EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases.

To develop recommendations for the management of medium to high-dose (ie, >7.5 mg but ≤100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.

Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative.

OBJECTIVE: A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. METHODS: An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. RESULTS: 570 patients (79% women, mean ± SD age 56 ± 13 years, disease duration 12.5 ± 10.3 years, disease activity score (DAS28) 4.1 ± 1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical -0.59 and mental -0.55, p<0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). CONCLUSION: The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.

Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice.

OBJECTIVE: To develop recommendations on monitoring for adverse events (AEs) of low-dose glucocorticoid (GC) therapy (≤7.5 mg prednisone or equivalent daily) in clinical trials and daily practice. METHODS: Literature was searched for articles containing information on incidence and monitoring of GC-related AEs using PubMed, EMBASE and Cochrane databases. Second, the authors searched for broad accepted guidelines on the monitoring of certain AEs (eg, WHO guidelines on screening for diabetes). Available data were summarised and discussed among experts (rheumatologists and patients) of the EULAR Task Force to decide which potential AEs should be monitored, how and at which interval. RESULTS: Data on monitoring proved to be scarce; most articles were focused on therapeutic effects of GCs, not on occurrence and monitoring of AEs. Most recommendations had to be based on consensus. Those for clinical trials aimed at getting insights into incidence, prevalence and clinical relevance of AEs to create a comprehensive and valid AE-profile of GC therapy. The set of AEs to monitor is therefore more extensive, and often consists of assessments at baseline and at end of trials. Recommendations for daily practice are meant to protect patients from real dangers, which can be prevented or treated. Standard care monitoring needs NOT be extended for patients on low-dose GC therapy, except for osteoporosis (follow national guidelines), and baseline assessments of ankle edema, fasting blood glucose and risk factors for glaucoma. CONCLUSION: Given the incompleteness of literature data, consensus-based recommendations on monitoring for GC-related AEs were created, separately for daily practice and clinical trials.

Patient and rheumatologist perspectives on glucocorticoids: an exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases.

OBJECTIVE: To explore perspectives among patients and rheumatologists on glucocorticoid (GC) therapy and European League Against Rheumatism (EULAR) recommendations on the management of systemic GC therapy in order to enhance implementation of the recommendations. METHODS: Rheumatologists (from eight countries) and patients (from five countries) acquainted with GCs participated in separate meetings, during which positive and negative aspects of GC therapy were discussed and possible adverse events (AEs) were ranked for importance; in addition participants were asked to evaluate the published EULAR recommendations. The reports from these meetings and themes related to implementation of the recommendations were discussed during an international forum of the experts who had formulated the recommendations and patient participants. RESULTS: In all, 140 patients (78% women; mean age 53 years; 61% patients with rheumatoid arthritis) and 110 rheumatologists (mean work experience 15 years) participated in the meetings. Osteoporosis, diabetes and cardiovascular diseases were ranked among the five most worrisome AEs by patients and rheumatologists. In both groups, there was agreement with most of the recommendations; the recommendations on GC information cards and GC use during pregnancy scored lowest. Ideas to improve implementation of the recommendations and a research agenda were generated. CONCLUSION: The patient and rheumatologist views on GCs corresponded to a large extent, reflected by concerns in both groups about osteoporosis, diabetes and cardiovascular diseases. Specific problems with the EULAR recommendations were identified and addressed to improve their implementation. This exercise shows that patient and rheumatologist perspectives should be included early in the process of formulating recommendations.

Overnight variations in cortisol, interleukin 6, tumour necrosis factor alpha and other cytokines in people with rheumatoid arthritis.

