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Biomedical subjects

D T Felson

Publications and source records attributed to D T Felson.

173 records · Page 10Linked to original sources

Epidemiology of hip and knee osteoarthritis.

This review has focused on the prevalence and risk factors associated with knee and hip osteoarthritis. Risk factors for knee osteoarthritis are obesity and major injury, and knee osteoarthritis probably fits into the generalized osteoarthritis diathesis. Repetitive use, such as in jobs requiring heavy labor and knee bending, probably increases the risk of knee osteoarthritis. Hip osteoarthritis is probably frequently secondary to developmental defects. As Rothman (182) has pointed out in discussing causation, this does not necessarily mean that the same factors do not also contribute to causing hip osteoarthritis. Yet, it appears that, in many cases, developmental defects are severe enough to be sufficient causes of hip osteoarthritis. To delineate other causes, it may be necessary to examine risk factors separately in those with and in those without developmental disease. Although large epidemiologic studies are best able to identify the relative contributions of specific risk factors while controlling for other risk factors, new studies need to focus on important unresolved questions. First, longitudinal studies with comprehensive follow-up using repeated radiographic assessments are needed to identify factors that cause development of disease or the onset of symptoms. Second, cohorts with early and possibly asymptomatic disease need to be followed to determine the causes of progression or regression of disease and the natural history of disease. Such cohorts may include those at high risk of injury such as sports enthusiasts or manual laborers.

Animals↗

Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study.

To assess the effect of postmenopausal use of estrogens on the subsequent risk of hip fracture, we performed a retrospective cohort study of 2873 women in the Framingham Heart Study. Information obtained at routine biennial examinations about the use of estrogens, body weight, age at menopause, smoking, and alcohol consumption was used to evaluate the risk of hip fracture among postmenopausal women who received estrogens. Hip fractures occurred in 179 postmenopausal women, at a rate that increased exponentially after the age of 50. The risk of fracture was inversely related to weight at all ages. The relative risk of hip fracture in subjects who had taken estrogens at any time was 0.65 after adjustment for age and weight (95 percent confidence interval, 0.44 to 0.98). The adjusted relative risk in women who had taken estrogens within the previous two years was further reduced, to 0.34 (95 percent confidence interval, 0.12 to 0.98). Taking estrogens within four years of menopause also protected against fracture. The number of women in each age group who took estrogens was insufficient for a definitive evaluation of risk, but recent use of estrogens appeared to be protective in women under the age of 65 (no fractures among those who took estrogens) and those 65 to 74. We cannot exclude some degree of selection bias among the women who received estrogen-replacement therapy. Nevertheless, this large cohort study supports the hypothesis that postmenopausal use of estrogens protects against subsequent hip fracture in women.

Age Factors↗

Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone.

Studies investigating steroid dose and avascular necrosis of bone (AVN) have found either a weak association or none at all. This quantitative review of published studies has evaluated the effects of steroid dose and bolus steroids on the risk of AVN. 22 papers with sufficient information for analysis were identified. The mean steroid dose for the cohort was plotted against the percentage in whom AVN developed. Total dose was divided into non-bolus (oral) and bolus dose, and doses 1, 3, 6, and 12 months after beginning steroids were tested separately for their association with AVN risk. There was a strong correlation between daily total dose and AVN rate (r = 0.61-0.80). Oral dose was strongly correlated with AVN rate (r = 0.70-0.86), but bolus dose was not associated with AVN risk. This strong association between AVN and steroid dose contrasts with the weak relations found in case-control studies from individual centres in which cases and controls received similar steroid regimens and therefore did not differ greatly in steroid dose. The method of deriving a single exposure level per study and comparing the amount of exposure across studies may be useful in assessing whether a drug's toxicity is dose dependent.

Adrenal Cortex Hormones↗

The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.

To investigate the prevalence of osteoarthritis (OA) of the knee in elderly subjects, we studied the Framingham Heart Study cohort, a population-based group. During the eighteenth biennial examination, we evaluated the cohort members for OA of the knee by use of medical history, physical examination, and anteroposterior (standing) radiograph of the knees. Radiographs were obtained on 1,424 of the 1,805 subjects (79%). Their ages ranged from 63-94 years (mean 73). Radiographs were read by a radiologist who specializes in bone and joint radiology, and were graded 0-4 according to the scale described by Kellgren and Lawrence. OA was defined as grade 2 changes (definite osteophytes), or higher, in either knee. Radiographic evidence of OA increased with age, from 27% in subjects younger than age 70, to 44% in subjects age 80 or older. There was a slightly higher prevalence of radiographic changes of OA in women than in men (34% versus 31%); however, there was a significantly higher proportion of women with symptomatic disease (11% of all women versus 7% of all men; P = 0.003). The age-associated increase in OA was almost entirely the result of the marked age-associated increase in the incidence of OA in the women studied. This study extends current knowledge about OA of the knee to include elderly subjects, and shows that the prevalence of knee OA increases with age throughout the elderly years.

Age Factors↗

A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia.

Sixty-two patients with fibromyalgia were randomly assigned to receive 25 mg of amitriptyline at night, 500 mg of naproxen twice daily, both amitriptyline and naproxen, or placebo in a 6-week, double-blind trial. Amitriptyline was associated with significant improvement in all outcome parameters, including patient and physician global assessments, patient pain, sleep difficulties, fatigue on awakening, and tender point score. Patients taking the combined naproxen-amitriptyline regimen experienced minor, but not significant, improvement in pain when compared with patients who took amitriptyline alone. Amitriptyline, or amitriptyline and naproxen, is an effective therapeutic regimen for patients with fibromyalgia.

Amitriptyline↗

The natural history of fibromyalgia.

