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Biomedical subjects

T Pincus

Publications and source records attributed to T Pincus.

At least 73 records · Page 4Linked to original sources
PubMed1997

Combination treatment of severe rheumatoid arthritis with cyclosporine and methotrexate for forty-eight weeks: an open-label extension study. The Methotrexate-Cyclosporine Combination Study Group.

OBJECTIVE: To determine whether the clinical benefit and favorable safety profile previously noted with the combination of cyclosporine (CSA) and methotrexate (MTX) given for 24 weeks in patients with rheumatoid arthritis (RA) would be maintained for a further 24 weeks, and whether the addition of CSA in patients who had previously been randomized to receive placebo + MTX would result in clinical benefit. METHODS: Eligible subjects from the initial study (weeks 0-24), in which the addition of placebo or CSA to MTX therapy was compared in patients with RA that was partially responsive to MTX, were enrolled. Patients who had received CSA + MTX continued this regimen for a further 24 weeks (weeks 24-48) (group 1; n = 48), and patients who had initially received placebo + MTX now received CSA + MTX for 24 weeks (weeks 24-48) (group 2; n = 44), in an open-label extension study. The primary outcome measures were the number of tender joints, number of swollen joints, physician and patient global assessments, pain, functional disability as measured by the modified Health Assessment Questionnaire, and erythrocyte sedimentation rate. RESULTS: Of the 92 patients enrolled, 80 (87%) completed the extension study. In patients in group 1, the clinically and statistically significant improvement in response outcomes previously noted at week 24, ranging from 25% to 50%, was maintained through week 48. In patients in group 2, the addition of CSA resulted in significant clinical improvement. By week 48, most outcome measures in group 2 patients were similar to those in group 1 patients. CSA treatment resulted in a small increase in serum creatinine levels, but only 1 patient was withdrawn from the study for this reason. CONCLUSION: The clinical improvement previously observed in patients treated with the CSA + MTX combination for 24 weeks was maintained for 24 subsequent weeks, without serious adverse effects, and was also observed in the patients whose treatment was switched from placebo + MTX to CSA + MTX.

Adult↗
PubMed1997

Measures of activity and damage in rheumatoid arthritis: depiction of changes and prediction of mortality over five years.

OBJECTIVE: To analyze various quantitative measures of inflammatory activity and joint damage, including articular, radiographic, laboratory, questionnaire, and physical function measures, in regard to changes in status in surviving patients and prediction of mortality in non-survivors over 5 years in a cohort of patients with rheumatoid arthritis (RA) monitored in the mid-1980s and early 1990s. METHODS: A comprehensive evaluation, which included a complete joint count, radiograph, laboratory tests, physical measures of function, and self-report questionnaire scales, was performed at baseline and 5 years later in 210 consecutive patients with RA. RESULTS: Five years after baseline, 206 of the 210 patients were accounted for: 37 had died, 130 had a comprehensive repeat assessment, and 39 had a more limited repeat assessment. In surviving patients, most measures of activity were generally unchanged or somewhat better, including joint tenderness, pain on motion, and swelling; erythrocyte sedimentation rate and rheumatoid factor; as well as questionnaire scores for pain, global status, helplessness, and difficulty in performing 8 activities of daily living (ADL) according to a modified Health Assessment Questionnaire (MHAQ). By contrast, measures of damage, including joint deformity, grip strength, walk time, and radiographic scores, indicated worse status. Mortality over 5 years was predicted significantly in univariable analyses by American College of Rheumatology (formerly the American Rheumatism Association) Functional Class, limited joint motion, scores for MHAQ, global status, helplessness, grip strength, walk time, button time, and number of comorbidities and duration of diseases, as well as the sociodemographic measures of age and formal education. In multivariable Cox regressions, age, comorbidities, MHAQ, and other measures of functional status were the most effective predictors of 5-year mortality. CONCLUSION: In patients with RA, most measures of inflammatory activity were unchanged and sometimes better, while measures of damage indicated worse status in the same patients over 5 years. Measures indicating functional disability, as well as age and comorbidities, predict 5-year mortality more effectively than radiographic and laboratory data. Measures of inflammatory activity may underestimate long-term outcomes in RA, and long-term studies should include measures of damage.

