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Biomedical subjects

D T Felson

Publications and source records attributed to D T Felson.

At least 73 records · Page 4Linked to original sources
PubMed1999

The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double-blind, sham-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. METHODS: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. RESULTS: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. CONCLUSION: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.

Adult↗
PubMed1999

Level of physical activity and the risk of radiographic and symptomatic knee osteoarthritis in the elderly: the Framingham study.

PURPOSE: Because osteoarthritis may be caused by "wear and tear," we examined the association between level of physical activity and risk of knee osteoarthritis in the elderly. SUBJECTS AND METHODS: Eligible subjects were participants in the Framingham Heart Study cohort who had radiographically normal knees at biennial exam 18 (1983-1985) and who also completed a physical activity questionnaire at exam 20 (1988-1989). Follow-up knee radiographs were obtained at biennial exam 22 (1992-1993). The study outcomes were the development of incident radiographic or symptomatic knee osteoarthritis between the baseline and follow-up exams. RESULTS: The number of hours per day of heavy physical activity was associated with the risk of incident radiographic knee osteoarthritis (odds ratio = 1.3 per hour, 95% confidence limits 1.1-1.6, P for trend = 0.006). Adjustment for age, sex, body mass index, weight loss, knee injury, health status, total calorie intake, and smoking strengthened this association (eg, odds ratio for > or = 4 hours heavy physical activity/day compared with no heavy physical activity = 7.0, 95% confidence limits 2.4-20, P for trend = 0.0002). Risk was greatest among individuals in the upper tertile of body mass index (odds ratio for > or = 3 hours/day of heavy physical activity = 13.0, 95% confidence limits 3.3-51). For incident symptomatic knee osteoarthritis, the results were similar, although the number of cases was small. No effects on these outcomes were observed from moderate and light physical activity, number of blocks walked, or number of flights of stairs climbed daily. CONCLUSIONS: Heavy physical activity is an important risk factor for the development of knee osteoarthritis in the elderly, especially among obese individuals. Light and moderate activities do not appear to increase risk.

Aged↗
PubMed1999

Early stopping of clinical trials in lupus and other uncommon rheumatologic diseases.

Use of statistical methods for early stopping of clinical trials allows more efficient and ethical utilization of subjects. In uncommon diseases, where the pool of potential subjects is limited, these methods provide a way to maximize the information gathered from trials. For trials in lupus, methods for early stopping should be more widely utilized. We discuss the ethics, practical aspects, pros and cons, and statistical foundations of some established methods for early stopping, with an emphasis on those that have available implementation in computer software. An example of the design and analysis of a treatment trial in systemic lupus erythematosus with the triangular test method of early stopping is also given.

Clinical Trials as Topic↗
PubMed1999

Evidence for decline in disability and improved health among persons aged 55 to 70 years: the Framingham Heart Study.

OBJECTIVES: This study detected secular change in disability and health among persons aged 55 to 70 years, the life period when increases in disability and morbidity begin and retirement occurs. METHODS: Cross-sectional comparisons were completed with data from similarly aged members of the original (n = 1760) and offspring (n = 1688) cohorts of the Framingham Heart Study, which represent 2 generations. Analyses were conducted by gender and on chronic disease subgroups by logistic regression. RESULTS: There was substantially less disability in the offspring cohort than in the original cohort. Thirty-six percent of offspring men were disabled vs 52% of original cohort men (P = .001); among women, these proportions were 54% vs 72% (P = .001). Fewer offspring perceived their health as fair or poor and fewer had chronic diseases. Offspring were more physically active and less likely to smoke or consume high amounts of alcohol, but their average weight was greater. The secular decline in disability was strongly evident among individuals with chronic diseases. CONCLUSIONS: Our findings depict a secular change toward a less disabled and globally healthier population in the period of life when retirement occurs.

Activities of Daily Living↗
PubMed1999

Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee.

Studies have shown a positive association between obesity and knee osteoarthritis. Studies evaluating hand or hip osteoarthritis and weight, however, have assessed x-ray osteoarthritis or been cross-sectional, or both, and results of these have been inconsistent. We assessed the association between body weight, body mass index, and incident symptomatic osteoarthritis in 134 matched case-control pairs of women who were part of a case-control study on estrogen replacement therapy and osteoarthritis. We identified incident symptomatic osteoarthritis cases of the hand, hip, and knee in women ages 20-89 years who were members of a health plan between January 1, 1990 and December 31, 1993. For each case we selected a control woman who was matched by closest date of birth to the case. Medical records were reviewed to obtain weight and height information for the period before disease onset. After controlling for estrogen use, smoking status, height, and health care use, we found that body weight was a predictor of incident osteoarthritis of the hand, hip, and knee. Odds ratios ranged from 3.0 to 10.5 for women in the upper tertiles of weight compared with women in the lowest tertile. Similar associations were observed for body mass index. Our results suggest that obesity is associated with the development of incident osteoarthritis at all joints studied.

