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Biomedical subjects

David T Felson

Publications and source records attributed to David T Felson.

At least 37 records · Page 2Linked to original sources

The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis.

OBJECTIVE: To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging (MRI) in patients with symptomatic knee osteoarthritis (OA), and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression. METHODS: Two hundred twenty-four men and women (mean age 66 years) were studied. Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup. Radiographs of the knee (with weight-bearing) were read for joint space narrowing (scale 0-3), with progression defined as any worsening in score. We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint, and defined cartilage loss as an increase in score (scale 0-4) at any region. We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI, using a generalized estimating equation proportional odds logistic regression, adjusted for baseline cartilage score, age, body mass index, and sex. The medial and lateral compartments were analyzed separately. RESULTS: In the medial compartment, 104 knees (46%) had cartilage loss detected by MRI. The adjusted odds ratio was 3.7 (95% confidence interval 2.2-6.3) for radiographic progression being predictive of cartilage loss on MRI. However, there was still a substantial proportion of knees (80 of 189 [42%]) with cartilage loss visible on MRI when no radiographic progression was apparent. Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region, but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss. Radiographic progression appeared specific (91%) but not sensitive (23%) for cartilage loss. Overall findings were similar for the lateral compartment. CONCLUSION: While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.

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The lateral view radiograph for assessment of the tibiofemoral joint space in knee osteoarthritis: its reliability, sensitivity to change, and longitudinal validity.

OBJECTIVE: To evaluate the reliability, validity, and sensitivity to change of tibiofemoral (TF) narrowing on lateral radiographic views. METHODS: In a natural history study of symptomatic knee osteoarthritis (OA), both lateral view and fluoroscopically positioned posteroanterior (PA) semiflexed view radiographs of the knee in 30 degrees of flexion and with weight bearing were obtained at baseline and at 30 months. Test-retest reliability was evaluated using repeat radiographs, with joint space width measured using electronic calipers. All radiographs were scored on a 0-3 scale, and progression of joint space loss was defined as narrowing of the joint space by 1 grade. We evaluated sensitivity to change compared with the PA view. We evaluated validity by examining whether knees with progression showed expected malalignment on full-limb films. RESULTS: Test-retest reliability of the TF joint space using the lateral view had a root mean square error of 0.303 mm, with 92.5% of repeats within 1 mm. More knees showed progression on the lateral view alone (n = 41) than on the PA view alone (n = 27). Compared with knees without joint space loss, knees with medial compartment loss on the lateral view only were more varus malaligned (P < 0.001), while those with lateral compartment loss were more valgus malaligned (P = 0.008). CONCLUSION: In the assessment of TF joint space loss, lateral view radiographs are reliable, valid, and more sensitive to change than fluoroscopically positioned PA radiographs.

Cartilage, Articular↗

Sex differences in musculoskeletal pain in older adults.

Little is known about sex differences in musculoskeletal pain in older persons. There were 682 women and 380 men aged 72 years and older who participated in the 22nd biennial exam of the Framingham Study (1992-1993). Participants were asked to identify pain locations on a homunculus showing all regions of the body. Pain was categorized according to number of regions, with the most disseminated pain classified as widespread pain (back pain and upper and lower extremity pain with bilaterality). Among the women, 63% reported pain in one or more regions, compared to 52% of men. Widespread pain was more prevalent among women than men (15 versus 5%, respectively). In both men and women, pain was associated with fair or poor self-rated health, history of back pain before age 65, and disability. Factors associated with pain only in women included body mass index, systolic blood pressure, and depressive symptoms. In men but not women, pain was associated with polyarticular radiographic osteoarthritis. In conclusion, musculoskeletal pain was more prevalent and more widespread in older women than older men. Men and women differ in the factors associated with musculoskeletal pain in older ages. Further research is needed to understand sex differences in musculoskeletal pain the older population.

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The sources of pain in knee osteoarthritis.

