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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.An online survey of professional year one (P1) through professional year four (P4) students was conducted from 2015 to 2019.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.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.

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.

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.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.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.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.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.

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.

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.The objective of this study was to determine cardiovascular, cerebrovascular, and renal event rates between NSAIDs versus NSAIDs plus misoprostol.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).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).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.

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.

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.

Introduction Quality of life (QoL) deficits have been noted among patients with venous thromboembolism (VTE) but understanding of the drivers of that poorer QoL is limited. The objective of this study was to examine associations between a variety of factors and QoL in patients with VTE. Methods Adult patients who had experienced at least one VTE episode within the past 2 years completed an online survey between May and July 2016 with responses to a variety of questions designed to ascertain QoL scores, Optum Short Form-12, and potential factors associated with these scores. Results Most of the 907 patients were female (56.7%) and Caucasian (88.6%). Physical and mental QoL scores below the general population average were present in 76.0 and 56.7% of patients, respectively. Multiple regression modeling revealed several factors associated with below average physical QoL scores including unemployment (odds ratio [OR] 3.77, 95% confidence interval [CI] 1.76–8.05), gastrointestinal bleeding (OR 2.54, 95% CI 1.28–5.01), high depression scores (OR 4.02, 95% CI 1.88–8.58), or difficulty accessing VTE care (OR 4.24, 95% CI 1.77–10.17). Factors associated with below average mental QoL scores included experiencing VTE within the last month (OR 3.85, 95% CI 1.58–9.41), unemployment (OR 2.83, 95% CI 1.30–6.16), or high depression (OR 3.85, 95% CI 1.60–9.28) and/or anxiety (OR 9.17, 95% CI 4.81–17.47) scores. Conclusion Most patients with recently diagnosed VTE reported below average QoL. Many of the factors associated with below average QoL are modifiable, indicating that patients with VTE could potentially benefit from interventions aimed at improving QoL.

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.

Real-world outcomes in patients with chronic stable angina treated with ranolazine and other antianginal medications as second- or third-line therapy are limited. In a historical cohort study of veterans with chronic stable angina, we compared time with coronary revascularization procedures, hospitalizations, and 1-year healthcare costs between new-users of ranolazine versus conventional antianginals (i.e., calcium channel blockers, β blockers, or long-acting nitrates) as second- or third-line. Weighted regression models calculated adjusted hazard ratios (HR) at up to 8-year follow-up, and adjusted incremental costs in the first year. Weighted groups comprised 4,699 ranolazine users and 31,815 conventional antianginal users. Percutaneous coronary intervention (PCI) occurred more often in ranolazine users compared with conventional antianginal users (HR 1.16; 95% confidence intervals [CI] 1.08 to 1.25, p

Introduction Venous thromboembolism (VTE) including deep vein thrombosis (DVT) or pulmonary embolism (PE) is associated with reduced survival, poorer quality of life, and substantial health-care-costs. Limited research, primarily qualitative, suggests that those with VTE may have elevated fear of recurrence, and associated emotional dysfunction and distress. Methods A national online survey was administered to 907 patients who had experienced a VTE event in the past two years. The survey assessed for the prevalence of self-reported bleeding harms associated with VTE, the levels of anxiety, depression, cognitive dysfunction and distress experienced by patients, and a range of potential psychosocial correlates that may be associated with these bleeding or emotional harms. Results The majority (63.0%) of respondents had experienced at least one bleeding related harm following their VTE diagnosis, and 40.6% indicated they experienced fear of another clot often or almost all the time. One-in-four (24.7%) and one-in-ten (11.6%) had abnormal levels of anxiety and depression, respectively. Structural equation modeling was used to define two composite latent bleeding harm and emotional harm factors. Emotional and bleeding harms were associated with younger age, a belief that one's health is due to luck, having multiple comorbidities, having a history of prior VTE events, having multiple barriers to VTE care, and experiencing medical mistakes in diagnosis or treatment. Emotional harms were uniquely predicted by having poorer health literacy, having low self-reported medication adherence, belief others are responsible for one's health, and more recent VTE events. Bleeding harms were uniquely predicted by having a lower frequency of primary care provider contact and having a history of switching between warfarin and direct oral anticoagulants for VTE treatment. Conclusions The findings show high levels of self-reported bleeding and emotional harms in a general population of VTE sufferers that are clearly associated with readily identifiable demographic, health status, and psychosocial characteristics. These represent targets for intervention and changes in clinical practice.

