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As research in pharmacy increasingly focuses on work‐related topics such as burnout, workforce management, and diversity, equity, and inclusion, there is a growing need for scholars to understand and use organizational research methods. However, these skills are not typically taught in pharmacy schools or postgraduate training programs, posing a challenge to researchers and peer reviewers alike. To address this gap, we aim to provide a practical introduction to organizational research methods with a focus on deductive, quantitative approaches. Given the growing interest in studying pharmacists' workplace well‐being, we use this as a theme for our review. We begin by discussing the importance of a thorough literature review and using theory to frame the research, develop study hypotheses, and select an appropriate research design. We also provide a list of example theories that researchers could use to study the topic of workplace well‐being. Next, we discuss key considerations for defining and measuring organizational constructs, including validity and reliability, and highlight potential pitfalls to avoid in survey research. Using several phenomena of interest in studies of workplace well‐being, we provide examples of construct definitions and illustrate how they could be operationalized as variables in a research study. Finally, we discuss important considerations for analyzing organizational data and describe skills that researchers should acquire or seek in potential collaborators. To aid researchers and peer reviewers, we provide a checklist summarizing our recommendations and references to additional resources. By equipping scholars with a better understanding of organizational research methods, we aim to enhance our understanding of pharmacists' work experiences and generate evidence to support workplace improvements that will benefit pharmacists and their efforts to provide patient care. [ABSTRACT FROM AUTHOR]

The Great Resignation marked a dramatic return to the steady, rising rate of job turnover that began over a decade ago, and recent reports suggest the profession of pharmacy is no exception. Rising concerns about pharmacist turnover follow a wave of articles about the prevalence of burnout in nearly every corner of the profession. However, this should come as no surprise, as burnout and turnover are often progressively worsening symptoms of the same disease: a toxic work environment. This review suggests that many current efforts to improve burnout in pharmacy will have limited impact because they place too much emphasis on individuals and not enough of it on the environments in which they work. Scientific frameworks for understanding burnout as a problem originating from work are discussed, distinguishing burnout from other dimensions of health and well‐being. These frameworks are then followed by an integration of empiric evidence from the organizational sciences and illustrative examples from pharmacy practice to explain how burnout emerges from an imbalance of job demands (e.g., workload, time pressure, work‐life conflict) and job resources (e.g., autonomy, rewards, social support). The review concludes with a proposed course correction—one that positions organizational leaders as the people who are best equipped to address burnout at its source through a structured process known as work redesign. By doing so, leaders can create work environments that not only reduce the risk of burnout among pharmacists but also enhance their ability to thrive. [ABSTRACT FROM AUTHOR]

The article highlights the significant prevalence of chronic health conditions (CHCs) in the U.S. workforce, emphasizing the necessity for organizations to adopt proactive measures to support affected employees. Topics discussed include the challenges workers with CHCs face, the limitations of reactive workplace interventions, and the importance of fostering supportive environments and effective supervisor training to enhance employee well-being and work ability.

Objective: To assess whether more severe urinary symptoms and poorer quality of life among patients on diuretic therapy are associated with decreased adherence to the diuretic regimen. Methods: Participants were recruited via ResearchMatch.org and sent a REDCap survey. The Overactive Bladder Questionnaire‐Short Form (OAB‐q SF) was used to assess urinary symptom bother and health‐related quality of life (HRQL). Participants were asked if they skip diuretic doses due to urinary symptoms with a bivariate (yes or no) outcome. Subgroup analyses of loop vs non‐loop diuretic and those taking the diuretic for a cardiovascular indication (hypertension or heart failure) were performed. Results: A total of 4029 surveys were sent, 285 were returned (7.1% response rate), and 279 were included in the study. Fifty‐three participants admitted to skipping diuretic doses due to urinary symptoms. Lower HRQL scores were significantly associated with poorer adherence scores among all participants (P <.001), among participants taking a loop diuretic (P <.001), and among participants with hypertension and heart failure (P <.039). Association between symptoms and adherence remained significant after adjustment in the multivariate model for the whole cohort and loop diuretic subgroup but lost significance in the hypertension and heart failure subgroup. Conclusions: Worsening quality of life due to urinary symptoms may be associated with poorer adherence to diuretics, particularly loop diuretics. [ABSTRACT FROM AUTHOR]

