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ID PMID Title PublicationDate abstract
15359000 Correcting biases in standard gamble and time tradeoff utilities. 2004 Sep The standard gamble (SG) method and the time tradeoff (TTO) method are commonly used to measure utilities. However, they are distorted by biases due to loss aversion, scale compatibility, utility curvature for life duration, and probability weighting. This article applies corrections for these biases and provides new data on these biases and their corrections. The SG and TTO utilities of 6 rheumatoid arthritis health states were assessed for 45 healthy respondents. Various corrections of utilities were considered. The uncorrected TTO scores and the corrected (for utility curvature) TTO scores provided similar results. This article provides arguments suggesting that the TTO scores are biased upward rather than having balanced biases. The only downward bias in TTO scores was small and probably cannot offset the upward biases. TheTTOscores are higher than the theoretically most preferred correction of the SG, the mixed correction. These findings suggest that uncorrected SG scores, which are higher than TTO scores, are too high.
14737877 Pressure pain thresholds in the craniofacial region of female patients with rheumatoid art 2003 Fall AIMS: To determine the temporomandibular joint (TMJ) pressure pain threshold (PPT) in female patients with rheumatoid arthritis (RA) and TMJ involvement in comparison with healthy females, in order to determine its clinical usefulness for local pain assessment. METHODS: Forty-two female patients with the diagnosis of RA, 17 of them positive and 25 negative for rheumatoid factor were investigated, as well as 17 healthy females. A pressure algometer was used to assess the PPT over the TMJ and (as a reference) the center of the glabella. The mean of the second and third TMJ PPT was used in the analysis, and the ratio between the TMJ PPT and the PPT of the reference site (PPT ratio) was calculated. Temporomandibular joint resting pain and pain upon maximum voluntary mouth opening was assessed by a visual analog scale on each side. RESULTS: The TMJ PPT (median/10th to 90th percentile) and PPT ratio were significantly lower in the RA patients (148/64 to 220 and 0.63/0.40 to 1.01, respectively) than in the healthy individuals (217/111 to 352 and 0.85/0.51 to 1.25), but the overlap was considerable. CONCLUSION: This study shows that the PPT of the TMJ in RA patients is lower than in healthy individuals and that it can be used for pain assessment. However, the clinical use of the TMJ PPT and PPT ratio measurements alone is limited from a diagnostic point of view.
12235453 Increased genotype frequency of N-acetyltransferase 2 slow acetylation in patients with rh 2002 Sep OBJECTIVES: Acetylation polymorphism can alter therapeutic responses and toxicity to certain xenobiotics and may also be a factor that influences a patient's susceptibility to certain diseases. We investigated whether patients with rheumatoid arthritis (RA) differed from healthy individuals with regard to genotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2). METHODS: NAT2 polymorphism was compared in 118 healthy subjects and 82 patients with RA. NAT2 alleles (*4, *5, *6, and *7) were determined by polymerase chain reaction-restriction fragment length polymorphism methods with deoxyribonucleic acid extracted from peripheral blood. RESULTS: A statistically significant increase in the proportion of homozygous slow acetylators with 2 mutated alleles (84.1%) was found among patients with RA in comparison with healthy subjects (52.5%; P <.0001). The risk of development of RA was almost 5-fold greater in slow acetylators than in fast acetylators (odds ratio, 4.79; 95% confidence interval, 2.28-10.21). There was no correlation between NAT2 polymorphism and presence of rheumatoid factor, extra-articular manifestations, and age at first occurrence of disease symptoms. CONCLUSIONS: NAT2 slow acetylation genotype may be a risk factor of individual susceptibility to RA.
