Contemporary Trends in the Use of and Expenditures on Digoxin in the United States.

BACKGROUND: Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other pharmacologic and device therapies, digoxin retains a role in select patients unable to tolerate or refractory to standard therapies. Contemporary utilization of and costs related to digoxin in the United States of America (USA) remain uncharacterized. The objective of this study was to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. METHODS: We utilized the Medical Expenditure Panel Survey to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. The Medical Expenditure Panel Survey is an overlapping panel survey that interviews households in the USA to ascertain their healthcare utilization and expenditures. Complex sampling procedures allow for nationally representative estimates of utilization and expenditures. We report the number of digoxin users and expenditures across key subgroups in 2-year increments from 2010 to 2017. RESULTS: The number of digoxin users in the USA declined by 47% from 766 users per 100,000 adults in 2010-11 to 402 users per 100,000 adults in 2016-17. While digoxin use declined among women and self-identified White adults, adults living at or below the federal poverty level and those who self-identified as Asian or Hispanic represent an increasing proportion of overall digoxin users. While nationwide digoxin expenditures declined by 26% from 2010-11 to 2012-13, they peaked at $260.3 million in 2014-15 and remained elevated at $188.7 million in 2016-17. CONCLUSIONS: Despite a nationwide trend towards declining use, digoxin remains prevalent amongst people of Asian and Hispanic descent in the USA. After a spike in cost in 2013, digoxin prices have yet to return to pre-spike levels. The role of digoxin in contemporary heart failure and arrhythmia management will continue to evolve as additional randomized and observational analyses become available.

Effects of adding low-dose ketamine to etomidate on serum cortisol levels in critically ill cardiac patients: a randomized clinical trial.

BACKGROUND: Etomidate was associated with an inhibition of adrenal steroid synthesis. This study aimed to evaluate the effects of adding low-dose ketamine to etomidate to minimize the decrease in serum cortisol level in critically ill cardiac patients. METHODS: Sixty adult cardiac patients, ≥ 18 years, who underwent upper endoscopy and Colonoscopy to manage acute anemia in the cardiac intensive care units were enrolled. Patients were randomly divided into two groups: (group (E): n = 30) received etomidate 0.2 mg/kg IV followed by etomidate 0.05 mg/kg IV, and (group (KE): n = 30) received ketamine 0.5 mg/kg IV, then etomidate 0.1 mg/kg IV, followed by etomidate 0.05 mg/kg IV. The primary outcome was Serum cortisol level at 6 h after the procedure. RESULTS: The mean postoperative cortisol level was significantly lower in group E (295.60 ± 49.218 nmol/L) versus group KE (461.00 ± 67.946 nmol/L), with 95% CI = 351.94 to 404.66; p = 0.000. In addition, the estimated serum cortisol reduction level was also significant between groups; In group E, the estimated cortisol level decreased nearly 53% from 632.40 ± 35.066 nmol/L to 295.60 ± 49.218 nmol/L 6 hours postoperative. While in group KE, the estimated cortisol level decreased only 27% from 639.13 ± 43.035 nmol/L to 461.00 ± 67.946 nmol/L. CONCLUSIONS: Single-dose ketamine (0.5 mg/kg) was helpful to decrease the total dose of etomidate and hence decreased the percentage of serum cortisol level in such critically ill patients with preservation of patient satisfaction. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov ( NCT04857450 ; principal investigator: Mostafa Mohammed Elsaid Elhamamsy; registration date: 23/04/ 2021).

Crossword puzzle as a learning tool to enhance learning about anticoagulant therapeutics.

BACKGROUND: Educational games make the learning process more enjoyable, fun, and create a competitive classroom environment that can positively affect learning. The purpose of this study was to evaluate pharmacy students' perceptions of crossword puzzles (CWPs) as a learning tool in the pharmacotherapy cardiovascular module focusing on anticoagulants' therapeutics and assessing if students' preference of learning style influenced their perception. METHODS: Clues for the puzzle were developed, validated, and piloted by course faculty. A free internet puzzle generator was used to create puzzles with 10 to 20 clues. Students were given 30 min to solve the puzzle following six hours of didactic lectures about the topic. An 8-item survey instrument and Pharmacists' Inventory of Learning Styles (PILS) questionnaire were administered to examine students' perceptions of the game and their learning style preference, respectively. RESULTS: Two hundred sixty-seven students participated in the activity from both undergraduate programs (BPharm and PharmD) over three consecutive course offerings. Most students expressed favorable perceptions of the puzzle. Female and BPharm students had significantly more favorable perceptions than male and PharmD students on several perception items. The dominant preferred learning style (PLS) was converger (35.6%), followed by assimilator (25.3%), while 15.1% had mixed learning styles. The study did not find a significant association between PLS and students' perceptions toward the CWP. CONCLUSIONS: The CWP game presented an innovative, creative, and easy active learning tool to enhance information recall, retention, and class engagement while accommodating all learning style preferences.

