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Theodore Pincus

Publications and source records attributed to Theodore Pincus.

At least 19 recordsLinked to original sources
PubMed2006

An index of patient reported outcomes (PRO-Index) discriminates effectively between active and control treatment in 4 clinical trials of adalimumab in rheumatoid arthritis.

OBJECTIVE: To analyze 2 indices composed of the 3 patient reported outcomes (PRO) in the American College of Rheumatology (ACR) Core Data Set--physical function, pain, and global estimate--without joint count or laboratory data, for capacities to distinguish active from control treatments in 4 pivotal clinical trials. METHODS: Data from 4 clinical trials involving adalimumab, in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARD) or as monotherapy, versus control treatment were made available to analyze properties of various indices. A categorical PRO-Index M was defined as "majority" improvement in 2 of the 3 PRO measures at 20%, 50%, and 70% levels; results were evaluated to analyze agreement with ACR20, ACR50, ACR70 responses and an "all Core Data Set measures" index based on 4 of the 7 measures having such levels of improvement. A continuous PRO-Index C was defined as the median or 2nd highest of 3 percentage differences from baseline to endpoint; results were evaluated to analyze agreement with a continuous ACR-N, "all Core Data Set measures" index, and Disease Activity Score 28 (DAS28). RESULTS: All indices distinguished active versus control treatment at similar levels, including PRO-Index M versus ACR20, ACR50, and ACR70 responses, and PRO-Index C versus DAS28. CONCLUSION: PRO indices based only on patient questionnaire data, without joint counts or laboratory tests, may be useful quantitative measures of therapeutic efficacy for use in standard rheumatology clinical care.

Adalimumab↗
PubMed2006

Changes in Health Assessment Questionnaire disability scores over five years in patients with rheumatoid arthritis compared with the general population.

OBJECTIVE: To analyze longitudinal data over 5 years for changes in Health Assessment Questionnaire (HAQ) scores in patients with rheumatoid arthritis (RA) and age- and sex-matched controls from the general population. METHODS: In 2000 and 2005, identical self-report questionnaires were mailed to a cohort of patients with RA and control cohort from the community. The questionnaire included the HAQ, which was used to assess functional status. Changes in HAQ scores over 5 years were analyzed. RESULTS: In 2000, 73% of 1,495 patients with RA and 77% of 2,000 general population controls responded to the questionnaire. In 2005, 84% of 2,022 patients with RA and 77% of 1,817 controls responded. A total of 863 patients with RA and 1,176 community controls responded in both 2000 and 2005 and were included in the analyses. Mean baseline HAQ scores were significantly higher in patients with RA than in controls (0.71 versus 0.17; P < 0.001). Over 5 years, the HAQ scores increased by 0.01 units per year in both the RA cohort and the community population; in both cohorts, the net change was primarily attributable to individuals over age 70 years. Changes in HAQ scores were similar in patients and controls who had low HAQ scores at baseline. Female patients with baseline HAQ scores of >or=0.5 had less potential for improvement than did controls. Among subjects in both groups who had HAQ scores >2, death was a common outcome over the next 5 years. CONCLUSION: Currently, progression of functional disability among patients with RA and among persons in the general population is largely explained by the aging process. Our results showing stable function scores over 5 years in most patients with RA who are younger than age 70 years provide further evidence of improved status of RA patients today compared with the major declines observed in previous decades.

Adult↗
PubMed2006

Utility of the Framingham risk score to predict the presence of coronary atherosclerosis in patients with rheumatoid arthritis.

The prevalence of ischemic heart disease and atherosclerosis is increased in patients with rheumatoid arthritis (RA). In the general population, but not in patients with systemic lupus erythematosus, the Framingham risk score identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. We examined the hypothesis that the Framingham score is increased and associated with coronary-artery atherosclerosis in patients with RA. The Framingham score and the 10-year cardiovascular risk were compared among 155 patients with RA (89 with early disease, 66 with long-standing disease) and 85 control subjects. The presence of coronary-artery calcification was determined by electron-beam computed tomography. The Framingham score was compared in patients with RA and control subjects, and the association between the risk score and coronary-artery calcification was examined in patients. Patients with long-standing RA had a higher Framingham score (14 [11 to 18]) (median [interquartile range]) compared to patients with early RA (11 [8 to 14]) or control subjects (12 [7 to 14], P < 0.001). This remained significant after adjustment for age and gender (P = 0.015). Seventy-six patients with RA had coronary calcification; their Framingham risk score was higher (14 [12 to 17]) than that of 79 patients without calcification (10 [5 to 14]) (P < 0.001). Furthermore, a higher Framingham score was associated with a higher calcium score (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.12 to 1.29, P < 0.001), and the association remained significant after adjustment for age and gender (OR = 1.15, 95% CI 1.02 to 1.29, P = 0.03). In conclusion, a higher Framingham risk score is independently associated with the presence of coronary calcification in patients with RA.

