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Biomedical subjects

D T Felson

Publications and source records attributed to D T Felson.

At least 109 records · Page 6Linked to original sources
PubMed1996

The effect of smoking at different life stages on bone mineral density in elderly men and women.

To assess the effect of smoking on bone mineral density (BMD) at different life stages, to examine whether the effect of smoking differs between men and women, and to discover whether its effect in women differs according to history of estrogen use, a cohort study was carried out with single cross-section measurement of BMD by single and dual photon absorptiometry. The setting was the Framingham Study, a population-based cohort study with over 40 years prospectively collected data on smoking. Subjects (n = 1164) consisted of cohort members participating in the 20th biennial Framingham examination (1988-1989). The measurements included in the study were BMD measured at the hip, spine and radius, smoking history ascertained at all Framingham Study examinations since 1948, and other factors affecting BMD (age, weight, estrogen use, caffeine use, alcohol use and physical activity). Neither current smoking, recent (last 10 years) smoking, nor early adulthood smoking resulted in significantly lower BMD at any skeletal site among women who had not taken estrogen. Among women who had taken estrogen, BMD at most sites was lower among current or recent smokers, although the small numbers of smokers made it difficult to find significant differences at all skeletal sites. Among men, a consistently lower BMD at all skeletal sites was observed for smokers regardless of when in their life they smoked (4-15.3% lower), although the effect of smoking during early adulthood was of a lesser magnitude (4-8% lower). Former male smokers who had quit < 10 years ago had lower BMD than men who had quit > or = 10 years ago. In conclusion, in women who had used estrogen, BMD was lower in current or recent smokers than it was in non-smokers. In men, smoking at any stage of life had adverse effects on the skeleton that was independent of weight, alcohol or caffeine use, implying other mechanisms for smoking's effect on bone.

Absorptiometry, Photon↗
PubMed1996

Weight and osteoarthritis.

Osteoarthritis is the most common form of arthritis. It increases in prevalence with age. About 5% of the US population is affected with hip or knee osteoarthritis; 9.5% of adults aged > 62 y have knee osteoarthritis. Because of its frequency and associated pain and disability, osteoarthritis accounts for much of the disability in lower extremities in the elderly. More than 70% of total hip and knee replacements are for osteoarthritis. Because osteoarthritis is so common, the modification of factors that increase osteoarthritis risk could prevent substantial pain and disability in the elderly and the use of costly health care services. Overweight persons are at high risk of osteoarthritis in the knee and probably also in the hips and hands. The mechanism by which overweight causes osteoarthritis is poorly understood; a contribution from both local increased force across the joint and systemic factors is likely. Better evidence is needed on the effects of weight loss, but preliminary studies suggest that weight loss can both prevent the onset of symptomatic disease and alleviate symptoms when present.

Body Mass Index↗
PubMed1996

Estrogen replacement therapy and the development of osteoarthritis.

Recent studies have indicated that estrogen users have a lower than expected rate of concurrent osteoarthritis. We assessed the association between estrogen replacement therapy and incident symptomatic osteoarthritis, using a nested case-control design. We identified all incident cases of hand, hip, and knee osteoarthritis in women members of the Fallon Community Health Plan, age 20-89 years, from January 1, 1990, to December 31, 1993. For each case, we selected a control woman matched by closest date of birth. We used pharmacy records to classify women as new users, past users, ongoing users (past and new users), and never-users of estrogen replacement therapy. There were 60 informative case-control pairs. After controlling for obesity and health care utilization, we found that new use of estrogen replacement therapy was a predictor of new osteoarthritis diagnosis. Past use was inversely associated with risk of osteoarthritis [adjusted odds ratio = 0.7; 95% confidence interval (CI) = 0.3-1.9]. For ongoing use of estrogen replacement therapy and osteoarthritis, the adjusted odds ratio was 1.4 (95% CI = 0.6-3.3). The associations between osteoarthritis and both new use of estrogen replacement therapy and utilization of services suggest that frequent medical care increases the likelihood of diagnosis of osteoarthritis.

Adult↗
PubMed1996

Lack of association between thyroid status and chondrocalcinosis or osteoarthritis: the Framingham Osteoarthritis Study.

OBJECTIVE: To assess whether current thyroid status is associated with chondrocalcinosis or osteoarthritis (OA), we examined the cross sectional association of serum thyrotropin (thyroid stimulating hormone, TSH) with chondrocalcinosis and with knee OA in members of the Framingham OA study. METHODS: Knee radiographs were taken at the 18th biennial examination (1983-85) and measurement of serum TSH at either the 15th (1977-79) or the 18th biennial examination. Chondrocalcinosis was dichotomized as absent or present and knee OA was based on a Kellgren and Lawrence score of grade 2 or greater in either knee. Thyroid status was determined by serum TSH concentration classed into clinically relevant categories: < or = 0.1 mU/l(low); > 0.1 < 0.4 mU/l (slightly low); 0.4 to 5.0 mU/l (normal); > 5 < or = 10 mU/l (slightly high); and > 10 mU/l (high). RESULTS: Data were collected on 577 men and 798 women. We found no association between elevated serum TSH concentration and chondrocalcinosis. Our results, though not statistically significant, suggest an inverse relation, with an odds ratio (OR) of 0.41 (95% CI 0.10, 1.73) for those subjects. in the highest TSH group and 1.79 (95% CI 0.39, 8.24) for those in the lowest TSH group, compared to subjects in the normal range. We found no association between serum TSH concentration and radiographic knee OA, with an OR of 0.85 (95% CI 0.47, 1.51) for those in the highest serum TSH group and 1.51 (95 CI 0.54, 4.22) for those in the lowest TSH group, compared to the normal group. Exclusion of subjects taking thyroid hormone confirmed these null results. CONCLUSION: There was no evidence, in a large unselected population of older persons, of a significant association between current thyroid status and either chondrocalcinosis or OA.

