The proportions for potentially inappropriate prescribing indicators varied (e.g. 50.1% with eGFR <30 were prescribed codeine, and 20.6% of opioid users were concurrently prescribed benzodiazepines, while 7.2% with eGFR <30 mL/min/1.73 m2 were prescribed morphine, and 7.0% were received more than one opioid concurrently). Opioid prescriptions declined with time (2013 cohort: 31.1% versus 2018 cohort: 24.5%; p <0.0001), as did indicators of potentially inappropriate prescribing. CONCLUSIONS: Opioid use was common in patients with CKD. While opioid prescriptions and potentially inappropriate prescribing have declined in recent years, interventions to improve pain management without the use of opioids and education on safer prescribing practices are needed.

Prescription opioid treatment for non-cancer pain and initiation of injection drug use: large retrospective cohort study.

OBJECTIVE: To assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance use. DESIGN: Retrospective cohort study. SETTING: Large administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies. PARTICIPANTS: Individuals age 11-65 years and without a history of substance use (except alcohol) at baseline. MAIN OUTCOME MEASURES: Episodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting <90 episode days), episodic (lasting ≥90 episode days; with <90 days' drug supply and/or <50% episode intensity), and chronic (lasting ≥90 episode days; with ≥90 days' drug supply and ≥50% episode intensity)). People with a chronic episode were matched 1:1:1:1 on socioeconomic variables to those with episodic or acute episodes and to those who were opioid naive. IDU initiation was identified by a validated administrative algorithm with high specificity. Cox models weighted by inverse probability of treatment weights assessed the association between opioid use category (chronic, episodic, acute, opioid naive) and IDU initiation. RESULTS: 59 804 participants (14 951 people from each opioid use category) were included in the matched cohort, and followed for a median of 5.8 years. 1149 participants initiated IDU. Cumulative probability of IDU initiation at five years was highest for participants with chronic opioid use (4.0%), followed by those with episodic use (1.3%) and acute use (0.7%), and those who were opioid naive (0.4%). In the inverse probability of treatment weighted Cox model, risk of IDU initiation was 8.4 times higher for those with chronic opioid use versus those who were opioid naive (95% confidence interval 6.4 to 10.9). In a sensitivity analysis limited to individuals with a history of chronic pain, cumulative risk for those with chronic use (3.4% within five years) was lower than the primary results, but the relative risk was not (hazard ratio 9.7 (95% confidence interval 6.5 to 14.5)). IDU initiation was more frequent at higher opioid doses and younger ages. CONCLUSIONS: The rate of IDU initiation among individuals who received chronic prescription opioid treatment for non-cancer pain was infrequent overall (3-4% within five years) but about eight times higher than among opioid naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.

Cohort profile: development and characteristics of a retrospective cohort of individuals dispensed prescription opioids for non-cancer pain in British Columbia, Canada.

PURPOSE: Prescription opioids (POs) are widely prescribed for chronic non-cancer pain but are associated with several risks and limited long-term benefit. Large, linked data sources are needed to monitor their harmful effects. We developed and characterised a retrospective cohort of people dispensed POs. PARTICIPANTS: We used a large linked administrative database to create the Opioid Prescribing Evaluation and Research Activities cohort of individuals dispensed POs for non-cancer pain in British Columbia (BC), Canada (1996-2015). We created definitions to categorise episodes of PO use based on a review of the literature (acute, episodic, chronic), developed an algorithm for inferring clinical indication and assessed patterns of PO use across a range of characteristics. FINDINGS TO DATE: The current cohort includes 1.1 million individuals and 3.4 million PO episodes (estimated to capture 40%-50% of PO use in BC). The majority of episodes were acute (81%), with most prescribed for dental or surgical pain. Chronic use made up 3% of episodes but 88% of morphine equivalents (MEQ). Across the acute to episodic to chronic episode gradient, there was an increasing prevalence of higher potency POs (hydromorphone, oxycodone, fentanyl, morphine), long-acting formulations and chronic pain related indications (eg, back, neck, joint pain). Average daily dose (MEQ) was similar for acute/episodic but higher for chronic episodes. Approximately 7% of the cohort had a chronic episode and chronic pain was the characteristic most strongly associated with chronic PO use. Individuals initiating a chronic episode were also more likely to have higher social/material deprivation and previous experience with a mental health condition or a problem related to alcohol or opioid use. Overall, these findings suggest our episode definitions have face validity and also provide insight into characteristics of people initiating chronic PO therapy. FUTURE PLANS: The cohort will be refreshed every 2 years. Future analyses will explore the association between POs and adverse outcomes.