Arthritis, Rheumatoid↗
PubMed2006

Advantages and limitations of quantitative measures to assess rheumatoid arthritis: joint counts, radiographs, laboratory tests, and patient questionnaires.

Medical care is advanced by quantitative measures, all of which have advantages and limitations. No single "gold standard" measure, analogous to blood pressure, is available for diagnosis, prognosis, and management of rheumatoid arthritis (RA). Four types of measures have been used, including joint counts, radiographs, laboratory tests, and patient questionnaires. Joint counts are the most specific measure for RA but are poorly reproducible and not performed in most standard care. Radiographs provide an objective record of joint damage, but are scored quantitatively only in clinical research and have little prognostic value for long-term outcomes such as work disability and mortality. Laboratory tests are helpful when positive but frequently are "false negative"--for example, rheumatoid factor (RF), erythrocyte sedimentation rate, or C-reactive protein are normal in 30% to 45% of patients. "False positive" results are also seen; most people with RF or antinuclear antibody do not have a disease. Patient questionnaires are useful to assess and monitor patient status and provide the most significant predictive measures for long-term work disability and mortality. A multidimensional health assessment questionnaire is useful in all rheumatic diseases, with scoring templates and medical history information to save time for the rheumatologist and patient in standard care.

Arthritis, Rheumatoid↗
PubMed2005

Patients seen for standard rheumatoid arthritis care have significantly better articular, radiographic, laboratory, and functional status in 2000 than in 1985.

OBJECTIVE: A comprehensive quantitative analysis of measures of disease activity and joint damage has not been available to compare patients in different eras in the same clinical setting. This study was undertaken to determine whether the clinical status of patients with rheumatoid arthritis (RA) has improved on average in recent years. METHODS: A quantitative cross-sectional evaluation, which included joint count, radiographic, laboratory, patient questionnaire, and physical function measures, and therapies, was performed in 125 consecutive RA patients seen from 1984 through 1986 ("1985 cohort"). A virtually identical assessment was performed in 150 patients seen from 1999 through 2001 ("2000 cohort"), in the same weekly academic clinic. Measures were compared using descriptive statistics and a median regression model, adjusted for age, duration of disease, level of formal education, and rheumatoid factor. RESULTS: Patients in 1985 had significantly poorer status compared with those in 2000: median 12 versus 5 swollen joints, Larsen radiographic score 20 versus 3, erythrocyte sedimentation rate 33 mm/hour versus 20, and modified Health Assessment Questionnaire 1.0 versus 0.4 (P < 0.019). Severe Disease Activity Scores >5.1 were seen in 69% of 1985 patients, compared with 30% in 2000. Methotrexate was taken by 10% of patients in 1985, versus 76% in 2000. The proportion of patients not taking any disease-modifying antirheumatic drugs was 66% in 1985 versus 13% in 2000. CONCLUSION: Patients receiving standard care for RA in this setting had significantly better status, including radiographic scores, in 2000 than in 1985, associated with aggressive treatment strategies, prior to the introduction of biologic agents.

Arthritis, Rheumatoid↗
PubMed2005

Continuous indices of core data set measures in rheumatoid arthritis clinical trials: lower responses to placebo than seen with categorical responses with the American College of Rheumatology 20% criteria.

