[Show abstract][Hide abstract]ABSTRACT: Objectives Lyme disease may be considered by rheumatologists in patients with recent-onset arthritis, even in the absence of suggestive symptoms. The aim of this study was to determine the diagnostic impact of routine Lyme serology in a French cohort of patients with recent-onset arthritis affecting at least 2 joints.
Methods We performed an ancillary study of a French prospective multicentre cohort established to monitor clinical, biological and radiographic data in patients with inflammatory arthritis in at least 2 joints, lasting for 6 weeks to 6 months. Borrelia IgM and IgG antibodies were sought routinely at baseline, using ELISA tests, independently from the physician's strategy for detecting a spirochetal infection. We recorded the proportion of patients with a final diagnosis of Lyme arthritis and evaluated the diagnostic performance of Lyme serology in this particular context. The clinical and biological characteristics of patients according to the Lyme serology results were analysed.
Results Of 810 patients, 657 (81.1%) were negative for IgM and IgG antibodies, 91 (11.2%) had only IgM antibodies, 49 (6%) had only IgG antibodies, and 13 (1.6%) had IgG and IgM antibodies. Thus, 7.6% had IgG positivity, consistent with exposure to Borrelia infection. IgG positivity was significantly more prevalent in the North and North-East regions of France (χ2=14.6, p<0.001). No patients received a definite diagnosis of Lyme arthritis.
Conclusions This study does not support routine Lyme serological testing in patients with recent-onset inflammatory arthritis affecting more than 1 joint.
[Show abstract][Hide abstract]ABSTRACT: Background Obesity is an increasing condition. Previous transversal studies suggested that obesity in patients with rheumatoid arthritis (RA) was associated with a higher disease activity, a poor quality of life and a lower radiographic damage but longitudinal studies are lacking.
Objectives We aimed to evaluate the impact of obesity at RA diagnosis on disease course including disease activity, health assessment questionnaire (HAQ-DI) and radiographic progression during the 3 first years.
Methods 628 patients from the French early arthritis ESPOIR cohort, fulfilling the 2010 ACR/EULAR criteria at baseline, were analyzed. Inclusion characteristics of normal weight (body mass index [BMI] 18.5 to 25), overweight (25-30) and obese (≥30 kg/m2) patients were compared using Khi2 and Kruskal Wallis. The outcome of DAS28 (and its components), HAQ-DI and Sharp score (and its components) was compared between BMI groups using repeated measures ANOVA and mixed models.
Results 353 patients had a normal BMI; 178 patients were overweight and 97 patients were obese. At baseline, obese patients were older and less frequently female, had lower rheumatoid factor levels, a higher Sharp score, lower C reactive protein and erythrocyte sedimentation rate, a higher insulin resistance, a lower practice of sport, higher IL-1RA and leptin levels, lower adiponectin and Dickkopf-related protein 1/sclerostin ratio. Repeated measures ANOVA showed a significant interaction between BMI groups and disease activity overtime with higher DAS28 (p=0.0002) (Fig. 1A), ESR (p=0.012) and disease activity on a visual analog scale (VAS) (p=0.002) and HAQ-DI (p=0.0001) (Fig. 1B) for obese patients. All these results were confirmed in mixed model using random effects model for time. Moreover, metabolic syndrome was associated with a higher DAS28 over time (p=0.011), independently of obesity. Total and erosion Sharp score were not significantly different between BMI groups whereas joint narrowing was significantly higher in obese patients (p=0.016)(Fig. 1C).
Conclusions Obesity at RA diagnosis is associated with a higher DAS28, a higher HAQ, a higher joint narrowing Sharp score over time but a similar total Sharp score than non-obese patients. Clinician should be aware of the differences that could influence the disease management.
Acknowledgements An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the ESPOIR study. Two additional grants from INSERM supported part of the biological database. The French Society of Rheumatology, Pfizer, Abbott, and Roche-Chugaï also supported the ESPOIR cohort.
Disclosure of Interest None declared
No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract]ABSTRACT: Background Influence of uveitis on clinical, epidemiological and imaging features in patients with inflammatory back pain (IBP) related to spondyloarthritis (SpA) needs to be known.