Effect of listing strategies on utilization of antitumor necrosis factor biologics infliximab and etanercept: a cross-sectional analysis from Ontario, Canada.

BACKGROUND: Use of costly biologic drugs for the treatment of chronic inflammatory diseases has increased significantly in recent years. However, biosimilar drugs offer an opportunity to ensure health system sustainability with robust uptake. OBJECTIVE: To study the effect of formulary listing strategies on the use of infliximab and etanercept innovator and biosimilar biologics. METHODS: This is a cross-sectional study of individuals in Ontario, Canada, dispensed a biologic prescription for infliximab or etanercept through Ontario's public drug program between January 1, 2010, and June 30, 2019. Quarterly utilization and costs were forecasted using Holt-Winters' exponential smoothing models to the second quarter (Q2) of 2022. Secondary analyses explored utilization for rheumatic conditions (RC) and inflammatory bowel disease (IBD). RESULTS: From Q1 2010 to Q2 2019, infliximab and etanercept users increased by 75.7% (n = 4,073 to 7,158), with a forecasted increase of 13.7% (n = 8,142; 95% CI = 7,438-8,847) by Q2 2022. Biosimilar users represented 13.8% (n = 539 of 3,905) of total infliximab users in Q2 2019, although this differed by indication with 6.9% for IBD (n = 187 of 2,712) and 26.6% for RC (n = 203 of 764). Etanercept biosimilar users represented 20.2% (n = 659 of 3,256) of total etanercept users for RC in Q2 2019. Biologics expenditures increased 109.7% during the study, amounting to $49.9 million in Q2 2019. CONCLUSIONS: Despite differing reimbursement restrictions between innovator infliximab and etanercept biologics, the uptake of their biosimilars was low and not noticeably different in the treatment of RC. Dynamic policy strategies are needed to improve the uptake of biosimilars, particularly for IBD. DISCLOSURES: Funding for this study was contributed by the Ontario Ministry of Health. The authors have no conflicts of interest to disclose.

Prescription opioid characteristics at initiation for non-cancer pain and risk of treated opioid use disorder: A population-based study.

BACKGROUND: Long-term prescription opioid use has been associated with adverse health outcomes, including opioid use disorder (OUD). We examined a population of opioid naïve individuals who initiated prescription opioids for non-cancer pain and investigated the associations between opioid prescription characteristics at initiation and time to treated OUD. METHODS: We conducted a retrospective population-based cohort study in Ontario, Canada among opioid naïve individuals aged 15 years and older dispensed an opioid for non-cancer pain between 2013 and 2016. We used the Narcotic Monitoring System to abstract opioid dispensing data. A multivariable Cox regression model was used to examine the association between average daily dose and time to treated OUD. RESULTS: We identified 1,607,659 opioid-naïve individuals who initiated a prescription opioid within the study period. The incidence of treated OUD within the study period was 86 cases per 100,000 person-years. Compared to an average daily dose of <20 morphine milligrams equivalent (MME), higher average daily doses at initiation were associated with greater hazard of treated OUD, 20-50 MME (HR 1.11, 95% CI: 1.02, 1.21), >50-90 MME (HR 1.29, 95% CI: 1.16, 1.44), >90-150 MME (HR 1.29, 95% CI: 1.06, 1.56), >150-200 MME (HR 2.49, 95% CI: 1.54, 4.03) and >200 MME (HR 4.15, 95% CI: 2.89, 5.97). Long-acting formulations and days' supply ≥11 days were also associated with greater hazard of treated OUD. CONCLUSION: Prescription opioid characteristics at initiation are associated with risk of treated OUD, identifying potentially important and modifiable risk factors among people initiating opioids for non-cancer pain.

Opioid Prescribing Practices for Women Undergoing Elective Gynecologic Surgery.

