Biomedical subjects
Publications and source records attributed to David T Felson.
Osteoarthritis is a disease affecting all joint structures, not just hyaline articular cartilage. It develops as a consequence of injurious activities acting on a vulnerable joint. The correlation between structural changes of the disease and joint symptoms is poor. Risk factors include age, obesity, and joint injury. Risk factors for symptoms include bone marrow edema, synovitis, and joint effusion.
OBJECTIVES: To evaluate the effect of nine disabling medical conditions upon recovery from functional limitations by elders. DESIGN: Retrospective analysis of prospective longitudinal cohort. SETTING: Community. PARTICIPANTS: Persons aged 65 and older in Framingham Heart Study. MEASUREMENTS: Change in function in elders from biennial Examinations 18 (1983-85; baseline) through 23 (1994-96). At each examination, subjects reported limitations in heavy household work, walking up and down stairs, walking half a mile, bathing, toileting, and continence. They were also directly observed for performance of transferring in and out of a chair, dressing, walking 50 feet, and carrying a 10-pound object 10 feet. The prevalence of functional limitations and the incidence of recovery from functional limitation by the subsequent examination for each task were calculated. The effects of congestive heart failure, cognitive impairment, diabetes mellitus, stroke, depressive symptoms, hip fracture, knee pain, claudication, and chronic obstructive pulmonary disease were evaluated. The relationship between the total number of comorbid conditions present (0, 1, 2, 3 or more), the presence of each individual condition at the start of each examination cycle, and the incidence of recovery from functional limitations were examined using generalized estimating equations. RESULTS: One thousand eight hundred twenty-five subjects were studied at baseline; 1,026 were available 10 years later. Mean age of subjects at baseline was 73.5 (range 61-95); 60.7% were women. The prevalence of functional limitations ranged from 3.1% to 29.8% at biennial Examination 18 and increased to 15.1% to 32.4% at Examination 23. The incidence of recovery ranged from 3.2% to 78.4% depending upon the task and the examination cycle. Increasing disease burden, as measured by the number of comorbidities, was associated with a decreased likelihood of recovery from functional limitations. Diabetes mellitus, stroke, depressive symptoms, hip fracture, and knee pain had the strongest adverse effect upon recovery from functional limitations. CONCLUSION: In these community-dwelling elders, recovery from prevalent functional limitations was frequent. Increasing disease burden was associated with a decreased incidence of recovery. Diabetes mellitus, stroke, depressive symptoms, hip fracture, and knee pain had the strongest adverse effect on recovery from functional limitations.
This study assessed the contribution of genetic and nongenetic factors to biological aging in American Caucasians. The studied sample included 1402 members of 288 pedigrees from the Framingham Heart Study. The original cohort participants received hand radiography in 1967-1969 (mean age, 58.7 years) and their offspring in 1992-1993 (mean age, 51.6 years). An osseographic score was applied to hand radiographs. Standardized residuals between Osseographic Scoring System-predicted age and actual age were used as a measure of biological age (BA). In variance component genetic analysis, sex, cohort, height, body mass index, and, in women, menopausal status and estrogen use, jointly explained approximately 6% of the total variance of BA. Genetic factors explained an additional 57%. Linkage analysis of covariate-adjusted BA suggested the presence of quantitative trait loci on chromosomes 3p, 7q, 11p, 16q, and 21q. In conclusion, the variation in BA measured by radiography was strongly governed by genetic factors in a sample of American adults.
Joint damage occurs when structures protecting the joint fail. Because osteoarthritis consists of end-stage joint damage, I propose that risk factors for disease can be best understood as either impairments of joint protectors, increasing joint vulnerability, or as factors that excessively load the joint, leading to injury. I review current knowledge using this paradigm, separating factors into those increasing joint vulnerability (malalignment, muscle weakness, genetic and ethnic predispositions, aging) and those that cause excessive loading (obesity; certain physical activities). Osteoarthritis and cartilage loss can occur without pain. This review focuses separately on factors associated with pain in those with osteoarthritis. To identify sources of pain in osteoarthritis, recent studies have compared magnetic resonance imaging findings of people with osteoarthritis with and without pain, focusing on structures known to have nociceptive innervations. Those with pain are more likely to have effusions, bone marrow lesions, synovial hypertrophy, and tendinitis and bursitis around the joint. This review creates a new paradigm for understanding risk factors for osteoarthritis, using joint vulnerability and loading as a framework and focuses separately on the emerging investigative area of sources of pain.
