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The objective of the study was to determine the specificities of renal cell carcinoma (RCC) in the department of Herault using the Herault Tumor Registry over 30 years.Data of this study were obtained from the Herault cancer database. We analysed the evolution of RCC from 1987 to 2016, including the incidence, mortality, cancer pathology and staging at the moment of diagnosis. We compared our results with national and international data.We identified 3769 newly diagnosed RCC: 2628 in men (69,7%) and 1141 in women (30,3%). In 2016, RCC was the 8th most frequent cancer, both genders combined, the 7th most frequent cancer in men and the 11th in women. New cases of RCC increased by 4.2 in men and 3.3 in women over the study period. The number of localised forms increased by 9% over 20 years. In 2016, the probability of having a RCC before the age of 75 was of 2.11% for a man and of 0.62% for a woman.Over 30 years, the incidence rate of RCC increased in the department of Herault; however, mortality decreased over the same period. This analytical data should be improved by the development of the Registry of Herault Specialised in Onco-Urology (RHESOU).3.

Background:ESPOIR is a longitudinal prospective cohort of adults with possible early RA (ClinicalTrials.gov: NCT03666091). Patients were referred by rheumatologists and general practitioners to one of the 14 regional centers in France. The objective and design of the cohort are described elsewhere (1). Patients received standard of care by their rheumatologists and were followed without predefined therapeutic strategiesObjectives:To report the current 10-year outcome of patients with early rheumatoid arthritis (RA) in the ESPOIR cohort, and predictors of outcome.Methods:From 2003 to 2005, 813 patients were included if they had early arthritis (< 6 months) with a high probability of RA developing and had never been prescribed disease modifying anti-rheumatic drugs (DMARDs). Multivariate logistic regression analysis was used to evaluate predictors of outcome.Results:In total, 521 (64.1%) RA patients were followed up for 10 years and 35 (4.3%) died, which appears similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174/521 (33.4%) received at least one biologic DMARD, 13.6 and 23.4% within 2 and 5 years. At year 10 (Table), mean DAS28 ESR was 2.5 ± 1.3; 273 (52.4%) patients were in DAS28 remission, 39.7% in CDAI remission, 40.1% in DAS28 sustained remission, and 14.1% in drug-free remission. Disability was well controlled overtime (Figure) and half of the patients achieved a HAQ Disability Index < 0.5; the SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 ± 17.9. A total of 82 (16.5%) patients required joint surgery including arthroplasty or arthrodesis in only 6.5% of the cases. A substantial number of patients showed new comorbidities, mainly cardiovascular or metabolic diseases over 10 years. Finally, positivity for anti-citrullinated protein antibodies was confirmed as a robust predictor of long-term outcome in patients with early RA.Table 1.Outcome in ESPOIR cohort and 1993 cohort at 10 yearsESPOIR cohort n=5211993 cohort n=112DAS28 ESR2.5 ± 1.3DAS44-2.2 ± 0.9SDAI7.5 ± 8.7CDAI6.8 ±8.3DAS28 ESR remission (n (%)273 (52.4)CDAI remission207 (39.7)DAS28 sustained remission, n (%)209 (40.1)DAS28 drug-free remission, n (%)75 (14.1)DAS28 ESR LDA336 (64.5)Rheumatoid nodules39 (7.5)Sicca syndrome314 (60.3)Patient global assessment24.0 ± 24.0HAQ DI score0.5 ± 0.60.75 ± 0.71HAQ DI < 0.5, n (%)280 (54.5)SF36 MCS46.7 ± 10.5SF36 PCS44.6 ± 9.2Pain (mm, VAS)16.6 ± 20.6Fatigue (mm, VAS)31.4 ± 27.023.2 ± 23.0ESR (mm/hr)14.4 ± 13.818.4 ± 16.5CRP level (mg/l)6.4 ± 16.59.3 ± 11.7Normal CRP (< 5 mg/l), n (%)336 (67.6)Total mSharp score*13.8 ± 19.635.4 ± 46.1Erosion score4.9 ± 9.418.4 ± 26.5)Joint narrowing score8.9 ± 12.132.1 ±23.2Joint surgery82 (16.5)26 (23.2)Joint arthroplasty/arthrodesis34 (6.5)20 (17.9)Data are mean (SD)DAS28, disease activity in 28 joints; HAQ DI, Health Assessment Questionnaire Disability Index; SF36 MCS, Medial Outcomes Study 36-item Short Form mental component summary; SF36 PCS, Medical Outcomes Study 36-item Short Form physical component summary; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VAS, visual analog scale; CDAI, Clinical Disease Activity Index; SDAI, Simple Disease Activity Index; *van der Heijde-modified Total Sharp scoreFigure 1.Health Assessment Questionnaire Disability Index (HAQ-DI) over 10 years Data are mean (SD).Conclusion:We report a very mild 10-year outcome of a large inception cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of early RA patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients than previously.References:[1]Combe B et al. Jt Bone Spine Rev Rhum. 2007;74:440–5Acknowledgements:We thank MC Boissier, G Falgaronne and F. Lioté for help in patient recruitment. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the cohort study. Two additional grants from INSERM supported part of the biological database. The French Society of Rheumatology, Abbvie, Pfizer, Lilly and more recently Fresenius and Biogen supported the ESPOIR cohort.Disclosure of Interests:Bernard Combe Speakers bureau: AbbVie; BMS; Gilead; Lilly; Merck; Pfizer; Roche-Chugai;, Consultant of: AbbVie; BMS; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Fresenius, Novartis, Pfizer, and Roche-Chugai., Nathalie Rincheval: None declared, Francis Berenbaum Speakers bureau: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Patrick BOUMIER: None declared, Alain Cantagrel Speakers bureau: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Consultant of: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Grant/research support from: Abbvie, Fresenius, MSD France, Novartis, Pfizer, and UCB, Philippe Dieudé Speakers bureau: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Consultant of: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer., Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Bruno Fautrel Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD and Pfizer, René-Marc Flipo Speakers bureau: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Consultant of: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Grant/research support from: Abbvie, Janssen, Novartis, Pfizer and Roche-Chugai, Philippe Goupille Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Grant/research support from: Abbvie, Biogen, MSD, Pfizer, Xavier Mariette Speakers bureau: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Consultant of: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Grant/research support from: Servier, Alain Saraux Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Grant/research support from: Roche-Chugai, Thierry Schaeverbeke Speakers bureau: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Consultant of: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Grant/research support from: Pfizer, AbbVie, BMS, Roche, UCB, Astra, MSD, Rigel, AB-sciences, Jean Sibilia Speakers bureau: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Consultant of: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Grant/research support from: AbbVie, Lilly, Pfizer, Roche, Olivier VITTECOQ Speakers bureau: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Grant/research support from: Novartis, Pfizer, Merck, and Bristol-Myers Squibb, Jean-Pierre Daures: None declared

Introduction ESPOIR est une cohorte de patients atteints d’arthrites debutantes. Les objectifs dans ce projet sont multiples : suivi exhaustif des patients, meilleure exploitation des comorbidites et hospitalisations, evaluation de l’impact medico-economique. Cet appariement offre une ouverture sur de nouvelles perspectives pour les travaux de recherche. Materiels et methodes La cohorte multicentrique francaise ESPOIR des 813 patients inclus entre 2002 et 2005, âges de 18 a 70 ans qui presentaient une arthrite recente a ete chainee par appariement probabiliste aux donnees SNDS a partir de 2007. Trente-cinq variables de la base ESPOIR ont ete utilisees dans l’ordre decroissant de leur capacite discriminante et de leur fiabilite. Pour pallier l’absence des donnees avant 2007 dans le SNDS l’ensemble du suivi ESPOIR a ete utilise. L’appariement a ete effectue par etape, permettant l’obtention de patients uniques apres chacune d’entre elle. La selection s’est d’abord faite sur les donnees administratives, les dates de soins, les etablissements et les dates de traitements de fond. La correspondance de ces bases appariees a ete faite sur le departement de residence, le mois de naissance, le diagnostic principal et le type de traitements de fond. Les patients non encore dedoublonnes a cette etape ont ete selectionnes successivement sur les actes de biologie et radiologie specifiques, les anti-inflammatoires, les traitements non specifiques et pour finir sur des ALD autres que polyarthrite rhumatoide et les deces. A la derniere etape de l’appariement, nous avons obtenu 3 groupes de patients : les patients uniques, les patients doublons et les patients impossible a retrouver car toutes leurs donnees se situent avant 2007. Le test non parametrique de Wilcoxon–Mann–Whitney a ete applique pour comparer la distribution des variables continues et le test du Chi2 a ete utilise pour tester l’association des variables categorielles entre les patients apparies et non apparies. Resultats Au total, 610 patients (75 %) ont ete apparies, 93 (11,5 %) ont des doublons, 110 (13,5 %) sont impossible a retrouver. Aucune difference significative n’ayant ete observe entre les deux derniers groupes, ils ont ete regroupes en non apparies. Les patients apparies et non apparies ont des caracteristiques demographiques similaires, par contre ils se differencient sur des criteres d’activite (nombre de synovites 6,1 ± 4,9 non apparies vs 7,6 ± 5,5 apparies, p = 0,0001), des caracteristiques radiologiques, des marqueurs biologiques (anti-CCP positifs 24,7 % non apparies vs 43,4 % apparies, p Conclusion Soixante-quinze pour cent des patients ESPOIR ont pu etre apparies avec la base du SNDS. Ces derniers semblent presenter des manifestations cliniques plus importantes, une positivite plus grande des marqueurs biologiques, et leur diagnostic de polyarthrite rhumatoide est plus probable. Dues a leurs caracteristiques, ces patients sont suivis plus longtemps dans la cohorte et ont certainement eu plus d’actes et de traitements, c’est pourquoi il semble plus facile de les apparier. A ce stade un appariement deterministe avec le NIR parait interessant pour verifier les caracteristiques des patients non apparies. Cette etude permettra la mise en place de nouveaux projets de recherche.

