Non-BRAF-targeted therapy,immunotherapy, and combination therapy for melanoma

Introduction: Melanoma is an aggressive disease characterized by a complex etiology. The discovery of key driving mutations (primarily BRAF mutations) led to the development of specific molecular inhibitors providing clinical benefit.

Areas covered: Although BRAF-specific drugs have perhaps yielded the best results in melanoma-targeted therapy, there still remain several limitations, mostly due to the emergence of resistance and the lack of efficacy in patients without BRAF mutation. Novel drugs are currently being tested in clinical trials and showed encouraging results. Such drugs can specifically target molecular pathways aberrantly activated or repressed during melanoma development (targeted therapy) or act in a way to enhance the host immune system to fight cancer (immunotherapy). Here we provide a detailed overview of the current clinical strategies, which lay beyond BRAF-targeted therapy, spanning from molecular-targeted therapy to immunotherapy and to combination therapy.

Expert opinion: Major advances in our understanding of the mechanisms behind melanoma development have led to the implementation of novel therapeutic drugs. Unfortunately, tools allowing prediction of responsiveness to a given treatment are not available yet. The increasing availability of high-throughput technologies will allow the elucidation of molecular mechanisms underlying responsiveness to cancer therapy and unveil an increased number of potential therapeutic targets.     

Hemophilia, AIDS, and occupational therapy

This article describes the blood clotting disorder of hemophilia, including its transmission, incidence, and physical and psychosocial effects. The epidemiology of persons with both hemophilia and HIV are discussed, as well as HIV's rapid spread due to contaminated blood products and the mechanisms commonly used to cope with HIV infection. Specific suggestions on occupational therapy intervention are provided, including helping clients learn to cope with HIV by transferring skills previously learned for coping with hemophilia; teaching stress reduction, anger management, communication, and energy conservation skills; educating families and helping them set appropriate goals; designing adaptive systems for dealing with neurological deficits; and designing exercise programs.     

Treatment of pulmonary embolism: anticoagulation, thrombolytic therapy, and complications of therapy

During the last two decades, considerable progress in technology and clinical research methods have led to advances in the approach to the diagnosis, prevention, and treatment of acute venous thromboembolism (VTE). Despite this, however, the diagnosis is often delayed and preventive methods are often ignored. Thus, the morbidity and mortality associated with VTE remain high. The therapeutic approach to acute VTE is discussed in this article, with a particular focus on the intensive care unit setting.     

Some epistemological remarks on behavior therapy,cognitive therapy and psychoanalysis

This article presents the thesis that beyond obvious differences and antitheses, psychoanalysis and behavior therapy have a common epistemological basis: associationism. It is cognitive therapy, which appears to have a different epistemological basis (rationalism and teleology),that reveals this unsuspected resemblance between psychoanalysis and behaviorism. These different epistemologies must be kept in mind when attempting to integrate cognitive therapy and behavior therapy.     

Lipid-lowering therapy with statins, a new approach to antiarrhythmic therapy

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) are the most effective and best-tolerated drugs to treat elevated levels of low-density lipoprotein cholesterol (LDL-C). In addition, they exhibit other effects unrelated to their lipid lowering effects (pleiotropic actions). In recent years, experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties, reducing the recurrences of supraventricular and life-threatening ventricular arrhythmias both in patients with and without coronary artery disease (CAD). Thus, statins may constitute a novel therapeutic approach to cardiac arrhythmias. This article reviews the antiarrhythmic properties of statins as well as the possible mechanisms involved, including the lowering of LDL-C levels, the improvement of endothelial dysfunction and autonomic function, the stabilization of the atherosclerotic plaques, the antioxidant, antiinflammatory, antithrombotic and cardioprotective properties and the modulation of transmembrane ion fluxes.