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For many years the search for structural associations of osteoarthritis (OA) pain were based on conventional radiographic imaging that predominantly visualizes bone. As well as being tomographic, magnetic resonance imaging (MRI) has the ability to directly visualize all the structures of a joint, including soft tissue and cartilage. Initial MRI studies focused on cartilage assessment, but recently there has been a growing body of work examining the correlation of structural findings with pain in OA and their relation to structural progression. Painful OA knees have more MRI-detected abnormalities and these pathologies are often correlated making individual contributions difficult to assess. However, in large cohort studies, both synovial hypertrophy and large synovial effusions were demonstrated to be more frequent in patients with OA knee pain. Similarly MRI-determined subchondral bone marrow oedema lesions (BME), particularly large ones, are associated with OA knee pain. Meniscal tears in OA knees, although common, have not been linked with pain. Improved, reliable quantification of the structural features and the rapid advances in MRI technology can only improve structure-pain understanding.
CONTEXT: Intra-articular hyaluronic acid is a US Food and Drug Administration-approved treatment for knee osteoarthritis (OA); however, its efficacy is controversial. OBJECTIVE: To evaluate whether intra-articular hyaluronic acid is efficacious in treating knee OA. DATA SOURCES: We searched for human clinical trials in MEDLINE (1966 through February 2003) and the Cochrane Controlled Trials Register, using the search terms (osteoarthritis, osteoarthrosis, or degenerative arthritis) and (hyaluronic acid, Hyalgan, Synvisc, Artzal, Suplasyn, BioHy, or Orthovisc). We also hand searched manuscript bibliographies that met inclusion criteria, selected rheumatic disease journals, and abstracts from scientific meetings. STUDY SELECTION: Included were published or unpublished, English and non-English, single- or double-blinded, randomized controlled trials comparing intra-articular hyaluronic acid with intra-articular placebo injection for the treatment of knee OA. Trials also were required to have extractable data on pain reported by 1 of the outcome measures recommended by the Osteoarthritis Research Society. DATA EXTRACTION: Two reviewers independently performed data extraction using standardized data forms. For each trial, we calculated an effect size (small-effect sizes, 0.2-0.5; large-effect sizes, 1.0-1.8, equivalent to a total knee replacement). We used a random-effects model to pool study results, the Cochrane Q test to evaluate heterogeneity, and a funnel plot and the Egger test to evaluate publication bias. DATA SYNTHESIS: The overall dropout rate in the 22 selected trials was 12.4%. The pooled effect size for hyaluronic acid was 0.32 (95% confidence interval [CI], 0.17-0.47). There was significant heterogeneity among studies (P<.001). Two outlier trials, both evaluating the highest-molecular-weight hyaluronic acid, had effect sizes in excess of 1.5. However, the third trial of the same compound showed a nearly null effect. When the 3 trials of this compound were removed, heterogeneity was no longer significant (P =.58), and the pooled effect size for intra-articular hyaluronic acid decreased to 0.19 (95% CI, 0.10-0.27). There was evidence of publication bias with an asymmetric funnel plot, a positive Egger test, and identification of 2 unpublished trials whose pooled effect size was 0.07 (95% CI, - 0.15 to 0.28). CONCLUSION: Intra-articular hyaluronic acid has a small effect when compared with an intra-articular placebo. The presence of publication bias suggests even this effect may be overestimated. Compared with lower-molecular-weight hyaluronic acid, the highest-molecular-weight hyaluronic acid may be more efficacious in treating knee OA, but heterogeneity of these studies limits definitive conclusions.
