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M Dougados

Publications and source records attributed to M Dougados.

At least 109 records · Page 6Linked to original sources

Diacerein as a disease-modulating agent in osteoarthritis.

This paper reviews the most recent clinical and experimental studies on diacerein, both of which are under investigation. Diacerein could be a disease-modulating agent in osteoarthritis because structural benefits have been reported in recent trials. Moreover, after an empirical use, studies return to the experimental field to understand the mechanism of action of this molecule. However, clinical trials using new sets of criteria could be conducted to estimate the structural modulating effect of diacerein; experimental studies must be performed to understand this effect.

Animals↗

Variability in urinary excretion of bone resorption markers: limitations of a single determination in clinical practice.

In this study we assessed the within and between-subject variability of the concentrations of two urinary markers, free deoxypyridinoline (DPD) and C telopeptide (CTX-I), in healthy patients with the aim of setting reliable thresholds to enable physicians to take decisions about individual patients with confidence.Between-subject variability for the women was 25.4% for DPD and 38.2% for CTX-I, and for the men was 12.9% for DPD and 23.8% for CTX-I. The coefficients of variation were similar for daily, weekly and monthly determinations, giving means of 13.8 and 28.1% for DPD and CTX-I respectively. Critical difference (CD) was lower for DPD than for CTX-I (about 44 and 80% respectively). The number of samples required to determine the true mean with a CD at the 5% level was 29 for DPD and more than 113 for CTX-I.DPD was the least biologically variable. One determination was not sufficient to determine bone resorption status and a 44% decrease in DPD levels and an 80% decrease in CTX-I levels were required to demonstrate the efficacy of antiresorptive therapy in individual patients.

Adult↗

EULAR recommendations for the management of knee osteoarthritis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials.

UNLABELLED: A task force for the EULAR standing committee for clinical trials determined the methodological and logistical approach required for the development of evidence-based guidelines for treatment of knee osteoarthirits (OA). METHODS: The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the databases of all European-language publications. All of the relevant studies were quality scored. The third stage involved determination of key clinical propositions by expert consensus employing a Delphi approach. The final stage involved ranking of these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus. RESULTS: Seven hundred and forty-four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. CONCLUSIONS: These are the first clinical guidelines on knee OA to combine an evidence-based approach and a consensus approach across a wide range of treatment modalities. It is apparent that only certain clinical propositions are supported by substantial research-based evidence. There is thus an urgent need for future well-designed trials to address key clinical questions.

Adult↗

Treatment of spondyloarthropathies. Recent advances and prospects in 2001.

The management of patients with spondyloarthropathy is undergoing radical changes in several areas and for several reasons. The main reason seems to be improved awareness of the fairly high prevalence of this group of disorders, which is close to that of rheumatoid arthritis. Evaluation of the various treatment modalities has benefited from work by the international Assessment in Ankylosing Spondylitis group (ASAS) group aimed at developing standardized evaluation criteria. Controlled treatment trials have provided useful information on non-pharmacological treatments such as physical exercise programs and patient information. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of the pharmacological treatment. Recent studies have shown that NSAIDs capable of selectively inhibiting type 2 cyclooxygenase have a better gastrointestinal safety profile and are as effective in relieving clinical symptoms as conventional NSAIDs. Importantly, maintenance treatment seems effective not only on peripheral joint manifestations but also on axial manifestations that fail to respond to NSAIDs. Thalidomide and TNF antagonists are promising maintenance agents.

Anti-Inflammatory Agents, Non-Steroidal↗

Evidence-based management of osteoarthritis: practical issues relating to the data.

Osteoarthritis (OA) is a major cause of pain and disability in the elderly. The perspective of OA as a dynamic process triggered by diverse insults is increasingly accepted. Objectives of management are patient education, relief of pain, optimization of function and modification of the OA process. Management should be individualized and should take into account factors relating to the person as well as the OA joint. There is a reasonable evidence base for several key elements of management. Recent review of the research evidence shows a skewed distribution in favour of drugs, particularly NSAIDs, and important gaps in clinically relevant knowledge. The restricted generalizability of the research data could be improved by improvements in study design and methods of reporting. Current published guidelines on management of OA are critically reviewed and compared.

Activities of Daily Living↗

Pharmacological therapy of osteoarthritis.