Activities of Daily Living↗
PubMed1997

Comparison of 3 quantitative measures of hand radiographs in patients with rheumatoid arthritis: Steinbrocker stage, Kaye modified Sharp score, and Larsen score.

OBJECTIVE: To compare 3 quantitative hand radiograph scores, Steinbrocker stage, Larsen score, and Sharp score modified by Kaye, to one another and to other measures of clinical status in a cross sectional analysis of hand radiographs of 173 patients with rheumatoid arthritis (RA). METHODS: Radiographs were scored and compared to other measures of clinical status according to correlation and cross tabulation analyses. RESULTS: In these cross sectional studies, radiographic scores according to all 3 methods were correlated at high levels (r(s) > 0.5) with one another and duration of disease, as well as with scores for physical joint deformity and limited motion; at lower levels (0.3 < r(s) < 0.5) with physical joint swelling scores, functional status, and age; and at low levels of marginal or no clinical importance (r(s) < 0.3) with physical joint tenderness scores, laboratory data, and pain scores. CONCLUSION: The 3 scoring methods give similar quantitative information concerning hand radiographs of patients with RA. The Larsen and modified Sharp scores are preferred measures, as the detailed information facilitates comparison of different patients and monitoring of individual patients over time.

Activities of Daily Living↗
PubMed1996

Formal education and five-year mortality in rheumatoid arthritis: mediation by helplessness scale score.

OBJECTIVE: To analyze scores on a scale designed to measure helplessness, a cognitive variable, as a possible mediator of the association between formal education level and mortality over 5 years in patients with rheumatoid arthritis (RA). METHODS: A cohort of 1,416 patients with RA from 15 private practices in 6 states and Washington, DC was monitored for over 5 years. Demographic, socioeconomic, therapy, functional status, and psychological variables were analyzed as possible predictors of mortality in invariable and multivariable Cox Proportional Hazards models. RESULTS: In a 5-year followup, 1,384 patients were accounted for (97.3%), including 174 who died versus 111 expected (standardized mortality ratio = 1.54). Higher mortality was associated significantly with low formal education, high age, poor scores for activities of daily living (ADL) on a modified health assessment questionnaire (MHAQ), and poor scores on a helplessness scale (all P < 0.01) in univariable analyses. High age, few years of formal education, and poor MHAQ ADL scores were all significant independent predictors of mortality when analyzed simultaneously in a Cox Proportional Hazards model. When helplessness scale scores were included in a model, scores greater than 2.4 (on a scale of 1 to 4), higher age, male gender, and increased MHAQ ADL difficulty scores were all independently significantly predictive of 5-year mortality (P < 0.05), while years of education was no longer a significant predictor. CONCLUSION: Scores on a helplessness scale appear to mediate a component of the association between formal education level and 5-year mortality in these patients with RA. Health professionals and policy makers might consider interventions directed at modification of helplessness as adjunctive to standard interventions to improve outcomes in RA.

Adult↗
PubMed1996

Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine.

INTRODUCTION: Cytochrome P4503A (CYP3A) is primarily responsible for the metabolism of cyclosporine and that of many other drugs. Several substrates of CYP3A have been investigated for use as pharmacologic probes to predict the CYP3A-metabolizing capacity of an individual and, therefore, the disposition of other CYP3A substrate drugs. One such measure of CYP3A activity is the 14C erythromycin breath test, which has been applied to the prediction of cyclosporine disposition. However, the test has practical limitations. Because of this, the 0- to 8-hour urinary dapsone recovery ratio has been studied as an alternative and more practical probe of CYP3A activity. METHODS: The dapsone recovery ratio and the 14C erythromycin breath test were correlated with cyclosporine concentrations in 16 patients with rheumatoid arthritis to determine the usefulness of the dapsone recovery ratio as an alternative to the 14C erythromycin breath test. The erythromycin breath test showed a fourfold variation between subjects and correlated weakly with trough cyclosporine concentrations (r = -0.50, p < 0.05), whereas the dapsone recovery ratio varied only approximately twofold between subjects and did not correlate with trough cyclosporine concentrations (r = 0.02, p = 0.94). The correlation between the dapsone recovery ratio and the erythromycin breath test (r = 0.22, p = 0.41) was not significant. CONCLUSIONS: These data suggest that results obtained with one probe in vivo may not apply to another CYP3A substrate. The poor quantitative relationship between cyclosporine concentrations and the erythromycin breath test limits its usefulness in the prediction of an individual's cyclosporine dose requirement.

