A Descriptive Analysis of Adverse Event Reports from the Quebec Cannabis Registry.

INTRODUCTION: Published data on the safety of natural medical cannabis (MC) when used in the real-world clinical practice setting are lacking. This study aimed to describe adverse events (AEs) reported across three years following MC initiation. METHODS: The Quebec Cannabis Registry (QCR) was a prospective registry of adults enrolled through participating physicians when they initiated MC between May 2015 and October 2018. Follow-up ended at MC discontinuation, loss to follow-up, three years, or end of data collection (May 2019). Data were collected at baseline and at follow-up visits every three months for the first two years, then once in the third year. Physicians filled adverse event (AE) reports, which were coded using MedDRA® preferred terms (PTs), and descriptive analyses were conducted. RESULTS: A total of 2991 patients were enrolled (mean age 50.9 years, 50.2% females). During follow-up, 108 patients (3.6%) experienced moderate or severe AEs, yielding 111 AE reports (three patients had two reports) and 214 AEs (average 1.9 AEs per report). Mild AEs were recorded as a reason for MC discontinuation for nine patients, but no AE reports were available. The most common PTs for ingested MC (62 reports) were dizziness (12.9%), nausea (11.3%), somnolence (9.7%), and vomiting (8.1%), and for inhaled MC (23 reports), headache (13.0%) was the most common. The most frequent PTs associated with tetrahydrocannabinol (THC)-dominant MC (25 reports) were dizziness and somnolence (12.0% each); for cannabidiol (CBD)-dominant MC (20 reports), vomiting (20.0%) was most common; and dizziness (17.2%), nausea (13.8%), somnolence (10.3%), and headache (8.6%) were the most frequent for balanced MC (58 reports). CONCLUSION: No new safety concerns were identified relative to the published literature, although notable differences in AE profile between modes of administration and cannabinoid content ratios should be considered by health professionals. Further work identifying and managing risk factors for AEs is warranted to maintain a favorable benefit-risk balance for MC.

Impact of the COVID-19 Pandemic on Patterns of Prescription Opioid Use: A Retrospective Cohort Study of Adults Without a Cancer Diagnosis Initiating Opioids Using Administrative Claims Data.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to disruptions of healthcare delivery and may thus have impacted patterns of prescription opioid use, including risk factors for long-term use. OBJECTIVE: We aimed to describe changes in patterns of prescription opioid use due to the COVID-19 pandemic in community-dwelling adults without a cancer diagnosis. METHODS: Using administrative claims data of the province of Quebec, Canada, a random sample of adults (aged ≥18 years) was selected. These were members of the public drug plan without a cancer diagnosis who initiated a prescription opioid in the outpatient setting between 1 January, 2018 and 28 December, 2020. We assessed the daily dose of initial prescription opioids, the number of days' supply of initial dispensing, and the total duration of opioid use over the first 6 months following initiation. We applied interrupted autoregressive integrated moving average models to examine weekly patterns of prescription opioids before and during the pandemic (starting at the lockdown). Our models included a step intervention function (immediate change) and a ramp intervention function (slope change). RESULTS: There were 112,650 and 34,261 patients who initiated opioid therapy, respectively, in the 115-week pre-pandemic period and in the 41-week pandemic period. At the start of the lockdown, there was a significant immediate decrease in opioid treatment initiation (-326; 95% confidence interval [CI] -419 to -234) and initial daily dose (-1.7 morphine milligram equivalents; 95% CI -2.7 to -0.7). Conversely, there was a significant immediate increase in the number of days' supply of initial dispensing (1.4 days; 95% CI 1.0 to 1.8) and the total duration of opioid use over 6 months (5.7 days; 95% CI 4.6 to 6.8). All these weekly measures returned to values close to those of the pre-pandemic period 10 weeks after the start of lockdown. CONCLUSIONS: Our findings showed that the COVID-19 lockdown had an impact on initial number of days' supply, which is a risk factor for long-term use and ultimately opioid-related harm. However, over time, prescription practices and use reverted to those observed in the pre-pandemic period.