In 2000, both the American College of Rheumatology (ACR) and the European League of Associations of Rheumatology (EULAR) published recommendations for the use of pharmacological therapy in the treatment of patients with lower limb osteoarthritis. These recommendations are based on the level of evidence observed in systematic reviews and/or meta-analyses of published randomized controlled trials as well as expert opinion. Acetaminophen (paracetamol) is considered as first-line oral therapy for symptomatic lower limb osteoarthritis with mild to moderate pain because it is more efficacious than placebo and is generally considered to be safe and well tolerated. Data obtained in recent trials and the results of a meta-analysis, however, show that acetaminophen is not as efficacious as non-steroidal anti-inflammatory drugs (NSAIDs) for pain at rest and pain on motion. Furthermore, data from a recent epidemiological study suggest that use of high-dose acetaminophen (>2 g/day) may convey the same magnitude of increased risk for serious upper gastrointestinal adverse events as NSAIDs.NSAIDs have demonstrated efficacy superior to placebo in patients with osteoarthritis. The newer cyclo-oxygenase (COX)-2-specific inhibitors (coxibs) have comparable efficacy to traditional dual inhibitor NSAIDs and have demonstrated a better gastrointestinal safety profile. Thus, for patients who have severe pain and/or signs of inflammation or who have failed to respond to acetaminophen, the use of a coxib should be considered, especially if the patient is at increased risk for serious upper gastrointestinal adverse events from a traditional NSAID.Compounds different from pure analgesics and NSAIDs are also used for the management of patients with osteoarthritis. Recent clinical trials have demonstrated statistically significant efficacy of such compounds (e.g. chondroitin sulphate, diacerhein, glucosamine sulphate) with the following characteristics: (1) the effect size seems to be of slightly lower magnitude than that seen for NSAIDs; (2) the onset of action is delayed for approximately 4 to 6 weeks; and (3) the symptomatic effect is maintained after stopping the treatment for periods of 4 to 8 weeks.The methodology for evaluating the possible structure-modifying effect of drugs has dramatically improved during the past decade. Two agents have demonstrated a beneficial structural effect: glucosamine sulphate in osteoarthritis of the knee, and diacerhein in osteoarthritis of the hip. The clinical relevance of such an effect needs to be further evaluated in long-term outcome studies.

Acetaminophen↗

Measurement of the radiological hip joint space width. An evaluation of various methods of measurement.

OBJECTIVE: To determine the most relevant method of measurement of the radiographic hip joint space width (JSW). DESIGN: Seventy hips were examined from 36 patients of the ECHODIAH study having had one to four X-rays of the pelvis during the 3-year course of the study. Minimum interbone distance (MIDc), mean width of both the whole joint space (MJSWL) and a region of interest of the joint space (MJSWroi) were measured using computerized analysis of digitized radiographs. MID was also measured using a graduated eyepiece (MIDge). Reproducibility of the measurement was assessed by the intraclass coefficient of correlation. Sensitivity to change was evaluated by the standardized response mean. RESULTS: The intraobserver intraclass coefficient of correlation of MIDc and MJSWroi was 0.98 and 0.94, respectively. The mean value degrees S.D. of MJSWL, MJSWroi, MIDc and MIDge was 3.3 degrees 0.9, 2.6 degrees 0.9, 2.4 degrees 0.9 and 2.6 degrees 1.2 mm, respectively. MIDge was significantly larger than MIDc (mean difference: 0.21 degrees 0.62 mm, P<0.001), in both normal and osteoarthritic hips. However, the difference between MIDge and MIDc varied largely when considering topography of femoral head migration. Whatever the method was, a significant (P<0.001) mean decrease of nearly 0.5 mm was found in osteoarthritic hips over the 3 year follow-up. The standardized response mean for MJSWL, MJSWroi, MIDge and MIDc was 0.73, 0.75, 0.79 and 0.85, respectively. Superiority of MIDc, in term of sensitivity to change, was mainly seen in osteoarthritic hips showing a superomedial or a concentric migration of the femoral head. CONCLUSION: Minimum interbone distance measured with a computer assisted method is suggested as the most suitable method for the evaluation of hip osteoarthritis (OA) progression.

Female↗

Laterally elevated wedged insoles in the treatment of medial knee osteoarthritis: a prospective randomized controlled study.