PURPOSE OF REVIEW: To review the mechanisms for the production of pain in knee osteoarthritis. RECENT FINDINGS: Nociception is produced by stimulation of unmyelinated and small myelinated fibers in the joint and surrounding tissue. To produce pain, the stimuli must be either repeated or spatially clustered. When they reach the spinal cord, stimuli are subject to two inhibitory effectors: interneurons and descending central neurons. Inflammation lowers the threshold for nociception. In the joint, tissues containing nociceptors include primarily the joint capsule, ligaments, synovium, bone, and in the knee, the outer edge of the menisci. Nociceptive stimuli are likely to emanate from one or more of these locations in people with knee pain. This review does not cover psychological aspects of pain. SUMMARY: Nociception in the knee is complex, and the nociceptive stimuli are related to but fundamentally different from those producing cartilage loss. Better appreciation for these processes will facilitate the development of new treatments.

Humans↗

Foot musculoskeletal disorders, pain, and foot-related functional limitation in older persons.

OBJECTIVES: To examine whether common musculoskeletal disorders of feet are associated with pain and foot-related functional limitation. DESIGN: A cross-sectional study using stratified random sampling. SETTING: A residential community. PARTICIPANTS: Ethnically diverse sample of elderly persons (n=784). MEASUREMENTS: Foot disorders (hallux valgus/bunion, pes planus (flat foot), pes cavus (high arch), hammertoe, mallet toe, claw toe, overlapping toes, bunionette, and plantar fasciitis), foot pain, the foot health functional status (FHFS, range 0-100, 100=no problems) scale, and walk time score (range 0-4, 4=fastest). RESULTS: Most commonly assessed musculoskeletal disorders, including hallux valgus and toe deformities, were not associated with pain or function limitation. Plantar fasciitis and, to a lesser extent, pes cavus were associated with worse FHFS scores; foot pain partially explained this association. Neither foot disorders nor foot pain were significantly associated with slower walk times. CONCLUSION: Many foot disorders had little relationship with foot pain or function and may not require clinical attention when asymptomatic. Risk factors and preventive and therapeutic interventions for plantar fasciitis require further longitudinal investigation.

Activities of Daily Living↗

Are foot disorders associated with functional limitation and disability among community-dwelling older adults?

The objectives of this study are to examine whether specific foot disorders and ankle weakness and foot pain are related to functional limitations or disabilities in elders. Community-dwelling adults 65 and older were enrolled in a population-based, cross-sectional study of foot disorders and health outcomes. Demographics, health status, comorbidities, self-reported foot and knee pain, function and disability, and observed structural foot disorders, body mass index, and ankle muscle strength were assessed on 717 participants. The associations of foot disorders, foot pain, and ankle muscle weakness with function and disability were examined with regression analyses. Foot disorders were not associated with functional outcomes or disability. Ankle weakness was associated with performance-based function (p = .005), self-report function (p lesser than .001), and disability (p = .009). Foot pain was associated with self-report function (p = .01) and disability (p = .007). Foot pain and ankle weakness seem to be related to important health outcomes among older adults.

Activities of Daily Living↗

Minimal disease activity for rheumatoid arthritis: a preliminary definition.

Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.

Arthritis, Rheumatoid↗

Structural factors associated with malalignment in knee osteoarthritis: the Boston osteoarthritis knee study.

