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Biomedical subjects

M Dougados

Publications and source records attributed to M Dougados.

At least 145 records · Page 8Linked to original sources
PubMed1999

Ankylosing spondylitis: what is the optimum duration of a clinical study? A one year versus a 6 weeks non-steroidal anti-inflammatory drug trial.

OBJECTIVE: To consider the relevance of the duration of a clinical trial in ankylosing spondylitis: long-term (i.e. 1 yr) vs short-term (i.e. 6 weeks) assessment of a non-steroidal anti-inflammatory drug (NSAID)-placebo controlled study. METHODS: The design was a prospective, multicentre, double-blind, placebo-controlled study of 6 weeks duration with a 12 months double-blind extension. Study drugs were placebo (n = 121) or active NSAID (n = 352). A decrease of at least 50% in pain and/or global assessment and/or functional impairment during the study defined the response to treatment. The percentage of patients discontinuing the study drug over time (life table analysis) permitted the evaluation of both the efficacy and toxicity. RESULTS: Among the 473 recruited patients, the percentage of responders was similar at 1 yr and week 6 with a highly statistically significant difference in favour of the active NSAID groups when compared to placebo (at 1 yr, 17% in the placebo group vs 37, 50 and 43% in the piroxicam 20 mg, meloxicam 15 mg and meloxicam 22.5 mg, respectively, for the patient's overall assessment) without any statistically significant difference between the three active groups. However, evaluation of the patients discontinuing the study drug during the 1 yr of the study permitted the detection of a statistically significant difference between the active NSAID groups. A lower percentage of patients taking meloxicam 22.5 mg had to discontinue the study drug when compared to either meloxicam 15 mg or piroxicam 20 mg (37% vs 53% and 53%, respectively, P < 0.05). By 52 weeks, drug-related upper gastrointestinal adverse events occurred in 13, 32, 20 and 18% in the placebo, piroxicam 20 mg, meloxicam 15 mg and meloxicam 22.5 mg groups, respectively. Some of the adverse events occurred only after week 6. CONCLUSION: This study suggests that a 1 yr trial might be of optimum value compared to a 6 week assessment in order to define better the efficacy and tolerability of NSAIDs in ankylosing spondylitis.

Adult↗
PubMed1999

Concordance between abdominal scintigraphy using technetium-99m hexamethylpropylene amine oxime-labelled leucocytes and ileocolonoscopy in patients with spondyloarthropathies and without clinical evidence of inflammatory bowel disease.

OBJECTIVE: To study the concordance between abdominal scintigraphy using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled leucocytes (ASTLL) and ileocolonoscopy in patients with spondyloarthropathies (SpA) and without clinical evidence of inflammatory bowel disease (IBD). PATIENTS AND METHODS: Fifteen patients with SpA (European Spondylarthropathy Study Group 1991 criteria) without clinical evidence of IBD were studied prospectively with ASTLL and ileocolonoscopy. RESULTS: This cohort consisted of seven men and eight women aged 31.8+/-10.5 yr (18-47) [mean age +/- S.D. (range)] and with a disease duration of 6.0+/-4.4 yr (0.4-15). ASTLL showed abnormal uptake in four patients. Ileocolonoscopy was abnormal in five patients, showing acute inflammatory lesions in one patient with reactive arthritis, undifferentiated chronic inflammatory lesions in two cases, and features indistinguishable from those of Crohn's disease in two cases. ASTLL was negative in two cases in which ileocolonoscopy showed inflammatory lesions and was positive (terminal ileum) in one case with normal ileocolonoscopy. The concordance between the two examinations was statistically significant (kappa = 0.53; P = 0.008). CONCLUSION: ASTLL may be an interesting tool to detect subclinical gut inflammation in patients with SpA.

Abdomen↗
PubMed1999

Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2.

The International Consensus Meeting on the Mode of Action of COX-2 Inhibition (ICMMAC) brought together 17 international experts in arthritis, gastroenterology and pharmacology on 5 6 December 1997. The meeting was convened to provide a definition of COX-2 specificity and to consider the clinical relevance of COX-2-specific agents. These compounds are a new class of drugs that specifically inhibit the enzyme COX-2 while having no effect on COX-1 across the whole therapeutic dose range. The objectives of the meeting were to review the currently available data regarding the roles and biology of COX-1 and COX-2, and to foster a consensus definition on COX-2 specificity. At the present time, no guidelines exist for the in vitro and in vivo assessment of COX specificity, and it was felt that consensus discussion might clarify some of these issues. The meeting also reviewed recent clinical data on COX-2-specific inhibitors. The following article reflects discussion at this meeting and provides a consensus definition of COX-2-specific inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Defining disease activity in ankylosing spondylitis: is a combination of variables (Bath Ankylosing Spondylitis Disease Activity Index) an appropriate instrument?