SummaryWhat is known and objective In order to improve public health, it is necessary to facilitate patients’ easy access to affordable high-quality primary health care, and one enhanced approach to do so may be to provide primary healthcare services in the community pharmacy setting. Discrete choice experiments to evaluate patient demand for services in pharmacy are relatively limited and have been hampered by a focus on only a few service alternatives, most focusing on changes in more traditional pharmacy services. The study aim was to gauge patient preferences explicitly for primary healthcare services that could be delivered through community pharmacy settings in the USA, using a very large sample to accommodate multiple service delivery options. Methods An online survey was administered to a total of 9202 adult patients from the general population. A subsequent online survey was administered to 50 payer reimbursement decision-makers. The patient survey included a discrete choice experiment (DCE) which showed competing scenarios describing primary care service offerings. The respondents chose which scenario would be most likely to induce them to switch from their current pharmacy, and an optimal patient primary care service model was derived. The likelihood this model would be reimbursed was then determined in the payer survey. Results and discussion The final optimal service configuration that would maximize patient preference included the pharmacy: offering appointments to see a healthcare provider in the pharmacy, having access to their full medical record, provide point-of-care diagnostic testing, offer health preventive screening, provide limited physical examinations such as measuring vital signs, and drug prescribing in the pharmacy. The optimal model had the pharmacist as the provider; however, little change in demand was evident if the provider was a nurse-practitioner or physician's assistant. The demand for this optimal model was 2-fold higher (25.5%; 95% Bayesian precision interval (BPI) 23.5%-27.0%) than for a base pharmacy offering minimal primary care services (12.6%; 95% BPI 12.2%-13.2%), and was highest among Hispanic (30.6%; 95% BPI: 25.7%-34.3%) and African American patients (30.7%; 95% BPI: 27.1%-35.2%). In the second reimbursement decision-maker survey, the majority (66%) indicated their organization would be likely to reimburse the services described in the optimal patient model if provided in the pharmacy setting. What is new and conclusion This United States national study provides empirical support for a model of providing primary care services through community pharmacy settings that would increase access, with the potential to improve the public health.

Background Atrial fibrillation (AF) is a comorbidity associated with heart failure and catecholaminergic polymorphic ventricular tachycardia. Despite the Ca 2+ ‐dependent nature of both of these pathologies, AF often responds to Na + channel blockers. We investigated how targeting interdependent Na + /Ca 2+ dysregulation might prevent focal activity and control AF. Methods and Results We studied AF in 2 models of Ca 2+ ‐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 (nNa v ) with ryanodine receptors and Na + /Ca 2+ exchanger. Catecholamine stimulation induced cellular and in vivo atrial arrhythmias in wild‐type mice only during pharmacological augmentation of nNa v 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 nNa v inhibition (tetrodotoxin or riluzole) implicating Na + /Ca 2+ 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 nNa V s mediate Na + ‐Ca 2+ crosstalk within nanodomains containing Ca 2+ release machinery and, thereby, contribute to AF triggers. Disruption of this mechanism by nNa v inhibition can effectively prevent AF arising from diverse causes.

EXECUTIVE SUMMARYThe Committee was charged with the responsibility for examining the need for change in pharmacy education and the models of leadership that would enable that change to occur across the academy. They also examined the question of faculty wellbeing in a time of change and made several recommendations and suggestions regarding both charges. Building upon the work of the previous Academic Affairs Committee, the 2018-19 AAC encourages the academy to implement new curricular models supporting personalized learning that creates engaged and lifelong learners. This will require transformational leadership and substantial investments in faculty development and new assessment strategies and resources. Recognizing that the magnitude of the recommended change will produce new stress on faculty, the committee identified the need for much additional work on student, faculty and leaders' wellbeing, noting the limited amount of empirical evidence on pharmacy related to stress and resilience. That said, if faculty and administrators are not able to address personal and community wellbeing, their ability to support their students' wellbeing will be compromised.

Objective. To gauge multiple dimensions of pharmacy students' professionalism, stress, and satisfaction with the Doctor of Pharmacy (PharmD) program. Methods. An online survey of first- through fourth-year pharmacy students was conducted from 2015-2018 to gauge the degree of students' professionalism (personal reflection, patient-centric care focus, cultural and interprofessional competencies), program stress (levels, sources, and burnout syndrome), and satisfaction. Multilevel structural equation modeling (SEM) determined the relationship between stress and satisfaction, and the degree to which these impacted levels of professionalism after adjusting for potential correlates (age, sex, financial stress, relationship status, race, and employment status). Results. Seven hundred sixty-four responses to the survey were received across the four calendar years. Of the students in the sample, 51% were female with a mean (SD) age of 26.6 (3.4) years. The overall response rate to the surveys was 86.2%. Professionalism was most strongly indicated by the measures of community-centeredness, patient-centeredness, and perceived benefits of being part of a team-based environment. The SEM model demonstrated an inverse relationship between the two composite latent constructs of stress and satisfaction. When modeled simultaneously, program satisfaction was found to be the more significant predictor of professionalism than stress after adjusting for associations with age, sex, and relationship status. Conclusion. Professionalism of pharmacy students is positively associated with students' satisfaction with the program, but professionalism is not independently significantly predicted by stress. Students who have positive responses to community- and patient-centeredness and who feel they benefit from engaging in a team-based environment are most likely to have greater professionalism.

