Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: a nested, case-control study

OBJECTIVE: To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. METHODS: We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA. RESULTS: We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]). CONCLUSION: RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.     

Direct medical costs and their predictors in patients with rheumatoid arthritis: a three-year study of 7,527 patients

OBJECTIVE: To estimate total direct medical costs in persons with rheumatoid arthritis (RA) and to characterize predictors of these costs. METHODS: Patients (n = 7,527) participating in a longitudinal study of outcome in RA completed 25,050 semiannual questionnaires from January 1999 through December 2001. From these we determined direct medical care costs converted to 2001 US dollars using the consumer price index. We used generalized estimating equations to examine potential predictors of the costs. Monte Carlo simulations and sensitivity analyses were performed to evaluate the varying prevalence and cost of biologic therapy. RESULTS: The mean total annual direct medical care cost in 2001 for a patient with RA was 9,519 US dollars. Drug costs were 6,324 US dollars (66% of the total), while hospitalization costs were only 1,573 US dollars (17%). Approximately 25% of patients received biologic therapy. The mean total annual direct cost for patients receiving biologic agents was 19,016 US dollars per year, while the cost for those not receiving biologic therapy was 6,164 US dollars. RA patients who were in the worst quartile of functional status, as measured by the Health Assessment Questionnaire, experienced direct medical costs for the subsequent year that were 5,022 US dollars more than the costs incurred by those in the best quartile. Physical status as determined by the Short Form 36 physical component scale had a similar large effect on RA costs, as did comorbidity. Medical insurance type played a more limited role. However, those without insurance had substantially lower service utilization and costs, and health maintenance organization patients had lower drug costs and total medical costs. Increased years of education, increased income, and majority ethnic status were all associated with increased drug costs but not hospitalization costs. Costs in all categories decreased after age 65 years. CONCLUSION: Estimates of direct medical costs for patients with RA are substantially higher than cost estimates before the biologic therapy era, and costs are now driven predominantly by the cost of drugs, primarily biologic agents. RA patients with poor function continue to incur substantially higher costs, as do those with comorbid conditions, and sociodemographic characteristics also play an important role in determination of costs.     

Behavioral and electrocortical evidence of an interaction between probability and task metrics in movement preparation

Recent neurophysiological evidence suggests that cognitive factors shape neural activity in cortical areas such as parietal (area 5), premotor, and primary motor cortex. The implication of these findings is that behavioral signatures of cognitive factors and movement-specific factors should likewise be interdependent. The present study provides evidence of this interdependence in both behavioral (reaction time) and electrophysiological (P300) measures. Subjects performed a two-choice pointing task, in which the angular distance between the two required movement directions (task metrics) and the probability of the two responses was varied. In a control condition, a single reaction was required in response to both stimuli to test for the influence of stimulus metrics. Results from the pointing task showed a clear interaction between the metrics and effects of probability. When the potential targets were widely separated (120 degrees), stimulus probability influences reaction time and P300 amplitude in the classic fashion (longer reaction times and larger P300 amplitudes to less probable responses). When pointing to targets that were narrowly separated (20 degrees), probability had no effect: both rare and frequent targets were "functionally frequent." The same interaction was not observed in the control condition, indicating that metrics were primarily influencing movement preparation rather than stimulus processing. The results are consistent with the theoretical framework of dynamic field theory and demonstrate that metrics are an important factor that must be taken into account when assessing the processes associated with movement preparation.     

Assessment of pain in rheumatoid arthritis: minimal clinically significant difference, predictors, and the effect of anti-tumor necrosis factor therapy

OBJECTIVE: To compare a visual analog pain scale (VAS) with the Medical Outcomes Study Short Form-36 Health Survey (SF-36) bodily pain; to define the minimal clinically important change (MCIC) for pain in observational studies; to define clinically useful cutpoints for pain; to quantify the predictors of pain; and to estimate the effect of anti-tumor necrosis factor (TNF) therapy on pain. METHODS: Over 6 years we studied 12,090 patients with rheumatoid arthritis (RA). Pain was assessed by VAS and SF-36 pain scales. RESULTS: Compared with the SF-36 scale, the 0-10 VAS pain scale was better correlated with all clinical variables. The mean VAS score was 3.4 (standard deviation 2.8), and the best cutpoint for an "acceptable" level of pain was 相似文献   

Resistance of rheumatoid arthritis patients to changing therapy: discordance between disease activity and patients' treatment choices

