Selatogrel: A Novel Subcutaneous P2Y12 Inhibitor.

ABSTRACT: The use of a P2Y12 inhibitor as a component of dual antiplatelet therapy in patients with an acute coronary syndrome (ACS) is well established. However, the P2Y12 inhibitors currently available have pharmacokinetic limitations due to delayed absorption, lack of enteral access for administration with oral formulations, need for intravenous access with cangrelor, or need for metabolization to be ideal in the critical 3-hour window during an ACS. Selatogrel is a novel, potent, reversible, and selective 2-phenylprimdine-4-carboxamide administered subcutaneously under development. Results from preclinical, phase 1, and phase 2 trials have confirmed that the agent provides sustained and reversible P2Y12 platelet inhibition with an acceptable safety profile. The most commonly reported adverse effects include minor bleeding and dyspnea. Phase 3 trials are being designed to understand the critical role this agent can play in upstream management of patients with ACS including a more defined understanding of the adverse effect profile, how to transition from this agent to an oral agent, who will be administering, and does this agent allow for a safe and quick transition to coronary artery bypass graft surgery if needed. Should it obtain approval, selatogrel has the potential to provide a unique and advantageous mechanism for P2Y12 inhibition.

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations.

There are currently more than 7 million patients taking a direct oral anticoagulant (DOAC), with more new prescriptions per year than warfarin. Despite impressive efficacy and safety data for the treatment of venous thromboembolism, patients with obesity or advanced renal impairment represented a small portion of the patients enrolled in the phase 3 clinical trials. Therefore, to evaluate the potential use of DOACs in these special populations, clinicians need to have an understanding of the pharmacokinetics and pharmacodynamics of these agents in these settings. Since data from randomized controlled trials are limited, data from observational trials are helpful in gaining comfort with the use of DOACs in these special populations. Selecting the appropriate dose for each agent is imperative in achieving optimal patient outcomes. We provide an extensive review of the pharmacokinetics, pharmacodynamics, phase 3 clinical trials, and observational studies on the use of DOACs in patients with advanced renal impairment, obesity, or other weight-related special populations to provide clinicians with a comprehensive understanding of the data for optimal drug and dose selection.

The PARTHENON Clinical Development Program: the Role of Ticagrelor in Patients with Atherothrombotic Disease.

Although the rate of cardiovascular disease (CVD)-related mortality has declined over the last decade, it is still the leading cause of mortality in the USA, accounting for over 1.4 million deaths annually. In addition, total direct (primarily hospital admissions) and indirect costs of CVD in the US is over $316 billion annually and is expected to grow to over $918 billion by 2030. Much of the etiology of CVD is due to atherosclerosis and its thrombotic complications, and central to this is the role of platelets. Atherosclerosis is a systemic disease, with meaningful morbidity and mortality when present in the coronary, cerebral, or major peripheral arteries. The recommended antiplatelet therapy differs based on the vascular bed impacted, with the optimal antiplatelet therapy yet to be defined. The PARTHENON program is a series of completed and ongoing phase III clinical trials investigating the efficacy and safety of ticagrelor in atherosclerotic CVD in comparison with established antiplatelet therapy or placebo. The overall aim of the program is to determine if more potent antiplatelet therapy, with different pharmacology, may reduce cardiovascular events in patients with atherosclerotic disease.

Management of Venous Thromboembolism: Recent Advances in Oral Anticoagulation Therapy.

OBJECTIVE: To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products. DATA SOURCES: Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information. STUDY SELECTION AND DATA EXTRACTION: Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions. DATA SYNTHESIS: The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy. CONCLUSIONS: The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.

Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

Impact of a high-fat meal on assessment of clopidogrel-induced platelet inhibition in healthy subjects.