Background:Multimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response.Objectives:The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis (ESPOIR cohort) and its possible impact on the therapeutic response.Methods:We included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed [1]. Each patient was assigned scores of binary aMMI (0= no comorbidity, 1= at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying anti-rheumatic drug (DMARD) according to the aMMI. Secondary endpoints were other disease activity scores and response criteria. We collected data from the visit preceding the first DMARD initiation (baseline visit) and the visit after at least 3 months of treatment (follow-up visit). The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated.Results:Analyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI= 0 or 1, respectively (p= 0.9), achieved CDAI low disease activity (Table 1). Similar results were found with counted and weighted aMMI. Use of other disease activity scores or response criteria did not show a significant impact of multimorbidity on the therapeutic response. Therapeutic maintenance was significantly better with binary aMMI = 1 than binary aMMI = 0. Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point (Table 2).Table 1.Impact of aMMIs on CDAI, DAS28 and SDAI low disease activity (LDA) achievement at follow-up visit (univariate analyses)LDA achievementCDAIpDAS28pSDAIpYesNoYesNoYesNoBinary aMMI, n (%)077 (45.3)93 (54.7)0.9*85 (50.0)85 (50.0)0.2*80 (47.1)90 (52.9)0.9*1135 (44.7)167 (55.3)131 (43.4)171 (56.6)141 (46.7)161 (53.3)Counted aMMI, mean (SD)1.0 (1.1)1.1 (1.1)0.71.0 (1.1)1.1 (1.1)0.21.1 (1.1)1.1 (1.1)1.0Weighted aMMI, mean (SD)4.1 (5.2)4.0 (4.7)0.94.0 (5.2)4.1 (4.7)0.34.0 (5.0)4.0 (4.9)1.0aMMI= adapted MultiMorbidity Index; CDAI= Clinical Disease Activity Index; SDAI= Simplified Disease Activity Index* Proportion of patients achieving LDA between patients with binary aMMI= 0 and binary aMMI= 1. Because of no statistically significant results, no multivariate analysis was performed.Table 2.Probability of first DMARD maintenance at 1, 3, 5 and 10 years (multivariate analysis)Time pointFirst DMARD maintained or stoppedBinary aMMI#Counted aMMI§011 year(n= 530)Maintenance (n= 300)22981.71 (0.93)OR [95% CI]*> 999 [286.2->999]221.3 [84.0-583.0]Withdrawal (n= 230)205250.12 (0.37)3 years(n= 493)Maintenance (n= 285)102751.66 (0.94)OR [95% CI]*153.9 [73.0-324.5]26.1 [15.1-45.3]Withdrawal (n= 208)175330.22 (0.64)5 years(n= 459)Maintenance (n= 116)91071.72 (1.05)OR [95% CI]*10.9 [5.1-23.3]2.2 [1.8-2.7]Withdrawal (n= 343)1631800.82 (1.0)10 years(n= 415)Maintenance (n= 40)2381.58 (0.84)OR [95% CI]*14.0 [3.3-59.1]1.6 [1.2-2.0]Withdrawal (n= 375)1582170.99 (1.12)#data are number of patients§ data are mean (standard error)* data are odds ratios (ORs) and 95% confidence intervals (95% CI) of still being on the first initiated DMARD at 1, 3, 5 and 10 years between patients with binary aMMI = 1 and binary aMMI = 0 and according to counted aMMI, per additional point.Conclusion:In the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.References:[1]Radner H, Yoshida K, Mjaavatten MD, et al. Development of a multimorbidity index: Impact on quality of life using a rheumatoid arthritis cohort. Semin Arthritis Rheum 2015;45:167–73.The variables included in multivariate analyses were sex, rheumatoid factor and/or anti-citrunillated peptide antibody positivity, age, CDAI at baseline visit, number of treatments at baseline visit.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) for expert monitoring and data management and all the investigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).Disclosure of Interests:Aurélie BELTAI: None declared, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche, Amandine Coffy: None declared, Cécile Gaujoux-Viala: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai and UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai and UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Alain Saraux Speakers bureau: AbbVie; Bristol-Myers Squibb; Lilly; Nordic; Novartis; Pfizer; Roche-Chugai; Sanofi and UCB, Consultant of: AbbVie; Bristol-Myers Squibb; Lilly; Nordic; Novartis; Pfizer; Roche-Chugai; Sanofi and UCB, Grant/research support from: AbbVie; Bristol-Myers Squibb; Lilly; Nordic; Novartis; Pfizer; Roche-Chugai; Sanofi and UCB, Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, Sandoz, Jean-Pierre DAURES: None declared, Charlotte Hua: None declared

Introduction Les recommandations nationales et internationales de prise charge de la polyarthrite rhumatoide (PR) proposent de prescrire des glucocorticoides (GC) a faibles doses et sur des durees courtes, si possible moins de 6 mois. Si la toxicite a court terme est bien documentee et parait faible, une controverse existe toujours sur le risque des GC a moyen et long termes. L’objectif de ce travail etait de determiner la tolerance de la corticotherapie a long terme chez les patients atteints de PR incidente dans le cadre de la cohorte ESPOIR. Patients et methodes Nous avons analyse les patients atteints de PR precoce (criteres ACR/EULAR 2010) dans la cohorte ESPOIR. Ils ont ete stratifies en deux groupes, avec ou sans traitement par GC, au moins une fois au cours de leur suivi (mediane de suivi de 10 ans IQR [9-10]). Le critere de jugement principal etait un critere composite defini par la survenue de deces, d’evenements cardiovasculaires (incluant ischemie myocardique, accident vasculaire cerebral, insuffisance cardiaque), d’infection severe, ou de fracture. Afin de reduire l’impact du biais de selection des traitements et des facteurs de confusion potentiels, un modele de Cox pondere par score de propension, methode IPTW (inverse probability of treatment weighting), a ete utilise. Resultats Parmi les 608 patients atteints de PR (480 femmes, âge moyen de 47,5 ± 12,1 ans), 397 patients (65 %) ont recu de faibles doses de prednisone (mediane 1,9 mg/jour [IQR 0,6-4,2]), principalement pendant les 6 premiers mois (70 %). La duree moyenne du traitement par GC etait de 44,6 ± 40,1 mois. Au total, 95 evenements ont ete identifies au cours du suivi : 10 deces, 18 evenements cardiovasculaires, 32 fractures et 35 infections severes. En analyse univariee a 10 ans, les patients prenant des GC ont connu significativement plus d’evenements (n = 71) que ceux sans GC (n = 24) (p = 0,035), en particulier des infections severes (n = 30 avec GC contre 5 sans GC, p = 0,009) ( Tableau 1 a), avec un effet dose cumulee (p = 0,007). En analyse multivariee (methode IPTW), le risque de survenue d’evenements est significativement associe au traitement par GC (p Tableau 2 ). Conclusion Cette analyse de la cohorte ESPOIR sur 10 ans met en evidence un risque eleve dose et temps-dependant de survenue d’evenements severes d’un traitement par GC a faible dose dans la PR incidente.

