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D T Felson

Publications and source records attributed to D T Felson.

At least 127 records · Page 7Linked to original sources
PubMed1994

A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis.

BACKGROUND: To study the relation between reported drug performance in published trials and support of the trials by the manufacturer of the drug under evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of arthritis. METHODS: All randomized control trials of NSAIDs published between September 1987 and May 1990 identified by MEDLINE were reviewed. If an article met the following criteria (n = 61), it was selected: trials involving adult patients with osteoarthritis or rheumatoid arthritis (n = 180), use of nonsalicylate NSAIDs marketed in the United States (n = 101), randomized control trial (n = 81), duration of the trial 4 or more days (n = 78), and use of an efficacy outcome measure (n = 61). Reviewers, "blinded" to manufacturer status, evaluated the narrative interpretation of results and extracted numeric data on efficacy and toxicity. Manufacturer-associated trials were defined as those that acknowledged an association with a pharmaceutical manufacturer. Because of the scarcity of non-manufacturer-associated trials (n = 9), we report only on the manufacturer-associated articles. RESULTS: Fifty-two publications (85.2%) representing 56 trials were associated with a manufacturer. The manufacturer-associated drug was reported as comparable with (71.4%) or superior to (28.6%) the comparison drug in all 56 trials. These narrative claims of superiority were usually justified with trial data. Of the trials identifying one drug as less toxic (n = 22), the manufacturer-associated drug's safety was reported as superior to the comparison drug in 86.4% of cases. Justification for the narrative interpretation of the trial findings regarding less toxicity was provided in only 12 (54.5%) of 22 trials. CONCLUSION: The manufacturer-associated NSAID is almost always reported as being equal or superior in efficacy and toxicity to the comparison drug. These claims of superiority, especially in regard to side effect profiles, are often not supported by trial data. These data raise concerns about selective publication or biased interpretation of results in manufacturer-associated trials.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

The lag time between onset of symptoms and diagnosis of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) may be biologically reversible if treated in the first several months, yet it is unknown whether patients are diagnosed that early. We investigated the lag time between symptom onset and diagnosis of RA in a population with excellent access to rheumatology care. METHODS: Using review of medical records, we evaluated all patients newly diagnosed as having RA from 1987 through 1990, at a health maintenance organization in central Massachusetts. Total lag time from symptom onset to first definite diagnosis was divided into medical encounter lag time (from symptom onset to first medical encounter) and diagnosis lag time (from first medical encounter to diagnosis). RESULTS: The median total lag time was 36 weeks (range 4 weeks to > 10 years). The median medical encounter lag time was 4 weeks (not all patients included in the analysis). The median diagnosis lag time was 18 weeks. Diagnosis lag time was shorter for patients with progressive disease and positive rheumatoid factor on the initial test. Of 25 patients with symmetric arthritis and positive rheumatoid factor, only 5 (20%) were diagnosed within 2 months, and 10 (40%) were diagnosed more than 6 months after symptom onset. CONCLUSION: RA diagnosis is usually delayed for several months after symptoms begin, in large part because of delay in diagnosis by the physician. Thus, the goal of initiating treatment extremely early may be unrealistic for most patients.

Arthritis, Rheumatoid↗
PubMed1994

The efficacy and toxicity of combination therapy in rheumatoid arthritis. A meta-analysis.

OBJECTIVE: To evaluate the efficacy and toxicity of combination therapy, compared with single second-line drug therapy, in rheumatoid arthritis. METHODS: This study was a meta-analysis of published trials that evaluated combinations of full-dose second-line drugs and compared them with single second-line drugs at full dose. Using a random effects model, we summarized the difference between improvement with combination therapy and improvement with single-drug therapy. RESULTS: Five trials that met inclusion criteria, which contained 749 entering patients and 516 completing patients, were identified. The mean +/- SEM difference in improvement in tender joint count between combination and single-drug therapy at end of trial (24-52 weeks) was 2.4 +/- 0.7 joints (out of 60) (P < 0.001). At end of trial the difference between therapies in swollen joint counts was 1.0 +/- 1.2 joints (P = 0.42). The difference in grip strength improvement was 3.7 +/- 4.3 mm Hg (P = 0.40), and for erythrocyte sedimentation rate it was 3.4 +/- 3.1 mm/hour (P = 0.27). In general, the differences in efficacy between combination and single-drug therapy were clinically marginal. Nine percent more combination therapy-treated patients experienced side effect-related discontinuation of therapy than patients receiving single-drug therapy (P = 0.008). CONCLUSION: Combination therapy, as it has been used in recent clinical trials, does not offer a substantial improvement in efficacy, but does have higher toxicity than single drug therapy. These combination therapy regimens are not recommended for widespread use. Other more aggressive regimens with additional drugs or higher drug doses than have been studied might be more efficacious, but with an even higher rate of toxicity.

