[Descriptive epidemiological study of acne on scholar pupils in France during autumn 1996]. / Epidémiologie descriptive de l'acné dans la population scolarisée en France métropolitaine pendant l'automne 1996.

BACKGROUND: Acne is the most common symptom prompting patients to consult a dermatologist. No previous study has been conducted in France to determine the prevalence of acne and describe the main epidemiological features. SUBJECTS AND METHODS: A cross sectional study was conducted in November 1996 and included 913 school children aged 11 to 18 years. This sample was statistically representative of the entire secondary school population in France during the 1996-1997 school year. The subjects were stratified by 5 criteria: age, sex, rural or urban residence, sun exposure, type of school. RESULTS: Taking the clinical diagnosis made by the dermatologist investigator as the main criteria, the overall prevalence of acne was 72 p. 100. It was 76.1 p. 100 using the new ECLA grading system previously described. The prevalence of acne was sex and age dependent: highest scores were found for girls aged 14-16 years and for boys aged 16-17 years. Genetic factors were very important for the outcome of acne. Finally, 41 p. 100 of the acneic subjects were following a treatment, prescribed by a dermatologist in two-third of the cases. DISCUSSION: These results are in agreement with those previously published in the literature although some differences were disclosed. It would appear important to distinguish between minimal acne with a few retentional pimples occuring during adolescence and severe acne (more than 20 pimples on the face) requiring early medical care to avoid scarring.

Cross-sectional epidemiological survey of rheumatoid arthritis patients seen in private practice in France. Descriptive results (1629 cases).

OBJECTIVE: To conduct an epidemiological study of rheumatoid arthritis patients seen by office-based rheumatologists in France (first semester of 1996). METHODS: Cross-sectional study of 1629 rheumatoid arthritis patients conducted by 373 office-based rheumatologists who volunteered for the study (one visit per patient). Each rheumatologist was to complete a 200-variable questionnaire for the first four rheumatoid arthritis patients who came to their office. RESULTS: Women contributed 81% of the sample (mean age, 57 years); 19% of patients were seen in the Paris area, 20% in the North East, 20% in the North West, 22% in the South East and 19% in the South West. Twenty-nine per cent of patients had a paid job and 21.1% (all women) were homemakers. Among the patients with a paid job, 44% were on sick leave, with the reason for the sick leave being the rheumatoid arthritis in 36% of cases. Nineteen per cent of patients had stopped working permanently because of their rheumatoid arthritis, after a mean disease duration of six years. Mean disease duration in the overall sample was eight years. The diagnosis was established within six months of symptom onset in 75% of cases. A family history of rheumatoid arthritis was found in 11% of patients and a family history of other autoimmune diseases in 2%. The disease was precipitated by a stressful life event in 17% of cases. Follow-up was being provided only by the study rheumatologist in 59% of cases and also by a general practitioner in 39%. The disease was quiescent in 9% of cases, minimally active in 32%, moderately active in 46% and severely active in 13%. Eighty-four per cent of patients were on one (78%) or more (6%) second-line drugs including methotrexate (45%), an antimalarial (17%), intramuscular gold (14%), tiopronin (9%), D-penicillamine (6%) and sulfasalazine (12%). Fifty-two per cent of patients were on steroid therapy (mean dose, 7.5 +/- 5.7 mg/d). Other drugs included nonsteroidal antiinflammatory agents (61%), analgesics (61%), gastroduodenal protective agents (45%) and anxiety-relieving agents (10%). Twenty-four per cent of patients had had one or more surgical procedures (mean, 3/patient) for their joint disease. CONCLUSION: This nation-wide epidemiological survey conducted in France provides a database on the socioeconomic and demographic characteristics of rheumatoid arthritis patients followed in private practice.

Albumin binding sites for etodolac enantiomers.

Non-steroidal anti-inflammatory drugs (NSAIDs) are strongly bound to human serum albumin (HSA), mainly to sites I and II. The aim of this study was to characterize the binding site(s) of etodolac enantiomers under physiological conditions (580 microM HSA) using equilibrium dialysis. The protein binding of etodolac enantiomers, alone or in various ratios, was studied in order to evaluate the potential competition between them. Our results showed that (S)-etodolac was more strongly bound to HSA than (R)-etodolac. The displacement of one enantiomer by its antipode was observed only at high concentrations of the competitor, and was more pronounced for (S)-form. Displacement studies of the enantiomers by specific probes of sites I and II of albumin, dansylamide, and dansylsarcosine, respectively, showed that (R)-etodolac was slightly displaced by both these probes whereas the free concentration of (S)-etodolac increased markedly in the presence of dansylsarcosine. Moreover, the binding of ligands to sites I and II is usually affected by alkaline pH, by chloride ions, and by fatty acids. For etodolac, the presence of 0.1 and 1 M chloride ions and increasing pH (5.5-9) decreased the binding of both enantiomers. The same result was obtained with addition of octanoic acid. Conversely, the addition of oleic, palmitic, or stearic acid to the protein solution increased the binding of (R)-etodolac, but decreased that of its antipode. All these findings suggest (R)- and (S)-etodolac interact mainly with site II of HSA, and that the (R)-isomer is also bound to site I under physiological conditions.

Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis.