11779763 Can intervention modify adverse lifestyle variables in a rheumatoid population? Results of 2002 Jan BACKGROUND: Rheumatoid arthritis (RA) is associated with significant excess morbidity and mortality. Cardiovascular disease is the commonest cause of premature death in patients with RA. In recognition of this, blood pressure, weight, and smoking history are routinely ascertained in the clinic and appropriate advice and treatment started. AIMS: To ascertain if attending a specialist nurse, in addition to routine medical care, would increase the success in dealing with lifestyle variables in a cohort of patients with RA. METHODS: Twenty two consecutive patients starting treatment with the disease modifying antirheumatic drug (DMARD) sulfasalazine were invited to attend an additional clinic dealing with lifestyle factors every 12 weeks over a 48 week follow up. Smoking and alcohol history, baseline demographic and metrology assessments were determined for all patients. Body mass index (BMI) was calculated, blood pressure recorded, function assessed by the Health Assessment Questionnaire (HAQ), and social deprivation determined by the Carstairs Index. Patients were advised on exercise and diet, and serum cholesterol was measured. RESULTS: Twenty women and two men, with a mean age of 52 years and mean disease duration of five years, were enrolled. Eight patients smoked and, unfortunately, none were persuaded to discontinue. Fifteen of the cohort were already taking regular exercise; one additional patient began swimming regularly. At baseline, 10 patients were found to have a high cholesterol, with a mean of 6.8 mmol/l. A 14% reduction in mean cholesterol was achieved by dietary modification, and three patients merited statin treatment. Obesity is a major problem in our population and 15 of the patients had grade I obesity with a mean BMI of 30.6; five of these gained a further 4.5 kg. Six patients with previously untreated hypertension were identified, but unfortunately five remained hypertensive and only two had received anti-hypertensive drugs. CONCLUSIONS: Educating patients in order to change lifestyle habits and influence outcome is a long term challenge facing all healthcare workers. In our cohort, most adverse lifestyle factors had already been recognised and discussed by the general practitioner or at prior clinic visits. Additional advice and input led to only modest improvement.
12578805 Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. 2003 Feb 15 The association of antioxidant vitamins and trace elements from foods and supplements with risk of rheumatoid arthritis was evaluated in a prospective cohort study of 29,368 women who were aged 55-69 years at baseline in 1986. Through 1997, 152 cases of rheumatoid arthritis were identified. After controlling for other risk factors, greater intakes (highest tertile vs. lowest) of supplemental vitamin C (relative risk (RR) = 0.70, 95% confidence interval (CI): 0.48, 1.09; p-trend = 0.08) and supplemental vitamin E (RR = 0.72, 95% CI: 0.47, 1.12; p-trend = 0.06) were inversely associated with rheumatoid arthritis. There was no association with total carotenoids, alpha- or beta-carotene, lycopene, or lutein/zeaxanthin, while there was an inverse association with beta-cryptoxanthin (RR = 0.59, 95% CI: 0.39, 0.90; p-trend = 0.01). Greater use of supplemental zinc (RR = 0.39, 95% CI: 0.17, 0.88; p-trend = 0.03) was inversely associated with rheumatoid arthritis, while any use of supplemental copper (RR = 0.54, 95% CI: 0.28, 1.03) and manganese (RR = 0.50, 95% CI: 0.23, 1.07) showed suggestive inverse associations with rheumatoid arthritis. Greater intakes of fruit (RR = 0.72, 95% CI: 0.46, 1.12; p-trend = 0.13) and cruciferous vegetables (RR = 0.65, 95% CI: 0.42, 1.01; p-trend = 0.07) also exhibited trends toward inverse associations with risk. When the antioxidants were modeled together, only beta-cryptoxanthin and supplemental zinc were statistically significant predictors. Intake of certain antioxidant micronutrients, particularly beta-cryptoxanthin and supplemental zinc, and possibly diets high in fruits and cruciferous vegetables, may be protective against the development of rheumatoid arthritis.
15224226 [Specialties in therapy of osteoporosis in inflammatory joint disease]. 2004 Jun The therapeutic specialties of osteoporosis in inflammatory rheumatic diseases has gained mounting interest in the last year. The paper describes special aspects of osteoporosis in rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematodes. The problems of glucocorticoid therapy are discussed intensively with regard to the recently published recommendations for glucocorticoid-induced osteoporosis. Risk factors of osteoporosis and the therapeutic implications are demonstrated intensively as well as the modifications of the recommendations.
12833655 IL-1 trap. Regeneron/Novartis. 2003 May Regeneron and Novartis are co-developing the interleukin (IL)-1 antagonist IL-1 trap for the potential treatment of rheumatoid arthritis. In July 2002, a phase II trial was initiated and results are expected mid-2003.