Understanding reporting practices and perceptions of barriers in adverse events following immunisation surveillance: A cross-sectional survey of paediatricians in Kerala, India.

PURPOSE: The role of health care professionals (HCPs) is central to adverse event following immunisation (AEFI) surveillance. A cross-sectional survey was conducted among paediatricians practising in Kerala, India, to assess their knowledge and reporting behaviour in AEFI surveillance as well as to identify barriers to reporting. RESULTS: A random sample of 380 paediatricians were contacted of whom, 243 (63.9%) participated in the survey. The understanding scores were distributed as follows: 30.9% very high or high, 40.3% moderate, and 28.8% low. Formal training was significantly associated with higher understanding scores, and increased AEFI detection and reporting. Only 42.0% of respondents had formal training; paediatricians in the public sector had higher access to training than those in the private sector. There were 141 respondents (58.0%) who identified an AEFI in the previous year, of whom 66 (46.8%) reported it. The main barriers to AEFI reporting were: difficulties with reporting process (28.9%); fear of raising public alarm (28.1%); time constraints (22.3%); fear of personal consequences (15.7%); and belief that health authorities rarely take useful action (11.6%). CONCLUSION: Training in AEFI surveillance should be prioritised for HCPs with greater emphasis in medical education programmes. Study showed that a user-friendly reporting mechanism and a blame-free culture are crucial to improve AEFI reporting practices.

Predictors of long-term use of prescription opioids in the community-dwelling population of adults without a cancer diagnosis: a retrospective cohort study.

BACKGROUND: Long-term opioid use is a known risk factor for opioid-related harms. We aimed to identify risk factors for and predictors of long-term use of prescription opioids in the community-dwelling population of adults without a diagnosis of cancer, to inform practice change at the point of care. METHODS: Using Quebec administrative claims databases, we conducted a retrospective cohort study in a random sample of adult members (≥ 18 yr) of the public drug plan who did not have a cancer diagnosis and who initiated a prescription opioid in the outpatient setting between Jan. 1, 2012, and Dec. 31, 2016. The outcome of interest was long-term opioid use (≥ 90 consecutive days or ≥ 120 cumulative days over 12 mo). Potential predictors included sociodemographic factors, medical history, characteristics of the initial opioid prescription and prescriber's specialty. We used multivariable logistic regression to assess the association between each characteristic and long-term use. We used the area under the receiver operating characteristic curve to determine the predictive performance of full and parsimonious models. RESULTS: Of 124 664 eligible patients who initiated opioid therapy, 4172 (3.3%) progressed to long-term use of prescription opioids. The most important associated factors in the adjusted analysis were long-term prescription of acetaminophen-codeine (odds ratio [OR] 6.30, 95% confidence interval [CI] 4.99 to 7.96), prescription of a long-acting opioid at initiation (OR 6.02, 95% CI 5.31 to 6.84), initial supply of 30 days or more (OR 4.22, 95% CI 3.81 to 4.69), chronic pain (OR 2.41, 95% CI 2.16 to 2.69) and initial dose of at least 90 morphine milligram equivalents (MME) per day (OR 1.24, 95% CI 1.04 to 1.47). Our predictive model, including only the initial days' supply and chronic pain diagnosis, had area under the curve of 0.7618. INTERPRETATION: This study identified factors associated with long-term prescription opioid use. Limiting the initial supply to no more than 7 days and limiting doses to 90 MME/day or less are actions that could be undertaken at the point of care.

Secondary Stroke Prevention: A Population-Based Cohort Study on Anticoagulation and Antiplatelet Treatments, and the Risk of Death or Recurrence.

