Trends in Oral Anticoagulant Use and Individual Expenditures Across the United States from 2014 to 2020.

BACKGROUND: Landmark clinical trials have expended the indications for the direct oral anticoagulants (DOACs), but contemporary data on usage and expenditure patterns are lacking. OBJECTIVE: This study aimed to assess annual trends in oral anticoagulant (OAC) utilization and expenditure across the United States (US) from 2014 to 2020. METHODS: We utilized the Medical Expenditure Panel Survey (MEPS) to study the trends of use and expenditures of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban between 2014 and 2020 in the US. Survey respondents reported OAC use within the past year, which was verified against pharmacy records. Payment information was obtained from the respondent's pharmacy and was categorized as third-party or self/out-of-pocket. Potential indications and medical conditions of interest for OAC therapy were identified from respondent-reported medical conditions. We estimated the national number of OAC users and total expenditures across age, sex, race, ethnicity, insurance, and medical condition subgroups. Trends of OAC users' characteristics, expenditure, and number of prescriptions were evaluated using the Mann-Kendall test for trends. RESULTS: Between 2014 and 2020, the number of warfarin users decreased from 3.8 million (70% of all OAC users) to 2.2 million (p = 0.007) [29% of all OAC users], while the number of DOAC users increased from 1.6 million (30% of all OAC users) to 5.4 million (p = 0.003) [70% of all OAC users]. The total expenditure of OACs in the US increased from $3.4 billion in 2014 to $17.8 billion in 2020 (p = 0.003), which was driven by the increase in DOAC expenditures (p = 0.003). CONCLUSIONS: DOACs have replaced warfarin as the preferred OAC in the US. The increased costs associated with DOAC use may decline when generic formulations are approved.

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Management of direct oral anticoagulant drug interactions in hospitalized patients.

Moderate-strong CYP3A4 or Pgp inhibitors and inducers alter direct oral anticoagulant (DOAC) pharmacokinetics. Whether the presence of a DOAC drug-drug interaction (DDI) prompts in- hospital changes in management remains unknown. We identified all hospitalized patients at our institution who were admitted with a clinically relevant DOAC DDI from 01/2021 to 06/2021. Clinically relevant DOAC DDIs were defined as those listed in the prescribing information or FDA CYP3A4/Pgp inhibitors clinical indexes. We assessed the prevalence of DOAC DDIs and categorized their management as: drug stopped, drug held, or drug continued. For drugs that were continued we assessed whether the dose of the DOAC or interacting drug was increased, decreased or unchanged during the admission. We ascertained the number of DOAC DDIs that prompted an automated prescribing alert in our electronic health record (EHR). Finally, we conducted a logistic regression model to compare users of DOACs with DDI who had their regimen adjusted versus those without adjustments, focusing on outcomes of rehospitalization and death, adjusting for age and gender. Among 3,725 hospitalizations with a DOAC admission order, 197 (5%) had a clinically relevant DOAC DDI. The DOAC and the interacting drug were continued at discharge for 124 (63%) hospitalizations. The most frequent adjustments were stopping the interacting drug (73%) and stopping the DOAC (15%). Only 7 (4%) of DOAC DDIs prompted an EHR alert. The adjusted odds ratios for rehospitalizations and death, respectively, among patients whose regimens were adjusted compared to those whose were not, were 1.29 (95% CI, 0.67 to 2.48; P = 0.44) and 1.88 (95% CI, 0.91 to 3.89; P = 0.09). Clinically relevant DDIs with DOACs occur infrequently among hospitalized patients and usually are managed without stopping the DOAC. The clinical impact of such DDIs and subsequent adjustments on thrombotic and hemorrhagic outcomes requires further investigation.

Current Gaps in the Provision of Safe and Effective Anticoagulation in Atrial Fibrillation and the Potential for Factor XI-Directed Therapeutics.

