[Show abstract][Hide abstract] ABSTRACT: Extracellular pH variations are seen as the principal endogenous signal that triggers activation of Acid-Sensing Ion Channels (ASICs), which are basically considered as proton sensors, and are involved in various processes associated with tissue acidification. Here, we show that human painful inflammatory exudates, displaying non-acidic pH, induce a slow constitutive activation of human ASIC3 channels. This effect is largely driven by lipids, and we identify lysophosphatidylcholine (LPC) and arachidonic acid (AA) as endogenous activators of ASIC3 in the absence of any extracellular acidification. The combination of LPC and AA evokes robust depolarizing current in DRG neurons at physiological pH 7.4, increases nociceptive C-fiber firing, and induces pain behavior in rats, effects that are all prevented by ASIC3 blockers. Lipid-induced pain is also significantly reduced in ASIC3 knockout mice. These findings open new perspectives on the roles of ASIC3 in the absence of tissue pH variation, as well as on the contribution of those channels to lipid-mediated signaling.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To evaluate influenza and pneumococcal vaccine coverage in patients taking biological therapy for chronic inflammatory joint disease and to identify factors associated with the decision to administer these two vaccines.
Retrospective cross-sectional questionnaire study of a cohort of 584 patients taking biological therapy for chronic inflammatory joint disease (rheumatoid arthritis or spondyloarthritis). We studied the influenza and pneumococcal vaccine coverage rates, information about these vaccines given to patients by the primary-care physician and rheumatologist, and reasons for not administering the vaccines.
Overall vaccine coverage rates were 44% for influenza and 62% for pneumococcus. Factors associated with being vaccinated were patient age, previous influenza vaccination, and patient information. Concern about adverse effects and absence of patient information by the primary-care physician and rheumatologist were associated with very low coverage rates.
This study showed insufficient vaccine coverage rates, particularly against influenza, in a population at high risk because of exposure to biological therapy. Patient information by healthcare professionals about influenza and pneumococcal vaccination has a major impact and should be renewed as often as possible.
No preview · Article · Dec 2015 · Joint, bone, spine: revue du rhumatisme
[Show abstract][Hide abstract] ABSTRACT: Objective:
Our objective was to compare the use of both anteroposterior (AP) extended-knee X-ray and semi-flexed X-ray (current gold standard) versus the use of semi-flexed X-ray alone to detect femoro-tibial osteoarthritis (OA).
Individuals 40 to 75 years of age with symptomatic hip and/or knee OA (Kellgren/Lawrence [KL] score≥2) were recruited using a multiregional prevalence survey in France. Both AP and schuss X-rays were performed and read; two years later, the same examiner, blinded to the results of the first reading, performed a second reading of the schuss X-ray. We compared the KL stages of each knee and analyzed osteophyte detection and localization, joint space narrowing (JSN), and the relationship to obesity.
The analysis included 350 participants with OA of various stages. Comparing the two readings showed that a higher proportion of patients had KL≥2 when the two X-ray views were combined (right knee: P<0.0001; left knee: P<0.001). There were no differences when using the schuss X-ray alone versus in combination with an AP X-ray in terms of detecting JSN, osteophytes. A comparison of schuss X-ray alone versus AP X-ray alone demonstrated the superiority of the schuss view for evaluating JSN (P=0.0001 and P=0.0001) and no difference in osteophyte detection.
Our study shows that the schuss view alone was sufficient for detecting knee osteophytes and JSN. Using one X-ray rather than two will reduce medical costs and irradiation burden. Using two views seems preferable for epidemiological studies.
No preview · Article · Nov 2015 · Joint, bone, spine: revue du rhumatisme
[Show abstract][Hide abstract] ABSTRACT: L’hidrosadénite suppurée (HS) sévère, traitée par infliximab, peut être associée à différentes formes de manifestation articulaire inflammatoire dont le mécanisme reste à préciser. Notre objectif est de déterminer la fréquence et la présentation clinique de ces manifestations rhumatologiques inflammatoires chez des patients atteints d’HS traités par infliximab.
[Show abstract][Hide abstract] ABSTRACT: Oxytocin, a neurohypophysial hormone, regulates bone metabolism in animal studies and postmenopausal women. In men, oxytocin is not associated with bone mineral density, bone turnover markers, or prevalent fractures, but weakly negatively with incident fragility fracture requiring further studies.
We previously showed that serum oxytocin (OT) level is associated with bone mineral density (BMD) and bone turnover rate in postmenopausal women. The aim of our study was to assess the relationship between circulating OT levels and bone status in men.
In 552 men aged 50 and older from the MINOS cohort, we measured serum levels of OT. We assessed the association of serum OT levels with BMD (lumbar, femoral neck, total hip), bone turnover markers (BTM) (serum N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (bone ALP), and C-terminal telopeptide of type I collagen (CTX-I)) and fracture risk.
In the univariate analysis, serum OT level was not associated with BMD at any site, BTM levels, or with prevalent or incident fracture. OT was significantly correlated with body mass index (BMI) (r = 0.17, p < 0.001), total or bioavalaible 17β-estradiol (r = 0.09, p = 0.04 and r = 0.20, p < 0.001, respectively), free testosterone (r = 0.17, p < 0.001), and leptin (r = 0.16, p < 0.001). Multivariate analysis did not show significant relationship between serum OT and BMD. After adjustment for age, BMI, interaction BMI/age, history of fall in the last year, and BMD, OT and prevalent fracture were not associated. By contrast, the same analysis with additional adjustment for prevalent fracture showed a weakly significant negative association between OT and incident fracture, e.g., after adjustment for femoral neck BMD, HR = 0.73, 95 %CI 0.55-0.99, p = 0.04.