Using claims databases of a public healthcare program (Quebec) for the years 2010-2013, we conducted a cohort study of patients with acute ischemic stroke (AIS) to describe secondary prevention treatments and determine how they stood against practice guidelines. We compared the risk of death or AIS recurrence over 1 year in patients treated with anticoagulants, antiplatelets, and/or other cardiovascular drugs. In the month after discharge, 44.3% of the patients did not receive the recommended treatment and > 20% did not have any treatment. Untreated patients were younger, had less comorbidities, and a more severe AIS. Anticoagulants and antiplatelets were associated with a reduced risk of death or recurrence (hazard ratio (HR) 0.27; 95% confidence interval (CI) 0.20-0.36 and HR 0.25; 95% CI 0.16-0.38, respectively) compared with the untreated group. Effect size was similar for the other treatments. Findings confirm treatment benefits shown in clinical trials and emphasize the importance of AIS secondary prevention.

Effectiveness of Risk Minimization Measures for Fentanyl Buccal Tablet (FENTORA) in Canada: A Mixed-Methods Evaluation Using Surveys, Medical Chart Records and Web Surveillance.

BACKGROUND: Fentanyl buccal tablet (FBT), a potent opioid, was approved in Canada in 2013 for breakthrough pain in opioid-tolerant adult cancer patients. Additional risk minimization measures (aRMMs), consisting of communications to patients and healthcare providers (HCPs), were implemented from November 2014 through September 2015. OBJECTIVES: The aim of this study was to assess the effectiveness of FBT aRMMs as measured by prescriber knowledge, understanding, and behavior regarding key safety concerns (off-label use, use in non-opioid-tolerant patients, misuse/abuse/diversion, and drug-drug interaction) and to evaluate illicit FBT use. METHODS: The study included three components: (1) a knowledge and understanding (KAU) survey of FBT prescribers conducted in two waves: November 2016-February 2017 and April-September 2018; (2) a retrospective prescription study of medical records of patients treated with FBT by a subgroup of prescribers from the KAU survey; and (3) Web surveillance of illicit FBT use in Canada using the search term FENTORA (May 2014-September 2018). The aRMMs were considered effective if the lower bound of the 95% confidence interval indicated that at least 65% of respondents met or partly met the knowledge objective for each key safety concern. RESULTS: KAU survey: Of 46 eligible HCPs, 97.8% met or partly met the knowledge objective on use in breakthrough pain cancer patients, 97.8% on use in opioid-tolerant patients, 89.1% on dose and titration, 100% on abuse/addiction, and 58.7% on drug-drug interaction. Retrospective prescription study: Of 22 FBT-treated patients identified from 14 HCPs, 45.5% had cancer, 50.0% recorded a breakthrough pain indication, and 36.4% reported opioid tolerance; however, only 13.6% of patients were prescribed FBT according to the approved indication. Web surveillance: Of 932 FBT posts in Canada, only 40 (4.3%) mentioned illicit use. CONCLUSIONS: The aRMMs as measured by the prescriber KAU were effective for most key safety messages; however, not all key messages of the aRMMs were stringently followed in routine practice.

Prescription of topical antiglaucoma agents for patients with contraindications to beta-blockers.

