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Background. Bleeding is a serious adverse drug reaction associated with warfarin therapy, often induced by interacting co-medication. Methods. We investigated the frequency and clinical consequences of warfarin drug interactions utilizing medical records of 6,772 warfarin-treated in-patients of Turku University Hospital. Results. A total of 48% of warfarin-treated in-patients were exposed to interacting co-medication. Adjusted odds ratio (OR) for bleeding was highest for cytochrome P450 2C9 (CYP2C9) inhibitors (OR 3.6; 95% confidence interval (CI) 2.4-5.6). Non-selective non-steroidal anti-inflammatory drugs (NSAID) and coxibs were associated with a bleeding risk of a similar magnitude (OR 2.6; 95% CI 1.6-4.2 and OR 3.1; 95% CI 1.4-6.7, respectively). Selective serotonin re-uptake inhibitors (SSRI) were associated with a remarkably higher bleeding risk than non-SSRIs (OR 2.6; 95% CI 1.5-4.3 and OR 1.2; 95% CI 0.3-4.3, respectively). Odds ratio for bleeding in the platelet aggregation inhibitor group was 1.6 (95% CI 0.8-3.1). Conclusion. We conclude that co-medication in warfarin-treated in-patients is common and should be carefully evaluated to decrease the bleeding risk associated with warfarin therapy. [ABSTRACT FROM AUTHOR]

Background. Because of the prominence of pain-related conditions and the growing complexities of clinical management we aimed to explore and attempt to dispel the several myths that surround these serious therapeutic issues. Aims. We aimed to provide a careful analysis of the evidence and draw factually based guidance for physicians who manage the broad range of patients with pain. Methods. Current myths were identified based on the authors' clinical, scientific, and academic experience. Each contributor addressed specific topics and made his own selection of primary references and systematic reviews by searching in MEDLINE, EMBASE, and CINAHL databases (1990-2008) as well as in the proceedings of the major digestive and rheumatology meetings. The writing and references provided by each contributor were collectively analyzed and discussed by all authors during several meetings until the final manuscript was prepared and approved. Results. Seven major 'historical' myths that may perpetuate habits and beliefs in clinical practice were identified. Each of them was thoroughly examined and dispelled, drawing conclusions that should help guide physicians to better manage patients with pain. Conclusions. Pain relief must be considered a human right, and patients with osteoarthritis pain should be treated appropriately with analgesic or/and anti-inflammatory drugs. The risk of gastrointestinal (GI) complications with traditional non-steroidal anti-inflammatory drugs (t-NSAIDs) is present from the first dose (with both short-term and long-term use), and strategies to prevent GI complications should be considered regardless of the duration of therapy. Compared with t-NSAIDs, coxib use is associated with a small but significant reduction of dyspepsia. While protecting the stomach, proton pump inhibitors do not prevent NSAID-induced intestinal damage. To this end, coxib therapy could be the preferred option, although further randomized studies are needed. A substantial number of patients who need NSAIDs are also taking low-dose aspirin for cardiovascular prophylaxis. From a GI perspective, the combination of aspirin plus a coxib provides a preferred option compared with aspirin plus a t-NSAID, for patients at high GI risk. As the incidence of renovascular adverse effects with t-NSAIDs and coxibs is similar, blood pressure should be monitored and managed appropriately in patients taking these drugs, although they should be avoided in those with severe congestive heart failure. Due to increased cardiovascular risk, which is dependent on the dose, duration of therapy, and base-line cardiovascular risk, both t-NSAIDs and coxibs should be used with caution in patients with underlying prothrombotic states and/or concomitant cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

It is now over 100 years since the arrival of aspirin and, from the mid-20th Century onwards, we have seen numerous attempts at providing society with safer and more efficacious nonsteroidal drugs. Ironically, while aspirin went from strength to strength with an ever-increasing pharmaceutical profile, new nonsteroidal anti-inflammatory drugs arrived and disappeared with rapid succession. Finally, there appears to have been a breakthrough with the development of the coxibs but concern has recently developed because of potential toxic cardiovascular reactions. Although originally studied in rheumatoid arthritis and degenerative arthropathy, the coxibs have now been investigated in ankylosing spondylitis and efficacy appears to be favorable and, to date, there is little evidence of toxicity, although problems in the nonspondylarthropathic arena may spill over into the seronegative spondylarthritides. [ABSTRACT FROM AUTHOR]

Since selective cyclooxygenase-2 inhibitors (coxibs) entered the market, there has been concern about the cardiovascular safety of coxibs. In addition, recent data suggest that classical non-steroidal anti-inflammatory drugs (NSAIDs) have a similar cardiovascular risk. Importantly, all of the clinical trials with NSAIDs and coxibs so far were not purpose-designed to specifically and prospectively address cardiovascular safety and were clearly underpowered to detect any meaningful differences. In this current uncertainty about safety of NSAIDs and coxibs, the definitive answer as to the net effect of coxibs and NSAIDs on cardiovascular events can only be provided by well designed adequately powered, long-term clinical trials, which is now under way. [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2 inhibitors were initially developed, then received regulatory approval and were subsequently widely marketed to achieve effective pain relief in patients with inflammatory conditions while decreasing gastrointestinal complications. Gastrointestinal symptoms as well as signs had been a major concern with the use of traditional non-steroidal anti-inflammatory drugs. Individual clinical judgements about the prescription of cyclooxygenase-2 inhibitors and non-steroidal anti-inflammatory drugs for relief of pain from inflammatory arthritis should not be limited to risks of cardiovascular disease but should also consider gastrointestinal complications, symptoms as well as signs, and other benefits which include, but are not limited to improvements in quality of life resulting from decreases in pain or impairment from musculoskeletal pain syndromes. [ABSTRACT FROM AUTHOR]

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed are titration of sustained acting opioids, tolerance versus opioid-resistance, opioids for osteoarthritis pain, and the potential usefulness of kappa opioid receptor agonists for visceral pain. [ABSTRACT FROM AUTHOR]

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed in this issue are the potential effect of nonsteroidal anti-inflammatory drugs on bone fractures, use of topical analgesics for osteoarthritis pain in a patient who is nonadherent with oral pharmacotherapy, and the use of transcutaneous nerve stimulation for cancer pain management. [ABSTRACT FROM AUTHOR]