Clinical pharmacy definition, required education, training and practice in Saudi Arabia: A position statement by the Saudi society of clinical pharmacy.

The Saudi Society of Clinical Pharmacy (SSCP) is a scientific and professional society in the field of clinical pharmacy that operates under the Saudi Commission for Health Specialties governance. The SSCP believes that there is a need to define and describe many aspects related to the clinical pharmacy profession in Saudi Arabia. Moreover, there is an increasing demand for promoting the concept of clinical pharmacy and developing a consensus regarding the scope of practice and clinical pharmacist's required postgraduate education and training in Saudi Arabia. This paper is intended to present several position statements by the SSCP that define the concept of clinical pharmacy, describe the required education and training, and highlight clinical pharmacists' scope of practice in Saudi Arabia. This paper calls for further investigations that examine the impact of clinical pharmacists on individual and population health levels.

Knowledge, Attitude, and Practice Towards COVID-19 Among Pharmacists: A Cross-Sectional Study.

PURPOSE: The COVID-19 outbreak has caused governments to put pandemic-related guidelines requiring compliance and understanding by healthcare professionals to mitigate its spread uncontrollably. We studied pharmacists' knowledge, attitude, and practice towards the COVD-19 outbreak compared with other healthcare workers during the pandemic in Saudi Arabia. METHODS: We surveyed pharmacists' socio-demographics (n=50) compared with other healthcare professionals (n=378) during lockdown starting in June 2020. We measured respondents' level of knowledge (n=10 questions, maximum score of 10), attitude (n=17 questions, maximum score of 80), and their practices (n=16 questions, maximum score of 80) towards COVID-19 infection. RESULTS: Median knowledge score was 8 (25th-75th percentiles: 7-9), attitude score 76 (70-80) and practice score 74 (68-78). Good knowledge predictors were >20 years working experience [OR: 2.05 (95% CI: 1.03-4.06); P=0.04] and >50% working in clinical practice [OR: 1.72 (95% CI: 1.12-2.66); P=0.01], in inverse relationship with paramedical professions [OR: 0.45 (95% CI: 0.45 (0.28-0.72)); P=0.001] and working in a university hospital [OR: 0.51 (95% CI: 0.33. 0.81); P=0.004]. Availability of pharmaceutical information and treatment options was associated with good attitude [OR: 2.19 (95% CI: 1.04-4.59); P=0.039] and acquaintance as primary information sources negatively associated with good attitude [OR: 0.34 (95% CI: 0.15-0.8); P=0.013]. Good practice predictors were female gender [OR: 3.84 (95% CI: 2.37-6.24); P<0.001], military hospital employment [OR: 2.32 (95% CI: 1.25-4.31); P=0.008], USA [OR: 3.41 (95% CI: 1.03-11.22); P=0.044] or UK [OR: 8.86 (95% CI: 1.91-41.07); P=0.005] qualifications, and information on supportive measures [OR: 2.2 (95% CI: 1.36-3.56); P=0.001]. CONCLUSION: Health workers displayed good knowledge about COVID-19, while profession and working experience predicted adequate knowledge, positive attitude, or practice towards disease management.

Multidrug-Resistant and Extensively Drug-Resistant Enterobacteriaceae: Prevalence, Treatments, and Outcomes - A Retrospective Cohort Study.

BACKGROUND: Drug-resistant gram-negative bacteria (GNB) are a global public health threat, especially in intensive care units (ICU). This study explored the prevalence of drug-resistant Enterobacteriaceae infections in an ICU in Saudi Arabia. The appropriateness of the antibiotic therapies used and their ability to improve the clinical outcomes were also assessed. METHODS: A retrospective study was conducted from 2015 to 2018 in the different ICUs of a tertiary-care hospital in Saudi Arabia. Positive cultures for multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Enterobacteriaceae, including Klebsiella pneumoniae, Escherichia coli, and Enterobacter sp., were included. The primary outcomes involved microbiological cure and 30 days in-hospital mortality rate, while the secondary outcome included the length of hospital stay (LOS). Regression models were used to assess the relationship between appropriateness of the antibiotic therapy and clinical outcomes. RESULTS: Of the 227 Enterobacteriaceae cultures included in this study, 60% were either MDR (n= 130) or XDR (n= 8) infections; no PDR Enterobacteriaceae cultures were identified. Majority of the patients were female (54%), and the average age was 60.1 ± 17.7 years. MDR/XDR cultures primarily comprised E. coli (51.4%), followed by K. pneumoniae (33%) and Enterobacter sp. (16%). Most commonly used antibiotics were piperacillin/tazobactam (53%), carbapenems (47%), and cephalosporins (21.3%). Antibiotic therapy was considered appropriate in only 85 of 138 (61.59%) patients. Microbiological cure rate was achieved in 40% of the cases, and in-hospital death rate was 84%. The average LOS was 27 days. Appropriateness of the antibiotic therapy prescribed could not predict any of the study outcomes. CONCLUSION: The study revealed a high prevalence of drug-resistant Enterobacteriaceae infections, which were associated with a high mortality rate. Therefore, it is essential to assess the effectiveness of antimicrobial stewardship program and infection prevention and control practices, particularly in critically ill patients.

Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure (HF) with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for torsades de pointes. The influence of HF with preserved ejection fraction (HFpEF) on response to drug-induced QT lengthening is unknown. METHODS AND RESULTS: We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched control subjects without HF. Serial 12-lead electrocardiograms were obtained for determination of QT intervals. Demographics, maximum serum ibutilide concentrations, area under the serum ibutilide concentration vs time curves, and baseline Fridericia-corrected QT (QTF) (417 ± 14 vs 413 ± 15 ms, P = .54) were similar in the HFpEF and control groups. Area under the effect (QTFvs time) curve (AUEC) from 0 to 1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519 ± 19 vs 497 ± 18 ms·h, P= .04), as was AUEC from 0 to 8.17 hours (3576 ± 125 vs 3428 ± 161 ms·h, P = .03) indicating greater QTF interval exposure. Maximum QTF (454 ± 15 vs 443 ± 22 ms, P = .18) and maximum percent increase in QTF from baseline (8.2 ± 2.1 vs 6.7 ± 1.9%, P = .10) in the 2 groups were not significantly different. CONCLUSIONS: HFpEF is associated with enhanced response to drug-induced QT interval lengthening.

Adherence to Statin Therapy and Attainment of LDL Cholesterol Goal Among Patients with Type 2 Diabetes and Dyslipidemia.

BACKGROUND: Statins are widely utilized antidyslipidemics with a proven track record of safety and efficacy. However, the efficacy of these therapeutic agents hinges on patients' adherence to their prescribed statins. OBJECTIVE: The primary objectives of this study were to examine the relationship between adherence to prescribed statins and its impact on the low-density lipoprotein (LDL) level, and to explore the factors that influence patient adherence to statins among patients with diabetes and dyslipidemia. METHODS: This was a retrospective, cross-sectional study using the electronic health records data of adults (≥18 years) with type 2 diabetes and dyslipidemia visiting outpatient clinics at a university-affiliated tertiary care center. Adherence to statin therapy was estimated using the proportion of days covered (PDC). Patients with diabetes were considered adherent to statins if they had a PDC of ≥80%. Treatment success was considered if the LDL level of < 2.6 mmol/L. RESULTS: Out of 10,226 of patients with diabetes, 1532 met the inclusion criteria and were included in the study. Seventy-nine percent of the patients with diabetes were on atorvastatin and 21% were on simvastatin. The vast majority of the patients with diabetes (77%) were considered adherent and about 42% achieved LDL-cholesterol goal < 2.6 mmol/L. No association between adherence to statin therapy and LDL goal attainment was observed. Women had lower odds of being adherent to statin therapy (AOR=0.66, 95% CI: 0.49-0.87) compared to men. Further, young adults (18-44 years) had lower odds of being adherent to statin therapy (AOR=0.58, 95% CI: 0.32-0.97) compared to older adults (age>65 years). CONCLUSION: The findings of this study highlight the need to examine the impact of adherence to statins on healthcare services utilization due to different complications of uncontrolled dyslipidemia.

Novel and Emerging Therapeutics for Primary Prevention of Cardiovascular Disease.

Cardiovascular disease is responsible for 205 deaths per 100,000 persons annually and is the leading cause of death worldwide. The public health burden of cardiovascular disease is expected to continue to grow as the prevalence of many cardiovascular risk factors increases. Several novel classes of glucose-lowering, lipid-lowering, and weight-loss therapeutics have shown mortality benefits in outcomes trials. However, a large proportion of subjects in those trials had established cardiovascular disease, so, as a result, the role of these novel therapeutics in primary cardiovascular prevention is controversial. In this review, we highlight recent advances in the pharmacotherapeutic management of the cardiovascular risk factors of hyperglycemia, dyslipidemia, and obesity. We examine key subgroups within recent cardiovascular outcome trials, weigh the risks and benefits of several novel therapeutics, and provide practical insight into the use of these agents. Our article concludes with a look toward the future and provides the practitioner and scientist with an early view of emerging therapeutics that may play an important role in primary cardiovascular prevention.

