Incorporating project management into the profession of pharmacy.

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High-dose nitroglycerin infusion description of safety and efficacy in sympathetic crashing acute pulmonary edema: The HI-DOSE SCAPE study.

BACKGROUND: Sympathetic crashing acute pulmonary edema (SCAPE) is a medical emergency in which severe, acute elevation in blood pressure results in acute heart failure and fluid accumulation in the lungs. Without prompt recognition and treatment, the condition often progresses rapidly to respiratory failure necessitating intubation and intensive care unit (ICU) admission. In addition to non-invasive positive pressure ventilation (NIPPV), high-dose nitroglycerin (HDN) has become a mainstay of treatment; however, an optimal dosing strategy has not been established. OBJECTIVE: The purpose of this study was to describe the characteristics and outcomes of patients who received an HDN infusion (≥ 100 µg/min) for the management of SCAPE in the Emergency Department (ED) of a large urban academic medical center. Outcomes were also analyzed to determine predictors of safety and efficacy including use of adjunct medication therapies. RESULTS: There were 67 adult patients who received HDN infusion for SCAPE from January 1, 2018 to December 31, 2018. The median (IQR) systolic blood pressure (SBP) on initiation of HDN infusion was 211 (192-233) mmHg. Patients were 63% male, 84% black, 51% had a history of heart failure (HF), and 36% had end-stage renal disease (ESRD). IV nitroglycerin (NTG) was initiated at a median (IQR) dose of 100 (100-200) mcg/min with median (IQR) peak rate in the first hour of 200 (127.5-200) mcg/min and an absolute maximum observed rate of 400 µg/min overall. 73% of patients received NIPPV, 48% sublingual (SL) or IV bolus nitroglycerin before HDN infusion, 58% loop diuretic, and 34% angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Rates of ICU admission, intubation, acute kidney injury (AKI) at 48 h, and hypotension were 37%, 21%, 13%, and 4% respectively. CONCLUSION: This is the largest to date study describing the use of an HDN infusion (≥100 µg/min) strategy for the management of SCAPE. HDN infusion may be a safe alternative strategy to intermittent bolus HDN.

Selection by design: Using job analysis to guide the selection of postgraduate pharmacy residents.

PURPOSE: To help ensure that we were accurately and consistently evaluating applicants to our postgraduate year 1 (PGY1) pharmacy residency program, we performed a job analysis to inform a redesign of our selection process. SUMMARY: A diverse panel of subject matter experts from our program was convened to develop a task inventory; a list of knowledge, skills, abilities, and other characteristics necessary for success in our program; and behavioral snapshots representing especially strong or weak resident performance (ie, critical incidents). After achieving a priori thresholds of consensus, these items were used to augment our application screening instrument (eg, development of anchored rating scales), build an online supplemental application consisting of a personality test and situational judgment test, develop a work sample consisting of a patient case presentation, and enhance the structure of our interviews (eg, by asking a consistent pattern of questions for all candidates). Preceptors reported that the redesigned process was more organized, easier to complete, and facilitated greater rating consistency. CONCLUSION: Job analysis represents an approach to designing selection processes that are more valid, reliable, transparent, and fair. Based on our experiences, recommendations for those who are considering changes to their selection process are provided.

Candidate reactions to a postgraduate year 1 pharmacy residency supplemental application.