OBJECTIVE: To determine if the pharmacokinetics of methotrexate (MTX) is modified by the coadministration of etodolac. METHODS: MTX (10 mg) was administered intramuscularly in the absence and presence of steady state levels of etodolac in 19 patients with rheumatoid arthritis. MTX levels were assayed by fluorescence polarization immunoassay. Concentrations of 7-hydroxymethotrexate (7-OH-MTX) were assayed by a reverse phase high performance liquid chromatography method. The unbound fraction was determined by ultrafiltration. RESULTS: When etodolac was coadministered with MTX, the highest observed concentration decreased and the mean residence time increased to become statistically significant. However, these differences are not of great clinical importance especially given that the area under the curve and clearances were unchanged. There were no significant differences in binding protein and 7-OH-MTX concentrations between MTX with and without etodolac administration. CONCLUSION: The pharmacokinetics of MTX is slightly modified by coadministration of etodolac. Moreover, no clinical toxicity was observed.

Stereoselective binding of etodolac to human serum albumin.

The protein binding of etodolac enantiomers was studied in vitro by equilibrium dialysis in human serum albumin (HSA) of various concentrations varying from 1 to 40 g/liter, by addition of each enantiomer at increasing concentrations. In the 1 g/liter solution, at the lowest drug levels, the (R)-form is more bound than its antipode, the contrary being observed at the highest drug levels. For higher albumin concentrations, S was bound in a larger extent than R. Using the displacement of specific markers of HSA sites I and II, studied by spectrofluorimetry, it was suggested that R and S are both bound to site I, while only S is strongly bound to site II.

[How to evaluate the long-term course of osteoarthritis. Tests for trials of fundamental treatments (spine excluded)]. / Comment évaluer l'évolution de l'arthrose à long terme. Tests pour les essais de traitements de fond (rachis exclu).

The best assessment tests for long term trials on osteoarthritis (OA) of the hip and knee are the following, in order of relevance value (consensus of french experts): 1) the loss of joint space thickness on successive radiographies; 2, 3) the indices of the severity for OA of the hip and knee; the investigator's overall opinion; 4) the patient's overall opinion (visual analogue scale of handicap); 5, 6, 7) the pain level (visual analogue scale); the time for going up and down a standard flight of stairs and the time of pain in this distance; the limitation of two articular movements; 8) the increase of either analgesics or NSAIDs consumption; 9) concerning OA of fingers, the number of joints newly involved on successive radiographies. At present, only the radiological tests 1 and 9 are validated. The clinical tests 2 to 8, valuable for short term trials, have yet to be validated for long term follow-up. Recommended duration of trials is three years. A rigorous organisation is necessary to avoid erroneous inclusions: all data recorded in the pre-inclusion visit have to be checked by the principal investigator. Since we have not yet a validated chondroprotective agent as a reference drug, the trial must be randomised, double blind, placebo controlled, parallel group study.

[Definitions and clinical experimentation of anti-osteoarthritis agents/chondro-protectors. Survey among private rheumatologists]. / Définitions et expérimentation clinique des anti-arthrosiques/chondroprotecteurs. Enquête auprès des rhumatologues libéraux.

Through osteoarthritis is the most common rheumatic disease its fundamental medicinal therapy(s) remain(s) still to be discovered. Definitions of the terms anti-osteoarthritic or chondroprotective agents vary according to the conceptual ideas in presence. They are discussed. In order to know the view point of private rheumatologists, a survey has been realised. 63 rheumatologists answered a questionnaire which included three parts: the first one, semantic, concerned definitions of anti-osteoarthritic and chondroprotective drugs and their respective place in therapeutic; a questionnaire of methodology was then exploring conception and organisation of clinical trials to assess such drugs in osteoarthritis; finally questions were asked on feasibility of such trials. The results are presented and discussed below.

[Efficacy, tolerability and therapeutic benefit of etodolac (Lodine 200) in rheumatologic practice]. / Efficacité, tolérance et bénéfice thérapeutique de l'étodolac (Lodine 200) en pratique rhumatologique.

Efficacy, safety and therapeutic benefit of etodolac (Lodine 200) in rheumatological practice. An open clinical trial performed by 974 rheumatologists enabled an evaluation of efficacy, safety and therapeutic benefit of etodolac (Lodine 200) on 4,947 patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis of the lower limbs; the initial dosage was 600 mg/d (for 2 weeks), then 400 to 600 mg/d (for 2 to 4 weeks, according to the indication). Efficacy, assessed by classical items for NSAID's, was shown to be excellent to good by 61-77 p. 100 of patients, according to the indication. 7.7 p. 100 of patients only dropped out for lack of efficacy. 20.4 p. 100 of patients developed adverse effect(s) (AE), but the relationship between etodolac and AE was assessed "possible" or "probable" only for 9.6 p. 100 of patients; this figure should be compared to the 7.6 p. 100 of patients who dropped out for AE and to the 92 p. 100 of patients who assessed the global safety as "excellent or good". The therapeutic benefit was estimated very favorable: 75 p. 100 of patients felt better than at the beginning of the study, 64.5 p. 100 of patients wished to continue the treatment and the (mean) benefit-risk ratio assessed with a logarithm scale (-1 to +1), ranged from 0.45 to 0.6 according to the indication. Therefore, this trial confirmed the good efficacy and safety profile of etodolac on a large scale in normal clinical practice in France, following assessments during controlled trials. It also permitted to perfect new items of evaluation for NSAID's, in particular for therapeutic benefit.