Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options

General Motors: A financialized account of corporate behaviour 1909–1940

This paper constructs an alternative account of resource stewardship at General Motors (GM) during the period 1909–1940. Alfred Chandler employed GM in his text ‘Strategy and Structure’ to explain the development of the modern corporation. This understanding can be employed to contrast an ‘old-economy’ with a ‘new-economy’ financialized corporate business model. In this paper we find that many elements of the financialized firm were present in the early history of GM’s development. Our analysis reveals the financialization of a non-financial corporation and how this influenced corporate behaviour and impacted on financial performance at GM during the period 1909–1940

CONFIDENCE dissemination meeting: summary on the scenario-based workshop

The CONFIDENCE dissemination workshop “Coping with uncertainties for improved modelling and decision making in nuclear emergencies” was held in December 2–5, 2019 (Bratislava, Slovak Republic). About 90 scientists and decision makers attended the workshop. The dissemination workshop allowed the presentation of the CONFIDENCE project results, demonstration of the applicability of the developed methods and tools in interactive discussion sessions and the collection of feedback from the participants. The results were disseminated not only in the form of presentations and posters but also through interactive workshops where all participants were involved in round table working groups. A fictive accidental release scenario taking place at a nuclear power plant was developed and used by each work package in the workshop to provide the basis for interactive sessions and discussions

Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score

Aims Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation. Methods and results Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48–0.71 (recurrence) and 0.61–0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% –19% for bleeding. Conclusion The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making

Multiple thromboembolism with multiple causes in a 69-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Aggressive, recurrent embolisms require accurate etiologic diagnosis. We describe the case of a 69-year-old Italian Caucasian woman with recurrent arterial embolisms in whom several sources and triggers of thrombosis were detected.</p> <p>Case presentation</p> <p>The patient, a 69-year-old Italian Caucasian woman, presented with a systemic embolism that was initially attributed to atrial fibrillation. The recurrence of embolisms despite anti-thrombotic therapy prompted a re-evaluation of the clinical presentation. New potential causes of thrombosis emerged in this patient, including thrombocytosis associated with the <it>JAK2 V617F </it>mutation and the very rare mural thrombosis of the descending aorta. A mural thrombus in the pulmonary artery was detected contiguous with the aortic mural thrombosis, raising the possibility of a clinically silent ductus Botalli as the initiating event. The patient was treated with warfarin, aspirin, hydroxyurea, and surgery.</p> <p>Conclusions</p> <p>The diagnosis was achieved via systematic use of imaging procedures and reconsideration of blood tests performed to explore the diagnosis of thrombosis. This allowed a deeper and more detailed analysis of the case beyond the conventional approach, which would have aimed to identify one cause for the condition at hand, in this case, atrial fibrillation. The broader approach that we used resulted in the diagnosis of multiple embolisms from multiple sites and multiple causes.</p