Venous thromboembolism (VTE) represents a major health-care problem. Understanding patient satisfaction with VTE care is an important health-care goal. A national online survey was administered to adults who had experienced a recent VTE event. The survey assessed patient satisfaction by: (1) satisfaction with VTE care provider; (2) likelihood to recommend VTE provider; and (3) satisfaction with communication between VTE care providers. Each question was correlated with patient demographics, patient care harms (ie, misdiagnosis, wrong treatment), patient beliefs concerning outcomes, and type of anticoagulant therapy. Respondents (907) were 52.4 ± 14.4 years, predominantly Caucasian, mostly women, and generally had health insurance. Most respondents were satisfied with VTE care providers, likely to recommend their VTE provider, and satisfied with communication between providers. Dissatisfaction was strongly associated with treatment mistakes, a wrong diagnosis or treatment, or delayed treatment. A national sample of VTE patients were generally satisfied with VTE care experiences. The VTE care dissatisfaction was strongly associated with perceived mistakes in VTE care. Interventions aimed at reducing, acknowledging, and communicating errors could be studied to improve VTE care satisfaction.

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.

Introduction Understanding potential harms associated with common anticoagulation treatment patterns in patients with venous thromboembolism (VTE) is important for multiple stakeholders. The purpose of this study is to report associations between different anticoagulation patterns and bleeding and emotional harms based on patients' self-reported care experiences. Methods Patients at least 18 years of age who had experienced a VTE event in the past two years and completed a national online survey between May and July 2016 were analyzed. The survey assessed the prevalence of self-reported bleeding and emotional harms associated with self-reported anticoagulation treatment patterns and other variables. Results Patients mean age was 52.4 (standard deviation 14.4) years and most were female (56.7%) and Caucasian (88.6%). Anticoagulant treatment patterns included warfarin (38.7%), direct oral anticoagulants (26.1%), and those who switched between anticoagulants (17.9%). Self-reported bleeding and emotional harms occurred in 63.6% and 56.3% of patients, respectively. Younger age, experiencing VTE more recently, and a prior history of anxiety, depression, or stroke were associated with increased odds of experiencing bleeding or emotional harm. Compared to warfarin, switching between anticoagulant types was associated with approximately twice the odds of experiencing bleeding harm, while DOAC therapy was associated with lower odds of experiencing emotional harm. Conclusion Self-reported bleeding and emotional harms occurred commonly during VTE treatment and were associated with identifiable clinical, demographic, and psychosocial characteristics such as younger age, history of depression and/or anxiety, and more recent VTE diagnosis. Switching between anticoagulants may be a marker for increased harm risk.

Purpose The perceived demand for and barriers to pharmacist prescribing in the community pharmacy setting were studied. Methods Qualitative interviews were conducted with 19 consumers, 20 community pharmacists, and 8 reimbursement decision-makers from payer organizations between April and June 2015. Respondents were invited to participate in a daylong interview process online. Interviews with consumers and pharmacists were conducted using online bulletin board technology. Telephone interviews were conducted with reimbursement decision-makers. As with all qualitative research, the sample sizes used were restrictive and sufficient to gauge the perceptions of those respondents only. Interview responses were not intended to be generalizable to the groups or populations from which the respondents came. Results There was a continuum of interest in pharmacist prescribing across the three constituencies. Consumers were predominantly resistant to the notion; however, one third were more positive about the idea. Community pharmacists were more open, particularly when prescribing was restricted to a limited set of conditions or medications. Reimbursement decision-makers were most receptive to the notion. Key barriers to pharmacist prescribing included low awareness of current pharmacist prescribing authority among consumers, concerns about the adequacy of pharmacist training, potential conflicts of interest when the prescriber was also a dispenser, and potential liability issues. Conclusion Consumer respondents were generally resistant to the notion of pharmacist prescribing, with most viewing pharmacists as dispensers and not prescribers. Community pharmacists were more open to the idea, while reimbursement decision-makers were the most receptive to the notion of pharmacist prescribing.