Adult↗
PubMed1994

Do occupation-related physical factors contribute to arthritis?

Occupational physical activities over many years can induce osteoarthritis in selected joints. Well-studied examples include evidence of osteoarthritis of the knees and spine in miners, osteoarthritis of the hip in farmers and increased rates of osteoarthritis of otherwise not usually affected upper extremity joints in pneumatic drill operators. Occupation-induced osteoarthritis may not be limited to these uncommon occupations but may, in fact, account for a large proportion of osteoarthritis in the population. Additional studies of this issue, which incorporate high-quality ergonomic assessments of occupational physical activities, are needed. People with pre-existing arthritis often experience work disability, especially when faced with physically demanding jobs in which they have little control over the pace or the specific physical demands of their labour.

Agriculture↗
PubMed1994

The effects of specific medical conditions on the functional limitations of elders in the Framingham Study.

OBJECTIVES: The purpose of this study was to identify associations between specific medical conditions in the elderly and limitations in functional tasks; to compare risks of disability across medical conditions, controlling for age, sex, and comorbidity; and to determine the proportion of disability attributable to each condition. METHODS: The subjects were 709 noninstitutionalized men and 1060 women of the Framingham Study cohort (mean age 73.7 +/- 6.3 years). Ten medical conditions were identified for study: knee osteoarthritis, hip fracture, diabetes, stroke, heart disease, intermittent claudication, congestive heart failure, chronic obstructive pulmonary disease, depressive symptomatology, and cognitive impairment. Adjusted odds ratios were calculated for dependence on human assistance in seven functional activities. RESULTS: Stroke was significantly associated with functional limitations in all seven tasks; depressive symptomatology and hip fracture were associated with limitations in five tasks; and knee osteoarthritis, heart disease, congestive heart failure, and chronic obstructive pulmonary disease, were associated with limitations in four tasks each. CONCLUSIONS: In general, stroke, depressive symptomatology, hip fracture, knee osteoarthritis, and heart disease account for more physical disability in noninstitutionalized elderly men and women than other diseases.

Activities of Daily Living↗
PubMed1994

World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials.

The WHO/ILAR core set of endpoints for rheumatoid arthritis clinical trials signifies progress in a continuing worldwide effort. This core set includes the following measures: pain, patient global assessment, physical disability, swollen joints, tender joints, acute phase reactants, and physician global assessment; in studies of one or more years' duration, radiographs of joints should be performed.

Antirheumatic Agents↗
PubMed1993

The effect of postmenopausal estrogen therapy on bone density in elderly women.

BACKGROUND: Estrogen therapy prevents bone loss in postmenopausal women who take it early in the postmenopausal period. The risk of fracture is highest much later in life, however. We studied whether bone mass in elderly women was affected by earlier estrogen use and how long women needed to take estrogen for it to have a beneficial effect on bone density later in life. METHODS: In 1988 and 1989, we measured bone mineral density at the femur, spine, shaft of the radius, and ultradistal radius in 670 white women in the Framingham Study cohort (mean age, 76 years; range, 68 to 96). These women had been followed prospectively through menopause and had been asked repeatedly about estrogen therapy. After excluding women who began taking estrogen after a fracture, we investigated whether postmenopausal estrogen therapy affected bone density; in these analyses we adjusted for age, weight, height, cigarette smoking, physical activity, and age at menopause. RESULTS: A total of 212 women (31.6 percent) had received estrogen therapy (mean estimated duration of treatment, 5 years). Only women who had taken estrogen for 7 to 9 years or for 10 or more years had significantly higher bone mineral density than women who had not taken estrogen (7 to 9 years of treatment, P < 0.05 at sites in the femur and the spine; > or = 10 years, P < 0.05 at all sites except the spine). In the women less than 75 years of age who had taken estrogen for seven or more years, the bone density was, averaging all sites, 11.2 percent greater than in women who had never received estrogen. Among women 75 years of age and older in whom the duration of therapy was comparable, bone density was only 3.2 percent higher than in women who had never taken estrogen. CONCLUSIONS: For long-term preservation of bone mineral density, women should take estrogen for at least seven years after menopause. Even this duration of therapy may have little residual effect on bone density among women 75 years of age and older, who have the highest risk of fracture.