Aged↗
PubMed1996

Musculoskeletal disease research: should we analyze the joint or the person?

OBJECTIVE: To illustrate newly developed statistical methods in analysis of correlated binary outcome data in musculoskeletal (MSK) disease. METHODS: We applied 3 alternative statistical approaches to evaluate the relation of several risk factors to presence of knee osteoarthritis using data from the Framingham Osteoarthritis Study. The methods were (1) an ordinary logistic regression model using each knee as an independent unit of observation; (2) an ordinary logistic regression model treating each person rather than the knee as the unit of analysis; and (3) generalized estimating equation (GEE) and polychotomous logistic regression (PCHLE) using each knee as the unit of analysis but accounting for the correlation between fellow knees. We discuss the advantages and disadvantages of each method with respect to validity, precision, and interpretability. RESULTS: The GEE and PCHLE models had clear advantages. They simultaneously evaluated the effects of person specific and knee specific risk factors, increased precision, enhanced the interpretability of variables, and provided new insights about how risk factors act. CONCLUSION: While the choice of statistical approach depends critically on the scientific question of interest, the GEE and PCHLE approaches will often be optimal in assessments of factors associated with MSK conditions affecting multiple correlated sites within the body, especially when the interest of the study focuses on site specific risk factors.

Age Factors↗
PubMed1995

Alcohol intake and bone mineral density in elderly men and women. The Framingham Study.

Alcohol consumption has multiple effects on bone, and alcoholic men have a high risk of osteoporotic fracture. The objective of this study was to assess the association between alcohol consumption and bone mineral density in elders. The authors evaluated 1,154 members of the Framingham Heart Study Cohort at biennial examination 20 (1988-1989). Subjects ranged in age from 68 to 96 years. Bone density was assessed at the radius (ultradistal and shaft) and at the proximal femur and spine. Alcohol consumption, assessed every 2 years from examination 12 (1967-1969) through examination 20, was averaged. The association of alcohol intake with bone density was examined after adjustment for age, weight, height, smoking, and, in women, age at menopause and years of estrogen use. Women who drank at least 7 oz (206.99 ml)/week of alcohol had higher bone densities at most sites (4.2-13.0% range with 7.7% average differences across all sites) than women in the lightest category of intake (< 1 oz (29.57 ml)/week). Men who were heavy drinkers (> or = 14 oz (414 ml)/week) also had higher bone densities than light drinkers, but the difference was less than in women (3.9% average across all sites). Lesser amounts of intake did not affect bone density. The authors conclude that alcohol intake of at least 7 oz (206.99 ml)/week is associated with high bone density in postmenopausal women, an effect possibly related to the augmentation of endogenous estrogen levels by alcohol.

Age Distribution↗
PubMed1995

The cost-effectiveness of liver biopsy in rheumatoid arthritis patients treated with methotrexate.

OBJECTIVE: To assess the cost-effectiveness of liver biopsy in monitoring rheumatoid arthritis (RA) patients for methotrexate (MTX)-induced cirrhosis. METHODS: A decision analytic model was used to compare a strategy of no biopsy versus strategies of biopsy after 5 years or 10 years of MTX treatment. RESULTS: Biopsy after 5 years of MTX treatment had a cost-effectiveness ratio of $1,891,830 per year of life saved, while biopsy after 10 years of treatment had a cost-effectiveness ratio of $52,374 per year of life saved. Sensitivity analyses revealed that the cost-effectiveness of biopsy was most dependent on the probability of cirrhosis. CONCLUSION: Liver biopsy to monitor for MTX-induced cirrhosis in RA patients is not cost effective after 5 years of treatment, and even biopsy after 10 years has a high cost.

Arthritis, Rheumatoid↗
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

Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization.

OBJECTIVE: To quantify the incidence of symptomatic hand, hip, and knee osteoarthritis (OA) among members of the Fallon Community Health Plan, a health maintenance organization located in central Massachusetts. METHODS: Incident OA was defined as the first evidence of OA by radiography (grade > or = 2 on the Kellgren-Lawrence scale of 0-4) plus joint symptoms at the time the radiograph was obtained or up to 1 year before the radiograph was obtained. RESULTS: The age- and sex-standardized incidence rate for hand OA was 100/100,000 person-years (95% confidence interval [95% CI] 86, 115), for hip OA 88/100,000 person-years (95% CI 75, 101), and for knee OA 240/100,000 person-years (95% CI 218, 262). The incidence of hand, hip, and knee OA increased with age, and women had higher rates than men, especially after age 50. A leveling off or decline occurred for both groups around the age of 80. CONCLUSION: In a large study of symptomatic OA we observed incidence rates that increased with age. In women ages 70-89, the incidence of knee OA approached 1% per year.

