Objective: To develop evidence based recommendations for the management of gout. Methods: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions on management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat, relative risk, odds ratio, and incremental cost-effectiveness ratio were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. Results: 12 key propositions were generated after three Delphi rounds. Propositions included both nonpharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT), and prophylaxis of acute attacks. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low animal purine diet) and treatment of associated comorbidity and risk factors were emphasised. Recommended drugs for acute attacks were oral non-steroidal anti-inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout. Allopurinol was confirmed as effective long term ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 to 2.24)) and can be used in patients with mild to moderate renal insufficiency but may be hepatotoxic. When gout is associated with the use of diuretics, the diuretic should be stopped if possible. For prophylaxis against acute attacks, either colchicine 0.5-1 mg daily or an NSAID (with gastroprotection if indicated) are recommended. Conclusions: 12 key recommendations for management of gout were developed, using a combination of research based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition. D espite reasonable understanding of its pathogenesis and the availability of effective treatment, gout is often misdiagnosed or diagnosed late in its clinical course, and even when correctly diagnosed treatment is often suboptimal. For example, a recent cross sectional study showed that the prevalence of predefined mismanagement of gout (no drug treatment, analgesic alone, or urate lowering therapy without prophylaxis) was over two times greater with physician management than with patient self management.

Summary. Background: Activation of coagulation and ®brino-lysis play a role in the pathophysiology of experimental arthritis. Objective: To determine the extent of activation of the coagulation and ®brinolytic pathways in different joint diseases in humans and to ascertain the factors that may in¯uence ®brin deposition within the joint. Methods: Plasma from normal subjects (controls, n 21) and plasma and synovial¯uid samples from patients with rheumatoid arthritis (RA; n 64), osteoarthritis (OA; n 29), spondyloarthropathy (SpA; n 22) and crystal arthritis (CA; n 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin±antithrombin III (TAT) complexes, and F1 2 (thrombin fragment), ®brin D-dimer and thrombin-activated ®brinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of in¯ammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for diseasespeci®c differences. Results: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 2 and D-dimers in their plasma. In the synovial¯uid, TF activity, TAT, D-dimers, and TAFI were signi®cantly higher in in¯ammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and D-dimer levels with CRP, TFPI, and TAT. In the synovial¯uid, TF activity correlated with plasma CRP levels, synovial¯uid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial D-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 2 and TAT. Conclusions: Activation of the coagulation and ®brinolytic cascades in the joint and in the circulation is evident in both in¯ammatory and degenerative joint diseases. Within the joint, in¯ammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent ®brin deposition is the most likely explanation for the observed ®ndings. In the plasma, the link between in¯ammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these ®ndings. RA is characterized by signi®cantly higher levels of TAT in the synovial¯uid and plasma than other arthritides. Although ®brinolytic activity is linked to in¯ammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why ®brin formation is so prominent in this condition compared with other joint diseases.

In contrast to irbesartan, losartan was uricosuric and decreased serum uric acid levels. Losartan 50 mg b.i.d. did not produce a greater fall in serum uric acid than losartan once a day. Losartan might be a useful therapeutic tool to control blood pressure and reduce serum uric acid levels in hypertensive patients with hyperuricaemia and gout.