BACKGROUND: While factors affecting the course of knee osteoarthritis are mostly unknown, lesions on bone scan and mechanical malalignment increase risk for radiographic deterioration. Bone marrow edema lesions on magnetic resonance imaging correspond to bone scan lesions. OBJECTIVE: To determine whether edema lesions in the subarticular bone in patients with knee osteoarthritis identify knees at high risk for radiographic progression and whether these lesions are associated with limb malalignment. DESIGN: Natural history study. SETTING: A Veterans Administration hospital in Boston, Massachusetts. PATIENTS: Persons 45 years of age and older with symptomatic knee osteoarthritis. MEASUREMENTS: Baseline assessments included magnetic resonance imaging of the knee and fluoroscopically positioned radiography. During follow-up at 15 and 30 months, patients underwent repeated radiography; at 15 months, long-limb films were obtained to assess mechanical alignment. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semi-quantitative grading. Generalized estimating equations were used to evaluate the relation of medial bone marrow edema lesions to medial progression and lateral lesions to lateral progression, before and after adjustment for limb alignment. RESULTS: Of 256 patients, 223 (87.1%) participated in at least one follow-up examination. Medial bone marrow lesions were seen mostly in patients with varus limbs, and lateral lesions were seen mostly in those with valgus limbs. Twenty-seven of 75 knees with medial lesions (36.0%) showed medial progression versus 12 of 148 knees without lesions (8.1%) (odds ratio for progression, 6.5 [95% CI, 3.0 to 14.0]). Approximately 69% of knees that progressed medially had medial lesions, and lateral lesions conferred a marked risk for lateral progression. These increased risks were attenuated by 37% to 53% after adjustment for limb alignment. CONCLUSION: Bone marrow edema is a potent risk factor for structural deterioration in knee osteoarthritis, and its relation to progression is explained in part by its association with limb alignment.
OBJECTIVE: To investigate the prevalence of knee, hip and hand osteoarthritis (OA) in the elderly of Beijing and to compare the prevalence of OA between the Beijing elders and the US Caucasians. METHODS: Using the same standardized instruments and protocol as those in the Framingham Osteoarthritis Study, home interview, clinical examination and radiography were conducted among 1012 males and 1507 females, all aged 60 and over, on 4 central districts of Beijing with informed consent. The data of survey were compared with those of the corresponding US study. RESULTS: The prevalence of radiographic and symptomatic knee osteoarthritis was 42.8% and 15.4% respectively among the women aged 60 and over in Beijing, higher than those in Caucasian women of the same age. The prevalence of radiographic and symptomatic knee osteoarthritis were 27.6% and 7.1% respectively among the men aged 60 and over in Beijing, similar to those in the Caucasian men of the same age. The prevalence of radiographic hand osteoarthritis among the Beijing men and women aged 60 and over were 44.5% and 47.0% respectively, lower than those among the contemporary Caucasian in US. The prevalence of hip osteoarthritis among the men and women aged 60 and over were only 0.4% and 0.6%, significantly lower than those among the contemporary Caucasian in US. CONCLUSION: Compared to the Caucasian contemporaries, fewer Beijing elderly suffer from hand and hip osteoarthritis. However, knee osteoarthritis is much more prevalent, affecting millions of elderly Chinese.
OBJECTIVE: Fewer Chinese subjects in Beijing have hip osteoarthritis (OA) compared with whites in the United States, but as many or more Chinese subjects have knee OA. If these differences are due to a systemic predilection for disease, then the prevalence of hand OA, the best indicator of generalized disease, should be different in China. The goals of this study were to estimate the prevalence of hand OA among elderly Chinese in Beijing, and to compare it with that among elderly whites in the United States. METHODS: We recruited a random sample of Beijing residents ages > or =60 years. Subjects answered questions on joint symptoms and provided posteroanterior radiographs of the hand. The protocol was identical to that used in the Framingham, Massachusetts OA Study. The hand radiographs from the Beijing OA Study were read intermingled with films from the Framingham OA Study. We defined a hand joint as having radiographic OA if it had a Kellgren and Lawrence grade >/=2. Symptomatic OA was present when both radiographic OA and self-reported pain were present in the same joint. We classified a subject as having radiographic or symptomatic hand OA if at least 1 hand joint had radiographic or symptomatic OA. We estimated the prevalence of hand OA in elderly subjects in Beijing and compared it with the prevalence of hand OA in elderly subjects from Framingham, using an age-standardized prevalence ratio. RESULTS: We obtained both symptom information and hand radiographs from 2,525 subjects. Despite the older age of the group, only 44.5% of men and 47.0% of women had radiographic hand OA. Symptomatic hand OA occurred in 3.0% of men and 5.8% of women. Compared with white men in Framingham, the Beijing Chinese men had a much lower prevalence of radiographic hand OA (age-adjusted prevalence ratio 0.64, 95% confidence interval [95% CI] 0.58-0.70) and symptomatic hand OA (age-adjusted prevalence ratio 0.25, 95% CI 0.16-0.34). The proportion of multiple hand joints affected by OA in Chinese men was also significantly lower than in white men. A similar magnitude of difference was also observed in the women. However, prevalence of symptomatic OA at the metacarpophalangeal (MCP) joints in Chinese men and prevalence of radiographic OA at the MCP joints in Chinese women were similar to those in their white counterparts in Framingham. CONCLUSION: Elderly Chinese subjects in Beijing had a much lower prevalence of hand OA than did elderly whites in Framingham, Massachusetts. Coupled with the exceedingly low prevalence of hip OA in China, these results may suggest that the overall predilection for OA is less among subjects in China than among whites in the United States.
