Austrian Science Fund, Austrian National Bank Memorial Fund, and participating hospitals.

In the Hokusai VTE Cancer study, edoxaban was non-inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer-associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1-4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days); no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9%) and 11 (2.1%) patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub-group occurred in 5 of 165 (3.0%) and in 3 of 140 (2.1%) patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer-associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit-risk weighting.

enous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially fatal disease. The estimated incidence of a first acute VTE is 0.7 to 1.4 per 1000 person-years and is mostly observed in patients older than 55 years. [1][2][3][4] While the incidence of DVT has remained constant over time, 5 hospital admissions for PE in the United States more than doubled over the last decades, 6 partly because of widespread use of sensitive imaging techniques detecting smaller, potentially insignificant emboli. 7 Even though the in-hospital case-fatality rate of PE has decreased in the United States between 1999 and 2008, 8 about 30% of patients with PE die within the first year after diagnosis. 4 The socioeconomic effect of VTE is significant, with estimated annual costs ranging from $13.5 billion to $27.2 billion in the United States. 9Clinical signs and symptoms of DVT include unilateral leg pain, redness, swelling, edema, warmth, and tenderness. Pulmonary embolism may present with dyspnea, chest pain, hemoptysis, syncope, tachycardia, and hypotension. The clinical presentation of VTE is often not specific, and DVT can be indistinguishable from cellulitis, hematoma, superficial thrombophlebitis, and congestive heart failure. Pulmonary embolism presents similarly to myocardial infarction, congestive heart failure, and other diseases. Consequently, imaging is needed to confirm the diagnosis of VTE. The diagnosis of VTE is made in a sequence of steps including assessment of the pretest probability, followed by D-dimer testing and imaging as appropriate (Figure 1). When VTE is diagnosed, immediate initiation of anticoagulant therapy is imperative. The choice among different anticoagulant agents and the duration of treatment are based IMPORTANCE Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially fatal disease.OBJECTIVE To summarize the advances in diagnosis and treatment of VTE of the past 5 years.EVIDENCE REVIEW A systematic search was conducted in EMBASE Classic, EMBASE, Ovid MEDLINE, and other nonindexed citations using broad terms for diagnosis and treatment of VTE to find systematic reviews and meta-analyses, randomized trials, and prospective cohort studies published between January 1, 2013, and July 31, 2018. The 10th edition of the American College of Chest Physicians Antithrombotic Therapy Guidelines was screened to identify additional studies. Screening of titles, abstracts, and, subsequently, full-text articles was performed in duplicate, as well as data extraction and risk-of-bias assessment of the included articles.FINDINGS Thirty-two articles were included in this review. The application of an age-adjusted D-dimer threshold in patients with suspected PE has increased the number of patients in whom imaging can be withheld. The Pulmonary Embolism Rule-Out Criteria safely exclude PE when the pretest probability is low. The introduction of direct oral anticoagulants has allowed for a simpli...

Prucalopride reduces esophageal acid exposure and accelerates gastric emptying in healthy male volunteers. These findings suggest that the drug could be effective for treatment of patients with reflux disease and functional dyspepsia.