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Objective: Ethnic groups may experience or report pain differently; thus, we compared ethnic differences on pain coping strategies and control beliefs, and the relationships of these variables to health status, among women with rheumatoid arthritis (RA)., Methods: Using a sample of 100 women (48 African-American, 52 Caucasian), we related pain coping strategies and control beliefs to pain severity, activity levels, and affective state, controlling for socioeconomics, behavioral impairment, and disease activity., Results: Ethnic groups did not differ in pain severity or negative affect, but African-Americans were less physically active. African-Americans used more coping techniques involving diverting attention and praying/hoping; Caucasians used more coping techniques involving ignoring pain. The relationships of praying/hoping and reinterpreting pain to RA adjustment differed by ethnic group. In contrast, ignoring pain, coping statements, and stronger control beliefs predicted better health status, and diverting attention predicted more pain for all patients., Conclusion: There are ethnic differences in the use of coping strategies that should be acknowledged when helping RA patients cope with their disease, but control beliefs and several coping strategies predict pain and adjustment, regardless of ethnicity.

Objective: To (1) validate the Short-Form Health Survey (SF-36) as a generic functional health status measure in patients with rheumatoid arthritis (RA); and (2) assess correlations between the SF-36 and other outcome measures used in the Minocycline in Rheumatoid Arthritis (MIRA) Trial., Methods: We conducted a cross sectional analysis of the final visit outcome measures from the 48 week, multicenter, placebo controlled, double blind MIRA trial. Multitrait scaling analyses assessed convergent and discriminant validity and internal consistency reliability of the SF-36 in the study patients. Responses to comparable items on the SF-36 and modified Health Assessment Questionnaire (M-HAQ) regarding physical functioning were compared and questions from both instruments were also compared to other RA outcome measures., Results: In patients with RA, the SF-36 had high internal consistency and reliability, high discriminant and high convergent validity. Moderate correlations were observed (r = -0.46 to -0.61, p < 0.01 in each case) for comparable items on the SF-36 and M-HAQ regarding dressing, walking, and bending. Joint tenderness score correlations with items on the M-HAQ and SF-36, and joint tenderness score correlations with the SF-36 scales were higher than for joint swelling scores. Physician and patient global assessments were most highly correlated (r = 0.58 and 0.66; p < 0.01, respectively) with the SF-36 bodily pain item., Conclusion: The SF-36 is a valid instrument for this RA population. The SF-36 correlates with the M-HAQ and the physician and patient global assessments. The usefulness of the SF-36 in measuring change in RA clinical trials requires testing in longitudinal studies.

Objective: To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial., Methods: A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and final visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease., Results: Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 placebo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference., Conclusion: Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted "newly involved" joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted.

This study examined the effects of emotional disclosure of stressful events on the pain, physical and affective dysfunction, and joint condition of patients with rheumatoid arthritis (RA). Patients were randomly assigned to talk privately about stressful events (disclosure group, n = 36) or about trivial topics (control group, n = 36) for 4 consecutive days. Disclosure resulted in immediate increases in negative mood. At 2 weeks the 2 groups did not differ on any health measure, but at 3 months disclosure patients had less affective disturbance and better physical functioning in daily activities. There was no main effect of disclosure on pain or joint condition, but among the disclosure patients, those who experienced larger increases in negative mood after talking demonstrated improvements in the condition of their joints. This study concludes that, among RA patients, verbal disclosure and emotional processing of stressful life events induces an immediate negative mood followed by improved psychological functioning.

Objective: To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design., Methods: Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores). These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment). The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available., Results: Percentages of minocycline-treated patients versus placebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004). Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate. Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between-group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group. Study design considerations indicated that application of the ACR criteria would reduce the required sample size., Conclusion: Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets. These findings support the use of the ACR criteria for defining improvement in RA clinical trials.

Objective: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial., Methods: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression., Results: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope., Conclusion: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.

Objective: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis., Design: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo., Setting: 6 clinical centers in the United States., Patients: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs., Measurements: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken., Results: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred., Conclusions: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined.

We utilized a standardized in vitro method which employs transmission electron microscopy to monitor the degree of surface activation (cytoplasmic spreading) and amount of aggregation displayed by platelet populations from 314 patients with one of five distinct rheumatic diseases and from 72 normal subjects. The percentage of patients in each group whose platelet populations were hyperactive was as follows: polymyalgia rheumatica, 75 percent; scleroderma, 65 percent; primary gout, 61 percent; rheumatoid arthritis, 57 percent; and degenerative joint disease, 40 percent. Pair-wise contrasts performed after an analysis of variance suggest the following differences and similarities: (1) the mean differential platelet count of the normal subjects differed from that in each disease state; (2) the platelet responsivity in patients with degenerative joint disease most closely resembled that in normal subjects; (3) the platelet response in polymyalgia rheumatica plus temporal arteritis was the most abnormal; and (4) platelet response in scleroderma, rheumatoid arthritis, and gout closely resembled each other. The increased platelet response in vitro may reflect the in vivo presence of disease-related "risk factors" (hyperuricemia, immune complexes, and atherosclerosis). Those patients with "triggered" platelet populations may be appropriate candidates for antiplatelet therapy.

The junction between cellular pannus and cartilage/bone was identified grossly on rheumatoid metacarpal heads. Its topography was displayed by scanning electron microscopy using macerated samples. A uniform pattern of resorption bays, typical of osteoclastic activity, was seen spreading over the surfaces of both calcified cartilage and subchondral bone. The contact area between pannus and cartilage/bone was found to represent an erosive front. Morphologic evidence suggested that osteoclasts were primarily responsible for the destructive process.