Benzodiazepine use in medical cannabis authorization adult patients from 2013 to 2021: Alberta, Canada.

BACKGROUND: Benzodiazepines are a class of medications that are being frequently prescribed in Canada but carry significant risk of harm. There has been increasing clinical interest on the potential "sparing effects" of medical cannabis as one strategy to reduce benzodiazepine use. The objective of this study as to examine the association of medical cannabis authorization with benzodiazepine usage between 2013 and 2021 in Alberta, Canada. METHODS: A propensity score matched cohort study with patients on regular benzodiazepine treatment authorized to use medical cannabis compared to controls who do not have authorization for medical cannabis. A total of 9690 medically authorized cannabis patients were matched to controls. To assess the effect of medical cannabis use on daily average diazepam equivalence (DDE), interrupted time series (ITS) analysis was used to assess the change in the trend of DDE in the 12 months before and 12 months after the authorization of medical cannabis. RESULTS: Over the follow-up period after medical cannabis authorization, there was no overall change in the DDE use in authorized medical cannabis patients compared to matched controls (- 0.08 DDE, 95% CI: - 0.41 to 0.24). Likewise, the sensitivity analysis showed that, among patients consuming ≤5 mg baseline DDE, there was no change immediately after medical cannabis authorization compared to controls (level change, - 0.04 DDE, 95% CI: - 0.12 to 0.03) per patient as well as in the month-to-month trend change (0.002 DDE, 95% CI: - 0.009 to 0.12) per patient was noted. CONCLUSIONS: This short-term study found that medical cannabis authorization had minimal effects on benzodiazepine use. Our findings may contribute ongoing evidence for clinicians regarding the potential impact of medical cannabis to reduce benzodiazepine use. HIGHLIGHTS: • Medical cannabis authorization had little to no effect on benzodiazepine usage among patients prescribed regular benzodiazepine treatment in Alberta, Canada. • Further clinical research is needed to investigate the potential impact of medical cannabis as an alternative to benzodiazepine medication.

Defining opioid naïve and implications for monitoring opioid use: A population-based study in Alberta, Canada.

PURPOSE: Reducing initial exposure of "opioid naïve" patients to opioids is a public health priority. Identifying opioid naïve patients is difficult, as numerous definitions are used. The objective is to summarize current definitions and evaluate their impact on opioid naïve measures in Alberta. METHODS: An exploratory data analysis of the literature was conducted over the last 10 years to identify definitions commonly used in the literature to define opioid naïve. Then, using these definitions as a guide, we descriptively report the proportion of patients in Alberta between 2017 and 2021 who would be considered as opioid naïve using these definitions and all opioid dispensing data. RESULTS: Three categories of definitions were broadly identified: (1) no opioid use within the previous 30 days/6 months/1 year, based on dispensation date; (2) no opioid use based on dispensation date plus days of supply; and, (3) exclusion of codeine from Definitions 1 and 2. Applying these definitions to the Alberta population showed a very wide range in the proportion who would be considered as opioid naïve. Overall, 36.4% of Albertans (n = 1 551 075) had an opioid dispensation in 2017-2021. The average age was 46.6 ± 18.8 and 52.8% were female. The proportion of opioid naïve were most affected by the "opioid free" period, with 97.4%, 83.2%, and 65.6% being classified as opioid naïve using time windows from Definition 1 (30 days, 6 months, 1 year of no prior opioid use). Definitions 2 and 3 did not materially change the results. Further extending the "opioid free" period to 2 years showed only 35% were opioid naïve. CONCLUSIONS: The most convenient definition for "opioid naïve" was the use of an "opioid free" period. The choice of window would depend on how the information may be used to assistant in clinical decisions with longer windows more likely to reflect true opioid naïve patients. Irrespective of definition used, a large proportion of opioid users would be considered opioid naïve in Alberta.

Development and Validation of a Machine Learning Model to Estimate Risk of Adverse Outcomes Within 30 Days of Opioid Dispensation.

