Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature.

OBJECTIVE: To compile and synthesize the available literature describing medical cannabis use across various disease states. DATA SOURCES: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. DATA SYNTHESIS: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. CONCLUSIONS: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.

Trends in Prevalence of Non-Valvular Atrial Fibrillation and Anticoagulation Therapy in a Japanese Region　- Analysis Using the National Health Insurance Database.

BACKGROUND: Direct oral anticoagulants (DOACs) are effective in reducing thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). However, little is known about trends in NVAF prevalence and DOAC prescriptions in daily clinical practice. This study investigated the current status and trends in NVAF prevalence and DOAC prescriptions in a region of Japan.Methods and Results:Annual data for the 4 years from May 2014 to May 2017 in the Tsugaru region of Aomori Prefecture, Japan, were obtained for analysis from the Japanese National Health Insurance database ("Kokuho" database [KDB]). The prevalence of NVAF in subjects aged 40-74 years increased gradually over the 4-year study period (1,094/57,452 [1.90%] in 2014, 1,055/56,018 [1.88%] in 2015, 1,072/54,256 [1.98%] in 2016, and 1,154/52,341 [2.20%] in 2017). The proportion of NVAF patients prescribed warfarin decreased (42%, 33%, 24%, and 21% in 2014, 2015, 2016, and 2017, respectively), the proportion of those prescribed DOACs increased (30%, 42%, 50%, and 57%, respectively), and the proportion not prescribed an oral anticoagulant (OAC) decreased (28%, 25%, 26%, and 22%, respectively). However, 17% of patients with a CHADS2score ≥2 were not prescribed an OAC in 2017. CONCLUSIONS: By using the KDB we found that the prevalence of NVAF has increased gradually from 2014 to 2017. In the Tsugaru region in Japan, DOACs prescriptions increased and warfarin prescriptions decreased over the 4-year period.

Trends in oral anticoagulant use in Qatar: a 5-year experience.

In Qatar, dabigatran was introduced in 2011 followed by rivaroxaban in 2014. In this study, we aim to explore the trends in oral anticoagulant use in Qatar over the past 5 years and to what extent did DOACs replace warfarin. We also explored the extent of switching between different anticoagulants (from warfarin to DOACs and vice versa). We collected all anticoagulant prescriptions dispensed as in- or out-patient from 2011 to 2015 in all Hamad Medical Corporation (HMC) hospitals. Overall number of patients using warfarin, dabigatran and rivaroxaban over the last 5 years collectively was calculated. Per each calendar year, we calculated the number of all 3 OAC used (warfarin, dabigatran and rivaroxaban), frequency of use of each one of the OAC prescribed and compared the change in proportion of DOACs to warfarin prescriptions over the years. Overall, 6961 patients were using OAC over the past 5 years among which 5849 (84%) used warfarin, 496 (7.1%) used dabigatran and 616 (8.8%) used rivaroxaban. Oral anticoagulants use increased gradually from 2091 in 2011 to 3688 in 2015. Number of patients receiving DOACs increased significantly compared to warfarin [11 (0.5%) in 2011 vs. 849 (23%) in 2015 (p < 0.0001)]. Since its introduction in 2014, number of rivaroxaban users increased significantly compared to dabigatran [212 (40.9%) in 2014 vs. 544 (64.1%) in 2015]. DOACs have been gradually replacing warfarin in Qatar and the trend of their use is similar to that reported in other countries. Warfarin remains the most commonly used oral anticoagulant.

Vitamin D exposures reported to US poison centers 2000-2014: Temporal trends and outcomes.

UNLABELLED: There has been an increased use of vitamin D both by prescription and by the public as a widely available supplement. We evaluated 15 years of single-substance vitamin D exposures to US poison centers. METHODS: Retrospective analysis of data from the National Poison Data System (NPDS) to evaluate clinical effects, trends, and outcomes of exposures to vitamin D over the period January 1, 2000 through June 30, 2014. Cases were limited to exposures involving vitamin D as a single substance. Multiple vitamin products that may have included vitamin D were not included in this study. RESULTS: From 2000 through June 30, 2014, there were 25,397 human exposures to vitamin D reported to NPDS. There was a mean of 196 cases per year from 2000 to 2005, followed by a 1600% increase in exposures between 2005 and 2011 to a new annual mean of 4535 exposures per year. The mean and median ages were 23.4 years and 10 years, respectively. There were no fatalities, but five (0.02%) major effect outcomes. Serious medical outcomes (major or moderate outcome) were infrequent, ranging from 2 patients/year to 22 patients/year. Clinical effects were primarily gastrointestinal (0.7-1.5%) and mild neurological effects (0.2-0.4%). There was a decline in the percentage of patients treated in a health care facility and of patients with serious medical outcome. CONCLUSION: Despite the enormous increase in number of exposures, there was not a significant increase in patients with a serious medical outcome. Rare severe outcomes may occur.