BACKGROUND: Ideal conditions for platelet reactivity testing are critical for optimal selection of a P2Y12 inhibitor. Data are inconsistent regarding the impact of high-fat meals on test assessment. METHODS: Participants included 12 healthy subjects not taking antiplatelet drugs after a 12-hour fast. After baseline assessment, subjects were given a 600 mg dose of clopidogrel. Four hours later, maximum platelet inhibition was tested in the fasting state by light transmission aggregometry (LTA), VerifyNow P2Y12, vasodilator-stimulated phosphoprotein (VASP), and whole blood aggregometry (WBA). Subjects were then provided a high-fat meal, and platelet function was evaluated two hours later. Change in measured platelet aggregation by LTA was the primary endpoint of the study. The Wilcoxon Rank Sum test was used to compare the change in platelet reactivity between fasting and non-fasting conditions. The Spearman rho (ρ) correlation coefficient was used to evaluate the association between fasting platelet reactivity and the change following a high-fat meal. RESULTS: No significant change occurred in maximal light transmission, as assessed by LTA with 5 µM ADP (p = 0.15) and with 20 µM ADP (p = 0.07). There was a significant change in the area under the curve with 5 µM ADP (p = 0.03) but not with 20 µM ADP (p = 0.18). Although there was no significant change with the VerifyNow P2Y12 assay (p = 0.16), the change was correlated with the initial fasting value (Spearman's rho p = 0.008). The VASP assay and WBA varied minimally. CONCLUSION: The high-fat meal did not significantly alter platelet function assessment of commonly used platelet function tests. Greater intra-subject variability existed for the optically-dependent compared with non-optically dependent tests. TRIAL REGISTRATION: NCT01307657.

Prevalence of CYP2C19 variant alleles and pharmacodynamic variability of aspirin and clopidogrel in Native Americans.

BACKGROUND: The prevalence of variant alleles of the CYP2C19 gene has been determined for most population groups, but not Native Americans. Furthermore, the overall effectiveness of clopidogrel and aspirin has not been well studied in Native Americans, although this group has high mortality rates for cardiovascular disease and diabetes. METHODS: We recruited 50 volunteers from the Oglala Sioux Tribe with coronary artery disease taking aspirin and clopidogrel. Whole blood was collected for analysis using the VerifyNow P2Y12 and aspirin tests. Samples from the coronary artery disease patients and 50 additional tribal volunteers (n = 100 total) were genotyped for CYP2C19 variants *2, *3, and *17. RESULTS: The allele frequencies for CYP2C19*2 and CYP2C19*17 in the population group were 11% (95% CI 7%-16%) and 9% (95% CI 5%-13%), respectively. No subjects carried the CYP2C19*3 allele. The median PRU (P2Y12 reaction units) in the population group was 194 with wide variability (range 29-400). There was no significant effect of genotype on platelet aggregation as measured by the VerifyNow P2Y12 test (P = .77). The median ARU (aspirin reaction units) for the group was 437 (range 350-659), and 73% had aspirin reaction unit values <550. CONCLUSIONS: The prevalence of variant CYP2C19 alleles is low in Native Americans of the Oglala Sioux Tribe compared with certain HapMap populations. The variable response to aspirin and clopidogrel in the Oglala Sioux Tribe is consistent with reported values for other groups as measured by the VerifyNow assay (Accumetrics, San Diego, CA).

Statins role in the prevention and treatment of sepsis.

Sepsis is a complex disease with typically poor outcomes. While the onset of sepsis is typically infectious, the detrimental consequences follow pathogen toxin release that produces activation of numerous cytokines and a pro-inflammatory response. These same cytokines also stimulate activation of coagulation and inhibit natural fibrinolysis. Despite decades of research targeted against these pathways the development of sepsis and mortality in patients with sepsis remains high. While statins were developed for reducing cholesterol in patients with atherosclerotic disease, we now know they have a number of other properties which may be helpful in the prevention and treatment of sepsis. Statins have demonstrated the ability to reduce a number of pro-inflammatory cytokines known to be detrimental in the development and progression of sepsis. Statins have also demonstrated the ability to limit the coagulation response and promote fibrinolysis in the setting of sepsis. Based on these encouraging pharmacologic properties of statins a number of trials have been conducted evaluating the impact of statins on the prevention and treatment of sepsis. Most of the trials to date have been retrospective cohort trials, with very few prospective randomized trials. While some trials fail to demonstrate a benefit of statins, most trials suggest a reduction in the development of sepsis and/or other important sepsis related outcomes. While the laboratory and early clinical experience with statins are encouraging, randomized controlled trials will be need to fully define the role of statins in the prevention and treatment of sepsis.

Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta-analysis.