The global prevalence of atrial fibrillation is rapidly increasing, in large part due to the aging of the population. Atrial fibrillation is known to increase the risk of thromboembolic stroke by five times, but it has been evident for decades that well-managed anticoagulation therapy can greatly attenuate this risk. Despite advances in pharmacology (such as the shift from vitamin K antagonists to direct oral anticoagulants) that have increased the safety and convenience of chronic oral anticoagulation in atrial fibrillation, a preponderance of recent observational data indicates that protection from stroke is poorly achieved on a population basis. This outcomes deficit is multifactorial in origin, stemming from a combination of underprescribing of anticoagulants (often as a result of bleeding concerns by prescribers), limitations of the drugs themselves (drug-drug interactions, bioaccumulation in renal insufficiency, short half-lives that result in lapses in therapeutic effect, etc.), and suboptimal patient adherence that results from lack of understanding/education, polypharmacy, fear of bleeding, forgetfulness, and socioeconomic barriers, among other obstacles. Often this adherence is not reported to treating clinicians, further subverting efforts to optimize care. A multidisciplinary, interprofessional panel of clinicians met during the 2023 International Society of Thrombosis and Haemostasis Congress to discuss these gaps in therapy, how they can be more readily recognized, and the potential for Factor XI-directed anticoagulants to improve the safety and efficacy of stroke prevention. A full appreciation of this potential requires a re-evaluation of traditional teaching about the "coagulation cascade" and decoupling the processes that result in (physiologic) hemostasis and (pathologic) thrombosis. The panel discussion is summarized and presented here.

When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review.

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.

Comprehensive Pharmacist-led Transitions-of-care Medication Management around Hospital Discharge Adds Modest Cost Relative to Usual Care: Time-and-Motion Cost Analysis.

Optimal medication management is important during hospitalization and at discharge because post-discharge adverse drug events (ADEs) are common, often preventable, and contribute to patient harms, healthcare utilization, and costs. Conduct a cost analysis of a comprehensive pharmacist-led transitions-of-care medication management intervention for older adults during and after hospital discharge. Twelve intervention components addressed medication reconciliation, medication review, and medication adherence. Trained, experienced pharmacists delivered the intervention to older adults with chronic comorbidities at 2 large U.S. academic centers. To quantify and categorize time spent on the intervention, we conducted a time-and-motion analysis of study pharmacists over 36 sequential workdays (14 519 min) involving 117 patients. For 40 patients' hospitalizations, we observed all intervention activities. We used the median minutes spent and pharmacist wages nationally to calculate cost per hospitalization (2020 U.S. dollars) from the hospital perspective, relative to usual care. Pharmacists spent a median of 66.9 min per hospitalization (interquartile range 46.1-90.1), equating to $101 ($86 to $116 in sensitivity analyses). In unadjusted analyses, study site was associated with time spent (medians 111 and 51.8 min) while patient primary language, discharge disposition, number of outpatient medications, and patient age were not. In this cost analysis, comprehensive medication management around discharge cost about $101 per hospitalization, with variation across sites. This cost is at least an order of magnitude less than published costs associated with ADEs, hospital readmissions, or other interventions designed to reduce readmissions. Work is ongoing to assess the current intervention's effectiveness.

Major cardiovascular events after COVID-19, event rates post-vaccination, antiviral or anti-inflammatory therapy, and temporal trends: Rationale and methodology of the CORONA-VTE-Network study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and thrombotic events in the early post-infection period and during convalescence. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied. METHODS: Adult patients, aged ≥18 years, with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at the participating centers of the registry are eligible for inclusion. A total of 10,000 patients have been included in this multicenter study, with Brigham and Women's Hospital (Boston, MA) serving as the coordinating center. Other sites include Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System. Data elements will be ascertained manually for accuracy. The two main outcomes are 1) a composite of venous or arterial thrombotic events, and 2) a composite of major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Clinical outcomes are adjudicated by independent physicians. Vaccination status and time of inclusion in the study will be ascertained for subgroup-specific analyses. Outcomes are pre-specified to be reported separately for hospitalized patients versus those who were initially receiving outpatient care. Outcomes will be reported at 30-day and 90-day follow-up. Data cleaning at the sites and the data coordinating center and outcomes adjudication process are in-progress. CONCLUSIONS: The CORONA-VTE-Network study will share contemporary information related to rates of cardiovascular and thrombotic events in patients with COVID-19 overall, as well as within key subgroups, including by time of inclusion, vaccination status, patients undergoing hemodialysis, the elderly, and sex-informed analyses such as comparison of women and men, or among pregnant and breastfeeding women.

Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients Across Two Time Periods.