Management of lower urinary tract symptoms related to benign prostatic hyperplasia in real-life practice in france: a comprehensive population study.

BACKGROUND: Male lower urinary tract symptoms (LUTS) are one of the most treated diseases, but little is known about patient trajectories in current clinical practice. OBJECTIVE: To describe the dynamic treatment patterns of LUTS presumably due to benign prostatic obstruction (BPO). DESIGN, SETTINGS, AND PARTICIPANTS: All prescriptions of α1-adrenergic receptor blocking agents (α1-blockers), 5α-reductase inhibitors (5-ARIs), and phytotherapy, and all surgeries related to BPO performed in France from 2004 to 2008 were identified using two distinct administrative claim databases maintained by the National Health Insurance system that covers the entire population. After linking the two data sets, all consecutive treatment events were analyzed for each patient. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Drug prescription details were assessed for each year, region, and prescriber qualification. Medical treatment initiation, interruption, evolution, and events after surgical management (hospital stay, reoperation, complication rates, and subsequent medical prescriptions) were also investigated. RESULTS AND LIMITATIONS: Overall, 2 620 269 patients were treated within 5 yr, with important geographic variations. Medical treatment was interrupted for approximately 16% of patients. The α1-blockers were prescribed most frequently, but phytotherapy surprisingly accounted for 27% of all monotherapies and 54% of all combination therapies. General practitioners and urologists (92% and 3.7% of overall prescribers, respectively) exhibited a similar prescription profile. Treatment initiation was medical in 95.4% of cases, consisting primarily of monotherapy using α1-blockers (60.3%), phytotherapy (31.8%), or 5-ARIs (7.9%). Treatment was modified at extremely high rates within 12 mo of initiation (8.7%, 14.6%, and 12.9%, respectively). The median hospital stay for surgical management was far higher than in clinical trials. Long-term surgical complications and reoperation rates favored open prostatectomy. Incidence of pharmacologic treatment after surgery was as high as 13.8% at 12 mo. CONCLUSIONS: This unique dynamic evaluation of clinical practice revealed unexpected results that contrast with previously published evidence from clinical trials. This approach may merit monitored and targeted measures to improve the level of care in the field.

Trends in use of high-risk medications for older veterans: 2004 to 2006.

OBJECTIVES: To examine the change in use of high-risk medications for the elderly (HRME), as defined by the National Committee on Quality Assurance's Healthcare Effectiveness Data and Information Set (HEDIS) quality measure (HEDIS HRME), by older outpatient veterans over a 3-year period and to identify risk factors for HEDIS HRME exposure overall and for the most commonly used drug classes. DESIGN: Longitudinal retrospective database analysis. SETTING: Outpatient clinics within the Department of Veterans Affairs (VA). PARTICIPANTS: Veterans aged 65 by October 1, 2003, and who received VA care at least once each year until September 30, 2006. MEASUREMENTS: Rates of use of HEDIS HRME overall and according to specific drug classes each year from fiscal year 2004 (FY04) to FY06. RESULTS: In a cohort of 1,567,467, high-risk medication exposure fell from 13.1% to 12.3% between FY04 and FY06 (P<.001). High-risk antihistamines (e.g., diphenhydramine), opioid analgesics (e.g., propoxyphene), skeletal muscle relaxants (e.g., cyclobenzaprine), psychotropics (e.g., long half-life benzodiazepines), endocrine (e.g., estrogen), and cardiac medications (e.g., short-acting nifedipine) had modest but statistically significant (P<.001) reductions (range -3.8% to -16.0%); nitrofurantoin demonstrated a statistically significant increase (+36.5%; P<.001). Overall HEDIS HRME exposure was more likely for men, Hispanics, those receiving more medications, those with psychiatric comorbidity, and those without prior geriatric care. Exposure was lower for individuals exempt from copayment. Similar associations were seen between ethnicity, polypharmacy, psychiatric comorbidity, access-to-care factors, and use of individual HEDIS HRME classes. CONCLUSION: HEDIS HRME drug exposure decreased slightly in an integrated healthcare system. Risk factors for exposure were not consistent across drug groups. Future studies should examine whether interventions to further reduce HEDIS HRME use improve health outcomes.