Although numerous tools exist to assess the clinical knowledge and skills of learners as they progress throughout the health professions curriculum, the measurement of professional attitudes, and behaviors (eg, empathy, integrity, teamwork) remains a challenge for educators. Situational judgment tests (SJTs) are a methodology for assessing how an individual's underlying knowledge, skills, traits, and other attributes are expressed when making decisions about job‐related scenarios. Studies have shown that SJTs can be a valuable predictor of future job performance among health professionals and recent research suggests that they may also be useful for the development of professional attitudes and behaviors. The primary advantage of SJTs is that they permit an assessment of these complex constructs among large groups of test‐takers, making them an appealing alternative or supplement to more resource‐intensive methods, such as situational interviews or objective structured clinical examinations. However, SJT development is a complex process and requires a set of knowledge and skills that may be unfamiliar to many clinician educators (eg, job analysis, assessments of validity, and reliability). The purpose of this review is to provide readers with an introduction to SJTs, including an overview of research to support their use, considerations regarding their content and development, and implications for practice and education. [ABSTRACT FROM AUTHOR]

Introduction: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. Research question: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. Design: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. Results: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; (P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. Discussion: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation. [ABSTRACT FROM AUTHOR]

Patients with heart failure with reduced ejection fraction often have one or more noncardiovascular comorbidities. The presence of concomitant disease states is associated with worse outcomes, including increased risk of mortality, decreased quality of life, and increased healthcare resource utilization. Additionally, the presence of heart failure with reduced ejection fraction complicates the management of these comorbidities, including varying safety and efficacy of therapies compared to those without heart failure. This article will review the literature on the pharmacologic management of common noncardiovascular comorbidities—including chronic obstructive pulmonary disease, depression, diabetes mellitus, gout, chronic kidney disease, and iron deficiency—in patients with heart failure with reduced ejection fraction, as well as provide recommendations for appropriate treatment selection in this population. [ABSTRACT FROM AUTHOR]

Gastrointestinal bleeding (GIB) is a frequent complication in patients with continuous-flow left ventricular assist devices (LVAD). We retrospectively evaluated eight patients implanted with a HeartWare LVAD between July 2017 and June 2020 who experienced at least one episode of GIB and were started on tamoxifen 20 mg once daily for secondary prevention. Tamoxifen was associated with a significant decrease in major GIB from a median of 3 (IQR 1.4–7) events/patient-year pre-tamoxifen initiation to 0 (IQR 0–0.9) events/patient-year post-tamoxifen initiation (p = 0.02). Transfusion of packed red blood cells also decreased from 16.8 (IQR 9.9–30.6) units/patient-year pre-tamoxifen initiation to 1.5 (IQR 0–7.5) units/patient-year post-tamoxifen (p = 0.04). Tamoxifen was well tolerated and no thromboembolic complications were observed. This small cohort study suggests that tamoxifen is associated with reduced GIB and transfusion requirements, with no apparent increase in thrombotic risk. A larger, randomized study is warranted to confirm the results of this exploratory analysis. [ABSTRACT FROM AUTHOR]

Background: Congestion predominates in exacerbations of heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), but evidence suggests that excess volume may be distributed differently in these 2 subgroups. Methods and Results: In this retrospective study, diuretic efficiency (DE, or net urine output per 40-mg of intravenous furosemide equivalent) during the first 72 hours was compared between patients hospitalized with HFrEF (n = 121) versus HFpEF (n = 120). Multivariate analysis was used to compare the 2 groups based on expected baseline differences (e.g., demographics, heart failure etiology, concomitant therapy). During the first 72 hours, mean daily diuretic doses were higher in patients with HFpEF versus HFrEF (172.0 vs. 159.9 mg, respectively, P = 0.026) but urine output was not significantly different (2603.3 mL vs. 2667.5 mL, respectively, adjusted P = 0.100). Similarly, mean cumulative DE did not differ (−673.5 vs. −637.8 mL/40-mg in the HFrEF and HFpEF groups, respectively, adjusted P = 0.884). An exploratory analysis of propensity-matched cohorts yielded similar findings. Correlations between the components of DE varied considerably and only became weak to moderately correlated toward the end of the observation period. Conclusions: Although cumulative DE did not differ between patients with HFrEF and HFpEF, variable correlations in the components of DE suggest there may be differences in diuretic response that warrant future analysis. [ABSTRACT FROM AUTHOR]

