Proceedings of the 2023 Cannabis Clinical Outcomes Research Conference.

The Consortium for Medical Marijuana Clinical Outcomes Research, a multi-university collaboration established by the state of Florida in the USA, hosted its third annual Cannabis Clinical Outcomes Research Conference (CCORC) in May 2023. CCORC was held as a hybrid conference, with a scientific program consisting of in-person sessions, with some sessions livestreamed to virtual attendees. CCORC facilitated and promoted up-to-date research on the clinical effects of medical cannabis, fostering collaboration and active involvement among scientists, policymakers, industry professionals, clinicians, and other stakeholders. Three themes emerged from conference sessions and speaker presentations: (1) disentangling conflicting evidence for the effects of medical cannabis on public health, (2) seeking solutions to address barriers faced when conducting clinical cannabis research - especially with medical cannabis use in special populations such as those who are pregnant, and (3) unpacking the data behind cannabis use and mental health outcomes. The fourth annual CCORC is planned for the summer of 2024 in Florida, USA.

Incident mental health episodes after initiation of gabapentinoids vs. dopamine agonists for early-onset idiopathic restless legs syndrome.

Limited long-term safety information exists for gabapentinoid treatment of idiopathic restless legs syndrome (RLS). We estimated incident mental health-related emergency department visits and hospitalizations with a primary mental health diagnosis (primary outcome) among early-onset idiopathic RLS patients following first-line treatment initiation and examined outcome risk with gabapentinoids compared with dopamine agonists (DAs). A retrospective cohort study was conducted using administrative claims data from 2012 to 2019. Adults with early-onset (18-44 years) idiopathic RLS initiating either gabapentinoids or DAs within 60 days of new diagnosis were followed up to two years. Incidence rates were calculated and a log-binomial regression model with propensity score weighting estimated relative risk of the outcome and of substance use disorders (SUDs) as a secondary analysis with gabapentinoids. Among a cohort of 6,672 patients, 4,986 (74.7%) initiated DAs and 1,686 (25.3%) gabapentinoids. Incidence of the primary outcome (49.8 [95% CI 40.8-69.3] per 1,000 person-years) and SUDs (49.5 [95% CI 40.6-59.9] per 1,000 person-years) were higher in the gabapentinoid group compared with the DA group. A statistically significant risk of mental health diagnoses with gabapentinoids was not detected, but SUD risk was significant after covariate adjustment. High-risk mental health comorbidities (i.e., SUDs) should be considered when initiating RLS treatments.

A Natural Language Processing Algorithm for Classifying Suicidal Behaviors in Alzheimer's Disease and Related Dementia Patients: Development and Validation Using Electronic Health Records Data.

This study aimed to develop a natural language processing algorithm (NLP) using machine learning (ML) and Deep Learning (DL) techniques to identify and classify documentation of suicidal behaviors in patients with Alzheimer's disease and related dementia (ADRD). We utilized MIMIC-III and MIMIC-IV datasets and identified ADRD patients and subsequently those with suicide ideation using relevant International Classification of Diseases (ICD) codes. We used cosine similarity with ScAN (Suicide Attempt and Ideation Events Dataset) to calculate semantic similarity scores of ScAN with extracted notes from MIMIC for the clinical notes. The notes were sorted based on these scores, and manual review and categorization into eight suicidal behavior categories were performed. The data were further analyzed using conventional ML and DL models, with manual annotation as a reference. The tested classifiers achieved classification results close to human performance with up to 98% precision and 98% recall of suicidal ideation in the ADRD patient population. Our NLP model effectively reproduced human annotation of suicidal ideation within the MIMIC dataset. These results establish a foundation for identifying and categorizing documentation related to suicidal ideation within ADRD population, contributing to the advancement of NLP techniques in healthcare for extracting and classifying clinical concepts, particularly focusing on suicidal ideation among patients with ADRD. Our study showcased the capability of a robust NLP algorithm to accurately identify and classify documentation of suicidal behaviors in ADRD patients.

Pragmatic Model and Faculty Toolkit for PharmD Student Engagement in Social and Administrative Pharmacy Research.