STUDY OBJECTIVE: To describe the opioid prescribing practices in opioid-naive women undergoing elective gynecologic surgery for benign indications and identify risk factors associated with increased perioperative opioid use. We also explored factors associated with new persistent opioid use in women with perioperative opioid use. DESIGN: Retrospective, population-based cohort study. SETTING: We used linked administrative data from a government-administered single-payer provincial healthcare system in Canada. This study was undertaken at ICES, a not-for-profit research institute in Ontario, Canada. PATIENTS: We followed opioid-naive adult women who underwent benign elective gynecologic surgery between 2013 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was perioperative opioid use defined as ≥1 opioid prescription from 30 days before to 14 days after surgery. New persistent opioid use after gynecologic surgery was defined as having filled 1 or more opioid prescriptions between 91 days and 180 days postoperatively. Multivariable log-linear regression analyses were employed to adjust for clinical and demographic data. Of the 132 506 patients included in our cohort, most (74.3%) underwent minor gynecologic procedures. Perioperative opioid use was documented in 27 763 (21.0%) patients, and there was a significant decreasing trend (p <.001) in the proportion of patients with perioperative opioid use from 21.8% in 2013 to 18.5% in 2018. Factors associated with increased perioperative opioid use included younger age; higher income quintile; urban dwellers; and diagnosis of infertility, endometriosis, or adnexal mass. Perioperative opioid use was an independent risk factor for persistent use (adjusted relative risk 1.40; 95% confidence interval, 1.13-1.72) and for every 65 patients prescribed opioids associated with gynecologic surgery, one developed new persistent opioid use. The highest risk factor for developing persistent use was filling a high-dose opioid prescription (adjusted relative risk5th quintileOME 2.33; 95% confidence interval, 1.83-2.96). CONCLUSION: One in 5 women who undergo a gynecologic procedure has a new exposure to opioids. For every 65 patients who fill an opioid prescription after their gynecologic surgery, one will experience prolonged opioid use.

Potential Cost Implications of Mandatory Non-Medical Switching Policies for Biologics for Rheumatic Conditions and Inflammatory Bowel Disease in Canada.

In 2018, TNFα inhibitors were the highest cost drug class for Canadian public drug programs. In 2019, two Canadian provinces announced mandatory nonmedical switching policies in an attempt to reduce their costs by increasing biosimilar uptake. The national impact of similar policies across Canada is unknown. We conducted a cross-sectional analysis of monthly publicly funded prescription claims for infliximab, etanercept, and adalimumab between June 2015 and December 2019. We reported the market share of biosimilars for infliximab and etanercept in 2019 for each province and estimated the cost savings that public payers could have realized in 2019 if mandatory switching policies had been implemented across Canada, including a sensitivity analysis, which assumed that governments receive a 25% rebate on all biologics. Provincial drug programs spent CAD $991.84 million on infliximab, etanercept, and adalimumab in 2019, and, when biosimilars were available, they constituted only 15.5% of national utilization of these drugs. In British Columbia, the implementation of a mandatory switching policy for patients with rheumatic conditions increased the biosimilar market share of infliximab and etanercept by 299% (from 19.7% to 78.5%). If applied nationwide to all three biologics for all indications, we estimate such policies could lead to annual savings of between CAD $179.71 million and CAD $425.64 million nationally. The overall market share of biosimilars remains low in all provinces where mandatory switching policies have not been introduced. The cost implications of successfully increasing biosimilar uptake would be substantial, particularly as more biosimilars reach the Canadian market.

Evaluating the intended and unintended consequences of opioid-prescribing interventions on primary care in British Columbia, Canada: protocol for a retrospective population-based cohort study.

