Drugs
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An association between hypercholesterolaemia and ischaemic stroke has not yet been clearly defined by observational studies. In clinical trials, however, cholesterol-lowering treatments appear to consistently reduce stroke risk. Data are now available from various primary prevention studies - ALLHAT-LLT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack, Lipid-Lowering Therapy), ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial, Lipid-Lowering Arm), CARDS (Collaborative Atorvastatin Diabetes Study, WOSCOPS (West of Scotland COronary Prevention Study) - and secondary prevention studies - 4S (Scandinavian Simvastatin Survival Study), CARE (Cholesterol and Recurrent Events), GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), HPS (Heart Protection Study), LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), TNT (Treating to New Targets) - confirming the ability of statins to reduce stroke risk. ⋯ Among secondary study endpoints, atorvastatin reduced the relative risks of stroke and TIA (-23%; p < 0.001), TIA alone (-26%; p = 0.004), and ischaemic stroke (-22%; p = 0.01). Overall, SPARCL study findings suggest that intensive atorvastatin therapy should be started immediately after a stroke or TIA. In summary, atorvastatin has developed a well defined role in the primary and secondary prevention of cerebrovascular disease, and appears to have a particularly prominent place in preventing such disease in CHD patients, and in the post-stroke and post-TIA setting in patients without CHD.
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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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For half a century, controlled hypotension has been used to reduce bleeding and the need for blood transfusions, and provide a satisfactory bloodless surgical field. It has been indicated in oromaxillofacial surgery (mandibular osteotomy, facial repair), endoscopic sinus or middle ear microsurgery, spinal surgery and other neurosurgery (aneurysm), major orthopaedic surgery (hip or knee replacement, spinal), prostatectomy, cardiovascular surgery and liver transplant surgery. Controlled hypotension is defined as a reduction of the systolic blood pressure to 80-90 mm Hg, a reduction of mean arterial pressure (MAP) to 50-65 mm Hg or a 30% reduction of baseline MAP. ⋯ The first and oldest technique is epidural anaesthesia, but depending on the surgery, it is not always appropriate. The most recent satisfactory technique is a combination treatment of remifentanil with either propofol or an inhalation agent (isoflurane, desflurane or sevoflurane) at clinical concentrations. In light of the current literature, and because of their safety and ease of use, these two techniques are preferred.
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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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In developed countries, the choice of an anaesthetic agent for induction of anaesthesia remains based mainly on its pharmacodynamic properties. Until now, cardiovascular effects were the main factor in this decision. However, other factors, such as the depth of anaesthesia and effects on cortisol synthesis, can modify this simplistic view. ⋯ Although most practitioners are not concerned with the cost of anaesthesia, cost-containment policies have led some institutions to restrict the use of the more expensive drugs to particular indications. However, this is too simplistic an approach for the reduction of global costs, as other direct medical costs, such as those for staffing, form a greater proportion of total costs than do direct drug costs. Cost-benefit and cost-efficacy studies of the anaesthetics used for induction of anaesthesia are needed to help anaesthetists to choose a drug based on both cost and pharmacodynamic or pharmacokinetic properties.