Importance: Machine learning approaches can assist opioid stewardship by identifying high-risk opioid prescribing for potential interventions. Objective: To develop a machine learning model for deployment that can estimate the risk of adverse outcomes within 30 days of an opioid dispensation as a potential component of prescription drug monitoring programs using access to real-world data. Design, Setting, and Participants: This prognostic study used population-level administrative health data to construct a machine learning model. This study took place in Alberta, Canada (from January 1, 2018, to December 31, 2019), and included all patients 18 years and older who received at least 1 opioid dispensation from a community pharmacy within the province. Exposures: Each opioid dispensation served as the unit of analysis. Main Outcomes and Measures: Opioid-related adverse outcomes were identified from administrative data sets. An XGBoost model was developed on 2018 data to estimate the risk of hospitalization, an emergency department visit, or mortality within 30 days of an opioid dispensation; validation on 2019 data was done to evaluate model performance. Model discrimination, calibration, and other relevant metrics are reported using daily and weekly predictions on both ranked predictions and predicted probability thresholds using all data from 2019. Results: A total of 853 324 participants represented 6 181 025 opioid dispensations, with 145 016 outcome events reported (2.3%); 46.4% of the participants were men and 53.6% were women, with a mean (SD) age of 49.1 (15.6) years for men and 51.0 (18.0) years for women. Of the outcome events, 77 326 (2.6% pretest probability) occurred within 30 days of a dispensation in the validation set (XGBoost C statistic, 0.82 [95% CI, 0.81-0.82]). The top 0.1 percentile of estimated risk had a positive likelihood ratio (LR) of 28.7, which translated to a posttest probability of 43.1%. In our simulations, the weekly measured predictions had higher positive LRs in both the highest-risk dispensations and percentiles of estimated risk compared with predictions measured daily. Net benefit analysis showed that using machine learning prediction may not add additional benefit over the entire range of probability thresholds. Conclusions and Relevance: These findings suggest that prescription drug monitoring programs can use machine learning classifiers to identify patients at risk of opioid-related adverse outcomes and intervene on high-risk ranked predictions. Better access to available administrative and clinical data could improve the prediction performance of machine learning classifiers and thus expand opioid stewardship efforts.

Opioid use in medical cannabis authorization adult patients from 2013 to 2018: Alberta, Canada.

BACKGROUND: The opioid overdose epidemic in Canada and the United States has become a public health crisis - with exponential increases in opioid-related morbidity and mortality. Recently, there has been an increasing body of evidence focusing on the opioid-sparing effects of medical cannabis use (reduction of opioid use and reliance), and medical cannabis as a potential alternative treatment for chronic pain. The objective of this study is to assess the effect of medical cannabis authorization on opioid use (oral morphine equivalent; OME) between 2013 and 2018 in Alberta, Canada. METHODS: All adult patients defined as chronic opioid users who were authorized medical cannabis by their health care provider in Alberta, Canada from 2013 to 2018 were propensity score matched to non-authorized chronic opioid using controls. A total of 5373 medical cannabis patients were matched to controls, who were all chronic opioid users. The change in the weekly average OME of opioid drugs for medical cannabis patients relative to controls was measured. Interrupted time series (ITS) analyses was used to assess the trend change in OME during the 26 weeks (6 months) before and 52 weeks (1 year) after the authorization of medical cannabis among adult chronic opioid users. RESULTS: Average age was 52 years and 54% were female. Patients on low dose opioids (< 50 OME) had an increase in their weekly OME per week (absolute increase of 112.1 OME, 95% CI: 104.1 to 120.3); whereas higher dose users (OME > 100), showed a significant decrease over 6 months (- 435.5, 95% CI: - 596.8 to - 274.2) compared to controls. CONCLUSIONS: This short-term study found that medical cannabis authorization showed intermediate effects on opioid use, which was dependent on initial opioid use. Greater observations of changes in OME appear to be in those patients who were on a high dosage of opioids (OME > 100); however, continued surveillance of patients utilizing both opioids and medical cannabis is warranted by clinicians to understand the long-term potential benefits and any harms of ongoing use.

Reducing prescribing of benzodiazepines in older adults: a comparison of four physician-focused interventions by a medical regulatory authority.

BACKGROUND: The inappropriate and/or high prescribing of benzodiazepine and 'Z' drugs (BDZ +) is a major health concern. The purpose of this study was to determine whether physician or pharmacist led interventions or a simple letter or a personalized prescribing report from a medical regulatory authority (MRA) was the most effective intervention for reducing BDZ + prescribing by physicians to patients 65 years of age or older. METHODS: This was a four-armed, one year, blinded, randomized, parallel-group, investigational trial in Alberta, Canada. Participants were fully licensed physicians (n = 272) who had prescribed 4 times the defined daily dose (4 + DDD) or more of any BDZ + to an older patient at least once in the 3rd quarter of 2016. All physician-participants were sent a personalized prescribing profile by the MRA. They were then randomized into four groups that received either nothing more, an additional personal warning letter from the MRA, a personal phone call from an MRA pharmacist or a personal phone call from an MRA physician. The main outcomes were prescribing behavior change of physicians at one year in terms of: change in mean number of older patients receiving 4 + DDD BDZ + and mean dose BDZ + prescribed per physician. To adjust for multiple statistical testing, we used MANCOVA to test both main outcome measures simultaneously by group whilst controlling for any baseline differences. RESULTS: All groups experienced a significant fall in the total number of older patients receiving 4 + DDD of BDZ + by about 50% (range 43-54%) per physician at one year, and a fall in the mean dose of BDZ + prescribed of about 13% (range 10-16%). However, there was no significant difference between each group. CONCLUSIONS: A personalized prescribing report alone sent from the MRA appears to be an effective intervention for reducing very high levels of BDZ + prescribing in older patients. Additional interventions by a pharmacist or physician did not result in additional benefit. The intervention needs to be tested further on a more general population of physicians, prescribing less extreme doses of BDZ + and that looks at more clinical and healthcare utilization outcomes.