Objectives To determine the prevalence of uveitis in patients with recent IBP suggestive of SpA, and to investigate the influence of uveitis on the overall features of patients presenting with recent IBP.
Methods The DESIR cohort is a prospective, multicenter French cohort of patients with early IBP (Calin or Berlin criteria) (>3 months and <3 years of duration) suggestive of SpA according to the investigator, including 708 patients (mean age 33.8 years, 53.8% female, 57.3% HLA B27 positive). Uveitis was defined by an ophthalmological episode diagnosed as uveitis by an ophthalmologist, or a painful red eye episode of at least 48 hours duration and/or necessitating local steroids. Data on the baseline demographic characteristics, functional status and quality of life, imaging features (standard X-Rays, MRI, Ultrasounds), BMD, and blood tests were compared in patients with and without uveitis. Both the date of the first symptom of IBP and the symptoms of uveitis were recorded, as well as the date of the visit. Factors associated with the presence of uveitis were identified both by uni and multivariate analysis (logistic regression).
Results The prevalence of uveitis in the DESIR cohort was 8.47% [95%CI 6.58-10.83] (n=60/708 patients). Uveitis occurred after the first symptoms of IBP in 45%, before in 37%, and simultaneously (±1month) in 18% of the cases. Presence of uveitis was significantly associated in univariate analysis with pain in cervical spine, infection preceding (less than 3 months) inflammatory disease, previous diagnosis of inflammatory bowel disease, some dimensions of SF36 (mental and physical health, relation), presence of Achilles enthesitis, elevated leukocyte count, serum creatinin levels, radiological hip involvement, and chronic sacro iliac MRI lesions. Uveitis is not associated with fulfilment of diagnosis criteria, HLA-B27, BASDAI, BASFI, ASDAS, BMD. A stepwise multivariate analysis found an association between uveitis and: pain in cervical spine, infection preceding inflammatory disease, previous diagnosis of inflammatory bowel disease, physical health limitation of SF36 (Table).
Conclusions In recent IBP suggestive of SpA, uveitis is associated with some particular rheumatologic and extra rheumatologic features. Our data, and in particular the association with IBD and infection might suggest a role of environmental factors in the incidence of uveitis in SpA.
Disclosure of Interest None Declared
No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract]ABSTRACT: 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.
The ESPOIR cohort included patients with early arthritis of <6 months' duration. Treatment was the standard of care. We had 5-year follow-up data for 573 patients. This study compared patients who had persistent moderate disease activity (Disease Activity Score in 28 joints (DAS28)>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.
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.
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.
No preview · Article · Jan 2014 · Annals of the rheumatic diseases
[Show abstract][Hide abstract]ABSTRACT: Background The Treat to Target and EULAR recommendations highlighted the need for achieving and maintaining remission in patients with early RA. We investigated if early RA patients with persistent moderate disease activity during the first year have in daily life a worst 3 to 5 year outcome than patients who achieved clinical remission.
Methods The ESPOIR cohort included 813 patients with early arthritis in at least 2 joints of less than 6 months disease duration. They were treated according to standard of care. Within the 573 patients who had a 5 year follow-up, 93 % fulfilled the ACR/EULAR criteria for RA. This study compared patients who were in persistent (at both the month 6 and month 12 visits) DAS28 remission (group.1) versus those who were in persistent (at both the M6 and M12 visits) moderate disease activity (DAS28>3.2 and ≤5.1)(group.2). The primary outcome measure was radiographic progression ((modified Total Sharp Score (mTSS)) at month 36. Secondary endpoints were clinical remission (DAS28, SDAI, ACR/EULAR), HAQ-DI, number of missed workdays at month 36 and 60. Fisher exact test was used to compare categorical variables and Kruskal-Wallis test for quantitative variables. Logistic regression analysis was performed to determine confounding factors of outcome.
Results Baseline characteristics were not significantly different between groups. Patients with persistent moderate disease activity during the first year, had greater radiographic progression, higher HAQ disability and number of missed days and lower rate of remission than those who achieved persistent remission (table).
