Pregabalin Does Not Increase Risk of Heart Failure Exacerbation in Patients With Pre-existing Heart Failure.

BACKGROUND: Through actions of calcium channel trafficking inhibition and sodium/water retention, pregabalin may increase the risk of acute heart failure (AHF). OBJECTIVE: The objective of this study was to determine the prevalence of heart failure (HF) acute exacerbations, measured by a composite of emergency department (ED) visits, per-patient per-year (PPPY) hospitalizations, time-to first ED admission, and time-to hospitalizations in pre-existing HF patients taking pregabalin compared with those who were pregabalin-naive. METHODS: A retrospective cohort study of pregabalin users with HF were propensity score-matched to pregabalin-naïve patients with HF to evaluate the composite of ED admissions or PPPY hospitalizations, time-to first ED admission, and time-to hospitalizations during the 365 days post-index. Doubly robust generalized linear regression and Cox-proportional hazard regression modeling were undertaken for analysis of differences between groups. RESULTS: The matched cohort of 385 pregabalin users and 3460 pregabalin nonusers were principally middle-aged, equally gender distributed, and primary Caucasian. Most patients were on guideline-directed HF medical therapy. The estimated cumulative incidence of the primary outcome was a hazard ratio of 1.099 (95% CI: 0.789-1.530; P = 0.58). CONCLUSION AND RELEVANCE: This large, single-center, cohort study shows pregabalin is not associated with an increased risk of AHF events in patients with pre-existing HF.

Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence.

Glaucoma is the leading cause of irreversible blindness, affecting 76 million globally. It is characterized by irreversible damage to the optic nerve. Pharmacotherapy manages intraocular pressure (IOP) and slows disease progression. However, non-adherence to glaucoma medications remains problematic, with 41-71% of patients being non-adherent to their prescribed medication. Despite substantial investment in research, clinical effort, and patient education protocols, non-adherence remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients' glaucoma medication non-adherence. We assessed glaucoma medication non-adherence with prescription refill data from the Marshfield Clinic Healthcare System's pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and the proportion of days covered (PDC). Non-adherence on each metric was defined as less than 80% medication coverage over 12 months. Genotyping was done using the Illumina HumanCoreExome BeadChip in addition to exome sequencing on the 230 patients (1) to calculate the heritability of glaucoma medication non-adherence and (2) to identify SNPs and/or coding variants in genes associated with medication non-adherence. Ingenuity pathway analysis (IPA) was utilized to derive biological meaning from any significant genes in aggregate. Over 12 months, 59% of patients were found to be non-adherent as measured by the MPR80, and 67% were non-adherent as measured by the PDC80. Genome-wide complex trait analysis (GCTA) suggested that 57% (MPR80) and 48% (PDC80) of glaucoma medication non-adherence could be attributed to a genetic component. Missense mutations in TTC28, KIAA1731, ADAMTS5, OR2W3, OR10A6, SAXO2, KCTD18, CHCHD6, and UPK1A were all found to be significantly associated with glaucoma medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (PDC80). While missense mutations in TINAG, CHCHD6, GSTZ1, and SEMA4G were found to be significantly associated with medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (MPR80). The same coding SNP in CHCHD6 which functions in Alzheimer's disease pathophysiology was significant by both measures and increased risk for glaucoma medication non-adherence by three-fold (95% CI, 1.62-5.8). Although our study was underpowered for genome-wide significance, SNP rs6474264 within ZMAT4 (p = 5.54 × 10-6) was found to be nominally significant, with a decreased risk for glaucoma medication non-adherence (OR, 0.22; 95% CI, 0.11-0.42)). IPA demonstrated significant overlap, utilizing, both standard measures including opioid signaling, drug metabolism, and synaptogenesis signaling. CREB signaling in neurons (which is associated with enhancing the baseline firing rate for the formation of long-term potentiation in nerve fibers) was shown to have protective associations. Our results suggest a substantial heritable genetic component to glaucoma medication non-adherence (47-58%). This finding is in line with genetic studies of other conditions with a psychiatric component (e.g., post-traumatic stress disorder (PTSD) or alcohol dependence). Our findings suggest both risk and protective statistically significant genes/pathways underlying glaucoma medication non-adherence for the first time. Further studies investigating more diverse populations with larger sample sizes are needed to validate these findings.

