American journal of therapeutics
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To assess the impact of individualized medication effectiveness tests (IMETs, or n-of-1 trials), on patients' short-term decision making about medications for chronic pain. Survey evaluation of patients undergoing a double-blind, crossover comparison of drug versus placebo, drug versus drug, or drug versus drug combination using paracetamol and ibuprofen in 3 pairs of treatment periods, randomized within pairs. General practice patients (supplemented by a few from 2 tertiary pain clinics) with either chronic pain (> or =3 months), or osteoarthritis (with pain for > or =1 month) severe enough to warrant consideration of long-term nonsteroidal antiinflammatory drug (NSAID) use but for whom there was doubt about the efficacy of NSAID or alternative. ⋯ IMETs provide useful information for clinical decisions. Paracetamol continues to be useful for patients with chronic pain whose optimal drug choice is in doubt. Our results provide a new (individual) perspective on the well-known recommendation for paracetamol as first-line treatment for chronic pain and demonstrate that it is feasible to provide IMETs nationally by mail and telephone.
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Chronic pain is a significant public health burden. Several international guidelines and influential reviews recommend the use of paracetamol (acetaminophen) as the first-line analgesic of choice for the management of chronic pain. These recommendations are based largely on the balance of evidence, which favorably demonstrates the efficacy, safety, and low cost of paracetamol relative to other analgesics. ⋯ Today, the results of our investigations into the individualization of pain management options continue to support this suggestion. Based on the data available to date, it still seems prudent to use NSAIDs only in those patients in whom there is good evidence of improved efficacy over paracetamol. In patients with chronic pain, paracetamol can play an important role as an NSAID sparer, with resultant benefits in terms of reduced adverse effects and cost savings.
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The idea that opioids modulate the immune system is not new. By the late 19th century, Cantacuzene, used morphine to suppress cellular immunity and lower the resistance of guinea pigs to bacterial infection. While exogenous opioids mediate immunosuppression, endogenous opiates exert opposite actions. ⋯ The immunosuppression mediated by opiates may explain the increased incidence of infection in heroin addicts. Opiates may also promote immunodeficiency virus infection by decreasing the secretion of alpha and beta chemokines (important inhibitory cytokines for the expression of HIV) and at the same time increasing the expression of chemoreceptors CCR5 and CCR3, coreceptors for the virus. The fact that peripheral immunosupression is mediated at least in part by opioid receptors located in the central nervous system and that intrathecally administered opioids do not exert the same immunosuppressive effects may have important clinical implications for those patients receiving long-term opioid therapy for malignant and nonmalignant pain.
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Randomized Controlled Trial Comparative Study Clinical Trial
Benefits and risks of granisetron versus ramosetron for nausea and vomiting after breast surgery: a randomized, double-blinded, placebo-controlled trial.
Women undergoing general anesthesia for breast surgery are at particular risk of postoperative nausea and vomiting. In a randomized, double-blinded, placebo-controlled trial, 90 patients scheduled for breast surgery, aged 33-63 years, received intravenously placebo, 3 mg granisetron, or 0.3 mg ramosetron (n = 30 of each) at the end of surgical procedure. A standard general anesthetic technique and postoperative analgesia were used. ⋯ Zero to 24 hours after anesthesia, no difference in the rate of patients having emetic symptoms and the severity of nausea was observed between the granisetron and ramosetron groups. The most common reported adverse events were headache and dizziness, and there were no difference in the incidence of adverse events due to the study drug among the 3 groups. In conclusion, prophylactic therapy with ramosetron is more effective than that with granisetron for the long-term prevention of postoperative nausea and vomiting in women undergoing general anesthesia for breast surgery.
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Meta Analysis Comparative Study
Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis.
There have been concerns that the risk of cardiovascular thrombotic events may be higher with cyclooxygenase (COX)-2-specific inhibitors than nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We evaluated cardiovascular event data for valdecoxib, a new COX-2-specific inhibitor in approximately 8000 patients with osteoarthritis and rheumatoid arthritis treated with this agent in randomized clinical trials. The incidence of cardiovascular thrombotic events (cardiac, cerebrovascular and peripheral vascular, or arterial thrombotic) was determined by analyzing pooled valdecoxib (10-80 mg daily), nonselective NSAID (diclofenac 75 mg bid, ibuprofen 800 mg tid, or naproxen 500 mg bid) and placebo data from 10 randomized osteoarthritis and rheumatoid arthritis trials that were 6-52 weeks in duration. ⋯ Thrombotic risk was consistently higher for users of aspirin users than nonusers of aspirin (placebo, 1.4% vs. 0%; valdecoxib, 1.7% vs. 0.2%; NSAIDs, 1.9% vs. 0.5%). The rates of events in users of aspirin were similar for all 3 treatment groups and across valdecoxib doses. Short- and intermediate-term treatment with therapeutic (10 or 20 mg daily) and supratherapeutic (40 or 80 mg daily) valdecoxib doses was not associated with an increased incidence of thrombotic events relative to nonselective NSAIDs or placebo in osteoarthritis and rheumatoid arthritis patients in controlled clinical trials.