Guideline-Directed Medical Therapy and Survival Following Hospitalization in Patients with Heart Failure.

BACKGROUND: Modification of guideline-directed medical therapy (GDMT) in hospitalized patients with heart failure (HF) has not been extensively evaluated. METHODS: The community surveillance arm of the Atherosclerosis Risk in Communities Study identified 6959 HF hospitalizations from 2005-2011. Predictors of GDMT modification and survival were assessed using multivariable logistic regression and Cox proportional hazards models. RESULTS: For 5091 hospitalizations, patient mean age was 75 years, 53% were female, 69% were white, and 81% had acute decompensated heart failure (ADHF). Regarding ejection fraction (EF), 31% of patients had HF with reduced EF (HFrEF), 24% had HF with preserved EF (HFpEF), and 44% were missing EF values. At admission, 52% of patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), 66% ß-blockers (BBs), 9% aldosterone-receptor antagonists, 16% digoxin, 10% hydralazine, and 29% nitrates. Modification of GDMT occurred in up to 23% of hospitalizations. Significant predictors of GDMT initiation included ADHF and HFrEF; discontinuation of medications was observed with select comorbidities. In HFrEF, initiation of any GDMT was associated with reduced 1-year all-cause mortality (adjusted hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.71) as was initiation of ACEI/ARBs, BBs, and digoxin. Discontinuation of any therapy versus maintaining GDMT was associated with greater mortality (HR 1.30, 95% CI 1.02-1.66). Similar trends were observed in HFpEF. CONCLUSIONS: Our study suggests that GDMT initiation is associated with increased survival, and discontinuation of therapy is associated with reduced survival in hospitalized patients with HF. Future studies should be conducted to confirm the impact of GDMT therapy modification in this population.

PARADIGM-HF Trial: Secondary Analyses Address Unanswered Questions.

Our aim was to summarize published secondary analyses of the PARADIGM-HF trial. In the original trial, published in September 2014, sacubitril/valsartan significantly reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared to enalapril. This summary provides a resource for clinicians to review subsequent analyses of the landmark trial evaluating the benefit of sacubitril/valsartan in various subgroups and providing information regarding optimal use of this new therapy in the broader heart failure population. A full list of publications of the existing PARDADIGM-HF post hoc analyses was obtained and summarized, grouped by focus (e.g., severity of illness, tolerability). Twenty-six publications and one abstract analyzing the PARADIGM-HF trial were reviewed, summarizing the most important results that compared the benefits of sacubitril/valsartan to enalapril, including pertinent subgroup information from each analysis. Key publications evaluated the treatment effect of sacubitril/valsartan based on heart failure severity (i.e., ejection fraction or heart failure risk scores), impact on alternate outcomes, influence of additional therapies, tolerability in patients with comorbidities (i.e., diabetes), long-term benefits, and cost-effectiveness. In addition, nine ongoing phase III and phase IV clinical trials with sacubitril/valsartan were briefly summarized to address potential future uses in more extensive heart failure settings. The benefit of sacubitril/valsartan over enalapril for the primary endpoint in the PARADIGM-HF trial is maintained throughout numerous secondary analyses. Though the subgroups analyzed are based on participants from a single clinical trial, clinicians can more confidently incorporate this novel therapy into practice with expanded knowledge of these existing analyses as well as ongoing prospective trials.

Fibrinolytic and Anticoagulation Therapy in Patients Undergoing Ultrasound-Assisted Catheter-Directed Thrombolysis for Pulmonary Embolism.