Survey of physician attitudes to using multisource feedback for competence assessment in Alberta.

BACKGROUND: The use of multisource feedback (MSF) for assessing physician performance is widespread and rapidly growing. Findings from early very small research studies using highly selected participants suggest high levels of satisfaction and support. However, after nearly two decades of experience using MSF to evaluate all physicians in Alberta, we are sceptical of this. OBJECTIVES: To determine physicians' actual opinions of MSF using the entire physician population of Alberta, Canada DESIGN: Online survey. SETTING: Alberta, Canada. PARTICIPANTS: All physicians with a full licence to practice in Alberta in 2015. INTERVENTIONS: All participants were asked to grade how well they thought MSF was at assessing various aspects of physician performance using a 10-point Likert-type scale. There was also a text response field for written comments. OUTCOMES: Mean responses to quantitative questions. Qualitative content and thematic analysis of open-ended text responses.We analysed the data using SPSS V.23 and NVivo V.11 and built a multivariate model highlighting the predictors of high and low opinions of MSF. RESULTS: Survey response rate was high for physicians with 2215 responses (25%). The mean rating for how successful MSF was at assessing a variety of dimensions, varied from a low of 5.03/10 for medical knowledge to a high of 6.38/10 for professionalism and communication. Canadian-trained MDs rated MSF significantly lower on every dimension by approximately 20% compared with non-Canadian-trained MDs. CONCLUSIONS: Alberta physicians have much lower opinions about the ability of MSF to measure any dimension of their performance than what has been suggested in the literature. Canadian-trained MDs have a particularly low opinion of MSF for reasons that remain unclear. The results of this survey offer a serious challenge to the effectiveness of a programme that is designed to promote self-reflection and performance improvement.

Concurrent use of opioids and benzodiazepines/Z-drugs in Alberta, Canada and the risk of hospitalisation and death: a case cross-over study.

OBJECTIVES: Coprescribing of benzodiazepines/Z-drugs (BZDs) and opioids is a drug-use pattern of considerable concern due to risk of adverse events. The objective of this study is to estimate the effect of concurrent use of BZDs on the risk of hospitalisations/emergency department (ED) visits and deaths among opioid users. DESIGN, SETTING AND PARTICIPANTS: We conducted a population-based case cross-over study during 2016-2018 involving Albertans 18 years of age and over who received opioids. From this group, we identified 1 056 773 people who were hospitalised or visited the ED, and 31 998 who died. INTERVENTION: Concurrent use of opioids and BZDs. OUTCOMES: We estimated the risk of incident all-cause hospitalisation/ED visits and all-cause mortality associated with concurrent BZD use by applying a matched-pair analyses comparing concurrent use to opioid only use. RESULTS: Concurrent BZD use occurred in 17% of opioid users (179 805/1 056 773). Overall, concurrent use was associated with higher risk of hospitalisation/ED visit (OR 1.13, p<0.001) and all cause death (OR 1.90; p<0.001). The estimated risk of hospitalisation/ED visit was highest in those >65 (OR 1.5; p<0.001), using multiple health providers (OR 1.67; p<0.001) and >365 days of opioid use (OR 1.76; p<0.001). Events due to opioid toxicity were also associated with concurrent use (OR 1.8; p<0.001). Opioid dose-response effects among concurrent patients who died were also noted (OR 3.13; p<0.001). INTERPRETATION: Concurrent use of opioids and BZDs further contributes to the risk of hospitalisation/ED visits and mortality in Alberta, Canada over opioid use alone, with higher opioid doses, older age and increased number of unique health providers carrying higher risks. Regulatory bodies and health providers should reinforce safe drug-use practices and be vigilant about coprescribing.

Medical Cannabis Authorization in Patients With Cancer in the Prelegalization Era: A Population-Based Study.