OBJECTIVE: Osteoarthritis (OA) is a multifactorial condition. The progression of knee OA is determined in part by mechanical effects on local structures. One of the mechanical influences on cartilage loss is limb alignment. We explored the structural factors associated with malalignment in subjects with symptomatic OA. METHODS: We conducted a cross-sectional assessment using The Boston Osteoarthritis of the Knee Study, a natural history study of symptomatic knee OA. Baseline assessments included knee magnetic resonance imaging (MRI) and information on weight and height. Long-limb radiographs to assess mechanical alignment were obtained at 15 months. Subarticular bone attrition, meniscal degeneration, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, marginal osteophytes, and cartilage morphology were assessed on MRI using a semiquantitative, multi-feature scoring method (Whole-Organ MRI Score) for whole-organ evaluation of the knee that is applicable to conventional MRI techniques. We also quantified the following meniscal position measures on coronal MRI images in both medial and lateral compartments: subluxation, meniscal height, and meniscal covering of the tibial plateau. Using the long-limb radiographs, mechanical alignment was measured in degrees on a continuous scale. The purpose of this cross-sectional analysis was to determine the individual and relative contribution of various structural factors to alignment of the lower extremity. We assessed the cross-sectional association between various structural factors and alignment of the lower extremity using a linear regression model. RESULTS: The 162 subjects with all measures acquired had a mean age of 67.0 years (SD 9.2), body mass index 31.4 (SD 5.6); 30% were female and 77% of knees had a Kellgren-Lawrence grade > or = 2. The main univariate determinants of varus alignment in decreasing order of influence were medial bone attrition, medial meniscal degeneration, medial meniscal subluxation, and medial tibiofemoral cartilage loss. Multivariable analysis revealed that medial bone attrition and medial tibiofemoral cartilage loss explained more of the variance in varus malalignment than other variables. The main univariate determinants of valgus malalignment in decreasing order of influence were lateral tibiofemoral cartilage loss, lateral osteophyte score, and lateral meniscal degeneration. CONCLUSION: Cartilage loss has been thought to be the major determinant of alignment. We found that other factors including meniscal degeneration and position, bone attrition, osteophytes, and ligament damage contribute to the variance of malalignment. Further longitudinal analysis is required to determine cause and effect relationships. This should assist researchers in determining strategies to ameliorate the potent effects of this mechanical disturbance.

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Current status of outcome measures in vasculitis: focus on Wegener's granulomatosis and microscopic polyangiitis. Report from OMERACT 7.

The complexity of assessing disease activity, disease status, and damage in the vasculitides reflects the multisystemic pathologic manifestations of these often chronic illnesses. Major progress has been made in the past decade in the development of validated and widely accepted outcome measures for use in clinical trials. Over time, these tools have been regularly revised, expanded, and supplemented with new measures of disease prognosis and damage. As a result clinical research in this area has become increasingly complex. This article critically reviews the current status of tools for assessing disease activity and damage in "ANCA-associated" vasculitides (Wegener's granulomatosis and microscopic polyangiitis), summarizes the current level of validation of each measure, addresses central problems and controversies to be considered during development of new vasculitis assessment tools, and proposes a series of research agendas for consideration by the vasculitis research community.

Clinical Trials as Topic↗

Knee adduction moment and development of chronic knee pain in elders.

OBJECTIVE: To determine whether the adduction moment at the knee during locomotor activity contributes to the development of future chronic knee pain. METHODS: We studied 132 community-dwelling elders who had undergone a full kinetic and kinematic motion analysis while performing 4 different activities: standing, walking, rising from a chair, and descending stairs. We contacted the participants 3-4 years after their baseline locomotion analysis and identified those who reported no knee pain at the time of motion analysis but who subsequently developed new chronic knee pain at followup. We examined whether the development of new chronic knee pain was associated with higher peak adduction moment at the knee during activities, measured at baseline. RESULTS: Of the 132 elders evaluated in 1995-1996, 118 (89%) were contacted in 1999. Of the 118 contacted, 80 (mean age 75 years; 78% women) had no lower extremity prosthetic joints at baseline, no known underlying inflammatory arthritis at baseline nor followup, and no baseline knee pain. At followup, 7 had developed new chronic knee pain defined as pain or stiffness on most days of the month and with walking 2 blocks or using stairs. Compared with those who did not develop knee pain, those who did develop new chronic knee pain had higher baseline adduction moments for all activities (P = 0.01), ranging from 8% higher during chair rise to 39% higher during stair descent. CONCLUSION: We found that greater adduction moment at the knee during activities contributes to the development of future chronic knee pain. Our results suggest that biomechanical factors may play an important role in the pathogenesis of knee pain and should be studied further.

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A surplus of positive trials: weighing biases and reconsidering equipoise.