PURPOSE: Anticoagulants often cause adverse drug events (ADEs), comprised of medication errors and adverse drug reactions, in patients. Our study objective was to determine the clinical characteristics, types, severity, cause, and outcomes of anticoagulation-associated ADEs from 2015-2020 (a contemporary period following implementation of an electronic health record, infusion device technology, and anticoagulant dosing nomograms) and to compare them with those of a historical period (2004-2009). METHODS: We reviewed all anticoagulant-associated ADEs reported as part of our hospital-wide safety system. Reviewers classified type, severity, root cause, and outcomes for each ADE according to standard definitions. Reviewers also assessed events for patient harm. Patients were followed up to 30 days after the event. RESULTS: Despite implementation of enhanced patient safety technology and procedure, ADEs increased in the contemporary period. In the contemporary period, we found 925 patients who had 984 anticoagulation-associated ADEs, including 811 isolated medication errors (82.4%); 13 isolated adverse drug reactions (1.4%); and 160 combined medication errors, adverse drug reactions, or both (16.2%). Unfractionated heparin was the most frequent ADE-related anticoagulant (77.7%, contemporary period vs 58.3%, historical period). The most frequent anticoagulation-associated medication error in the contemporary period was wrong rate or frequency of administration (26.1%, n = 253), with the most frequent root cause being prescribing errors (21.3%, n = 207). The type, root cause, and harm from ADEs were similar between periods. CONCLUSIONS: We found that anticoagulation-associated ADEs occurred despite advances in patient safety technologies and practices. Events were common, suggesting marginal improvements in anticoagulant safety over time and ample opportunities for improvement.

Effects of Intensive Systolic Blood Pressure Lowering on End-Stage Kidney Disease and Kidney Function Decline in Adults With Type 2 Diabetes Mellitus and Cardiovascular Risk Factors: A Post Hoc Analysis of ACCORD-BP and SPRINT.

OBJECTIVE: To determine the effects of intensive systolic blood pressure (SBP) lowering on the risk of major adverse kidney outcomes in people with type 2 diabetes mellitus (T2DM) and/or prediabetes and cardiovascular risk factors. RESEARCH DESIGN AND METHODS: This post hoc ACCORD-BP subgroup analysis included participants in the standard glucose-lowering arm with cardiovascular risk factors required for SPRINT eligibility. Cox proportional hazards regression models compared the hazard for the composite of dialysis, kidney transplant, sustained estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, serum creatinine >3.3 mg/dL, or a sustained eGFR decline ≥57% between the intensive (<120 mmHg) and standard (<140 mmHg) SBP-lowering arms. RESULTS: The study cohort included 1,966 SPRINT-eligible ACCORD-BP participants (40% women) with a mean age of 63 years. The mean SBP achieved after randomization was 120 ± 14 and 134 ± 15 mmHg in the intensive and standard arms, respectively. The kidney composite outcome occurred at a rate of 9.5 and 7.2 events per 1,000 person-years in the intensive and standard BP arms (hazard ratio [HR] 1.35 [95% CI 0.85-2.14]; P = 0.20). Intensive SBP lowering did not affect the risk of moderately (HR 0.96 [95% CI 0.76-1.20]) or severely (HR 0.92 [95% CI 0.66-1.28]) increased albuminuria. Including SPRINT participants with prediabetes in the cohort did not change the overall results. CONCLUSIONS: This post hoc subgroup analysis suggests that intensive SBP lowering does not increase the risk of major adverse kidney events in individuals with T2DM and cardiovascular risk factors.

Non-Sterile to Sterile Compounding: An Unconventional Response During the COVID-19 Pandemic.

The drug supply chain has suffered many interruptions over the past decade. The COVID-19 pandemic exacerbated an already fragile infrastructure for supplying critical medications to hospitals and health-systems. The purpose of this paper is to provide insight to the history, thought-processes, and response to critical medication shortages during the COVID-19 pandemic, with a focus on hydromorphone infusions and the action steps taken to engage in non-sterile to sterile (NSTS) compounding. Over a period of 6 weeks, we compounded 1,613 NSTS hydromorphone infusion bags. All lots were cleared for sterility, particulate, potency, and endotoxin testing by an outside FDA registered laboratory. We did not have any safety reports filed specific to the NSTS compounded hydromorphone infusion bags. Over a period of 15 weeks, 715 infusions were consumed. The drug supply chain suffers frequent interruptions and critical shortages, particularly in times of a natural disaster or a global pandemic. Non-sterile to sterile compounding is often associated with risks of inaccuracies, impurities, and contamination. There are instances in which non-sterile to sterile compounding is appropriate and should be considered in times of drug shortages to support the care of hospitalized patients.

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.

Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants: A Review.

Importance: Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs. Observations: Among 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities. Conclusions and Relevance: Dose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

Optimization of DOAC management services in a centralized anticoagulation clinic.