OBJECTIVE: To describe indices that are continuous counterparts of categorical responses to the American College of Rheumatology 20% improvement criteria (ACR20), ACR50, and ACR70, which extend rheumatoid arthritis (RA) clinical trial results and recognize clinical worsening (as well as improvement) with active and placebo treatments. METHODS: Data from a clinical trial of leflunomide, methotrexate, and placebo treatment over 1 year were reanalyzed. Percent change was computed for each of the 7 components of the ACR core set of outcome measures. Four continuous indices were computed: 1) ACR-N (lowest of 3 values: number of swollen joints, number of tender joints, and median of the other 5 measures); 2) composite (median of all 7 measures [3 patient and 3 assessor measures plus erythrocyte sedimentation rate]); 3) patient-only (median of physical function, pain, and global status); and 4) assessor-only (median of number of swollen joints, number of tender joints, and global status). Means, medians, categorical 20%, 50%, and 70% responses, and continuous probability plots were computed according to each index for the 3 treatment groups and were compared with one another and with standard ACR20, ACR50, and ACR70 responses. RESULTS: Mean levels of improvement calculated using the different methods, in patients taking leflunomide, placebo, and methotrexate, respectively, were as follows: ACR-N 20%, -12%, and 13%; composite 43%, 9%, and 33%; patient-only 36%, 0%, and 26%; assessor-only 50%, 20%, and 44%; and ACR20 52%, 26%, and 46%. Differences between leflunomide and placebo were 30-36%, and differences between methotrexate and placebo were 24-26%. CONCLUSION: Continuous indices may be an informative addition to categorical ACR 20%, 50%, or 70% responses to compare efficacies of various treatments in RA, and to describe lower responses to placebo by recognizing worsening as well as improvement.

Antirheumatic Agents↗
PubMed2005

Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors.

OBJECTIVE: To compare the prevalence and severity of coronary-artery atherosclerosis in patients with early and established rheumatoid arthritis (RA) and controls. METHODS: Electron-beam computed tomography was used to measure the extent of coronary-artery calcification in 227 subjects, of whom 70 had early RA, 71 had established RA, and 86 were controls. Coronary-artery calcification calculated according to the Agatston calcium score was compared in patients and controls, and its relationship to clinical characteristics was examined. Adjusted odds ratios (ORs) were obtained with the use of proportional odds logistic regression models to determine independent associations of early and established RA and coronary-artery calcification. RESULTS: Calcium scores were higher in patients with established RA (median 40.2, interquartile range [IQR] 0-358.8) compared with those with early disease (median 0, IQR 0-42.6) and controls (median 0, IQR 0-19.2) (P = 0.001). Coronary-artery calcification occurred more frequently in patients with established RA (60.6%) than in patients with early RA (42.9%) and control subjects (38.4%) (P = 0.016) The OR for the likelihood of having more severe coronary-artery calcification (defined as an Agatston score >109) in patients with established disease was 3.42 (P = 0.002) after adjusting for cardiovascular risk factors. Among patients with RA, smoking (OR 1.02, P = 0.04) and an elevated erythrocyte sedimentation rate (OR 1.02, P = 0.05) were associated with more severe coronary-artery calcification after adjustment for age and sex. CONCLUSION: The prevalence and severity of coronary calcification is increased in patients with established RA and is related, in part, to smoking and an increased erythrocyte sedimentation rate.

Adult↗
PubMed2005

The disease activity score is not suitable as the sole criterion for initiation and evaluation of anti-tumor necrosis factor therapy in the clinic: discordance between assessment measures and limitations in questionnaire use for regulatory purposes.

OBJECTIVE: The Disease Activity Score (DAS) is widely used in clinical trials. A DAS of 5.1 defines the level of severe rheumatoid arthritis (RA) and is the criterion for the initiation of anti-tumor necrosis factor therapy in the UK and The Netherlands. In North America, similar rules are sometimes imposed. However, it is not known how accurately the DAS characterizes RA activity. The present study was undertaken to determine the concordance between DAS scores and physicians' assessments of RA activity, to investigate factors relating to discrepancies, and to assess the suitability of using the DAS in individual patients. METHODS: Six hundred sixty-nine RA patients were assessed using the DAS and other clinical measures. A physician's global estimate of RA activity was performed using an 11-point predefined scale and a standard definition of disease activity. RESULTS: The DAS and physician global assessment had substantially different distributions of values. The level of agreement (Kendall's tau-a) between DAS scores and physician global assessments was 49% (95% confidence interval 45-53%), Lin's coefficient of concordance was 0.62, and the Bland-Altman 95% limits of agreement were -3.17 and 3.99. These results suggest poor-to-moderate concordance between the 2 measures of disease activity. CONCLUSION: The DAS and the physician's assessment of RA activity do not approach, value, and weight RA variables to the same extent, suggesting that RA activity is not evaluated similarly by North American physicians and with the DAS. The scales do not have acceptable levels of concordance. There is too much inherent variability in the DAS and other RA scales (e.g., the Health Assessment Questionnaire) to recommend them as sole determinants of RA activity for clinical or regulatory purposes.