Age Factors↗
PubMed1993

A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have well-known gastrointestinal and renal toxic reactions. Effects of NSAIDs on blood pressure are less appreciated. A meta-analysis was performed to determine the hypertensive effects of NSAIDs and rank them by magnitude of change in mean arterial pressure (MAP). METHODS: A literature search of published English-language studies of NSAIDs and their effects on blood pressure was done. Studies were included if they met the following criteria: (1) the studies were intervention studies; (2) NSAIDs at any dose or aspirin at doses of 1.5 g/d or greater were included; (3) documentation of blood pressure was provided; and (4) the studies were 24 hours in duration. Studies were excluded if 20% or more of their participants dropped out or if the dose of antihypertensive drugs was adjusted while the subjects were taking NSAIDs. The major outcome was change in MAP while patients were receiving NSAIDs. Each NSAID arm was extracted from its trial. Information on possible confounders, including subject age, trial quality, amount of dietary salt intake, and whether study subjects were hypertensive or normotensive, was recorded. We calculated the average change in MAP on each NSAID, adjusting for confounders. RESULTS: Fifty-four studies with 123 NSAID treatment arms met inclusion criteria. The mean age of subjects was 46 years. Of the 1324 participants, 1213 subjects (92%) were hypertensive. The effects of NSAIDs on blood pressure were found solely in hypertensive subjects. Among these, the increase in MAP after adjusting for amount of dietary salt intake was 3.59 mm Hg for indomethacin (57 treatment arms), 374 mm Hg for naproxen (four arms), and 0.49 mm Hg for piroxicam (four arms). The MAP decreased by 2.59 mm Hg for placebo (10 arms), 0.83 mm Hg for ibuprofen (six arms), 1.76 mm Hg for aspirin (four arms), and 0.16 mm Hg for sulindac (23 arms). The effects on MAP by using placebo, sulindac, and aspirin were statistically significantly different from indomethacin. CONCLUSIONS: In short-term use, NSAIDs vary considerably in their effect on blood pressure. Of the drugs studied, indomethacin and naproxen were associated with the largest increases in blood pressure. The average effects of piroxicam, aspirin, ibuprofen, and sulindac were negligible.

Anti-Inflammatory Agents, Non-Steroidal↗
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

Bone mineral density and knee osteoarthritis in elderly men and women. The Framingham Study.

OBJECTIVE: To examine the possible inverse relationship between osteoporosis and osteoarthritis (OA) by evaluating the association between bone mineral density (BMD) and knee OA in the Framingham Study cohort. METHODS: Of the 1,154 Framingham Study cohort subjects in whom BMD measurements were obtained at biennial examination 20, 932 (81%) had had knee OA assessed during the Framingham Knee OA Study 4 years earlier. BMD of the proximal femur and radius was measured by densitometry. Knee OA was assessed from a weight-bearing anteroposterior radiography and graded on a scale of 0 (no OA) to 4 (severe OA). Osteophytes and joint space narrowing were also evaluated separately. Linear regression was used to test the association of BMD with knee OA, with osteophytes, and with joint space narrowing, after adjustment for age, body mass index, and mean number of cigarettes smoked per day. RESULTS: The subjects included 572 women and 360 men with an age range of 63-91 years (mean 71 years). Of these, 351 had no OA, 269 had grade 1 OA, 170 had grade 2 OA, 93 had grade 3 OA, and 49 had grade 4 OA. Mean femoral BMD at the 3 proximal femur sites was 5-9% higher in men and women with either grade 1, grade 2, or grade 3 knee OA, compared with those with no knee OA (P < 0.0001). Mean femoral BMD in those with grade 4 OA was not higher than in those with no OA. Radius BMD was not associated with knee OA in subjects of either sex. Women with osteophytes had higher BMD compared with women with no osteophytes. Mean BMD did not differ across levels of joint space narrowing. CONCLUSION: We conclude that, among women, femoral BMD is higher in those with osteophytosis of the knee, and BMD is not necessarily associated with joint space narrowing.

Aged↗
PubMed1993

Incidence of rheumatoid arthritis in central Massachusetts.