Previous meta-analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)-associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta-analysis on the effectiveness of AA versus PCC products for FXaI-associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn-Randomized Studies (MINORS) checklist and one question from the Joanna Briggs Institute (JBI) Critical Appraisal of Case Series tool to assess the risk of bias. Random-effects meta-analyses were performed to provide a pooled estimate for the effect of AA versus PCC products on hemostatic efficacy, in-hospital mortality, 30-day mortality, and thrombotic events. Low-moderate risk of bias studies were meta-analyzed separately, as well as combined with high risk of bias studies. Eighteen comparative evaluations of AA versus PCC were identified. Twenty-eight percent of the studies (n = 5) had low-moderate risk and 72% (n = 13) had a high risk of bias. Studies with low-moderate risk of bias suggested improvements in hemostatic efficacy [Odds Ratio (OR) 2.72 (95% Confidence Interval (CI): 1.15-6.44); one study], lower in-hospital mortality [OR 0.48 (95% CI: 0.38-0.61); three studies], and reduced 30-day mortality [OR 0.49 (95% CI: 0.30-0.80); two studies] when AA was used versus PCC products. When studies were included regardless of the risk of bias, pooled effects showed improvements in hemostatic efficacy [OR 1.36 (95% CI: 1.01-1.84); 12 studies] and reductions in 30-day mortality [OR 0.53 (95% CI: 0.37-0.76); six studies] for AA versus PCC. The difference in thrombotic events with AA versus PCC was not statistically significant in the low-moderate, high, or combined risk of bias groups. The evidence from low-moderate quality real-world studies suggests that AA is superior to PCC in enhancing hemostatic efficacy and reducing in-hospital and 30-day mortality. When studies are assessed regardless of the risk of bias, the pooled hemostatic efficacy and 30-day mortality risk remain significantly better with AA versus PCC.

Antithrombotic therapy with Transcatheter aortic valve replacement.

Aortic valve replacement is a necessary management strategy for patients with severe aortic stenosis. The use of transaortic valve replacement (TAVR) has increased significantly over the last decade and now exceeds traditional surgical aortic valve replacement. Since the valve systems used in TAVR consist of bioprosthetic valve tissue encased in a metal stent frame, antithrombotic therapy recommendations cannot be extrapolated from prior data with differently constructed surgical bioprosthetic or mechanical valves. Data on the use of antithrombotic therapy with TAVR are a rapidly developing area of medicine. Choice of agents depends on several patient factors. Patients undergoing TAVR also have a relatively high incidence of subclinical valve thrombosis. The clinical impact of this phenomenon and the implications for antithrombotic therapy continue to evolve. It is critical for clinicians who treat patients undergoing TAVR to have a firm understanding of practice guidelines, the evolving evidence, and its implications for the use of antithrombotic therapy in these patients.

Prospective Observational Evaluation of Predatory Journals in Critical Care Pharmacy Practice: Defining Characteristics Associated With Receiving Unsolicited Invitations to Publish.

Open-access publishing promotes accessibility to scholarly research at no cost to the reader. The emergence of predatory publishers, which exploit the author-pay model by charging substantial publication fees for publication in journals with questionable publishing processes, is on the rise. Authors are solicited through aggressive marketing tactics, though who is targeted is not well described. The purpose of this study was to identify characteristics associated with critical care pharmacists that make them targets of unsolicited invitations to publish. A prospective, observational study of critical care pharmacists was performed. Participants archived emails received by their professional email that were unsolicited invitations to submit their original work for publication in a journal (unsolicited journals). Variables were evaluated to determine which were associated with unsolicited invitations; these were compared to legitimate journals, defined as all PubMed-indexed journals in which the participants were previously published. Twenty-three pharmacist participants were included, all of whom were residency and/or fellowship trained and practicing in an academic medical center. Participants had a median of 7 years of experience since their post-graduate training, 6 years since their last change in professional email address, and 2 years since their first PubMed-indexed publication. From these participants, 136 unsolicited and 59 legitimate journals were included. The average number of invitations increased 1.04 (95% CI, 1.02-1.05) times for every additional PubMed-indexed publication (P < .001). Most unsolicited journals were considered predatory. Legitimate and unsolicited journals differed significantly. The number of previous PubMed-indexed publications strongly correlates with the likelihood of critical care pharmacists receiving unsolicited publication invitations, often from predatory journal.

