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Biomedical subjects

D Felson

Publications and source records attributed to D Felson.

At least 19 recordsLinked to original sources
PubMed2006

Classification of osteoarthritis biomarkers: a proposed approach.

OBJECTIVE: Osteoarthritis (OA) biomarkers are needed by researchers and clinicians to assist in disease diagnosis and assessment of disease severity, risk of onset, and progression. As effective agents for OA are developed and tested in clinical studies, biomarkers that reliably mirror or predict the progression or amelioration of OA will also be needed. METHODS: The NIH-funded OA Biomarkers Network is a multidisciplinary group interested in the development and validation of OA biomarkers. This review summarizes our efforts to characterize and classify OA biomarkers. RESULTS: We propose the "BIPED" biomarker classification (which stands for Burden of Disease, Investigative, Prognostic, Efficacy of Intervention and Diagnostic), and offer suggestions on optimal study design and analytic methods for use in OA investigations. CONCLUSION: The BIPED classification provides specific biomarker definitions with the goal of improving our ability to develop and analyze OA biomarkers, and to communicate these advances within a common framework.

Arthrography↗
PubMed2006

Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) of articular cartilage has evolved to be an important tool in research on cartilage (patho)physiology and osteoarthritis (OA). MRI provides a wealth of novel and quantitative information, but there exists no commonly accepted terminology for reporting these metrics. The objective of this initiative was to propose a nomenclature for definitions and names to be used in scientific communications and to give recommendations as to which minimal methodological information should be provided when reporting MRI-based measures of articular cartilage in OA. METHODS: An international group of experts with direct experience in MRI measurement of cartilage morphology or composition reviewed the existing literature. Through an iterative process that included a meeting with a larger group of scientists and clinicians (December 2nd, 2004, Chicago, IL, USA), they discussed, refined, and proposed a nomenclature for MRI-based measures of articular cartilage in OA. RESULTS: The group proposes a nomenclature that describes: (1) the anatomical location and (2) the structural feature being measured, each name consisting of a metric variable combined with a tissue label. In addition, the group recommends minimal methodological information that should be described. CONCLUSIONS: Utilization of this nomenclature should facilitate communication within the scientific community. Further, the uniform adoption of comprehensive nomenclature to describe quantitative MRI- features of articular cartilage should strengthen epidemiological, clinical, and pharmacological studies in OA.

Cartilage, Articular↗
PubMed2006

MRI and non-cartilaginous structures in knee osteoarthritis.

Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy.

Bone Marrow↗
PubMed2004

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement.

BACKGROUND: In clinical trials, at the group level, results are usually reported as mean and standard deviation of the change in score, which is not meaningful for most readers. OBJECTIVE: To determine the minimal clinically important improvement (MCII) of pain, patient's global assessment of disease activity, and functional impairment in patients with knee and hip osteoarthritis (OA). METHODS: A prospective multicentre 4 week cohort study involving 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. Patients assessed their response to treatment on a five point Likert scale at the final visit. An anchoring method based on the patient's opinion was used. The MCII was estimated in a subgroup of 814 patients (603 with knee OA, 211 with hip OA). RESULTS: For knee and hip OA, MCII for absolute (and relative) changes were, respectively, (a) -19.9 mm (-40.8%) and -15.3 mm (-32.0%) for pain; (b) -18.3 mm (-39.0%) and -15.2 mm (-32.6%) for patient's global assessment; (c) -9.1 (-26.0%) and -7.9 (-21.1%) for WOMAC function subscale score. The MCII is affected by the initial degree of severity of the symptoms but not by age, disease duration, or sex. CONCLUSION: Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients.

Adult↗
PubMed2004

Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state.

BACKGROUND: The patient acceptable symptom state (PASS) is the value beyond which patients can consider themselves well. This concept can help in interpreting results of clinical trials. OBJECTIVE: To determine the PASS estimate for patients with knee and hip osteoarthritis (OA) by assessing pain, patient's global assessment of disease activity, and functional impairment. METHODS: A 4 week prospective multicentre cohort study of 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment of disease, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. The patients assessed their satisfaction with their current state at the final visit. An anchoring method based on the patient's opinion was used. RESULTS: For patients with knee and hip OA, the estimates of PASS were, respectively, 32.3 and 35.0 mm for pain, 32.0 and 34.6 mm for patient global assessment of disease activity, and 31.0 and 34.4 points for WOMAC function score. The PASS varied moderately across the tertiles of baseline scores but not across age, disease duration, or sex. CONCLUSION: The use of PASS in clinical trials would provide more meaningful results expressed as a proportion of patients in an acceptable symptom state.