OBJECTIVE: To determine whether there is a secular decline in the incidence of rheumatoid arthritis (RA), as has been suggested by previous studies. METHODS: In the absence of comprehensive data in the United States population, we estimated RA incidence in a health maintenance organization population from 1987 through 1990 and compared the rates with those in an earlier, similarly performed study from Rochester, Minnesota, which covered the years 1950 through 1974. RA estimates were based on our review of medical records of patients who had been diagnosed as having RA or related diseases during the period of January 1, 1987 through December 31, 1990. RESULTS: Annual age-standardized incidence of classic or definite RA (according to the American College of Rheumatology [formerly, the American Rheumatism Association] 1958 criteria) in patients aged 18 or older was 22 per 100,000 in men and 60 per 100,000 in women. The incidence of RA increased with age, with a marked increase in women older than 50. CONCLUSION: We found no secular change in RA incidence compared with the similarly ascertained historical data.

Adolescent↗
PubMed1993

Effects of weight and body mass index on bone mineral density in men and women: the Framingham study.

We evaluated the association of weight and bone mass in elderly male and female subjects of the Framingham osteoporosis study, a subset of the Framingham study cohort. By examining the differences in the correlations of weight with bone mass among men and women in weight-bearing and non-weight-bearing sites and weight change since early adulthood, we attempted to understand different ways in which weight or body mass index affects bone mass. During biennial examination 20 of the Framingham cohort (1988-1989), 693 women and 439 men (mean age 76 years) had proximal femur bone mineral density assessed by dualphoton absorptiometry (DPA) and radius bone mass assessed by single-photon absorptiometry. The majority of these subjects also had spine measurements by DPA. Subjects had been weighed repeatedly over 40 years. After adjusting for other factors affecting bone density, we found that both recent weight and body mass index explained a substantial proportion of the variance in bone mineral density for all sites in women (8.9-19.8% of total variance, all p < 0.01) and for only weight-bearing sites (femur and spine) in men (2.8-6.9% of total variance, all p < 0.01). For bone mineral density at the proximal radius, weight and body mass index accounted for < 1% of variance in men (p NS). Weight change since biennial examination 1 (1948-1951) was the strongest explanatory factor for bone mineral density among women at all sites, but weight change did not affect radius bone mineral density in men. The effect of weight and of weight change on bone mineral density was in general much less in men than in women. Our results suggest that the strong effect of weight on bone mineral density is due to load on weight-bearing bones sexes. The sex difference is unexplained but may be due to adipose tissue production of estrogen in women after menopause.

Absorptiometry, Photon↗
PubMed1993

The course of osteoarthritis and factors that affect it.

The natural history of knee, hip, and hand osteoarthritis (OA) is variable. Pathologic changes of OA generally remain stable or worsen, although some patients with hip osteoarthritis may actually sustain reconstitution of joint space. Even with stable pathology, patients often experience symptomatic improvement. Risk factors for OA progression include elderly age, coexistent crystal disease, concurrent OA in multiple joints (generalized disease), neuropathy, and, for knees, obesity.

Humans↗
PubMed1993

Hypertension increases the risk of renal deterioration in systemic lupus erythematosus.

OBJECTIVE: To assess the effect of hypertension on the development of renal functional deterioration, end stage renal disease and death in patients with systemic lupus erythematosus (SLE). METHODS: Person-years analysis using regression techniques to adjust for other baseline risk factors for adverse renal and patient survival outcomes. RESULTS: Six hundred eighty-five patients with SLE were followed for a total of 4,137 person-years. The risk of renal deterioration (doubling of serum creatinine) and endstage renal disease (ESRD) both increased with increasing baseline mean arterial pressure (MAP) (both p > 0.05). Even after adjustment for age, sex, baseline serum creatinine, C3, erythrocyte sedimentation rate, hematocrit, anti-DNA antibodies, and proteinuria, those in the highest quartile of MAP had 2.3 times the odds of renal deterioration at 12 months and 4.6 times the odds of ESRD compared to those in the lowest quartile of MAP (both p < 0.01 comparing highest to lowest quartile of MAP). Also, hypertension increased the risk of mortality, especially between one and 2 years after blood pressure determination. The effect of hypertension was also independent of corticosteroid dose. CONCLUSION: In patients with SLE, hypertension is a potent independent risk factor for adverse renal outcomes, and it also increases the risk of death.

Adult↗