12718750 A novel mechanism for the regulation of IFN-gamma inducible protein-10 expression in rheum 2003 Chemokines play an essential role in the progression of rheumatoid arthritis (RA). In the present study we examined the expression and regulatory mechanisms of IFN-gamma inducible protein (IP)-10 in RA synovitis. RA synovial fluid contained greater amounts of IP-10 than did synovial fluid from patients with osteoarthritis. Immunolocalization analysis indicated that IP-10 was associated mainly with infiltrating macrophage-like cells, and fibroblast-like cells in the RA synovium. The interaction of activated leukocytes with fibroblast-like synoviocytes resulted in marked increases in IP-10 expression and secretion. Moreover, induction of IP-10 was mediated via specific adhesion molecules, as indicated by the finding that both anti-integrin (CD11b and CD18) and intercellular adhesion molecule-1 antibodies significantly inhibited IP-10 induction. These results suggest that IP-10 expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leukocytes with fibroblast-like synoviocytes, and that IP-10 may contribute to the recruitment of specific subpopulations of T cells (Th1 type) from the bloodstream into the synovial joints.
11961179 Platelet function is inhibited by non-selective non-steroidal anti-inflammatory drugs but 2002 Apr BACKGROUND: Interaction with platelet function by non-steroidal anti-inflammatory drugs (NSAIDs) is related to the inhibition of cyclo-oxygenase-1 (COX-1). In patients with rheumatoid arthritis (RA), only one of the COX-2-selective NSAIDs (nabumetone) has been demonstrated to spare platelet function partially. OBJECTIVE: To compare the effects of the COX-2-selective inhibitor, meloxicam, with those of the non-selective NSAID, naproxen, on platelet function and thromboxane levels in RA patients. METHODS: In this randomized, controlled, cross-over trial, 10 RA patients used meloxicam 7.5 mg bid and naproxen 500 mg bid, each during a 2-week period. Washout periods were applied. Before and after each 2-week period of NSAID intake, laboratory studies were performed. RESULTS: Platelet aggregation was significantly less influenced, thromboxane levels were less inhibited (246 vs 117 pg/ml) and bleeding times were less prolonged with meloxicam than with naproxen (3.2 vs 2.3 min). Moreover, the results of all tests during meloxicam exposure were comparable with baseline values. CONCLUSION: In RA patients, meloxicam, a representative of the selective COX-2 inhibitors, does not interfere with platelet function and thromboxane levels, in contrast with naproxen (a non-selective COX inhibitor).
11959760 Calcium apatite crystals in synovial fluid rice bodies. 2002 May BACKGROUND: Rice bodies can occur in the joints in many rheumatic conditions, but they are most common in rheumatoid arthritis. They are generally believed to occur rarely in patients with osteoarthritis, but one study reported rice bodies with apatite crystals. OBJECTIVE: To report on a series of joint fluids with rice bodies containing apatite clumps and examine their clinical pictures. METHODS: All synovial fluid analysis reports for 10 years were reviewed for rice bodies and eight patients were reported on. A series of patients with a variety of diseases with synovial fluid rice bodies found to contain calcific material is described. All were examined by compensated polarised light and alizarin red stain, and four were examined by electron microscopy. RESULTS: The eight patients all had alizarin red S chunks embedded throughout the rice body. Transmission electron microscopy disclosed the presence of a matrix of collagen, fibrin, and amorphous materials containing typical apatite crystals. Clinical diagnoses, radiographic findings, and leucocyte counts varied, but six of the eight patients had had previous repeated corticosteroid injections into the joints. CONCLUSION: Aggregates of apatites may be more common than previously recognised in rice bodies as they are not routinely sought. Whether they are a result of joint damage or depot steroid injections and whether that might contribute to further joint injury now needs to be investigated.
12498769 Intraarticular gene transfer of TNFR:Fc suppresses experimental arthritis with reduced sys 2002 Dec Tumor necrosis factor alpha (TNFalpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Blockage of TNFalpha actions by systemic administration of TNF antagonists has recently been shown to ameliorate joint symptoms in RA patients. In the present study, a streptococcal cell wall (SCW)-induced rat arthritis model was used to evaluate the effect of different gene transfer routes of a TNF antagonist on the development and severity of arthritis. Successful delivery of a plasmid DNA encoding a rat TNF receptor-immunoglobulin Fc (TNFR:Fc) fusion gene prompted the subsequent administration of a recombinant adeno-associated virus (rAAV) vector encoding the antagonist, either locally (intraarticular) or systemically (intramuscular). The TNFR:Fc gene, delivered by either route, resulted in profound suppression of the arthritis as reflected in decreased inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and mRNA expression of joint proinflammatory cytokines. Increased bioactive serum TNFR levels were detected as a result of rAAV-ratTNFR:Fc administration, concomitant with a decrease in circulating TNFalpha. Administration of the rAAV-ratTNFR:Fc vector to one joint also suppressed arthritis in the contralateral joint. Importantly, intraarticular administration resulted in significantly lower systemic distribution of the gene product. Hence, the use of rAAV as the delivery vector for TNFR:Fc effectively suppressed SCW-induced arthritis and may provide an approach for local delivery of antiarthritic therapy.