Background:We previously failed to find any significant difference with regard to severe outcomes (death, severe infections, fractures, cardiovascular diseases [CVD]) between recent-onset RA patients taking or not low-dose GC treatment in a 7-year analysis of the ESPOIR cohort (1).Objectives:To explore the 10-year tolerability profile of GC use in patients with early RA.Methods:We analysed data from the early arthritis (less than 6 months disease duration) ESPOIR cohort. Patients were stratified in two groups, with or without GC treatment at least once during their follow-up (median 10 years IQR [9-10]). The primary outcome was a composite of death, CVD (including myocardial ischemia, cerebrovascular accident and heart failure), severe infection and fracture. In order to reduce the impact of treatment selection bias and potential confounding factors, the weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method.Results:Among the 608 RA patients (480 women, mean age of 47.5 ± 12.1 years), 397 patients (65%) received low-dose prednisone (median 1.9 mg/day [IQR 0.6-4.2], mainly during the first 6 months (70%). The mean duration of GC treatment was 44.6 months ± 40.1. Overall, 95 events were identified during follow-up: 10 deaths, 18 CVD, 32 fractures and 35 severe infections. Based on univariate analysis at 10 years, patients taking GC experienced significantly more events (n=71) than those without GC (n=24) (p=0.035), especially severe infections (n=30 with GC versus 5 without GC, p=0.009) (table 1), with a cumulative dose effect (p=0.007).On weighted Cox time-dependent analysis, using the IPTW propensity score method, the risk of events over time was significantly associated with GC treatment (p ) (figure 1 and table 2).Table 1.Primary outcome and events at 10 years: univariate analysisTotal study population (n=608)Without GCWith CGP ValuePrimary outcome95 (15.6%)24 (11.4%)71 (17.9%)0.035Death10 (1.6%)1 (0.5%)9 (2.3%)0.103Cardiovascular diseases18 (3%)3 (1.4%)15 (3.8%)0.177Severe infections35 (5.8%)5 (2.4%)30 (7.6%)0.009Fractures32 (5.3%)15 (7.1%)17 (4.3%)0.137Table 2.Time-dependent relationship between glucocorticoids treatment and risk of eventsestimated by hazard ratioTime (Months)Hazard Ratio (95% CI)120.46 (0.23 - 0.90)240.62 (0.36 - 1.08)360.83 (0.52 - 1.33)481.12 (0.73 - 1.72)601.52 (0.96 - 2.40)722.05 (1.19 - 3.52)842.77 (1.44 - 5.34)963.74 (1.69 - 8.26)1085.05 (1.98 - 12.91)1206.83 (2.29 - 20.35)Figure 1.Time-dependent relationship between glucocorticoids treatment and risk of eventsestimated by hazard ratio (HR)Conclusion:This 10-year analysis of the ESPOIR cohort supports a dose and time-dependent impact of very low-dose GC treatment in early RA, with a long-term high risk of severe outcomes.Disclosure of Interests:Camille Roubille Consultant of: Servier, Pfizer, Novartis, Amandine Coffy: None declared, Nathalie Rincheval: None declared, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Jean-Pierre Daures: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB

Resume Objectifs Evaluer la duree moyenne de traitement par fondaparinux 2,5 mg (ARIXTRA®) en medecine generale ambulatoire dans son indication de thromboprophylaxie medicale et decrire la population rejointe. Methodes Etude epidemiologique prospective, observationnelle, nationale et multicentrique realisee a la demande de la Commission de la transparence. Les medecins generalistes devaient inclure les 3 premiers patients adultes, traites en ambulatoire, consideres comme a haut risque d’evenements thromboemboliques veineux, alites pour une affection medicale aigue et ayant l’instauration d’un traitement par fondaparinux 2,5 mg en thromboprophylaxie. Resultats Deux cent dix-sept medecins ont inclus 840 patients. Les patients etaient âges de 63,6 ± 18,1 ans en moyenne, 63 % etaient des femmes. La duree totale reelle de traitement par fondaparinux 2,5 mg etait connue pour 797 patients et etait en moyenne de 15,8 ± 12,4 jours (min–max : 1–90 jours, mediane : 10 jours). Pour 57 %, la duree etait comprise entre 6 et 14 jours (duree indiquee dans les mentions legales). Parmi les 834 patients analyses, 569 (68 %) presentaient au moins une pathologie aigue a risque thromboembolique et avaient au moins un facteur de risque thromboembolique personnel renseigne. L’indication a ete conforme a l’ensemble des mentions du resume des caracteristiques du produit du fondaparinux 2,5 mg pour 52 % des patients (n = 434/834 patients). Conclusion Les resultats de l’etude ArchiMed montrent un usage du fondaparinux 2,5 mg en conditions reelles de medecine generale ambulatoire le plus souvent conforme aux recommandations, quant a sa duree de traitement et dans son indication de prevention en situation medicale aigue. Cependant, un ecart a egalement ete observe, aussi bien en termes de duree de traitement, qu’en termes d’indication initiale, dans des situations considerees a risque thromboembolique veineux par le prescripteur.

Resume Objectifs Evaluer la duree moyenne de traitement par fondaparinux 2,5 mg a l’hopital, dans son indication thromboprophylaxie en prevention medicale et decrire la population rejointe. Methode Etude epidemiologique prospective, observationnelle, nationale et multicentrique realisee a la demande de la Commission de la transparence, en complement du volet ville, precedemment mene en medecine generale. Dans le volet hopital, les pharmaciens hospitaliers devaient inclure les 15 premiers patients adultes, hospitalises (hors services de chirurgie), ayant l’instauration d’un traitement par fondaparinux 2,5 mg en thromboprophylaxie medicale. Resultats Cinquante-trois pharmaciens hospitaliers (49,5 %) ont inclus 718 patients âges de 71 ± 16 ans en moyenne (53 % > 75 ans) dont 54 % etaient des femmes. La duree totale reelle de traitement par fondaparinux 2,5 mg, etait en moyenne de 19,1 jours (min–max : 1–295 jours, mediane : 11 jours). Pour 41 % des patients, la duree totale de traitement etait comprise entre 6 et 14 jours. Quatre-vingt-cinq pour cent des patients avaient au moins une pathologie associee a la prescription d’un traitement par fondaparinux 2,5 mg. Dix pour cent des patients avaient au moins un facteur de risque renseigne par le medecin ou etaient âges de plus de 75 ans. La mise en perspective des caracteristiques des patients du volet hopital et du volet ville montre des differences de profil. Conclusion ArchiMed hopital, qui s’inscrit dans une categorie d’etudes qui s’apparente a des « audits de pratique », montre que la prescription du fondaparinux 2,5 mg en conditions reelles d’utilisation a l’hopital est globalement en adequation avec les recommandations pour l’indication de prevention en situation medicale aigue.

Summary What is known and Objective: In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High-dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high-dose methotrexate as it relates to event-free survival (EFS) in children with ALL. Methods: Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (Vd) of the drug were estimated by the nonmem computer program and also compared between both groups. Results and Discussion: Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse. What is new and Conclusion: Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single-drug pharmacokinetic estimates within a complex multiple-agent protocol appear to be unreliable. However, therapeutic drug monitoring of high-dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.

The Internet has become a major source of health information for consumers. Nevertheless the quality of medical information varies widely and is generally poor. Aim This study aimed to evaluate the quality of information delivered on French-speaking Internet about the diabetic foot. Methods Websites were selected using three popular search engines and introducing “foot + diabetes” and “foot + diabetic” as keywords. Two diabetologists independently evaluated the quality of information using a specially created scoring grid (range 0–52) based on acknowledged and published criteria with items relevant to general characteristics of the site and to information content. One hundred and twenty websites were selected but only 27 were included for analysis. Results Agreement between the two raters was close for global score and site content but lower for site characteristics. Averaged global score ranged from 8 to 44. Only five sites were assessed as very advisable with a score higher than 39; in contrast 18 sites were judged as not advisable at all (score lower than 26). Conclusion This study, the first to be devoted to information about the diabetic foot on the Internet, clearly shows the variability and the general poor quality of information delivered by the great majority of French-speaking websites. Regulation organisms are urgently needed for checking and labelling public oriented health information in order to make the Internet a performing tool for patient information.

International audience; OBJECTIVE:To evaluate the mean duration of treatment course with fondaparinux 2.5 mg (ARIXTRA(®)) in the setting of ambulatory general medicine, with respect to its indication in thromboprophylaxis for medically ill patients and to describe the population treated.METHODS:Observational, prospective, national, multicenter, pharmaco-epidemiological study, performed in France, at the request of the Transparency Commission (a division of the French Health Regulatory Authority). The general practitioners had to include the first three adult patients, considered as patients at high risk of venous thromboembolic events and immobilized for acute medical illness, treated with initiation of thromboprophylaxis by fondaparinux 2.5 mg.RESULTS:Two hundred and seventeen general practitioners included 840 patients. The mean age of patients was 63.6±18.1 years, and 63% of patients (n=520/831) were females. The real total administration duration of the treatment by fondaparinux 2.5 mg was known for 797 patients and was 15.8±12.4 days on average (range: 1-90 days, median: 10 days). In 40% of patients, the duration ranged from 6 to 14 days [duration consistent with the summary of product characteristics (SmPC)]. Among the 834 patients analyzed, 569 (68%) suffered from at least one acute illness and had at least one risk factor for venous thromboembolism (VTE). The indication did fully comply with the summary of product characteristics of fondaparinux 2.5 mg in 52% of the patients (n=434/834 patients).CONCLUSION:The results of the ArchiMed study support that the thromboprophylaxis treatment with fondaparinux 2.5 mg in ambulatory general medicine, and the associated medical conditions were usually consistent with the SmPC or guidelines. However, a difference was found for the duration and the initial indication, in situations that may be regarded as presenting a risk by the prescriber.