OBJECTIVE: We aim to describe the development of a pharmacy student workgroup as an experiential education model to provide social and administrative pharmacy research opportunities and provide a toolkit for faculty seeking to increase student research engagement via this model. METHODS: Three pharmacy faculty with diverse training backgrounds but a common interest in opioid medications established a workgroup named the Opioid Research Workgroup. The workgroup consisted of first-year pharmacy students, research interns, and advanced graduate trainees. A hierarchical leadership model of supervision was implemented, whereby students reported progress on research tasks directly to an advanced graduate trainee leading a project team. To understand students' perspectives on the research experience and educational outcomes, students were asked to complete an anonymous voluntary survey after a year of participation. RESULTS: Since its establishment, the workgroup has published multiple conference abstracts, manuscripts, and grants. Students' overall satisfaction with the Workgroup on a scale of 1-5, 5 being very high, was 4.69. The successful scalability and longevity of this model are dependent on administrative support that protects faculty resources. The toolkit provided offers resources for those interested in adapting this model. CONCLUSION: Our experience with the pragmatic model of pharmacy student engagement in research proved successful in terms of research output and student training experience. Although the model can be applied across a variety of health science clinical and research topics, and faculty can leverage this approach to increase productivity in research output, faculty must ensure that resources are available to support this effort.

Protocol of a Combined Cohort and Cross-Sectional Study of Persons Receiving Medical Cannabis in Florida, USA: The Medical Marijuana and Me (M3) Study.

Significant knowledge gaps regarding the effectiveness and safety of medical cannabis (MC) create clinical challenges for MC physicians, making treatment recommendations and patients choosing treatment among the growing number of options offered in dispensaries. Additionally, data describing the characteristics of people who use MC and the products and doses they receive are lacking. The Medical Marijuana and Me (M3) Study was designed to collect patient-centered data from MC users. We aim to describe preferred MC use patterns that patients report as "most effective" for specific health conditions and symptoms, identify user characteristics associated with such use patterns, characterize adverse effects, including cannabis use disorder, identify products and patient characteristics associated with adverse effects, describe concurrent prescription medication use, and identify concomitant medication use with potential drug-MC interaction risk. Among MC initiators, we also aim to quantify MC use persistence and identify reasons for discontinuation, assess MC utilization pattern trajectories over time, describe outcome trajectories of primary reasons for MC use and determine factors associated with different trajectories, track changes in concomitant substance and medication use after MC initiation, and identify factors associated with such changes. M3 is a combined study comprised of: (1) a prospective cohort of MC initiators completing surveys at enrollment, 3 months, and 9 months after MC initiation and (2) a cross-sectional study of current MC users. A multidisciplinary committee including researchers, physicians, pharmacists, patients, and dispensary personnel designed and planned study protocols, established study measures, and created survey questionnaires. M3 will recruit 1,000-1,200 participants aged ≥18 years, with ∼50% new and ∼50% current MC patients from MC clinics across Florida, USA. Study enrollment started in May 2022 and will continue until the target number of patients is achieved. Survey domains include sociodemographic characteristics, physical and mental health, cannabis use history, reasons for MC use and discontinuation, MC products and use patterns, concurrent use of prescription medications and other substances, and side effects. Data collected in the M3 Study will be available for interested researchers affiliated with the Consortium for Medical Marijuana Clinical Outcomes Research. The M3 Study and Databank will be the largest cohort of current and new MC users in Florida, USA, which will provide data to support MC-related health research necessary to inform policy and clinical practice and ultimately improve patient outcomes.

Enhancing active learning of medication errors in the PharmD curriculum through a multi-perspective video-based experience.