In this issue, Fries and Krishnan raise provocative new ideas to explain the surfeit of positive industry sponsored trials evaluating new drugs. They suggest that these trials were designed after so much preliminary work that they were bound to be positive (design bias) and that this violates clinical equipoise, which they characterize as an antiquated concept that should be replaced by a focus on subject autonomy in decision making and expected value for all treatments in a trial. We contend that publication bias, more than design bias, could account for the remarkably high prevalence of positive presented trials. Furthermore, even if all new drugs were efficacious, given the likelihood of type 2 errors, not all trials would be positive. We also suggest that clinical equipoise is a nuanced concept dependent on the existence of controversy about the relative value of two treatments being compared. If there were no controversy, then trials would be both unnecessary and unethical. The proposed idea of positive expected value is intriguing, but in the real world such clearly determinable values do not exist. Neither is it clear how investigators and sponsors, who are invested in the success of a proposed therapy, would (or whether they should) develop such a formula.

Bias↗

Association of squatting with increased prevalence of radiographic tibiofemoral knee osteoarthritis: the Beijing Osteoarthritis Study.

OBJECTIVE: To examine the association between squatting, a common daily posture in China, and the prevalence of radiographic osteoarthritis (OA) in different knee compartments among Chinese subjects from Beijing, and to estimate how much of the difference in prevalence of knee OA between Chinese subjects in Beijing and white subjects in Framingham, Massachusetts is accounted for by the impact of squatting. METHODS: We recruited a random sample of Beijing residents age > or =60 years. Subjects answered questions on joint symptoms, and knee radiographs were obtained. Subjects were also asked to recall the average amount of time spent squatting each day at age 25 years. Radiographic films (weight-bearing anteroposterior and skyline views) were read for Kellgren/Lawrence (K/L) grade and individual radiographic features. Medial disease was defined when radiographs showed a K/L grade of > or =2 at the tibiofemoral joint and a medial joint space narrowing score of > or =1, and lateral disease was assessed in a comparable manner in the lateral compartments. We examined the association of squatting with the prevalence of tibiofemoral OA as well as with the prevalence of patellofemoral knee OA, while adjusting for age and other potential confounding factors. We used the same approach to assess the relationship between squatting and tibiofemoral OA in the medial compartment and in the lateral compartment. Finally, we estimated the impact of squatting at age 25 on the difference in prevalence of knee OA between Chinese subjects in Beijing and white subjects in the Framingham OA Study. RESULTS: Squatting was very common among the Chinese subjects: approximately 40% of men and approximately 68% of women reported squatting > or =1 hour per day at age 25. The prevalence of tibiofemoral OA increased as the time spent squatting at age 25 increased in both the men and the women. Compared with subjects who squatted <30 minutes per day at age 25, the multivariable-adjusted prevalence odds ratios of tibiofemoral OA were 1.1 for time spent squatting of 30-59 minutes/day, 1.0 for 60-119 minutes/day, 1.7 for 120-179 minutes/day, and 2.0 for > or =120 minutes/day among the men (P for trend = 0.074), and the respective odds ratios among the women were 1.4, 1.3, 1.2, and 2.4 (P for trend = 0.077). A weaker association with patellofemoral OA was found. Prolonged squatting in daily life was more strongly associated with medial knee OA than with lateral disease in the men, but had a similar effect on both knee compartments in the women. After adjusting for the impact of squatting, the age-adjusted difference in prevalence of tibiofemoral OA was reduced from an excess of 14.4% to 9.5% in the Chinese women, but the difference in prevalence of tibiofemoral OA in the Chinese men increased after adjustment for age and squatting, from 2.9% lower to 7.0% lower as compared with their white counterparts. CONCLUSION: Prolonged squatting is a strong risk factor for tibiofemoral knee OA among elderly Chinese subjects in Beijing, and accounts for a substantial proportion of the difference in prevalence of tibiofemoral OA between Chinese subjects in Beijing and white subjects in Framingham.

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Chopstick arthropathy: the Beijing Osteoarthritis Study.