Introduction Heart failure (HF) is a complex clinical syndrome with a significant economic and health burden. While practice guidelines recommend a multidisciplinary approach in HFrEF care, the impact of pharmacist participation on HF outcomes remains inconclusive. Methods A systematic review and meta-analysis was performed and reported according to PRISMA guideline from five databases including PubMed, Embase, Cochrane, Scopus and CINAHL. Randomized controlled trials (RCTs) that evaluated pharmacist interventions compared were compared with usual care in HFrEF patients. Data were pooled using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes were all-cause hospitalization and health-related quality of life (HRQoL) at 6 months. Results Twenty-nine trials identified 6,965 predominantly HFrEF patients. The average age was 72.0 years (IQR 66.0-76.0) and 48% were men (IQR 40.0%-68.0%). The majority of trials included NYHA FC II-III with median left ventricular ejection fraction (LVEF) of 38.5% (IQR 34.5-49.5%). Pharmacist interventions were associated with a significant reduction in all-cause mortality (RR 0.74; 95% CI 0.60-0.91; p= 0.004) and all-cause hospitalizations (RR 0.86; 95% CI 0.75-0.99; p =0.034). There was a significant improvement in 4 domains of SF-36 including role physical (SMD 0.20, 95% CI 0.04 to 0.37, p=0.015), role emotional (SMD 0.17, 95% CI 0.00 to 0.33, p=0.047), mental health (SMD 0.33, 95% CI 0.17 to 0.50, p Conclusions Pharmacist interventions in HFrEF population significantly reduced all-cause mortality and all-cause hospitalizations. Several dimensions of quality of life were also improved. Integration of pharmacist into a HFrEF care team or care pathway should be strongly considered as an important element of a multidisciplinary team.

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.

Health care in the US remains dysfunctional despite well-intentioned efforts to revitalize the system. Delivery is fragmented, per capita investment is the highest of any nation in the world, and the return on the health care dollar ranks as one of the lowest of industrialized nations.[1-3][1]

Summary What is known and objective Non-adherence to controller asthma medications is an important public health problem. It is estimated to occur in 30–70% of individuals and is a significant risk factor for asthma morbidity and mortality. The aim of this study was to determine the level of adherence, as indicated by refill rates, to controller asthma medications in a community pharmacy setting. Methods Secondary analyses of a community pharmacy dispensing database in 15 locations throughout Utah. Results and discussion The dispensing records of 2193 patients who received controller medications for asthma in a 12-month period, and had a minimum of 6-month potential coverage (180 days) from the date of their first receipt of a controller medication in that period, were examined. Using standard metrics to gauge adherence, the proportion of days covered (PDC) and the medication possession ratio (MPR), the average coverage for controller asthma medications across a 6-month period (180 days) was poor, averaging less than 50% of days’ availability. Standard cut-offs (≥80% medication availability) indicated that only 14–16% of patients had ‘satisfactory’ adherence over their 6-month follow-on period. Females and older patients had significantly greater satisfactory adherence. Medication adherence was significantly greater with inhaled corticosteroid (ICS)–long-acting β2-agonist (LABA) combinations than with ICS alone. What is new and conclusion This study confirms the considerable scope of the asthma therapy non-adherence problem. Therefore, it is imperative to conduct survey-based research linked directly to pharmacy-based dispensing data to derive patient behavioural, attitudinal and environmental factors that may contribute to the issue, and then pilot and evaluate interventions for change.

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.

Objectives The study objective was to determine the level and correlates of self-reported medication low adherence in the US general population. Setting A 30 min cross-sectional online survey was conducted with a national sample of adults. Participants 9202 adults (aged 18+) who had filled at least three or more prescriptions at a community pharmacy in the past 12 months. Primary and secondary outcome measures Self-reported medication adherence was measured with the 8-item Morisky Medication Adherence Scale. Results Low adherence was reported by 42.0%, 29.4% had medium adherence and 28.6% had high adherence. Low adherence was significantly associated with: lower age, being of Hispanic origin or African-American, having difficulty with healthcare, medication or transportation costs, needing the support of others to access primary care, health limiting activity, using multiple providers, infrequent visits to primary care providers and visiting an emergency department >3 times in last 12 months. Conclusions A very high level of low medication adherence is seen in the general population, particularly for ethnic minorities, those who use multiple healthcare providers and those who experience barriers to access for regular primary care. As clinical, patient education and counselling, and healthcare policy initiatives are directed to tracking the problem of low medication adherence, these should be priority populations for research and interventions.