OBJECTIVE: Disease activity has been defined using a self-administered instrument, focusing on fatigue, axial pain, peripheral pain, enthesopathy and morning stiffness [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)]. This validated instrument is simple and takes 40 s to complete, but whether the index is an accurate expression of the component parts, or whether additional weighting would enhance its efficacy, is unclear. METHODS: Four hundred and seventy-three patients with ankylosing spondylitis received placebo or active non-steroidal anti-inflammatory drug (NSAID) for 6 weeks, and changes between entry and completion were captured by BASDAI and the individual components. Principle component analysis (PCA) was used to explore the best combinations of variables in decreasing order of explained total dispersion and to assess whether a single sum (or algebraic expression) best defined disease activity status. RESULTS: At entry, the correlation between BASDAI and the first axis was 0.99, 0.11 with the second, and zero thereafter. Data at study end and relating to change revealed a 100% correlation (R = 1) between the first axis and the sum, with zero for the remainder. CONCLUSIONS: The data support BASDAI as being a valid and appropriate composite to define disease activity in ankylosing spondylitis. Developed as a simple sum of its components, BASDAI has excellent content validity.

Aged↗
PubMed1999

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.

OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

Antirheumatic Agents↗
PubMed1999

Are radiological joint space widths of normal hips asymmetrical?

BACKGROUND: To be certain that the joint space width is abnormal in the case of hip joint pain when compared with the contralateral hip requires knowledge of physiological dissymmetry. AIM OF THE STUDY: To assess interindividual variability and dissymmetry in pelvic radiological joint space width. METHODS: Pelvic radiographs of subjects without hip joint disease. Measurement with a 0.1 mm graduated magnifying glass and 0.5 mm graduated flat ruler at the hip superointermediate site (vertical going through the femoral head centre). After randomisation of the side to measure, analysis of nine groups of 19 plain films by one investigator blind for the result of the contralateral side. RESULTS: The difference between the left and right hip was plotted against the corresponding mean for all 171 normal subjects. This shows the frequency and the limits of the asymmetry at each measurement site. The asymmetry is independent of interindividual variability of the joint space width and greater than the measurement error in most subjects. CONCLUSION: This study confirms the interindividual variability of hip joint space width, shows the frequency of hip joint space asymmetry and defines its limit.

Female↗
PubMed1999

Individual smallest detectable difference in bone mineral density measurements.

Bone mineral density (BMD) measurement is a major outcome measure in osteoporosis. The BMD changes observed must exceed the variability inherent in the measurement process to be considered related to disease progression. The objective of the study was to estimate short-term variability of BMD measurement and to propose a cut-off value for the smallest detectable BMD changes for an individual. To estimate the short-term variability, 70 healthy postmenopausal women aged 53 +/- 4 years (group 1) and 57 elderly osteoporotic postmenopausal women aged 80 +/- 6 years (group 2) had two repeated BMD measurements of the lumbar spine (L2-L4) and the proximal femur with dual-energy X-ray absorptiometry, with complete repositioning within 1 h. Cut-offs derived from short-term variability were either estimated from the coefficient of variation (CV) (which is a function of the measured value) or from the standard deviation (SD), and applied to 330 postmenopausal women (group 3) who had BMD measurements at baseline and 2 years later. The short-term intrasubject variability was greater at the lumbar spine in group 2 versus group 1 (0.0123 vs. 0.0059 g/cm2, p < 10-4), whereas it was not at the femoral neck (0.0098 vs. 0.0076 g/cm2, p = 0.28). There was no statistically significant correlation between short-term intrasubject variability (SD) and BMD as demonstrated with an analysis of covariance (p values ranging from 0.17 to 0.90). Cut-offs estimated with SD and CV were individually applied to group 3 patients. Using these two cut-offs, discrepancies in assessment of progression were observed in 1.7-8.6% of cases. Short-term BMD variability is constant in a wide range of BMD values. Consequently, to determine cut-off values for the smallest detectable differences in BMD at the individual level, precision errors should be based on SD (expressed in absolute units) rather than on CV (expressed in percentage).

Absorptiometry, Photon↗
PubMed1999

Treatment of patients with Paget's disease of bone.