International audience; OBJECTIVE:To evaluate the average duration of in-hospital treatment with fondaparinux 2.5mg prescribed for venous thromboprophylaxis in acutely ill medical patients and to describe the treatment population.METHODS:Prospective, observational, national, multicentre, epidemiological study, performed in France at the request of the Transparency Commission of the French National Health Authority (Haute Autorité de Santé). This is part of a larger study program that also included a study with similar design in the general practice setting. The hospital practice part of the study was conducted by hospital pharmacists who were asked to include the first 15 adult subjects hospitalized in a non-surgical ward for whom fondaparinux 2.5mg was initiated for prophylaxis.RESULTS:Fifty-three pharmacists (49.5%) included a total of 718 patients. The average age was 71 ± 16 years (47%

Resume Objectif Cet article a pour ambition de detailler et d’expliquer la methodologie de l’enquete MISSION (Menopause : risque de cancer du sein, morbidite et prevalence) dont les buts sont de determiner en France la prevalence du cancer du sein et de la morbidite hors cancer du sein, chez la femme menopausee suivie par un gynecologue et traitee par un Traitement Hormonal Substitutif (THS) ou non. Materiel et methode Six mille six cents femmes menopausees [3300 sous THS — a l’etude uniquement : pour l’œstrogene : œstradiol par voie orale ou cutanee ; pour le progestatif associe le cas echeant : progesterone naturelle et assimiles ou l’un des derives pregnanes (a l’exception de specialites contenant du medroxyprogesterone acetate) ou nor-pregnanes — et 3300 sans THS] seront recrutees en France par 825 gynecologues investigateurs membres ou non de la Federation Nationale des Colleges de Gynecologie Medicale (FNCGM) du 5 janvier 2004 au 28 fevrier 2005. Il s’agit d’une enquete de type historico-prospective avec tirage au sort des cas recrutes. Elle est menee a l’initiative du Laboratoire Theramex-Merck sous l’egide d’un Centre Collaborateur de l’O.M.S. (Organisation Mondiale de la Sante) pour les aspects de Sante Publique des affections rhumatismales et de l’osteoporose et en collaboration avec un groupe d’experts multidisciplinaires. Conclusion Les premiers resultats contribueront a l’amelioration de nos connaissances en sante de la femme et apporteront des elements propres a un hypothetique particularisme a la francaise sur le relationnel entre THS et cancer du sein.

To determine prognostic factors for remission in early rheumatoid arthritis.191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of1.6, was used as the outcome measure. Baseline clinical, laboratory, genetic, and radiographic data (with radiographic scores determined by Sharp's method, modified by van der Heijde) were obtained.48 patients (25.1%) fulfilled the remission criteria at the three year follow up visit, and 30 (15.7%) at three and five years. On univariate analysis by Fisher's exact test, remission at three years and persistent remission at five years were closely correlated with baseline DAS values, C reactive protein level, Ritchie score, health assessment questionnaire score, duration of morning stiffness, and to a lesser extent baseline total radiological scores and rheumatoid factor negativity. No significant correlation was found with sex, age, extra-articular manifestations, erythrocyte sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline independent variables predictive of remission were low DAS, Ritchie score, morning stiffness duration, and total radiographic score.Baseline prognostic factors for remission in early rheumatoid arthritis were mainly clinical markers of disease activity and radiological scores.

To compare the diagnostic values of three T2-weighted sequences in unselected brain 0.5-T magnetic resonance (MR) imaging examinations.MR imaging was performed in 102 patients because of neurologic symptoms or the follow up "previously known disease." The protocol comprised three T2-weighted sequences: turbo spin-echo (SE), turbo fluid-attenuated inversion-recovery (FLAIR), and gradient and SE (GRASE) sequences. In a prospective, blinded analysis, sequences were compared quantitatively and qualitative by three independent readers for lesion detection and characterization.Twenty-four patients had normal findings, and 78 had abnormal findings, with 121 final diagnoses. Quantitatively, the "white" cerebrospinal fluid (CSF) sequences, turbo SE and GRASE, had higher contrast-to-noise ratios (CNRs) than the "black" CSF sequence, FLAIR, with respect to the signal intensity of white manner, but lower CNRs than FLAIR with respect to the signal intensity of CSF. Qualitatively, for lesion detection, sensitivity and accuracy were significantly higher for FLAIR than for turbo SE or GRASE (P.05); there was no statistically significant difference between turbo SE or GRASE. FOR lesion characterization, FLAIR was significantly superior to GRASE and turbo SE for white matter disease (P.05), superior to only turbo SE (P.05) for vascular disease, and not superior to GRASE or turbo SE for tumors.The black CSF T2-weighted turbo FLAIR sequence is a useful adjunct to the usual white CSF T2-weighted sequences in unselected brain 0.5-T MR imaging.

International audience; OBJECTIVE: To investigate if patients with early RA with persistent moderate disease activity during the first year after diagnosis have a worse 3-5 year outcome than those who achieve sustained clinical remission within the first year, in a daily life setting. METHODS: The ESPOIR cohort included patients with early arthritis of 3.2 and ≤5.1) at both the 6- and 12-month visits, with those who were in sustained DAS28 remission. The primary outcome was radiographic progression at the 36-month visit. Secondary endpoints were clinical remission (DAS28 score, Simplified Disease Activity Index, ACR/EULAR criteria), Health Assessment Questionnaire-Disability Index (HAQ-DI) and number of missed workdays at months 36 and 60. A Fisher exact test was used to compare categorical variables, and the Kruskal-Wallis test for quantitative variables. Logistic regression analysis was used to determine predictors of outcome. RESULTS: Patients were aged 48.1±12.5 years and their duration of symptoms was 103.2±52.1 days. Mean baseline DAS28 was 5.1±1.3. Persistent moderate disease activity (107 patients) rather than sustained remission (155 patients) during the first year was associated with increased radiographic disease progression at 3 years (OR=1.99 (95% CI 1.01 to 3.79)), increased HAQ-DI at 3 and 5 years (5.23 (2.81 to 9.73) and 4.10 (2.16 to 7.80), respectively), a 7-11 times smaller chance of achieving clinical remission and a five times greater number of missed workdays. CONCLUSIONS: Patients with early RA with persistent moderate disease activity during the first year had a worse outcome than patients who achieved sustained clinical remission. Persistent moderate disease activity affects long-term structure, remission rate and functional and work disability. Such patients may benefit from intensive treatment.

Background Diabetes was found to be increased in patients with rheumatoid arthritis (RA). Objectives The objective of this study was to evaluate the impact of hyperglycemia and diabetes on clinical activity and radiographic progression within the first 3 years in patients with early RA. Methods Patients of the ESPOIR cohort with early RA meeting the ACR/EULAR 2010 criteria and with data available for fasting blood sugar at baseline were analyzed. Glycemic status was analyzed with 2 different definitions: i) history of type I or II diabetes; ii) baseline blood sugar splitted into 3 categories: normal ( Results 26 patients were known to be diabetic and 619 patients were non-diabetic. At baseline, 479 patients had normal blood sugar; 96 had pre-diabetic levels and 26 had diabetic levels. These three groups initially differed on age, body mass index, presence of rheumatoid factor, and score DAS28 Sharp erosion. In multivariate analysis, DAS28 during the first three years were significantly higher in patients with hyperglycemia (p Conclusions In early RA, blood sugar level is an independent predictor of disease activity and structural progression at 3 years, with a dose-dependent effect. Beyond cardiovascular complications, the measurement of blood sugar in patients with early RA may also help to assess more precisely the prognosis of the disease. Disclosure of Interest None declared