Payers' Perspectives on Pharmacist-Directed Care in a Community Pharmacy Setting.

Background: The United States is spending an increasing share of its national income on health care while American citizens are not receiving the commensurate benefit of longer, healthier lives. Pharmacists are in a position to provide high-quality care; however, a paucity of data exists on payers' perspectives on insurance reimbursement for pharmacist-provided, community-delivered clinical services. Objective: To understand payers' perspectives toward pharmacist-provided community-delivered advanced clinical services. Methods: A 15-minute online survey was administered to determine payers' preferences and attitudes of impact about care being provided in a community pharmacy setting by a pharmacist. Results: The study recruited 50 payers from a diverse set of US organizations. The likelihood for reimbursement for a suite of pharmacist-provided, community-delivered clinical services was likely/very likely (66%), neutral (22%), and unlikely/very unlikely (12%). Pharmacists were viewed positively by payers for the provision of these services. Payers think that more clinical services should be offered in the community pharmacy. Trust in pharmacist-provided information services on general health and medications, and pharmacist competency were strongly positive. Conclusions and Relevance: A quantitative assessment of payer attitudes for pharmacist-provided, community-delivered advanced clinical practice was positive. Payers were positive about pharmacist contributions to the provision of heath and medication information. Continued development and deployment of advanced clinical services at the community pharmacy appears to be a financially viable model.

Understanding patients' care barriers in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a major health care problem. There are common barriers to quality healthcare but are these barriers the same for VTE patients? A national online survey was administered to adults who had experienced a recent VTE event. The survey assessed perceptions of VTE care barriers: (1) Difficulty to meet healthcare costs related to VTE care; (2) difficulty to meet costs for VTE prescription medications; (3) difficulty with transportation to get VTE care; and (4) the degree of support of others needed to get VTE care. Each question was correlated with patient demographics including income level, place of residence, current work status, and health insurance; care related patient harms experienced with the VTE episode; number of lifetime VTE events; beliefs concerning VTE outcomes, and oral anticoagulant therapy type. Logistic regression analysis was used to determine the effect of independent variables on barriers to VTE care. Approximately 30% of VTE patients reported at least one significant barrier to VTE care. Patients rated healthcare costs and VTE prescription medication costs mildly difficult. The odds of reporting barriers were positively associated with the number of DVTs experienced in the previous 2 years. VTE-related depression was also moderately associated with increased odds of reporting significant VTE care barriers. Nearly 1 in 3 VTE sufferers reported significant barriers to VTE care, with healthcare costs and VTE medication costs being the most common. Efforts to identify patients who may experience barriers should be sought early in care.

Pharmacist's Demand for Optimal Primary Care Service Delivery in a Community Pharmacy: The OPTiPharm Study.

BACKGROUND: The US population continues to expand providing the need for primary health care services. Community pharmacies integrated with medicine may provide greater access while providing high quality care. OBJECTIVE: To gauge pharmacists' demand for primary health care services delivered through community pharmacies. METHODS: An online survey was administered to determine community pharmacists' preferences for varying primary care services that could be offered in the community pharmacy setting. A Discrete Choice Experiment was employed to show pharmacists competing scenarios with varied primary care service offerings in the community pharmacy setting. Attributes evaluated were operation hours, service provider, medical records, service logistics, physical examinations, point-of-care diagnostic testing, preventative care, and drug prescribing. Respondents chose the scenario most likely to induce switching employment from base pharmacy to one providing advanced services. RESULTS: The optimal service delivery model from 291 community pharmacists comprised: inclusion of patient prescriptions and health information into the patient's medical record; provision of point of care testing and vital sign, including blood pressure, heart rate and breathing rate, and blood sugar and cholesterol measurement; and pharmacists prescribing (under physician oversight). Pharmacists were 4 times more likely to switch employment from their current pharmacy to their choice for advanced pharmacy services. Pharmacist demand was highest among those with a PharmD, less experience, working >40 hours per week, and in rural areas. CONCLUSIONS: This study provides empirical support for the model of pharmacists playing a greater role in the provision of primary care health services through community pharmacy settings.