Introduction: The growth in applicants to postgraduate year one (PGY1) pharmacy residency programs outpaces the number of available positions, requiring that residency program directors (RPDs) evaluate an increasing number of qualified candidates. Discrepancies exist in the characteristics thought to distinguish exemplary candidates and the methods for selecting them. Objectives: To characterize the burdens of the selection process, summarize methods for selecting PGY1 residents based on a systematic review, and list best practices for improving the process. Methods: Burdens were characterized by collecting applicant costs via survey and program costs and workload estimates via interviews of RPDs at small, medium, and large programs. For the systematic review, a medical librarian searched for articles pertaining to resident selection. Articles underwent a title/abstract screen and full text screen by two authors and a third served as tiebreaker. Data were summarized in descriptive form, and consisted of study methodology, selection method(s) of interest, and principal findings. Results: The median cost to applicants was $1756 (interquartile range [IQR] $1271‐$2423). The median cost to residency programs was $5068 (IQR $3943‐$12 310). Program directors spent a median of 56.5 hours on selection; a median of 22.0 and 21.3 hours were spent by each preceptor and current resident, respectively. A total of 51 articles (22 surveys and 29 other designs) were included in the systematic review. Biographical data, interviews, and references were among the most commonly explored evaluation methods. Articles consisted primarily of descriptions of selection methods, summaries of RPD attitudes regarding these methods or characteristics desired in a resident, or factors that predicted a successful match. Few articles investigated the validity and reliability of selection methods. Conclusion: Selection is a cumbersome process for both applicants and programs alike. Fortunately, numerous opportunities exist to improve the process, and these should serve as the basis of future research. [ABSTRACT FROM AUTHOR]

Burnout is high among health care professionals. In physicians, burnout is linked to suboptimal well‐being and patient care, but the overall landscape of pharmacist burnout is unknown. Synthesis of available data regarding pharmacist burnout is needed to better understand its effects on well‐being and professional practice. This systematic review sought to determine the prevalence and intensity of burnout in pharmacists. The aim of the study was the systematic review of articles on pharmacist burnout. PubMed, Embase, Cochrane Central Register of Controlled Trials, and PsycINFO were searched for articles through February 13, 2019. Search strategies combined terms for pharmacists and burnout (including job satisfaction, stress, and resilience). The primary outcome was the proportion of pharmacists who met criteria for burnout. Secondary outcomes included the mean scores for Maslach Burnout Inventory (MBI) subscales, difference between pharmacist practice settings, and factors contributing to burnout. Raw scores and threshold proportions were pooled using a Hartung‐Knapp random‐effects model. Five articles reported the proportion of high emotional exhaustion (EE) and depersonalization (DP) and low personal accomplishment (PA), and nine articles reported individual MBI subscale scores, which were included for quantitative analysis. The proportion values of pharmacists with MBI subscale scores consistent with burnout were 41% (95% CI 27%‐54%), 20% (95% CI 7%‐32%), and 32% (95% 14%‐50%) for high EE, high DP, and low PA, respectively. Mean MBI subscales scores were 23.53 (95% CI 21.68‐25.39), 7.07 (95% CI 6.22‐7.92), and 36.51 (95% CI 34.34‐38.67) for EE, DP, and PA, respectively. Substantial heterogeneity was observed. The burnout prevalence among pharmacists is lower than previously reported, but notable. The average MBI subscale scores for high EE or DP or low PA in pharmacists did not meet criteria for burnout. [ABSTRACT FROM AUTHOR]

Oral sotalol, used in adults for sinus rhythm control, is initiated at 80 mg b.i.d. and titrated to a maximum safe dose. The US Food and Drug Administration recommends monitoring the corrected QT interval (QTc) for at least 3 days, until steady‐state exposure of the drug is reached, before patient discharge, which can significantly impact the total cost of treatment. The objectives of this research were to design an accelerated intravenous sotalol loading and maintenance therapy that will reduce the hospital length of stay and to also evaluate the pharmacoeconomic impact in a hospital setting. Pharmacokinetic simulations of sotalol plasma concentrations vs. times profiles were performed to determine the optimal intravenous/oral transition regimen. A cost minimization analysis from the health sector perspective was conducted to assess the cost savings for these proposed accelerated regimens. For a chosen target dose of 120 mg b.i.d., two infusions of 40 mg over 1 hour and 20 mg over 0.5 hour, each followed up by an evaluation of QTc, can be administered followed immediately by the target oral maintenance dose of 120 mg at the end of the second infusion. Consequently, steady‐state exposure and, therefore, steady‐state QTc are obtained on the first day of therapy, facilitating an earlier hospital discharge. Two and 1‐day mean total cost of −$3,123 (95% confidence interval (CI), −$3,640, −$2,607) −$4,820 (95% CI, −$5,352, −$4,288) were observed for this strategy, respectively. We are proposing an intravenous to oral transition strategy for sotalol that has the potential to significantly reduce cost and increase patient convenience. [ABSTRACT FROM AUTHOR]

