Drugs
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Several large-scale clinical trials have assessed the efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome. In primary prevention, CARDS (Collaborative Atorvastatin Diabetes Study) showed that atorvastatin 10 mg/day (vs placebo) reduced relative risk of the composite primary endpoint (acute coronary heart disease [CHD] events, coronary revascularisation, or stroke) by 37% (p = 0.001). This decrease was similar to decreases in major cardiovascular events in the ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm) trial and HPS (Heart Protection Study). ⋯ In CHD patients with metabolic syndrome (n = 5584) in a sub-analysis of the TNT trial, intensive versus lower-dosage atorvastatin therapy reduced the relative risk of major cardiovascular and cerebrovascular events by 29% (p < 0.0001). The analysis also revealed that CHD patients with, rather than those without, metabolic syndrome had a 44% greater level of absolute cardiovascular risk, thus clearly underscoring the clinical feasibility of administering intensive lipid-lowering therapy to CHD patients with metabolic syndrome. In summary, several patient populations, from definitive, large-scale studies, are now available to corroborate the integral place of atorvastatin--in line with various regional and internationally accepted disease management guidelines--in the primary and secondary prevention of cardiovascular events in patients with diabetes and/or metabolic syndrome.
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Voriconazole (VFEND), a synthetic second-generation, broad-spectrum triazole derivative of fluconazole, inhibits the cytochrome P450 (CYP)-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the cell membrane and halting fungal growth. In the US, intravenous and/or oral voriconazole is recommended in adults for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, disseminated infections caused by Candida spp., oesophageal candidiasis, and in patients with scedosporiosis and fusariosis who are refractory to or intolerant of other antifungal therapy. In Europe, intravenous and/or oral voriconazole is recommended in adults and paediatric patients of at least 2 years of age for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, fluconazole-resistant serious invasive Candida spp. infections, scedosporiosis and fusariosis. ⋯ On the other hand, the numerous drug interactions associated with voriconazole may limit its usefulness in some patients. Further clinical experience will help to more fully determine the position of voriconazole in relation to other licensed antifungal agents. In the meantime, voriconazole is a valuable emerging option for the treatment of invasive aspergillosis and rare fungal infections, including Fusarium spp. and Scedosporium spp. infections, and provides an alternative option for the treatment of candidiasis, particularly where the causative organism is inherently resistant to other licensed antifungal agents.
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Review
Viral respiratory tract infections in transplant patients: epidemiology, recognition and management.
Viral respiratory tract infections (RTIs) are common causes of mild illness in immunocompetent children and adults, with occasional significant morbidity or mortality in the very young, very old or infirm. However, recipients of solid organ transplants (SOT) or haematopoietic stem cell transplants (HSCT) are at markedly increased risk for significant morbidity or mortality from these infections. The infections are generally acquired by transmission of large respiratory droplets and can be nosocomial in origin with many documented outbreaks on specialised transplant units. ⋯ These newer assays may also detect emerging pathogens of significance, one of which is human metapneumovirus. While diagnostic techniques have advanced significantly in the past decade, well established and effective specific treatments for these infections remain elusive. The epidemiology, clinical presentation, diagnosis and treatment of the common viral RTIs in SOT or HSCT recipients are reviewed, and recommendations presented based on a thorough review of recent literature.
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Review
Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients.
Morbidity and mortality caused by invasive Aspergillus infections are increasing. This is because of the higher number of patients with malignancies treated with intensive immunosuppressive therapy regimens as well as their improved survival from formerly fatal bacterial infections, and the rising number of patients undergoing allogeneic haematopoietic stem cell or organ transplantation. Early initiation of effective systemic antifungal treatment is essential for a successful clinical outcome in these patients; however, clinical clues for diagnosis are sparse and early microbiological proof of invasive aspergillosis (IA) is rare. ⋯ Well designed, prospective randomised studies on infection control measures effective to prevent aspergillosis are lacking. Prophylactic systemic antifungal treatment with posaconazole significantly improves survival and reduces IA in acute myeloid leukaemia patients and reduces aspergillosis incidence rates in patients with intermediate-to-severe graft-versus-host reaction emerging after allogeneic haematopoietic stem cell transplantation. Voriconazole prophylaxis may be suitable for prevention of IA as well; however, the results of large clinical trials are still awaited.
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Dihydropyridine calcium channel antagonists have been maligned in recent years because of concerns regarding their cardiovascular and overall safety profile. Specifically, it was widely publicised in the mid-1990s that these agents might increase the risk of myocardial infarction, gastrointestinal bleeding and cancer. Data linking these agents with increased cardiovascular risk were based on nonrandomised studies and implicated short-acting, immediate-release agents. ⋯ Dihydropyridine calcium channel antagonists demonstrate a highly desirable profile when administered as part of combination therapy. Combinations of dihydropyridine calcium channel antagonists and ACE inhibitors or angiotensin receptor antagonists display additive efficacy and an enviable adverse-effect profile. Collectively, the cardiovascular benefit, metabolic neutrality and homogeneous blood pressure response illuminated in recent studies, and reviewed here, represent a reaffirmation of the benefit of long-acting dihydropyridine calcium channel antagonists and should serve to help reinforce the critical importance of these agents in the therapeutic armamentarium against cardiovascular disease.