Critical appraisal of dabigatran in the treatment of deep vein thrombosis and pulmonary embolism

Objective To compare the safety and efficacy of dabigatran to warfarin for the treatment of deep vein thrombosis and pulmonary embolism. Background Venous thromboembolism (VTE) is a disease comprised of two conditions: deep vein thrombosis and pulmonary embolism. VTE is a major cause of morbidity and mortality worldwide with an annual incidence estimated at 1–3 cases per 1,000 individuals. This incidence increases with age from 0.1 per 1,000 in adolescence to eight per 1,000 in those 80 years of age and older. As the proportion of patients 65 years of age and older expands, the number of patients presenting with VTE will also increase. Anticoagulation remains the cornerstone of VTE treatment. Traditionally, vitamin K antagonists have been used to minimize the risk of thrombus extension and for secondary prevention. Unpredictable pharmacokinetics and pharmacodynamics, routine monitoring, drug–food and drug–drug interactions, and potentially severe adverse events have all been cited as barriers to optimal care. Dabigatran has been proposed as a suitable alternative to warfarin therapy in the treatment of VTE. Therefore, a critical appraisal of dabigatran’s safety and efficacy is necessary to determine its role in therapy. Conclusion Dabigatran remains an alternative to warfarin therapy for the treatment of VTE. However, dabigatran also has distinct disadvantages that warrant consideration. Clinicians must ensure that drug characteristics align with patient characteristics to optimize patient outcomes

Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction

Background Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF. Aims To measure echocardio-Doppler-derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF. Methods We selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO2)]. We measured the transmitral E and A flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E′ velocity. We also indexed the E′ to the DT, as additional measure of impaired relaxation (E′DT), and calculated the diastolic functional reserve index (DFRI), as the product of E′ at rest and change in E′ with exercise. Results E′ velocity, at rest and peak exercise, as well as the DFRI positively correlated with peak VO2, whereas DT, E′DT, and E/E′ with exercise inversely correlated with peak VO2. Of note, the E′DT at rest also significantly predicted E′ velocity at peak exercise (R = +0.81, P \u3c 0.001). Exercise E′ was the only independent predictor of peak VO2 at multivariable analysis (R = +0.67, P = 0.005). Conclusions The E′ velocity at peak exercise is a strong and independent predictor of aerobic exercise capacity as measured by peak VO2 in patients with HFpEF, providing the link between abnormal myocardial relaxation with exercise and impaired aerobic exercise capacity in HFpEF

RAM$mart Financial Wellness for Health Profession Students

College students today are graduating with more debt than ever before. As such, it is critical that our graduates are equipped with the right skills and frame of mind to manage their finances. This includes understanding their income, taxes, and expenses; managing debt; budgeting; saving; and retirement planning. Money management can be intimidating for anyone, regardless of background or education. While online resources are made available to our students, these resources are often overlooked, and do not necessarily set out to engage students or address the issues they may face in a convincing or compelling way. Most of the financial resources easily accessible on the web and on VCU’s sites are intended for undergraduate students. However, graduate students and in particular students in the health sciences professional programs (medicine, dentistry, pharmacy) can accrue a tremendous amount of debt, but are not exposed to as many mandatory or voluntary budgeting and financial resources. The RAM$mart Financial Wellness Program is a set of online modules that will allow students the opportunity to learn the basic principles of money and debt management. We are focusing this phase on professional students in the Schools of Medicine, Pharmacy, and Dentistry, with the intent to engage the whole VCU student population in the future. The RAM$mart Financial Wellness Program will include modules on a variety of money management topics designed to get the attention of students and to provide them with practical steps they can take at the beginning of, and throughout, their graduate professional education to minimize debt accumulation. There will also be modules designed to inform students of various loan payback options upon their degree completion, and of available community and online financial resources. Through attention-grabbing and entertaining modules, including such things as humorous video snippets and interactive questions, students’ awareness of budgeting and financial responsibility will increase significantly

PCSK9 Inhibitors in Secondary Prevention – An Opportunity for Personalized Therapy