Background The quantification of health improvements is essential, notably in the current context of increasingly expensive therapies and more and more limited resources. Preference-based measures of health have become important for estimating health states in calculating quality-adjusted life years (QALYs), an essential component of cost-utility analysis. The SF-6D is an indirect preference-based health-related quality of life instruments increasingly being used for economic evaluation of clinical interventions and health programs. Data on economic as well as QoL outcomes among early axial Spondyloarthtritis (axSpA) patients remain scarce. Objectives To evaluate the validity of an utility measure, the SF-6D, in early axSpA especially concerning the ability of this measure to reflect the change in patients9 condition over time. Methods DESIR (Devenir des Spondyloarthropathies Indifferenciees Recentes) is a French, multicentre, longitudinal cohort of 708 patients with early inflammatory back pain suggestive of axSpA. SF-6D utility measures were assessed in 607 patients over 1 year. To investigate whether the change in SF-6D is a valid measure of change in axSpA health status, we used Spearman9s product-moment correlation to compare change scores for SF6D with those for external measures of health, the HAQ, SF36 physical component, SF36 mental component and AS-QOL from baseline to 6 and 12 months. Responsiveness was tested by the effect size (ES) at 6 and 12 months for the entire sample and subgroups by disease evolution (increase or decrease-stabilization in BASDAI). Bootstrap methods were used to estimate 95% confidence intervals [95% CI]. Sensitivity to change of the HAQ was calculated as a benchmark. Results At baseline, mean value of SF-6D was 0.69±0.12 (range 0.30 to 0.95). The distribution was near normal. Few missing values were observed: 2.4%. No floor or ceiling effects were evidenced. Correlations of the SF6D change with change in HAQ and physical component of SF-36 scores were moderate at 6 months (r=-0.42 and 0.44, respectively). Correlations with change in mental component of SF-36 and AS-QOL scores were good (r=0.60 and -0.60, respectively). Correlations were stable over 1 year. For the entire sample at 6 months, the SF-6D was more sensitive to change than the HAQ: ES 0.36 [95% CI 0.28;0.44] versus -0.22 [-0.28;-0.17]. The SF-6D was more responsive than the HAQ for improved condition: ES 0.45 [0.37;0.54] vs -0.32 [-0.38;-0.26] without difference for patients with deteriorated condition: ES SF-6D -0.23 [-0.41;-0.04] vs 0.33 [0.18;0.50] for HAQ. Results were similar at 12 months. Conclusions The SF-6D is valid and able to reflect the change in patients9 condition over time, especially improvement, in patients with early inflammatory back pain suggestive of axSpA. Disclosure of Interest None declared

Background Patients and physicians often differ in their perceptions of rheumatoid arthritis (RA) disease activity, as quantified by the patient9s global assessment (PGA) and by the evaluator9s global assessment (EGA). The quest for understanding the reasons for discrepancies in evaluations of disease activity becomes particularly important in the context of recent recommendations that define Boolean-based ACR EULAR remission as the treatment target. Objectives The objectives of this study were: 1) to explore the extent and reasons for this discordance 2) to determine if this discordance at baseline is associated with RA outcomes at 1 year (remission, function and structure) in early RA in daily clinical practice. Methods Patients: from the French cohort of EA ESPOIR (at least 2 swollen joints for less than 6 months, DMARD naive), fulfilling the ACR-EULAR criteria for RA at baseline Analyses: At baseline, agreement between PGA and EGA (Bland-Altman plot) was assessed. Multivariate linear regression was used to determine the patient and EA features independently associated with discordance (calculated as PGA − EGA). Logistic regression was used to analyze discordance as |PGA − EGA| ≥20. Multivariate logistic models were used to determine if discordance at baseline is associated with remissions (Boolean, SDAI and DAS28), functional stability (HAQ ≤0.5 and deltaHAQ ≤0.25) and absence of radiographic progression (delta Sharp score Results In 645 patients with ERA (mean age=48.8±12.2 years, 77% female, 48.7% ACPA+) agreement was better at both ends of the spectrum, especially for patients with high disease activity. Evaluation of disease activity yielded discordant scores between the patients and their physicians in 30% of our cohort: 153 patients (24%) had higher PGA scores, 41 patients (6%) had higher EGA scores, and 451 patients (70%) had concordant PGA and EGA scores (|PGA − EGA| In multivariate linear regression center-adjusted, higher PGA has been found to be associated with absence of fulfilling ACR 1987 revised criteria for RA (p=0.0005), higher levels of fatigue (p In multivariate analyses, discordance at baseline was not associated with remission, function and structural progression at 1 year. Conclusions In early RA, the discordance between PGA and EGA is multifactorial with objective measures like low SJC and absence of ACR 1987 revised criteria for RA, but also patient reported outcomes like high level of fatigue and low mental status, and environmental factor: living alone. Discordance between PGA and EGA at baseline was not associated with RA outcomes at 1 year. Understanding the reasons for a discordant view of disease activity will help to facilitate the sharing of decision-making in the management of RA. Disclosure of Interest None declared

The are few outstanding serous markers in the treatment of bronchial cancer. ACE lacks sensitivity and specificity and cannot be used as a diagnostic marker. It has been described as a marker of tumoral mass, although not in our study. Prognostic significance was observed, but only in a univariate analysis. Sensitivity of SCC TA4 varied between studies. In our population, the ROC curve for SCC TA4 showed poor discrimination potential. NSE was shown to be a useful marker in the treatment of patients with small cell cancers. Cytokeratins are expressed by all bronchial cancers. Cytokeratin 19 is a sub-unit detected in simple epithelia and their neoplastic counterparts. During tumoral cell lysis, certain fragments of this cytokeratin may be liberated. The immunoradiometric assay described here is able to detect fragments of cytokeratin 19 (called Cyfra 21-1) in serum. Our study established a correlation between Cyfra 21-1 levels and the cancer stage for NCPC, but not for CPC. In addition, Cyfra 21-1 concentration may be used as a tumoral mass marker. Patients with high Cyfra 21 levels must undergo special treatment to find remote tumors.

In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High-dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high-dose methotrexate as it relates to event-free survival (EFS) in children with ALL.Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (V(d) ) of the drug were estimated by the NONMEM computer program and also compared between both groups.Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse.Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single-drug pharmacokinetic estimates within a complex multiple-agent protocol appear to be unreliable. However, therapeutic drug monitoring of high-dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.

The French health policy PMSI project (Program for a Medical Information System) is mainly aimed at development of cost analysis based on diagnosis related groups. An indicator of the relative costs of anaesthetics, the relative complexity index (ICR beta), was defined as the result of a computation of different indexes of surgical and anaesthetic procedures such as duration, patients ASA status, degree of emergency, stay in the recovery room. The aims of this study were 1) to analyze relative part of each index in ICR beta value and in ICR beta variance and 2) to assess the value of ICR beta as a cost or a complexity index. The study included 14,435 anaesthetics analyzed with the Dunn and Clarks multiple linear regression. Mean ICR beta was 267.28. The duration of the procedure accounted for 46% of the ICR beta value and surgery for 25%. The anaesthesia and the recovery accounted for 15% of the ICR beta value, but only for 0.0341 and 0.0347 respectively of the ICR beta variance. The product of the surgical procedure index by the ASA status index accounted for 0.259 of the ICR beta variance and the duration index for 0.650. The comparison of homogeneous groups with regard to the surgical procedure shows that intravenous anaesthesia accounts for 12.4% of the ICR beta value, inhalational anaesthesia for 13.84%, but exceeds 15% for regional anaesthesia (44.5% for caudal anaesthesia). For appendectomies (n = 114) duration index is still an important parameter in ICR beta variance (delta R2 = 0.354) but equivalent to the emergency index (delta R2 = 0.363).(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE—To determine the influence of HLA-DRB*1 genes on susceptibility to and severity of rheumatoid arthritis (RA) in patients with late onset compared with younger onset disease. METHODS—The clinical, biological, and HLA-DRB1 typing characteristics of two groups of patients were studied retrospectively. Group 1 consisted of 262 patients whose disease onset was before or at the age of 60 (young onset RA (YORA)). Group 2 included 60 patients whose illness began after the age of 60 (elderly onset RA (EORA)). RESULTS—The shared epitope level was similarly increased in both groups of patients compared with normal controls (195/262 (74%) in group 1 and 43/60 (72%) in group 2 v 645/1609 (40.1%) in controls). No differences were noted between the two groups of patients for each separate disease related allele. In contrast, when studying all HLA-DRB1*04 RA related alleles as a group, these alleles were underrepresented in EORA compared with YORA (22/60 (37%) v 135/262 (52%); odds ratio 2.0; 95% confidence interval 1.0 to 3.3). An inverse trend was seen for HLA-DRB1*01 alleles. There were no differences in biological characteristics or extra-articular manifestations between the patient groups. The differences noted in radiological evaluation or the number of prescribed disease modifying antirheumatic drugs seemed to be linked with differences in disease duration. CONCLUSION—HLA-DRB1 RA related alleles influence both EORA and YORA. However, HLA-DRB1*04 RA linked alleles are not as closely associated with RA in the elderly as they are in younger patients. This suggests that the importance of these genes in the susceptibility to RA may be lower in elderly patients.

Background: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. Objective: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. Methods: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to “distribute 100 points” among the seven domains. The average ranks of importance of these domains were then computed. Results: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. Conclusion: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.