Purpose To determine the type and frequency of formalized (structured education developed to meet a set of predefined goals and provide educational content and learning materials) and nonformalized physical examination (PE) training offered to pharmacy residents in adult patient care‐focused residency programs in the United States and Puerto Rico. Methods: A survey was distributed to a random sample of 1000 postgraduate year one and two adult patient care residency program directors. Participants were queried to determine if they offered PE training and the types of training offered. Barriers to and reasons for not providing PE training were assessed. Descriptive statistics were performed. Results: There were 122 respondents. Thirteen (10.7%) programs provide formalized PE training and six of these were postgraduate year 1 residencies (46.2%). Informal PE training resources were provided in 97/117 (82.9%) programs. The duration and scope of training programs varied. Forty‐four of 116 (37.9%) responding programs required components of the PE in one or more rotations. The most commonly cited reasons for those who have not considered a formalized training program (n = 94) were that performing a PE is not part of the residency program (56.4%), lack of perceived value (45.7%), that PE is not part of the practice of the organization (43.6%), lack of trained clinicians (35.1%), lack of awareness that this type of training is available (35.1%), and lack of time in the schedule (31.9%) (respondents were able to select more than one). Conclusion: Many pharmacy organizations endorse PE, yet formalized PE training does not appear to be routinely offered in adult patient care‐focused residency programs. Reasons for not offering a formalized training program suggest that raising awareness of the benefits of pharmacists learning PE is warranted. As pharmacists seek provider status, the need to increase PE training in pharmacy residency programs may be necessary. [ABSTRACT FROM AUTHOR]

Social media has evolved considerably since its humble beginnings in the late 1990s. Today, three billion individuals worldwide use social media. While its traditional use has been to connect with family and friends, social media has also been integrated into many other areas of society, including health care. Today, many health care professionals, including pharmacists, use social media for developing their own personal brand, professional networking, professional development, scholarly activity, pharmacy education, and even patient care. Despite the benefits of actively engaging with social media, the available evidence would suggest that pharmacists' engagement with social media for professional use has been limited. This is likely due to several well‐publicized criticisms of social media, including the potential for users to segregate themselves into echo chambers of only like‐minded individuals, inability to confirm the accuracy of shared information, its potential as a distractor from other tasks and responsibilities, and personal and patient privacy concerns. Fortunately, most of these concerns can be minimized if pharmacists develop a strategy for social media engagement that is intentional and consistent with their personal goals. Pharmacists should consider becoming not only passive "lurkers" on social media but also creating original content that shares knowledge and encourages conversations with others. We propose that pharmacists use a design‐based approach to ensure their use of social media is effective and sustainable. The "ABCDE" approach includes analyzing one's goals and audience, brainstorming ideas for how best to use social media, creating content that is relevant, practical, and useful, disseminating content efficiently and effectively, and periodically evaluating how well one's goals are being met and identifying opportunities for improvement. [ABSTRACT FROM AUTHOR]