Adult↗
PubMed1999

ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology.

We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.

Antirheumatic Agents↗
PubMed1998

Degenerative displacement of lumbar vertebrae. A 25-year follow-up study in Framingham.

STUDY DESIGN: The authors assessed degenerative lumbar displacement in a population-based cohort of 217 men and 400 women who had lateral lumbar radiographs performed at the mean age of 54 years and again at 79 years, and who had completed interviews on back symptoms and functional performance in connection with the follow-up examination. OBJECTIVES: To assess the prevalence and incidence of degenerative slippage and its association with back pain and physical disability. SUMMARY OF BACKGROUND DATA: Degenerative displacement of lumbar vertebrae may cause instability, nerve root compression, and spinal stenosis. Its incidence in the older population and association with back pain and disability are unknown. METHODS: The authors assessed the prevalence and incidence of degenerative slippage from lateral lumbar radiographs performed 25 years apart and its association with back pain and physical disability from interviews performed in connection with the follow-up examination. RESULTS: At the follow-up examination, 23 (12%) men and 100 (25%) women had developed degenerative slippage exceeding 3 mm; two of them had this already at the baseline. A forward displacement was found in 8 men and 76 women (P < 0.0001 for difference between the genders) and a backward one in 16 men and 35 women. On average, forward slip was 18% +/- 5.5, and backward slip, 15% +/- 4.0 of the anteroposterior diameter of the vertebra below. At the time of the second lumbar radiograph, 39 (32%) of the subjects with slippage, compared with 90 (19%) of the controls, had pain, aching, or stiffness in their back on most days (P = 0.001). After adjustment for endplate sclerosis, which was also related to pain (P = 0.015), slippage still had association with daily back symptoms (P = 0.009). However, subjects with slippage had not experienced more back symptoms during the preceding year or in earlier ages of life, and they did not report more disability than the controls. CONCLUSIONS: Degenerative displacement of lumbar vertebrae is common in an older population and is associated with increased prevalence of daily back symptoms. However, two thirds of the subjects with degenerative displacement do not report ongoing back symptoms, and the disorder is also unrelated to long-term back pain and physical disability.

Adult↗
PubMed1998

The association of estrogen replacement therapy and the Raynaud phenomenon in postmenopausal women.

BACKGROUND: Hormonal factors may play an important role in the pathophysiology of the Raynaud phenomenon. Experimental studies have shown an increased vasoconstrictor response to estrogen, a response that can be prevented by the addition of progesterone. OBJECTIVE: To measure the association between estrogen replacement therapy (alone and with progesterone) and the Raynaud phenomenon. DESIGN: Cross-sectional study. SETTING: Framingham Offspring Study. PARTICIPANTS: 497 postmenopausal women. MEASUREMENTS: Prevalence of the Raynaud phenomenon according to hormone use. Covariates measured included age, body mass index, smoking, alcohol consumption, and beta-blocker use. RESULTS: Forty-nine women were classified as having the Raynaud phenomenon (9.9%). The prevalence of this phenomenon was 8.4% among women who did not receive estrogen, 19.1% among women receiving estrogen alone, and 9.8% among women receiving estrogen plus progesterone. The adjusted odds ratio for the Raynaud phenomenon was 2.5 (95% CI, 1.2 to 5.3) for unopposed estrogen and 0.9 (CI, 0.3 to 2.6) for estrogen plus progesterone, with nonusers as the reference group. CONCLUSIONS: Unopposed estrogen therapy was associated with the Raynaud phenomenon in postmenopausal women. This association was not present in women who were receiving combined hormone therapy.

Cross-Sectional Studies↗
PubMed1998

Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States.

