Journal of clinical pharmacology
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To date, the actual relationship between antimuscarinics for overactive bladder (OAB) syndrome and the subsequent risk of a fracture remains unclear. The aim of this retrospective cohort study was to demonstrate the association between antimuscarinics for OAB and fractures using a large population-based data set. Data used in this study were taken from the Taiwan Longitudinal Health Insurance Database 2005. ⋯ Results revealed that the incidence rate of fracture per 100 person-years within the 3-year follow-up period were 3.01 (95% confidence interval [CI], 2.65-3.40) for OAB patients who received antimuscarinics and 2.77 (95%CI, 2.60-2.95) for those OAB patients who did not receive antimuscarinics. The adjusted hazard ratio (HR) for a subsequent fracture for OAB patients who received antimuscarinics was 1.11 (95%CI, 0.97-1.28) compared with those OAB patients who did not receive antimuscarinics. Consequently, we concluded that antimuscarinics for OAB was not significantly predictive of fracture.
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Oliceridine is a novel G protein-biased ligand at the μ-opioid receptor that differentially activates G protein coupling while mitigating β-arrestin recruitment. Unlike morphine, oliceridine has no known active metabolites; therefore, analgesic efficacy is predictably linked to its concentration in the plasma. Oliceridine is primarily hepatically metabolized by CYP3A4 and CYP2D6. ⋯ The simulations also revealed that a 1-mg "supplemental dose" given 0.25 hour after the loading dose would decrease NPRS scores further in almost one-third of patients. In addition, if oliceridine is administered prn, a longer interval between doses is observed in simulated PM patients, consistent with their reduced oliceridine clearance. Because this longer average dosing interval is predicted to decrease oliceridine exposure in PM patients, the need to know the patient's CYP2D6 genotype for dosing is effectively obviated.
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Randomized Controlled Trial Comparative Study
A Randomized Double-Blind Controlled Trial of Intravenous Meloxicam in the Treatment of Pain Following Dental Impaction Surgery.
This randomized, controlled phase 2 study was conducted to evaluate the analgesic efficacy, safety, and tolerability of single intravenous (IV) doses of 15 mg, 30 mg, and 60 mg meloxicam compared with oral ibuprofen 400 mg and placebo after dental impaction surgery. The primary efficacy end point was the sum of time-weighted pain intensity differences for 0-24 hours postdose. Among 230 evaluable subjects, meloxicam IV 60 mg produced the greatest reduction in pain, followed by the 30-mg and 15-mg doses. ⋯ There were no deaths, serious adverse events, or discontinuations due to adverse events. The incidence of subjects with ≥1 treatment-emergent adverse event was greatest in the placebo group, followed by the groups that received ibuprofen, meloxicam IV 15 mg, 30 mg, and 60 mg. Nausea was the most commonly reported treatment-emergent adverse event.
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The Federal Policy for the Protection of Human Subjects, generally referred to as the "Common Rule," is the basis for the human research protection policies of 16 signatory federal agencies and governs virtually all federally funded research involving humans. The Common Rule was originally published in 1991. It has been recognized that changes to the Common Rule are needed to accommodate changes in the research environment and advances in information technology. ⋯ The 21st Century Cures Act, which became law in December 2016, enables faster drug approvals by expanding the kinds of evidence, beyond traditional clinical trials, that the FDA can consider when reviewing new drug applications. For example, the law allows greater use of surrogate markers and data from "real-world experience" to evaluate a drug's efficacy. The Cures Act requires HHS and the FDA to harmonize differences between the Common Rule and FDA regulations for protection of human subjects in research.
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Review Meta Analysis
Haloperidol Versus 5-HT3 Receptor Antagonists for Postoperative Vomiting and QTc Prolongation: A Noninferiority Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.
Haloperidol is an antipsychotic with well-known antiemetic potential. It is underutilized for postoperative nausea vomiting due to reported corrected QT interval (QTc) prolongation. This meta-analysis evaluates its safety and efficacy as an antiemetic in the perioperative period. ⋯ Publication bias was unlikely (Egger test, X-intercept = 2.07, P = 0.10). We conclude that haloperidol is equivalent to the well-established 5-HT3 -RAs in preventing vomiting during the first day after surgery. The incidence of QTc prolongation with haloperidol is statistically equivalent to 5-HT3 -RAs and thus should not be the factor that discourages its use for treatment/prophylaxis of postoperative nausea vomiting.