The natural history of fibromyalgia was studied in 39 treated patients. All patients were surveyed by interviews conducted in 1983 (at an average of 1.3 years after diagnosis), in 1984, and again in 1985. Throughout the survey period, more than 60% of patients had moderate to severe continuing symptoms, and almost all took medications regularly to control symptoms. Younger patients (P = 0.02), those with less severe symptoms at the initial survey (P = 0.005), and those with isolated Raynaud's phenomenon (P = 0.04) were more likely to be doing well 2 years later, although symptom remission was usually transitory.

Adult↗

A prospective evaluation of 118 patients with the fibromyalgia syndrome: prevalence of Raynaud's phenomenon, sicca symptoms, ANA, low complement, and Ig deposition at the dermal-epidermal junction.

One hundred eighteen consecutive patients with fibromyalgia were evaluated prospectively. Immunoglobulin deposits at the dermal-epidermal junction were found in only 4 of 36 patients. Twelve patients (14%) had at least one positive antinuclear antibody (ANA) test. Eight patients (7%) had at least one low C3. Thirty-five patients (30%) has a history of Raynaud's phenomenon and 22 (18%) had sicca symptoms, defined as symptomatic dry eyes and mouth and a positive Schirmer test. The 35 patients with Raynaud's phenomenon had a significantly higher prevalence of sicca symptoms, positive ANA or low C3 compared to the 83 patients who did not have Raynaud's phenomenon. Thus, a subset of patients with fibromyalgia may have features suggestive of a systemic connective tissue disorder.

Adult↗

Referral of musculoskeletal disease patients by family and general practitioners.

We surveyed general and family practitioners to evaluate their patterns of referring musculoskeletal disease patients to rheumatologists and orthopedists. Patients who had rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were most often referred to rheumatologists, whereas patients with osteoarthritis, persistent low back pain, and post-traumatic knee pain were most often referred to orthopedists. As conditions worsened in severity, referrals were more frequent. Patients with conditions that were difficult to diagnose, such as possible shoulder tendinitis that was unresponsive to initial nonsteroidal therapy, undiagnosed polyarthritis, and intermittent knee swelling with pain, were most often treated without referral and, when referred, were most often sent to orthopedists. Belief in the effectiveness of rheumatologists or orthopedists correlated strongly with reported referral behavior, yet most respondents considered themselves capable of managing the majority of patients with musculoskeletal diseases. Neither practice arrangement, board certification, nor educational background affected referral behavior. However, younger physicians were more likely (P = 0.002) to refer patients to rheumatologists. Multivariate analysis showed that the significant predictors of global referral behavior were belief in the effectiveness of subspecialists and a small number of musculoskeletal problems seen by the generalist. The predictors of referral to rheumatologists were belief in rheumatologist efficacy and young physician age.

Adult↗

Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis.

In an effort to clarify the role of immunosuppressive drugs in the management of lupus nephritis, we pooled data from all published clinical trials in which patients had been randomly assigned to receive either prednisone alone or prednisone plus cyclophosphamide or azathioprine. The pooled analysis showed that patients receiving immunosuppressive drugs had less renal deterioration (P = 0.006), were less likely to have end-stage renal disease (P = 0.023), and were less likely to die from kidney disease (P = 0.024) than patients receiving steroids alone. There were no significant differences with respect to deaths from nonrenal causes or overall mortality. When cyclophosphamide and azathioprine were considered separately, both were associated with a 40 per cent reduction in the rates of adverse renal outcomes, although because the treatment groups were smaller, many of these differences were not statistically significant. A power analysis showed that a study of 100 high-risk patients (development of renal insufficiency in 50 per cent) would be needed to prove that an immunosuppressive agent is 50 per cent superior to steroids alone in preventing renal deterioration. We conclude that immunosuppressive drugs and steroids together are more effective than steroids alone in treating lupus nephritis and that published trials have reached false negative conclusions because of small sample sizes.

Azathioprine↗

Misuse of statistical methods in Arthritis and Rheumatism. 1982 versus 1967-68.

Articles published in Arthritis and Rheumatism in 1982 were compared with those from 1967-68 to evaluate trends in statistical methods and in the quantity and character of statistical misuse. Results show that among articles in 1982 using statistics, 66% contained methodologic errors. The percentage was similar in 1967-68, although fewer articles used statistics. In 1967-68 the most common error was failure to identify the statistical method used, whereas in 1982 multiple testing errors predominated, specifically, use of the t-test to compare 3 or more groups and comparison of 2 groups on multiple variables. The availability of calculators and computers which readily perform complex data analysis may underly the emergence of multiple testing errors. To compare multiple groups, we suggest using analysis of variance instead of the t-test. To avoid multiple testing errors, we recommend limiting the number of tests performed, lowering the alpha (significance) level, or using multivariate techniques.

Arthritis↗

Muscle mass and fat mass in relation to bone mineral density in very old men and women: the Framingham Heart Study.

Aim of the study was investigate the cross-sectional relationship between body composition and bone mineral density (BMD) in very old men and women. The study sample consisted of 504 women and 285 men, aged 72-93 yr, participating in examination 22 (1992-1993) of the Framingham Heart Study. Total body BMD, regional BMD, and soft-tissue body composition was measured by dual-energy X-ray absorptiometry. Both muscle mass and percentage body fat were positively associated with total body BMD in women. After adjustment for age, physical activity, smoking status, estrogen use, and thiazide use, BMD increased with increasing tertile of muscle mass (p = 0.007) and with increasing tertile of percentage body fat (p = 0.0001) in women. In men muscle mass, not percentage body fat, was positively associated with BMD. After adjustment for potential confounders, BMD remained associated with muscle mass only (p = 0.02). These results were similar for leg BMD and arm BMD. The study suggests that the influence of muscle and fat mass on bone mineral density is different between very old men and women.

Absorptiometry, Photon↗