BACKGROUND: In Canada, public drug plans may restrict the use of newer topical antiglaucoma agents. The goals of this retrospective study were to estimate the proportion of patients who, at the initiation of topical glaucoma therapy, had contraindications to the use of topical beta-blockers and to identify whether changes in formulary listing status (from restricted-drug list to generally available drug list) influenced the use of topical glaucoma agents in patients with contraindications to beta-blockers. METHODS: Claims databases administered by the Régie de l'assurance maladie du Quebec were used to identify incident users of beta-blockers (betaxolol and timolol) and newer antiglaucoma agents (brimonidine, dorzolamide and latanoprost) among patients aged 35 years or older. Drug claims and physician diagnoses were used to determine the prevalence of the following contraindications to the use of beta-blockers (including warnings and precautions): asthma or chronic bronchitis, diabetes, dysrhythmia and heart failure, all in the year preceding the initiation of therapy; or use of systemic beta-blockers at the time glaucoma therapy was started. The observation period was divided into 2 phases: the time during which newer agents were on the restricted-drug list (first-line use being limited to patients with contraindications to the use of beta-blockers; January 1997 to March 1999) and the time during which these agents were on the generally available drug list (that is, after reimbursement restrictions were relaxed; April 1999 to June 2000). RESULTS: Of the 20 309 eligible patients, 59.8% were female, and the mean age was 72 years. Contraindications to topical beta-blocker therapy were significantly more frequent among the patients using newer antiglaucoma agents than among those using beta-blockers (71.5% vs. 55.5%, p < 0.0001). Asthma and chronic bronchitis were also more frequent among the patients using the newer agents than among those using beta-blockers (43.1% vs. 22.5%, p < 0.0001). Among the patients without contraindications to topical beta-blocker therapy, the overall proportions started on therapy with a newer agent were 22.7% when there were reimbursement restrictions and 30.0% when the restrictions were relaxed (p < 0.0001). CONCLUSIONS: Among patients with contraindications to the use of beta-blockers, newer topical antiglaucoma agents were used more often than beta-blockers. Among patients without such contraindications, the use of the newer agents increased modestly when reimbursement restrictions were relaxed.

Effectiveness and cost-effectiveness of antibiotic treatments for community acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB).

BACKGROUND: The antibacterial activity, tolerability profile and duration of treatment associated with antibiotics are important therapy attributes when considering treating patients for lower respiratory tract infections (LRTIs), such as community acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB). OBJECTIVES: To investigate the effectiveness and cost-effectiveness of oral antibiotics used in the treatment of LRTIs. METHODS: A cohort of inhaled corticosteroids users who were diagnosed with a LRTI and dispensed a prescription for one of the antibiotics under study on the same day as the diagnosis was selected from the administrative health databases of the Régie de l'assurance maladie du Québec (RAMQ). The risks of treatment failure were estimated using a logistic regression analysis. Treatment failure was defined as another prescription for any antibiotic, an emergency room visit or hospitalization for LRTIs, or death, in the 20 days following the dispensation of the first antibiotic prescribed. A cost-minimization analysis was performed in which only the drug costs related to the first antibiotic filled were considered. RESULTS: A total of 3,610 episodes of LRTIs were studied. There were no significant differences between antibiotics in terms of their respective adjusted odds ratios for rates of failure. However, the lower cost associated with azithromycin was significantly different from the costs associated with any other antibiotic (p<0.0001). CONCLUSION: Clinical effectiveness appears to be similar amongst second line antibiotics that are commonly used in the treatment of LRTIs in the community. Using a cost-minimization analysis, azithromycin appears to be the most cost-effective antibiotic treatment in this setting.

Oral anticoagulants and the risk of osteoporotic fractures among elderly.

PURPOSE: Coumadin-based oral anticoagulants are associated with a decrease in bone mass density, but their role in fracture risk is equivocal. Because the use of oral anticoagulants is prevalent among the elderly, as is the risk and morbidity of osteoporotic fractures, the association between osteoporotic fractures and oral anticoagulants needs to be clarified. METHOD: We conducted a case-control study on a 10% random sample of subjects aged 70 years and older enrolled in the Quebec universal health insurance plan between 1992 and 1994. Incident cases of a first osteoporotic fracture were identified by International Classification of Diseases, Ninth Revision codes. Exposure was defined as one or more prescriptions of oral anticoagulants dispensed before the osteoporotic fracture. Ten controls for each case, matched by age and date of osteoporotic fracture, were identified. RESULTS: Among 1523 cases, 48 (3.2%) were ever exposed to oral anticoagulants; among 15,205 controls, 461 (3.0%) were ever exposed (crude odds ratio: 1.0: 95% confidence interval: 0.7-1.5). These negative results persisted after adjusting for potential confounding variables and stratifying exposure into cumulative dose and treatment duration. CONCLUSIONS: Coumadin-based oral anticoagulants are not significantly associated with osteoporotic fractures among the elderly, providing reassurance for elderly patients on long-term oral anticoagulants.