Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.

Impact of a novel preceptor collaborative advanced pharmacy practice experience curriculum on student-perceived ability and confidence.

BACKGROUND AND PURPOSE: A novel teaching collaborative for acute care medicine advanced pharmacy practice experiences (APPEs) was formed by five faculty preceptors. The primary goal of the collaborative model was to ensure that acute care medicine APPEs provided students with opportunities to achieve Accreditation Council of Pharmacy Education Standards 2016, including strengthening students' ability to be practice- and team-ready. EDUCATIONAL ACTIVITY AND SETTING: The collaborative model included group discussions, video modules, patient cases, journal scans, and case presentations among student pharmacists completing an adult or pediatric acute care APPE. Anonymous, voluntary pre-/post-surveys were completed by a cohort of students who participated in the collaborative model from May 2018 to April 2019. Survey questions assessed student-perceived ability/confidence related to interprofessional (IP) relationships and decision-making skills for adult and pediatric patients, as well as value of activities. FINDINGS: From the cohort of 67 students, 54 pre-survey and 45 post-survey responses were obtained. Post-rotation, students showed an increase in confidence to practice pharmacy on an IP team (39% vs. 100%, P < .001). Significant increases were also found for therapeutic decision-making regarding antibiotics, anticoagulants, and pharmacokinetics for adult and pediatric patients. Among students completing the post-survey, video modules were the most valued component of the model. SUMMARY: A collaborative APPE model resulted in consistent increases in student-perceived ability and confidence related to care of adult and pediatric patients. This APPE model could be adapted within different care settings and pharmacy curricula.

Topiramate in the treatment of cocaine use disorder.

PURPOSE: The literature on topiramate use in cocaine-dependent patients was reviewed. SUMMARY: Six randomized, double-blind, controlled clinical trials evaluating the use of topiramate in patients who were cocaine dependent were analyzed. The results from the studies indicated that topiramate, when used in combination with cognitive behavioral therapy, may be effective in reducing short-term cocaine use and should be considered as a possible treatment option. Other trials suggested that topiramate was not effective in patients with a dual diagnosis of opioid and cocaine dependence. Two trials suggested that short-term abstinence assisted by pharmacotherapy is a predictor of longer-term (6 months and 1 year, respectively) abstinence. Cocaine use is dependent on multiple factors; therefore, a reduction in use or craving is not definitively associated with abstinence. However, decreased use reduces potential patient harm and the amount of money spent on illicit cocaine. The findings of this literature review should be used to encourage the completion of more trials that are appropriately designed. Topiramate was shown to be effective for increasing cocaine abstinence, the proportion of cocaine nonuse days, and the proportion of patients to attain 3 consecutive weeks of cocaine abstinence and decreasing the abuse liability of cocaine. Conflicting results in clinical trials do not provide a definitive answer regarding topiramate's efficacy in managing cocaine dependence. CONCLUSION: Available research neither validates nor invalidates the hypothesis that topiramate is efficacious in attaining abstinence in cocaine-dependent patients.

Geographic region and racial variations in polypharmacy in the United States.

PURPOSE: Medications can have unintended effects. High medication use populations may benefit from increased regimen oversight. Limited knowledge exists concerning racial and regional polypharmacy variation. We estimated total medication distributions (excluding supplements) of American black and white adults and assessed racial and regional polypharmacy variation. METHODS: REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort data (n = 30,239 U.S. blacks and whites aged ≥45 years) were analyzed. Home pill bottle inspections assessed the last two weeks' medications. Polypharmacy (≥8 medications) was determined by summing prescription and/or over-the-counter ingredients. Population-weighted logistic regression assessed polypharmacy's association with census region, race, and sex. RESULTS: The mean ingredient number was 4.12 (standard error = 0.039), with 15.7% of REGARDS using 8 ingredients or more. In crude comparisons, women used more medications than men, and blacks and whites reported similar mean ingredients. A cross-sectional, logistic model adjusting for demographics, socioeconomics, and comorbidities showed increased polypharmacy prevalence in whites versus blacks (OR [95% CI]: 0.63, [0.55-0.72]), women (1.94 [1.68-2.23]), and Southerners (broadly Southeasterners and Texans; 1.48 [1.17-1.87]) versus Northeasterners (broadly New England and upper Mid-Atlantic). Possible limitations include polypharmacy misclassification and model misspecification. CONCLUSION: Polypharmacy is common. Race and geography are associated with polypharmacy variation. Further study of underlying factors explaining these differences is warranted.