OBJECTIVE: Despite advances in rheumatoid arthritis (RA) treatment, patients' decisions regarding therapy often deviate from expert recommendation. This study was undertaken to investigate patients' acceptance and satisfaction with therapy, willingness to change therapy, and reasons for not changing. METHODS: Participants (n = 6,135) completed an 11-item questionnaire concerning treatment preferences. Eight questions assessed reasons for not wanting to change therapy. The contribution of individual predictors was determined by logistic regression analysis. RESULTS: Questionnaire responses showed that 63.8% of the patients would not want to change therapy as long as their condition didn't get worse; 77.3% were satisfied with their medications, while 9.4% were dissatisfied. These assessments were weakly related to RA activity and functional status. Side effects had occurred in 22.4% of the patients during the previous 6 months, and in 65.5% at some period during their lifetime. Predictors of unwillingness to change therapy were satisfaction with RA control, which had an odds ratio (OR) of 6.8 (95% confidence interval [95% CI] 5.8-8.0), risk of side effects (OR 4.4 [95% CI 3.8-5.2]), physician opinion (OR 1.9 [95% CI 1.6-2.2]), fear of loss of control (OR 1.8 [95% CI 1.6-2.1]), lack of better medications (OR 1.4 [95% CI 1.2-1.6]), and costs (OR 1.3 [95% CI 1.1-1.6]). There was little difference in results between patients who were receiving biologic agents and those who were not. CONCLUSION: There is substantial discrepancy between declared satisfaction with therapy and measured RA activity and functional status. Most RA patients are satisfied with their therapy, even many with abnormal scores. Fear of loss of control of RA and fear of side effects are major patient concerns. Maintenance of current status, rather than future improvement, appears to be a high priority for patients.     

Minimal disease activity, remission, and the long-term outcomes of rheumatoid arthritis

OBJECTIVE: To determine the prevalence of minimal disease activity (MDA) and remission in patients with rheumatoid arthritis (RA), to assess the effect of anti-tumor necrosis factor (anti-TNF) therapy on MDA, and to determine the extent to which MDA status improves long-term outcomes. METHODS: Using the Patient Activity Scale (PAS) as a surrogate, we assessed the prevalence of MDA and remission in 18,062 patients with RA using the newly developed Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria for MDA. RESULTS: MDA was noted in 20.2% of 18,062 patients and persistent MDA, operationally defined as having MDA during >or=2 consecutive 6-month observation periods, occurred in 13.5% of 7,433 patients followed longitudinally. Disease activity at remission levels was noted in 7%. Among patients with MDA, 82% received disease-modifying antirheumatic drugs or biologic agents. Following anti-TNF initiation, the cumulative probability of achieving MDA at 2 and 6 years was 4.1% and 7.6%, respectively, and persistent MDA probabilities were 2.7% and 4.5%, respectively. Regardless of RA duration, patients with MDA had substantially better outcomes, including a 10-fold reduction in work disability and an approximately 2-fold reduction in total joint replacement and mortality. CONCLUSION: Remission remains uncommon in RA, and the prevalence of new remission in community practice is substantially lower than noted in published trials of biologic therapy. On average, persons with MDA appear to have persistently mild RA. This might be the effect of milder RA and/or more effective treatment in early RA. The PAS had satisfactory levels of agreement with the full MDA criteria and appears suitable for use in clinical and epidemiologic research.     

Converting modified health assessment questionnaire (HAQ), multidimensional HAQ,and HAQII scores into original HAQ scores using models developed with a large cohort of rheumatoid arthritis patients

Objective

The Stanford Health Assessment Questionnaire Disability Index (HAQ) is the gold standard functional status questionnaire in rheumatology, but it is lengthy. Three shorter versions, the modified HAQ (MHAQ), the Multidimensional HAQ (MDHAQ), and the HAQII are often used in outcomes research as HAQ substitutes. We developed conversion formulas between these modified versions and the original HAQ.

Methods

Analysis was limited to the comparison of rheumatoid arthritis (RA) patients at a random observation when the HAQ was recorded in conjunction with the MHAQ (n = 29,596), the MDHAQ (n = 13,665), or the HAQII (n = 15,823). Development models were randomly limited to 80% of the data (development sample) and the remaining 20% was used for model validation.

Results

Two conversion formulas were developed for each of the MHAQ, the MDHAQ, and the HAQII: a short model and a long model inclusive of questions common to both the modified measures and the original HAQ. Short models explained 81–83%, and long models 82–86%, of the variance. Predicted HAQ values of zero were assigned to all cases with an MDHAQ or HAQII score of zero, with remaining cases used for model estimation. Bland‐Altman plots demonstrated good concordance between actual and predicted values for each measure. The validation sample closely approximated the results from the development sample (0.005 ≤ ΔR² ≤ 0.009) for each measure.

Conclusion

We have developed and validated highly accurate conversion formulas from the MHAQ, MDHAQ, and HAQII to the original HAQ in a large sample of RA patients. The developed models are useful for conversion of measures in the research setting. Because of substantial variability at the individual patient level, application of the formulas to individual patients is inadvisable.