Resume A partir du recueil informatise de 102 468 anesthesies effectuees en cinq ans (1983–1987), la frequence et les causes des arrets cardiaques (AC) survenus en periode peroperatoire ou en salle de reveil sont analysees de maniere retrospective. Sur les 186 AC releves, 29 sont lies partiellement ou totalement a l'anesthesie. Le taux de recuperation des AC non lies a l'anesthesie est de 8,3 % et celui des AC lies a l'anesthesie de 62 %. La mortalite liee a l'anesthesie est de 1,1/10 000. Les trois causes principales d'AC lies a l'anesthesie sont le surdosage ± hypovolemie (n = 9), les AC de cause non reconnue (n = 8) et les hypoxies (n = 6). Un score ASA eleve et les anesthesies rachidiennes augmentent le risque d'AC lies a l'anesthesie (8 AC sur 12 981 anesthesies regionales vs 21 AC sur 89 487 anesthesies generales; p = 0,017). L'urgence et le moment de l'anesthesie ne sont pas des facteurs de risque. La survenue de l'AC a l'induction et les causes univoques comme les hypoxies ou les surdosages ± hypovolemie induisent un bon pronostic. En revanche, ni le score ASA, ni l'urgence ne sont des facteurs pronostiques. Le devenir des AC survenant sous anesthesie rachidienne (7/8 recuperes) semble meilleur que sous anesthesie generale (p = 0,08; ns). De l'analyse de ces resultats peuvent etre degagees diverses regles de securite anesthesique.

Objectives:Patient-reported outcomes (PROs) have been increasingly recognised as important in rheumatoid arthritis (RA). The objective of this study was to assess the frequency of use of different PROs in recently published RA articles and to compare the tools used through a systemic literature review.Methods:(1) Data source: In PUBMED MEDLINE database, articles reporting any type of clinical study for adult patients with RA, published between February 2005 and February 2007, and reporting any type of PRO. Articles were excluded if they did not concern adult RA or if they did not report any PROs. (2) Data extraction: demographic characteristics of patients, study design, treatment assessed and all PROs. (3) Data analysis: descriptive.Results:Of 109 reports, 50 (45%) were randomised controlled trials and 59 were other types of studies. A total of 63 questionnaires or tools for PROs were used, corresponding to 14 domains of health. Frequently reported domains (and most frequent tools) were: function, 83% (most frequent tool, health assessment questionnaire, HAQ); patient global assessment, 61% (most frequent tool, visual analogue scale, VAS); pain, 56% (VAS); and morning stiffness 27%. Domains such as fatigue, coping or sleep disturbance were infrequently reported.Conclusions:PROs are reported with great heterogeneity in recently published trials in RA. Some domains that appear important from the patient’s perspective are infrequently reported. Further work is needed in this field.

To assess the radiological damage progression in patients with recent rheumatoid arthritis in sustained remission.A cohort of 191 patients with active early (1 year) rheumatoid arthritis was prospectively assessed at baseline, 3 and 5 years by the Disease Activity Score (DAS) and the Sharp-van der Heijde Score (SHS) for radiographic damage. Patients in remission (DAS1.6) at the 3-year and 5-year time points were compared with patients with a persistently active rheumatoid arthritis by Wilcoxon's signed rank test.57 patients died, were lost to follow-up or had incomplete data; 30 (15.7% of those who completed) patients were in remission at 3 and 5 years. The SHS in these two groups was not significantly different at baseline (p = 0.15), but was lower in the remission group at 5 years (p = 0.0047). The median (IQR) radiographic score increased from 0.5 (0-7) at baseline to 2.5 (0-14) after 5 years for the remission group (p = 0.18) and from 2 (0-7) to 13 (3-29) in the group with active rheumatoid arthritis (p0.001). 5 (16.7%) patients in remission had relevant progression of radiographic damage (ie, progression4.1 points) and 6 (20%) presented new erosions in a previously unaffected joint between the third and the fifth years.Patients with early rheumatoid arthritis in sustained remission did not present statistically significant radiographic degradation at the group level; nevertheless, 16.7% of these patients did present degradation. Absence of progression should be part of the remission definition in rheumatoid arthritis.

La difficulte de depistage de masse organise de cancer du poumon repose sur la specificite de ce cancer, c’est-a-dire l’existence d’un seul facteur de risque principal (et de quelques autres qui entrent en interaction avec lui).

To analyse antimicrobial resistance trends of Proteus mirabilis urinary tract isolates from 1999 to 2005 at the Nîmes University hospital.We retrospectively collected non-duplicate urinary tract infections and colonization isolates from inpatients between 1 January 1999 and 31 December 2005.One thousand and eight non-duplicate urinary tract isolates were studied, 63.1% were from females and the mean age was 76 years. The mean resistance rate was 59.0% for amoxicillin (AMX), 48.0% for piperacillin (PIP), 3.9% for cefotaxim, 33.9% for amoxicillin plus clavulanic acid (AMC) and 2.8% for piperacillin plus tazobactam (TZP). A significant increase in resistance was observed for AMC and TZP. The mean resistance rate was 35.0% for norfloxacin, 34.8% for ofloxacin and 23.5% for ciprofloxacin. No significant increase in resistance to fluoroquinolones was seen except for ciprofloxacin whereas a significant increase was observed for aminoglycosides. The mean rate resistance for cotrimoxazole was 33.2% with a significant decrease in the resistance during the study period.P. mirabilis stilled sensitive to cefotaxim or ceftazidim and to TZP. The significant increase in the rate resistance to AMC and TZP could be explained by production of beta-lactamases and in particular extended-spectrum beta-lactamases. The increase in resistance observed for fluoroquinolones become a major concern. Amikacine was the most active aminoglycosides. These data suggested for the re-enforcement of the antimicrobial susceptibility surveillance in order to optimise the rational use of antibiotics.

To describe the ovarian cancer incidence and mortality trends in France from 1980 to 2000.Incidence data were obtained from 9 French departments covered by cancer registries which systematically record all cancers, of which those of the ovary. Mortality data has been provided by INSERM bureau in charge of the analysis of death certificates.With 4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer still shows a poor prognosis. Age adjusted incidence and mortality rates are almost stable over the study period at an annual rate of 9 by 100000 for incidence and 5.5 by 100000 for mortality. However the risk of developing this cancer and the risk of dying from it, steadily decreased for the cohort born in 1930 to 1950, and the beginning of this reduction corresponds exactly to the beginning of oral contraception. We present comparisons between departments and analyze the border-line tumors in parallel with invasive cancers.The cancer of the ovary represents only a small part of female cancers (3.8%) in France and its incidence is stable over time, but its prognosis is very bad.

The emergence of Escherichia coli (E. coli) resistance to fluoroquinolones (FQs) increased and spread gradually worldwide since the early 1990s. The selective pressure of FQs is the main mechanism responsible for the emergence of FQ resistance as shown by in vitro studies. Clinical trials are required to prove the causality between exposure to FQs and emergence of resistance. But this would not be ethical in humans. Non experimental studies must answer several principles to establish causality: association, anteriority, and directional change. We described and compared the contribution of observational and quasi-experimental studies implemented to answer several of these principles. Quasi-experimental studies using interventional models (ARIMA models with transfer function), can answer several of these principles, unlike observational studies. Thus, in addition to assessment of the association, they were able to show that the exposure to FQs precedes the emergence of FQ resistance to E. coli. They were also able to estimate the time necessary for the emergence of resistance and the dose effect, and to show if this association was reversible.

Objective: To describe the characteristics of rheumatoid arthritis in patients managed by hospital based rheumatologists in France. Methods: All public and non-profit private hospitals in France were invited to participate in a cross sectional study. Clinical data on the day of inclusion and health resources used for rheumatoid arthritis over the previous 12 months (treatments, medical devices, physician visits, examinations, hospital admissions, and other health professional care) were recorded. Results: 1109 patients from 75 centres located throughout the country were included (846 female; mean disease duration, 10.6 years; mean age, 56.7 years). Active disease (swollen joint count ⩾6, tender joint count ⩾6, and two of: morning stiffness ⩾45 min, C reactive protein ⩾20 mg/l, erythrocyte sedimentation rate >28 mm/h) was observed in 146 patients (13.2%). Mean (SD) DAS 28 was 4.51 (1.55). Severe extra-articular manifestations were reported in 8.4%. ACR functional status was: class I, 19%; class II, 28%; class III, 31%; class IV, 22%. Comorbidity was observed in 44.9% of cases, particularly chronic pulmonary disease and coronary or peripheral vascular disease. Average AIMS2-SF dimension scores were between 4.56 and 6.18, and mean HAQ was 1.32 (0.77). Disease modifying antirheumatic drugs (DMARDs) were prescribed for 82.1% of the patients. During the previous four weeks, one DMARD was used in 62.5%, and two or more in 19.5%. Corticosteroids were prescribed in 72%. Conclusions: In a rheumatoid arthritis population managed by hospital based rheumatologists, the disease was active in 13% and severe in more than one third of cases.