15361385 Attitudes to early rheumatoid arthritis: changing patterns. Results of a survey. 2004 Oct OBJECTIVE: To determine if rheumatologists have changed their views on diagnosis and treatment of early rheumatoid arthritis (RA). METHODS: Three consecutive questionnaires were sent out to international rheumatologists in 1997, 2000, and 2003. The following aspects of early RA were covered: definition; patient referral time; diagnostic means; follow up intervals; and treatment strategies. All initial participants who responded to at least one of the follow up surveys were included in the analysis. RESULTS: RA is now defined by a smaller number of affected joints (monarthritis: 9.8% respondents in 1997 v 17.4% in 2003), and shorter symptom duration (<3 months: 65.5% in 1997 v 85.8% in 2003). Early referrals (<6 weeks) increased (8.9% in 1997 v 17.4% in 2003). Serological test for diagnosis was mostly rheumatoid factor (100% in 2003), but anti-CCP was already used by 17.4% in 2003. Follow up of patients with early RA intensified (every 2 weeks: 16.1% in 1997 v 30.4% in 2003; every month: 47.8% in 2003 v 64.3% in 1997). Treatment with disease modifying antirheumatic drugs (DMARDs) mainly comprised methotrexate, sulfasalazine, and antimalarial drugs. Leflunomide was among the two favourite DMARDs of 10.9% in 2003, whereas no biological agent was so. In 2003, 46.7% respondents started treatment with DMARDs if RA was suspected (30.9% in 1997); no one waited for erosions to occur (7.3% in 1997). CONCLUSION: The data obtained in this study suggest that the concept of diagnosing and treating RA early is accepted by a large proportion of the rheumatological community.
15188375 Correlation of polymorphic variation in the promoter region of the interleukin-1 beta gene 2004 Jun OBJECTIVE: Significant variation in interleukin-1 beta (IL-1 beta) protein secretion between subjects has been observed when using a lipopolysaccharide (LPS)/ATP-mediated ex vivo blood stimulation assay. To explore the potential relationships between genetic polymorphisms in the IL1B cytokine gene and cellular responses to inflammatory stimuli such as LPS, we investigated the hypothesis that polymorphisms within the promoter and exon 5 of the IL1B gene contribute to the observed differences in IL-1 beta protein secretion. METHODS: The IL1B gene polymorphisms C-511T, T-31C, and C3954T were tested for association with LPS-induced secretion of IL-1 beta protein as measured by an ex vivo blood stimulation assay. Samples from 2 independent study populations (n = 31 and n = 25) were available for use in the ex vivo assay after consent was obtained to analyze the DNA. RESULTS: A specific haplotype, composed of the T allele at -511 and the C allele at -31, was significantly associated with a 2-3-fold increase in LPS-induced IL-1 beta protein secretion. This association was observed in both of the independent study populations (P = 0.0084 and P = 0.0017). CONCLUSION: These data suggest that polymorphisms within the promoter region of the IL1B gene contribute to observed differences in LPS-induced IL-1 beta protein secretion.