OBJECTIVE: To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles (used as control) in patients with medial femoro-tibial knee osteoarthritis (OA). DESIGN: 6-month prospective randomized controlled study. PATIENTS: outpatients with painful medial femoro-tibial knee OA. OUTCOME MEASURES: patient's overall assessment of disease activity (5 grade scale), WOMAC index subscales and concomitant treatments. STATISTICAL ANALYSIS: Performed as an intention-to-treat analysis. Main criterion: improvement in the patient's assessment of activity (defined as a reduction of 1 grade or more at month 6 compared to baseline, and no intraarticular injection or lavage during the study). Secondary criteria for assessment: (a) improvement in the patient's assessment of activity at months 1 and 3 compared to baseline, (b) improvement in the WOMAC subscales at months 1, 3 and 6, compared to baseline (defined as an improvement of at least 30%, and no intraarticular injection or lavage during the study) and (c) concomitant therapies (analgesics and NSAIDs). RESULTS: The baseline characteristics of the 156 recruited patients (41 males, 115 females, mean age 64.8 years) were not different in the two treatment groups. At months 1, 3 and 6 the percentages of patients with improvement in assessment of disease activity, in WOMAC pain, joint stiffness, and physical functioning subscales were similar in the two groups. The number of days with NSAIDs intake during the previous 3 months was decreased at month 6 compared with baseline in the group furnished with laterally wedged insoles (14.1 days+/-28 vs 9.9 days+/-27, P=0.04, Wilcoxon paired test), while it remained unchanged in the other group (15.5 days+/-24 vs 15+/-28, P=0.56). Compliance and tolerance were satisfactory. Compliance was different between the two groups at month 6, with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group (87.8% vs 74.3%;P=0.032). CONCLUSION: This study failed to demonstrate a relevant short-term symptomatic effect of laterally-wedged insoles in medial femoro-tibial OA. However, the decrease in NSAIDs consumption together with better compliance in the treated group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA.

Aged↗

Use of longitudinal data analysis in the determination of a global score for total hip replacement indication in osteoarthritis patients.

BACKGROUND: A composite index would help in medical practice for considering total hip replacement (THR) in hip osteoarthritis. In association with other parameters, such as age or general status, this index could serve to objectively determine the time to THR surgery, and might be used as an outcome measure in therapeutic trials. The objective of this study was to propose such an index, taking into account symptomatic, structural and therapeutic variables, and impact on lifestyle. METHODS: A curve-fitting procedure and a marginal model were used to highlight the average change in the variables over time. A discrete Cox model, with time-dependent covariates. was then performed to study the association between the variables and hip surgery, leading to the construction of a composite index. RESULTS: The smoothing and fitting analysis suggested takes into account not only the variables, but also the changes in their values during the preceding year, when studying the association between variables and hip surgery. Five covariates were retained in the Cox model, among them only one concerns the changes during the preceding year, showing that the values of the covariates are more important that their changes during the preceding year for THR indication. The coefficients of the model were transformed into new coefficients, so that their sum provided a severity score with individual values 0-100. DISCUSSION: Based on the values of reliable variables recorded during the four last visits, this score can be regarded as a valid index able to objectively help with THR indications. This score might also be used as an outcome measure in therapeutic trials.

Aged↗

Measurement of joint space width in hip osteoarthritis: influence of joint positioning and radiographic procedure.

OBJECTIVES: We assessed the influence of patient positioning and radiographic procedure, and defined a smallest detectable difference (SDD) in hip osteoarthritis (OA). METHODS: OA hip patients each had a standardized pelvic radiograph and, 5 min later, a modified pelvic radiograph with the feet internally rotated 5 degrees (part 1 of the study), the X-ray beam centred on the umbilicus (part 2), or another standardized pelvic radiograph (part 3). RESULTS: Corresponding mean differences in joint space width (JSW) measurements (limits of agreement) between views were +0.03 (-0.53 to +0.59), -0.31 (-1.15 to +0.53) and -0.02 (-0.48 to +0.44) mm. The two views differed significantly in mean JSW in part 2 of the study (P=1.6x10(-4)), but not in part 1 (P=0.375) and part 3 (P=0.580). The SDD estimate was 0.46 mm. CONCLUSIONS: Modifying the X-ray beam and foot rotation increases variability in JSW measurements. Use of urograms to evaluate radiological progression should be avoided. A change greater than 0.46 mm could define radiological hip OA progression.

Aged↗

Ultrasonic backscatter and transmission parameters at the os calcis in postmenopausal osteoporosis.