Adult↗
PubMed1995

The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.

OBJECTIVE: To determine the incidence of radiographic knee osteoarthritis (OA) and symptomatic OA (symptoms plus radiographic OA), as well as the rate of progression of preexisting radiographic OA in a population-based sample of elderly persons. METHODS: Framingham Osteoarthritis Study subjects who had knee radiographs and had answered questions about knee symptoms in 1983-1985 were reexamined in 1992-1993 (mean 8.1-year interval) using the same protocol. Subjects were defined as having new (incident) radiographic OA if they developed grade > or = 2 OA (at least definite osteophytes or definite joint space narrowing). New symptomatic OA was present if subjects developed a combination of knee symptoms and grade > or = 2 OA. Progressive OA was diagnosed when radiographs showing grade 2 disease at baseline showed grade > or = 3 disease on followup. RESULTS: Of 1,438 participants in the original study, 387 (26.9%) died prior to followup. Of the 1,051 surviving subjects, 869 (82.7%) participated in the followup study (mean +/- SD age 70.8 +/- 5.0 at baseline). Rates of incident disease were 1.7 times higher in women than in men (95% confidence interval [CI] 1.0-2.7), and progressive disease occurred slightly more often in women (relative risk = 1.4; 95% CI 0.8-2.5) but rates did not vary by age in this sample. Among women, approximately 2% per year developed incident radiographic disease, 1% per year developed symptomatic knee OA, and about 4% per year experienced progressive knee OA. CONCLUSION: In elderly persons, the new onset of knee OA is frequent and is more common in women than men. However, among the elderly, age may not affect new disease occurrence or progression.

Aged↗
PubMed1995

Problems and suggested solutions in creating an archive of clinical trials data to permit later meta-analysis: an example of methotrexate trials in rheumatoid arthritis.

Because data archives contain patient-based rather than study-based data, they can address meta-analytic questions on uncommon outcomes and on predefined patient subsets, questions that are difficult to address using the traditional meta-analytic approach based on grouped data. We report the tasks involved in establishing the first data archive of rheumatoid arthritis trials. In general, problems stem from the heterogeneity of trials in the archive and we suggest some solutions. In the initial phases, difficulties include recruitment and incomplete participation of trial investigators, whereas later on, other issues arise, such as quality control, coping with different dataset designs, and incomplete documentation. Other issues include heterogeneous measures, missing variables, and comparing data across different visit intervals and trial lengths. Suggested solutions include requesting trial data in predefined archive-wide structures and asking for all possible documentation for each dataset. Data cleaning is necessary, as is rescaling of variables or developing unit-free outcomes, and estimating data for missing variables. Archive design should allow for referencing a patient's data among various datasets. Although one goal is to reduce the quantity of data in the archive while retaining information content, data from early stages of archive building must be accessible for developing new analysis datasets. Documentation of archive building and software choices are discussed. Our experience suggests data archiving for meta-analysis is time consuming and expensive, yet it provides a useful method for analyzing data from multiple trials.

Archives↗
PubMed1995

Methodological and statistical approaches to criteria development in rheumatic diseases.

We have discussed methodological and statistical considerations in developing disease classification and assessment criteria. In choosing cases with disease and nondisease controls, classification criteria should be developed with an eye toward face, content and construct validity, and toward their ultimate applicability. The validity of disease criteria should be tested in a patient sample different from the one used to develop the criteria. Several analytic approaches are available to reduce the candidate diagnostic elements to those that will define the presence of disease. Methodological issues in the assessment of disease severity, activity or damage are similar to those faced in criteria development studies, although the analytic concerns are different and the options more varied.

Humans↗
PubMed1995

Assessing the activity of rheumatoid arthritis.

Disease activity in rheumatoid arthritis is not easily measured. The validity of current measures has been reviewed. Recent international efforts have resulted in consensus over a minimum (WHO/ILAR) core set of endpoints in RA trials: pain, patient and physician (assessor) global assessment, physical disability, swollen joint count, tender joint count, acute phase reactants; and for studies of one or more years' duration: radiographs of joints. The near future will hopefully see validation of new measures, also in terrains not currently covered by the core set.

Arthritis, Rheumatoid↗
PubMed1995

Weight and osteoarthritis.

Overweight persons are at high risk of osteoarthritis (OA) in the knee, and probably in the hips and hands. The mechanism by which overweight causes OA is poorly understood, with a likely contribution from both local increased force across the joint and systemic factors. Better evidence is needed on the effects of weight loss, but preliminary studies suggest that weight loss can both prevent the onset of symptomatic disease and alleviate symptoms, when present.

Humans↗