Bmc Med
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The phosphatidylinositol 3-kinase (PI3K) pathway is commonly deregulated in cancer. In recent years, the results of the first phase I clinical trials with PI3K inhibitors have become available. ⋯ In this review we propose possible strategies to optimize the clinical development of PI3K inhibitors: by exploring the potential role of PI3K isoform-specific inhibitors in improving the therapeutic index, molecular characterization as a basis for patient selection, and the relevance of performing serial tumor biopsies to understand the associated mechanisms of drug resistance. The main focus of this review will be on PI3K isoform-specific inhibitors by describing the functions of different PI3K isoforms, the preclinical activity of selective PI3K isoform-specific inhibitors and the early clinical data of these compounds.
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More than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD) using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial. ⋯ Proteins in the serum of CAD patients predominantly reflected (1) a positive acute phase, inflammatory response and (2) alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.
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There is a need for the development of effective universal preventive approaches to the common mental disorders, depression and anxiety, at a population level. Poor diet, physical inactivity and smoking have long been recognized as key contributors to the high prevalence noncommunicable diseases. ⋯ On the basis of this most recent evidence, we consequently argue for the inclusion of depression and anxiety in the ranks of the high prevalence noncommunicable diseases influenced by habitual lifestyle practices. We believe that it is both feasible and timely to begin to develop effective, sustainable, population-level prevention initiatives for the common mental illnesses that build on the established and developing approaches to the noncommunicable somatic diseases.
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Apps have been enthusiastically adopted by the general public. They are increasingly recognized by policy-makers as a potential medium for supporting self-management of long-term conditions. We assessed the degree to which current smartphone and tablet apps for people with asthma offer content and tools of appropriate quality to support asthma self-management. ⋯ No apps for people with asthma combined reliable, comprehensive information about the condition with supportive tools for self-management. Healthcare professionals considering recommending apps to patients as part of asthma self-management should exercise caution, recognizing that some apps like calculators may be unsafe; that no current app will meet the need of every patient; and that ways of working must be adapted if apps are to be introduced, supported and sustained in routine care. Policy-makers need to consider the potential role for assurance mechanisms in relation to apps. There remains much to be done if apps are to find broad use in clinical practice; clinicians cannot recommend tools that are inaccurate, unsafe or lack an evidence base.