Paget's disease is a progressive bone disease, monostotic or polyostotic, characterised by hypertrophy of affected bones and accelerated disorganised bone remodelling. It results in bone deformities and pain, with a risk for articular and neurological complications, and fractures. The risk of complications, and thus the therapeutic decision, is a function of the age of the patient, and the severity and the activity of the disease. Bisphosphonates are first-line therapy for Paget's disease, and the advent of the new bisphosphonates permits a dramatic improvement in treatment. The optimal treatment regimen should obtain normalisation or quasi-normalisation of markers of bone remodelling. This result has the potential for a long-term control of the disease.

Biomarkers↗
PubMed1999

Requirement for total hip arthroplasty: an outcome measure of hip osteoarthritis?

OBJECTIVE: To assess if total hip arthroplasty (THA) is a valid outcome measure of hip osteoarthritis (OA), in respect to clinical and radiological assessments. METHODS: A prospective 3 year study of patients who had painful hip OA with an initial radiographic joint space width > or =1 mm at the narrowest point. Dependent variable was THA. Patient data including body mass index, OA structural severity by radiograph, OA symptomatic severity (pain, function), and OA localization were recorded at entry. Pelvic radiographs were obtained before THA, when available, and once yearly during the study. RESULTS: During the study 106 of 506 patients underwent THA. Risk was estimated (Kaplan-Meier method) to be 8+/-1, 16+/-2, and 23+/-2% after 1, 2, and 3 years, respectively. Factors predisposing to requirement for surgery were: age > or =70 years, female sex, superolateral migration of the femoral head, joint space width <2 mm, Kellgren-Lawrence grade > or =3, pain (visual analog scale) > or =50 mm, and Lequesne index > or =10 with a relative risk of 1.65, 1.71, 1.96, 1.85, 1.89, 1.86, and 2.59, respectively. Mean change in joint space width was 0.22+/-0.50 vs 0.97+/-1.35 mm/year in patients without and with THA, respectively (p<0.0001). Changes in radiological joint space width during the first year were highly predictive of requirement for THA during the 2 following years (risk of 5, 13, 25, and 79% in patients with a radiological joint space width worsening during the first year of 0, < or =25, >25 and < or =50, and >50%, respectively). CONCLUSION: These data suggest that THA could be considered as a valid outcome measure in OA. However, further studies should be conducted in other countries with different health care systems to evaluate the inter-country reliability of this measurement.

Aged↗
PubMed1999

Selection of instruments in the core set for DC-ART, SMARD, physical therapy, and clinical record keeping in ankylosing spondylitis. Progress report of the ASAS Working Group. Assessments in Ankylosing Spondylitis.

To select specific instruments for each domain of the core set for endpoints in ankylosing spondylitis (AS), we gathered all instruments described in the literature to assess the domains chosen as endpoints in AS and sent them to 43 members of the Assessments in Ankylosing Spondylitis (ASAS) Working Group. The following domains were taken into account: function, pain, spinal mobility, patient global assessment, morning stiffness, peripheral joints and entheses, acute phase reactants, x-ray spine, x-ray hips, fatigue. For each instrument the members were asked to judge if the instrument was feasible and relevant. If an instrument was judged to be not feasible or not relevant by more than 50% of the respondents the instrument was deleted from the list. These data were presented during an ASAS workshop and the final decisions were about which instruments to include in the core set. This process was repeated separately for the settings disease controlling antirheumatic therapy (DC-ART), symptom modifying antirheumatic drugs (SMARD) and physical therapy, and clinical record keeping. The response rate to the questionnaire was 72%. For each domain one or more instruments were selected, except for Entheses and Fatigue. The chosen instruments were similar for the 3 above settings. Core sets of specific instruments were selected for the OMERACT filter test for relevance and feasibility. For all these instruments the remaining aspects of the OMERACT filter (truth and discrimination) should be assessed by literature review and if needed by additional research. It is recommended to use these instruments in all research projects in AS.

Antirheumatic Agents↗
PubMed1999

A comparative study of the usefulness of the Bath Ankylosing Spondylitis Functional Index and the Dougados Functional Index in the assessment of ankylosing spondylitis.

To determine whether the Bath Ankylosing Spondylitis Functional Index (BASFI, score 0-10) or Dougados Functional Index (DFI, score 0-40) is superior in measuring physical function in ankylosing spondylitis (AS) we studied 191 consecutive outpatients with AS in the Netherlands, France, and Belgium. The participating centers are secondary and tertiary referral centers. The external criterion for disease activity (DA) was: both patient and physician assessment of disease activity on a visual analog scale (VAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The external criterion for damage was 2 radiological scores of the spine; BASRI-s (Bath Ankylosing Spondylitis Radiology Index-spine) and a modified SASSS (Stoke Ankylosing Spondylitis Spine Score). Median scores for BASFI and DFI were 2.5 (range 0-10) and 8.5 (range 0-35), respectively. Spearman correlation coefficient between both indexes was 0.89. The average correlation with disease activity variables was 0.42 for BASFI and 0.41 for DFI. For both BASFI and DFI the correlation with BASRI-s was 0.42 and with SASSS 0.36. When distinguishing between patients with high and low disease activity, sensitivity for both indexes was between 76 and 94%, while specificity was between 66 and 87% for all 3 DA measures. Average misclassification between BASFI, DFI and DA was 23 and 27%, respectively. Both BASFI and DFI correlate equally well with disease activity and damage.