Recurrent venous thromboembolism in a patient with heterozygous factor v leiden mutation.

OBJECTIVE: To report a patient case identifying risk for recurrent venous thromboembolism (VTE) associated with heterozygous Factor V Leiden mutation. CASE SUMMARY: A 54-year-old Caucasian male was diagnosed with heterozygous Factor V Leiden mutation in 2008 after experiencing a deep vein thrombosis (DVT) and bilateral pulmonary embolism. The patient was treated appropriately and started on anticoagulation therapy with warfarin through an anticoagulation management clinic. After approximately 17 months of warfarin therapy without incident, warfarin was discontinued. Within 2 months after discontinuation of anticoagulation therapy, the patient experienced his second DVT and left pulmonary artery embolus. DISCUSSION: The risk of recurrent venous thromboembolism (VTE) in patients with heterozygous Factor V Leiden mutation is documented as an approximate 1.4-fold increase compared to patients without thrombophilia. However, the risk increases dramatically when nonreversible (age) or reversible risk factors (obesity, smoking, and long air flights) are present in this population. CONCLUSION: Based on recent literature, heterozygous Factor V Leiden mutation exponentially increases the risk of recurrent VTE, especially in the presence of other risk factors. Health care providers should complete a comprehensive review of the patients' other risk factors when deciding on duration of anticoagulation therapy for patients with positive heterozygous Factor V Leiden mutation.

Medication adherence and stroke/TIA risk in treated hypertensives: results from the REGARDS study.

BACKGROUND: The extent to which low medication adherence in hypertensive individuals contributes to disparities in stroke and transient ischemic attack (TIA) risk is poorly understood. METHODS: Investigators examined the relationship between self-reported medication adherence and blood pressure (BP) control (<140/90 mm Hg), Framingham Stroke Risk Score, and physician-adjudicated stroke/TIA incidence in treated hypertensive subjects (n = 15,071; 51% black; 57% in Stroke Belt) over 4.9 years in the national population-based REGARDS cohort study. RESULTS: Mean systolic BP varied from 130.8 ± 16.2 mm Hg in those reporting high adherence to 137.8 ± 19.5 mm Hg in those reporting low adherence (P for trend < .0001). In logistic regression models, each level of worsening medication adherence was associated with significant and increasing odds of inadequately controlled BP (≥140/90 mm Hg; score = 1, odds ratio [95% confidence interval], 1.20 [1.09-1.30]; score = 2, 1.27 [1.08-1.49]; score = 3 or 4, 2.21 [1.75-2.78]). In hazard models using systolic BP as a mediator, those reporting low medication adherence had 1.08 (1.04-1.14) times greater risk of stroke and 1.08 (1.03-1.12) times greater risk of stroke or TIA. CONCLUSION: Low medication adherence was associated with inadequate BP control and an increased risk of incident stroke or TIA.

Generic medications and blood pressure control in diabetic hypertensive subjects: results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