In vivo human time-exposure study of orally dosed commercial silver nanoparticles.

Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receive increasing health assessment. We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content were determined. No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems are warranted to assert human toxicity thresholds. FROM THE CLINICAL EDITOR: In this study, the effects of commercially available nanoparticles were studied in healthy volunteers, concluding no detectable toxicity with the utilized comprehensive assays and tests. As the authors rightfully state, further studies are definitely warranted. Studies like this are much needed for the more widespread application of nanomedicine.

Icosapent ethyl for treatment of elevated triglyceride levels.

OBJECTIVES: To review the pharmacology, pharmacokinetics, clinical trial data, adverse effects, and formulary considerations of icosapent ethyl for the treatment of high triglyceride (TG) levels. DATA SOURCES: A literature search with keywords Vascepa, icosapent ethyl, AMR101, and eicosapentaenoic acid of articles up to July 2013, along with the package insert for Vascepa and current guidelines for hypertriglyceridemia. STUDY SELECTION/DATA EXTRACTION: Two phase-III, placebo-controlled, randomized, double-blind, 12-week clinical trials were included in this review: the MARINE trial and ANCHOR study. The MARINE trial consisted of mainly overweight Caucasian men with fasting TG ≥500 and ≤2000 mg/dL taking 4 g/day icosapent ethyl, 2 g/day, or placebo. The ANCHOR study consisted of mainly overweight Caucasians with type-2 diabetes mellitus on statin therapy, with fasting TG ≥200 and <500 mg/dL taking 4 g/day icosapent ethyl, 2 g/day, or placebo. DATA SYNTHESIS: The MARINE trial showed a placebo-corrected median decrease in TG of 33.1% for patients receiving 4 g/day icosapent ethyl, with no significant change in low-density lipoprotein cholesterol (LDL-C) levels. TG was reduced by 19.7% in those taking 2 g/day. The ANCHOR study showed a placebo-corrected decrease in TG of 21.5% with a 6.3% decrease in LDL-C for patients taking 4 g/day icosapent ethyl as add-on to statin therapy. TG was reduced by 10.1% in those taking 2 g/day. The main adverse effect observed was joint pain (2.3%). CONCLUSIONS: Icosapent ethyl is effective in reducing TG levels without increasing LDL-C, and has efficacy similar to other TG-lowering therapies with fewer adverse effects or interactions.

Community pharmacists' occupational satisfaction and stress: a profession in jeopardy?

OBJECTIVES: To quantify and model drivers of community pharmacists' self-reported levels of occupational satisfaction and stress and to identify key segments for possible intervention by the profession. DESIGN: Descriptive nonexperimental study. SETTING: United States during January to February 2012. PARTICIPANTS: 303 independent and community chain pharmacists. INTERVENTION: Online survey instrument of previously validated occupational stress and satisfaction attribute batteries. RESULTS: Participants reported a high level of dissatisfaction with current employment, with more than 50% stating that they were considering quitting their jobs. Dissatisfaction was higher among those with a doctor of pharmacy degree and those employed in community chains. Occupational stress and satisfaction were highly correlated with the intention to search for a new position. Approximately 20% of respondents felt that stress from their employment adversely affected their mental health and well-being, physical health, quality of the work, or relationships with family and friends. CONCLUSION: Substantive levels of occupational dissatisfaction and stress exist among pharmacists currently in community practice. These negative attributes are associated with a damaging promotion of community practice-a marker of a negative trajectory in sustaining this practice environment. The results of this study have implications for the health care industry, commercial pharmacy vendors, independent pharmacies, the profession, and academic training institutions as they prepare the pharmacy workforce of the future for potentially dissatisfying and stressful work environments.

