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Biomedical subjects

Jean-Pierre Raynauld

Publications and source records attributed to Jean-Pierre Raynauld.

12 recordsLinked to original sources
PubMed2006

BLISS index for analyzing knee osteoarthritis trials data.

OBJECTIVES: Different pain thresholds were investigated, using the WOMAC Pain Scale (WOMAC-P) to determine if they could differentiate between treatment groups (hylan G-F 20 vs. appropriate care) at low and very low levels of state attainment in patients with knee osteoarthritis (OA). A method, termed the BLISS (Bellamy et al. Low Intensity Symptom State-attainment) Index, for analyzing OA knee clinical trials data, was proposed. STUDY DESIGN AND SETTING: Five analyses were performed: time to first BLISS day, BLISS days over 12 months, patients with a BLISS response at month 12, patients with a BLISS response at any time, and number of BLISS periods over 12 months. For each analysis, five levels of WOMAC-P were examined: <or=5 normalized units (NU), <or=10, <or=15, <or=20, and <or=25 (higher=more pain). RESULTS: More patients in the hylan G-F 20 group achieved BLISS states in all five analyses. These differences were statistically significant for all pain threshold levels except <or=5 NU. CONCLUSION: Five methods of measuring BLISS attainment using four prespecified threshold levels of pain were able to statistically discriminate between treatment groups. This method may potentially provide an approach, to defining which patients not only improve but also achieve a good state of health, at low and very low levels of pain intensity. BLISS-10 is a therapeutically attainable very low symptom state at which clinically important, statistically significant between-group differences are detectable, and therefore may provide a benchmark against which therapeutic interventions can be assessed. However, the value to patients, of this and other low and very low intensity pain states, requires further elaboration.

Biocompatible Materials↗
PubMed2006

Most recent developments in strategies to reduce the progression of structural changes in osteoarthritis: today and tomorrow.

Osteoarthritis (OA), the most common of all arthritic conditions, is a social and financial burden to all nations. The most recent research has significantly advanced our understanding of the cause of OA and risk factors associated with it. These findings have provided useful information that has helped in the daily management of patients with OA. Some preventative measures and a number of therapeutic agents and drugs are available, which may help to reduce the progression of OA in certain patients. Moreover, the most recent progress in research has significantly enhanced our knowledge of the factors involved in the development of the disease and of the mechanisms responsible for its progression. This has allowed identification of several new therapeutic targets in a number of pathophysiological pathways. Consequently, the field is opening up to a new era in which drugs and agents that can specifically block important mechanisms responsible for the structural changes that occur in OA can be brought into development and eventually into clinical trials.

Antirheumatic Agents↗
PubMed2006

Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study.

OBJECTIVE: Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA. METHODS: The study group comprised 2,483 patients with medial compartment knee OA and 2-4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression. RESULTS: A reduction of approximately 20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of >or=0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo. CONCLUSION: Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.

Adult↗
PubMed2005

Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes.

The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 +/- 3.0% for global cartilage and -5.5 +/- 4.3% for the medial compartment at 12 months, and -5.7 +/- 4.4% and -8.3 +/- 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression.

Aged↗
PubMed2005

The effectiveness of hylan G-F 20 in patients with knee osteoarthritis: an application of two sets of response criteria developed by the OARSI and one set developed by OMERACT-OARSI.

OBJECTIVE: Secondary analyses of a previously conducted 1-year randomized controlled trial were performed to assess the application of responder criteria in patients with knee osteoarthritis (OA) using different sets of responder criteria developed by the Osteoarthritis Research Society International (OARSI) (Propositions A and B) for intra-articular drugs and Outcome Measures in Arthritis Clinical Trials (OMERACT)-OARSI (Proposition D). METHODS: Two hundred fifty-five patients with knee OA were randomized to "appropriate care with hylan G-F 20" (AC+H) or "appropriate care without hylan G-F 20" (AC). A patient was defined as a responder at month 12 based on change in Western Ontario and McMaster Universities Osteoarthritis Index pain and function (0-100 normalized scale) and patient global assessment of OA in the study knee (at least one-category improvement in very poor, poor, fair, good and very good). All propositions incorporate both minimum relative and absolute changes. RESULTS: Results demonstrated that statistically significant differences in responders between treatment groups, in favor of hylan G-F 20, were detected for Proposition A (AC+H=53.5%, AC=25.2%), Proposition B (AC+H=56.7%, AC=32.3%) and Proposition D (AC+H=66.9%, AC=42.5%). The highest effectiveness in both treatment groups was observed with Proposition D, whereas Proposition A resulted in the lowest effectiveness in both treatment groups. The treatment group differences always exceeded the required 20% minimum clinically important difference between groups established a priori, and were 28.3%, 24.4% and 24.4% for Propositions A, B and D, respectively. CONCLUSION: This analysis provides evidence for the capacity of OARSI and OMERACT-OARSI responder criteria to detect clinically important statistically detectable differences between treatment groups.

