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

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

First-line medications for alcohol use disorders among public drug plan beneficiaries in Ontario.

OBJECTIVE: To examine use of first-line alcohol use disorder (AUD) medications (naltrexone and acamprosate) among public drug plan beneficiaries in the year following an AUD diagnosis. DESIGN: Retrospective population-based cohort study. SETTING: Ontario. PARTICIPANTS: Individuals eligible for public drug plan benefits who had an AUD diagnosis at a hospital visit between April 1, 2011, and March 31, 2012. MAIN OUTCOME MEASURES: Number of AUD medications dispensed to public drug plan beneficiaries who had a recent hospital visit with an AUD diagnosis, and number of prescriptions dispensed per person. RESULTS: A total of 10 394 Ontarians between 18 and 65 years of age were identified who had a hospital visit with an AUD diagnosis and were eligible for public drug plan benefits. The rate of AUD medications dispensed in the subsequent year was 3.56 per 1000 population (95% CI 2.51 to 4.91; n = 37). This rate did not differ significantly by sex (P = .83). CONCLUSION: Very few public drug plan beneficiaries are dispensed first-line AUD medications in the year following an AUD diagnosis.

Statins and the risk of herpes zoster: a population-based cohort study.

BACKGROUND: Statins are widely used lipid-lowering drugs with immunomodulatory properties that may favor reactivation of latent varicella-zoster virus infection. However, whether statins increase the risk of herpes zoster is unknown. METHODS: We conducted a population-based retrospective cohort study of Ontario residents aged ≥ 66 years between 1 April 1997 and 31 March 2010 to examine the association between statin use and incidence of herpes zoster. We used propensity score matching to ensure similarity between users and nonusers of statins, and Cox proportional hazard models to assess differences in outcomes between study groups. To test the specificity of our findings, we examined the association between statin exposure and knee arthroplasty. RESULTS: During the 13-year study period, we matched 494 651 individuals treated with a statin to an equal number of untreated individuals. In the main analysis, the rate of herpes zoster was higher among users of statins relative to nonusers of these drugs (13.25 vs 11.71 per 1000 person-years, respectively; hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.10-1.17). The attributable fraction of exposed individuals was 11.6%. In a prespecified analysis, we found a similar risk of herpes zoster among statin users in the subgroup of patients with diabetes (HR, 1.18; 95% CI, 1.09-1.27). As expected, we found no association between statin use and knee arthroplasty (HR, 1.04; 95% CI, .99-1.09). CONCLUSIONS: Among older patients, treatment with statins is associated with a small but significantly increased risk of herpes zoster.

Deploying Artificial Intelligence for Thoracic Imaging Around the World.

PURPOSE: Artificial intelligence (AI) thoracic imaging applications are increasingly being deployed in low- and middle-income countries (LMICs). Radiologists have a critical gatekeeping role to ensure the effective and ethical implementation of AI solutions. RAD-AID International uses a three-pronged implementation strategy to overcome challenges pervasive in LMICs. METHODS: During a similar period, an AI software for chest radiography (CXR) interpretation was deployed at two tertiary hospitals located in Guyana and Nigeria. The three-pronged implementation strategy of clinical education, infrastructure implementation, and phased AI introduction was used. A PACS with a cloud component was installed at each institution. Radiology residents and attending physicians at these institutions completed an introduction-to-AI course to prime them for the use of AI solutions. A phased introduction of the AI software was performed to allow local validation as well as trust building and workflow integration. Local validation processes were used at each site by comparing AI outputs with standardized prospectively generated reports by local radiologists and study team members, allowing for slight differences in the goals of AI software use between sites. RESULTS: The PACS was successfully installed at both institutions. Thirty participants completed the introduction-to-AI course with an average pre-knowledge test score of 75% and an average posttest score of 95%. The focus of the validation process at various sites was reflective of the intended use of the AI software. In Guyana, it revealed an 87% concordance rate between radiologists and the AI model for triaging normal versus abnormal findings on CXR. In Nigeria, an 85% concordance rate between radiologists and the AI model for reporting tuberculosis on CXR was noted. The AI software was successfully deployed and is being used as intended at both institutions. CONCLUSIONS: There are unique barriers to the adoption of AI in LMICs requiring an implementation strategy in collaboration with local institutions and industry partners to ensure success.

Evaluation of the fentanyl patch-for-patch program in Ontario, Canada.