Scholarly Activity of Tenure-Track Faculty in US Departments of Pharmacy Practice.

Objective. To quantitatively determine scholarly activity among tenure-track faculty at US departments of pharmacy practice over a 10-year period.Methods. A search of PubMed was performed for articles by department of pharmacy practice tenure track (DPP-TT) faculty from January 1, 2010, through December 31, 2019. DPP-TT faculty working in departments of pharmacy practice were identified through faculty rosters published on the American Association Colleges of Pharmacy website or college or school internet sites. Tenure-track faculty listed as working in a department of pharmacy practice, clinical pharmacy, or pharmacotherapy were included. An objective third party confirmed the data obtained. Each publication was classified by scope (eg, clinical pharmacology, health economics/outcome research, biomedical informatics, basic science, review, editorial/letter, or case report). DPP-TT faculty productivity was calculated by dataset frequency distribution. Descriptive statistics and analysis of variance were used to compare data across demographic strata.Results. One hundred thirty-seven institutions employed 2147 pharmacy practice faculty. These faculty published 20,059 (9.3±16.3/10 years/faculty member) papers. Six institutions had no tenure-track designation. There was a 2.5-fold increase in publication rates from 2010-2019 (P < 0001). Public vs private schools' productivity was 207.8 vs 69.0 publications per institution, respectively (P < 001). The ratio of male to female DPP-TT faculty per institution was 62% to 38%, with male faculty publishing an average of 12.1±19.1 each, and female faculty publishing an average of 7.4±13.8 each (P < 0001). Faculty ranks were 37% assistant professor; 36% associate professor; and 26% professor, with an average of 4.0±7.3, 8.6±12.4, and 17.4±24.6 publications per faculty, respectively. Regionally, US pharmacy practice faculty located in the West produced the most publications, followed by those in the Northeast, South, and Midwest (P < 0001).Conclusions. These national DPP-TT publication data demonstrate that scholarly productivity increased from 2010 through 2019, across a wide variety of publication scopes.

Prospective, randomized, controlled, trial to assess ASA DOSing by body mass index in HEalthy volunteers (DOSE study).

STUDY OBJECTIVE: Aspirin (ASA) has demonstrated inconsistent results in primary prevention of cardiovascular disease (CVD). Guidelines are also inconsistent in the recommendation of routine ASA use for primary prevention of CVD, but advocate dosing as a "one-size-fits-all" approach. DESIGN: An intention-to-treat, double-blind, randomized, controlled, clinical trial comparing three treatment arms of ASA 81, 325, and 500 mg daily dosed for 14 days were evenly randomized across the dosing categories to measure the impact of dosing by body mass index (BMI) (20-24.9, 25-29.9, ≥30 kg/m2 ) on ASA anti-platelet effects. SETTING: University Ambulatory Clinic. PATIENTS: Healthy volunteers defined as individuals who were medication free without acute or chronic significant health problems. INTERVENTION: Change in ASA reactivity unit (ARU), salicylate levels, and thromboxane B2 (TxB2) levels were measured across BMI dosing categories and time. MAIN RESULTS: Fifty-four participants with a mean (±SD) age of 34.4 ± 10.9 years (M:F; 23:31) completed the study. Baseline ARU and TxB2 levels were not significantly different between obese and non-obese individuals. BMI was not a predictor of platelet inhibition. There was no interaction between gender and platelet activation at baseline or following ASA treatment. ASA 81 mg was associated with a lower ARU response (approximate 50% lower response) than either the 325-mg or the 500-mg doses of ASA. TxB2 and salicylate levels exhibited lower trends at 81 mg compared with higher doses. CONCLUSIONS: In healthy male and female participants administered ASA for 14 days, obesity is not associated with increased basal platelet activation or ASA resistance. ASA 81 mg was significantly less effective in reducing platelet aggregation compared with ASA 325 and 500 mg, independent of BMI.