tudy Objective To determine the effect of dobutamine versus milrinone on out-of-hospital mortality in treatment of patients with acute decompensated heart failure (ADHF). Design Propensity score weighted, retrospective cohort study with mortality as primary outcome. Setting An academic health-care system. Patients 500 adult patients with a prior history of heart failure, who survived a hospitalization for ADHF that included treatment with dobutamine or milrinone between January 1, 2006 and April 30, 2014. Measurements and Main Results ADHF events were defined as a hospitalization with receipt of an intravenous loop diuretic or a Brain-type natriuretic peptide (BNP) value greater than 400 pg/mL during the hospitalization. Patients were followed until death or 180 days from hospital discharge. Risk ratios (RR) for mortality associated with dobutamine compared to milrinone were calculated at 15, 30, and 180 days post-discharge using Poisson regression with robust error variance. Mean age was 62.7 years, 65.4% were male, and 48.2% had a mean left ventricular ejection fraction (LVEF) 40% or lower. Overall, 55 (18%) of dobutamine-treated versus 23 (12%) of milrinone-treated patients died during follow-up (RR, 1.27; 95% CI, 0.76-2.13; p=0.360). For death from cardiovascular causes the RR for dobutamine was 1.49 (95% CI, 0.79-2.82, p=0.214). For death from worsening heart failure the RR for dobutamine was 2.55 (95% CI, 1.07-6.10, p=0.035). A trend towards significance was observed at 15-days post-discharge for all mortality analyses (all p-values

Nanotechnology produces a wide range of medicinal compounds, including nanoparticulate silver, which are increasingly introduced in various forms for consumer use. As with all medicinal compounds, potential drug interactions are an important consideration for ingested silver nanoparticles. Nanoparticulate silver-drug interactions may be mediated through induced oxidative stress in liver tissue where the majority of systemically bioavailable silver nanoparticles is found. To investigate whether an orally ingested commercially available colloidal silver nanoproduct produces pharmacokinetic interference on select cytochrome P450 enzymes, a prospective, single-blind, controlled in vivo human study using simultaneous administration of standardized probes for P450 enzyme classes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was conducted. Oral ingestion of a commercial colloidal silver nanoproduct produces detectable silver in human serum after 14 days of dosing. This silver, however, elicits no demonstrable clinically significant changes in metabolic, hematologic, urinary, physical findings or cytochrome P450 enzyme inhibition or induction activity. Given their increasingly broad, diverse human exposures, future characterization of human cytochrome P450 enzyme activity for other systemically bioavailable nanotechnology products are warranted.

Objective To describe the legal, professional, and consumer status of prescribers dispensing legend and over-the-counter drugs in the United States. Methods Legal and academic databases were searched to identify those states that permit prescribers to dispense medications to patients and any limitations on such practice. In addition, prescribers and patients-consumers were surveyed to learn about the prevalence and perceptions of such practice. The use of drug samples was explicitly excluded from the study. Main Results Surveys were obtained from 556 physicians, 64 NPs, and 999 patient-consumers of drugs dispensed by prescribers. Forty-four states authorize prescriber dispensing. Midlevel practitioners (i.e., NPs and physician assistants) are authorized to dispense in 43 states. Thirty-two states do not require dispensing prescribers to compete additional registration to dispense medications, and 30 states require some level of compliance with pharmacy practice requirements. Prescriber dispensing is common, independent of patient age or insurance coverage. Prescriber dispensing appears driven by physician and patient perceptions of convenience and cost reductions. Future dispensing is likely to increase due to consumers' satisfaction with the practice. Consumer self-reported adverse drug reactions (ADRs) were equivalent between pharmacist- and physician-dispensed drugs, but urgent and emergency clinic ADR consultations were slightly lower with physician dispensing. Conclusions Prescriber dispensing is firmly entrenched in the U.S. health care system, is likely to increase, does not appear to increase ADRs, and may reduce urgent care and emergency department visits. The reduction in urgent care and emergency department visits requires further study to confirm these preliminary findings.

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.

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.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.

To review the pharmacology, pharmacokinetics, clinical trial data, adverse effects, and formulary considerations of icosapent ethyl for the treatment of high triglyceride (TG) levels.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.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 and500 mg/dL taking 4 g/day icosapent ethyl, 2 g/day, or placebo.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%).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.

Enhanced in vitro human and ex vivo rat platelet aggregation from direct exposure to silver nanoparticles is previously reported. Given the increasing human use of engineered silver nanoscale products, platelet aggregation prompted by silver nanoparticles may contribute to human cardiovascular events. To understand how direct washed platelet exposure to silver nanoparticles translates to ex vivo platelet aggregation, the authors conducted a placebo-controlled, single-blind, dose-monitored, cross-over study design in 18 healthy human volunteers. After 2 weeks of daily oral silver nanoparticle ingestion, platelet aggregation was evaluated by light transmission aggregometry in response to collagen and ADP agonists, both at baseline and after silver nanoparticle or placebo diluent oral dosing. Final percent aggregation (PA) and the changes in PA were determined using a paired design (i.e., active and placebo solutions). Enhanced ex vivo platelet activation was not detectable at peak serum silver concentrations10 µg/L. Further studies of colloidal silver nanoparticles on human platelet activities are warranted.

