Drugs
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Managing epilepsy during pregnancy is to balance the maternal and fetal risks associated with uncontrolled seizures against the potential teratogenic effects of antiepileptic drugs (AEDs). A rational approach requires knowledge of such risks as well as an understanding of the effects of pregnancy on seizure control and of gestational effects on AED disposition. Uncontrolled tonic-clonic seizures are potentially hazardous to the mother and, although strict evidence is lacking, are generally also assumed to be more harmful to the fetus than are AEDs. ⋯ Valproic acid should be avoided if possible. Any major change in the treatment of a woman with epilepsy should ideally be completed before conception. Regular monitoring of drug concentrations is recommended during pregnancy, in particular for lamotrigine and oxcarbazepine.
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Bronchiectasis is characterised by permanent dilatation of the bronchi that arises from chronic inflammation predominantly caused by bacterial infection. This condition remains a major cause of excess respiratory morbidity and treatment is generally only partly successful. There is an urgent need for improved anti-inflammatory medication to treat bronchiectasis. ⋯ There are concerns about the development of resistance, especially to non-tuberculous mycobacteria, with prolonged macrolide use. The evidence available suggests that both medications have a role in the management of bronchiectasis. More definitive trials of ICS and macrolides in bronchiectasis will clarify the likely benefit of these therapies.
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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.