Longitudinal analysis of PharmD program students' satisfaction and stress.

INTRODUCTION: The University of Utah College of Pharmacy conducted an annual survey to gauge the relationship between multiple dimensions of students' satisfaction, and stress, with the doctor of pharmacy (PharmD) program and perceptions of future career plans. METHODS: An online survey of professional year one (P1) through professional year four (P4) students was conducted from 2015 to 2019. RESULTS: There were a total of 953 non-unique survey respondents. The overall response rate was 86.8%. The study population was 51% female and 49% male with a mean age of 26.7 ± 3.3 years. Students were moderately to very satisfied with the curriculum across the four years of the program. Students were highly to moderately likely to recommend the program. Likelihood to recommend the pharmacy career was similar for the P1 and second professional year 2 (P2) but declined over the four years. Students were moderately to neutrally affected by stress, highest in the P2 and third professional year. Financial issues were rated as the highest stress across the four years. Gender was not statistically associated with satisfaction, although women had higher stress impacting their health than men. Likelihood to recommend the PharmD program and pharmacy career was rated higher by younger students. CONCLUSIONS: Student satisfaction with the PharmD program should be a priority since higher education is a service industry. Academic pharmacy should consider whether pedagogical and social mechanisms are in place to ensure that their programs are helping students manage stress and promote satisfaction.

Reduced risk of NSAID-Induced adverse events with concomitant use of misoprostol (MICRO study).

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used medications for pain, even though they increase the risk for adverse cardiovascular events. OBJECTIVES: The objective of this study was to determine cardiovascular, cerebrovascular, and renal event rates between NSAIDs versus NSAIDs plus misoprostol. METHODS: A population-based historical cohort of U.S. veterans receiving prescription NSAIDs (1,681,609) versus NSAIDs plus misoprostol (5972 misoprostol users) was followed for 5 years. In an intent-to-treat analysis, NSAID and NSAID plus misoprostol groups were compared using propensity score-weighted Poisson regression models to estimate incident rate ratio (IRR) and Cox regression to estimate hazard ratio (HR). RESULTS: The most prescribed NSAIDs were diclofenac and ibuprofen. The mean follow-up was 35.2 ± 14.5 months. There were 439 total cardio-renal events (5.62/1000 patient-months) in the NSAID group and 419 patients (5.01/1000 patient-months) in the NSAID plus misoprostol group (Hazard Ratio (HR): 0.89; 95% confidence interval [CI]: 0.78-1.019; p = 0.09). The risk of cardiovascular event was lower in the NSAID plus misoprostol group (HR: 0.56; 95% CI: 0.34-0.93; p < 0.0001). Cerebrovascular event rates were lower in the NSAID plus misoprostol group (HR: 0.74; 95% CI: 0.60-0.94, p < 0.0001) and for renal (HR: 0.67; 95% CI: 0.49-0.89, p < 0.0001) events. All-cause mortality rate was not different between the two groups (HR: 1.05; 95% CI: 0.88-1.25, p = 0.61). CONCLUSION: Compared with NSAID use alone, the concomitant use of NSAID plus misoprostol is associated with a reduced risk of NSAID-induced cardiovascular, cerebrovascular, and renal adverse events. These data support the development of a safer NSAID when combined with misoprostol.

Angiotensin-converting enzyme inhibitors reduce community-acquired pneumonia hospitalization and mortality.