INTRODUCTION: We created and assessed an immersive instructional series of video-based activities for pharmacy student evaluation of medication errors via root cause analysis (RCA). METHODS: A novel series of video vignettes showed a medication error from the perspectives of each healthcare team member involved. Students were engaged in a series of activities to guide them through RCA interspersed with the vignettes. A pre/post-assessment tool measured student-perceived skills and attitudes in medication error prevention and handling. Per item pre/post-mean scores were compared using Mann-Whitney U tests with Bonferroni correction. RESULTS: From N = 270 students, 231 and 163 completed the anonymous pre- and post-assessment, respectively. Most students positively endorsed attitude items at both assessment intervals, with no significant changes in mean for "learning how to improve patient safety is an appropriate use of time in pharmacy school" (pre-assessment = 4.26; post-assessment = 4.23). However, there were significant improvements in the skills items "I am confident in my ability to analyze a case to find the root causes of an error" (pre = 3.44; post = 3.85) and "I can identify the key factors in systems and processes that could lead to a medication error" (pre = 3.55; post = 3.88). CONCLUSIONS: Pharmacy students reported significantly improved self-perceived skills in handling and preventing medication errors, but not in attitudes, following the immersive instructional activity. There are opportunities to expand such an immersive instructional series in an interprofessional setting, which may yield different findings.

Predictive Modeling for Suicide-Related Outcomes and Risk Factors among Patients with Pain Conditions: A Systematic Review.

Suicide is a leading cause of death in the US. Patients with pain conditions have higher suicidal risks. In a systematic review searching observational studies from multiple sources (e.g., MEDLINE) from 1 January 2000-12 September 2020, we evaluated existing suicide prediction models' (SPMs) performance and identified risk factors and their derived data sources among patients with pain conditions. The suicide-related outcomes included suicidal ideation, suicide attempts, suicide deaths, and suicide behaviors. Among the 87 studies included (with 8 SPM studies), 107 suicide risk factors (grouped into 27 categories) were identified. The most frequently occurring risk factor category was depression and their severity (33%). Approximately 20% of the risk factor categories would require identification from data sources beyond structured data (e.g., clinical notes). For 8 SPM studies (only 2 performing validation), the reported prediction metrics/performance varied: C-statistics (n = 3 studies) ranged 0.67-0.84, overall accuracy(n = 5): 0.78-0.96, sensitivity(n = 2): 0.65-0.91, and positive predictive values(n = 3): 0.01-0.43. Using the modified Quality in Prognosis Studies tool to assess the risk of biases, four SPM studies had moderate-to-high risk of biases. This systematic review identified a comprehensive list of risk factors that may improve predicting suicidal risks for patients with pain conditions. Future studies need to examine reasons for performance variations and SPM's clinical utility.

Treatment initiation and utilization patterns of pharmacotherapies for early-onset idiopathic restless legs syndrome.

OBJECTIVE/BACKGROUND: Restless legs syndrome (RLS) is a complex condition associated with circadian rhythm that disrupts sleep and can cause multisystemic consequences. This study assesses pharmacotherapy treatment initiation, estimates annual treatment prevalence, and assesses treatment patterns for early-onset idiopathic RLS. METHODS: We used the MarketScan Commercial Claims Database from 2012 to 2019 to conduct a new user retrospective cohort study. Annual treatment prevalence was calculated from a cross-sectional sample. Newly diagnosed adults with early-onset (18-44 years) idiopathic RLS who initiated on and off-label gabapentinoids, dopamine agonists, or levodopa/carbidopa were included. Among monotherapy users who had one year of insurance enrollment, treatment patterns (single fill, continuous use of initiated therapy, switching, and add-on therapy) were examined and mean time on the initial treatment (as a measure of persistence) was calculated. RESULTS: In total, 6, 828 patients were initiated on monotherapy treatment for early-onset idiopathic RLS in which 4,638 met all inclusion criteria. In 2019, annual prevalence of monotherapy treatment of diagnosed patients for ropinirole was 171.3/1,000 patients; 85.0/1,000 patients for pramipexole; and 132.1/1,000 patients for gabapentin. Overall, 22.3% (n = 1,033) of patients maintained their initiated pharmacotherapy for the entire year. Rotigotine had the longest persistence (mean 185.4 [161.4 SD] days) but this user group was the smallest (n = 29). Gabapentin enacarbil, pregabalin, and rotigotine use was low (2.8% total). CONCLUSION: Ropinirole, pramipexole, and gabapentin were initiated most often for early-onset idiopathic RLS. FDA-approved agents for RLS, including gabapentin enacarbil and rotigotine, were used less frequently. In general, persistence was low for all RLS study drugs examined.

Prescription Patterns of Adjuvant Pain Medications Following an Opioid Supply Restriction Law: An Interrupted Time Series Analysis.