The use of alemtuzumab for induction therapy in orthotopic heart transplantation remains controversial, despite its observed benefits in other transplant populations. This study aimed to evaluate whether alemtuzumab conferred a lower risk of rejection while reducing toxicities commonly attributed to standard immunosuppression in orthotopic heart transplantation. We included adult patients who underwent orthotopic heart transplantation and received induction therapy with alemtuzumab (n = 26) or standard immunosuppression (n = 26). The primary end point was freedom from grade ≥2 rejection at 12 months. Baseline characteristics were similar between the groups with the exception of poorer renal function in the alemtuzumab group (P < .05). The primary end point of freedom from grade ≥2 rejection at 12 months was not different between alemtuzumab and standard therapy (76.9% vs 96.2%, P = .077), likely due to similarities in the rates of antibody-mediated rejection in the 2 groups. However, grade ≥2 acute cellular rejection was considerably lower with alemtuzumab (0% vs 19.2%, P = .02), as was acute cellular rejection of any severity (50% vs 7.7%, P = .004). Deterioration in renal function was significantly greater among patients receiving standard therapy as evidenced by decreases in glomerular filtration rate (-25.6 vs -9.2 mL/min, P = .032). No differences in hematologic or infectious complications were observed. In conclusion, alemtuzumab reduced several important rejection-related outcomes while ameliorating the toxicities associated with standard immunosuppression therapy, making it a promising agent for induction in orthotopic heart transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular disease remains a leading cause of morbidity and mortality. Since the description of its therapeutic potential, aspirin has been a cornerstone of therapy following vascular events. However, aspirin in the primary prevention setting is controversial and major guideline groups provide inconsistent recommendations. Thus, there is variability in practice as providers are faced with a balance of therapeutic benefit and drug-induced harm. Areas covered: This article provides a critical appraisal of both past and present data for aspirin in the primary prevention setting. PubMed and Cochrane Central Register databases were searched from inception to May 1st, 2019. Expert opinion: The decision to initiate or withdraw aspirin for primary prevention requires an understanding of the equilibrium between efficacy and safety. In adults greater than 70 years of age, low to moderate cardiovascular risk, controlled diabetes, or at high risk of bleeding, initiation of aspirin for primary prevention should generally be avoided. Instead, risk factor modification should be prioritized. The net benefit of aspirin in those at high risk for cardiovascular disease and in those with uncontrolled diabetes is largely unknown. Ultimately, initiation or withdrawal of aspirin therapy must involve discussion of the patient's wishes and treatment expectations. [ABSTRACT FROM AUTHOR]

Objectives: To characterize anticoagulation practices with the Impella percutaneous ventricular assist device (pVAD).Background: Managing anticoagulation in patients being supported by the Impella pVAD is made challenging by several unique features of the device. These include the release of a dextrose-based purge solution containing unfractionated heparin (UFH), the need to concurrently administer systemic anticoagulation with intravenous UFH, and the lack of an alternative strategy in patients with contraindications to UFH.Methods: To characterize anticoagulation practices with the Impella pVAD, we conducted a survey of centers in the United States performing a high volume of Impella cases, which we defined as > 1 per month. Centers were contacted via email or phone and individuals who agreed to participate were provided with a link to complete the survey online. The primary measures of interest were variations in practice across centers and variations from the manufacturer's recommendations.Results: Practices varied considerably among respondents (65 of 182 centers, or 35.7%) and often diverged from manufacturer recommendations. Approximately half of centers (52.4%) reported using a UFH concentration of 50 units/mL in the purge solution, whereas most of the remaining centers (41.3%) reported using lower concentrations. Strategies for the initiation and adjustment of systemic therapy also varied, as did practices for routinely monitoring for hemolysis. Nearly one-fifth of centers (16.7%) had not developed an alternative strategy for the purge solution in patients with contraindications to UFH. Most centers (58.4%) reported using argatroban or bivalirudin in this scenario, a strategy that diverges from the manufacturer's recommendations.Conclusions: Given these findings, studies to determine a systematic approach to anticoagulation with the Impella device are warranted. [ABSTRACT FROM AUTHOR]

We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6-12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y12 inhibitor used. Each category review was followed by a discussion providing insight into the quality of evidence and implications for practice. We found that the risk of bleeding with TT was higher than with DT, without demonstrated added benefit of reducing major adverse cardiovascular events. TT use should be minimized in patients with high bleeding risk, and patient-specific factors should be critically analyzed to select appropriate antiplatelet and anticoagulant agents. [ABSTRACT FROM AUTHOR]

Percutaneous mechanical circulatory support ( MCS) devices, including the intraaortic balloon pump, Impella, and TandemHeart, are often used for hemodynamic support in the setting of refractory cardiogenic shock. The thrombotic and bleeding complications associated with these devices is well recognized, and the Impella and TandemHeart devices have unique anticoagulation considerations that may influence patient outcomes. Both devices typically require use of a heparinized purge solution in combination with intravenous unfractionated heparin, thereby providing multiple sources of heparin exposure. Each device also has specific monitoring requirements and goal ranges. This review provides an overview of percutaneous MCS devices commonly used in the acute management of left ventricular failure, with an emphasis on pharmacologic considerations. We review recent evidence and guidelines and provide recommendations for appropriate use of anticoagulation during device support. Approaches to managing heparinized purge solutions, monitoring, and the utility of nonheparin anticoagulants are also provided because high-quality evidence in the literature is limited. [ABSTRACT FROM AUTHOR]