OBJECTIVE: To investigate temporal improvements in blood pressure (BP) control in subjects with diabetes and policy changes regarding generic antihypertensives. RESEARCH DESIGN AND METHODS: In a cross-sectional study we used logistic regression models to investigate the temporal relationship between access to generic antihypertensive medications and BP control (<130/80 mmHg) in 5,375 subjects (mean age, 66 ± 9 years; 61% African American) with diabetes and hypertension (HTN) enrolled in the national Results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study between 2003 and 2007. At enrollment, BP was measured and medications in the home determined by medication label review by a trained professional. Generic antihypertensive medication status was ascertained from the U.S. Food and Drug Administration. RESULTS: The percentage of subjects accessing generically available antihypertensive medications increased significantly from 66% in 2003 to 81% in 2007 (P < 0.0001), and the odds of achieving a BP <130/80 mmHg in 2007 was 66% higher (odds ratio 1.66 [95% CI 1.30-2.10]) than in 2003. Nevertheless, <50% of participants achieved this goal. African American race, male sex, limited income, and medication nonadherence were significant predictors of inadequate BP control. There was no significant relationship between access to generic antihypertensives and BP control when other demographic factors were included in the model (0.98 [0.96-1.00]). CONCLUSIONS: Among African American and white subjects with HTN and diabetes, BP control remained inadequate relative to published guidelines, and racial disparities persisted. Although access to generic antihypertensives increased, this was not independently associated with improved BP control, suggesting that poor BP control is multifactorial.

The association of statin use and statin type and cognitive performance: analysis of the reasons for geographic and racial differences in stroke (REGARDS) study.

BACKGROUND: Statin use and type have been variably associated with impaired or improved cognitive performance. HYPOTHESIS: To assess the association of statin use and type (lipophilic vs hydrophilic) and cognitive impairment. METHODS: Cross-sectional analysis of 24 595 participants (7191 statin users and 17 404 nonusers) age > or = 45 years, from a population-based national cohort study (Reasons for Geographic And Racial Differences in Stroke) enrolled between January 2003 and October 2008, with oversampling from the southeastern Stroke Belt and African Americans. Statin use and type were documented in participants' homes by a trained health professional. Cognitive performance was assessed with a prior validated instrument of global cognitive status (Six-Item Screener). Cognitive impairment was defined as a score of < 4. RESULTS: Overall, an association of cognitive impairment and statin use was observed (8.6% of users vs 7.7% of nonusers had cognitive impairment, P = 0.014); but, after adjusting for variables known to be associated with cognition (age, gender, race, income, education level, and cardiovascular disease), the association was attenuated (odds ratio [OR]: 0.98, confidence interval [CI]: 0.87-1.10). No association was observed between statin type (lipophilic vs hydrophilic) and cognition (OR: 1.03, CI: 0.86-1.24), and there were no regional differences in cognitive impairment in statin users (8% in the Stroke Belt and 7.9% in other regions, P = 0.63). CONCLUSIONS: Statin use and type were marginally associated with cognitive impairment. After adjusting for known variables that affect cognition, no association was observed. No regional differences were observed. This large study found no evidence to support an association between statins and cognitive performance.

Blood pressure control in diabetes: temporal progress yet persistent racial disparities: national results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

OBJECTIVE: Despite widespread dissemination of target values, achieving a blood pressure of <130/80 mmHg is challenging for many individuals with diabetes. The purpose of the present study was to examine temporal trends in blood pressure control in hypertensive individuals with diabetes as well as the potential for race, sex, and geographic disparities. RESEARCH DESIGN AND METHODS: We analyzed baseline data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national, population-based, longitudinal cohort study of 30,228 adults (58% European American and 42% African American), examining the causes of excess stroke mortality in the southeastern U.S. We calculated mean blood pressure and blood pressure control rates (proportion with blood pressure <130/80 mmHg) for 5,217 hypertensive diabetic participants by year of enrollment (2003-2007) using multivariable logistic regression models. RESULTS: Only 43 and 30% of European American and African American diabetic hypertensive participants, respectively, demonstrated a target blood pressure of <130/80 mmHg (P < 0.001). However, a temporal trend of improved control was evident; the odds of having a blood pressure <130/80 mmHg among diabetic hypertensive participants of both races enrolled in 2007 (as compared with those enrolled in 2003) were approximately 50% greater (P < 0.001) in multivariate models. CONCLUSIONS: These data suggest temporal improvements in blood pressure control in diabetes that may reflect broad dissemination of tighter blood pressure control targets and improving medication access. However, control rates remain low, and significant racial disparities persist among African Americans that may contribute to an increased risk for premature cardiovascular disease.

Does differential prophylactic aspirin use contribute to racial and geographic disparities in stroke and coronary heart disease (CHD)?