OBJECTIVE: To investigate overnight variations in absolute values and patterns of cytokines including interleukin 6 (IL6) and tumour necrosis factor alpha (TNFalpha) in rheumatoid arthritis (RA), and to relate any changes to those occurring in blood cortisol. METHODS: A total of 16 people (8 female) with active RA and who had received no recent glucocorticoids were admitted overnight. Blood samples were obtained at 13 time points between 21.00 and 10.00. RESULTS: The geometric mean IL6 concentration rose significantly from 35 pg/ml at 22:00 to 64 pg/ml at 07:15 (repeated measures analysis of variance (ANOVA), p<0.001). The geometric mean cortisol concentration rose significantly overnight from 57 ng/ml at 01:00 to 229 ng/ml at 07:15 (repeated measures ANOVA, p<0.001). Neither TNFalpha nor the other cytokines measured changed significantly. Using cubic regression modelling IL6 began to rise before cortisol (range 0.01 to 4.83 h) in eight participants and after cortisol (range 1.11 to 5.14 h) in three participants. In a random coefficient model including data from all participants, the estimated mean IL6 value began to rise 3.05 h before the estimated mean cortisol value, with the IL6 peak occurring 0.70 h before the cortisol peak. CONCLUSION: The mean IL6 and cortisol concentrations showed a significant overnight variation. Neither TNFalpha nor the other cytokines measured changed significantly. In a random coefficient model IL6 began to rise approximately 3 h, and reached a peak about 40 min, before cortisol. These studies confirm that there are abnormalities in plasma cortisol and IL6 concentrations and dynamics. The data also link the overnight rise in IL6 to the circadian variation in symptoms.

Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative.

BACKGROUND: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. OBJECTIVE: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. METHODS: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to "distribute 100 points" among the seven domains. The average ranks of importance of these domains were then computed. RESULTS: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. CONCLUSION: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.

EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases.

OBJECTIVE: To develop evidence-based recommendations for the management of systemic glucocorticoid (GC) therapy in rheumatic diseases. METHODS: The multidisciplinary guideline development group from 11 European countries, Canada and the USA consisted of 15 rheumatologists, 1 internist, 1 rheumatologist-epidemiologist, 1 health professional, 1 patient and 1 research fellow. The Delphi method was used to agree on 10 key propositions related to the safe use of GCs. A systematic literature search of PUBMED, EMBASE, CINAHL, and Cochrane Library was then used to identify the best available research evidence to support each of the 10 propositions. The strength of recommendation was given according to research evidence, clinical expertise and perceived patient preference. RESULTS: The 10 propositions were generated through three Delphi rounds and included patient education, risk factors, adverse effects, concomitant therapy (ie, non-steroidal anti-inflammatory drugs, gastroprotection and cyclo-oxygenase-2 selective inhibitors, calcium and vitamin D, bisphosphonates) and special safety advice (ie, adrenal insufficiency, pregnancy, growth impairment). CONCLUSION: Ten key recommendations for the management of systemic GC-therapy were formulated using a combination of systematically retrieved research evidence and expert consensus. There are areas of importance that have little evidence (ie, dosing and tapering strategies, timing, risk factors and monitoring for adverse effects, perioperative GC-replacement) and need further research; therefore also a research agenda was composed.

Effects of glucocorticoids on radiological progression in rheumatoid arthritis.

BACKGROUND: Glucocorticoid use in rheumatoid arthritis (RA) is widespread. Two Cochrane Reviews have been published examining the short term clinical benefit of low dose glucocorticoids compared to non-steroidal anti-inflammatory drugs and demonstrate good short term and medium term clinical benefits. The possibility that glucocorticoids may have a fundamental 'disease modifying' effect in RA, which would be seen by a reduction in the rate of radiological progression, has been raised by several authors. OBJECTIVES: To perform a systematic review of studies evaluating glucocorticoid efficacy in inhibiting the progression of radiological damage in rheumatoid arthritis. SEARCH STRATEGY: A search of MEDLINE (from 1966 to 22 February 2005) and the Cochrane Controlled Trials Register was undertaken, using the terms 'corticosteroids' and 'rheumatoid arthritis' expanded according to the Cochrane Collaboration recommendations. Identified abstracts were reviewed and appropriate reports obtained in full. Additional reports were identified from the reference lists and from expert knowledge. SELECTION CRITERIA: Randomized controlled or cross-over trials in adults with a diagnosis of rheumatoid arthritis in which prednisone or a similar glucocorticoid preparation was compared to either placebo controls or active controls (i.e. comparative studies) and where there was evaluation of radiographs of hands, or hands and feet, or feet by any standardised technique. Eligible studies had at least one treatment arm with glucocorticoids and one without glucocorticoids. DATA COLLECTION AND ANALYSIS: Standardised data extraction obtain the mean and standard deviation (SD) of change in erosion scores over 1 year or 2 years. (Where SD for change was not given a conservative estimate was taken from baseline data.) At least two authors selected the studies and extracted the data. Radiographic erosion scores were expressed as a percentage of the maximum possible score for the method used. The results were pooled after weighting in a random effects model to provide a standardised mean difference (SMD). MAIN RESULTS: The initial search produced 217 citations, and 15 were added from experts, abstracts and review of reference lists. Authors of 4 trials being prepared for publication (and subsequently published) kindly shared their data. After application of eligibility criteria 15 studies and 1,414 patients were included. The majority of trials studied early RA (disease duration up to 2 yrs), and the mean cumulative dose of glucocorticoid was 2,300 mg prednisone equivalent (range 270 mg - 5,800 mg) over the first year. Glucocorticoids were mostly added to other disease modifying anti-rheumatoid drug (DMARD) treatment. The standardised mean difference in progression was 0.40 in favour of glucocorticoids (95% CI 0.27, 0.54). In studies lasting 2 years (806 patients included), the standardised mean difference in progression in favour of glucocorticoids at 1 year was 0.45 (0.24, 0.66) and at 2 years was 0.42 (0.30, 0.55). All studies except one showed a numerical treatment effect in favour of glucocorticoids. The beneficial effects of glucocorticoids were generally achieved when used in conjunction with other DMARD treatment. AUTHORS' CONCLUSIONS: Even in the most conservative estimate, the evidence that glucocorticoids given in addition to standard therapy can substantially reduce the rate of erosion progression in rheumatoid arthritis is convincing. There remains concern about potential long-term adverse reactions to glucocorticoid therapy, such as increased cardiovascular risk, and this issue requires further research.