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OBJECTIVE: To evaluate, using magnetic resonance imaging (MRI), the prevalence of periarticular lesions in older persons with or without knee pain, and to assess the association of these lesions with knee pain. METHODS: Subjects ages 45 years and older, with or without knee pain, were recruited from Veterans Affairs medical centers and from the community. Weight-bearing posteroanterior, skyline, and lateral radiographs were obtained in all subjects. Subjects were divided into 3 groups: those with radiographic OA (ROA) and knee pain (n = 376), those with ROA and no knee pain (n = 51), and those with neither ROA nor knee pain (n = 24). A single knee (the more symptomatic one in subjects with knee pain) was imaged with a 1.5T scanner using T1- and T2-weighted and proton-density spin-echo imaging sequences. MRIs were read for the presence of periarticular lesions, which were categorized (according to their general location) as being either peripatellar (prepatellar, superficial infrapatellar, deep infrapatellar) or "other periarticular lesions" (semimembranosus-tibial collateral ligament bursitis, anserine bursitis, iliotibial band syndrome, tibiofibular cyst). RESULTS: Patients with knee pain had more severe radiographic disease than did subjects who were asymptomatic. Peripatellar lesions (prepatellar or superficial infrapatellar) were present in 12.1% of the patients with knee pain and ROA, in 20.5% of the patients with ROA and no knee pain, and in 0% of subjects with neither ROA nor knee pain (P = 0.116). However, other periarticular lesions were present in 14.9% of patients with both ROA and knee pain, in only 3.9% of patients with ROA but no knee pain, and in 0% of the group with no knee pain and no ROA (P = 0.004). CONCLUSION: Although peripatellar lesions are equally common among subjects with knee pain and those without knee pain, other periarticular lesions (including bursitis and iliotibial band syndrome) are significantly more common among subjects with knee pain and may contribute to pain in these individuals.
OBJECTIVE: Isolated studies have suggested that continuous measures of response may be better than predefined, dichotomous definitions (e.g., the American College of Rheumatology 20% improvement criteria [ACR20]) for discriminating between rheumatoid arthritis (RA) treatments. Our goal was to determine the statistical power of predefined dichotomous outcome measures (termed "a priori"), compared with that of continuous measures derived from trial data in which there was no predefined response threshold (termed "data driven"), and to evaluate the sensitivity to change of these measures in the context of different treatments and early versus later-stage disease. In order to generalize beyond results from a single trial, we performed simulation studies. METHODS: We obtained summary data from trials comparing disease-modifying antirheumatic drugs (DMARDs) and from comparative coxib-placebo trials to test the power of 2 a priori outcomes, the ACR20 and improvement of the Disease Activity Score (DDAS), as well as 2 data-driven outcomes. We studied patients with early RA and those with later-stage RA (duration of <4 years and 4-9 years, respectively). We performed simulation studies, using the interrelationship of ACR core set measures in the trials to generate multiple trial data sets consistent with the original data. RESULTS: The data-driven outcomes had greater power than did the a priori measures. The DMARD comparison was more powerful in early disease than in later-stage disease (the sample sizes needed to achieve 80% power for the most powerful test were 64 for early disease versus 100 for later disease), but the coxib-versus-placebo comparison was less powerful in early disease than in later disease (the sample sizes needed to achieve 80% power were 200 and 100, respectively). When the effects of treatment on core set items were small and/or inconsistent, power was reduced, particularly for a less broadly based outcome (e.g., DDAS) compared with the ACR20. CONCLUSION: The simulation studies demonstrate that data-driven outcome definitions can provide better sensitivity to change than does the ACR20 or DDAS. Using such methods would improve power, but at the expense of trial standardization. The studies also show how patient population and treatment characteristics affect the power of specific outcome measures in RA clinical trials, and provide quantification of those effects.