BACKGROUND: Rising use of prescription opioids is a major public health concern associated with increased risk of mortality worldwide. Fentanyl, a synthetic opioid available in patch form, is particularly concerning given its high potency. To curb the misuse and diversion of fentanyl patches, a Patch-for-Patch (P4P) program was implemented in some counties in Ontario between 2012 and 2015. The program requires that patients prescribed fentanyl must return used patches to the pharmacy before receiving more patches. OBJECTIVE: To evaluate the impact of the P4P program on fentanyl and non-fentanyl dispensing and opioid-related hospitalizations and deaths. METHODS: We conducted a repeated cross-sectional time-series analysis among counties that implemented the P4P program using Ontario administrative claims data. Because intervention dates varied by county due to staggered program initiation, we aligned all intervention months and examined outcome rates in the 5 years preceding and 12 and 24 months following implementation. We explored the monthly rate of prescriptions dispensed for fentanyl and non-fentanyl opioids, opioid toxicity-related hospital and emergency department visits, and opioid-related deaths. We modeled each outcome using an interventional autoregressive integrated moving average (ARIMA) model and tested the impact of the P4P program using a ramp function. RESULTS: We analyzed 16 counties that implemented the P4P program and had at least 12 months of follow-up. The introduction of the P4P program was associated with a 30.5% decline in the volume of fentanyl patches dispensed at 24 months (from 1,277-888 patches per 10,000 population; p = 0.04). In contrast, there was no significant change in the rate of non-fentanyl opioid dispensing (p = 0.32), opioid toxicity related hospitalizations and emergency department visits (p = 0.4) or opioid-related deaths (p = 0.96) in the 12 months following implementation of the program. CONCLUSIONS: We found that the implementation of a P4P program in select counties in Ontario was associated with a lower volume of fentanyl patches dispensed by pharmacies, without an increase in use of other opioids. The program had no measurable impact on rates of opioid toxicity-related hospital visits or deaths. Policymakers should consider the use of P4P programs as part of larger opioid strategy.

Impact of a Graduated Approach on Opioid Initiation and Loss of Earnings Following Workplace Injury: A Time Series Analysis.

OBJECTIVE: The aim of this study was to explore the impact of the Ontario Workplace Safety and Insurance Board's (WSIB's) graduated approach to opioid management on opioid prescribing and disability claim duration. METHODS: We studied patterns of opioid use and disability claim duration among Ontarians who received benefits through the WSIB between 2002 and 2013. We used interventional time series analysis to assess the impact of the WSIB graduated formulary on these trends. RESULTS: After the introduction of the graduated formulary, initiation of short- and long-acting opioids fell significantly (P < 0.0001). We also observed a shift toward the use of short-acting opioids alone (P < 0.0001). Although disability claim duration declined, this could not be ascribed to the intervention (P = 0.18). CONCLUSION: A graduated opioid formulary may be an effective tool for providers to promote more appropriate opioid prescribing.

High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study.

AIMS: To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity. DESIGN: Interventional time-series analysis. SETTING: Ontario, Canada, from 2003 to 2014. PARTICIPANTS: Ontario Drug Benefit (ODB) beneficiaries aged 15 to 64 years from 2003 to 2014. INTERVENTIONS: Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010) and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011). MEASUREMENTS: Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions. FINDINGS: Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03) which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43). Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7%) over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68) or enactment of the NSAA (p-value = .59). CONCLUSIONS: Although the Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain led to a decline in opioid prescribing rates among ODB beneficiaries these guidelines and subsequent Ontario legislation did not result in a significant change in rates of opioid-related hospitalizations. Given the prevalence of high dose opioid prescribing in this population, this suggests that improved strategies and programs for the safe prescribing of long-acting opioids are needed.

The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario.

Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96-$747) for those who survived and $2,021 (IQR $993-$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management.

Self-Monitoring of Blood Glucose Levels: Evaluating the Impact of a Policy of Quantity Limits on Test-Strip Use and Costs.