Adolescent↗
PubMed1999

Clinical relevance of C-reactive protein in axial involvement of ankylosing spondylitis.

To evaluate C-reactive protein (CRP) as a potential useful criterion of symptomatic severity of ankylosing spondylitis (AS), we conducted both a cross sectional and a longitudinal (6 week) clinical study in 443 patients with axial involvement in AS. During the 6 weeks of the study, patients received either a placebo or an active nonsteroidal antiinflammatory drug (NSAID). At baseline, CRP was increased in 173 patients (39%). A multivariate analysis in which CRP was the dependent variable and all clinical assessment criteria (pain, range of motion, functional disability, hemoglobin, platelet count) the independent variables showed that range of motion and laboratory signs of inflammation were the most significant variables to explain the CRP values. A similar multivariate analysis conducted on the changes in the variables during the 6 weeks of the study concluded that night pain and laboratory signs of inflammation were the most significant variables explaining the changes in CRP values. The capacity of CRP to discriminate between an active NSAID and a placebo was moderate. This study suggests than an increase in CRP in patients with AS with axial involvement is not a rare phenomenon and might be correlated with the clinical severity of the disease. This outcome measure does not seem to be of great interest in the short term evaluation of fast acting drugs. However, the longterm clinical significance of such an increase in CRP remains to be investigated.

Adult↗
PubMed1999

Outcome variables in ankylosing spondylitis: evaluation of their relevance and discriminant capacity.

The clinical status of ankylosing spondylitis (AS) can be defined by several domains (e.g., pain, function, metrology, laboratory) and subcomponents within each domain (e.g., pain using visual analog scale, Schober's within metrology). Our aim was (1) To define groups of highly correlated variables in order to determine the most relevant; and (2) to evaluate the capacity of different clinical and biological variables that best discriminate between placebo and active nonsteroidal drugs in AS. Patients with active AS (n=423) were followed prospectively over 6 weeks while receiving placebo (n=121) or active nonsteroidal antiinflammatory drugs (n=352). Eighteen variables were studied, including global assessment, pain, stiffness, functional indices, metrology, disease activity index, and laboratory markers. Statistics included (1) Evaluation of the relevance of the different domains by multivariate analysis (CART tree-structure classification; variable clustering); and (2) evaluation of the discriminant capacity by univariate analysis [i.e., differences in the standardized response mean (SRM) (mean change/SD) between placebo and active drug. A value > or =0.60 was considered relevant]. Four clusters were identified (patient's subjective perception, inflammatory symptoms, metrology, laboratory data) with multiple correlation R2 revealing the most relevant variables to be the Bath Ankylosing Spondylitis Functional Index (BASFI; 0.75), night pain (0.62), Schober's test (0.58), and platelet count (0.55), respectively, within each cluster. In terms of discriminant power (SRM) the patient perceived global status (0.84), lumbar pain (0.73), night pain (0.71), physician global assessment (0.66), and BASFI (0.65) were most relevant in the univariate analysis. Among the 4 most relevant domains are subjective perception, inflammatory symptoms, metrology, and laboratory. Multivariate analysis of the data reveals that the spinal pain and the patient global assessment are the variables that best discriminate between placebo and active nonsteroidal drug in short term studies.

Adult↗
PubMed1999

Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis.