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.

In observational studies, higher uric acid levels are associated with metabolic syndrome, diabetes, and kidney disease.The objective of this study is to examine whether reduction of plasma uric acid with febuxostat, a xanthine oxido reductase inhibitor, impacts adipose tissue oxidative stress, adipokines, and markers of systemic inflammation or kidney fibrosis.This was a double-blinded randomized controlled trial.Academic university setting was used.Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included.Adipose tissue thiobarbituric acid reducing substances (TBARS) and adiponectin concentrations and urinary transforming growth factor-β (TGF-β) were primary endpoints. Plasma C-reactive protein, high molecular weight-adiponectin, interleukin-6, tumor necrosis factor-α, and TBARS and albuminuria were among predefined secondary endpoints.Participants were randomly assigned to febuxostat (n = 40) or matching placebo (n = 40) and followed for 24 weeks.Baseline plasma uric acid levels were 426 ± 83 µmol/L; 95% completed the study. Estimated glomerular filtration rate (eGFR) declined from 54 ± 17 mL/min/1.73 mRelatively modest sample size and short duration of follow-up.In this population with progressive diabetic nephropathy, febuxostat effectively reduced plasma uric acid. However, no detectable effects were observed for the prespecified primary or secondary endpoints.The study was registered in clinicaltrials.gov (NCT01350388).Dans les études observationnelles, des taux élevés d’acide urique sont associés à un syndrome métabolique, au diabète et à l’insuffisance rénale.Cette étude visait à déterminer si l’utilisation de febuxostat, un inhibiteur de la xanthine oxydoréductase, pour réduire le taux d’acide urique dans le plasma avait une incidence sur le stress oxydatif du tissu adipeux, les adipokines, les marqueurs de l’inflammation systémique ou sur la fibrose kystique.Il s’agit d’un essai à double insu, randomisé et contrôlé.L’étude s’est effectuée en contexte universitaire.Les participants à cette étude étaient des adultes obèses ou en surpoids, présentant une hyperuricémie ainsi qu’une néphropathie diabétique de type 2.Les critères principaux incluaient la concentration d’adiponectine et de substances réagissant avec l’acide thiobarbiturique (TBARS) dans les tissus adipeux, de même que le facteur de croissance transformant urinaire (TGF-β). Les critères secondaires incluaient les protéines C-réactives du plasma, l’adiponectine de poids moléculaire élevé, l’interleukine-6, le facteur de nécrose tumorale alpha, les TBARS ainsi que l’albuminurie.On a prescrit, de façon aléatoire, du febuxostat (n = 40) ou un placebo (n = 40) aux participants, et ces derniers ont été suivis sur une période de 24 semaines.Les valeurs initiales d’acide urique dans le plasma se situaient à 426 ± 83 µmol/L. La grande majorité des participants (95%) a complété l’étude. Le débit de filtration glomérulaire estimé a chuté de 54 ± 17 mL/min/1,73 mLa taille relativement modeste de l’échantillon, de même que la courte durée du suivi constituent les limites de l’étude.Dans la population observée, soit des patients atteints de néphropathie diabétique progressive, l’administration de fébuxostat a réduit de façon efficace les taux plasmatiques d’acide urique. Par ailleurs, aucun effet apparent n’a été observé sur les critères primaires et secondaires préétablis.Cette étude a été enregistrée sur clinicaltrials.gov (NCT01350388).

This study determined the degree of adherence to medications for glaucoma among patients refilling prescriptions in community pharmacies. Methods: Data abstracted from the dispensing records for 3615 adult patients (18 years or older, predominantly over 45) receiving glaucoma medications from two retail pharmacy chains (64 stores in total) were analyzed. From a 24-month historic data capture period, the 12-month levels of adherence were determined using standard metrics, the proportion of days covered (PDC) and the medication possession ratio (MPR). The overall 12-month mean PDC was only 57%, and the mean MPR was 71%. Using a criterion by which 80% coverage was considered satisfactory adherence, only 30% had satisfactory overall 12-month PDC coverage, and only 37% had satisfactory overall 12-month MPR coverage. Refill adherence increased with age and was highest in the 65-and-older age group (p < 0.001). Differential adherence was found across medication classes, with the highest satisfactory coverage seen for those taking alpha2-adrenergic agonists (PDC = 36.0%; MPR = 47.6%) down to those taking direct cholinergic agonists (PDC = 25.0%; MPR = 31.2%) and combination products (PDC = 22.7%; MPR = 31.0%). Adherence to glaucoma medications in the community setting, as measured by pharmacy refill data, is very poor and represents a critical target for intervention. Community pharmacists are well positioned to monitor and reinforce adherence in this population.