Ultrasound technology has emerged as a new tool in the assessment of osteoporosis. Ultrasound parameters usually are measured in transmission; there is a potential for the analysis of backscattered signals to provide information on bone microarchitecture. The aim of this study was to explore a new technological development of the method, adding backscatter coefficient to transmission parameters, and to examine the appropriate thresholds to identify postmenopausal osteoporotic women. We examined 210 postmenopausal women (including 60 with osteoporotic fractures) and 30 healthy premenopausal controls. They had lumbar spine and hip bone mineral density (BMD) measurement and quantitative ultrasound (QUS) evaluation at the os calcis, measured in transmission (broadband ultrasound attenuation [BUA], speed of sound [SOS], ratio of transit time [dt] to BUA [dt/BUA], and "strength" index [STI]) and reflexion (broadband ultrasound backscattering [BUB]). The standardized CVs (sCVs) were between 2.27 % and 3.40 % for QUS measured in transmission and 4.41% for BUB. The odds ratio (OR) for fracture discrimination adjusted for age was 2.77 for hip BMD and between 1.6 and 2.9 for QUS. After adjustment for hip BMD, ORs were still highly significant for SOS, STI, and dt/BUA. According to hip BMD T score, prevalence of osteoporosis in our population was 39%. To detect the same prevalence, T scores ranged between -0.95 and -1.42 for QUS. QUS parameters have adequate ability to discriminate osteoporotic patients from controls. The World Health Organization (WHO) threshold for diagnosis of osteoporosis does not apply to this technology. The clinical utility of BUB at the os calcis, in addition to usual ultrasound parameters, is not yet proven. However, BUB evaluation, which does not require two transducers and may be implemented in conventional reflection mode systems, warrants further studies.

Aging↗

Tumour necrosis factor-alpha blockers in rheumatoid arthritis: review of the clinical experience.

Tumour necrosis factor (TNF)-alpha has been found to play a central role in the pathogenesis of rheumatoid arthritis, leading to development of novel drug therapies that neutralise the deleterious effects of this cytokine. This new concept of immunobiological treatment of rheumatoid arthritis has yielded successful results. Although the 2 currently available TNFalpha blockers, infliximab and etanercept, differ in structure, mechanism of action and pharmacokinetics, they have provided similar benefits both in clinical improvement and in slowing and even arresting the progression of radiographic damage. This therapeutic response seems to be unequalled by "conventional" treatments in rheumatoid arthritis, and is incontestably a turning point in the therapeutic management of this disease.

Antibodies, Monoclonal↗

Towards a definition of "difference" in osteoarthritis.

To assess existing information regarding detectable differences in osteoarthritis (OA), a systematic literature search was conducted up to December 1999. Thirty-three articles were considered methodologically relevant to the definition and categorization of detectable differences in OA. It was determined that the musculoskeletal literature contains a wealth of information that relates to observed changes, much of which is derived from the clinical trials literature, but there have been relatively few methodological studies that have systematically evaluated the nature, categorization, and relevance of the change. Furthermore, most of those that have been published take the perspective of an individual or groups of experts other than that of the patient. This summary of the current literature reveals that the diverse sources of information go part way towards developing an understanding of detectable differences and their importance in the area of OA research and clinical practice. Stakeholders' interests as well as factors that modulate perceptions of importance need to be taken under consideration. In particular, the patient's perspective of the importance of change at an individual level requires further evaluation. This area of clinical research is relatively underdeveloped, but there is considerable opportunity for progress.

Clinical Trials as Topic↗

Disease controlling antirheumatic therapy in spondyloarthropathy.

The management of spondyloarthropathy (SpA) is based more on clinical presentation (axial vs peripheral involvement) than on actual disease diagnosis. Treatment is aimed at controlling inflammation, ankylosis, and abnormal posture. Nonsteroidal antiinflammatory agents are the cornerstone of treatment for patients with axial involvement. If these do not work, disease controlling antirheumatic therapy is usually prescribed. Several drugs, particularly sulfasalazine, produce clinically significant improvement in patients with articular peripheral involvement. In contrast, the therapeutic options for patients with refractory axial involvement are very limited. For this group, "potential" (pamidronate, thalidomide) or "specific" (infliximab) tumor necrosis factor blockers are of potential interest and deserve further evaluation. Therapeutic efficacy is monitored chiefly according to clinical variables, although biochemical markers such as C reactive protein are also helpful.

Antirheumatic Agents↗