Conclusions This study demonstrated that early RA patients with persistent moderate disease activity during the first year of the disease had a worst outcome than patients who achieved clinical remission. Moderate disease activity state had substantial impact on structure, function and health outcomes. Patients should benefit from more intensive therapeutic strategy.
Disclosure of Interest B. Combe: None Declared, I. Logeart Employee of: Pfizer, M. Belkacemi: None Declared, T. Schaeverbeke: None Declared, J.-P. Daures: None Declared, M. Dougados: None Declared
No preview · Article · Jun 2013 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract]ABSTRACT: Mastermind-like domain containing 1 (MAMLD1) is a causative gene for the fetal development of male external genitalia. Almost 10% of patients with both severe and non-severe hypospadias exhibit mutations of MAMLD1. The aim of this work was to determine whether polymorphisms of MAMLD1 are a genetic risk factor for hypospadias.
This study included 150 hypospadias with a range of severities and 150 controls. Direct sequencing of the MAMLD1 coding exons and their flanking splice sites was performed. In silico secondary and tertiary structure prediction and accessibility of changed amino acids were evaluated using JPred, Netsurf and PHYRE software. Functional studies of the transactivation of haplotypes on Hes3 promoter were performed in vitro using cDNAs of missense variants of MAMLD1.
The p.P286S polymorphism was identified in 17/150 patients and 12/150 controls (11.3% vs. 8.0%, p = 0.32). The p.N589S polymorphism was identified in 22/150 patients and 12/150 controls (14.6% vs. 8.0%, p = 0.068). The double polymorphism (S-S haplotype) was present in 16/150 patients and 6/150 controls (10.6% vs. 4.0%, p = 0.044, OR = 2.87, CI from 1.09 to 7.55). The association of polymorphisms consistently revealed a modification in the structure prediction or amino acid accessibility in all three in silico models. The P286S, N589S and P286S + N589S proteins did not exhibit reduced transactivating activity on Hes3 promoter.
Polymorphisms of MAMLD1 gene are frequent in patients with hypospadias. Although no change in transactivation was noted on Hes3 promoter, the in silico studies and the significantly increased incidence of the S-S haplotype in hypospadiac patients raise the hypothesis of a particular susceptibility conferred by these variants.
No preview · Article · Dec 2011 · Journal of pediatric urology
[Show abstract][Hide abstract]ABSTRACT: To study the contribution of routine viral screening tests in patients with early rheumatoid arthritis (RA) or a potential for progressing to RA.
Eight hundred thirteen patients with swelling of at least 2 joints for at least 6 weeks and a symptom duration of less than 6 months in the ESPOIR cohort were screened for parvovirus B19 (IgG and IgM anti-parvovirus B19 antibodies), hepatitis B virus (HBV; hepatitis B surface antigen), hepatitis C virus (HCV; anti-HCV antibodies), and human immunodeficiency virus (HIV; anti-HIV-1 and -2 antibodies).
Parvovirus B19 testing was performed in 806 patients and showed longstanding immunity in 574 (71.2%) and no antibodies in 223 (27.7%). Among the 9 remaining patients (7 IgG positive/IgM positive, 1 IgG negative/IgM positive, and 1 IgG indeterminate/IgM positive), only 2 (0.25%; 95% confidence interval [95% CI] 0-0.99%) had a positive polymerase chain reaction test for parvovirus B19; these patients (women ages 34 and 40 years) had no extraarticular signs. HIV seroprevalence was 0.12% (n = 1 of 813; 95% CI 0.01-0.8%) and HCV seroprevalence was 0.86% (n = 7 of 808, 95% CI 0.38-1.86%). HCV-related arthritis was diagnosed in 4 patients (0.5%). HCV-seropositive patients had significantly higher transaminase levels than the other patients (P = 0.001), with no significant differences for the other laboratory data. HBV seroprevalence was 0.12% (n = 1 of 808; 95% CI 0.01-0.8%); the positive HBV status was known before study inclusion, and the patient had no diagnosis of HBV-related arthritis. Finally, routine viral testing identified 2 patients with parvovirus B19 infection and 3 with HBV infection (0.6%; 95% CI 0.2-1.5%). Cost was €85.05 per patient (total €68,720).
Routine serologic testing did not contribute substantially to the diagnosis in this context.
