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Biomedical subjects

D Furst

Publications and source records attributed to D Furst.

At least 37 records · Page 2Linked to original sources
PubMed1999

Randomized clinical trials and longitudinal observational studies in systemic lupus erythematosus: consensus on a preliminary core set of outcome domains.

The OMERACT module on systemic lupus erythematosus (SLE) dealt with the definition of preliminary core sets of outcome domains for randomized clinical trials (RCT) and longitudinal observational studies (LOS). After lectures introducing the problems and addressing the key issues, 6 discussion groups, 3 each for LOS and RCT, discussed and weighted more than a dozen possible items for use as outcome domains. The means of the respective 3 groups were calculated. For both RCT and LOS the same outcome domains received more than 10 of a total maximum of 100 points: disease activity, health related quality of life (HRQOL), damage, and toxicity/adverse events. However, the weights for HRQOL and damage were different for LOS and RCT. A final vote led to the acceptance of these 4 variables as a preliminary core set for outcome in SLE by more than 80% of the participants. This core set will allow for improved design, performance, and evaluation of future studies in SLE. However, a number of domains not included in the core set were regarded as important for further analysis and research.

Decision Making↗
PubMed1998

Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA. METHODS: Two hundred seventy-four patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Efficacy parameters were assessed monthly. Cumulative response rates (percentage of patients meeting the criteria for response at any time during the study) were analyzed utilizing 3 sets of composite criteria: the Paulus criteria, the American College of Rheumatology criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts. RESULTS: Eighty-three percent of patients completed 24 weeks of treatment. Numeric trends in favor of the 20 microg/day treatment group were seen with all 3 cumulative composite measures. However, a statistically significant increase (P = 0.035) in response rate for the 20 microg/day group versus placebo was detected using only the Paulus criteria. The presence of serum antibodies to CII at baseline was significantly associated with an increased likelihood of responding to treatment. No treatment-related adverse events were detected. The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells. CONCLUSION: Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent. Further controlled studies are required to assess the efficacy of this treatment approach.

Administration, Oral↗
PubMed1995

American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis.

OBJECTIVE: Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. METHODS: Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. RESULTS: The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. CONCLUSION: We present a definition of improvement which we hope will be used widely in RA trials.

Adult↗
PubMed1995

Health status instruments / utilities.

Rheumatologists and other interested professionals at the OMERACT II conference formed small groups to discuss whether it was sensible to use a generic health status instrument in musculoskeletal disease trials. These instruments promise the possibility of comparison of health status between disease states. However, data is lacking on validity of the current generation of instruments to support their use. Participants had little personal experience with these instruments. After inspection, many voiced strong concerns over comprehensiveness and responsiveness. Many dimensions of health relevant for patients with this group of diseases were felt to be underrepresented. The dimension of adverse effects was universally absent, although this is more a problem of state of the art in trial methodology than a problem of these measures. Although there is little data, the small number of response categories in the dimensions covered, plus the lack of comprehensiveness, make it likely that responsiveness will be low. Further research, especially the adoption of one or more generic measures alongside specific measures, both in trials and in observational studies, is necessary to validate and improve the current generic measures. Until that time, valid conclusions and health policy regarding musculoskeletal diseases cannot be based on generic measures of health status.

Health Status↗
PubMed1993

The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials.

OBJECTIVE: To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials. METHODS: We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome. RESULTS: The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count). The committee also proposes specific ways of measuring each outcome. CONCLUSION: We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies.

Arthritis, Rheumatoid↗
PubMed1993

The course of skin involvement in systemic sclerosis over three years in a trial of chlorambucil versus placebo.

OBJECTIVE: To describe the course of cutaneous involvement in systemic sclerosis (SSc; scleroderma) over 3 years, in the context of a placebo-controlled drug trial. METHODS: The course of skin tethering (assessed by a semiquantitative skin scoring technique) was documented annually for 3 years in 64 SSc patients with early (< 3 years duration at entry), intermediate (3-8 years duration), or late (> 8 years duration) diffuse or limited SSc. RESULTS: Mean +/- SD entry skin scores were significantly greater in the 33 diffuse SSc patients (13.1 +/- 5.0) than in the 31 limited SSc patients (4.3 +/- 2.1) (P < 0.001). In patients with diffuse SSc, the skin score remained stable for the first 12 months, but had decreased significantly by 24 months (P < 0.022) and 36 months (P < 0.004). In those with limited SSc, the skin score did not change significantly over 3 years. CONCLUSION: Trials of treatments designed to affect skin thickening/tethering should be conducted in patients who have diffuse SSc (of short, intermediate, or long duration) at entry. The best time to study therapies designed to affect skin thickening may be in the first year after entry.

Adult↗
PubMed1993

Variability of immunologic and clinical features in patients with rheumatoid arthritis studied over 24 hours.