Our aim was to determine whether C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) is more appropriate in measuring disease activity in ankylosing spondylitis (AS). We studied 191 consecutive outpatients with AS in The Netherlands, France, and Belgium. Patients were attending secondary and tertiary referral centers. The external criterion for disease activity was: physician and patient assessment of disease activity on a visual analog scale (VAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In each measure we defined 3 levels of disease activity: no activity, ambiguous activity, and definite disease activity. The patients with AS (modified New York criteria) were divided into 2 groups: those with spinal involvement only (n=149) and those who also had peripheral arthritis and/or inflammatory bowel disease (IBD) (n=42). For each criterion of disease activity, the patients with no activity and with definite activity were included in receiver operator curves and used to determine cutoff values with the highest sensitivity and specificity. We also calculated Spearman correlations. The median CRP and ESR were 16 mg/l and 13 mm/h, respectively, in the spinal group and 25 mg/l and 21 mm/h, respectively, in the peripheral/IBD group. In both groups the Spearman correlation coefficients between CRP and ESR were around 0.50. There was moderate to poor correlation between CRP, ESR, and the 3 disease activity variables (0.06-0.48). Sensitivity for both ESR and CRP was 100% for physician assessment and between 44 and 78% for patient assessment of disease activity and the BASDAI, while specificity was between 44 and 84% for all disease activity measures. The positive predictive values of CRP and ESR in our setting were low (0.15-0.69). We conclude that neither CRP nor ESR is superior to assess disease activity.

Adult↗
PubMed1999

Radiological scoring methods in ankylosing spondylitis: reliability and sensitivity to change over one year.

Our aim was to compare reliability and sensitivity to change of different radiological scoring methods in ankylosing spondylitis (AS). Two trained observers scored 30 AS radiographs twice with an interval of 4 weeks. The same two observers scored 187 AS radiographs in pairs, at baseline and after one year followup, to measure change and agreement on change. The sacroiliac (SI) joints were scored in 5 grades by the New York method and the SASSS (Stoke Ankylosing Spondylitis Spine Score). Hips were graded 0-5 (according to Larsen). Cervical and lumbar spine were graded (0-4, Bath Ankylosing Spondylitis Radiological Index, BASRI), and scored in detail (0-72, SASSS). SASSS of the cervical and lumbar spine scored on the anterior sites of the vertebrae proved most reliable, with both intra and interobserver intraclass correlation coefficients (ICC) between 0.87 and 0.97. BASRI was only moderately reliable, with Cohen's kappa ranging between 0.50 and 0.82 for intra, and 0.38-0.64 for interobserver reliability. Similarly, SI joint scores (New York, SASSS) showed intraobserver kappa between 0.56 and 0.84, and interobserver reliability with kappa between 0.37 and 0.47. Larsen hip scores proved unreliable: moderate intraobserver kappa of 0.47-0.58 and low interobserver kappa of 0.29. After retraining, interobserver kappa did not improve (0.45 and 0.17). In retrospect, a one year period was too short to measure sensitivity to change. Observers agreed that no change occurred in up to 89% of cases. A measurable change of deterioration or improvement occurred rarely. We conclude that in AS, only the SASSS method for the spine and the BASRI reached good reliability. Other methods for spine, SI joints, and hips were moderately reliable at best. There was moderate to good agreement on no change between the observers. No method showed change over a period of one year in a considerable number of patients.

Arthrography↗
PubMed1999

Arthroscopic evaluation of post-traumatic patellofemoral chondropathy.

OBJECTIVE: To evaluate clinically and arthroscopically post-traumatic patellofemoral chondropathy. METHODS: Fifty-nine patients with post-traumatic patellofemoral chondropathy were included in a cross sectional study and 46 of them completed a 6 month longitudinal study. Evaluation of the disease, performed once in the cross sectional study and twice (at entry and after 6 months) in the longitudinal study, included clinical and arthroscopic variables evaluating disease activity and severity. Arthroscopy was performed under local anesthesia in an outpatient procedure using a small arthroscope. Chondropathy was evaluated by the overall assessment of the investigator using a visual analog scale, and by the Société Française d'Arthroscopie (SFA) scoring system (SFA score: 0-100). Synovitis was assessed by the "synovitis score," which represents a composite index taking into account intensity, extent and location of synovial abnormalities. RESULTS: In the cross sectional study, severity of chondropathy correlated with age, body mass index, disease duration, functional impairment (Lequesne's index and maximum number of steps descended), patellofemoral crepitus on active motion, limitation of flexion, and presence and amount of synovitis. Knee effusion correlated with the presence of synovitis, but no correlation was found between pain or functional impairment and presence or amount of synovitis. In the longitudinal study, no statistically significant change in chondropathy was observed after 6 months followup despite a statistically significant improvement in pain, function, and knee effusion after this period. However, a statistically significant correlation was found between the progression of patellofemoral chondropathy and the presence and amount of synovitis at baseline. Synovitis was present at baseline in 10 patients. Changes in SFA scores were 1.2 +/- 1.6 and -0.1 +/- 1.0 in the groups of patients with and without synovitis, respectively (p = 0.0062). CONCLUSION: These data suggest that synovitis might have a deleterious effect on the evolution of post-traumatic patellofemoral chondropathy or might be a marker for active cartilage breakdown.

Adult↗