[Show abstract][Hide abstract]ABSTRACT: BACKGROUND Over the past decades, an increasing trend in male external genital malformations such as cryptorchidism and hypospadias
has led to the suspicion that environmental chemicals are detrimental to male fetal sexual development. Several environmental
pollutants, including organochlorine pesticides, polychlorinated biphenyls, bisphenol A, phthalates, dioxins and furans have
estrogenic and anti-androgenic activity and are thus considered as endocrine-disrupting chemicals (EDCs). Since male sex differentiation
is critically dependent on the normal production and action of androgens during fetal life, EDCs may be able to alter normal
male sex differentiation.
Full-text · Article · Aug 2011 · Human Reproduction
[Show abstract][Hide abstract]ABSTRACT: To determine predictors of short-term radiographic progression in an inception cohort of patients with early arthritis.
Patients presenting with synovitis of at least two joints for 6 weeks to 6 months were included in the Etude et Suivi des POlyarthrites Indifferenciées Récentes (ESPOIR) cohort. Univariate analysis was used to determine the relationship between baseline variables and radiographic outcome (assessed by the modified total Sharp score (mTSS)) after 6 and 12 months. Stepwise multiple logistic regression was used to select independent predictive factors. The sensitivity and specificity of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) at baseline in discriminating between erosive and non-erosive disease were determined by receiver operating characteristic (ROC) curves.
From data available for 736 patients, radiographic progression at 6 months was independently predicted by baseline ACPA, human leucocyte antigen (HLA)-DRB1*01 and/or 04 genes, erythrocyte sedimentation rate and mTSS. Interestingly, the season of onset of the first symptoms was associated with the severity of early arthritis (OR 1.66, 95% CI 1.07 to 2.59, in winter and spring vs summer and autumn). Univariate analysis revealed similar results for season at 12 months (OR 1.68, 95% CI 1.20 to 2.37). The peak of the ROC curves for radiographic outcome occurred with ACPA and RF values similar to the cut-offs provided by manufacturers.
The authors found the onset of arthritis symptoms during winter or spring associated with greater radiographic progression at 6 months for patients with early arthritis. These data could reinforce the role of environmental factors in the development and outcome of rheumatoid arthritis.
Full-text · Article · Jul 2011 · Annals of the rheumatic diseases
[Show abstract][Hide abstract]ABSTRACT: Education of patients with chronic hepatitis C has been proposed to increase response to therapy with peginterferon and ribavirin. We performed a prospective study to determine the effects of systematic consultation by a nurse on patient adherence and the efficacy of therapy.
We analyzed data from 244 patients who received either systematic consultation after each medical visit from a nurse who used a standard evaluation grid and provided information about the disease and treatment (group A [GrA], n = 123) or the conventional clinical follow-up procedure (group B [GrB], n = 121). Treatment lasted 24 to 48 weeks.
Characteristics of each group were similar at baseline, including prior treatment (42.6% in GrA and 36.0% in GrB). Overall, GrA had significantly better adherence to treatment than GrB (74.0% vs 62.8%), especially among patients who received 48 weeks of treatment (69.7% vs 53.2%; P < .03). Significantly more patients in GrA had a sustained virologic response, compared with GrB overall (38.2% vs 24.8%; P < .02), as well as treatment-naive patients (47.1% vs 30.3%; P < .05), and those with genotypes 1, 4, or 5 infections (31.6% vs 13.3%; P < .007). There were no differences between GrA and GrB in response of patients with genotypes 2 or 3 infections or advanced fibrosis. Prognostic factors for a sustained virologic response (based on bivariate and multivariate analyses) were virologic response at week 12 (odds ratio [OR], 1.9; P < .0001), genotypes 2 or 3 (OR, 2.9; P < .0001), therapeutic education (OR, 2.5; P < .02), and lack of previous treatment (OR, 2.3; P < .005).
Therapeutic education by a specialized nurse increases the response of patients with hepatitis C to therapy, particularly in difficult-to-treat patients.
No preview · Article · Jun 2011 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
[Show abstract][Hide abstract]ABSTRACT: Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate.
To identify the optimal CD4 cell count at which cART should be initiated.
Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L.
HIV clinics in Europe and the Veterans Health Administration system in the United States.
20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis.
Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.
Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations: CD4 cell count at cART initiation was not randomized. Residual confounding may exist.
Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.
Full-text · Article · Apr 2011 · Annals of internal medicine
[Show abstract][Hide abstract]ABSTRACT: Guidelines are the cornerstone of health care decision making and are based on the best available evidence, ideally large randomized controlled trials (RCTs). Although guidelines target typical patients, RCTs are often based on narrow inclusion and exclusion criteria.
We explored to what extent typical patients, such as those consulting general practitioners for allergic rhinitis, differ from patients enrolled in RCTs.
We conducted a prospective cohort study including all the consecutive patients with allergic rhinitis cared for by general practitioners in the Languedoc-Roussillon region of France within 2 weeks during the grass pollen season. We evaluated how the characteristics of these patients differed from those of patients included in the 4 largest placebo-controlled RCTs of persistent and intermittent allergic rhinitis.
Three hundred eleven patients seen by 48 general practitioners were enrolled in this study. Only 7.4% (95% CI, 4.5% to 10.3%) of the patients would have been enrolled in the RCTs. The primary reasons for this difference were as follows: diagnosis of allergy based on skin test results, serum specific IgE levels, or both (20.4%); severity of allergic rhinitis (11.5%); other chronic diseases (11.4%); history of sinusitis (10.4%); and asthma comorbidity (10.1%). A sensitivity analysis excluding contraception and the diagnosis of allergy showed that the percentage of representative patients increased to 20.2% (95% CI, 15.8% to 24.7%).
Only a small proportion of patients with allergic rhinitis seen in the primary care setting for allergic rhinitis would be eligible for RCTs. Thus guideline developers and health decision makers need to make careful judgments about the directness of the evidence from RCTs conducted in highly controlled settings.
Full-text · Article · Apr 2011 · The Journal of allergy and clinical immunology
[Show abstract][Hide abstract]ABSTRACT: Research on the skull base is important to improve our understanding of the growth and development of the modern human skull. To study the growth of the human fetal skull base, we assessed a new geometric morphometric tool, which does not require the use of bone landmarks.
Seven dry fetal skulls of an estimated gestational age ranging from 15 to 27 weeks were studied. Each skull was scanned using a standard CT scan and the image sets were post-processed to extract volumetric data by segmenting the skull base into predefined regions of interest. Our method of analysis was based on the inertial properties of reconstructed volumes.
The volumetric study of the skulls highlighted an asynchronous speed of growth between the pre and post-chordal parts of the skull base whose preferential growth are in the vertical and horizontal planes. We also found different speeds of growth in the pre-chordal part depending on the type of ossification (endochondral or membranous). The overall shape of the skull base bones were preserved during the period studied except for the petrous pyramids. The expansion of bone parts was isometric with reference to a central point that was located at the intrasphenoidal synchondrosis. Finally, the analysis of the basicranial angles corroborated data from the literature in the sagittal plane and allowed their study also in the frontal and horizontal planes.
This three-dimensional volumetric approach is a necessary complement to studies that are performed in the sagittal plane and are based on the identification of landmarks. The geometric morphometric method used by authors permitted to obtain original informations on the growth kinetics and bone tridimensional movements of the human fetal skull base.
Full-text · Article · Feb 2011 · Early human development
[Show abstract][Hide abstract]ABSTRACT: The medical decision-making community has an extensive literature on the use of receiver operating characteristic (ROC) graphs for diagnostic testing. Heagertybiet al. have recently developed this ROC curve theory within the context of survival data (Biometrics 2000; 56:337-344). The time-dependent ROC method allows evaluating the accuracy of a marker to predict a time-dependent failure, whereas the classic methodology focuses on diagnosis. One limitation to this approach, however, is to analyse a single failure. In many medical situations, a marker can be useful to predict different competitive failures. For example in kidney transplantation, the terminal evolution can be a return to dialysis or the death of the patient. With this application in mind, our paper proposes an extension of the time-dependent ROC method for analysing the accuracy of a marker to predict two competitive events.
No preview · Article · Dec 2010 · Statistics in Medicine