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D T Felson

Publications and source records attributed to D T Felson.

At least 145 records · Page 8Linked to original sources
PubMed1993

Choosing a core set of disease activity measures for rheumatoid arthritis clinical trials.

Rheumatoid arthritis (RA) clinical trials often include at least 10 measures of disease activity (e.g., tender and swollen joint counts, erythrocyte sedimentation rate, patient pain, grip strength, etc.), and each trial contains different measures. Using dissimilar disease activity (outcome) measures to assess therapies makes it impossible to judge therapies against a common standard. Furthermore, multiple statistical testing is performed, and outcome measures are often used which are insensitive to change. Ultimately, to compare different RA therapies, the same outcomes should be measured in all trials. In the first stage of an effort to develop a core set of outcome measures to be used in all RA trials, we present an approach to the selection of the measures. This approach is based on a critical evaluation of whether commonly used outcome measures have construct, face, content, criterion, and discriminant validity. In addition, our approach includes testing whether these measures are redundant. Also, selected evidence on the validity of currently used outcome measures is reviewed.

Arthritis, Rheumatoid↗
PubMed1993

Habitual physical activity is not associated with knee osteoarthritis: the Framingham Study.

We evaluated the potential risk factor by examining levels of habitual physical activity during middle age, and knee osteoarthritis (OA) in later years in the Framingham Cohort. Weight-bearing knee radiographs were obtained during the 18th biennial examination (1983-85), when the 1,415 subjects had a mean age of 73 years. Cohort members had been asked at 1954-57 and 1971-73 about the number of hours spent daily at various levels of physical activity, ranging from sedentary to heavy activity. Physical capacity measures, such as forced expiratory volume in one second and resting pulse rate, were also examined for association with OA. In the cohort, 97/589 men and 154/826 women had OA. We found no association between habitual physical activity and knee OA after adjusting for age, body mass index, knee injury, smoking and education. In the highest quartile of habitual physical activity compared to the least active, the aOR for men was 1.34 (95% CI: 0.66, 2.74) and for women was 1.09 (95% CI: 0.63, 1.90). There was no increase in the risk of knee OA with increasing physical activity in either men or women. Physical capacity measures were also unassociated with OA. Of interest, men with high levels of habitual physical activity had significantly elevated rates of asymptomatic osteophytes, [aOR = 2.14, (95% CI: 1.01, 4.54)], suggesting that habitual physical activity may influence development of osteophytes but not of more severe or symptomatic knee OA. In sum, habitual physical activity does not increase the risk of knee OA for men or women.

Aged↗
PubMed1992

Smoking eliminates the protective effect of oral estrogens on the risk for hip fracture among women.

OBJECTIVE: To determine if the association between smoking and osteoporotic fractures is related to the quantity of cigarettes smoked and to determine if smoking modifies the protection by estrogens. DESIGN: Cohort study. SETTING: A population-based cohort study, the Framingham Study. PARTICIPANTS: A total of 2873 women in the Framingham Study followed through examination 19 (1985-1987). MEASUREMENTS: All fractures of the proximal femur sustained by women in the Framingham Study from 1948 to 1987 were ascertained. At almost all examinations, available information on cigarette smoking was used to classify women as "ever smokers" compared with "never smokers," and, among "ever smokers," "current" compared with "former smokers." A similar classification for estrogen use was created. Information on potentially confounding variables was taken from each examination, including age, adiposity (weight/height2), alcohol consumption (ounces per week), and caffeine intake (coffee and tea). RESULTS: Overall, 207 hip fractures occurred among 34,700 woman-examinations of observation. In the entire cohort, current smoking did not appear to increase hip fracture risk (adjusted odds ratio [AOR], 1.22; 95% CI, 0.76 to 1.95; P greater than 0.2). Also overall, current estrogen use appeared to be protective (AOR, 0.38; CI, 0.12 to 1.21, P = 0.10). Among current smokers, however, estrogen use did not protect against fracture (AOR for current use, 1.26; CI, 0.29 to 5.45), whereas estrogen was protective in nonsmokers (AOR for current or past use, 0.37; CI, 0.19 to 0.75; P = 0.005). CONCLUSIONS: Overall, smoking does not appear to increase the risk for hip fracture in women. Although estrogen replacement protects nonsmokers from fracture, smoking may negate the protective skeletal effects of estrogen replacement therapy.

Administration, Oral↗
PubMed1992

Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham Study.