BACKGROUND: Pneumonia is a global disorder and a common reason for prolonged hospitalization. Angiotensin-converting enzyme inhibitors (ACEi) have pleiotropic effects that support a role in modulating pneumonia, but results have been controversial. OBJECTIVES: The present study was conducted to elucidate an ACEi-induced pneumonia benefit in at-risk neurologically impaired population and to determine whether a mortality benefit exists. METHODS: A cohort study using a large health-system of 29,011 unique ACEi users and 1635 case patients 65 years of age or older without neurological disorders affecting swallowing who were admitted with community-acquired pneumonia hospitalization and followed up from January 1, 2015 to December 31, 2019 (5 years). The association between ACEi use and pneumonia hospitalization and mortality were determined after propensity score matching using Cox and logistic regression. RESULTS: The experimental cohort was 74.9 ± 7.3 years and 51% were male. ACEi users had lower odds of acquiring pneumonia versus ACEi non-users (odds ratio) 0.72 [95% Confidence Interval (CI) 0.51 to 0.99]; p = 0.048. The risk of short-term mortality (<30 days) (HR) 0.42, p < 0.001 and long-term mortality (≥30 day) (HR) 0.83, p < 0.002 was significantly lower for ACEi users compared with the ACEi non-users. CONCLUSIONS: ACEi use in patients at risk of pneumonia without neurological swallowing disorders is associated with reduction in hospitalization and lowering of short- and long-term mortality. Given the high incidence of morbidity and mortality associated with pneumonia, and the susceptibility in older populations with underlying cardiovascular or renal disease or social dependencies, our data support the prescribing of ACEi in these populations to reduce pneumonia hospitalization risk as well as short- and long-term mortality.

Use of Angiotensin receptor blockers in cardiovascular protection: current evidence and future directions.

OBJECTIVE: To differentiate angiotensin II receptor blockers (ARBs) by vascular effects and outcomes in trials on cardio-protective endpoints. DATA SOURCES: MEDLINE searches were conducted from January 2003 to March 2009 using the following search terms: renin-angiotensin-aldosterone system (RAAS) blockade or inhibition; angiotensin II receptor blocker (ARBs); cardio-protection; vascular protection; end-organ protection; candesartan; eprosartan, irbesartan; losartan; olmesartan; telmisartan; and valsartan. Ongoing and recruiting clinical trials were identified via Clinicaltrials.gov (July 2008). STUDY SELECTION AND DATA ABSTRACTION: Pertinent basic science research and clinical trials with cardiovascular endpoints and information from reviews, American Heart Association 2009 statistics, and The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines were included in this review. DATA SYNTHESIS: ARBs differ in their vascular protective pleiotropic effects and pharmacokinetic properties, which may contribute to their pharmacological protection to reduce cardiovascular morbidity and mortality, independently of their blood pressure (BP)-lowering effects. CONCLUSION: Emerging data show that ARBs are effective in hypertension, left ventricular hypertrophy, postmyocardial infarction, and heart failure. To what extent their pleiotropic effects, independent of BP lowering, contribute to these outcomes will be the focus of research in the coming years. Well-designed, comparative-effectiveness studies are needed to clinically differentiate this class of agents. The future will be marked by multifunctional ARBs that will pharmacologically do more than antagonize the angiotensin type I (AT(1)) receptor.

Nanosilver particle effects on drug metabolism in vitro.