Our study focused on aromatase cytochrome P450 (CYP19) expression in ovarian epithelial normal and cancer cells and tissues. Aromatase mRNA expression was analyzed by real-time PCR in ovarian epithelial cancer cell lines, in human ovarian surface epithelial (HOSE) cell primary cultures, and in ovarian tissue specimens (n=94), including normal ovaries, ovarian cysts and cancers. Aromatase mRNA was found to be expressed in HOSE cells, in BG1, PEO4 and PEO14, but not in SKOV3 and NIH:OVCAR-3 ovarian cancer cell lines. Correlation analysis of aromatase expression was performed according to clinical, histological and biological parameters. Aromatase expression in ovarian tissue specimens was higher in normal ovaries and cysts than in cancers (P0.0001). Using laser capture microdissection in normal postmenopausal ovaries, aromatase was found to be predominantly expressed in epithelial cells as compared to stromal component. Using immunohistochemistry (IHC), aromatase was also detected in the epithelium component. There was an inverse correlation between aromatase and ERalpha expression in ovarian tissues (P0.001, r=-0.34). In the cancer group, no significant differences in aromatase expression were observed according to tumor histotype, grade, stage and survival. Aromatase activity was evaluated in ovarian epithelial cancer (OEC) cell lines by the tritiated water assay and the effects of third-generation aromatase inhibitors (AIs) on aromatase activity and growth were studied. Letrozole and exemestane were able to completely inhibit aromatase activity in BG1 and PEO14 cell lines. Interestingly, both AI showed an antiproliferative effect on the estrogen responsive BG1 cell line co-expressing aromatase and ERalpha. Aromatase expression was found in ovarian epithelial normal tissues and in some ovarian epithelial cancer cells and tissues. This finding raises the possibility that some tumors may respond to estrogen and provides a basis for ascertaining an antimitogenic effect of AI in a subgroup of ovarian epithelial cancers.

In studies of disease states and their relation to evolution, data on the state are usually obtained at in frequent time points during follow-up. Moreover in many applications, there are measured covariates on each individual under study and interest centres on the relationship between these covariates and the disease evolution. We developed a continuous-time Markov model with use of time-dependent covariates and a Markov model with piecewise constant intensities to model asthma evolution. Methods to estimate the effect of covariates on transition intensities, to test the assumption of time homogeneity and to assess goodness-of-fit are proposed. We apply these methods to asthma control. We consider a three-state model and we discuss in detail the analysis of asthma control evolution.

Health related quality of life (HRQOL) indicators take into account the personal perception of health, and are proposed as an alternative for efficacy indicators in medical and therapeutic decision making. They provide, due to elaboration and validation of a questionnaire, a standardised assessment of the health status perception. This paper provides a review of a variety of HRQOL instruments developed for patients suffering end-stage renal disease (ESRD). Generic instruments are designed to be applicable in general population and disease-targeted instrument are potentially more sensitive to the characteristics of a specific population. Among HRQOL instruments, we found 4 generic questionnaires (the Sickness Impact Profile, the SF 36, the Nottingham Health Profile and the EQ-5D), 3 disease-targeted questionnaires developed for ESRD patient undergoing dialysis (the Kidney Disease Quality of Life instrument, the Kidney Disease Questionnaire and the Choice Health Experience Questionnaire), 1 questionnaire specific for ESRD patients (the HRQOL questionnaire), and 2 specific disease-targeted instruments for renal transplant (the Kidney Transplant Questionnaire and the ESRD Symptom Checklist-Transplantation Module). In France, very few studies on the quality of life of ESRD patients were published; no specific questionnaire validated in French is yet published.

Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification.We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service.The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost.This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.

The subjective aspects of the doctor-patient relationship may impact disease management methods applied to migraine patients. This prospective study compared the medical attitudes of doctors towards migraine headache in relationship to their personal sensitivity to this disease. The study concerned data on the health care management of migraine headache by 711 general practitioners, 325 of whom suffer from migraine headache themselves, 227 who do not suffer from migraines, but who have a close family member that does, and 159 who neither suffer from migraine headache, nor have anyone close who does. Each doctor filled out a medical practice questionnaire concerning this pathology and included one migraine patient in the survey. Each patient answered a specific quality of life questionnaire. It was shown that doctors suffering from migraine headache themselves declared having more migraine patients in their practices than the other doctors. Nonetheless, the doctor's sensitivity to migraine headache does not seem to have an impact on the diagnosis and therapeutic care of patients; diagnosis criteria are the same within the three groups and correspond to international headache society criteria. Furthermore, the therapeutic means applied, whether acute first or second intention treatment, or long-term treatment, do not differ amongst the three groups. Quality of life and patients' feelings about medical support were significantly related to the doctor's level of sensitivity towards the disease: they were highest amongst patients treated by doctors suffering from migraines themselves, and lowest amongst patients treated by doctors with no close family members suffering from migraines. Although therapeutical attitudes do not vary, the quality of life perceived by patients is better when the doctors themselves are concerned by the disease.

Optimal modalities of surveillance of colorectal cancers (CRC) resected for cure have not been determined so far and the overall improvement of 5-year survival related to surveillance has not been demonstrated.To retrospectively evaluate modalities, results and costs of follow-up of patients during the 5 years following the resection for cure of CRC.We studied medical and economical data from records of 256 patients registered in the cancer registry of the Herault area who underwent a potentially curative resection of CRC in 1992. We analyzed comparatively modalities of follow-up in patients who were followed according to recommendations from the 1998 French consensus conference (standard follow-up) and in those who had a simplified follow-up. We evaluated cumulative costs of follow-up.Nine patients died in the postoperative period. Recurrence rate was 27% (69 patients). Sixty-nine patients had a standard follow-up (30% of the 231 classified patients) and 162 patients (70%) had a simplified follow-up. The specific survival rate (taking into account only death related to CRC) 5 years after resection for cure was 75%. The 5-year specific survival rate after diagnosis of recurrence was 12% in the patients with recurrent disease within the 5 years after initial therapy. The 5-year survival rate after standard and simplified follow-up were 85% and 79%, respectively (P=0.25). Total cost of follow-up of the 256 patients was 1 085 507 French francs (FF). Mean follow-up cost per patient was 5 527 FF. Cost of the examinations not recommended by the consensus conference represented 30% of the expenses. Individual total cost of the follow-up of patients alive 5 years after the diagnosis of the recurrence was 120 356 FF.In Herault area, clinicians carried out in 70% of the patients a simplified follow-up and in 30% of the cases a reinforced follow-up in comparison with French recommendations. Survival rates were not significantly different between the 2 groups.

Clinical evaluation is a multifactorial process producing as many clinical scores as there are clinical dimensions. For a medicoeconomical analysis however, a single global score would be most useful. The aim of this work was to examine methods allowing relative quantification of items on multidimensional clinical scores in order to determine an appropriate solution for weighted items aggregation.Several techniques for item weighting, developed as part of a multi-criteria decision-making tool (AMCD Aide Multi-Critère à la Décision), were examined. Two methods were applied to multidimensional assessment of disability in order to estimate the weight that should be assigned to each of its six items before aggregation in a unique score. The AHP method was used with an interview of 20 functional rehabilitation specialists. The Diakoulaki method was based on the observation of thirty patients with chronic back pain and in thirty patients with vascular hemiplegia.The three weighting schemes were very different from the uniform weighting and were not correlated with each other. The items best weighted by the AHP method were "physical independence" and "mobility". For the Diakoulaki method, they were "social integration" and "economic independence" for the chronic back pain patients, and "awareness of the outside world" and "economic independence" for the vascular hemiplegia patients. Application of these three weighting schemes to theoretical patients produced very different assessments of global disability.Weighting schemes are useful to quantify the relative importance of individual clinical items. The choice of the weighting method is determinant and depends on the objective of the investigator. If the objective is a global score, the first step is to estimate the weight of the individual items, either when applying a validation process for a new multidimensional clinical score, or secondarily to adapt a validated score to a particular protocol.

To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis (RA).A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospectively followed up for 3 years. Radiologic scores (as determined by Sharp's method, modified by van der Heijde) and radiologic progression were used as outcome measures. Numerous baseline clinical, laboratory, genetic, and radiographic data were obtained.The change in the total radiologic score for the patients followed up over 3 years was a mean +/- SD increase of 6.1 +/- 6.2. Radiologic progression was observed in 71 of the 172 patients for whom there were data at the end of the study. By univariate analysis with Fisher's exact test, radiologic scores and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM and IgA rheumatoid factor positivity, antiperinuclear antibody positivity, radiologic scores, duration of morning stiffness, and RA-associated HLA-DRB1*04 genes. No correlation was demonstrated with sex, age, Disease Activity Score, swollen or tender joint counts, extraarticular manifestations, Health Assessment Questionnaire score, Ritchie Articular Index, patient's assessment of pain, positivity for anti-heat-shock protein 90-kd antibodies, anticalpastatin antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin antibodies, and HLA-DRB1*01 genes. The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity, DRB1*04 genes, pain score, and total radiologic score. Progression of joint damage was predicted by the ESR, IgM rheumatoid factor positivity, DRB1*04 genes, and erosions score at baseline.Prognostic factors for radiographic damage in early RA were identified. A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients.