OBJECTIVE: To evaluate the effect of weight loss in preventing symptomatic knee osteoarthritis in women. DESIGN: Cohort analytic study. SETTING: The Framingham Study, based on a sample of a defined population. PATIENTS: Women who participated in the Framingham Knee Osteoarthritis Study (1983 to 1985): Sixty-four out of 796 women studied had recent-onset symptomatic knee osteoarthritis (knee symptoms plus radiographically confirmed osteoarthritis) were compared with women without disease. MEASUREMENTS: Recalled date of symptom onset was used as the incident date of disease. Historical weight was defined as baseline body mass index up to 12 years before symptom onset. Change in body mass index was assessed at several intervals before the current examination. Odds ratios assessing the association between weight change and knee osteoarthritis were adjusted for age, baseline body mass index, history of previous knee injury, habitual physical activity level, occupational physical labor, smoking status, and attained education. RESULTS: Weight change significantly affected the risk for the development of knee osteoarthritis. For example, a decrease in body mass index of 2 units or more (weight loss, approximately 5,1 kg) over the 10 years before the current examination decreased the odds for developing osteoarthritis by over 50% (odds ratio, 0.46; 95% Cl, 0.24 to 0.86; P = 0.02). Among those women with a high risk for osteoarthritis due to elevated baseline body mass index (greater than or equal to 25), weight loss also decreased the risk (for 2 units of body mass index, odds ratio, 0.41; P = 0.02). Weight gain was associated with a slightly increased risk for osteoarthritis, which was not statistically significant. CONCLUSION: Weight loss reduces the risk for symptomatic knee osteoarthritis in women.

Aged↗
PubMed1992

Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials.

OBJECTIVE: Preferred drugs for rheumatoid arthritis (RA) should be those that have maximal efficacy with the least toxicity. We evaluated the efficacy and toxicity tradeoffs for drugs frequently used in the treatment of RA. METHODS: We updated 2 metaanalyses of published clinical trials, by adding trials published through 1990 and trials of azathioprine (AZA). We tested 3 different definitions of efficacy, each plotted against 3 different toxicity measures, for antimalarial drugs, methotrexate (MTX), auranofin, injectable gold, D-penicillamine, sulfasalazine (SSZ), AZA, and placebo. Efficacy measures included composite efficacy (a combination of joint count, grip strength, and erythrocyte sedimentation rate), tender joint count alone, and a measure based on how many patients dropped out due to inefficacy. Toxicity measures were the proportion dropping out due to toxicity, the same dropouts with side effects weighted for severity using a modification of a published toxicity index, and the proportion with severe toxicities (defined as a score of at least 7 of 10 on the toxicity index). The latter were usually organ toxicities (e.g., cytopenias and renal involvement). RESULTS: All 9 efficacy/toxicity tradeoff plots suggested that MTX and antimalarial drugs had the highest efficacy relative to toxicity. MTX scored among the most efficacious of the drugs and, of these, had the least toxicity. Antimalarial drugs, though showing only moderate efficacy, had the lowest toxicity rate of all the drugs. SSZ scored close to MTX but was, in general, slightly more toxic. CONCLUSION: In the short-term context of clinical trials, antimalarial drugs and MTX have the best efficacy/toxicity tradeoffs and may, therefore, be the preferred drugs.

Antimalarials↗
PubMed1992

Bone mineral density in elderly men and women: results from the Framingham osteoporosis study.

Our study investigated bone mineral density of the proximal femur and ultradistal and proximal radius in a population of elderly men and women. The Framingham study started in 1948, following a population-based sample for evaluation of cardiovascular risk factors and events. During the 20th biennial Framingham examination (1988-89) we conducted the Framingham osteoporosis study, measuring bone mineral density in the proximal femur and distal and proximal radius for 1154 study participants. Ages ranged from 68 to 98 years, with a mean age of 76 years. Bone mineral density was measured using Lunar SP2 and DP3 densitometers. This cross-sectional study evaluates mean bone mineral density measurements at each site by 5 year age intervals for men and women, testing for trends in bone density with age. Analyses were repeated adjusting for weight and height. Among the 446 and 708 women, bone mineral density of the femur and bone mineral content of the proximal radius were inversely and significantly related to age in both sexes and were considerably higher in men than women at all sites. The linear decline with age group in our cross-sectional study remained after multivariate adjustment for height and weight. The ultradistal radius showed no significant correlation with age for either sex. There were significant correlations between the bone measurements made at different sites for both men and women (range in r = 0.27-0.89). Cross-sectional curves of bone mineral density with age showed no significant differences in slope between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Fibromyalgia syndrome in patients infected with human immunodeficiency virus. The Boston City Hospital Clinical AIDS Team.