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is the primary cause of ASCVD and reducing LDL-C levels with statin therapy significantly reduces ASCVD risk; however, significant residual risk remains. Two monoclonal antibodies (mAbs), alirocumab and evolocumab, that target proprotein convertase subtilisin/kexin-type 9 (PCSK9), reduce LDL-C levels by up to 60% when used in combination with statins and significantly reduce the risk of recurrent ASCVD events in both stable secondary prevention and acute coronary syndrome populations. Pre-specified analyses of recent randomized controlled trials have shed light on how best to prioritize these therapies to maximize their value in select high risk groups. These data have also informed recent clinical practice guidelines and scientific statements resulting in an expanded role for PCSK9-mAbs compared to previous guidelines, albeit there are notable differences between these recommendations. Ongoing research is exploring the long-term safety of PCSK9-mAbs and their role in the acute setting as well as patients without prior myocardial infarction or stroke. Novel therapies that inhibit PCSK9 synthesis via small interfering RNA, such as inclisiran, are also in development and may reduce LDL-C levels similar to PCSK9-mAbs but with less frequent administration. Nonetheless, the PCSK9-mAbs are a breakthrough therapy and warrant consideration in very-high risk patients who are most likely to benefit. Such a personalized approach can help to ensure cost-effectiveness and maximize their value

Pharmacological Approaches For the Management of Patients with Moderately Elevated Triglycerides (150-499 mg/dL)

Hypertriglyceridemia, defined as serum triglyceride (TG) levels \u3e 150 mg/dL, now affects over one-quarter of the U.S. adult population and is associated with an increased risk of atherosclerotic cardiovascular disease. Available guidelines for managing hypertriglyceridemia vary with respect to triglyceride thresholds and severity of disease. Lifestyle modifications and management of secondary causes (e.g., diabetes) remain the first step in managing hypertriglyceridemia, with pharmacotherapy reserved to reduce the risk of pancreatitis and/or further reduce TG levels. Several classes of lipid-lowering agents are available with variable TG-lowering efficacy. While there is no consensus regarding the choice of initial TG-lowering pharmacotherapy, there is general agreement that the decision depends on the degree of hypertriglyceridemia and atherosclerotic cardiovascular disease risk. This review will discuss available and emerging lipid-lowering therapies for the management of moderately elevated TG, defined as TG 150-499 mg/dL

Evolving Role of Non-Statin Therapy for the Management of Dyslipidemia and Cardiovascular Risk Reduction: Past, Present, and Future

A plethora of evidence supports the use of statin therapy for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet residual risk among high-risk patients receiving statin therapy remains high. Moreover, statin-associated muscle symptoms and other statin-associated adverse effects (e.g., increased risk of diabetes mellitus) limit the use of statins in high-risk patient populations. Of particular concern are individuals with established ASCVD, familial hypercholesterolemia (FH), or diabetes mellitus plus multiple ASCVD risk factors, all of whom require high-intensity statins, which are more commonly associated with an increased risk of adverse effects

Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2)

Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of con-firmed HF cases in the United States. However, there are no highly effective evidence-basedtreatments currently available for these patients. Inflammation correlates positively withadverse outcomes in HF patients. Interleukin (IL)-1, a prototypical inflammatory cytokine, hasbeen implicated as a driver of diastolic dysfunction in preclinical animal models and a pilot clini-cal trial. The Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2) is a phase 2, 2:1 ran-domized, double-blind, placebo-controlled clinical trial that will test the hypothesis that IL-1blockade with anakinra (recombinant human IL-1 receptor antagonist) improves (1) cardiorespi-ratory fitness, (2) objective evidence of diastolic dysfunction, and (3) elevated inflammation inpatients with HFpEF (http://www.ClinicalTrials.gov NCT02173548). The co–primary endpointswill be placebo-corrected interval changes in peak oxygen consumption and ventilatory effi-ciency at week 12. In addition, secondary and exploratory analyses will investigate the effectsof IL-1 blockade on cardiac structure and function, systemic inflammation, endothelial function,quality of life, body composition, nutritional status, and clinical outcomes. The D-HART2 clinicaltrial will add to the growing body of evidence on the role of inflammation in cardiovascular dis-ease, specifically focusing on patients with HFpEF

Review of offshore CO2 storage monitoring: operational and research experiences of meeting regulatory and technical requirements

Legislation for offshore storage has been developing over the last decade or so and is currently most developed in Europe. Although the large-scale operating sites in Europe were started prior to the regulations coming into force, any planned sites will need to meet these regulatory requirements. Our review of monitoring experiences from both the operating sites and research at experimental injection sites and in areas of natural CO2 seepage suggest that broadly, the technical and regulatory challenges of offshore monitoring can be met. A full report reviewing offshore monitoring including tool capabilities, practicalities and costs is available from IEAGHG (released Q1 2016)