Recent advances in the management of venous thromboembolism

Venous thromboembolism (VTE) is a spectrum of diseases that includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Anticoagulant treatment is the mainstay of therapy for VTE. Unfractionated heparin (UFH) or low molecular weight heparin (LMWH) followed by vitamin K antagonists have been the treatment of choice for most patients with VTE, with the aim to prevent thrombus extension or embolization and recurrent VTE. Fondaparinux, a selective, indirect, parenteral factor Xa inhibitor, is now also approved for the initial treatment of VTE and represents an important alternative to UFH or LMWH. Secondary prevention of VTE with vitamin K antagonists is usually prescribed for a minimum of three months, with the duration of treatment based on the presence or absence of major identifiable risk factors for the index event. Patients with permanent risk factors or patients with recurrent DVT or PE require life long secondary prevention. Over the last years, new oral anticoagulant agents have been developed and are now undergoing extensive clinical evaluation in several settings, including the treatment of VTE. New oral anticoagulants include selective, direct thrombin inhibitors, such as dabigatran etexilate, and selective, direct factor Xa inhibitos, such as rivaroxaban, apixaban or edoxaban. All these drugs are admistered at fixed daily doses and do not require laboratory monitoring. The positive results of the first completed clinical trials suggest that a new era in the management of VTE is about to begin

Ship Motions and Added Resistance with a BEM in frequency and time domain

This thesis is focused on the calculation of ship motions and on the evaluation of added resistance in waves. A partial desingularized panel method based on potential theory has been developed. Rankine sources are distributed on the hull and at small distance above the free surface. In such way only the free surface is desingularized. This choice allows to consider also thin hull shapes at the bow where desingularization could cause numerical problems. The main advantage of this approach leads to reduce the computational time, especially when non linear effects are considered, provided an adequate source-panel center vertical distance is selected. The fluid domain boundaries have been represented as a structured grid consisting of flat quadrilater panels. In the linear case the boundary conditions have been applied on the mean body wetted surface and the free-surface is considered at the calm water level. By using an Eulerian timestepping integration scheme the kinematic and dynamic boundary conditions are updated on the free-surface at every time-step. After the potential is obtained, the pressure on the mean hull surface can be calculated and forces and moments can be determined by integrating the pressure on the body surface. Therefore in two-dimensional environment an introduction of non-linear effects has been analysed. In particular a 2D body exact method has been developed. The added resistance is determined by a near field method integrating the second-order pressure on the body surface. Then it is corrected using a semi-empirical method to allow to consider the wave reflection of short waves. The adequacy of the results has been verified applying the code to different test cases and comparing the numerical output with experimental data available in literature. Furthermore in order to discuss the improvements obtained with this present method the results have been compared with another numerical method in frequency domain

Milvexian and other drugs targeting Factor XI: a new era of anticoagulation?

For almost 90 years, the discovery and development of anticoagulant drugs have focused on maximizing their antithrombotic efficacy while minimizing the risk of bleeding, in addition to providing manageable compounds with predictable and/or monitorable effects [...]

Low-molecular-weight heparins in the treatment of venous thromboembolism

Venous thromboembolism is a common disease that is associated with considerable morbidity if left untreated. Recently, low-molecular-weight heparins (LMWHs) have been evaluated for use in acute treatment of deep venous thrombosis and pulmonary embolism. Randomized studies have shown that LMWHs are as effective as unfractionated heparin in the prevention of recurrent venous thromboembolism, and are as safe with respect to the occurrence of major bleeding. A pooled analysis did not show substantial differences among different LMWH compounds used, but no direct comparison of the different LMWHs is currently available. Finally, in patients with pulmonary embolism, there is a relative lack of large studies of daily practice. It could be argued that large prospective studies, in patients who were treated with LMWHs from the moment of diagnosis, are needed

Infinite time blow-up for the three dimensional energy critical heat equation in bounded domains

We consider the Dirichlet problem for the energy-critical heat equation \begin{equation*} \begin{cases} u_t=\Delta u+u^5,~&\mbox{ in } \Omega \times \mathbb{R}^+,\\ u(x,t)=0,~&\mbox{ on } \partial \Omega \times \mathbb{R}^+,\\ u(x,0)=u_0(x),~&\mbox{ in } \Omega, \end{cases} \end{equation*} where $\Omega$ is a bounded smooth domain in $\mathbb{R}^3$. Let $H_\gamma(x,y)$ be the regular part of the Green function of $-\Delta-\gamma$ in $\Omega$, where $\gamma \in (0,\lambda_1)$ and $\lambda_1$ is the first Dirichlet eigenvalue of $-\Delta$. Then, given a point $q\in \Omega$ such that $3\gamma(q)<\lambda_1$, where $$\gamma(q)=\sup\{ \gamma>0: H_\gamma(q,q)>0 \},$$ we prove the existence of a non-radial global positive and smooth solution $u(x,t)$ which blows up in infinite time with spike in $q$. The solution has the asymptotic profile $$u(x,t)\sim 3^{\frac{1}{4}} \bigg(\frac{\mu(t)}{\mu(t)^2+|x-\xi(t)|^2}\bigg)^{\frac{1}{2}} \quad \text{as}\quad t \to \infty,$$ where $$-\ln \mu(t)= 2\gamma(q) t(1+o(1)),\quad \xi(t)=q+O\big(\mu(t)\big) \quad \text{as}\quad t \to \infty.$$Comment: 74 pages, 1 figur

Role of new anticoagulants for the prevention of venous thromboembolism after major orthopaedic surgery and in hospitalised acutely ill medical patients.

SummaryAnticoagulation therapy for the prevention of venous thromboembolic events is indicated in patients after major orthopaedic surgery and in hospitalised acutely ill medical patients, who have a high or moderate risk of venous thromboembolism (VTE), respectively. Clinical trials have clearly demonstrated that short-term anticoagulation reduces the risk of VTE in these patient groups and that longer-term anticoagulation is beneficial for some indications. Evidence-based guidelines for throm-boprophylaxis have been developed based on these studies. However, despite these guidelines, thromboprophylaxis is still underused, or used suboptimally, in many patients. This is, in part, because of the limitations of traditional anticoagulants such as unfractionated heparin, lowmolecular-weight heparin, synthetic pentasaccharides, and vitamin K antagonists. Newer oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran etexilate, have certain advantages over traditional agents. They can be administered orally at a fixed dose without routine coagulation monitoring and have minimal food and drug interactions. These characteristics may result in better adherence to guidelines and improved patient outcomes. This review provides an overview of phase III clinical trial data for these newer anticoagulants in major orthopaedic surgery and in hospitalised acutely ill medical patients, and discusses their potential for extended use in the post-hospital discharge setting. All three newer oral anticoagulants are approved in many countries for the prevention of VTE after hip replacement or knee replacement surgery in adult patients, and it is likely that these drugs will contribute considerably towards reducing the substantial healthcare burden associated with VTE.</jats:p