OBJECTIVE: To provide a single source for the best available estimates of the national prevalence of arthritis in general and of selected musculoskeletal disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain). METHODS: The National Arthritis Data Workgroup reviewed data from available surveys, such as the National Health and Nutrition Examination Survey series. For overall national estimates, we used surveys based on representative samples. Because data based on national population samples are unavailable for most specific musculoskeletal conditions, we derived data from various smaller survey samples from defined populations. Prevalence estimates from these surveys were linked to 1990 US Bureau of the Census population data to calculate national estimates. We also estimated the expected frequency of arthritis in the year 2020. RESULTS: Current national estimates are provided, with important caveats regarding their interpretation, for self-reported arthritis and selected conditions. An estimated 15% (40 million) of Americans had some form of arthritis in 1995. By the year 2020, an estimated 18.2% (59.4 million) will be affected. CONCLUSION: Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.

Adolescent↗
PubMed1998

Evidence for a Mendelian gene in a segregation analysis of generalized radiographic osteoarthritis: the Framingham Study.

OBJECTIVE: To investigate the inheritance of generalized osteoarthritis (OA). METHODS: OA was identified on hand and knee radiographs obtained from members of the Framingham Study cohort (the parents) in 1967-1970 and 1992-1993, and from their adult children in the Framingham Offspring Study in 1993-1994. All hand and knee radiographs evaluated for OA were graded using the Kellgren and Lawrence (K/L) scale. A measure of generalized OA was defined as the count of the number of hand and knee joints affected, as determined by the proportion of joints with a K/L grade > or =2. The OA count, treated as a continuous variable, was adjusted for age, body mass index, and a measure of physical activity for each joint area (hand or knee). Calculations were made separately for each generation and each sex, and correlations were analyzed against the standardized residual of OA. Segregation analysis was used to test whether OA aggregated in families, and if its transmission fit a Mendelian pattern. RESULTS: A total of 337 nuclear families with 2 parents and at least 1 biologic offspring were studied. In parents, the mean age was 61.2 years at the time of hand radiographs and 72.8 years at the time of knee radiographs, which were mostly obtained at a later examination. The mean age at the time of radiographs in offspring was 53.9 years. Using standardized residuals, parent-offspring and sibling-sibling correlations ranged from 0.115 to 0.306. In segregation analyses, models testing the hypotheses of no familial aggregation, no familial transmission, or a Mendelian gene alone were all rejected (P < 0.001 for each of these models). The best-fitting models were mixed models with a Mendelian mode of inheritance and a residual multifactorial component. The Mendelian recessive model provided the best fit. CONCLUSION: These analyses support a significant genetic contribution to OA, with evidence for a major recessive gene and a multifactorial component, representing either polygenic or environmental factors.

Adult↗
PubMed1998

Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent?

OBJECTIVE: To determine whether improvement of more than 20% in core set parameters should be required before patients are characterized as improved in rheumatoid arthritis (RA) clinical trials. METHODS: Data from 6 RA trials were reanalyzed to evaluate the discriminant validity (ability to differentiate active treatment from control) of 4 proposed definitions of improvement: the current American College of Rheumatology (ACR) definition (a 20% threshold for core set parameters [ACR 201), a 50% threshold (ACR 50), a 70% threshold (ACR 70), and an ordinal definition in which a patient could be classified in any of 3 categories (unimproved, ACR 20, or ACR 50). To evaluate the discriminant validity of these 4 definitions of improvement, we characterized each patient in each trial as improved or not, based on each definition, and computed a chi-square value differentiating the active treatment group from the control group, with the corresponding P value. RESULTS: With an increase in the threshold for improvement, the percentage of placebo-treated patients who were classified as experiencing response dropped dramatically in all trials, as did the percentage of patients receiving active therapy (second-line drug, combination therapy, tumor necrosis factor p75-Fc fusion protein) who were classified as experiencing response. Generally, the drop in active treatment response rates was greater than the drop in placebo response rates, leaving the difference between the 2 groups less at the higher thresholds. Therefore, chi-square values fell as the threshold for response was raised. The ordinal definition of improvement yielded chi-square values similar to those obtained using ACR 20 alone. CONCLUSION: Adopting a definition of efficacy in RA trials that requires 50% or 70% improvement in core set parameters would likely compromise statistical power and make it more difficult to distinguish between 2 treatments with different efficacy. ACR 20 should continue to be the primary measure of efficacy in RA trials, with higher thresholds for improvement being determined and reported as secondary efficacy measures.

Antirheumatic Agents↗
PubMed1998

Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study.

OBJECTIVE: To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women. METHODS: A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983-1985) to examination 22 (1992-1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n = 162), and current users (n = 40). Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OA was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was defined as either development of radiographic OA that was not present at baseline (incident OA) or progression of baseline radiographic OA by > or =1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck. RESULTS: During 8 years of followup, 17.4% of knee radiographic scores worsened by 1 grade and 5.8% by 2 or 3 grades among never users of ERT. Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than 1 grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee OA compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5). CONCLUSION: This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA. The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA.