PURPOSE: To prospectively assess rheumatic manifestations of human immunodeficiency virus (HIV) disease in a municipal hospital clinic population in which intravenous drug use was the most common risk factor for HIV infection. PATIENTS AND METHODS: Patients with documented HIV infection were evaluated for rheumatic disease using a standardized questionnaire and examination. Patients with fibromyalgia were compared with HIV-infected patients without fibromyalgia and with fibromyalgia patients without known risk factors for HIV infection. RESULTS: Thirty-seven of 140 patients with HIV infection had muskuloskeletal symptoms. Three of these 37 patients had arthritis, but none had Reiter's syndrome or psoriatic arthritis. Thirty (81%) of 37 patients had chronic musculoskeletal symptoms (for 3 months or longer). Twenty of 30 patients with chronic musculoskeletal symptoms had polyarthralgia, and of those, 15 (75%) were found to have either definite or probable fibromyalgia syndrome. Therefore, fibromyalgia syndrome was found in 41% of HIV-infected patients with musculoskeletal symptoms and in approximately 11% of all HIV-infected patients. Fibromyalgia patients with HIV infection had a longer duration of HIV infection (p = 0.01) and more frequently reported past depressed mood (p = 0.001) than HIV-infected patients without fibromyalgia. Compared with 301 patients with fibromyalgia syndrome and no known risk behavior for HIV, known HIV-infected patients with fibromyalgia were more commonly male (p = 0.001) and reported current depressed mood more frequently (p = 0.0001). CONCLUSION: Few patients with arthritis were noted among HIV-infected patients who had intravenous drug use as risk behavior. By comparison, fibromyalgia syndrome appeared to be a common cause of musculoskeletal symptoms in this patient population.

Acute Disease↗
PubMed1992

Educational attainment and osteoarthritis: differential associations with radiographic changes and symptom reporting.

Educational attainment has been negatively associated with the prevalence, morbidity and mortality of many diseases. With knee osteoarthritis as an example, we used NHANES I data to examine whether the cross-sectional association between formal education and disease is due to known risk factors, and also whether educational attainment is more strongly associated with self-reported symptoms or with radiographic change. We found univariate associations between osteoarthritis and low levels of education. For radiographic knee osteoarthritis in women, and in both sexes combined, this relationship was explained by controlling for known risk factors, which included age, knee injury, race, obesity, and occupation. However, even after adjusting for these major risk factors and the presence of radiographic changes, reporting of knee pain and arthritis at any site remained significantly associated with low educational attainment, especially for those with less than or equal to 8 years of education.

Adult↗
PubMed1992

Bias in meta-analytic research.

With the proliferation of meta-analyses in the medical literature have come conflicting studies. In addition, observance of guidelines for the performance of meta-analyses has been spotty. Bias may explain conflicting studies and differentiate carefully performed meta-analyses from others. Meta-analysts may fail to anticipate biases which threaten their study's validity. The three stages at which bias can be injected into a meta-analysis are finding studies, selection of the identified studies for the meta-analysis and extraction of data from the selected studies. This manuscript reviews specific types of bias which are common at each of these stages.

Bias↗
PubMed1991

Thiazide diuretics and the risk of hip fracture. Results from the Framingham Study.

Thiazide diuretics may preserve bone mass and prevent elderly women's osteopenic fractures, but studies have not distinguished between thiazide preparations or examined former users. We performed a case-control study looking at thiazide use and subsequent hip fracture in postmenopausal female members of the Framingham Study cohort. Cases who had experienced a first hip fracture (n = 176) were compared with age-matched controls (n = 672). Results showed a modest protective effect of any recent thiazide use (not significant). However, recent pure thiazide users experienced significant protection against fracture (adjusted odds ratio, 0.31; 95% confidence interval, 0.11 to 0.88), whereas recent users of combination drugs containing thiazides experienced no protection (adjusted odds ratio, 1.16; 95% confidence interval, 0.44 to 3.05). Combination drugs generally contained only 25 mg of hydrochlorothiazide, suggesting that the small amount of thiazide was insufficient to preserve bone mass. Former thiazide users were not protected against fracture. In sum, recent pure thiazide use in women protects against hip fracture.