Analgesics↗
PubMed2004

Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes.

OBJECTIVE: To evaluate the change in osteoarthritic (OA) knee cartilage volume over a two-year period with the use of magnetic resonance imaging (MRI) and to correlate the MRI changes with radiologic changes. METHODS: Thirty-two patients with symptomatic knee OA underwent MRI of the knee at baseline and at 6, 12, 18, and 24 months. Loss of cartilage volumes were computed and contrasted with changes in clinical variables for OA and with standardized semiflexed knee radiographs at baseline at 1 and 2 years. RESULTS: Progression of cartilage loss at all followup points was statistically significant (P < 0.0001), with a mean +/- SD of 3.8 +/- 5.1% for global cartilage loss and 4.3 +/- 6.5% for medial compartment cartilage loss at 6 months, 3.6 +/- 5.1% and 4.2 +/- 7.5% at 12 months, and 6.1 +/- 7.2% and 7.6 +/- 8.6% at 24 months. Discriminant function analysis identified 2 groups of patients, those who progressed slowly (<2% of global cartilage loss; n = 21) and those who progressed rapidly (>15% of global cartilage loss; n = 11) over the 2 years of study. At baseline, there was a greater proportion of women (P = 0.001), a lower range of motion (P = 0.01), a greater circumference and higher level of pain (P = 0.05) and stiffness in the study knee, and a higher body mass index in the fast progressor group compared with the slow progressor group. No statistical correlation between loss of cartilage volume and radiographic changes was seen. CONCLUSION: Quantitative MRI can measure the progression of knee OA precisely and can help to identify patients with rapidly progressing disease. These findings indicate that MRI could be helpful in assessing the effects of treatment with structure-modifying agents in OA.

Arthrography↗
PubMed2003

Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the safety and efficacy of long-term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA). METHODS: In a randomized, double-blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50-foot walking time. Clinical symptoms were assessed just before each injection. RESULTS: At the 1-year and 2-year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid-injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline-injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05). CONCLUSION: Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long-term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.

Adult↗
PubMed2003

Quantitative magnetic resonance imaging of articular cartilage in knee osteoarthritis.

PURPOSE OF REVIEW: Attempts to evaluate knee cartilage damage and progression seem logical in osteoarthritis research. Magnetic resonance imaging allows for precise visualization of joint structures such as cartilage, bone, synovial tissues, ligaments and menisci, and their pathologic changes. RECENT FINDINGS: Recent advances in magnetic resonance technology have enabled researchers to evaluate cartilage damage and progression over the cross-sectional and longitudinal planes. Although anatomic changes can be seen, for many years the quantification of the cartilage changes has been the real challenge. Quantitative assessment of cartilage morphology using magnetic resonance imaging with fat-suppressed gradient echo sequences and digital postprocessing techniques provides high accuracy and adequate precision for cross-sectional and longitudinal studies in osteoarthritis patients. Recent data on precision, reliability, and sensitivity to change of quantitative parameters of cartilage morphology in osteoarthritis are presented in this review. Longitudinal studies currently available suggest that changes of cartilage volume, potentially as much as 5% per year, occur in osteoarthritis in most knee compartments, exceeding the variability of these measurements. SUMMARY: Magnetic resonance imaging provides reliable and quantitative data on cartilage status throughout all compartments of the knee, and robust acquisition protocols for multicenter trials are now available. Magnetic resonance imaging technology should hopefully reduce the number of patients needed in clinical trials, improve retention of these patients, and reduce the overall costs and the length of clinical trials of treatment response to disease-modifying osteoarthritis drugs.

Cartilage, Articular↗
PubMed2003

Computer-aided method for quantification of cartilage thickness and volume changes using MRI: validation study using a synthetic model.

The primary objective of this study was to develop a computer-aided method for the quantification of three-dimensional (3-D) cartilage changes over time in knees with osteoarthritis (OA). We introduced a local coordinate system (LCS) for the femoral and tibial cartilage boundaries that provides a standardized representation of cartilage geometry, thickness, and volume. The LCS can be registered in different data sets from the same patient so that results can be directly compared. Cartilage boundaries are segmented from 3-D magnetic resonance (MR) slices with a semi-automated method and transformed into offset-maps, defined by the LCS. Volumes and thickness are computed from these offset-maps. Further anatomical labeling allows focal volumes to be evaluated in predefined subregions. The accuracy of the automated behavior of the method was assessed, without any human intervention, using realistic, synthetic 3-D MR images of a human knee. The error in thickness evaluation is lower than 0.12 mm for the tibia and femur. Cartilage volumes in anatomical subregions show a coefficient of variation ranging from 0.11% to 0.32%. This method improves noninvasive 3-D analysis of cartilage thickness and volume and is well suited for in vivo follow-up clinical studies of OA knees.

Algorithms↗