Adult↗
PubMed2003

An index of the three core data set patient questionnaire measures distinguishes efficacy of active treatment from that of placebo as effectively as the American College of Rheumatology 20% response criteria (ACR20) or the Disease Activity Score (DAS) in a rheumatoid arthritis clinical trial.

OBJECTIVE: To evaluate the capacity of a pooled index of only the 3 patient self-report questionnaire measures among the 7 American College of Rheumatology (ACR) core data set (Core Data Set) measures to distinguish efficacy of active treatment of rheumatoid arthritis (RA) with leflunomide or methotrexate versus placebo in a randomized, controlled clinical trial, and to compare the results with those obtained using the ACR 20% response criteria (ACR20), Disease Activity Score (DAS), and other pooled indices. METHODS: The 7 ACR Core Data Set measures of 1) joint swelling, 2) joint tenderness, 3) physician global assessment, 4) erythrocyte sedimentation rate (ESR), 5) functional disability, 6) pain, and 7) patient global assessment were combined into the following 5 pooled indices: "All Core Data Set" (all 7 measures), "Assessor Only" (measures 1-3), "Assessor + ESR" (measures 1-4), "Patient Only" (measures 5-7), and "Patient + ESR" (measures 4-7). The capacity of each of these 5 indices to detect differences between active treatment and placebo treatment was compared with that of the ACR20 and the DAS using 4 different analytic methods, each of which presented advantages and limitations. Agreement of the indices with one another and with the ACR20 and the DAS was analyzed according to pairwise kappa statistics and Z scores in multivariate logistic regression models. RESULTS: Each of the 5 indices, including "Patient Only," had a similar capacity to detect greater efficacy of leflunomide and methotrexate versus placebo in this clinical trial, according to each of 4 methods, at similar levels of statistical and clinical significance. CONCLUSION: A pooled index of patient self-report questionnaire Core Data Set measures appears to be as informative as ACR20 responses, DAS scores, and pooled indices of all and assessor-derived Core Data Set measures for distinguishing between active treatment and placebo treatment in this RA clinical trial.

Antirheumatic Agents↗
PubMed2002

The contribution of type of daily activity to loading across the hip and knee joints in the elderly.

OBJECTIVE: In the elderly, we evaluated loading across the hip or knee joints during different daily activities. METHODS: Elderly people drawn from the community entering an exercise study underwent a full kinetic and kinematics analysis of five different activities, standing, walking, arising from a chair, going downstairs and bending over. Inverse dynamic equations were used to compute forces and torques across the knees and hips during all of these activities. RESULTS: 132 elderly people, mean age 75, participated. Compressive forces across the knees and hips were, by far, the greatest vector forces and were highest during stair descent and, to a lesser extent, during walking. Compressive forces were lowest during standing. The highest moments were flexion and adduction moments, and these were maximal during stair descent. CONCLUSION: Of the five activities we studied, descending stairs was associated with the highest calculated forces and torques across the knees and hips, and that may account for its tendency to cause joint symptoms and for its possible association with osteoarthritis incidence.

Activities of Daily Living↗
PubMed2002

Unwillingness of rheumatoid arthritis patients to risk adverse effects.

OBJECTIVE: To evaluate patient willingness to accept the risk of adverse effects (AEs) commonly associated with arthritis medications. METHODS: Rheumatoid arthritis patients were asked to rate their willingness to take a medication associated with 17 specific AEs using a visual analogue scale. RESULTS: We interviewed 100 patients. Eighty-one were currently using one or more disease-modifying anti-rheumatic drugs (DMARDs) and 29 had previously experienced AEs related to DMARDs. Seventy-five stated that they were doing very well or well with respect to their arthritis compared with other people their age. Thirty-five per cent of those interviewed were unwilling to accept the risk of cosmetic changes, 38% were unwilling to accept the risk of temporary discomfort and 45% were unwilling to accept the risk of major toxicity. Patients who had previously experienced AEs were more willing to accept the risk of cosmetic changes (83 vs. 58%, P=0.02), temporary discomfort (79 vs. 55%, P=0.02) and major toxicity (83 vs. 44%, P=0.001) compared with those who had not previously experienced AEs. CONCLUSIONS: Many rheumatoid arthritis patients are very concerned about potential drug toxicity. However, risk adversity appeared to be attenuated by past experience with AEs. Our results suggest that certain patients, especially those with milder disease activity, might be reluctant to accept commonly used arthritis medications if they are fully informed of their potential toxicity.