Background Objectives To determine prognostic factors of remission in early RA. Methods A cohort of 191 patients with RA and disease duration shorter than 1 year were prospectively followed-up for 3 years. Numerous baseline clinical, laboratory, genetic and radiographic data (Sharp’s method modified by van der Heijde) were obtained. Remission, defined by a Disease Activity Score (DAS) Results Forty eight patients (25.1%) fulfilled the remission criteria at the 3-year follow-up visit. According to Fisher?s exact test, remission was closely related with baseline values of DAS, HAQ score, morning stiffness, tender joint count, C-reactive protein and radiologic scores. No statistically significant correlation was demonstrated for sex, age, extraarticular manifestations, IgM and IgA rheumatoid factors, anti-perinuclear Ab, anti-keratin Ab, anti-HSP 90, anti-calpastatin Ab, antinuclear Ab, YKL-40 and HLA-DRB1* genotypes. The logistic regression analysis revealed that the independent variables able to predict the 3-year remission were: DAS, HAQ score, morning stiffness and total radiographic score. Conclusion Pronostic factors of remission in early RA were mainly clinical markers of disease activity and radiological scores. Reference Prevoo, et al. Br J Rheumatol. 1996;35:1101

The Cox proportional hazards model restricts the hazard ratio to be linear in the covariates. A survival model based on data from a clinical trial is developed using spline functions with variable knots to estimate the log hazard function. Moreover, the main point of the method is that a knot, seen as free parameters for a piecewise linear spline, represents a break point in the log hazard function which may be interpreted as a threshold value. The likelihood ratio test is used to select the final model and to determine the threshold number for a covariate. Confidence intervals for these threshold values are computed by bootstrapping the data. Two examples illustrate the method.

A food-frequency questionnaire (FFQ) used to assess usual food intake in Southern France has been validated by the classical means of multiple-day food records. To minimise over-estimation of the correlation between the dietary assessments by the FFQ and the reference method, which occurs if the random errors of questionnaire and reference measurement are positively correlated, a triangular comparison, the method of triads, was used.We applied the triads model by comparing the FFQ with two multiple-day food records and three biomarkers. Only 87 subjects were included and completed the protocol. One biomarker (beta-carotene) was used for the 87 subjects and two biomarkers (urinary nitrogen and potassium) were measured in only 40 subjects.For beta-carotene intake assessment, the triad model, including the weighed multiple records (PETRA), was the best with estimates of validity coefficient of 0.39 [confidence interval (CI) 0.18-0.60] for the FFQ, 0.52 (CI 0.24-0.86), for PETRA and 0.85 (CI 0.43-1) for plasma levels of the nutrient. For protein and potassium intake assessment, the triad model including the estimated multiple records was the best only for the estimates of FFQ validity coefficient (0.61; CI 0.28-0.96 and 0.31; CI 0.09-0.66 respectively).Accuracy of the dietary assessment methods permitted a satisfactory estimation of the validity coefficient for beta-carotene intake by the FFQ, despite a small sample. However, the validity coefficients for protein and potassium showed wide CI values, indicating that a sample size50 subjects appears unsatisfactory for validation.

There are many scores for the evaluation of asthma. However, most do not take into account the evolutionary aspects of this illness. We propose a model for the clinical course of asthma by a homogeneous Markov model process based on data provided by the A.R.I.A. (Association de Recherche en Intelligence Artificielle dans le cadre de l'asthme et des maladies respiratoires).The criterion used is the activity of the illness during the month before consultation. The activity is divided into three levels: light (state 1), mild (state 2) and severe (state 3). The model allows the evaluation of the strength of transition between states.We found that strong intensities were implicated towards state 2 (lambda(12) and lambda(32)), less towards state 1 (lambda(21) and lambda(31)), and minimum towards state 3 (lambda(23)). This results in an equilibrium distribution essentially divided between state 1 and 2 (44.6% and 51.0% respectively) with a small proportion in state 3 (4.4%).In the future, the increasing amount of available data should permit the introduction of covariables, the distinction of subgroups and the implementation of clinical studies. The interest of this model falls within the domain of the quantification of the illness as well as the representation allowed thereof, while offering a formal framework for the clinical notion of time and evolution.

To determine outcomes in patients with onset within the last year of peripheral inflammatory arthritis that does not meet classification criteria for any specific disease.Symptoms and laboratory tests were evaluated at baseline and 14 to 60 months later in 43 patients, 32 women and 11 men, with a mean age of 50 years.At baseline, a presumptive clinical diagnosis was made in 16 of the 43 patients. Diagnoses at last follow-up were undifferentiated inflammatory arthritis in seven cases, mild rheumatoid arthritis in 18, psoriatic arthritis in two, Sjögren's syndrome in two, lupus in one, and paraneoplastic syndrome in one. The remaining 12 patients were free of inflammatory joint symptoms; three had symptoms of osteoarthritis and nine were asymptomatic. Factors present at baseline and predictive of progression to definite rheumatoid arthritis were a positive test for rheumatoid factor, presence of an HLA DRB1*04 allele, and a presumptive clinical diagnosis of rheumatoid arthritis.55% of our patients developed a specific inflammatory joint disease, and 42% developed rheumatoid arthritis, which was consistently mild. Resolution of all inflammatory joint symptoms occurred in 28% of cases. A number of clinical laboratory, and genetic findings of use for predicting the outcome of undifferentiated arthritis were identified.

To report the validation of 2 questionnaires of quality of life in chronic hepatitis C and the first results in 100 patients.The questionnaire included 118 items and took 30 to 45 minutes to answer. It included a general index, the Nottingham Health Profile, with 38 items in 6 themes (physical mobility, social isolation, emotional reactions, pain, sleep and energy) and a specific index, the Montpellier Specific Index, with 80 items in 7 themes: symptoms, food, alcohol and tobacco, work, relations with other people, perception of disease.The questionnaires were self-administered to the 100 first patients with chronic hepatitis C without cirrhosis before treatment; 55 men, 45 women, average age 40 year-old, median Knodell's score 8 and median METAVIR score A2 F1. Reduction in the quality of life was frequent and was not highly correlated with biological, virological and histological parameters; it was associated with psychological disorders, reduced sexuality and apprehension of the future.This study showed the feasibility, validation, sensitivity and agreement of a quality of life questionnaire, which included a general index and a specific index of chronic hepatitis C in France. These initial results must be confirmed in studies during antiviral treatment of patients.

The aim of this investigation was to report incidence of childhood leukemia, lymphoma and thyroid neoplasms in children under 15 years of age living in the vicinity of the French Marcoule nuclear reprocessing plant.This exhaustive and retrospective survey was carried out between 1985 and 1995 in children aged under 14 at the time of diagnosis and living inside a 35 kilometer zone around the nuclear site. 656 practitioners, 109 medical analysis laboratories and 5 hospitals or cancer institutes were investigated. A panel of experts checked each case.48 cases of acute leukemia (39 acute lymphoid leukemia and 9 acute myeloid leukemia), 15 cases of lymphoma (8 Hodgkin lymphomas--53%--and 7 non hodgkinian lymphomas including 5 Burkitt lymphomas), 1 case of chronic myeloid leukemia and 1 case of papillary thyroid cancer, appeared among the 1,116,442 children-years followed. The total incidences of leukemias and lymphomas were respectively 4.12 and 1.29.10(-5). Standardised Incidence Ratios, calculated according to Poisson methods and bayesian inference, with various reference rates did not show any excess of risk: 100.67 (95% confidence interval 72-131) for leukemia. Children under 5 years old and living in non exposed areas to dominant winds or downstream rhodanian water drawing presented a 3 or 4 fold decreased risk of leukemia than others (the latter still having an identical risk to that of the general population). This was not true for lymphomas, nor for the other age groups.Over the entire zone, children do not have an increased risk of malignant hematology disease but health monitoring by a systematic collection of cases remains useful around Marcoule. The assumption of aquiferous or air contamination thus still remains questionable: further studies investigating models of contamination are needed to take into account all other nonionizing leucemogenic factors (benzene and viral injection in particular) or correlation studies between health indicators and dosimetry.

To conduct an epidemiological study of rheumatoid arthritis patients seen by office-based rheumatologists in France (first semester of 1996).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.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.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.