Peripartum cardiomyopathy ( PPCM) is an uncommon, idiopathic complication of pregnancy associated with significant (10-30%) mortality. The disease occurs late in pregnancy or in the months following delivery, resulting in reduced systolic function and heart failure ( HF) symptoms. Limited direction is provided for the management of PPCM, and the safe and effective use of medications in pregnant and breastfeeding women with PPCM presents a unique challenge. Although several HF therapies in pregnant and lactating women are supported by robust evidence, evidence to support the use of other therapies is significantly lacking. Current guidelines recommend treatment as in other forms of HF with reduced left ventricular ejection fraction ( LVEF) but with consideration for the important nuances in this population as well as the unique and potential teratogenic effects of these therapies. Since most patients with PPCM recover their LVEF, the duration of therapy is currently unknown and warrants further study. We review the available literature surrounding pharmacologic and device therapy for PPCM and provide insight into managing patients with the condition. [ABSTRACT FROM AUTHOR]

Study Objective To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure ( ADHF) and loop diuretic resistance. Design Retrospective cohort study. Setting Large urban academic medical center. Patients Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/day or higher (or an equivalent dose of IV bumetanide), during hospitalization, and who then received at least one dose of IV chlorothiazide (88 patients) or oral metolazone (89 patients) to augment diuresis. Measurements and Main Results The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type diuretic administration, and the study was designed to test for the noninferiority of metolazone. Safety end points included changes in renal function and electrolyte concentrations. The mean dose of IV loop diuretic therapy (in IV furosemide equivalents) at baseline (before thiazide-type diuretic administration) was higher in the chlorothiazide group (mean ± SD 318.9 ± 127.7 vs 268.4 ± 97.6 mg/day in the metolazone group, p=0.004), but net UOP was similar (mean ± SD 877.0 ± 1189.0 ml in the chlorothiazide group vs 710.6 ± 1145.9 ml in the metolazone group, p=0.344). Mean doses of chlorothiazide and metolazone were 491 ± 282 mg and 5.8 ± 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 ± 1443.0 ml vs 2030.2 ± 1725.0 ml in the chlorothiazide and metolazone groups, respectively, p=0.308). For the primary efficacy end point, metolazone met the threshold for noninferiority by producing a net UOP of 1319.6 ± 1517.4 ml versus 1397.6 ± 1370.7 ml for chlorothiazide (p=0.026 for noninferiority). No significant differences in renal function were observed between the groups. Although hypokalemia was more frequent in the chlorothiazide group (75% with chlorothiazide vs 60.7% with metolazone, p=0.045), no significant differences in the rates of severe hypokalemia or other electrolyte abnormalities were observed between the groups. Conclusion Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities. Given the significant cost disparity between the two agents, these findings suggest that oral metolazone may be considered a first-line option in this patient population. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy ( CAV) is a common complication following heart transplantation ( HT), resulting in diminished graft survival. The preferred strategy for preventing CAV is optimal medical management; however, for patients who develop CAV, delaying disease progression through effective medication management is equally important. A review of the literature regarding medication management of CAV was conducted via a search of the MEDLINE database. Studies were included if they were published in English, conducted in humans ≥ 18 years of age or older, and used noninvestigational medications. Immunosuppressive medications such as the antiproliferative mycophenolate, the calcineurin inhibitor tacrolimus, and the proliferation signal inhibitors sirolimus and everolimus have been shown to prevent the development of CAV. Certain cardiovascular medications, such as HMG-CoA reductase inhibitors (statins), gemfibrozil, calcium channel blockers, and angiotensin-converting enzyme inhibitors, have also demonstrated efficacy in preventing this disease process. Prevention of CAV has also been observed with prophylaxis against cytomegalovirus infection and antioxidant medications. Despite being commonly used in HT patients, neither antiplatelet agents nor glycemic control have proved effective at preventing CAV. Only sirolimus has been shown to arrest the progress of existing CAV. [ABSTRACT FROM AUTHOR]