Impact of erythropoiesis-stimulating agent prescribing at an Asian cancer center, after release of safety advisories.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) provide symptom relief and decrease blood transfusion support among patients with chemotherapy-induced anemia. However, due to increased cardiovascular events associated with off-labeled usage of ESAs, the FDA incorporated black box warnings in 2007 to include the following key points: (a) ESAs should be used only to treat anemia due to concomitant chemotherapy of a noncurative intent and (b) target hemogloblin level should not exceed 12 g/dL. Thus, this study was designed to compare the prescribing of epoetin alfa at National Cancer Centre Singapore before and after FDA black box updates. The secondary objective of this study was to evaluate the appropriateness of efficacy and toxicity monitoring of epoetin alfa. METHODS: This was a retrospective, single-centered, drug utilization review. Patients who received at least one dose of epoetin alfa were included in this study. Utilization of epoetin alfa was segregated into two time periods: January 1, 2005 to October 15, 2007 (S1, Pre-safety advisories changes) and October 16, 2007 to December 10, 2009 (S2, Post-safety advisories changes). RESULTS: A total of 171 patients were prescribed epoetin alfa at NCCS during the two time periods. However, only 139 patients were eligible for analysis, with 91 and 48 patients in S1 and S2 respectively. After safety advisory changes, there were more (18.2%) metastatic patients and fewer (19.1%) patients with cardiovascular co-morbidities who were prescribed epoetin alfa, the mean hemogloblin level when epoetin alfa was initiated was lowered by 0.46 g/dL, more (43%) dose adjustments were made for 'excessive' responders and more (40.7%) patients had fewer blood transfusions after epoetin alfa therapy (p < 0.05). However, blood pressure control, iron studies, and supplementation did not improve (p > 0.05). CONCLUSION: This study suggested that oncologists have generally adopted the new ESA safety warnings and adjusted prescribing habits.

Changes in ciprofloxacin utilization as shown in a large pharmacy claims database: effects of proximity to criminal anthrax exposure in October 2001.

OBJECTIVE: Identify, during the period of criminal anthrax exposures in October 2001, changes in utilization of ciprofloxacin and geographic patterns of any identified variations. DESIGN: Observational. SETTING: United States. PATIENTS: Individuals making prescription claims through a pharmacy benefits management company. INTERVENTIONS: Analysis of AdvancePCS pharmacy claims database. MAIN OUTCOME MEASURES: Percentage change in ciprofloxacin utilization for 2000 and 2001 and, by locale, for September and October 2001. RESULTS: Utilization of ciprofloxacin tablets was significantly lower in calendar year 2001 than in calendar year 2000 (median decline, 10.3%) for all months except October, when utilization of ciprofloxacin increased 9.8%. During the period of anthrax exposures (October 2001 versus September 2001), affected geographic areas, including New York (an increase of 62.5%), some other Mid-Atlantic states, and Florida (28.5%), had some of the highest percentage increases in the rate of ciprofloxacin utilization. CONCLUSION: Many Americans actively sought prophylaxis with ciprofloxacin during the course of the October 2001 anthrax attack and that utilization was higher in, but not limited to, locales with publicized cases of disease. Pharmacists, clinicians, and public health officials should note that such behavior may be expected in the event of a similar attack and should be familiar with current recommendations for the assessment and management of anthrax exposure.

Relational database for drug-use review of Tennessee Medicaid claims.

The development of a relational database from Tennessee Medicaid files for the purpose of retrospective drug-use review (DUR) and application of the database for DUR of angiotensin-converting-enzyme inhibitors (ACEIs) are described. Computer queries were designed to create profiles of physicians' or pharmacies' experiences from claims data and other Medicaid data. Outlying patients (patients for whom at least one DUR criterion was unmet) were grouped according to their physicians or pharmacies. Thresholds for defining outlying physicians and pharmacies (i.e., those with more than a specified number of outlying patients) were based on the provider population instead of the patient population as a whole; aggregating patient outliers by provider allowed trends of inappropriate practices to be detected. As the threshold for outlying providers rose, the number of such providers fell, as did the number of outlying patients with whom they were associated. Stratification of the outliers by provider for specific drug-drug interactions and drug-disease complications afforded the option to set individual thresholds for outlying providers based on individual subsets; for example, for ACEIs, a threshold of greater than five patient outliers could be set for the criterion of no concurrent potassium supplements and a threshold of greater than three, for the criterion of no unmonitored concurrent lithium therapy. Tennessee patients formerly covered by Medicaid are now enrolled in managed care plans, and the flexibility of the database has allowed it to be modified accordingly. The relational database allows flexibility in the analysis of certain patterns of drug use. Such a database may be useful to other Medicaid programs that are converting to managed care models.