OBJECTIVE: Several investigators have speculated that mechanical stress might play an important role in the development of hand osteoarthritis (OA). Chopsticks, used universally as eating utensils in China, increase joint loading in the first through third fingers. We conducted a population-based survey among elderly Chinese individuals living in Beijing, to explore whether chopsticks use is associated with prevalent hand OA. METHODS: We recruited a sample of persons ages 60 years and older, using door-to-door enumeration in randomly selected neighborhoods in Beijing. Subjects answered questions about the hand with which they use chopsticks, handedness, and pincer grip activities. Bilateral posteroanterior hand radiographs were obtained, and each joint was graded according to the Kellgren/Lawrence (K/L) scale. We defined a subject as having radiographic OA if at least 1 of his or her hand joints had radiographic OA (K/L score of > or =2). We defined a particular hand group (i.e., distal interphalangeal [DIP] joints, proximal interphalangeal [PIP] joints, or metacarpophalangeal [MCP] joints) as having OA if at least 1 joint of the group had radiographic OA. We calculated the prevalence of OA for each hand joint and, according to the status of chopsticks use, performed a matched analysis to examine the relationship between chopsticks use and the prevalence of hand OA. In the analysis, we excluded persons who reported a previous hand injury. Because most subjects used chopsticks with their dominant hand (a hand they would be expected to use more for all manual tasks), we also performed the analysis among subjects who reported that they had no hand preference when performing other activities and subjects who denied other pincer grip activities. RESULTS: A total of 1,008 men and 1,499 women were assessed. The prevalence ratio for OA of the thumb IP joint in the chopsticks hand was 1.2 (range 1.1-1.4) in men and 1.6 (range 1.4-1.7) in women; the prevalence ratio for OA of the second and third PIP joints was 1.5 (range 1.1-2.2) in men and 1.4 (range 1.2-1.7) in women; and the prevalence ratio for OA of the second and third MCP joints was 1.4 (range 1.2-1.6) in men and 1.4 (range 1.2-1.6) in women. The prevalence ratios in these joints were greater than the ratios in other MCP, PIP, or DIP joints from the same hand that were unlikely to be involved by chopsticks use, especially among women. Similar results were observed when the analyses were limited to ambidextrous subjects and subjects who did not engage in any other pincer grip activities. Thumb IP joint OA affected 26% of the entire population studied, and chopsticks use accounted for 19% of the risk of OA developing in this joint in men and 36% of the risk in women. CONCLUSION: This epidemiologic study investigated the relationship of chopsticks use to hand arthropathy. The results suggest that chopsticks use is associated with an increased prevalence of OA in the IP joint of the thumb, and in the second and third PIP and MCP joints.

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The effect of body weight on progression of knee osteoarthritis is dependent on alignment.

OBJECTIVE: Whereas obesity increases overall loading of the knee, limb malalignment concentrates that loading on a focal area, to the level at which cartilage damage may occur. This study evaluated whether the effect of body weight on progression of knee osteoarthritis (OA) differs depending on the degree of limb malalignment. METHODS: The study population comprised 228 veterans and community recruits with symptomatic knee OA (pain on most days and radiographic disease) who volunteered to participate in a natural history study and from whom baseline radiographs were obtained to assess alignment; 227 (99.6%) completed a 30-month followup. Of 403 knees assessed at baseline, 394 (97.8%) were followed up. Participants' body mass index (BMI) was assessed at each examination. The main outcome measure was progression of knee OA, defined as narrowing of the tibiofemoral joint space by 1 grade (semiquantitative scale 0-3) on radiographs of the fluoroscopically positioned knee. The association between BMI and the risk of knee OA progression was assessed after adjusting for age, sex, and limb alignment, using logistic regression and generalized estimating equations. RESULTS: Of 394 knees, 90 (22.8%) showed disease progression, and limb alignment was strongly associated with progression risk. The risk of progression increased with increasing weight (for each 2-unit increase in BMI, odds ratio [OR] for progression 1.08, 95% confidence interval [95% CI] 1.00-1.16). However, among those knees with neutral alignment (0-2 degrees ), increases in BMI had no effect on risk of progression (OR 1.00), and in those with severe malalignment (> or =7 degrees ), the effect was similarly null (OR 0.93). The effect of BMI on progression was limited to knees in which there was moderate malalignment (OR per 2-unit increase in BMI 1.23, 95% CI 1.05-1.45). CONCLUSION: Although elevated BMI increases the risk of knee OA progression, the effect of BMI is limited to knees in which moderate malalignment exists, presumably because of the combined focus of load from malalignment and the excess load from increased weight. This has implications for clinical recommendations and for trials testing weight loss in those with knee OA.

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