Adult↗
PubMed1996

Prevalence of self-reported depression in patients with rheumatoid arthritis.

The prevalence of self-reported depressive symptoms was investigated in a case-control study of patients with rheumatoid arthritis (RA) attending an out-patient clinic at the Middlesex Hospital. Patients selected their own controls, matched for age and sex. Previous attempts to measure depressive symptoms in RA have suffered from measurement error due to criterion contamination, where psychological symptoms augment depressive scores. A total of 163 patients (77% of the sample) and 115 matched pairs completed the Hospital Anxiety and Depression Scale (HADS). The results indicated that RA patients are more depressed and anxious than controls. The prevalence of depression above the cut-point was 15%. This figure is comparable to other reports adjusted for criterion contamination, but is lower than that of other studies which employ 'contaminated' tools. The depression scale of the HADS appeared to be relatively free of criterion contamination. Subject to further reliability testing, the HADS may be a practical screening tool for practitioners to assess patients in need of psychological interventions.

Arthritis, Rheumatoid↗
PubMed1996

Pain patients' bias in the interpretation of ambiguous homophones.

This study describes an investigation into the interpretation of ambiguous homophones by chronic pain patients and non-pain control patients. Participants were presented auditorily with a list of homophones and asked to write down the word they had just heard. Following a two-minute distraction task they completed a free-recall task. A significant bias towards pain interpretation was exhibited by the pain patients and this effect appears to be independent of anxiety and depression. Both groups reported awareness of the ambiguity of some words, and the analysis was repeated for each participant excluding the words reported to be ambiguous. Pain patients still showed the bias towards pain interpretation. The free-recall task also demonstrated a memory bias for pain stimuli in pain groups. The results provide further evidence that chronic pain is associated with biases in the processing of information. Future research should aim to investigate the role of these biases in the maintenance of chronic pain.

Anxiety Disorders↗
PubMed1996

Eosinophilia-myalgia syndrome: patient status 2-4 years after onset.

The clinical status of patients with the eosinophilia-myalgia syndrome (EMS) was studied 2-4 years after its description in 2 databases: (1) a structured review of 205 patients with EMS completed by 15 physicians 18-24 months after onset, which included symptoms, physical findings, laboratory data, and responses to treatments; (2) a self-report questionnaire completed by 344 patients with EMS 42-48 months after onset. Most patients continued to experience symptoms, but almost none experienced new signs of acute inflammation more than one year after onset of EMS. These databases, while presenting information concerning longterm outcomes of more patients with EMS than other reported sources, remain limited by patient selection and the absence of information concerning clinical symptoms before development of EMS.

Eosinophilia-Myalgia Syndrome↗
PubMed1995

Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group.