OBJECTIVES: To determine the relationship between back symptoms and limitations in nine specific functional activities. DESIGN: A cross-sectional study. SETTING: This study was conducted as part of the Framingham Heart Study, a population-based study performed on a representative sample of community-living residents of Framingham, Massachusetts. PARTICIPANTS: Subjects consisted of 1,007 surviving members of the original cohort who participated in the 22nd Biennial Examination in 1992-93. Ages ranged from 70 to 100. MEASUREMENTS: Subjects were asked whether they experienced pain, aching, or stiffness in their back on most days and whether they had difficulty performing nine specific functional skills. Odds ratios (ORs) and confidence intervals are reported for the entire sample and within categories of sex. The proportion of functional limitations attributable to back symptoms and the proportion of limitations ascribed by subjects to back symptoms among subjects with these limitations are also reported. RESULTS: The results provide evidence of a relationship between back symptoms and functional limitations. ORs were highest for difficulty standing in one place for about 15 minutes, pushing or pulling a large object, and walking half a mile. Of those with back symptoms, 43% to 63% of limitations in activities were due to back symptoms. Among all subjects, back symptoms were so prevalent that 18% to 34% of all functional limitations were attributable to back symptoms. The association between back symptoms and functional limitations was especially strong in women. CONCLUSION: Back symptoms account for a large percentage of functional limitations in older adults, especially in women.
In the hierarchy of research designs, the results of randomized controlled trials are considered the highest level of evidence. Randomization is the only method for controlling for known and unknown prognostic factors between two comparison groups. Lack of randomization predisposes a study to potentially important imbalances in baseline characteristics between two study groups. There is a hierarchy of evidence, with randomized controlled trials at the top, controlled observational studies in the middle, and uncontrolled studies and opinion at the bottom. This hierarchy has not been supported in two recent publications in the New England Journal of Medicine which identified nonsignificant differences in results between randomized, controlled trials, and observational studies. The current authors provide an approach to organizing published research on the basis of study design, a hierarchy of evidence, a set of principles and tools that help clinicians distinguish ignorance of evidence from real scientific uncertainty, distinguish evidence from unsubstantiated opinions, and ultimately provide better patient care.
BACKGROUND: Meniscal tears are frequently found during magnetic resonance imaging of osteoarthritic knees. However, the prevalence and clinical relevance of these tears have not been determined. This study was designed to investigate the relationship between meniscal tears and osteoarthritis and between such tears and pain in patients with osteoarthritis. METHODS: Magnetic resonance imaging and plain radiography of the knee were performed in a group of 154 patients with clinical symptoms of knee osteoarthritis and a group of forty-nine age-matched asymptomatic controls. Pain scores (according to a 100-mm visual analog scale) and functional scores (according to the Western Ontario and McMaster University Osteoarthritis Index [WOMAC]) were determined for ninety-one of the patients with symptomatic osteoarthritis. Meniscal tears were defined as tears extending to an articular surface as seen on magnetic resonance imaging. RESULTS: A medial or lateral meniscal tear was a very common finding in the asymptomatic subjects (prevalence, 76%) but was more common in the patients with symptomatic osteoarthritis (91%) (p < 0.005). In the group with symptomatic osteoarthritis, a higher Kellgren-Lawrence radiographic grade was correlated with a higher frequency of meniscal tears (r = 0.26, p < 0.001), and men had a higher prevalence of meniscal tears than did women (p < 0.01). However, there was no significant difference with regard to the pain or WOMAC score between the patients with and those without a medial or lateral meniscal tear in the osteoarthritic group (p = 0.8 to 0.9 for all comparisons). The power of the study was 80% to detect a difference in the WOMAC scores of 15 points and a difference in the scores on the visual analog scale of 16 mm. CONCLUSIONS: Meniscal tears are highly prevalent in both asymptomatic and clinically osteoarthritic knees of older individuals. However, osteoarthritic knees with a meniscal tear are not more painful than those without a tear, and the meniscal tears do not affect functional status. These data do not support the routine use of magnetic resonance imaging for the evaluation and management of meniscal tears in patients with osteoarthritis of the knee. LEVEL OF EVIDENCE: Diagnostic study, Level I-1 (testing of previously developed diagnostic criteria in series of consecutive patients [with universally applied reference "gold" standard]). See p. 2 for complete description of levels of evidence.
This article summarizes the process proposed to come to a definition of low disease activity in rheumatoid arthritis (RA). The purpose of this definition is to aid the interpretation of trial and longitudinal study results. A conceptual proposal is "a disease activity state that is deemed a useful treatment target by both physicians and patients." An operant definition can be derived by judgmental (opinion-based) or statistical (data-based) approaches, but the first seems more appropriate. Once a few candidate definitions have been selected, their usefulness and prognostic validity can be tested in longitudinal datasets.