BACKGROUND: Florida House Bill 21 (HB21) was implemented in July 2018 to limit prescriptions of Schedule II opioids for acute pain patients, but it is unclear whether such restrictions have a collateral influence on the utilization of commonly prescribed adjuvant pain medications. OBJECTIVE: The objective of this study was to assess whether this law was associated with a change in use patterns of gabapentinoids, benzodiazepines, and muscle relaxants. METHODS: We obtained prescription claims for medications dispensed from January 1, 2015, to June 31, 2019, from a health plan serving a large Florida employer. Interrupted time series analyses were conducted to compare pre-HB21 and post-HB21 implementation changes in the mean monthly number of users and prescriptions for gabapentinoids, benzodiazepines, and muscle relaxants. RESULTS: There was a 6% immediate increase (relative risk: 1.06; 95% confidence interval: 1.02, 1.11) in the monthly proportion of gabapentinoid users, and an 11% immediate increase in the monthly proportion of gabapentinoids prescriptions (relative risk: 1.11; 95% confidence interval: 1.04, 1.18) per 1000 patients following law implementation. However, after the law, we observed a significant reduction in trend for the monthly proportion of muscle relaxants and benzodiazepine users. CONCLUSIONS: An increased number of patients and prescriptions were observed for gabapentinoids, while fewer patients received benzodiazepines and muscle relaxants after HB21. In previous studies, opioid prescription restriction laws are shown to reduce opioids, but this work suggests that these laws may also have unintended consequences for the use of adjunctive medications that were not intended to be affected.

Changes in Prescribing by Provider Type Following a State Prescription Opioid Restriction Law.

BACKGROUND: Many states have implemented opioid days' supply restriction policies, leading to reductions in opioid prescribing. Although research within certain provider types exist, no study has evaluated a restriction policy by various provider types. OBJECTIVE: To evaluate changes in opioid utilization following a days' supply restriction policy stratified by provider type: surgery, emergency medicine, primary care, specialty care, and dentistry. DESIGN: Interrupted time series (ITS) PARTICIPANTS: Opioid prescription claims of patients in a private health plan serving a large Florida employer from 1/1/2015 to 3/31/2019. Provider types were determined using the Healthcare Provider Taxonomy Code associated with the national provider identifier (NPI). INTERVENTIONS: Florida's opioid restriction policy implemented on July 1, 2018. MAIN MEASURES: Changes in mean morphine milligram equivalent (MMEs), mean days' supply, and mean number of units dispensed per opioid prescription before and after policy implementation. KEY RESULTS: There were 10,583 opioid initial prescriptions dispensed. Treating providers were classified as surgery (16.4%; n = 1732), emergency care (14.3%; n = 1516), primary care (21.2%; n = 2241), specialty care (11.4%; n = 1207), and dentistry providers (23.7%; n = 2511). Significant reductions in mean days' supply were observed across most provider types ranging from 14% reduction for dentistry providers to 41% reduction for specialty care providers. Significant changes were observed for emergency care and specialty care providers with a 30% (p = 0.001)and 29% (p < 0.001) reduction in mean MME, respectively, and a 27% (p = 0.040) reduction in mean number of units dispensed in emergency care providers, after implementation. Pre-implementation trends in opioid prescribing varied by provider type impacting the effects of the opioid days' supply restriction policy. CONCLUSIONS: Pre-policy opioid prescribing varied by provider type with a differential impact on mean MMEs, mean days' supply, and mean number of units dispensed per prescription following implementation.

Co-utilization of opioids and nonbenzodiazepine hypnotic drugs in U.S. ambulatory care visits, 2006-2016.