Disease activity measures in patients with rheumatoid arthritis (RA) are influenced by many factors. Bedrest has been long recognized to effect decreased disease activity. In addition, most patients note maximal levels of pain and stiffness in the early morning hours with improvement in the afternoon. Cytokines and hormones with circadian rhythms may also contribute to variability in disease status during the day. Our purpose was to investigate variability of clinical and immunologic measures over a 24-h period of hospitalization in patients with RA. Production of rheumatoid factors and immunoglobulins, joint counts and questionnaire evaluations were measured 3 to 6 times over a 24-h period of hospitalization in 10 patients with RA who were not receiving steroids or second line drugs. Total joint counts were significantly decreased as soon as 4 h after admission, and continued to decrease during the 24-h period of observation. Significant decreases in mononuclear cell proliferation and antibody synthesis were also observed. Our findings are consistent with the presence of decreased levels of immunostimulatory mediators in hospitalized patients especially during late afternoon or evening hours.

Activities of Daily Living↗
PubMed1989

Elevated BAL fluid histamine levels and parenchymal pulmonary disease in rheumatoid arthritis.

To determine the amount of histamine in BAL fluid in subjects with RA and to ascertain if elevated histamine levels were associated with parameters of active pulmonary disease, we measured BAL fluid histamine levels in 31 subjects with RA and 36 normal subjects. The subjects with RA had a significantly greater mean BAL histamine level than the normal subjects, (313 +/- 154 pg/ml vs 18 +/- 8 pg/ml; p less than 0.05). When the subjects with RA were divided into three groups based on chest radiograms (1 = normal; 2 = pleural disease only; 3 = interstitial or nodular disease), we found that subjects in group 3 had significantly lower values for TLC and D. Subjects in group 3 also had higher percentages of BAL neutrophils and eosinophils and higher BAL histamine levels (group 1, 115 +/- 52 pg/ml; group 2, 30 +/- 30 pg/ml; and group 3, 1,182 +/- 709 pg of histamine per milliliter). Moreover, BAL histamine levels were negatively correlated with TLC (r = -0.46; p = 0.01) and FVC (r = -0.45; p = 0.01) and positively correlated with BAL neutrophils (r = 0.6; p = 0.0003) and BAL eosinophils (r = 0.89; p = 0.0001). These data suggest that the BAL histamine level may be a useful marker to determine the activity of pulmonary disease in RA.

Arthritis, Rheumatoid↗
PubMed1988

The pharmacokinetics of etodolac in serum and synovial fluid of patients with arthritis.

The pharmacokinetics of etodolac have been evaluated in five patients with arthritis given 200 mg etodolac, twice daily, at 12-hour intervals, for 7 days. Albumin and total protein concentrations were markedly lower in synovial fluid than in serum, and etodolac free fraction was significantly higher. Etodolac readily penetrated into the synovial fluid, and in the postdistributive phase the concentration of free etodolac (i.e., the drug responsible for pharmacologic activity) remained higher than that in serum at all times. No differences in the half-life of etodolac elimination were noted.

Acetates↗
PubMed1988

Type A personality components and the blood pressure response to dynamic exercise.

One hundred and eleven healthy male subjects underwent cycle ergometry testing and completed a Jenkins type A personality survey. The subjects were divided into three equal groups with respect to their distribution on the Jenkins scales. The groups were compared for heart rate (HR), systolic blood pressure (SBP), the ratio of SBP/HR, and VO2 max/kg during rest and at exercise. Repeated measures MANOVA indicated that high scoring type A had lower HR values during exercise with no differences in SBP. However, the SBP/HR ratio was higher in the high type A group. The same was true for the component of hard-driving and competitiveness. Those scoring highest in this component also had higher VO2 max/kg body weight. From the description it could be conjectured that those with higher scores on type A components push themselves harder and thus achieve improvement in fitness. No clear explanation exists for the relative differences in SBP response.

Adult↗
PubMed1985

A statistical reevaluation of the STAI anxiety questionnaire.

This study examined the capability and efficiency of two commonly used scales, the trait and trait and state inventories (Spielberger et al., 1970), to measure anxiety construct (N = 100). The probabilistic Rasch Model (Wright & Masters, 1982) was applied to athletes' responses to trait and state anxiety items before competition (stress). The analysis indicated that several items of both scales produce misfit responses, share identical locations on the continuum, and do not produce equal units of measurement. The findings question the generalizability of the research on anxiety. Recommendations for improving the anxiety tests are made.

Adult↗
PubMed1984

Auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. Cooperative systematic studies of rheumatic diseases.

Two hundred eight patients were studied in a prospective, controlled, double-blind multicenter trial comparing auranofin (AUR), gold sodium thiomalate (GST), and placebo. One hundred sixty-one patients completed at least 20 weeks of therapy. Response to a variety of measures of efficacy was generally modest for both gold treatment groups although improvement was continuing in both groups at the end of the study. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated more improvement in patients with anemia and thrombocytosis compared to the other treatment groups and both gold preparations were superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Twenty-seven percent of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant cause. Only 6% of patients on AUR were withdrawn for untoward drug effect. The time of onset of the adverse reactions is discussed. The two gold preparations were similar in efficacy although AUR was better tolerated.