tudy Objective To assess clinical characteristics, pharmacotherapy treatment patterns, resource utilization and associated charges, and morbidity and mortality outcomes among a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) in an academic medical center setting. Design Retrospective analysis. Data Source Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System. Patients A total of 989 adults with prevalent (preexisting) HFrEF, identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x (heart failure) between January 1, 2007, and June 30, 2013, and who had a left ventricular ejection fraction of 40% or lower. Measurements and Main Results The cohort had a mean age of 64 ± 15 years and was predominantly white (71%) and male (74%). Patients received β-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists (ARAs) at rates of 79%, 69%, and 29%, respectively. Patients achieved target doses of β-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a β-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (β-blocker, an ACEI or ARB, and an ARA). Univariate and multivariate logistic regression models were used to assess the association between baseline characteristics with the presence of triple therapy. Two variables were statistically significant in both models: increasing age was associated with a lower odds of triple therapy (univariate: odds ratio [OR] 0.760, 95% confidence interval [CI] 0.673–0.857; multivariate: OR 0.768, 95% CI 0.625–0.942), whereas receipt of an implantable cardiac device was associated with a 2-fold increase in the odds of triple therapy (univariate: OR 2.1, 95% CI 1.4–3.1; multivariate: OR 2.1, 95% CI 1.3–3.5). During a mean ± SD follow-up of 36 ± 27 months, all-cause mortality was 0.12 per person-year. There were 1311 all-cause hospitalizations of which 611 (47%) were for worsening heart failure. The rate of all-cause and heart failure–specific hospitalizations was 0.44 and 0.21 per person-year of follow-up, respectively. The median length of stay was 6.4 ± 8.8 days, and the median charge was $22,310. The 30-day all-cause readmission rate was 20%, and the primary reason for readmission was heart failure in 65% of cases. Conclusion This study demonstrates the continuing significant disease and economic burden for patients with HFrEF. Challenges remain in utilization of established disease-modifying therapy and in the treatment of patients with HFrEF and multiple comorbidities.

Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1] Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1] Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1] Nancy M

A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2012.07.012

Use of electronic medical record (EMR) data for evaluating healthcare processes and outcomes is relatively new. Using EMR data, this study evaluated the time from antihypertensive initiation to the first follow-up office visit controlling for adverse events (AEs) and other factors that could influence follow-up timing. Findings were compared to treatment guidelines which recommend monthly follow-up in treatment naive patients until blood pressure (BP) levels are controlled.Treatment-naïve hypertensive adult patients in the General Electric Centricity EMR database (1996-2006) with a new antihypertensive prescription were evaluated. Time from treatment initiation to first office visit was identified and stratified by occurrence of AEs and therapy change. BP was assessed at 120 +/- 30 days.The mean +/- SD time from first antihypertensive prescription (index date) to the first office visit was 96.2 +/- 160.6 days; 38% returned within a month of treatment initiation. Controlling for baseline demographic and clinical characteristics, the adjusted time until first office visit was shorter for those with an AE and therapy change than for those with neither event (61 vs. 158 days). Of the patients with follow-up BP data for analysis (n = 27,875), more of those seen within a month of treatment initiation achieved BP goal at 120 days (140/90 mmHg) than those who were not seen within a month (64.3 vs. 61.7% respectively; p0.001).This study demonstrates that EMR data can be used to assess quality measures which in turn can inform efforts to improve treatment outcomes. Specifically, this study evaluated mean time to first office visit after antihypertensive therapy initiation controlling for clinical factors that could influence office visit intervals based on data available in a national EMR dataset. A key limitation of this study is that the EMR may not represent patient care delivered by other providers, thus, use of antihypertensives, changes in therapy, and office visits may be underreported.

This compilation is part of a series of articles identifying important literature in cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic management of acute decompensated and chronic heart failure and provides an update of the heart failure bibliography published in Pharmacotherapy in 2004. Most of the cited works present the results of landmark clinical studies that have shaped the management of patients with heart failure. Limited primary literature is available for some topics, thus pertinent review articles are also listed. In addition, consensus documents formed by expert panels are reviewed. This compilation may serve as a teaching tool, reference resource, or update of the literature for pharmacy clinicians, physicians, and students.