Aged↗
PubMed1998

Longitudinal analysis of the relationship between serum insulin-like growth factor-I and radiographic knee osteoarthritis.

OBJECTIVE: To examine the relation between serum insulin-like growth factor I (IGF-I) levels and both incident and progressive radiographic knee osteoarthritis (OA) in the Framingham Osteoarthritis Study. DESIGN: Subjects had bilateral weight-bearing, anterior-posterior knee radiographs performed in 1983-1985 and again in 1992-1993. IGF-I levels were measured from blood specimens obtained in 1988-1989 by a competitive binding radio-immunoassay (RIA) after separation with octadecasilyl-silica cartridges of serum IGF-I from binding proteins. Participants without baseline radiographic OA [Kellgren and Lawrence grades (K&L) = 0-1] were classified as having incident disease if they had K&L > or = 2 grades at follow-up. Progressive OA was defined as an increase in K&L score of > or = 1 in knees with baseline OA (K&L > or = 2). All analyses were knee-based and sex-specific. We examined IGF-I tertiles in relation to the risk of incident and progressive radiographic OA separately, adjusting for age, body mass index (BMI), and baseline K&L score, and used generalized estimating equations to adjust for the correlation between fellow knees. RESULTS: Four hundred and forty-one participants had knee radiographs and serum IGF-I levels measured. No associations were found for serum IGF-I levels and incident [women: OR = 0.9 (0.6-1.7), men OR = 1.2 (0.6-2.6)] or progressive [women OR = 0.9 (0.6-1.6), men OR = 0.9 (0.3-3.0)] radiographic knee OA in either sex. Neither did we observe any association between IGF-I and worsening of individual radiographic features of OA (i.e., osteophyte growth and joint space loss). CONCLUSION: In summary, this longitudinal study did not demonstrate any association of serum IGF-I and incident or progressive radiographic knee OA. Further studies are needed to clarify the role of IGF-I in OA.

Case-Control Studies↗
PubMed1998

Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study.

BACKGROUND: Low muscle mass has been assumed to be associated with disability, but no studies confirming this association have been published. High body weight and high body mass index, both rough indicators of body fatness, have been shown to increase the risk for disability; however, the specific role of body fatness has not been studied. METHODS: The relations of skeletal muscle mass and percent body fat with self-reported physical disability were studied in 753 men and women aged 72 to 95 years. Cross-sectional data from biennial examination 22 (1992-1993) of the Framingham Heart Study were used. Body composition was assessed by dual-energy x-ray absorptiometry. Disability was scored as any versus none on a 9-item questionnaire. RESULTS: Total body and lower extremity muscle mass were not associated with disability in either men or women. However, a strong positive association between percent body fat and disability was observed. The odds ratio for disability in those in the highest tertile of body fatness was 2.69 (95% confidence interval 1.45-5.00) for women and 3.08 (1.22-7.81) for men compared to those in the lowest tertile. The increased risk could not be explained by age, education, physical activity, smoking, alcohol use, estrogen use (women only), muscle mass, and health status. Analyses restricting disability to mobility items gave similar results. CONCLUSIONS: In contrast to current assumptions, low skeletal muscle mass was not associated with self-reported physical disability. Persons with a high percent body fat had high levels of disability. Because it cannot be ruled out that persons with low skeletal muscle mass dropped out earlier in the study, prospective studies are needed to further assess the relationship between body composition and physical disability.

Absorptiometry, Photon↗
PubMed1998

The effects of estrogen on osteoarthritis.

The prevalence of osteoarthritis is higher in women than men, and in women it increases dramatically in the years after menopause. These observations and others reporting a painful form of hand osteoarthritis after the menopause suggest that loss of estrogen at the time of menopause increases a woman's risk of getting osteoarthritis. This article reviews biologic evidence for hormone sensitivity of cartilage, animal studies testing the effect of estrogen on the joints of ovariectomized animals, and human epidemiologic and clinical studies evaluating endogenous estrogen levels and estrogen replacement therapy and their relation to the occurrence of osteoarthritis. Overall the evidence for a role of estrogen in osteoarthritis is conflicting. Epidemiologic studies of women who take estrogen replacement therapy, however, consistently report that these women have a lower prevalence of osteoarthritis than women not taking estrogen, suggesting a possible therapeutic role for estrogen in osteoarthritis.

Animals↗