Is There a Renaissance of Glucocorticoids in Rheumatoid Arthritis?

The first therapeutic use of glucocorticoids was in a patient with severe rheumatoid arthritis and the symptomatic benefit was astounding. Adverse effects from increasingly large doses led to them being overshadowed, dismissed as inappropriate treatment, and ignored for 20 years - but in the last 2 decades, the accumulating evidence and clinical practice suggest there is a justified renaissance in their use as a first-line treatment.

Hypothalamo-pituitary-adrenal axis dysregulation in patients with rheumatoid arthritis after the dexamethasone/corticotrophin releasing factor test.

A defective hypothalamo-pituitary-adrenal axis response to inflammatory cytokines may contribute to the pathophysiology of rheumatoid arthritis (RA). The purpose of this study was to define further the mechanisms responsible for this dysregulation. Six normal individuals and seven patients with active RA were recruited and given an oral dose of dexamethasone at 2300 h the evening before the study. The next day, an i.v. catheter was fitted at 1300 h. Blood samples were collected between 1400 h and 1700 h before and after infusion (at 1500 h) of corticotrophin releasing factor (CRF). Plasma was separated and stored at-20 degrees C before radioimmunoassay for ACTH, cortisol and dihydroepiandrosterone (DHEA). Before the CRF challenge, ACTH and cortisol were significantly increased and DHEA significantly decreased in the patients with RA compared with the controls. Neither ACTH nor DHEA was significantly altered after CRF infusion. Control individuals did not mount a cortisol response to infusion of CRF. Similarly, four of the patients with RA did not respond to CRF. However, in contrast to the controls, three of the patients mounted an immediate and sustained cortisol response after receiving CRF. These data reveal that three of the seven patients with RA were able to escape from dexamethasone suppression and mount a cortisol response to CRF challenge. This suggests that there may be a subpopulation of patients with RA who have impaired glucocorticoid feedback. The implications of this alteration for disease progression remain to be determined.

Multiple HLA associations and disease susceptibility.

A strong association between a particular HLA antigen and a given disease may mask a secondary, weaker association. Applying a stepwise analysis to published HLA-DR frequencies in rheumatoid arthritis demonstrates an increased frequency of DRI not otherwise apparent.

Systemic low-dose glucocorticoid treatment in rheumatoid arthritis.

Glucocorticoids provide a large, immediate improvement in the symptoms of rheumatoid arthritis. At doses acceptable for long-term treatment, however, symptoms gradually re-emerge. Relatively low doses of glucocorticoids can, for several years, substantially retard the rate of joint destruction shown on radiographs. This differential effect implies the coexistence of two pathologic processes within diseased joints. Long term, low dose glucocorticoid therapy probably increases the risk of serious adverse effects, but an evidence-based case can be made for the limited use of low dose glucocorticoid treatment in early disease.