Background: In 2017, the Brigham and Women's Hospital Anticoagulation Management Service (BWH AMS) expanded services to patients on direct oral anticoagulants (DOACs). We have since updated our DOAC management plan and adjusted the workflow of our clinic. Objectives: This report describes how our DOAC management has evolved and describes key interventions made. Additionally, we report on the results of a survey completed by referring physicians that assessed perspectives regarding centralized DOAC management by BWH AMS pharmacists. Methods: An analysis was completed of all patients referred to the BWH AMS and the number of interventions completed and documented in our anticoagulation management software. A survey with eight questions was sent to 110 referring physicians (selected based on referring to the AMS within the past 1.5 years). Results: Over 4 years, 1622 patients on DOACs were referred to the BWH AMS, amounting to 3154 DOAC encounters. A total of 212 interventions for medication procurement, 171 dose adjustment interventions, and 603 coordinated procedure plans were completed. Of the 32 physicians who responded to the survey, many believed that the quality and safety of anticoagulation therapy was improved with BWH AMS management. Despite provider satisfaction with pharmacist-led care in DOACs, physicians expressed concerns regarding the lack of provider awareness of the clinic and possible duplicative efforts. Conclusion: We plan to evolve the DOAC clinic model to optimize its clinical and operational value and to improve our delivery of care using electronic tools to move toward a population management approach for DOAC management.

Implementation of Pharmacy Executive Quality and Safety Walkrounds at a Tertiary Academic Medical Center.

Background: Executive Quality and Safety WalkRounds (EWRs) is a tool that engages department leadership in discussion with the front-line employees to solicit feedback to improve quality and safety. The purpose of this study was to evaluate the impact of the implementation of pharmacy department specific EWRs on quality and safety at a tertiary academic medical center. Method: This was a single-center, retrospective analysis conducted at Brigham and Women's Hospital between November 2016 and November 2019. This study aimed to analyze the implementation of EWRs conducted every other month throughout various service areas and satellites of the pharmacy department. Data evaluated included the number of EWRs conducted, the specific areas visited, the total number of action items recommended by the staff, along with the total number of action items that were completed or remained in process. Results: During the study period, 17 visits were completed in 12 different BWH pharmacy sub-departments. A total of 98 operational, technological, and environmental action items were recommended by staff to improve quality and safety. Of the 98 action items documented, 95 (96.9%) were completed by time of our analysis. Conclusion: Pharmacy department EWRs are an important and systematic process of communication between the pharmacy leadership and frontline staff. Pharmacy department EWRs have resulted in safety and quality improvements at different levels in the pharmacy department. The EWRs program at the pharmacy department was effective in identifying and completing safety initiatives to improve the safety culture of the department.

Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US.

AIM: To conduct a cost-effectiveness analysis (CEA) on the use of andexanet alfa for the treatment of factor Xa inhibitor-related intracranial hemorrhage (ICH) from the US third-party payer and societal perspectives. METHODS: CEA compared andexanet alfa to prothrombin complex concentrate for the treatment of patients receiving factor Xa inhibitors admitted to hospital inpatient care with an ICH. The model comprised two linked phases. Phase 1 utilized a decision tree to model the acute treatment phase (admission of a patient with ICH into intensive care for the first 30 days). Phase 2 modeled long-term costs and outcomes using three linked Markov models comprising the six health states defined by the modified Rankin score. RESULTS: The analysis showed that the strategy of using andexanet alfa for the treatment of factor Xa inhibitor-related ICH is cost-effective, with incremental cost-effectiveness per quality-adjusted life-year gained of $35,872 from a third-party payer perspective and $40,997 from a societal perspective over 20 years. LIMITATIONS: (1) Absence of head-to-head trials comparing therapies included in the economic model, (2) lack of comparative long-term data on treatment efficacy, and (3) bias resulting from the study designs of published literature. CONCLUSION: Given these results, the use of andexanet alfa for the reversal of anticoagulation in patients with factor Xa inhibitor-related ICH may improve quality of life and is likely to be cost-effective in a US context.

Characteristics of the ideal clinical pharmacy residency candidate: A survey of residency program directors and preceptors in Saudi Arabia.