INTRODUCTION: Between 2015 and 2018, there were over 40 000 opioid-related overdose events and 4551 deaths among residents in British Columbia (BC). During this time the province mobilised a variety of policy levers to encourage physicians to expand access to opioid agonist treatment and the College of Physicians and Surgeons of British Columbia (CPSBC) released a practice standard establishing legally enforceable minimum thresholds of professional behaviour in the hopes of curtailing overdose events. Our goal is to conduct a comprehensive investigation of the intended and unintended consequences of these policy changes. Specifically, we aim to understand the effects of these measures on physician prescribing behaviours, identify physician characteristics associated with uptake of the new measures, and measure the effects of the policy changes on patients' access to quality primary care. METHODS AND ANALYSIS: This is a population-level, retrospective cohort study of all BC primary care physicians who prescribed any opioid medication for opioid-use disorder or chronic non-cancer pain during the study period, and their patients. The study period is 1 January 2013-31 December 2018, with a 1-year wash-in period (1 January 2012-31 December 2012) to exclude patients who initiated long-term opioid treatment prior to our study period or whose pain type (ie, 'chronic non-cancer', 'acute', 'cancer or palliative', or 'other') cannot be confirmed. The project combines five administrative health datasets under the authority of the BC Ministry of Health, with the CPSBC's Physician Registry, BC Cancer Agency's Cancer Registry and Vital Statistics' Mortality data. We will create measures of prescribing concordance, access, continuity, and comprehensiveness to assess primary care delivery and quality at both the physician and patient level. We will use generalised estimating equations, interrupted time series, mixed effects models, and funnel plots to identify factors related to changes in prescribing and evaluate the impact of the changes to prescribing policies. Results will be reported using appropriate Enhancing the QUAlity and Transparency Of health Research guidelines (eg, STrengthening the Reporting of OBservational studies in Epidemiology). ETHICS AND DISSEMINATION: This study has been approved by McGill University's Institutional Review Board (#A11-M55-19A), and the University of British Columbia's Research Ethics Board (#H19-03537). We will disseminate results via a combination of open access peer-reviewed journal publications, conferences, lay summaries and OpEds.

Characteristics of high-drug-cost beneficiaries of public drug plans in 9 Canadian provinces: a cross-sectional analysis.

BACKGROUND: Drugs are the fastest growing cost in the Canadian health care system, owing to the increasing number of high-cost drugs. The objective of this study was to examine the characteristics of high-drug-cost beneficiaries of public drug plans across Canada relative to other beneficiaries. METHODS: We conducted a cross-sectional study among public drug plan beneficiaries residing in all provinces except Quebec. We used the Canadian Institute for Health Information's National Prescription Drug Utilization Information System to identify all drugs dispensed to beneficiaries of public drug programs in 2016/17. We stratified the cohort into 2 groups: high-drug-cost beneficiaries (top 5% of beneficiaries based on annual costs) and other beneficiaries (remaining 95%). For each group, we reported total drug costs, prevalence of high-cost claims (> $1000), median number of drugs, proportion of beneficiaries aged 65 or more, the 10 most costly reimbursed medications and the 10 medications most commonly reimbursed. We reported estimates overall and by province. RESULTS: High-drug-cost beneficiaries accounted for nearly half (46.5%) of annual spending, with an average annual spend of $14 610 per beneficiary, compared to $1570 among other beneficiaries. The median number of drugs dispensed was higher among high-drug-cost beneficiaries than among other beneficiaries (13 [interquartile range (IQR) 7-19] v. 8 [IQR 4-13]), and a much larger proportion of high-drug-cost beneficiaries than other beneficiaries received at least 1 high-cost claim (40.9% v. 0.6%). Long-term medications were the most commonly used medications for both groups, whereas biologics and antivirals were the most costly medications for high-drug-cost beneficiaries. INTERPRETATION: High-drug-cost beneficiaries were characterized by the use of expensive medications and polypharmacy relative to other beneficiaries. Interventions and policies to help reduce spending need to consider both of these factors.

New Opioid Use after Invasive Mechanical Ventilation and Hospital Discharge.

Rationale: Patients who receive invasive mechanical ventilation (IMV) are usually exposed to opioids as part of their sedation regimen. The rates of posthospital prescribing of opioids are unknown.Objectives: To determine the frequency of persistent posthospital opioid use among patients who received IMV.Methods: We assessed opioid-naive adults who were admitted to an ICU, received IMV, and survived at least 7 days after hospital discharge in Ontario, Canada over a 26-month period (February, 2013 through March, 2015). The primary outcome was new, persistent opioid use during the year after discharge. We assessed factors associated with persistent use by multivariable logistic regression. Patients receiving IMV were also compared with matched hospitalized patients who did not receive intensive care (non-ICU).Measurements and Main Results: Among 25,085 opioid-naive patients on IMV, 5,007 (20.0%; 95% confidence interval [CI], 19.5-20.5) filled a prescription for opioids in the 7 days after hospital discharge. During the next year, 648 (2.6%; 95% CI, 2.4-2.8) of the IMV cohort met criteria for new, persistent opioid use. The patient characteristic most strongly associated with persistent use in the IMV cohort was being a surgical (vs. medical) patient (adjusted odds ratio, 3.29; 95% CI, 2.72-3.97). The rate of persistent use was slightly higher than for matched non-ICU patients (2.6% vs. 1.5%; adjusted odds ratio, 1.37 [95% CI, 1.19-1.58]).Conclusions: A total of 20% of IMV patients received a prescription for opioids after hospital discharge, and 2.6% met criteria for persistent use, an average of 300 new persistent users per year in a population of 14 million. Receipt of surgery was the factor most strongly associated with persistent use.