Aged↗
PubMed1991

Secular changes in published clinical trials of second-line agents in rheumatoid arthritis.

The present investigation was undertaken to explore changes over time in the design and reporting of trials of second-line drugs in rheumatoid arthritis, in the characteristics of patients included in the trials, and in the sources of funding. We studied 105 trials of second-line agents for the treatment of rheumatoid arthritis, including placebo-controlled and comparative trials involving 8 different agents. Three time periods, 1945-1969, 1970-1979, and 1980-1989, were compared. We found little change in the standards for reporting on the design of trials or for reporting information on patient dropout and drug side effects, some increase in the complexity of the statistical methods used, but no increase in the use of power analysis (reported in only 13% of trials). The average age of patients in clinical trials has increased. In recent years, there has been a substantial shift from placebo-controlled to comparative trials, and it is increasingly common for trials to be financially supported by pharmaceutical companies. The possible effects of secular trends should be considered when combining or comparing results of trials conducted in different years.

Age Factors↗
PubMed1991

Development of preliminary criteria for response to treatment in fibromyalgia syndrome.

We developed a set of preliminary response criteria for use in future clinical trials in fibromyalgia syndrome. We determined outcome measures from a previously reported clinical trial which best distinguished patients treated with effective medication from those treated with placebo or ineffective medication, using stepwise logistic regression analysis. Several combinations of outcome measures were identified and plotted in the form of receiver operating characteristic (ROC) curves. The combination of variables possessing the greatest area under the ROC curve included (1) physician global assessment score less than or equal to 4 (0 = extremely well, 10 = extremely poorly), (2) patient sleep score less than or equal to 6 (0 = sleeping extremely well, 10 = sleeping extremely poorly), and (3) tender point score less than or equal to 14 (maximum possible tender point score equalled 20). These criteria accurately distinguished those treated with effective drug from those treated with placebo when tested in an unreported therapeutic trial of cyclobenzaprine. The criteria identified 11 of 14 patients in the amitriptyline trial and 4 of 6 patients in the cyclobenzaprine trial who attained improvement measured independently. The methodology used to define these preliminary criteria may be applied to refine the criteria as additional sensitive and clinically relevant outcomes are developed.

Amitriptyline↗
PubMed1991

Occupational physical demands, knee bending, and knee osteoarthritis: results from the Framingham Study.

We sought to assess occupational joint use and osteoarthritis (OA) longitudinally in a large population with multiple occupations. Subjects were members of the Framingham Heart Study cohort followed over 40 years with occupational status assessed at the beginning of the Heart Study [from Examination 1 (1948-51) through Examination 6 (1958-61)] and knee OA assessed by weight bearing knee radiograph at Examination 18 (1983-85) when mean age of subjects was 73 years. Each subject's job was characterized by its level of physical demand and whether the job was associated with knee bending. Odds ratios (OR) testing the association of job demand with OA were adjusted by logistic regression for age, body mass, knee injury history, smoking, and educational level. Men whose jobs required knee bending and at least medium physical demands had higher rates of later radiographic knee OA (at least definite osteophytes) than men whose jobs required neither (43.4 vs 26.8%; OR of OA = 2.22, 95% CI 1.38, 3.58). Rates of severe radiographic OA (osteophytes and joint space narrowing) and of bilateral radiographic OA were also significantly increased in these men. Few women had jobs requiring knee bending or that were physically demanding and these jobs were generally unassociated with later radiographic OA. Only a small number of men (n = 28) had symptomatic knee OA, and we could not confirm that it was associated with occupation in men. Thus, among men, occupations which combine knee bending and physical demands may be an important cause of radiographic OA.

Aged↗
PubMed1990

Time for changes in the design, analysis, and reporting of rheumatoid arthritis clinical trials.

We have proposed a set of changes in the design, analysis, and reporting of RA clinical trials which emphasizes the standardization of trials. We have suggested limiting the number of outcome measures used to those most sensitive to change and using uniform measurements of the same outcome measures in all clinical trials. We have also suggested that investigators focus on enumerating which patients improve in a trial, rather than on the mean level of improvement in treated patients versus the control patients. Finally, we have suggested the reporting of confidence intervals rather than simply stating P values. With the inauguration of these changes and more attention to other issues relevant to the quality of clinical trials, we hope that drug treatments of rheumatoid arthritis can be more easily compared with respect to effectiveness.

Arthritis, Rheumatoid↗