OBJECTIVE: Residency positions are highly competitive. Pharmacy students who are familiar with the ideal qualities of residency candidates and the expectations of residency programs may be more likely to obtain one of these coveted positions. This study identifies the characteristics that residency program directors (RPDs) and preceptors use to define an ideal residency candidate. METHODS: This is a cross-sectional, descriptive study that surveyed pharmacy RPDs and preceptors across the Kingdom of Saudi Arabia. The questionnaires are comprised of two sections: demographic information and characteristics of the residency candidates. Over a five-month period (May 1, 2020 - September 30, 2020), the survey was sent electronically to the participants. RESULTS: Of the 78 surveys returned, 68 surveys were included (RPDs: 36, Preceptors: 32) and 12 surveys (15.17%) were excluded due to incompleteness. Number of RPDs responded to the survey represents (65%) of the total RPDs in Saudi Arabia. The mean response scores from the results of the Likert scale [strongly agree (1) - strongly disagree (5)] - suggest that a candidate's performance during the interview (mean score = 1.5), their professional appearance (1.5), an alignment between a candidate's interests and the program focus (1.6), and previous hospital experience (1.8) mattered most. While being from the same region (3.4), having an advanced degree (2.8) and the cumulative Grade Point Average (2.7) mattered the least. We find that previous hospital experience (29%), familiarity with the program (16%), research experience (15%), Saudi Commission for Health Specialists aggregate score (10%), and letters of recommendation (4%) are considered the top five factors. CONCLUSION: Residency candidates should focus on training in clinical settings. Offering mock interviews and Saudi Pharmacist Licensure Examination practice tests and involving pharmacy students in clinical research may increase their chance in securing a residency position.

Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in Patients with Provoked Venous Thromboembolism and Enduring Risk Factors: Rationale and Design of the HI-PRO Trial.

Patients with acute venous thromboembolism (VTE) in the setting of transient provoking factors are typically treated with short-term anticoagulation. However, the risk of recurrence may be increased in the presence of enduring risk factors. In such patients, the optimal duration of treatment remains uncertain. HI-PRO is a single-center, double-blind randomized trial. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) following a major provoking factor, including major surgery or major trauma, who completed at least 3 months of standard-dose therapeutic anticoagulation and have at least one enduring risk factor (such as obesity or heart failure) will be considered for inclusion. Patients will be randomized to apixaban 2.5 mg twice daily or placebo for 12 months. The primary efficacy outcome will be symptomatic recurrent VTE-a composite of DVT and/or PE at 12 months after randomization. Secondary efficacy outcomes include a composite of death due to cardiovascular causes, nonfatal myocardial infarction, stroke or systemic embolism, major adverse limb events, or coronary or peripheral ischemia requiring revascularization at 12 months, and individual components of these outcomes. The primary safety outcome is major bleeding according to the International Society on Thrombosis and Haemostasis definition. The study plans to enroll 600 patients (300 per arm) to have 80% power for detecting a 75% relative risk reduction in the primary outcome. Active recruitment began in March 2021. HI-PRO will provide clinically meaningful data on whether patients with provoked VTE and enduring risk factors have fewer adverse clinical outcomes if prescribed low-intensity extended-duration anticoagulation.

Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.

Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review.

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.

Stability of alteplase for ultrasound-facilitated catheter-directed thrombolysis.

Ultrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the risk of bleeding that accompanies systemic administration of higher alteplase doses. Some studies suggest that alteplase given over 2 to 6 hours is safe and effective, but there are few data to support the stability of alteplase under these conditions. Therefore, we undertook this in vitro study to determine the duration of alteplase stability. Alteplase was prepared in solutions of 8 mg in 100 mL, 6 mg in 150 mL, and 8 mg in 200 mL. Solutions were administered through the EkoSonic Endovascular System (with and without ultrasound) to simulate administration over 2, 4, and 6 hours. Alteplase was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). Assays were performed at time 0 and at 30-minute intervals during simulated infusion. An enzyme-linked immunosorbent assay was used to measure alteplase concentrations at time 0 and at 15-minute intervals during simulated infusion. By using RP-HPLC in the absence of ultrasound, the alteplase concentration remained within 1% of the original concentration through 120, 240, and 360 minutes of infusion. By using RP-HPLC for measurement, alteplase in the presence of ultrasound degraded steadily over time to ∼90% of its original amount in 120 minutes, ∼80% in 240 minutes, and ∼70% in 360 minutes. The remaining alteplase was available for enzymatic activity. Alteplase solutions of 0.04 and 0.08 mg/mL degraded steadily over time during simulated ultrasound-facilitated catheter-directed administration. Alteplase that did not degrade remained available for enzymatic activity.