Evaluation of opioid discontinuation after non-orthopaedic surgery among chronic opioid users: a population-based cohort study.

BACKGROUND: Many patients use opioids chronically before surgery; it is unclear if surgery alters the likelihood of ongoing opioid consumption in these patients. METHODS: We performed a population-based matched cohort study of adults in Ontario, Canada undergoing one of 16 non-orthopaedic surgical procedures and who were chronically using opioids, defined as (1) an opioid prescription that overlapped the index date and (2) either a total of 120 or more cumulative calendar days of filled opioid prescriptions, or 10 or more prescriptions filled in the prior year. Each surgical patient was matched based on age, sex, Charlson comorbidity index, and daily preoperative opioid dose to three non-surgical patients who were also chronic opioid users. The primary outcome was time to opioid discontinuation. RESULTS: The cohort included 4755 surgical and 14 265 matched non-surgical patients. After adjustment for sociodemographic characteristics and comorbidities, surgery was associated with an increased likelihood of opioid discontinuation (adjusted hazard ratio: 1.34, 95% confidence interval [CI]: 1.27, 1.42). Among surgical patients, factors associated with a reduced odds of discontinuation included a mean preoperative opioid dose above 90 morphine milligram equivalents (adjusted odds ratio [aOR]: 0.39; 95% CI: 0.32, 0.49) or filling a prescription for oxycodone (aOR: 0.73; 95% CI: 0.56, 0.98). Receipt of an in-patient Acute Pain Service consultation (aOR: 1.34; 95% CI: 1.06, 1.69) or residing in the highest neighbourhood income quintile (aOR: 1.35; 95% CI: 1.04, 1.79) were associated with a greater odds of opioid discontinuation. CONCLUSIONS: For chronic opioid users, surgery was associated with an increased likelihood of discontinuation of opioids in the following year compared with non-surgical chronic opioid users.

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.

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.

Do Diagnostic and Procedure Codes Within Population-Based, Administrative Datasets Accurately Identify Patients with Rectal Cancer?

BACKGROUND: Procedural and diagnostic codes may inaccurately identify specific patient populations within administrative datasets. PURPOSE: Measure the accuracy of previously used coding algorithms using administrative data to identify patients with rectal cancer resections (RCR). METHODS: Using a previously published coding algorithm, we re-created a RCR cohort within administrative databases, limiting the search to a single institution. The accuracy of this cohort was determined against a gold standard reference population. A systematic review of the literature was then performed to identify studies that use similar coding methods to identify RCR cohorts and whether or not they comment on accuracy. RESULTS: Over the course of the study period, there were 664,075 hospitalizations at our institution. Previously used coding algorithms identified 1131 RCRs (administrative data incidence 1.70 per 1000 hospitalizations). The gold standard reference population was 821 RCR over the same period (1.24 per 1000 hospitalizations). Administrative data methods yielded a RCR cohort of moderate accuracy (sensitivity 89.5%, specificity 99.9%) and poor positive predictive value (64.9%). Literature search identified 18 studies that utilized similar coding methods to derive a RCR cohort. Only 1/18 (5.6%) reported on the accuracy of their study cohort. CONCLUSIONS: The use of diagnostic and procedure codes to identify RCR within administrative datasets may be subject to misclassification bias because of low PPV. This underscores the importance of reporting on the accuracy of RCR cohorts derived within population-based datasets.

Second-generation anti-depressants and risk of new-onset seizures in the elderly.

BACKGROUND: Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants. METHODS: We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index. RESULTS: We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk. CONCLUSIONS: The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.

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.