If we detected significant heterogeneity (P 0
January 5, 2022
If we detected significant heterogeneity (P 0.1) we calculated random effects estimates. Appraisal of trial quality We assessed the quality of the tests according to a predefined list of criteria.26 To assess the potential for bias we evaluated the method of randomisation, concealment of allocation, blinding of trial investigators and patients, handling of dropouts and withdrawals, and analysis relating to intention to treat. was 10.1 mm (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13 weeks. The results were heterogeneous, and the effect size for pain reduction was 0.32 (0.24 to Chlormadinone acetate 0.39) inside a random effects model. In 10 tests that did not exclude non-responders to NSAID treatment the results were homogeneous, with an effect size for pain reduction of 0.23 (0.15 to 0.31). Summary NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long term use of NSAIDs for this condition. As severe adverse effects are associated with oral NSAIDs, only limited use can be recommended. Introduction Osteoarthritis of Chlormadinone acetate the knee is the most common type of osteoarthritis,1 the prevalence of which is definitely rising in parallel with the increasing age of the population.2 The condition Chlormadinone acetate is associated with pain and inflammation of the joint capsule,3-5 impaired muscular stability,6,7 reduced range of motion,8 and functional disability.9 Treatment guidelines for knee osteoarthritis recommend pharmacological intervention, initially with paracetamol and subsequently having a non-steroidal anti-inflammatory drug (NSAID).10 In a recent UK survey, 15% PPP2R1B of individuals with osteoarthritis used paracetamol, whereas 50% reported regular use Chlormadinone acetate of NSAIDs. Of the second option, 32% were using traditional NSAIDs and 18% were using cyclo-oxygenase-2 inhibitors (coxibs).11 This common use is definitely one explanation for the interest in tolerability and efficacy issues regarding these medicines.10,12,13 The recent introduction of coxibs seemed to promise a reduction in serious adverse events related to NSAIDs,13,14 but this remains controversial.15-18 Guidelines from your Western League Against Rheumatism (EULAR) state that both pharmacological and non-pharmacological interventions are needed for optimal treatment of knee osteoarthritis.19 The various potentially effective pharmacological interventions in the clinicians’ disposal19 highlight the need for information concerning treatment efficacy. Meta-analyses can be used for reliable comparison of the effectiveness of different interventions.20 Effect size measures the magnitude of a treatment effect independent of sample size.21 There is no current operational definition for what constitutes a sufficiently large effect size for any therapeutic treatment to be considered as useful, but a value of 0.2 is usually considered small, 0.5 moderate, and 0.8 large.22 A recent systematic review of therapeutic alternatives in knee osteoarthritis gives Chlormadinone acetate no effect sizes for paracetamol and an imprecise range (0.47-0.96), derived from a minority of available tests, for NSAIDs.19 Neither other reviewers nor the Cochrane library provide comprehensive and robust effect size data for the efficacy of either of these interventions in osteoarthritis of the knee.10,13,23-25 Calculations of effect size require data for mean change and standard deviation (SD). If not offered, these data can be obtained by indirect means from standard errors, P ideals, ideals, and 95% confidence intervals when sample sizes are known. The lack of data on effect size is definitely amazing because treatment with NSAIDs for knee osteoarthritis is made to the point of being a research against which additional interventions are often compared. We carried out a meta-analysis of published randomised placebo controlled tests to estimate the analgesic effectiveness of NSAIDs, including coxibs, in individuals with knee osteoarthritis. Methods Protocol specification We specified a detailed review of protocol before analysis. This included a sequential three step reviewing process of identifying relevant randomised placebo controlled tests from Medline, Embase, and the Cochrane central register of controlled tests; evaluating their methodological quality relating to predefined criteria (Jadad level)26; and calculating their pooled effect as the mean difference in switch between NSAID organizations and placebo organizations in mm on a visual analogue level and as a unitless effect size. Literature search We carried out the literature search from 1966 to April 2004. In addition, we crosschecked research lists in systematic reviews, searched conference abstracts, and talked to clinical specialists. We included papers in English, German, and Scandinavian. Our key search terms were knee, osteoarthritis, randomised, controlled, placebo, NSAID, coxib, cox-2 inhibitor. Inclusion criteria Trials had to study patients whose knee osteoarthritis had been verified by clinical exam according to the American College of Rheumatology criteria and by x ray. The symptoms had to have been present for more than three months. All tests had to be randomised, blinded, placebo controlled, and of parallel design. Pain intensity had to be scored within the subscale of pain on Western Ontario and McMaster Universities osteoarthritis index (WOMAC)27 or on.