BACKGROUND: Ultrasound-assisted, catheter-directed thrombolysis (UA-CDT) relieves right ventricular stress without a significant increase in the risk of bleeding compared to systemic thrombolysis. Although concomitant anticoagulation is provided to prevent thrombus expansion, the optimal anticoagulation regimen in patients receiving UA-CDT remains unknown. OBJECTIVE: We sought to describe anticoagulation practices for patients receiving UA-CDT. METHODS: Patients receiving UA-CDT for acute pulmonary embolism (PE) between Jan 1, 2013 to Sept 30, 2014 at a single center were analyzed. We collected patient characteristics, fibrinolytic and anticoagulant usage as well as clinical outcomes. RESULTS: Fourteen patients were included in the final analysis. The mean alteplase dose was 16.8 ± 5.6 mg and 24.3 ± 3.4 mg in unilateral and bilateral PE, respectively. Mean unfractionated heparin (UFH) rates were 7.4 (±2.17) IU/kg/hr and 12.4 (±3.1) IU/kg/hr during and after fibrinolytic therapy, respectively. The median aPTT was 42.4 sec [IQR 34.5-51.8] and 77.9 sec [IQR 66.5-96.8] during and after fibrinolytic therapy, respectively. There were no recurrent VTE within 30 days of hospital discharge. One patient had a major bleeding event (intracranial hemorrhage). CONCLUSION: In patients with acute PE, our institution utilized low levels of anticoagulation during fibrinolytic administration and therapeutic doses after completion of fibrinolytic infusion. Standardized protocols for anticoagulation during UA-CDT are warranted.

Contribution of medications and risk factors to QTc interval lengthening in the atherosclerosis risk in communities (ARIC) study.

RATIONALE, AIMS, AND OBJECTIVES: Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening. METHOD: The Atherosclerosis Risk in Communities study assessed 15 792 participants with a resting, standard 12-lead electrocardiogram and ≥1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we excluded participants with QRS ≥ 120 milliseconds (n = 2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36 602 person-visit observations for 14 160 cohort members controlling for age ≥ 65 years, female sex, left ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person. RESULTS: Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of risk factors, Known QTPMs and ≥2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ≥2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone. CONCLUSION: Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors.

Direct oral anticoagulants in patients with atrial fibrillation and renal impairment, extremes in weight, or advanced age.

A growing number of patients with an indication for stroke prevention in atrial fibrillation have kidney-, age-, or weight-related alterations in pharmacokinetics that affect dosing of direct oral anticoagulants. Because these patients were excluded from or comprised a small number of patients in clinical trials, there is a lack of evidence to guide clinicians. As a consequence, many patients do not receive oral anticoagulation despite a high risk for atrial fibrillation-related stroke. Here, we present a review of direct oral anticoagulant pharmacokinetics and a review of the available clinical evidence in patients with weight-, kidney-, and age-related disease.

Comparison of Ambulatory, High-Dose, Intravenous Diuretic Therapy to Standard Hospitalization and Diuretic Therapy for Treatment of Acute Decompensated Heart Failure.

Innovative treatment strategies for decompensated heart failure (HF) are required to achieve cost savings and improvements in outcomes. We developed a decision analytic model from a hospital perspective to compare 2 strategies for the treatment of decompensated HF, ambulatory diuretic infusion therapy, and hospitalization (standard care), with respect to total HF hospitalizations and costs. The ambulatory diuretic therapy strategy included outpatient treatment with high doses of intravenous loop diuretics in a specialized HF unit whereas standard care included hospitalization for intravenous loop diuretic therapy. Model probabilities were derived from the outcomes of patients who were treated for decompensated HF at Brigham and Women's Hospital (Boston, MA). Costs were based on Centers for Medicare and Medicaid reimbursement and the available reports. Based on a sample of patients treated at our institution, the ambulatory diuretic therapy strategy was estimated to achieve a significant reduction in total HF hospitalizations compared with standard care (relative reduction 58.3%). Under the base case assumptions, the total cost of the ambulatory diuretic therapy strategy was $6,078 per decompensation episode per 90 days compared with $12,175 per 90 days with standard care, for a savings of $6,097. The cost savings associated with the ambulatory diuretic strategy were robust against variation up to 50% in costs of ambulatory diuretic therapy and the likelihood of posttreatment hospitalization. An exploratory analysis suggests that ambulatory diuretic therapy is likely to remain cost saving over the long-term. In conclusion, this decision analytic model demonstrates that ambulatory diuretic therapy is likely to be cost saving compared with hospitalization for the treatment of decompensated HF from a hospital perspective. These results suggest that implementation of outpatient HF units that provide ambulatory diuretic therapy to well-selected subgroup of patients may result in significant reductions in health care costs while improving the care of patients across a variety of health care settings.

Regulatory, legislative, and policy updates with anticoagulant use.

Thromboembolism afflicts millions of patients annually in the United States and is associated with a significant cost burden. Recent advances in oral anticoagulation have provided clinicians with more options for management of these diseases. Accordingly, regulatory, legislative, and policy-making organizations have intervened with the aim of improving patient outcomes, ensuring patient safety, and reducing costs. There have been a number of recent developments in surveillance, litigation, and regulatory oversight that clinicians should recognize. In this review article we summarize key updates related to the management of anticoagulant therapy as it relates to thrombosis prevention and treatment.