Nonsteroidal antiinflammatory drugs ( NSAIDs) are used in the management of a variety of conditions, but their prevalence is likely underreported as a result of widespread availability and the perception that nonprescription therapies are unnecessary to report during medication history taking. However, NSAIDs are associated with a number of adverse effects, especially in patients with cardiovascular disease ( CVD). Patients with CVD and comorbidities for which NSAIDs may provide symptomatic relief (e.g., osteoarthritis, rheumatoid arthritis) tend to be older, which places them at greater risk of harm. For these reasons, the use of NSAIDs in patients with CVD is a significant public health concern. An understanding of the risks associated with NSAIDs is critical for clinicians across practice settings. In this review, we detail the safety of NSAIDs in patients with CVD, provide recommendations on their use in specific disease states, and discuss therapeutic alternatives. [ABSTRACT FROM AUTHOR]

Aim: An algorithm that uses clinical factors and CYP2C19 genotype to guide P2Y12 inhibitor selection in high-risk patients undergoing percutaneous coronary intervention was implemented at our institution. We sought to evaluate use of this algorithm and identify which factors influenced P2Y12 inhibitor selection. Patients & methods: This retrospective cohort study included 264 patients receiving percutaneous coronary intervention from July-December 2012. Results: CYP2C19 genotype was obtained in 229 patients; of these, 30% were intermediate or poor metabolizers. CYP2C19 intermediate or poor metabolizer phenotype was among the strongest predictors for selecting prasugrel or ticagrelor as maintenance therapy (p < 0.001), and was the only significant predictor of a change in therapy (p < 0.001). Conclusion: These findings suggest that using CYP2C19 genotype to guide P2Y12 inhibitor selection is feasible. Original submitted 27 October 2014; revision submitted 19 December 2014 [ABSTRACT FROM AUTHOR]

Study Objective To assess the short-term efficacy and safety of an accelerated intravenous iron regimen in hospitalized patients with heart failure and iron deficiency. Design Prospective, single-arm, open-label study. Setting Large tertiary care medical center. Patients Thirteen patients with New York Heart Association class III- IV heart failure, anemia (hemoglobin level ≤ 12.0 g/dl), and iron deficiency (ferritin level < 100 ng/ml, or ferritin level of 100-300 ng/ml with transferrin saturation < 20%) hospitalized between April 2011 and December 2013. Intervention All patients received sodium ferric gluconate 250 mg in 100 ml of normal saline intravenously over 2 hours twice/day until the iron deficit was corrected or the patient was discharged. Measurements and Main Results Changes in hematologic parameters were assessed at 1-4 weeks after therapy. Patients received a mean ± standard deviation ( SD) total iron dose of 1269 ± 207 mg over 3.4 ± 1.0 days. After a mean ± SD follow-up of 13.1 ± 5.6 days, intravenous iron increased hemoglobin level by 1.2 g/dl (95% confidence interval [ CI] 0.45-1.9, p=0.005), ferritin level by 364.2 ng/ml (95% CI 129.7-598.7, p=0.007), and transferrin saturation by 10.5% (95% CI 6.5-14.6%, p<0.001). Changes in hemoglobin level did not correlate with volume status, as determined by differences in body weight. No significant changes in blood pressure or heart rate were observed. Adverse events were few and minor in severity (e.g., nausea, constipation, and abdominal discomfort). Conclusion An accelerated intravenous iron regimen improved hematologic parameters and was well tolerated in hospitalized patients with advanced heart failure. A randomized multicenter trial comparing this regimen with placebo is warranted. [ABSTRACT FROM AUTHOR]

Despite advances in the management of heart failure ( HF), quality of life and other outcomes remain suboptimal for many patients. Anemia and iron deficiency are comorbidities associated with adverse outcomes, although their pathophysiology in the setting of HF is not entirely understood. Anemia and iron deficiency may exist independently and may be a consequence of the systemic inflammatory state characterized by chronic HF. However, it is unclear whether serum hemoglobin concentrations and other hematologic parameters serve as markers for the severity of disease or represent novel therapeutic targets. Research in this area has focused primarily on therapies known to be effective for these conditions in other chronic disease states with similar pathophysiologic features (e.g., end-stage renal disease). Despite its many practical advantages, minimal evidence exists to support the use of oral iron supplementation in this setting. In contrast, intravenous iron has been the subject of several recent investigations, demonstrating improvements in both surrogate and clinical end points, although benefits seem to be the most substantial in patients with concomitant anemia. Erythropoietin-stimulating agents demonstrated early promise in retrospective analyses and small prospective trials, but their benefit was outweighed by a lack of improvement in clinical outcomes and an excess number of thromboembolic events in the largest trial of patients with anemia and HF to date. For acute symptomatic anemia, blood transfusion may be considered, although few trials have included patients with HF, and caution must be exerted in those who are hemodynamically unstable. Based on the currently available evidence, treatment of iron deficiency appears to confer benefit in patients with HF, whereas strategies aimed at improving hemoglobin alone do not. Included is a review of the pathophysiology of these conditions in the setting of HF, clinical trials evaluating pharmacologic therapy, and recommendations for management. [ABSTRACT FROM AUTHOR]