Nanosilver particles are present in consumer and health care products. Their effects on human microsomal cytochrome P450 (P450) activities and induction in luciferase reporter-engineered Caco-2 (MDR1.C) and HepG2 (DPX2 and 1A2DRE) cells have been investigated. The LD(50) values were ∼ 4 µg silver/ml for HepG2 and 5 µg/ml for Caco-2 cells. At silver concentrations that showed no decreased cell viability (<1 µg silver/ml), the pregnane X receptor (PXR)-driven 4.5-fold induction response of MDR1.C cells to 50 µM omeprazole was unaffected. In DPX2 cells, the PXR-driven 5.5- and 6.5-fold induction responses to omeprazole and 10 µM rifampicin were attenuated to 4- and 3.5-fold, respectively. Nanosilver particles alone showed no induction. In 1A2DRE cells, the aryl hydrocarbon receptor-driven 5.5-fold induction response to omeprazole was attenuated to 4-fold. In 1A2DRE cells, nanosilver alone elicited slight induction at 1 µg/ml. The inhibition of human P450-selective activities by nanosilver particles in vitro was proportional to the silver/microsomal protein ratio. At a fixed (0.5 mg/ml) protein concentration, P450-selective activities differed in sensitivity (IC(50) value). Coumarin 7-hydroxylation and 7-ethoxy-4-trifluoromethylcoumarin O-deethylation exhibited the highest IC(50) values (33.5 and 31.9 µM, respectively) and S-mephenytoin 4-hydroxylation exhibited the lowest (6.4 µM). Other IC(50) values were, in ascending order, 8.0 to 9.3 µM (testosterone 6ß-hydroxylation, 7-benzyloxyquinoline debenzylation, and diclofenac 4-hydroxylation), 16.0 µM (chlorzoxazone 6-hydroxylation), 21.2 µM [7-methoxy-4-(aminomethyl)-coumarin O-demethylation], and 24.4 µM (7-methoxyresorufin O-demethylation). An investigation of 70 µM nanosilver particles showed that microsomal NADPH cytochrome c reductase activities were inhibited <12%. From our in vitro observations, we extrapolated that nanosilver particles reaching the liver may be a potential source of drug-drug interactions.

Fostering PharmD Skills Related to Research and Quality Improvement Through Mentored Projects.

Objective. To assess the impact of a Doctor of Pharmacy (PharmD) capstone project on students' ability to conduct research and quality improvement, and to assess the feasibility of requiring projects in the core curriculum. Methods. Project proposals were solicited from faculty members and local colleagues, and students matched with an individual project and mentor. After developing a written research proposal in their third professional year, students completed the project with mentor oversight in their third and fourth professional years, culminating with a poster session and completion of a manuscript prior to graduation. Students' knowledge of biostatistics, research confidence, and attitudes regarding research were evaluated using a validated survey instrument. Students and mentors were surveyed for feedback, and students' publications and presentations were tracked. Results. Sixty-one students (97%) completed their projects on time. Students' confidence in their ability to understand and participate in research increased, but improvement in statistical knowledge and interest in conducting future research projects was minimal. Fifty-eight percent of students presented posters at national conferences. Thirteen (21%) published manuscripts in peer-reviewed journals. Students and mentors responded positively overall about the program and the associated time requirements. Conclusion. Requiring PharmD students to complete a capstone project prior to graduation was feasible and increased student confidence in their ability to participate in research and the number of student and faculty poster presentations and peer-reviewed publications. These findings support the consideration of the Academy that analysis, synthesis, and creation of new knowledge can be successfully implemented into the core PharmD curricula.

Lifetime Prevalence and Correlates of Patient-Perceived Medical Errors Experienced in the U.S. Ambulatory Setting: A Population-Based Study.

