American journal of therapeutics
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The burden of ischemic stroke in the United States continues to increase each year. Patients with stroke with the most severe disability require a disproportionately large share of healthcare resources. ⋯ We review the rationale, current literature, and future directions of mechanical devices for stroke thrombolysis. We also review pertinent issues related to thrombolysis-related intracerebral hemorrhage and appropriate patient selection.
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Randomized Controlled Trial Comparative Study
The relative bioavailability of morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA®) and an extended release morphine sulfate capsule formulation (KADIAN®) in healthy adults under fasting conditions.
Morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA®, King Pharmaceuticals®, Inc., Bristol, TN), indicated for the management of chronic, moderate to severe pain, contain extended release morphine pellets with a sequestered naltrexone core (MS-sNT). If the product is tampered with by crushing, naltrexone, a μ-opioid antagonist, is intended for release to mitigate morphine-induced subjective effects. The primary end point of this randomized 2-way crossover study in healthy fasted volunteers was evaluation of morphine bioequivalence between MS-sNT (treatment A) and morphine sulfate extended release capsules (KADIAN®, treatment B). ⋯ Analysis of variance of ln-transformed ratios of least squares mean of the area under the concentration time curve (AUC) from time 0 to last measurable concentration (AUC0-t) and AUC from time 0 to infinity (AUCinf) and maximum serum concentration (Cmax) for treatments A versus B were performed. Ratios and 90% confidence intervals for least squares mean for AUC0-t (102.2%; 98.6-105.9%), AUCinf (97.4%; 91.2-104.1%), and Cmax (93.8%; 82.4-106.7%) indicated bioequivalence between the 2 formulations. When subjects who vomited during the 12-hour dosing interval were excluded, the confidence interval for AUC0-t and AUCinf fell within the 80%-125% range, but the lower limit for Cmax was 76.9%.
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Randomized Controlled Trial Comparative Study
A randomized, open-label pilot study comparing desirudin and argatroban in patients with suspected heparin-induced thrombocytopenia with or without thrombosis: PREVENT-HIT Study.
Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. ⋯ There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.
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The natural history and optimal treatment for unruptured cerebral aneurysm and arteriovenous malformations (AVMs) remains unknown. The prevalence of intracranial aneurysms is estimated to be between 1% and 5%. The annual risk of rupture for small aneurysms in the anterior circulation is low. ⋯ The annual risk of rupture of AVMs that did not present with hemorrhage is low at approximately 0.9% per year. Factors that increase the risk of rupture include hemorrhagic presentation, deep AVM location, or deep venous drainage associated with the AVM. The treatment options for AVM available include conservative management, microsurgery, endovascular treatment, radiosurgery, or a combination of methods.
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Arginine vasopressin (AVP) is increased in patients with heart failure (HF). Its actions are linked to free water reabsorption (V2-) and arteriolar vasoconstriction (V1a receptor). AVP can exacerbate the cardiorenal syndrome with excess fluid retention and afterload increase. ⋯ In conclusion, it was demonstrated that in an acute HF model, CON lowered, whereas TOL increased afterload. The results suggest that dual V1a/V2 blockade in the acute HF setting could be beneficial compared with selective V2 blockade. Chronic experiments are needed to determine whether this finding can translate into a sustained clinical advantage.