Adult↗
PubMed2001

Preference for disclosure of information among patients with rheumatoid arthritis.

OBJECTIVE: To quantify preference for disclosure of information among patients with rheumatoid arthritis (RA) and to examine sex-specific correlates of information preference. METHODS: We interviewed patients with RA and assessed preference for disclosure of information using 4 questions from the previously validated "Information Preference Seeking Scale." Three questions addressed preference for disclosure of side effects and 1 question addressed preference for disclosure of therapeutic options. Associations between preference for information and patient characteristics were examined using stepwise multiple linear regression. RESULTS: One hundred RA patients (mean age 68+/-12 years; 73% female) were interviewed; 89 respondents agreed or strongly agreed with all 4 statements reflecting a preference for full disclosure, and an additional 8 respondents agreed or strongly agreed with 3 of the 4 statements. The mean score (+/- SD) for information preference was 86+/-13, on a scale from 0 to 100 where 100 reflected a strong preference for full disclosure. In bivariate analyses, female sex and current employment were associated with stronger preferences for being informed (mean score for women 88+/-11, for men 80+/-15 [P = 0.02]; for employed 92+/-11, for unemployed 84+/-13 [P = 0.04]). Multivariate sex-specific analyses demonstrated that current employment and higher education level were positively associated with preference for disclosure among women and men, respectively. CONCLUSION: The results of our survey suggest that RA patients want to be fully informed about the risks associated with medications and about alternative options. The challenge remaining for rheumatologists is how to effectively communicate the risks and benefits related to the many options that are currently available for RA patients.

Adult↗
PubMed2000

Immunoadsorption for the treatment of rheumatoid arthritis: final results of a randomized trial. Prosorba Trial Investigators.

A double-blind, randomized, placebo controlled study was conducted to determine the efficacy of a promising immunoadsorption treatment device containing staphylococcal protein A (Prosorba Immunoadsorption Column, Cypress Bioscience, Inc., San Diego, CA, U.S.A.) in patients with refractory rheumatoid arthritis (RA). Eligibility criteria required adult RA patients who had failed either methotrexate or 2 other disease modifying antirheumatic drugs (DMARD) and who had predefined active disease. All disease-modifying agents were discontinued at least 30 days prior to entry. Patients received 12 weekly procedures after being randomized to the active treatment arm or to the sham treatment arm (apheresis only). Evaluations were double-blinded and occurred at baseline and periodically for 24 weeks thereafter. Primary efficacy was assessed at 7 and 8 weeks after the completion of 12 treatments (at trial Weeks 19 and 20) using the American College of Rheumatology (ACR) definition of improvement (1,2), and results from the assessments at Weeks 19 and 20 were averaged. Ninety-nine randomized patients had a mean disease duration of 15.4 years and received an average of greater than 5 DMARD regimens prior to entry. Analysis of patients who completed all treatments and follow-up indicated that 15 of 36 (41.7%) column-treated patients responded compared to 5 of 32 (15.6%) sham-treated patients (p < or = 0.003). Intent to treat analysis of all patients who were randomized in the study indicated 15 of 52 (28.9%) column-treated patients responded compared to only 5 of 47 (10.6%) patients who received sham treatments (p = .005). Common adverse events (AEs) included joint pain, fatigue, joint swelling, and hypotension. Central line usage was clearly associated with significant AEs during this trial and is not recommended. Hemoglobin, hematocrit, and mean corpuscular volume values decreased similarly in both treatment arms, attributed to phlebotomy for laboratory and scientific studies and to small, repetitive (normal) apheresis losses. Other AEs such as nausea, rash, pruritus, flushing, and fever occurred in 1 to 6% of treatments in each arm (NS). There was no significant increase in AEs in column-treated patients compared to sham-treated patients. Protein A immunoadsorption was proven to be a new therapeutic alternative in patients with severe, refractory disease.

Adult↗
PubMed1999

Meniscal subluxation: association with osteoarthritis and joint space narrowing.