What is a safe waiting time for coronary artery bypass surgery?

To determine the factors that influenced doctors' prioritization and decisions on safe waiting time for coronary artery bypass surgery, 50 'paper patients', based on a random sample of cases who actually had surgery, were assessed by 33 clinicians. We used linear regression models to reflect the impact of clinical and non-clinical 'cues' on safe waiting time and priority decisions. The benefits of surgery tended to be over-estimated. For example, the average perceived gain in life expectancy for patients with left main-stem disease was 6.74 years. However, models incorporating only the perceptions of benefit as independent variables (i.e. the anticipated symptom reduction, MI risk reduction and life expectancy extension), had only modest explanatory power (mean R2 was 0.55 for safe waiting time, and 0.56 for priority decisions). Models which incorporated perceptions of benefit and the cases' clinical and non-clinical characteristics had generally much higher explanatory power (mean R2, 0.83 and 0.86, respectively). Lifestyle and demographic variables had much less impact on the doctors' judgements than the major clinical cues of angina severity and left main-stem stenosis. Demographic and lifestyle cues had different impacts on safe waiting time and priority for about 25% of doctors.

The stated and tacit impact of demographic and lifestyle factors on prioritization decisions for cardiac surgery.

In a clinical judgement analysis, we used linear regression models to reflect the impact of clinical and non-clinical cues on priority decisions, by comparing the stated prioritization policies of 30 clinicians with their actual policies as revealed by an appraisal of 50 'paper patients'. Correspondence was modest for some cues, e.g. 25 doctors said they accounted for age, but age only had a significant bearing in the derived decision models of two doctors. Correspondence between the derived and expressed weights was greatest for clinical angina grade and the presence of left main stem stenosis. Correlation between the rank order of importance between the two models was poor for most of the cues, and statistically significant only for smoking. However, stated policies made it appear that lifestyle factors such as smoking habit would influence prioritization decisions for most clinicians but policies derived from actual prioritization decisions seldom related to lifestyle or demographic variables. There were significant differences in the degree of correlation between the two models according to the experience of the clinician. However, correspondence was not significantly better for doctors with cardiological training than those without. The overall contribution of demographic and lifestyle factors to decision making appears to be small, suggesting that they should be omitted from prioritization guidelines.

Prognostic criteria in rheumatoid arthritis: can we predict which patients will require specific anti-rheumatoid treatment?

UNLABELLED: Longitudinal studies of rheumatoid arthritis (RA) have shown that joint damage often occurs early in the disease. Therefore, the early treatment of RA with "disease modifying" drugs is gaining acceptance. However, many patients presenting with inflammatory polyarthropathy will follow a benign course. Rheumatologists need to be able to target the use of potentially toxic drugs to those cases where the benefits clearly outweigh the risks. This approach requires reliable assessment of the prognosis at an early stage in the disease process. We have critically evaluated a large number of published studies which claim to provide clinically useful information regarding the prognosis of RA. CONCLUSION: The majority of studies have methodological flaws which limit their value. A small number of published studies exist which provide useful data about estimating the prognosis of RA. Currently evaluated prognostic indicators are only moderately successful and there is an urgent need for methodologically sound research in this area.

Cytidine deaminase may be a useful marker in differentiating elderly onset rheumatoid arthritis from polymyalgia rheumatica/giant cell arteritis.

OBJECTIVE: PMR/GCA is a relatively common inflammatory disease in the elderly population. Clinical differentiation from a polymyalgic onset of RA in the elderly can be difficult. We have examined in a preliminary study the hypothesis that serum cytidine deaminase (CD) may be valuable in the differential diagnosis of these disorders. METHODS: CD was assayed by a spectrophotometric method in 20 patients with active PMR/GCA, both before and after treatment with prednisolone, and was compared with serum CD levels in 20 patients with active RA. RESULTS: CD levels were within the normal range (< 10 units/ml) in 36 of the 40 samples from patients with PMR/GCA: The mean CD in pre-treatment samples was 8.64 units/ml (SD 7.09), and after treatment 7.20 units/ml (SD 3.53). The mean serum CD in the RA patients was 21.33 units/ml (SD 8.94), significantly higher than in PMR/GCA (p < 0.0001). CONCLUSION: Serum CD levels were significantly different when proven PMR was compared with established, long-standing RA. Therefore, serum CD could be a useful diagnostic marker for differentiating PMR/GCA from active RA in older patients.