Background: The rate of safety harm self-perceived medical errors and harms reported in the U.S. ambulatory system is not well characterized. Objectives: To determine the prevalence of U.S. adult ambulatory care patient self-perceived safety harms and to gauge the degree of association between harms with various patient characteristics and outcomes. Methods: A large U.S. cross-sectional online survey of 9206 ambulatory care adults was assessed for their perception of medical errors and harms during care (misdiagnosis, mistakes in care, and wrong or delayed treatment) and also included patient demographics, health status, comorbidities, insurance status, income, barriers to care (affordability, transportation, and family and social support), number of visits to primary health care services in the past 12 months, and use of urgent or emergency care in the last 12 months. Results: The overall rate of self-perceived medical errors and harms among adult patients in the ambulatory care setting was 36%. Female patients, independent of age, and those with multiple comorbidities or barriers to care, reported the highest number of medical errors. Utilization of multiple providers was associated with a greater number of reported medical errors, often resulting in changing health care providers. Patients who reported having trouble affording health care or navigating the system to receive care also reported higher levels of harm. They were cared for by multiple providers, often switch providers, and their care is associated with greater utilization of health care resources. Patients reporting the highest rates of harm had greater use of hospital and emergency room care. Conclusions: This large U.S. adult ambulatory care study provides evidence that patient self-perceived medical errors and harms reported by patients are common. Patient self-perceived medical errors and harms occur most commonly in women, with poor health, limitation of activities, and who have three or more comorbidities.

A Modeling Exercise to Identify Predictors of Student Readiness for Advanced Pharmacy Practice Experiences.

Objective. To model the relationship of common pharmacy education assessment data including student demographics, pre-pharmacy performance, core didactic performance, and external testing measures to identify predictors of student readiness for advanced pharmacy practice experiences (APPEs). Methods. The associations between 23 predictive covariates from 226 graduating students from 2015-2018 (5786 observations) and APPE readiness as measured by midpoint core APPE scores were modeled. Multiple linear and Poisson regression models with backward selection were used. A selection criterion of p >.10 was used for covariate elimination from the model. Three models were evaluated: average of all midpoint core APPE rotation scores; average of midpoint acute care pharmacy practice and ambulatory care APPE rotation scores; and number of midpoint core clerkship failing scores. Results. The average age of the population at admission was 25.4±4.5 years, 47% were female, and 75.2% had prior degrees. Across the three prediction models, knowledge-retention covariates were the strongest predictors. Total score on the Pharmacy Curriculum Outcomes Assessment was a modest yet consistent predictor across the models. All other significant predictors were unique to the various models. Conclusion. This four-year, population-based modeling study of the relationship of common pharmacy education assessment data to APPE midpoint scores shows a modest correlation with knowledge-based measures. There is a need for greater innovation in this area of research.

Tetrodotoxin-Sensitive Neuronal-Type Na+ Channels: A Novel and Druggable Target for Prevention of Atrial Fibrillation.

Background Atrial fibrillation (AF) is a comorbidity associated with heart failure and catecholaminergic polymorphic ventricular tachycardia. Despite the Ca2+-dependent nature of both of these pathologies, AF often responds to Na+ channel blockers. We investigated how targeting interdependent Na+/Ca2+ dysregulation might prevent focal activity and control AF. Methods and Results We studied AF in 2 models of Ca2+-dependent disorders, a murine model of catecholaminergic polymorphic ventricular tachycardia and a canine model of chronic tachypacing-induced heart failure. Imaging studies revealed close association of neuronal-type Na+ channels (nNav) with ryanodine receptors and Na+/Ca2+ exchanger. Catecholamine stimulation induced cellular and in vivo atrial arrhythmias in wild-type mice only during pharmacological augmentation of nNav activity. In contrast, catecholamine stimulation alone was sufficient to elicit atrial arrhythmias in catecholaminergic polymorphic ventricular tachycardia mice and failing canine atria. Importantly, these were abolished by acute nNav inhibition (tetrodotoxin or riluzole) implicating Na+/Ca2+ dysregulation in AF. These findings were then tested in 2 nonrandomized retrospective cohorts: an amyotrophic lateral sclerosis clinic and an academic medical center. Riluzole-treated patients adjusted for baseline characteristics evidenced significantly lower incidence of arrhythmias including new-onset AF, supporting the preclinical results. Conclusions These data suggest that nNaVs mediate Na+-Ca2+ crosstalk within nanodomains containing Ca2+ release machinery and, thereby, contribute to AF triggers. Disruption of this mechanism by nNav inhibition can effectively prevent AF arising from diverse causes.