BACKGROUND: Patients with severe rheumatoid arthritis who are treated with methotrexate frequently have only partial improvement. METHODS: In a six-month randomized, double-blind trial, we compared combination therapy with cyclosporine (2.5 to 5 mg per kilogram of body weight per day in two divided doses at 12-hour intervals) and methotrexate (at the maximal tolerated dose) with methotrexate and placebo in 148 patients with rheumatoid arthritis who had residual inflammation and disability despite partial but substantial responses to prior methotrexate treatment. The primary outcome measure was the change in the number of tender joints. RESULTS: The mean (+/- SD) dose of cyclosporine at the final treatment was 2.97 +/- 1.02 mg per kilogram per day. As compared with the placebo group, the patients in the treatment group had a net improvement in the tender-joint count of 25 percent, or 4.8 joints (95 percent confidence interval, 0.7 to 8.9; P = 0.02), and in the swollen-joint count of 25 percent, or 3.8 joints (95 percent confidence interval, 1.3 to 6.3; P = 0.005); improvement in overall disease activity as assessed by the physician (19 percent, P < 0.001) and the patient (21 percent, P < 0.001); and improvement in joint pain (23 percent, P = 0.04) and in the degree of disability (26 percent, P < 0.001). The mean erythrocyte sedimentation rate increased by 4.2 mm per hour in the cyclosporine group and decreased by 4.8 mm per hour in the placebo group (P = 0.006). Thirty-six patients (48 percent) in the cyclosporine group and 12 patients (16 percent) in the placebo group (P < 0.001) met the 1993 criteria for improvement of the American College of Rheumatology (more than 20 percent improvement in the numbers of both swollen and tender joints and improvement in three of five other variables). Seventeen patients in the cyclosporine group and 12 patients in the placebo group were withdrawn from the study; 2 patients in the cyclosporine group died, 1 from viral pneumonia and the other in a motor vehicle accident. Serum creatinine concentrations increased by a mean of 0.14 +/- 0.27 mg per deciliter (12 +/- 24 mmol per liter) in the cyclosporine group and by 0.05 +/- 0.19 mg per deciliter (4 +/- 17 mmol per liter) in the placebo group (P = 0.02). CONCLUSIONS: In a six-month study, patients with severe rheumatoid arthritis and only partial responses to methotrexate had clinically important improvement after combination therapy with cyclosporine and methotrexate. Side effects were not substantially increased. Long-term follow-up of patients treated with this combination is needed.

Arthritis, Rheumatoid↗
PubMed1995

The eosinophilia-myalgia syndrome: status of 205 patients and results of treatment 2 years after onset.

OBJECTIVE: To describe the course of the eosinophilia-myalgia syndrome during a 2-year period. DESIGN: 15 physicians completed a structured review form to describe symptoms, physical findings, laboratory data, and responses to treatments in 205 patients with the eosinophilia-myalgia syndrome at the onset of illness and after 18 to 24 months of follow-up. SETTING: 15 university and private clinical practice settings. PATIENTS: 205 patients for whom follow-up data were available and who met four criteria at diagnosis: eosinophil count of 1000 cells/mm3 or greater; presence of fasciitis, peripheral neuropathy, polyradiculopathy, interstitial pulmonary disease, pulmonary hypertension, or myocardial involvement; history of L-tryptophan consumption; and absence of other conditions that could account for these findings. INTERVENTION: Empirical interventions by the physicians. MEASUREMENTS: Symptoms, physical findings, laboratory test results, biopsy findings, radiographic reports, therapeutic interventions, and responses to these interventions. RESULTS: After 18 to 24 months, all symptoms except cognitive changes were reported to have improved in most patients. Nearly all physical findings were also reported to have improved or resolved in most patients; only peripheral neuropathy was unchanged. No evidence of ongoing inflammatory disease was reported. Prednisone was reported to be helpful in 79% of patients who received it during the acute phase of the syndrome. No other treatment was reported to be consistently beneficial. CONCLUSIONS: 18 to 24 months after the onset of illness, most symptoms and physical findings in most patients with the eosinophilia-myalgia syndrome resolved or improved. Cognitive changes were reported to be worse in 32% of patients. Prednisone was helpful in the acute phase of illness. No treatment was clearly valuable in management of the later phase of the syndrome.

Adult↗
PubMed1995

Practical management of osteoarthritis. Integration of pharmacologic and nonpharmacologic measures.

Pharmacotherapy should play an adjunctive role to nonpharmacologic measures in the overall management of patients with symptoms due to osteoarthritis. Patients should be instructed in how to rest or unload involved joints; protect them through appropriate manipulation of their environment and appropriate methods of lifting and bending; and maintain and improve muscle strength and flexibility to ensure joint stability and prevent contractures. In most patients, acetaminophen in doses of up to 4 g/d is preferable to nonsteroidal anti-inflammatory drugs (NSAIDs) as a first-choice agent because of its lower toxicity. If NSAIDs are used, they should be prescribed initially in lower (analgesic) doses. Ibuprofen may be the preferred initial NSAID because it can be given in low doses for short durations, has been associated with lower rates of gastrointestinal tract side effects, and is inexpensive.

Acetaminophen↗