Rational use of phosphodiesterase inhibitors represents an ongoing controversy in contemporary pharmacotherapy for heart failure. In randomized clinical trials, phosphodiesterase inhibitors increased cardiac output at the expense of worsening the rates of sudden cardiac death and cardiovascular mortality. Preliminary findings from ongoing clinical and preclinical investigations of phosphodiesterase activity suggest that combined use of phosphodiesterase inhibitors with beta-adrenergic antagonists may prevent these adverse outcomes. Compartmentation of cyclic adenosine 3',5'-monophosphate signaling may prove critical in determining myocardial response to combination therapy.

Study Objective. To determine whether coadministration of misoprostol with the nonsteroidal antiinflammatory drug diclofenac lessens the increase in blood pressure and improves the alterations in renal hemodynamics induced by diclofenac. Design. Prospective, randomized, double-blind, placebo-controlled, crossover study. Setting. Two university research centers. Patients. Nineteen senior (mean age 62 yrs [range 55–73 yrs]), salt-sensitive patients with stage 1 or 2 hypertension. Intervention. After a 3-week antihypertensive withdrawal lead-in phase, patients received either diclofenac 75 mg alone or diclofenac 75 mg plus misoprostol 200 μg twice/day for 14 days. After a 10-day washout period, patients received the alternate treatment. Measurements and Main Results. Blood pressure was measured by 24-hour ambulatory blood pressure monitoring, effective renal plasma flow (ERPF) rate was determined by para-aminohippurate clearance, and glomerular filtration rate (GFR) was measured by iothalamate clearance. Mean arterial pressure (MAP = diastolic blood pressure + 0.33[systolic - diastolic blood pressure]) and rate-pressure product (RPP = systolic blood pressure x heart rate x 10−2) were also used to compare treatment groups. Diclofenac alone increased MAP by a mean ± SEM of 5.0 ± 1.0 mm Hg and RPP by 337 ± 181 units compared with baseline. The ERPF rate and GFR decreased by 40.5 ± 26.9 ml/minute and 14.1 ± 6.5 ml/minute, respectively. Diclofenac plus misoprostol decreased the diclofenac-induced increase in MAP by 3.3 ± 1.0 mm Hg (95% confidence interval [CI] 1.1–5.3 mm Hg, p=0.004) and decreased the RPP by 724 ± 238 units (95% CI 225–1223 units, p=0.007). The ERPF rate increased by 56.1 ± 35.0 ml/minute (95% CI −24.7–137.0 ml/min, p=0.15) and GFR by 18.1 ± 7.1 ml/minute (95% CI 1.9–34.5 ml/min, p=0.03). Diclofenac alone was relatively well tolerated; no adverse effects were reported with diclofenac plus misoprostol. Conclusion. In senior salt-sensitive patients with hypertension, coadministration of misoprostol with diclofenac attenuated the blood pressure elevation and renal vasoconstrictive effects of diclofenac and was well tolerated.

This study investigated the addition of the direct renin inhibitor aliskiren to amlodipine in patients with mild to moderate hypertension that was inadequately controlled with amlodipine alone. Following once-daily treatment with amlodipine 5 mg for 4 weeks, patients whose hypertension responded inadequately to therapy (mean sitting diastolic blood pressure [DBP] 90-109 mm Hg) (n=545) were randomized to 6 weeks of double-blind treatment with amlodipine 5 mg plus aliskiren 150 mg, amlodipine 5 mg, or amlodipine 10 mg. At the study's end, mean systolic blood pressure and DBP reductions with the combination of aliskiren 150 mg and amlodipine 5 mg (11.0/8.5 mm Hg) were significantly greater (P.0001) than with amlodipine 5 mg (5.0/4.8 mm Hg)--the comparator group--but similar to amlodipine 10 mg (9.6/8.0 mm Hg). All treatments were well tolerated. Edema occurred more frequently with amlodipine 10 mg (11.2%) than with combination therapy (2.1%) or amlodipine 5 mg (3.4%). In conclusion, aliskiren 150 mg plus amlodipine 5 mg shows similar but not better blood pressure-lowering efficacy when compared with amlodipine 10 mg in patients not completely responsive to amlodipine 5 mg; less edema was noted with combination therapy.

There has been a 10-year hiatus in the approval of a new pharmacotherapy for patients with chronic heart failure with a reduced ejection fraction (HFrEF). Combining an angiotensin receptor blocker, valsartan, with sacubitril, an inhibitor of neprilysin, results in increasing levels of natriuretic peptides that counterbalance high circulating levels of neurohormones in HFrEF. This has resulted in the development of a new agent, LCZ696. A comprehensive overview of LCZ696, its pharmacology, its role in the pathophysiology of HFrEF, completed and future clinical trial information, specific critical issues, and the place of LCZ696 in HFrEF therapy are presented.