OBJECTIVES: To evaluate the impact of new quantity limits for blood glucose test strips (BGTS) in August 2013 on utilization patterns and costs in the elderly population of Ontario, Canada. METHODS: We conducted a population-based, cross-sectional time series analysis of all individuals 65 years of age and older who received publically funded BGTSs between August 1, 2010, and July 31, 2015, in Ontario, Canada. The number of BGTSs dispensed and the associated costs were measured for 4 diabetes therapy subgroups-insulin, hypoglycemia-inducing oral agents, non-hypoglycemia-inducing oral agents, and no drug therapy-each month during the study period. We used interventional autoregressive integrated moving average (ARIMA) models to assess the impact of Ontario's policy change on test strip use and costs. RESULTS: In the course of the study period, 657,338,177 test strips were dispensed to elderly patients in Ontario, at a total cost of CAN$482.3 million. Introduction of quantity limits was associated with significant reductions in the number of monthly strips dispensed and the associated costs (p<0.0001). In the year following the policy's implementation, test strip use decreased by 22.2% compared with the prior year (from 145,232,024 test strips to 113,007,795 test strips, a net decrease of 32,224,229 strips), resulting in a 22.5% reduction in costs (from $106.5 million to $82.6 million, a net cost reduction of approximately $24 million). CONCLUSIONS: The introduction of quantity limits, aligned with guidance from the Canadian Diabetes Association, led to immediate significant reductions in BGTS dispensing and costs. More research is needed to assess the impact of this policy on patient outcomes.

Impact of legislation and a prescription monitoring program on the prevalence of potentially inappropriate prescriptions for monitored drugs in Ontario: a time series analysis.

BACKGROUND: The increased use of opioid analgesics, sedative hypnotics and stimulants, coupled with the associated risks of overdose have raised concerns around the inappropriate prescribing of these monitored drugs. We assessed the impact of new legislation, the Narcotics Safety and Awareness Act, and a centralized Narcotics Monitoring System (implemented November 2011 and May 2012, respectively), on the dispensing of prescriptions suggestive of misuse. METHODS: We conducted a time series analysis of publicly funded prescriptions for opioids, benzodiazepines and stimulants dispensed monthly in Ontario from January 2007 to May 2013, based on information in the Ontario Public Drug Benefit Database. In the primary analysis, a prescription was deemed potentially inappropriate if it was dispensed within 7 days of an earlier prescription and was for at least 30 tablets of a drug in the same class as the earlier prescription, but originated from a different physician and a different pharmacy. RESULTS: After enactment of the new legislation, the prevalence of potentially inappropriate opioid prescriptions decreased by 12.5% in 6 months (from 1.6% in October 2011 to 1.4% in April 2012; p = 0.01). No further significant change was observed after the introduction of the narcotic monitoring system (p = 0.8). By May 2013, the prevalence had dropped to 1.0%. Inappropriate benzodiazepine prescribing was significantly influenced by both the legislation (p < 0.001) and the monitoring system (p = 0.05), which together reduced potentially inappropriate prescribing by 50.0% between October 2011 and May 2013 (from 0.4% to 0.2%). The prevalence of potentially inappropriate prescribing of stimulants was significantly influenced by the introduction of the monitoring system in May 2012, falling from 0.7% in April 2012 to 0.3% in May 2013 (p = 0.02). INTERPRETATION: For a select group of drugs prone to misuse and diversion, legislation and a prescription monitoring program reduced the prevalence of prescriptions suggestive of misuse. This suggests that regulatory interventions can promote appropriate prescribing which could potentially be applied to other jurisdictions and drugs of concern.

Backing up the stories: The psychological and social costs of chronic low-back pain.

BACKGROUND: Chronic low-back pain is a widespread condition whose significance is overlooked. Previous studies have analyzed and evaluated the medical costs and physical symptoms of chronic low-back pain; however, few have looked beyond these factors. The purpose of this study was to analyze and evaluate the personal and psychosocial costs of chronic low-back pain. METHODS: To measure the various costs of chronic low-back pain, a questionnaire was generated using a visual analog scale, the Depression Anxiety and Stress Scale, the Short Form 36 Health Survey, and the 1998-1999 Australian Bureau of Statistics Household Expenditure Survey (for demographic questions). The comprehensive survey assessing physical, mental, emotional, social, and financial health was administered to 30 subjects aged 18 years or older who had visited a tertiary spine service with complaints of chronic low-back pain. RESULTS: It was found that subjects scored significantly higher on scales for depression, anxiety, and stress after the onset of chronic low-back pain than before the onset of back pain. Subjects also reported a reduction in work hours and income, as well as a breakdown in interpersonal relationships, including marital and conjugal relations. CONCLUSION: Chronic low-back pain affects the ability of a patient to work, creating both financial and emotional problems within a home. Relief is delayed for patients because of the sparse allocation of resources for chronic spinal care and inadequate prevention education. Despite this, many patients are exhorted to return to work before they are physically, mentally, or emotionally free of pain, resulting in poor outcomes for recovery. Ultimately, this aggregates into an adverse macrosocial effect, reducing not only the quality of life for individuals with chronic low-back pain but also workforce productivity.