PURPOSE: The purpose of this study was to gauge postgraduate year 1 (PGY1) pharmacy residency candidates' reactions to supplemental applications, as well as aspects specific to our process, including a personality test and situational judgment test (SJT). METHODS: After rank lists were submitted, applicants to our program were invited to complete an online survey. Outcomes of interest included candidates' perceptions of relevance and fairness. Whether candidates' attitudes differed based on the receipt of an interview offer was also assessed. RESULTS: Of 199 applicants to our program for the 2021-2022 training year, 48 applicants (24.1%) completed the survey, 15 of whom had received an interview offer. Most (64.6%) agreed that supplemental applications were useful, and nearly all (95.8%) indicated that they were willing to submit one for programs in which they were most interested. The process was seen as being fair, although ratings were higher among those who received interview offers. Most respondents believed that the personality test and SJT were relevant to the role of a resident, but attitudes towards the SJT were generally more favorable and less likely to vary according to whether candidates received an interview offer. Candidates believed that the personality test and SJT were not as representative of them as letters of reference or their curriculum vitae, but perceptions of academic performance varied. CONCLUSION: Applicants responded positively to our supplemental application and indicated that they would be willing to complete one for programs of interest. These findings should help assuage concerns about the use of supplemental applications, particularly when short-answer or essay formats are avoided.

Statin gap in patients living with HIV: assessing dose appropriateness.

OBJECTIVES: Patients living with HIV (PLWH) are predisposed to atherosclerotic cardiovascular disease (ASCVD), resulting in concomitant antiretroviral and statin use. A statin prescribing gap for PLWH has been reported, but appropriateness of statin selection and dosing (ASD) has not been described. METHODS: This is a comparative, retrospective study reviewing ASD in PLWH vs. uninfected patients at two outpatient clinics within an academic medical centre. Adults > 21 years old indicated for statin therapy were included. The primary outcome was percentage of PLWH prescribed an appropriately dosed statin, accounting for clinical- and patient-related variables, compared with uninfected patients. The secondary outcome was to identify patient characteristics associated with inappropriately dosed statins. RESULTS: After propensity score matching, 879 PLWH and 879 uninfected patients were included for analysis. Fewer PLWH (27.8%, n = 244) were prescribed an ASD compared with uninfected patients (40.5%, n = 356, P < 0.001). Similar rates of statin omission were seen in both populations (P = 0.11). More PLWH received too low a dose compared with the uninfected population (P < 0.0064). There were lower ASD rates in PLWH for subgroups of patients with clinical ASCVD (P = 0.00013) and 10-year ASCVD risk ≥7.5% (P = 0.00055), but not in patients with low-density lipoprotein cholesterol ≥190 mg/dL or diabetes. CONCLUSIONS: Although a statin gap exists in both PLWH and uninfected patients, the clinical significance may be greater for PLWH given the increased risk of ASCVD. This study confirms a larger statin gap in PLWH, particularly when underdosing of statin medications is considered. Additional analysis is warranted to investigate reasons for the ASD gap and beneficial clinical interventions.

Meeting the challenge: Implementation of a collaborative quality improvement initiative for a multi-site pharmacy residency and fellowship program.

INTRODUCTION: The American Society of Health-System Pharmacists (ASHP) accreditation standards for postgraduate training programs require a continuous improvement plan as a method of quality improvement (QI). The University of Maryland (UM) Residency and Fellowship Program offers several residency and fellowship programs. The primary objective of this QI project was to assess the perceived effectiveness of the UM's training program in preparing trainees for their desired career goals. A secondary objective was to acquire suggestions from graduates to assist in QI. METHODS: A 12-question electronic survey was sent to UM residents and fellows who graduated between 2012 and 2016. Survey questions addressed the graduate's perception of their training experience. Graduates were also asked how well certain skills were taught based on core ASHP requirements. Participation was voluntary and responses were anonymous. RESULTS: Seventy-five graduates were identified for potential inclusion, and 43 (57%) completed the survey. Findings revealed 88% of graduates were practicing in a position that matched their training and 95% indicated that their program prepared them adequately for their current job. CONCLUSIONS: The ASHP accreditation standards for pharmacy residency programs require an ongoing process of QI. This study provides support for use of an electronic survey as a helpful tool to assess effectiveness of a residency program.

Comparing Diuresis Patterns in Hospitalized Patients With Heart Failure With Reduced Versus Preserved Ejection Fraction: A Retrospective Analysis.

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.

Pharmacologic Management of Gout in Patients with Cardiovascular Disease and Heart Failure.