Adult↗
PubMed2005

Patient preference in a crossover clinical trial of patients with osteoarthritis of the knee or hip: face validity of self-report questionnaire ratings.

OBJECTIVE: To analyze correlational validity of self-report responses regarding patient preference between 2 drugs at the conclusion of a crossover double-blind clinical trial in patients with osteoarthritis (OA) of the knee or hip. METHODS: Patients were randomized to 6 weeks' treatment of diclofenac/misoprostol or acetaminophen, followed by crossover to 6 weeks of the other drug. Patient preference was queried at the final visit: "Please compare control of your arthritis during the first and second periods as 'much better' or 'better' in the first period, 'no different' or 'better' or 'much better' in the second period." Patient preference ratings were evaluated in comparisons with 4 independent self-report measures within each treatment period: (1) change in Western Ontario McMaster (WOMAC) questionnaire scores; (2) change in pain visual analog scale (VAS) on a multidimensional Health Assessment Questionnaire (MDHAQ); (3) patient ratings of drug efficacy; and (4) patient report of change in arthritis status, as well as investigator ratings of the more efficacious drug. RESULTS: Among 173 patients, diclofenac/misoprostol was rated as "much better" by 54 and "better" by 45, acetaminophen was rated as "better" by 18 and "much better" by 17, and "no difference" by 39 patients. Spearman rank correlations for patient preferences were significant for changes in WOMAC scores, pain VAS, and independent patient ratings of drug efficacy and changes in arthritis status within each treatment period, as well as with physician ratings of the more efficacious drug (p < 0.001). CONCLUSION: Significant correlational validity is documented for patient self-report of preferences between 2 drugs compared to independent measures within each treatment period in this crossover clinical trial in patients with OA of the knee or hip.

Acetaminophen↗
PubMed2005

Preliminary evaluation of a visual analog function scale for use in rheumatoid arthritis.

OBJECTIVE: Key outcomes in rheumatoid arthritis (RA) are evaluated with multi-item ratings scales such as the Health Assessment Questionnaire (HAQ) and visual analog scales (VAS) such as pain and patient and physician global. As VAS scales are easy to use and particularly effective in research and patient care, we studied the characteristics, association, and psychometric properties of a VAS function scale (VAS-F) to determine if it could be used in RA studies and clinical practice. METHODS: A total of 394 patients with RA completed the HAQ, the HAQ-II, and a VAS functional scale. In addition, they completed standard assessments of pain, global, fatigue, sleep problems, joint count, and the Medical Outcome Study Short-Form 36 (SF-36) physical component summary score (PCS) and vitality and total pain scores. RESULTS: The HAQ-II was correlated with VAS-F at 0.76, but distributional characteristics of the HAQ and VAS-F differed, as the VAS-F scale results contained more higher scores as well as more lower scores compared with the HAQ-II and HAQ. Kendall's tau concordance analyses indicated that VAS scales were more concordant with other VAS than with non-VAS scales. Concordance of VAS-F was greatest with VAS global and was similar overall with VAS pain, sleep disturbance, fatigue, and quality of life. By contrast, the PCS, a multi-item scale, was more concordant with HAQ-II and HAQ. There was little to no difference between the VAS-F and the 2 HAQ with regard to concordance with the multi-item joint count, SF-36 vitality, and SF-36 total pain. CONCLUSION: The distribution differences between HAQ and HAQ-II and the VAS-F suggest that patients do not see minor limitations as problematic, but rate major limitations as being particularly limiting and worthy of high ratings. A VAS functional scale represents a patient-weighted functional assessment in which additional interpretation is given to the meaning of the limitations by the patient. VAS-F scales may be suitable for use in the clinic and in research. However, studies to assess sensitivity to change are required to determine the appropriate role of this scale.

Activities of Daily Living↗