Drugs
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Letrozole is a highly selective, nonsteroidal, third-generation aromatase inhibitor approved for first-line and extended adjuvant therapy in postmenopausal women with hormone-responsive, early-stage breast cancer. Binding of letrozole to the haeme component of the cytochrome P450 subunit of aromatase inhibits estrogen biosynthesis throughout the body. As first-line adjuvant therapy in approximate, equals 8000 postmenopausal women with hormone-responsive, early-stage breast cancer, once-daily letrozole 2.5mg significantly prolonged disease-free survival (DFS; primary endpoint) and reduced the risk of relapse at distant sites relative to once-daily tamoxifen 20mg in the ongoing Breast International Group 1-98, double-blind, multinational trial. ⋯ Extended adjuvant therapy with once-daily letrozole 2.5mg significantly prolonged DFS relative to placebo treatment at a median follow-up of 30 months (primary endpoint) in the MA-17 trial in approximate, equals 5000 postmenopausal women who were disease free after 4.5-6 years of tamoxifen therapy for hormone-responsive, early-stage breast cancer. Letrozole treatment for up to 5 years was generally well tolerated in this clinical setting. As first-line treatment, relative to tamoxifen, letrozole was associated with a significantly lower incidence of venous thromboembolitic events, vaginal bleeding, hot flushes and night sweating, whereas the incidence of cardiac failure, bone fractures and arthralgia was higher in letrozole recipients.
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Bacterial meningitis in adults is a severe disease with high fatality and morbidity rates. Experimental studies have shown that the inflammatory response in the subarachnoid space is associated with an unfavourable outcome. In these experiments, corticosteroids, and in particular dexamethasone, were able to reduce the inflammatory cascades in the subarachnoid space. ⋯ On the basis of the available evidence, adjunctive dexamethasone therapy should be initiated before or with the first dose of antibacterials and continued for 4 days in all adults with suspected or proven bacterial meningitis, regardless of bacterial aetiology. In patients with both meningitis and septic shock, dexamethasone therapy cannot be unequivocally recommended, but the use of lower doses seems reasonable at present. Since prompt use of dexamethasone and appropriate antibacterials improves the prognosis of adults with bacterial meningitis, hospitals will require protocols to include dexamethasone with the initial antibacterial therapy.
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Biochemical markers of bone turnover are used increasingly during the clinical development of drugs for the treatment of metabolic bone diseases such as Paget's disease, osteoporosis and cancer that has metastasised to the bone. However, assessing the optimal value of these markers is often complicated, and such an assessment is an obvious prerequisite for rational use of the markers and, consequently, potential improvement of clinical drug development. Biochemical markers of bone turnover are substances in the blood or urine that are produced or released during bone remodelling. ⋯ However, their role in the development of new drugs is still limited to dose selection, and potential relationships with clinical outcomes remain to be investigated in instances of new mechanisms of action. Biochemical markers of bone turnover are a valuable asset for drug development, but their rational use is determined by a number of variables. Correctly manipulating these may improve clinical development of drugs for the treatment of patients with metabolic bone diseases such as osteoporosis and cancer metastatic to the bone.
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Randomized Controlled Trial Multicenter Study
Efficacy and safety of budesonide and formoterol in one pressurised metered-dose inhaler in adults and adolescents with moderate to severe asthma: a randomised clinical trial.
Inhaled corticosteroids (ICSs) are the preferred maintenance therapy for adults and children with mild, moderate and severe persistent asthma, with the addition of a long-acting beta(2)-adrenoceptor agonist to ICS therapy recommended for patients with moderate or severe persistent asthma. The efficacy and safety of the combination of budesonide and formoterol delivered via dry powder inhaler (DPI) is well documented. ⋯ In this population, twice-daily budesonide/formoterol pMDI provides asthma control significantly greater than the monocomponents or placebo and comparable with budesonide pMDI + formoterol DPI. Safety profiles were similar for all treatments.
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Review Comparative Study
Remifentanil : a review of its analgesic and sedative use in the intensive care unit.
Remifentanil (Ultiva), a 4-anilidopiperidine derivative of fentanyl, is an ultra-short-acting micro-opioid receptor agonist indicated to provide analgesia and sedation in mechanically ventilated intensive care unit (ICU) patients. Analgesia-based sedation with remifentanil is a useful option for mechanically ventilated patients in the ICU setting. Its unique properties (e.g. organ-independent metabolism, lack of accumulation, rapid offset of action) set it apart from other opioid agents. ⋯ Moreover, it allows fast and predictable extubation, as well as being associated with a shorter duration of mechanical ventilation and quicker ICU discharge than comparators in some studies. In addition, remifentanil is generally well tolerated in this patient population. Thus, remifentanil is a welcome addition to the currently available pharmacological agents employed in the management of mechanically ventilated ICU patients.