Anti-Inflammatory Agents↗
PubMed1983

Prevalence and clinical correlates of pulmonary arterial hypertension in progressive systemic sclerosis.

Forty-nine patients with progressive systemic sclerosis who had undergone extensive studies including pulmonary artery catheterization as part of an ongoing prospective study of the natural course of progressive systemic sclerosis were evaluated. The overall prevalence of pulmonary arterial hypertension in this population of patients with progressive systemic sclerosis was 33 percent, and among 10 subjects with the CREST syndrome the prevalence of pulmonary hypertension was 50 percent. The relation between pulmonary arterial hypertension documented at catheterization and abnormal results of noninvasive studies suggesting pulmonary hypertension, including physical examination, chest x-ray, electrocardiography, echocardiography, single-breath diffusing capacity, and vital capacity, was studied. Diffusing capacity was significantly lower in those patients with definite pulmonary hypertension (mean pulmonary artery pressure of 22 mg Hg or more) compared with those with a normal mean pulmonary artery pressure, and a diffusing capacity below 43 percent of predicted showed the greatest sensitivity (67 percent) of any single diagnostic test in detecting definite pulmonary hypertension. Chest x-ray suggesting pulmonary hypertension was the least sensitive of the tests evaluated, but showed the greatest specificity (100 percent) in identifying patients with pulmonary hypertension. A classification matrix based on discriminant function analysis utilizing the combination of diffusing capacity below 43 percent of predicted and chest x-ray and electrocardiographic findings correctly identified 75 percent of patients with definite pulmonary hypertension and 97 percent of patients with a normal pulmonary artery pressure, but failed to identify correctly patients with mild pulmonary hypertension (mean pulmonary artery pressure of 20 mm Hg). These findings indicate that specific noninvasive studies are helpful in assessing the likelihood of normal or definitely elevated pulmonary artery pressures in patients with progressive systemic sclerosis, but patients with mild pulmonary hypertension are not likely to be identified by these noninvasive studies.

Adult↗
PubMed1981

Lack of sensitivity of measurements of Vd/Vt at rest and during exercise in detection of hemodynamically significant pulmonary vascular abnormalities in collagen vascular disease.

Wasted ventilation fraction (Vd/Vt) normally declines substantially during exercise in persons without lung disease. Failure of Vd/Vt to decrease during exercise has been reported to be one of the earliest abnormalities in patients with dyspnea caused by pulmonary vaso-occlusive disease, suggesting that measurement of Vd/Vt at rest and during exercise are useful in the diagnosis of pulmonary vascular disorders. We studied pulmonary hemodynamic and Vd/Vt responses to exercise in 11 patients in the supine position with suspected pulmonary vascular involvement caused by progressive systemic sclerosis, systemic lupus erythematosus, or recurrent pulmonary emboli, 10 of whom had dyspnea at rest and/or on exertion. In contrast to previous reports of no change or an increase in Vd/Vt during exercise in patients with pulmonary vascular disease, we found Vd/Vt to decrease significantly during exercise in 8 of 9 patients in whom mean pulmonary artery pressures were abnormally elevated at rest and/or during exercise. Our findings suggest that normal responses of Vd/Vt to exercise do not exclude hemodynamically significant pulmonary vaso-occlusive disease.

Adult↗
PubMed1979

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate.

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.

Adult↗
PubMed1979

Quantitation and characterization of soluble immune complexes precipitated from sera by polyethylene glycol (PEG).

Polyethylene glycol (PEG) was used to isolate immune complexes from sera. Complexes were then quantified and partially characterized by a variety of immunological techniques. Complexes were detected in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Felty's syndrome and vasculitis, but not in polymyositis, scleroderma or Behçets syndrome. The level of immune complexes correlated with disease activity in SLE and RA patients. Rheumatoid factors and anti-DNA antibodies were enriched by PEG precipitation of RA and SLE sera, respectively, thus these antibodies appeared to be present in the form of soluble immune complexes. Immune complexes usually contained all three immunoglobulin classes, IgG, IgM and IgA. Complexes from RA patients were generally larger and often contained Clq, while C3 was found almost exclusively in SLE complexes which also tended to be smaller. Such compositional differences may one day explain the differences in clinical manifestations of various immune complex-mediated diseases.

Antibodies, Antinuclear↗
PubMed1978

Association of HLA antigen a9 with progressive systemic sclerosis (scleroderma).

Upon evaluation of 40 subjects with progressive systemic sclerosis (PSS), a significant association of HLA antigens A9 and Aw24 (a subgroup of A9) was found with diffuse scleroderma. HLA-Aw23 (a second subgroup of A9) was also increased in the patients, however, this was not statistically significant. Diffuse scleroderma appears to be one of the few diseases that shows an association with the HLA-A locus.

Epitopes↗