OBJECTIVE(S): This study aimed to characterize the co-utilization of non-benzodiazepine sedative 'Z'-drugs with opioids at ambulatory care visits in the United States. DESIGN: A cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) from 2006 to 2016 was completed. SETTING AND PARTICIPANTS: Ambulatory care visits in the United States involving adult patients with an opioid prescription were included in the analysis. OUTCOME MEASURES: The primary outcome was initiation or continuation of a Z-drug (zolpidem, eszopiclone, or zaleplon) in a patient visit in conjunction with an opioid medication. RESULTS: The authors analyzed 564,090,296 visits (weighted from a sample of 28,773) with a reported opioid prescription. Co-utilization of opioids with Z-drugs fluctuated during the study period beginning at 4.0% in 2006 (95% CI 2.2%-5.7%), 6.3% in 2012 (3.7%-8.9%), and 4.7% in 2016 (2.8%-6.5%). Among all opioid visits in the study period, co-utilization with a Z-drug was not significantly different among female patients compared with male patients (5.26% vs. 4.63%, P = 0.26). Among visits with concomitant opioid and Z-drugs, 7.0% reported new initiation of both medications in the same visit. CONCLUSION: At ambulatory care visits between 2006 and 2016, co-utilization of opioids and Z-drugs fluctuated with some differences by sex. Major regulatory advisories and policy changes during this period may have contributed to these varying rates of utilization. Additional work is needed to identify predictors of co-utilization and downstream consequences more widely.

Cannabis use assessment and documentation in healthcare: Priorities for closing the gap.

Several factors, including the lack of a systematic cannabis use assessment within healthcare systems, have led to significant under-documentation of cannabis use and its correlates in medical records, the unpreparedness of clinicians, and poor quality of cannabis-related electronic health record data, limiting its utilization in research. Multiple steps are required to overcome the existing knowledge gaps and accommodate the health needs implied by the increasing cannabis use prevalence. These steps include (1) enhancing clinician and patient education on the importance of cannabis use assessment and documentation, (2) implementing a standardized approach for comprehensive cannabis use assessment within and across healthcare systems, (3) improving documentation of cannabis use and its correlates in medical records and electronic health records by building in prompts, (4) developing and validating reliable computable phenotypes of cannabis use, (5) conducting research utilizing electronic health data to study a wide array of related health outcomes, (6) and establishing evidence-based guidelines to inform clinical practices and policies. Integrating comprehensive cannabis use assessment and documentation within healthcare systems is necessary to enhance patient care and improve the quality of electronic health databases. Employing electronic health record data in cannabis-related research is crucial to accelerate research in light of the existing knowledge gaps on a wide array of health outcomes. Thus, improving and modernizing cannabis use assessment and documentation in healthcare is an integral step on which research conduct and evidence generation primarily rely.

Chronic Opioid Therapy Utilization Following an Acute Pain Prescription Supply Restriction Law: An Interrupted Time Series Analysis.

BACKGROUND: Florida House Bill 21 (HB21) was implemented in July 2018 to limit Schedule II opioids prescriptions for patients with acute pain to a 3-day supply. Little is known about the potential unintended effects that such opioid restriction policies may have on chronic pain patients, who are exempt from the law. OBJECTIVE: We aimed to evaluate the effect of HB21 on opioid utilization measures among a cohort of chronic opioid therapy (COT) patients. STUDY DESIGN: A quasi-experimental design with interrupted time series analyses. SETTING: Pharmacy claims from January 1, 2015 to June 31, 2019 from a large employer-based health plan in Florida. METHODS: COT patients were those who received a ≥ 70 days' supply of opioids in the prior 90 days, representing 15,310 patients. Interrupted time series analyses were conducted to compare the following monthly measures among COT patients before and after HB21 implementation: 1) number of COT patients, 2) daily Morphine Milligram Equivalents [MMEs], 3) days' supply of prescriptions. RESULTS: There was a significant 25% reduction in the trend (pre-HB21 RR: 0.95, 95% CI: 0.93, 0.96 versus post-HB21 RR: 0.70, 95% CI: 0.65, 0.76) and an 8% immediate decrease (RR: 0.92, 95% CI: 0.88, 0.97) in the monthly prevalence of COT patients after HB21 implementation. However, no significant change was observed in trends for monthly number of days supplied per prescription, monthly MMEs per COT patient-day, or total MMEs per prescription. LIMITATIONS: Our study used data from employer-based private health insurance and did not include a longer post-policy period to adjust for implementation lag. CONCLUSION: Fewer patients received COT after HB21; however, patients who continued to receive COT experienced no significant changes in their regimen. The study did not assess whether COT patients were appropriately tapered or if therapeutic alternatives were initiated for new chronic pain patients.