Gout is the most common inflammatory arthritis and is often comorbid with cardiovascular disease (CVD). Hyperuricemia and gout are also independent risk factors for cardiovascular events, worsening heart failure (HF), and death. The recommended treatment modalities for gout have important implications for patients with CVD because of varying degrees of cardiovascular and HF benefit and risk. Therefore, it is critical to both manage hyperuricemia with urate-lowering therapy (ULT) and treat acute gout flares while minimizing the risk of adverse cardiovascular events. In this review, the evidence for the safety of pharmacologic treatment of acute and chronic gout in patients with CVD and/or HF is reviewed. In patients with CVD or HF who present with an acute gout flare, colchicine is considered safe and potentially reduces the risk of myocardial infarction. If patients cannot tolerate colchicine, short durations of low-dose glucocorticoids are efficacious and may be safe. Nonsteroidal anti-inflammatory drugs should be avoided in patients with CVD or HF. The use of canakinumab and anakinra for acute gout flares is limited by the high cost, risk of serious infection, and relatively modest clinical benefit. For long-term ULT, allopurinol, and alternatively probenecid, should be considered first-line treatments in patients with CVD or HF given their safety and potential for reducing cardiovascular outcomes. An increased risk of cardiovascular death and HF hospitalization limit the use of febuxostat and pegloticase as ULT in this population. Ultimately, the selection of agents used for acute gout management and long-term ULT should be individualized according to patient and agent cardiovascular risk factors.

Financial impact of an analgosedation protocol for mechanically ventilated patients in a cardiovascular intensive care unit.

PURPOSE: The primary objective was to evaluate the impact of an analgosedation protocol in a cardiac intensive care unit (CICU) on daily doses and costs of analgesic, sedative, and antipsychotic medications. METHODS: We conducted a single-center quasi-experimental study in 363 mechanically ventilated patients admitted to our CICU from March 1, 2011, to April 13, 2013. On March 1, 2012, an analgosedation protocol was implemented. Patients in the pre-implementation group were managed at the cardiologist's discretion, which consisted of a continuous sedative-hypnotic approach and opioids as needed. Patients in the implementation group were managed using this protocol. RESULTS: The mean ± S.D. per-patient doses (mg/day) of propofol, lorazepam, and clonazepam decreased with the use of an analgosedation protocol (propofol 132,265.7 ± 12,951 versus 87,980.5 ± 10,564 [p = 0.03]; lorazepam 10.5 ± 7.3 versus 3.3 ± 4.0 [p < 0.001]; clonazepam 9.9 ± 8.3 versus 1.1 ± 0.5 [p = 0.03]). The mean daily cost of propofol and lorazepam also significantly decreased (33.5% reduction in propofol cost [p = 0.03]; 69.0% reduction in lorazepam cost [p < 0.001]). The per-patient dose and cost of fentanyl (mcg/day) declined with analgosedation protocol use (fentanyl 2,274.2 ± 2317.4 versus 1,026.7 ± 981.4 [p < 0.001]; 54.8% decrease in fentanyl cost [p < 0.001]). CONCLUSION: The implementation of an analgosedation protocol significantly decreased both the use and cost of propofol, lorazepam, and fentanyl. Further investigation of the clinical impact and cost-effectiveness of a critical care consultation service with implementation of an analgosedation protocol is warranted in the CICU.

An aspirin a day? Clinical utility of aspirin therapy for the primary prevention of cardiovascular disease.

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.

Focused Update on Pharmacologic Management of Hypertensive Emergencies.

