Lancet
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There has been a recent increase in the prevalence of asthma worldwide; however, the 5-10% of patients with severe disease account for a substantial proportion of the health costs. Although most asthma cases can be satisfactorily managed with a combination of anti-inflammatory drugs and bronchodilators, patients who remain symptomatic despite maximum combination treatment represent a heterogeneous group consisting of those who are under-treated or non-adherent with their prescribed medication. ⋯ Aberrant communication between an injured airway epithelium and underlying mesenchyme contributes to disease chronicity and refractoriness to corticosteroids. The importance of identifying underlying causative factors and the recent introduction of novel therapeutic approaches, including the targeting of immunoglobulin E and tumour necrosis factor alpha with biological agents, emphasise the need for careful phenotyping of patients with severe disease to target improved management of the individual patient's needs.
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The common disease asthma is probably not a single disease, but rather a complex of multiple, separate syndromes that overlap. Although clinicians have recognised these different phenotypes for many years, they have remained poorly characterised, with little known about the underlying pathobiology contributing to them. ⋯ However, there is no standardised method to define asthma phenotypes. This Review analyses some of the methods that have been used to define asthma phenotypes and proposes an integrated method of classification to improve our understanding of these phenotypes.
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Peripartum cardiomyopathy (PPCM) is a disorder in which initial left ventricular systolic dysfunction and symptoms of heart failure occur between the late stages of pregnancy and the early postpartum period. It is common in some countries and rare in others. The causes and pathogenesis are poorly understood. ⋯ Effective treatment reduces mortality rates and increases the number of women who fully recover left ventricular systolic function. Outcomes for subsequent pregnancy after PPCM are better in women who have first fully recovered heart function. Areas for future research include immune system dysfunction, the role of viruses, non-conventional treatments such as immunosuppression, immunoadsorption, apheresis, antiviral treatment, suppression of proinflammatory cytokines, and strategies for control and prevention.
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Cardiovascular disease is the leading cause of death, with 80% of cases occurring in developing countries. We therefore aimed to establish whether use of evidence-based multidrug regimens for patients at high risk for cardiovascular disease would be cost-effective in low-income and middle-income countries. ⋯ Regimens of aspirin, two blood-pressure drugs, and a statin could halve the risk of death from cardiovascular disease in high-risk patients. This approach is cost-effective according to WHO recommendations, and is robust across several estimates of drug efficacy and of treatment cost. Developing countries should encourage the use of these inexpensive drugs that are currently available for both primary and secondary prevention.
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The HIV-1 pandemic is a complex mix of diverse epidemics within and between countries and regions of the world, and is undoubtedly the defining public-health crisis of our time. Research has deepened our understanding of how the virus replicates, manipulates, and hides in an infected person. ⋯ This transformation has yet to be realised in those parts of the world that continue to bear a disproportionate burden of new HIV-1 infections and are most affected by increasing morbidity and mortality. This Seminar provides an update on epidemiology, pathogenesis, treatment, and prevention interventions pertinent to HIV-1.