OBJECTIVE: Since complete meniscectomy leads to knee OA, we investigated the potential links among meniscal subluxation, joint space narrowing and symptomatic OA. MATERIALS AND METHODS: 233 cases with symptomatic knee OA and 58 asymptomatic controls underwent radiography and MR imaging of the knee. Joint space narrowing was measured on weight-bearing PA fluoroscopy-positioned radiographs. The amount of medial or lateral meniscal subluxation was measured on coronal MR images. The prevalence and severity of meniscal subluxation was compared in cases and controls. We evaluated the correlation of the degree of meniscal subluxation with joint space narrowing, Kellgren and Lawrence grade, and two major risk factors for the development of OA, age and weight. RESULTS: Cases had more medial and lateral subluxation than controls. Mean medial meniscal subluxation was 5.1 mm in cases and 2.8 mm in controls (P=0.001). Modest degrees of meniscal subluxation were common in both cases and controls: 81% of cases and 64% of controls had >/=3 mm of subluxation; age and gender adjusted (P=0.006). Severe degrees of subluxation were almost unique to OA cases (e.g. prevalence of >/=7 mm, 35% cases vs. 7% controls, P< 0.001). Among controls, severe degrees of subluxation were present only in those with radiographic joint space narrowing (defined as >/=grade 1 narrowing on a 0-3 scale). In cases, there was a strong correlation between the degree of medial meniscal subluxation and the severity of medial joint space narrowing (r=0.56, P=0.0001). Similar results were present in the lateral compartment. Meniscal subluxation did not correlate with age or weight. CONCLUSION: Meniscal subluxation is highly associated with symptomatic knee OA. In subjects with osteoarthritis, increasing meniscal subluxation on MR correlates with the severity of joint space narrowing.

Adult↗
PubMed1999

Imaging in rheumatoid arthritis: results of group discussions.

None of the current scoring methods for radiological damage in rheumatoid arthritis (RA) is ideal. The objective for RA imaging at OMERACT IV was to start discussion about the problems and applicability of the current scoring methods for radiological damage and to start discussion on the challenge of new imaging techniques. The RA imaging module comprised preconference reading material, plenary sessions, small group discussions, and a plenary report of the group sessions, combined with interactive voting. The OMERACT filter guided the discussions. Priorities for further research in imaging studies were: (1) pathologies versus features on radiographs; (2) relation with longterm outcome; and (3) definition of minimum clinically important difference.

Arthritis, Rheumatoid↗
PubMed1998

The use of radiographs to evaluate shoulder pain in the ED.

This study was conducted to describe the utilization of plain radiography in the initial evaluation of shoulder pain in the emergency department (ED) and assess the feasibility of developing guidelines for the selective use of shoulder radiographs by determining whether clinical variables are able to discriminate between subjects having therapeutically informative versus uninformative X-rays. The study was a chart review of all adult ED patients presenting to the Boston University Medical Center Hospital (Boston, MA) between January 1994 and January 1996 with a chief complaint that included shoulder pain. Subjects with X-rays were classified into two groups, those with therapeutically informative X-rays (ie, identified conditions requiring specific therapy) and those with therapeutically uninformative X-rays (ie, did not result in specific therapy). Recursive partitioning techniques were then used to identify clinical variables that best distinguished between therapeutically informative and uninformative radiographs. Three hundred twelve patients were included in the analysis, of whom 185 (59%) had shoulder X-rays performed. Thirty-seven (20%) radiographs were therapeutically informative, including 13 glenohumeral dislocations, 3 acromioclavicular joint separations, and 21 fractures. Deformity present on shoulder examination was the strongest discriminating variable and correctly classified 21 of 23 subjects as having informative X-rays. Of the remaining patients (n = 162), only those older than 43.5 years with a history of a precipitating fall (n = 40) had a high likelihood of having therapeutically informative X-rays. No patients without a deformity or precipitating fall (n = 90) had an informative X-ray. These data show that X-rays for the initial evaluation of shoulder pain in the ED are overutilized. This preliminary model suggests that clinical variables are able to distinguish between patients with informative versus uninformative X-rays. Prospective studies are needed to derive valid decision rules for selective use of shoulder radiographs in the ED.

Adolescent↗
PubMed1996

Are risk factors for patellofemoral and tibiofemoral knee osteoarthritis different?