Lower mortality with andexanet alfa vs 4-factor prothrombin complex concentrate for factor Xa inhibitor-related major bleeding in a U.S. hospital-based observational study.

Background: Well-designed studies with sufficient sample size comparing andexanet alfa vs 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice to evaluate clinical outcomes are limited. Objectives: To compare in-hospital mortality in patients hospitalized with rivaroxaban- or apixaban-related major bleeding who were treated with andexanet alfa or 4F-PCC. Methods: An observational cohort study (ClinicalTrials.gov identifier: NCT05548777) was conducted using electronic health records between May 2018 and September 2022 from 354 U.S. hospitals. Inclusion criteria were age ≥18 years, inpatient admission with diagnosis code D68.32 (bleeding due to extrinsic anticoagulation), a record of use of the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa or 4F-PCC treatment during index hospitalization, and a documented discharge disposition. Multivariable logistic regression on in-hospital mortality with andexanet alfa vs 4F-PCC was performed. The robustness of the results was assessed via a supportive propensity score-weighted logistic regression. Results: The analysis included 4395 patients (andexanet alfa, n = 2122; 4F-PCC, n = 2273). There were 1328 patients with intracranial hemorrhage (ICH), 2567 with gastrointestinal (GI) bleeds, and 500 with critical compartment or other bleed types. In the multivariable analysis, odds of in-hospital mortality were 50% lower for andexanet alfa vs 4F-PCC (odds ratio [OR], 0.50; 95% CI, 0.39-0.65; P < .01) and were consistent for both ICH (OR, 0.55; [0.39-0.76]; P < .01) and GI bleeds (OR, 0.49 [0.29-0.81]; P = .01). Similar results were obtained from the supporting propensity score-weighted logistic regression analyses. Conclusion: In this large observational study, treatment with andexanet alfa in patients hospitalized with rivaroxaban- or apixaban-related major bleeds was associated with 50% lower odds of in-hospital mortality than 4F-PCC. The magnitude of the risk reduction was similar in ICH and GI bleeds.

When a Pharmacist Health Assessment Simulation Becomes a Real Patient-Provider Experience.

This commentary presents two simulated pharmacist training events during which concerning medical issues were discovered. The simulation exercises, the pharmacist's responsibility in those exercises, and the need to plan for unexpected findings when conducting simulation events are discussed.

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Real-world management of oral factor Xa inhibitor-related bleeds with reversal or replacement agents including andexanet alfa and four-factor prothrombin complex concentrate: a multicenter study.

Aim: We describe the real-world utilization and outcomes associated with managing oral factor Xa inhibitor (FXai)-related major bleeds. Materials & methods: Electronic records from 45 US hospitals were queried (ICD-10-CM billing codes D68.32, T45.515x or T45.525x) to identify major bleed hospitalizations related to FXai use. Patient demographics, bleed type (intracranial hemorrhage, gastrointestinal, critical compartment, traumatic, other), FXai taken, reversal or replacement agents administered (including andexanet alfa, four-factor prothrombin complex concentrate, fresh frozen plasma, others), in-hospital mortality and length of stay were recorded. Results: Of 3030 FXai-related hospitalizations for major bleeds, patients averaged 68 years old and 47% were women. In-hospital mortality was highest for intracranial hemorrhage (23%, n = 507) and lowest for gastrointestinal bleeds (4%, n = 1453). In-hospital mortality was lowest (4%) for bleeds managed with andexanet alfa (n = 342), compared with 10% for four-factor prothrombin complex concentrate (n = 733), 11% for fresh frozen plasma (n = 925) and 8% for both other agents (n = 794) and no agents (n = 438). Median length of stay was 5 days across all agents, while ICU length of stay was shorter andexanet alfa (2 days) compared with other agents (3 days). Conclusion: In-hospital mortality differed by bleed type and agents administered. Andexanet alfa was associated with the lowest rate of in-hospital mortality across all bleed types.