CONTEXT: Studies show that patients with cancer use cannabis to manage symptoms and side effects. Medical cannabis is regulated by Health Canada; authorization patterns among cancer patients have not been well described. OBJECTIVES: The aim of the study is to describe medical cannabis authorization in Alberta, Canada. METHODS: The Alberta Cancer Registry was used to identify all patients aged 18 years and older diagnosed with invasive cancer from April 1, 2014 to December 31, 2016. These cases were linked to records from the College of Physicians and Surgeons of Alberta. Univariate and multivariate logistic regression models were constructed to determine factors associated with medical cannabis authorization. RESULTS: We identified 41,889 patients with cancer between April 1, 2014 and December 31, 2016. Of these patients, 1070 (2.6%) had a medical cannabis authorization. Fifty-one percent (541 of 1070) were authorized to use medical cannabis within one year of diagnosis, 52% (248 of 549) within one year of the start of systemic therapy, and 41% (128 of 312) within one year of the start of radiation therapy. Patients aged 18-29 (odds ratio [OR] 12.4; 95% CI 7.8-19.8), patients living in the Calgary zone (OR 1.8; 95% CI 1.6-2.1), those with advanced disease (Stage III/IV: OR 1.2; 95% CI 1.0-1.4), and those receiving systemic therapy (OR 2.0; 95% CI 1.7-2.4) were more likely to have an authorization for medical cannabis (P < 0.001). CONCLUSION: A small proportion of patients with cancer were authorized to use medical cannabis between 2014 and 2016 in Alberta. Authorization was associated with a cancer diagnosis and receiving treatment. Younger patients, those with advanced stage disease, and those undergoing systemic treatment were predictors of medical cannabis authorization.

Characterisation of concurrent use of prescription opioids and benzodiazepine/Z-drugs in Alberta, Canada: a population-based study.

OBJECTIVE: The objective of this study is to characterise concurrent use of benzodiazepine receptor modulators and opioids among prescription opioid users in Alberta in 2017. DESIGN: A population based retrospective study. SETTING: Alberta, Canada, in the year 2017. PARTICIPANTS: All individuals in Alberta, Canada, with at least one dispensation record from a community pharmacy for an opioid in the year 2017. EXPOSURE: Concurrent use of a benzodiazepine receptor modulator and opioid, defined as overlap of supply for both drugs for at least 1 day. MAIN OUTCOME MEASURES: Prevalence of concurrency was estimated among subgroups of patient characteristics that were considered clinically relevant or associated with inappropriate medication use. RESULTS: Among the 547 709 Albertans who were dispensed opioid prescriptions in 2017, 132 156 (24%) also received prescriptions for benzodiazepine receptor modulators. There were 96 581 (17.6%) prescription opioid users who concurrently used benzodiazepine receptor modulators with an average of 98 days (SD=114, 95% CI 97 to 99) of total cumulative concurrency and a median of 37 days (IQR 10 to 171). The average longest duration of consecutive days of concurrency was 45 (SD=60, 95% CI 44.6 to 45.4) with a median of 24 days (IQR 8 to 59). Concurrency was more prevalent in females, patients using an average daily oral morphine equivalent >90 mg, opioid dependence therapy patients, chronic opioid users, patients utilising a high number of unique providers, lower median household incomes and those older than 65 (p value<0.001 for all comparisons). CONCLUSIONS: Concurrent prescribing of opioids and benzodiazepine receptor modulators is common in Alberta despite the ongoing guidance of many clinical resources. Older patients, those taking higher doses of opioids, and for longer durations may be at particular risk of adverse outcomes and may be worthy of closer follow-up for assessment for dose tapering or discontinuations. As well, those with higher healthcare utilisation (seeking multiple providers) should also be closely monitored. Continued surveillance of concurrent use of these medications is warranted to ensure that safe drug use recommendations are being followed by health providers.

Benzodiazepine receptor agonist dispensations in Alberta: a population-based descriptive study.

BACKGROUND: There is increasing concern over the use of benzodiazepine receptor agonists (BZRAs). The objective of this study was to describe BZRA dispensations in the province of Alberta in 2015 according to age, sex and appropriateness. METHODS: A population-based descriptive study of people 10 years of age or older with at least 1 BZRA dispensation in Alberta, Canada, between Jan. 1 and Dec. 31, 2015, was conducted. Prevalence of BZRA use, characteristics of BZRAs dispensations, use at the individual level and appropriateness were determined. RESULTS: A total of 372 870 people received 2 463 585 BZRA dispensations in Alberta in 2015. Prevalence of use at the population level was 10% overall, increased with age (p value for trend < 0.001) and was consistently highest among females. Twenty percent of patients used both Z-drugs and benzodiazepines. BZRA users had an average of 7 dispensations (standard deviation [SD] 20), 137 days of use overall (SD 123) and a maximum period of consecutive use of 90 days (SD 95). Days of consecutive use were highest among those aged 65 years or older (126 d). A total of 62 795 (17%) people used more than 1 distinct BZRA ingredient concurrently and 10% had 3 or more distinct prescribers. INTERPRETATION: The prevalence of BZRA use was high and a substantial proportion of use appeared to be potentially inappropriate. This study supports the need for continued monitoring for the prescribing and use of these medications at the population level.