OBJECTIVE: To determine whether patellofemoral (PF), tibiofemoral (TF), and combined patterns of knee osteoarthritis (OA) differ in their strengths of associations with any of the known risk factors for knee OA, and especially to evaluate whether body mass index (BMI) correlates with all 3 patterns, or only with tibiofemoral disease, as previously suggested. METHODS: We obtained anteroposterior and lateral knee radiographs on 608 participants at the 22nd biennial examination of the Framingham cohort study (1992-3). The presence or absence of OA in the TF and PF compartments of each knee was scored, and subjects were classified on the basis of the pattern of compartmental involvement in their 2 knees. The strength of association of age, sex, BMI, chondrocalcinosis, and knee injury was computed for PF, TF, and combined pattern of knee OA using multiple logistic regression. RESULTS: The mean age and BMI of the sample were 80.7 yrs (SD 5.0) and 25.4.kg-2 (SD 3.7), respectively. PF, TF, and combined patterns of knee OA were present in 5.3, 23.0 and 19.7%, respectively. Elevated BMI was a risk factor for all 3 patterns of disease (adjusted OR for highest vs lowest tertile of BMI 3.7, 1.9, and 7.0 for PF, TF, and combined pattern, respectively). Risk factor profiles were broadly similar for TF and PF OA, with the possible exception of knee injury in men (adjusted OR = 2.0 for PF, 3.7 for TF OA). Risk factors were generally more strongly associated with the combined pattern of OA. CONCLUSION: Obesity is an important risk factor for PF, TF, and combined patterns of knee OA. The relationships of these patterns with the risk factors investigated here appear similar and are strongest for the combined pattern.

Aged↗
PubMed1995

Health status instruments / utilities.

Rheumatologists and other interested professionals at the OMERACT II conference formed small groups to discuss whether it was sensible to use a generic health status instrument in musculoskeletal disease trials. These instruments promise the possibility of comparison of health status between disease states. However, data is lacking on validity of the current generation of instruments to support their use. Participants had little personal experience with these instruments. After inspection, many voiced strong concerns over comprehensiveness and responsiveness. Many dimensions of health relevant for patients with this group of diseases were felt to be underrepresented. The dimension of adverse effects was universally absent, although this is more a problem of state of the art in trial methodology than a problem of these measures. Although there is little data, the small number of response categories in the dimensions covered, plus the lack of comprehensiveness, make it likely that responsiveness will be low. Further research, especially the adoption of one or more generic measures alongside specific measures, both in trials and in observational studies, is necessary to validate and improve the current generic measures. Until that time, valid conclusions and health policy regarding musculoskeletal diseases cannot be based on generic measures of health status.

Health Status↗
PubMed1994

The overall and temporal association of cancer with polymyositis and dermatomyositis.

OBJECTIVE: To summarize the association of cancer with adult polymyositis (PM) and dermatomyositis (DM) and to test whether myositis precedes or follows cancer diagnosis, with the latter suggesting that myositis is paraneoplastic. METHODS: Using primary patient data, we performed an analysis of all published case control and cohort studies evaluating the association of myositis and malignancy. We evaluated the overall association of cancer within 10 years of myositis diagnosis and separately assessed cancer occurrence in periods 5 years before and 5 years after myositis diagnosis. RESULTS: Four case control or cohort studies met inclusion criteria providing 1078 myositis cases (565 PM and 513 DM) with a comparable number of controls. One hundred fifty-three myositis patients had cancer within 10 years of diagnosis. Despite reports of no myositis association with cancer, each study's data suggested an association of both PM and DM with cancer. Overall odds ratio (OR) for the association of cancer with DM = 4.4 (9.5% CI 3.0, 6.6) and for PM, OR = 2.1 (95% CI 1.4, 3.3). Cancer risk was high both before and after DM diagnosis, but for PM, cancer risk was increased only after myositis diagnosis. CONCLUSION: DM is associated with cancer, and our results suggest that DM is often paraneoplastic. The high rate of malignancy only after PM diagnosis is consistent with cancer detection bias, but may suggest joint susceptibility of affected individuals to both cancer and myositis.

Case-Control Studies↗
PubMed1987

Lack of amyloid in abdominal fat aspirates from patients undergoing long-term hemodialysis.

Recent reports describe the carpal tunnel syndrome (CTS) due to amyloid infiltration of the beta 2 microglobulin protein as a frequent complication of long-term hemodialysis. Carpal synovial and cystic bone lesion amyloid deposits have been reported; however, the extent of systemic amyloid deposition has not been determined. We examined 30 patients undergoing long-term hemodialysis for CTS and performed abdominal fat tissue aspiration for amyloid staining to evaluate the presence of systemic amyloid disease. In this group, CTS was frequent (37%) and its prevalence correlated with the duration of hemodialysis. In all patients, the abdominal fat tissue, stained with Congo red, was negative for amyloid deposits. These results confirm that CTS is a frequent complication of long-term hemodialysis; however, in this study, no detectable amyloid deposits were found in abdominal subcutaneous fat tissue. Thus, abdominal fat aspiration may not be a reliable screening test for hemodialysis-associated amyloidosis.

Abdomen↗