15345497 Expression of resistance markers to methotrexate predicts clinical improvement in patients 2005 Apr BACKGROUND: Methotrexate is transported into the cell by the reduced folate carrier (RFC) and out of the cell by members of the multidrug resistance protein family (MRP). Transport proteins may affect the therapeutic efficacy of this drug in patients with rheumatoid arthritis. OBJECTIVE: To investigate the potential benefit of the presence of RFC and the absence of functional MRP for the efficacy of methotrexate treatment. METHODS: The study involved 163 patients (116 female, 47 male; mean age 59.5 years) on methotrexate (mean weekly dose 12.2 mg). RFC was determined using reverse transcriptase polymerase chain reaction, and MRP function by flow cytometry, using a calcein acetoxymethylesther/probenecid assay. Clinical response to methotrexate was evaluated by the EULAR response criteria and the ACR 20% improvement criteria. The clinical data were obtained at the beginning of methotrexate treatment and at the time of blood sampling during ongoing therapy. Patients were divided into four groups according to the presence (+) or absence (-) of RFC and functional (f) MRP. RESULTS: fMRP+/RFC+ and fMRP-/RFC- patients more often had good EULAR response rates (60%, p = 0.014, and 53%, p = 0.035, respectively) in comparison with the fMRP-/RFC+ group (29%); fMRP+/RFC- patients had a low frequency of good disease activity responses. CONCLUSIONS: Absence of fMRP plus presence of RFC did not prove to be related to beneficial effects of methotrexate, but the lack or the presence of both fMRP and RFC led to a significantly better therapeutic outcome. Determination of these markers may predict responsiveness to methotrexate.
12684695 Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes an 2003 May Methotrexate (MTX), widely used in the treatment of rheumatoid arthritis (RA), inhibits dihydrofolate reductase (DHFR) and folate-dependent enzymes. Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) are key enzymes in the folate metabolism and both have been shown to be polymorphic affecting the enzyme activity. To clarify the association between these genetic variations and MTX-related toxicity and efficacy in the treatment of RA, a total of 167 Japanese individuals with RA, including 52 and 63 patients treated with low-dose MTX with or without adverse effects, respectively, and 52 patients without MTX administration were analyzed. Among the 93 patients treated with MTX for >2 months, significantly more patients homozygous for the triple-repeat allele of the polymorphism in the promoter region of the TYMS gene required higher dose of MTX compared to those having at least a double-repeat allele (P=0.033). The incidence of > or =50% improvement in the serum CRP level was significantly higher in patients homozygous for the deletion allele of the polymorphism in the 3'-untranslated region (UTR) of the TYMS gene (P=0.0383). The allele frequency of the insertion/deletion polymorphism in the TYMS 3'UTR in Japanese was significantly different from that in Caucasians (P<0.0001), as was the tandem-repeat polymorphism in its promoter region. On the other hand, MTHFR C677T and A1298C polymorphisms showed no association with MTX-related toxicity or efficacy. Our results suggest that the genotyping for the TYMS polymorphisms may become a useful indicator in determining the appropriate dose of MTX in patients with RA.
11886967 An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with a 2002 Feb OBJECTIVE: To examine the allelic association of the single nucleotide polymorphism (CTLA4A/G) in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA4) gene with early rheumatoid arthritis (RA). METHODS: One hundred and twenty-three unrelated white probands with early RA from the north-east of England and 349 local ethnically matched controls were studied. The CTLA4A/G polymorphism was genotyped with a polymerase chain reaction (PCR) method and digestion with the restriction enzyme Bst71I. Probands were also screened by allele-specific PCR for alleles HLA DRB1*01 and DRB1*04. RESULTS: The frequency of the G allele at CTLA4A/G was significantly increased in probands with early RA compared with controls [43 vs 36%; P=0.028, odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01-1.82]. Most of this increased frequency was attributable to RA individuals with coexisting autoimmune thyroid disease or type 1 diabetes (58 vs 36% in controls; P=0.005, OR 2.50, CI 1.29-4.84). The frequency of the G allele in RA patients without autoimmune endocrinopathy was 40%, which was not significantly different from that in controls (P=0.140). CONCLUSION: The association between the CTLA4 G allele and early RA is largely explained by individuals with RA who have coexisting autoimmune endocrinopathies.
12666306 [Fabry's disease associated with rheumatoid arthritis. Multisystemic crossroads]. 2003 Jan Fabry's disease is a rare congenic disorder of glycosphingolipid catabolism resulting from deficient activity of the alpha galactosidasa. Is an X-linked disorder and in hemizygous males the activity of this enzyme is very low, resulting in severe manifestations. Fabry disease is confirmed by the lack alfa-galactosidase in serum. In the literature have been reported a few cases of coexistent Fabry's disease and connective disorders, but there is not cases of rheumatoid arthritis coexistent. This report describes a case of a female with Fabry's disease who vas subsequently diagnosed with rheumatoid arthritis. The suspect diagnosis was very important because the two disorders are multisystem and new symptoms could be attributed to Fabry's disease. The accumulation of lipids may results in numerous pathogenic autoantibodies, which could make immunocomplex. This is the potential pathogenic mechanisms explaining the association between Fabry's disease and autoimmune diseases.