PURPOSE OF REVIEW: Hypertensive emergency is defined as a systolic blood pressure > 180 mmHg or a diastolic blood pressure > 120 mmHg with evidence of new or progressive end-organ damage. The purpose of this paper is to review advances in the treatment of hypertensive emergencies within the last 5 years. RECENT FINDINGS: New literature and recommendations for managing hypertensive emergencies in the setting of pregnancy, stroke, and heart failure have been published. Oral nifedipine is now considered an alternative first-line therapy, along with intravenous hydralazine and labetalol for women presenting with pre-eclampsia. Clevidipine is now endorsed by guidelines as a first-line treatment option for blood pressure reduction in acute ischemic stroke and may be considered for use in intracranial hemorrhage. Treatment of hypertensive heart failure remains challenging; clevidipine and enalaprilat can be considered for use in this population although data supporting their use remains limited.

Antithromboembolic Strategies for Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

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.

Diuretic Resistance in Acute Decompensated Heart Failure: A Challenging Clinical Conundrum.

Most patients with acute decompensated heart failure (ADHF) present with signs and symptoms of volume overload, and those with a significant history of diuretic exposure may demonstrate varying degrees of diuretic resistance. Although this phenomenon is commonly reported, no consensus definition exists and recommendations regarding an optimal therapeutic approach remain limited. Optimizing the use of intravenous (IV) loop diuretic therapy is the most common initial approach, and therapy may be augmented by the addition of a thiazide-type diuretic or an IV vasodilator. Patients whose resistance to diuretic therapy is due to low cardiac output may require inotropic therapy, and other options (eg, ultrafiltration and vasopressin antagonists) may be considered in select populations. The purpose of this review is to describe diuretic resistance and its underlying mechanisms in ADHF, as well as the most commonly employed strategies for overcoming it. A stepwise approach to managing volume overload in patients with ADHF and diuretic resistance is also provided.

Clinical Practice Guideline: Safe Medication Use in the ICU.

OBJECTIVE: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015. STUDY SELECTION: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed. DATA EXTRACTION: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of the question with his/her quality of evidence assessment and proposed strength of recommendation, then the draft was reviewed by the relevant subcommittee. The subcommittee collectively reviewed the evidence profiles for each question they developed. After the draft was discussed and approved by the entire committee, then the document was circulated among all members for voting on the quality of evidence and strength of recommendation. DATA SYNTHESIS: The committee followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation system to determine quality of evidence and strength of recommendations. CONCLUSIONS: This guideline evaluates the ICU environment as a risk for medication-related events and the environmental changes that are possible to improve safe medication use. Prevention strategies for medication-related events are reviewed by medication use process node (prescribing, distribution, administration, monitoring). Detailed considerations to an active surveillance system that includes reporting, identification, and evaluation are discussed. Also, highlighted is the need for future research for safe medication practices that is specific to critically ill patients.

Observation of Patients Transitioned to an Oral Loop Diuretic Before Discharge and Risk of Readmission for Acute Decompensated Heart Failure.

BACKGROUND: Heart failure (HF) is associated with high 30-day readmission rates and places significant financial burden on the health care system. The aim of this study was to determine if the duration of observation on an oral loop diuretic before discharge is associated with a reduction in 30-day HF readmission in patients with acute decompensated HF (ADHF). METHODS AND RESULTS: This was a retrospective study of adult patients admitted for ADHF at a large academic medical center. A total of 123 patients were included. Baseline characteristics were similar between groups. The primary outcome of 30-day HF readmission occurred in 11 of 61 patients (18%) observed on an oral loop diuretic for <24 hours and in 2 of 62 patients (3.2%) observed on an oral loop diuretic for ≥24 hours (P = .023). Readmissions for 60- and 90-day HF were also significantly lower in patients observed for ≥24 hours (P = .014 and P = .049, respectively). Associations became stronger after multivariate analysis (P < .001). Observation for <24 hours and previous admission within 30 days were independent predictors of 30-day HF readmission (P = .03). CONCLUSIONS: Observation of patients on an oral loop diuretic for <24 hours was associated with significantly higher 30-day HF readmission. Therefore, observation on an oral loop diuretic for ≥24 hours before discharge in patients presenting with ADHF should be strongly considered.

Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance.

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.