Clinical therapeutics
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Disease management of stable coronary artery disease consists of controlling hemostasis and lipid regulation. No treatment strategies preventing plaque erosion or rupture are yet available. Cholesterol crystal-induced inflammation leading to plaque destabilization is believed to be an important factor contributing to plaque instability and might well be amenable to treatment with anti-inflammatory drugs. Colchicine has anti-inflammatory properties with the potential to address both the direct and indirect inflammatory mechanisms in the plaque. ⋯ The body and quality of evidence regarding the efficacy of colchicine for secondary prevention of stable and acute phases of coronary artery disease will be greatly expanded in the upcoming years, providing less biased and more accurate effect estimates. If colchicine's anti-inflammatory characteristics translate to improved event-free cardiovascular survival, this relatively safe, low-cost, and well-known drug may become the third pillar (next to lipid regulation and platelet inhibition) in the medical management of stable coronary artery disease.
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Clinical therapeutics · Jan 2019
Review Meta AnalysisEffects of Perioperative Dexmedetomidine on Postoperative Mortality and Morbidity: A Systematic Review and Meta-analysis.
Major postoperative complications translate into increased health care resource utilization, prolonged hospital stays, and increased mortality. We aimed to assess the effects of perioperative dexmedetomidine use on postoperative mortality and the prevalence of major complications after cardiac and noncardiac surgery. ⋯ Dexmedetomidine use may help to reduce postoperative 30-day mortality, durations of mechanical ventilation, ICU stay, and hospital stay, and the prevalences of delirium, atrial fibrillation, and cardiac arrest in patients who undergo cardiac surgery. The majority of the benefits of dexmedetomidine were not significant in patients undergoing noncardiac surgery. An increased risk for bradycardia should be taken into consideration when prescribing dexmedetomidine. International Prospective Register of Systematic Reviews identifier: CRD42017070791.
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Because inflammation is a key process implicated in the pathogenesis of atherosclerosis at all stages, including plaque formation, progression, instability, and rupture, and because colchicine has unique anti-inflammatory properties, this review article summarizes the pathophysiologic mechanisms underpinning inflammation in atherosclerosis and acute coronary syndrome (ACS), outlines anti-inflammatory therapeutic approaches that have been tested thus far, and evaluates the evidence supporting the potential role of colchicine in improving outcomes and reducing cardiovascular morbidity and mortality in patients after ACS. ⋯ Despite promising results in small prospective observational and randomized trials, there is a need for more evidence evaluating the role of colchicine as a secondary preventive agent after ACSs.
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Clinical therapeutics · Oct 2018
Randomized Controlled Trial Multicenter StudyAnalgesic Efficacy of an Acetaminophen/Ibuprofen Fixed-dose Combination in Moderate to Severe Postoperative Dental Pain: A Randomized, Double-blind, Parallel-group, Placebo-controlled Trial.
Acute pain is a significant burden to the individual and to society. There is a clear need for a pain medication that provides improved analgesia over common analgesics, without compromising tolerability. The goal of this study was to determine the efficacy of a new fixed-dose combination of acetaminophen 975 mg and ibuprofen 292.5 mg (FDC 975/292.5) relative to acetaminophen or ibuprofen monotherapy, or placebo. ⋯ Overall, the fixed-dose combination of acetaminophen and ibuprofen provided greater and more rapid analgesia than comparable doses of either agent alone or placebo in adults after removal of impacted third molars. ClinicalTrials.gov identifier: NCT01420653.
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Clinical therapeutics · Oct 2018
Randomized Controlled Trial Comparative StudyBioavailability of Edaravone Sublingual Tablet Versus Intravenous Infusion in Healthy Male Volunteers.
Edaravone is a free-radical scavenger. Edaravone 30mg IV has been approved for use in the treatment of acute ischemic stroke in Japan and China, and for amyotrophic lateral sclerosis in Japan and the United States. Considering the inconvenience of IV infusion in clinical practice, an oral tablet formulation of edaravone was developed but failed in 2011 due to poor bioavailability. More recently, a sublingual (SL) tablet formulation of edaravone 30mg was developed by a Good Manufacturing Practices-compliant manufacturer in China. This study explored the bioavailability of the SL tablet of edaravone and aimed to provide evidence to support decision making in future clinical development. ⋯ The bioavailability of the SL tablet of edaravone was 91.94%. Compared with IV administration, Cmax with SL administration was ∼17% lower and Tmax was statistically significantly longer. The exposure differences can be addressed by modifying the strength of the SL tablet, and then conducting a second study to demonstrate the pharmacokinetic bioavailability of the sublingually administered new strength versus IV infusion of edaravone.