CONTEXT: Aspirin use may reduce the risk of stroke and coronary heart disease. Differential use for vascular prophylaxis may contribute to racial and geographic disparities in stroke and coronary heart disease morbidity or mortality. OBJECTIVE: To assess the prevalence and predictors of aspirin use for primary prophylaxis of stroke in the general population free of clinically diagnosed stroke or coronary heart disease. DESIGN AND SETTING: Cross-sectional analysis of 16,908 participants (age 45 or greater), from a population-based national cohort study (REasons for Geographic And Racial Differences in Stroke) enrolled from February 2003-August 2006 with oversampling from the southeastern Stroke Belt and African Americans. Individuals with a prior stroke or coronary heart disease, or regular use of aspirin for pain relief were excluded from analyses. MAIN OUTCOME MEASURES: Aspirin use and reasons for use were assessed using a computer-assisted telephone interview. RESULTS: Prophylactic aspirin use was substantially higher among whites (34.7%) than African Americans (27.2%; p<0.0001). There was a higher prevalence of aspirin use for prophylaxis in the Stroke Belt (32.1%) than in the rest of the nation (30.8%; p=0.07). After adjustment for measures of socio-economic status, the odds ratio of aspirin use in the rest of the nation compared to Stroke Belt was 0.90 (95% CI 0.84-0.97). There was a higher likelihood of prophylactic aspirin use among participants who were white, male, older, past cigarette smokers, or of higher socio-economic status (higher income or education). CONCLUSIONS: In this study, aspirin use to prevent stroke and coronary heart disease was higher among whites than African Americans, raising the possibility that differential aspirin use could contribute to the racial disparities in vascular disease mortality. Counter to our hypothesis, aspirin use was more common in the Stroke Belt than the rest of the country, so differential aspirin use in the Stroke Belt is unlikely to contribute to geographic disparities in stroke.

Treatment of alcohol withdrawal syndrome with carbamazepine, gabapentin, and nitrous oxide.

PURPOSE: To evaluate the potential use of carbamazepine, gabapentin, and nitrous oxide as alternatives to symptom-triggered benzodiazepine administration for the treatment of alcohol withdrawal syndrome (AWS), a literature review was conducted. SUMMARY: English-language reports of clinical trials of these agents in AWS, particularly trials that compared them with benzodiazepines or anticonvulsants or used them as benzodiazepine-sparing therapy, were reviewed. Six randomized, double-blind trials compared carbamazepine with agents used in the United States. The results suggest that carbamazepine may be useful for this indication, particularly in outpatient settings, although adverse effects and drug interactions may limit its usefulness. The role of gabapentin is unclear because of the lack of randomized, double-blind, controlled trials and the conflicting results of existing case series and open-label trials. Two poorly designed trials of nitrous oxide had conflicting results. CONCLUSION: Because of the limitations in evidence accrued so far, the routine use of carbamazepine and gabapentin for the treatment of AWS cannot be recommended, and nitrous oxide should be avoided for this indication.

Using the humanities to strengthen the concept of professionalism among first-professional year pharmacy students.

OBJECTIVES: To engage pharmacy students at the McWhorter School of Pharmacy in an authentic discussion of professionalism early in their education. METHODS: A booklet was prepared that included several classic short stories and essays that dealt with professionalism. This booklet was sent to all entering students in the class of 2008 and 2009 during the summer prior to their first-professional year of the PharmD program. The stories and essays were discussed in small groups with faculty facilitation during orientation when the students first arrived on campus. A survey instrument was created and administered to assess the impact of this innovative approach to enhancing professionalism. RESULTS: The program was well received and engaged our pharmacy students in a productive discussion on professionalism. Both classes' mean scores on survey items related that the students were engaged in the discussion of professionalism. Survey results pertaining to professional behavior also indicated increased awareness of the importance of professionalism. CONCLUSION: Enhancing professionalism requires a culture change that necessitates addressing professionalism at its core, a calling to serve, in a persistent and continual manner. Requiring students to read and think about professionalism in a novel way, before they even begin their first-professional year of pharmacy school, appears to be an effective approach to nurturing/encouraging professionalism.