Pharmacotherapy
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Anemia of critical illness, a commonly encountered clinical situation, is hematologically similar to that of chronic anemia, except that the onset is generally sudden. The etiology is usually multifactorial, occurring as a consequence of direct inhibitory effects of inflammatory cytokines, erythropoietin deficiency, blunted erythropoietic response, blood loss, nutritional deficiencies, and renal insufficiency. Although anemia is not well tolerated by critically ill patients, aggressive treatment of anemia can be just as detrimental as no treatment. ⋯ These studies have generated interest in the administration of exogenous erythropoietin and iron therapy. Unfortunately, the accurate determination of iron status can be a rather difficult task, an undertaking that is made even more difficult by the presence of comorbid conditions that can affect the commonly used parameters for guiding iron therapy. The use of erythropoiesis-stimulating agents is rapidly gaining acceptance, although they also present potential problems of their own.
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Stroke is a leading cause of death and the primary cause of serious, long-term disability in the United States. Joint guidelines from the American Heart Association (AHA) and American Stroke Association (ASA), as well as recent guidelines from the Eighth American College of Chest Physicians (ACCP) Conference on Antithrombotic and Antiplatelet Therapy, recommend aspirin, clopidogrel, or extended-release dipyridamole plus aspirin as acceptable first-line options for secondary prevention of ischemic events in patients with a history of ischemic stroke or transient ischemic attack (TIA). The ACCP strongly recommends the combination of extended-release dipyridamole plus aspirin over aspirin monotherapy (highest level of evidence) and suggests clopidogrel monotherapy over aspirin monotherapy (lower level of evidence). ⋯ The CHARISMA trial compared aspirin plus clopidogrel with aspirin alone in a population at high risk for atherothrombotic events using the composite outcome of myocardial infarction, stroke, and death from cardiovascular causes. Data from ESPRIT add to evidence that the combination of aspirin plus extended-release dipyridamole is superior to aspirin alone. The findings of the CHARISMA trial reinforce recommendations from both AHA-ASA and ACCP that the combination of aspirin and clopidogrel be reserved for special populations requiring this antiplatelet combination (e.g., those who have had coronary artery stenting).
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Breast cancer is the second leading cause of cancer death in women. Treatment options for advanced-stage disease, although numerous, remain suboptimal. Lapatinib and ixabepilone are two new agents approved by the United States Food and Drug Administration (FDA) in 2007 for the treatment of locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). ⋯ The most common toxicities with lapatinib are diarrhea (65%) and hand-and-foot syndrome (53%), whereas peripheral neuropathy (62%), fatigue (56%), and neutropenia (54%) are most common with ixabepilone. Though the conventional standard end point of overall survival has not yet been assessed in clinical trials, these agents have been shown to improve surrogate markers of clinical benefit: progression-free survival and the related time to progression. Future clinical trials should focus on elucidation of optimal combination or sequential therapies, as well as patient-specific therapies based on tumor characteristics, such as biomarkers and tumor subtypes.
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To investigate the effect of intravenous propacetamol, a parenteral bioprecursor of acetaminophen, on systemic blood pressure in critically ill patients with fever, and to establish the prevalence and clinical significance of this effect. ⋯ Intravenous propacetamol, given in antipyretic doses, caused a significant decrease in blood pressure 15 minutes after administration in febrile critically ill patients. This drug-induced hypotension was clinically relevant in that interventions to control blood pressure were required. Thus, clinicians should be aware of this potential deleterious effect, particularly in specific populations such as critically ill patients.