12951317 Cytomegalovirus infection in a patient with rheumatoid arthritis. 2003 Aug Background. - Pulmonary dysfunction in rheumatoid arthritis (RA) patients treated with low-dose methotrexate is usually caused by bacterial infection and less frequently by an immunoallergic reaction to the drug (acute hypersensitivity pneumonitis). Opportunistic infections are a rare cause. We report a case of cytomegalovirus pneumonia during bone marrow aplasia in a patient with RA taking methotrexate and cyclosporine.Conclusions. - Cytomegalovirus infection is a rarely reported cause of pulmonary dysfunction. This diagnosis should be considered in immunocompromised RA patients with no other satisfactory explanation for pulmonary dysfunction.
11879547 Cytokine mRNA and protein expression in primary-culture and repeated-passage synovial fibr 2002 Constitutive mRNA expression and secretion of proinflammatory and anti-inflammatory cytokines was comparatively analyzed in rheumatoid arthritis (RA) synovial fibroblasts (SFB), isolated from primary culture or derived by repeated passage; normal-skin fibroblasts were used as controls. First-passage RA-SFB (n = 3) secreted large amounts of IL-6 (15,800 +/- 2,110 pg/ml; mean +/- SEM), but only limited amounts of tumor necrosis factor (TNF)-alpha (22.1 +/- 1.1 pg/ml) or IL-10 (35.7 +/- 34.2 pg/ml; only one of three samples was positive). IL-1beta, IL-15, and IL-18 were not detectable at the protein level and showed very low mRNA levels by semiquantitative RT-PCR. In repeated-passage RA-SFB (tenth passage), protein secretion was significantly lower for IL-6 (one-twentieth of the initial level) and TNF-alpha (two-thirds), and markedly reduced for IL-10 (one-quarter, with only one of three samples positive). While the decrease of IL-10 protein from first to tenth passage was paralleled by a corresponding decrease of mRNA, the relative mRNA levels for IL-6 and TNF-alpha were actually increased (20-fold and 300-fold, respectively), indicating post-transcriptional and/or post-translational regulation of these cytokines. Due to highly variable levels among individual patients, however, no significant differences were observed for any cytokine mRNA between primary-culture and repeated-passage RA-SFB (ninth passage). Likewise, no significant differences were detectable between RA-SFB and normal-skin fibroblasts (primary-culture and repeated-passage). By producing high amounts of IL-6 and limited amounts of TNF-alpha, RA-SFB may contribute to the (im)balance of proinflammatory and anti-inflammatory cytokines in the inflamed joint.
15123034 Corticosteroids--from an idea to clinical use. 2004 Feb Corticosteroids form the basis of treatment in many inflammatory rheumatic diseases, both as systemic treatment and as treatment with local injections to reduce inflammation. In 1948 the first systemic treatment of a patient with a rheumatic disease was given to a woman with severe rheumatoid arthritis (RA); the impressive effect in this patient, and in another 15 patients, was reported by Dr Hench and co-workers in 1949. Systemic corticosteroid treatment was rapidly adopted and used not only for patients with RA but also for those with other rheumatic diseases such as systemic lupus erythematosus-as well as other disorders such as asthma-with a similar positive effect. In the following year, 1950, the Nobel Prize was awarded for the discovery of the structure and biological effects of the adrenal cortex hormones. This open trial was followed by several controlled trials conducted in the UK in which the effects of cortisone were compared with the effects of aspirin in patients with RA-interestingly, without any significant clinical benefit for the cortisone-treated patients. It was not until 1959, in yet another multi-centre trial in Britain, that a significant effect on functional capacity and general well-being was reported after 2 years of treatment with prednisolone, compared to aspirin, in patients with early RA. Despite the dramatic effects that were observed in the severely ill RA patients reported by Hench and co-workers it took 10 years to demonstrate that this effect was superior to the effect of aspirin when the two compounds were compared in controlled trials. Why was this so? One explanation could be in the study designs and the different outcome measures used in the various studies. Perhaps the results in the first comparative studies would have been different if individual response criteria had been used. This is discussed in this chapter.