Coagulopathy, Venous Thromboembolism, and Anticoagulation in Patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic, and patients with the infection are referred to as having COVID-19. Although COVID-19 is commonly considered a respiratory disease, there is clearly a thrombotic potential that was not expected. The pathophysiology of the disease and subsequent coagulopathy produce an inflammatory, hypercoagulable, and hypofibrinolytic state. Several observational studies have demonstrated surprisingly high rates of venous thromboembolism (VTE) in both general ward and intensive care patients with COVID-19. Many of these observational studies demonstrate high rates of VTE despite patients being on standard, or even higher intensity, pharmacologic VTE prophylaxis. Fibrinolytic therapy has also been used in patients with acute respiratory distress syndrome. Unfortunately, high quality randomized controlled trials are lacking. A literature search was performed to provide the most up-to-date information on the pathophysiology, coagulopathy, risk of VTE, and prevention and treatment of VTE in patients with COVID-19. These topics are reviewed in detail, along with practical issues of anticoagulant selection and duration. Although many international organizations have produced guidelines or consensus statements, they do not all cover the same issues regarding anticoagulant therapy for patients with COVID-19, and they do not all agree. These statements and the most recent literature are combined into a list of clinical considerations that clinicians can use for the prevention and treatment of VTE in patients with COVID-19.

Dual Antiplatelet Therapy for Long-term Secondary Prevention of Atherosclerotic Cardiovascular Events.

PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is currently recommended to prevent further ischemic events after percutaneous coronary intervention and acute coronary syndrome (ACS). Guidelines currently recommend a minimum of 6 months after elective drug-eluting stent placement and at least 12 months of DAPT after ACS; however, the benefits of prolonged treatment are unclear. The purpose of this review was to conduct a detailed examination of the data refuting or supporting the use of DAPT beyond 1 year in patients with ACS and in patients receiving percutaneous coronary intervention with stenting. METHODS: A search of PubMed was performed to identify articles published in the last 20 years that addressed the role of DAPT beyond 12 months' duration. FINDINGS: A number of studies have shown ischemic benefits associated with prolonging DAPT beyond 12 months, but this finding is dependent on the patient population studied and the quality of the study design. Many studies also show that longer duration therapy has been associated with increased bleeding risk. In patients with previous myocardial infarction completing at least 1 year of DAPT, continuing DAPT with a reduced dose of ticagrelor 60 mg BID is a regimen to be considered for these patients; in general ACS patients, a reduced dose of 60 mg BID of ticagrelor after the first year of DAPT should be considered; and in the post-percutaneous coronary intervention patients, DAPT beyond 1 year should be considered after careful evaluation of the patient's thrombotic and bleeding risks. IMPLICATIONS: The duration of DAPT, and the choice of P2Y12 inhibitor, should be tailored to the individual patient. To optimize patient outcomes, the benefits and risks associated with prolonging DAPT need to be evaluated, considering comorbidities and the presence of bleeding and ischemic risk factors. Despite some limitations, risk scores, such as the DAPT score, are available to help guide decisions for the best approach for each patient.

The Impact of Eliminating Backward Navigation on Computerized Examination Scores and Completion Time.

Objective. To determine whether elimination of backward navigation during an examination resulted in changes in examination score or time to complete the examination.Methods. Student performance on six examinations in which backward navigation was eliminated was compared to performance on examinations administered to pharmacy students the previous year when backwards navigation was allowed. The primary comparison of interest was change in student performance on a subset of identical questions included on both examinations. Secondary outcomes included change in total examination score and completion time.Results. No significant reduction in examination scores was observed as a result of eliminating backward navigation. The average time that students spent on a question was significantly reduced on two of the six examinations.Conclusion. Restricting pharmacy students' ability to revisit questions previously answered (elimination of backward navigation) on an examination had no adverse effect on scores or testing time when assessed across three years of the didactic pharmacy curriculum.

Betrixaban: Safely Reducing Venous Thromboembolic Events with Extended Prophylaxis.

Although venous thromboembolism prophylaxis of acute medically ill patients is commonly employed, a percentage of high-risk patients still have venous thromboembolic events within 30 days of discharge. Research over the last several years has attempted to identify characteristics of these high-risk patients to facilitate provision of extended prophylaxis and venous thromboembolic event reduction; however, extended prophylaxis has been associated with a significant increase in the risk for major bleeding until recently. Betrixaban, a new oral direct Xa inhibitor with once-daily dosing and limited renal elimination, significantly reduces the risk of venous thromboembolism without increasing the risk for major bleeding. Consequently, betrixaban is the only anticoagulant approved by the Food and Drug Administration for preventing venous thromboembolism with extended prophylaxis in acute medically ill patients.