Low dose corticosteroids in early rheumatoid arthritis. Can these drugs slow disease progression?

The role of corticosteroids in treating rheumatoid arthritis is controversial, but recourse to the available evidence of efficacy should guide patient management decisions. Earlier evidence suggested that symptomatic control could be improved for periods of 6 to 12 months, but not longer, without increasing doses to unacceptably high levels. The effect of corticosteroids on joint destruction has been unclear. Recent findings from a controlled clinical trial show that prednisolone 7.5 mg/day can significantly retard the rate of erosive progression in patients with relatively early disease (< 2 years' duration). These results have implications for both disease management and our understanding of the pathogenesis of joint destruction in rheumatoid arthritis.

General practitioners miss disability and anxiety as well as depression in their patients with osteoarthritis.

BACKGROUND: General practitioners (GPs) integrate physical, psychological, and social factors when assessing patients, particularly those with chronic diseases. Recently, the emphasis has been on assessment of depression but not of other factors. AIM: To determine functional disability, psychological morbidity, social situation, and use of health and social services in patients with osteoarthritis and examine GP knowledge of these factors. METHOD: Two hundred patients completed a validated postal questionnaire about functional disability (Health Assessment Questionnaire [HAQ]), mood (Hospital Anxiety and Depression Scale [HAD]), employment status, who they lived with, welfare benefits received, and use of health and social services. A similar questionnaire was completed by the patient's GP, including a HAQ. However, a three-point scale was used to assess depression and anxiety. RESULTS: Forty-seven per cent of patients were moderately or severely disabled (HAQ > 1). GPs underestimated functional disability: mean patient HAQ = 1.04 (95% confidence interval [CI] = 0.92-1.16), mean GP HAQ = 0.74 (95% CI = 0.65-0.83), and there was low correlation between patient and GP scores (kappa = 0.24). There was moderate prevalence of depression and high prevalence of anxiety, which the GP often did not recognise: patient depression = 8.3% (95% CI = 4.1%-12.8%), GP depression = 6.0% (95% CI = 2.4%-9.6%), kappa = 0.11; patient anxiety = 24.4% (95% CI = 17.8%-31.0%), GP anxiety = 11.9% (95% CI = 6.9%-16.9%), kappa = 0.19. Only 46% of severely disabled patients (HAQ > 2) were receiving disability welfare benefits. GPs were often unaware of welfare benefits received or the involvement of other professionals. CONCLUSION: GPs frequently lack knowledge about functional disability, social factors, and anxiety as well as depression in their patients with osteoarthritis.

Non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the knee.

OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last perfomed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading osteoarthritis was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac vesus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences betw

Patient education for adults with rheumatoid arthritis.

BACKGROUND: Because of the unpredictability people with arthritis face on a daily basis, patient education programmes have become an effective complement to traditional medical treatment giving people with arthritis the strategies and the tools necessary to make daily decisions to cope with the disease. OBJECTIVES: To assess the effectiveness of patient education interventions on health status in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched MEDLINE, EMBASE and PsycINFO and the Cochrane Controlled Trials Register. A selection of review articles (see references) were examined to identify further relevant publications. There was no language restriction. SELECTION CRITERIA: Randomised controlled trials (RCT's) evaluating patient education interventions that included an instructional component and a non-intervention control group; pre- and post-test results available separately for RA, either in the publication or from the studies' authors; and study results presented in full, end-of-study report. MAIN RESULTS: Thirty-one studies with relevant data were included. We found significant effects of patient education at first follow-up for scores on disability, joint counts, patient global assessment, psychological status, and depression. A trend favouring patient education was found for scores on pain. Physician global assessment was not assessed in any of the included studies. The dimensions of anxiety and disease activity showed no significant effects. At final follow up no significant effects of patient education were found, although there was a trend favouring patient education for scores on disability. REVIEWER'S CONCLUSIONS: Patient education as provided in the studies reviewed here had small short-term effects on disability, joint counts, patient global assessment, psychological status and depression. There was no evidence of long-term benefits in adults with rheumatoid arthritis.