Acute decompensated heart failure ( ADHF) is associated with substantial morbidity and mortality, and represents a considerable financial burden to society. Historically, few prospective, randomized, double-blinded trials have investigated the optimal management of ADHF, and most guideline recommendations are based primarily on expert opinion. However, in the last decade, a considerable amount of research has added to the understanding of the management of ADHF in both patients with fluid overload and low cardiac output. In addition, as mechanical circulatory support devices and heart transplantation continue to evolve, significant advances have also been made with regard to the proper selection of patients for advanced surgical options. Finally, several novel pharmacologic agents have shown promise in early trials and may represent the next steps in ADHF management. Although advances have been made over the past decade, many questions remain. [ABSTRACT FROM AUTHOR]

Atrial fibrillation ( AF) is a cardiac arrhythmia associated with significant morbidity and mortality, affecting more than 3 million people in the United States and 1-2% of the population worldwide. Its estimated prevalence is expected to double within the next 50 years. During the past decade, there have been significant advances in the treatment of AF. Studies have demonstrated that a rate control strategy, with a target resting heart rate between 80 and 100 beats/minute, is recommended over rhythm control in the vast majority of patients. The CHA2 DS2≥ (congestive heart failure, hypertension, age ≥ 65 yrs, diabetes mellitus, stroke or transient ischemic attack, vascular disease, female gender) scoring system is a potentially useful stroke risk stratification tool that incorporates additional risk factors to the commonly used CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke transient ischemic attack) scoring tool. Similarly, a convenient scheme, termed HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), to assess bleeding risk has emerged that may be useful in select patients. Furthermore, new antithrombotic strategies have been developed as potential alternatives to warfarin, including dual-antiplatelet therapy with clopidogrel plus aspirin and the development of new oral anticoagulants such as dabigatran, rivaroxaban, and apixaban. Vernakalant has emerged as another potential option for pharmacologic conversion of AF, whereas recent trials have better defined the role of dronedarone in the maintenance of sinus rhythm. Finally, catheter ablation represents another alternative to manage AF, whereas upstream therapy with inhibitors of the renin-angiotensin-aldosterone system, statins, and polyunsaturated fatty acids could potentially prevent the occurrence of AF. Despite substantial progress in the management of AF, significant uncertainty surrounds the optimal treatment of this condition. [ABSTRACT FROM AUTHOR]

Pharmacotherapeutic approaches for the management of pulmonary arterial hypertension (PAH) have expanded greatly in the last 10 years. Pulmonary arterial hypertension is a relatively rare disease and is associated with myriad disease processes. The older term for PAH, primary PAH, has been changed to represent these differences and to distinguish it from postcapillary PAH associated with left-sided heart failure. Limitations in evaluating treatment approaches for PAH include its rarity, the small number of patients included in clinical trials, and issues regarding the use of placebo-controlled trials in a disease with such a high mortality rate if left untreated. Management options include the use of prostacyclin and prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase inhibitors, as well as traditional background therapy with diuretics, digoxin, calcium channel blockers, and warfarin. Numerous drugs are under investigation to evaluate their possible roles in management. Combination therapy is increasingly becoming a standard approach to therapy, with mounting literature to document effectiveness. Current or emerging roles for the pharmacist in the management of PAH largely involves ensuring access to drug therapy, facilitating specialty pharmacy dispensing, and providing patient counseling. Newer roles may include future drug development, optimized use of investigational drugs, and specialized disease management programs. This compilation includes a series of articles identifying important literature in cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic management of pulmonary arterial hypertension ( PAH). Most of the cited works present the results of significant human clinical studies that have shaped the management of patients with PAH. Limited primary literature is available for some topics, so in addition, consensus documents prepared 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. [ABSTRACT FROM AUTHOR]