In men, serum OT levels are not associated with BMD, bone turnover rate, or prevalent fractures. The weak negative relationship with fracture risk requires further studies.
No preview · Article · Jun 2015 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: L’étude visait à évaluer la couverture vaccinale contre la grippe et le pneumocoque chez des patients atteints de rhumatismes chroniques inflammatoires sous biothérapies, et analyser les facteurs associés à la prise de décision de la vaccination.
No preview · Article · Mar 2015 · Revue du Rhumatisme
[Show abstract][Hide abstract] ABSTRACT: Objectives To evaluate pneumococcal (PV) and influenza (IV) vaccination status in patients (pts) on biotherapies by researching influencing factors.
Methods Pts on biotherapies seen between February and July 2013 were questioned about PV and IV status. Variables analysed: age, sex, disease, treatment, immunisation status, reason for non-vaccination and history of pulmonary infection on biotherapy. Percentage comparisons were performed using chi-square and McNemar's tests.
Results 594 pts were analysed (406 F + 188 M): 307 rheumatoid arthritis (RA) (51 M +256 F, mean age 59 years); 277 spondyloarthritis (SpA) (135 M +142 F, mean age 48 years); and 10 other diseases. In the RA group, 189 pts were treated with anti-TNFs: 115 with etanercept (Etn); 37 with adalimumab (Ada); 19 with infliximab (Inf); 13 with certolizumab (Cer); and 5 with golimumab (Gol). 118 other pts were treated with another biotherapy, including 42 with rituximab (Rtx); 38 with tocilizumab (To); 24 with abatacept (Aba); and 14 with anakinra (Ana);151 pts had at least 2 biotherapies. One DMARD was combined in 60% and cortisone in 35%. In the SpA group, 271 were treated with anti-TNFs (Ada 121, Etn 85, Inf 46, Gol 14, Cer 5) and 6 with other biotherapies, 86 pts had at least 2 biotherapies. One DMARD was combined in 28% and cortisone in 5%.
The 2012-2013 winter IV (recommended for 37% by the general practitioner [GP]; 45% for RA and 28% for SpA), and in 63% after age 65, and in 79% by the rheumatologist (including 82% for RA and 75% for SpA, and in 93% after age 65) was given to 260 pts (43.77%; including 44% for RA and 43% for SpA and in 62% of pts >65 years). Pts having refused were 47%, (55% were RA and 39% were SpA), generally because of fear (45% RA and 32% SpA).
PV over the last 5 years (recommended in 14% by the GP, including 16% for RA and 12% for SpA, and in 24% after age 65, and in 78% by the rheumatologist in RA and SpA, and in 86% after age 65) had been done for 370 pts (62.29%; including 60% in RA and 65% in SpA, and in 70% over age 65). Pts having refused were 25% (31% RA and 17% SpA). In total, 37% had two vaccinations (53% after age 65): 33% one of two; 30% neither of the two. 67 pts (48 RA) had an infection (11%), including 20 hospitalisations.
Variables selected for a better vaccination: a prior IV; the recommendation by the GP and the rheumatologist (p<0.001); age >65 years (IV p<0.001, PV p=0.02). The other parameters were not influencing (type and number of biotherapies, DMARDs, cortisone, disease). Infections were not lower in those vaccinated compared to those non-vaccinated (number of pts too low). The PV was up-to-date more frequently than the IV (p<0.001) in the two diseases. Fear of side effects was one of the causes of non-vaccination.
Conclusions The rate of IV was 44% compared to 62% for PV. Age influences the vaccination status, as well as the information given to the patient. This should be repeated with pts and physicians in order to improve protection.
Disclosure of Interest : None declared
No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Background Few data have been published about the diagnostic value of standard AP view and Schuss X rays association
Objectives Our objective is to compare the contribution to diagnosis of the association standard AP view and Schuss X rays versus the single Schuss X ray.
Methods Studied population: From 2007 to 2009, a general population, two-phase study was conducted in 6 French centers to estimate the prevalence of knee and/or hip OA gather a cohort which included only patients with Kellgren Laurence (KL) ≥2 (KHOALA (1)). During this prevalence study we obtained X-rays from 3707 subjects aged 40 to 75 years old. For the current work, we selected the first 304 participants regardless of their stage. X-rays reading: A first reading of standard AP + Schuss views was carried out by an expert rheumatologist (BM), and then a second reading of Schuss X-rays only was carried out remotely (blinded to the results of the first lecture), by the same examiner. Delay between the two readings was 2 years. Analysis focused on the comparison of KL stage of each knee, as well as on osteophytes detection and localization (Medial Condyle (MC), Lateral (LC), Medial Tibial Plateau (MTP) or Lateral (LTP) ranked from 0 to 3), Joint space narrowing (JSN) (ranked from 0 to 4) and bone sclerosis (MC, LC, MTP, LTP).
Results Mean age was 58 years (8.6), Body Mass Index (BMI) was 29.8 (5.4).
Comparison of 2 readings showed a significantly higher proportion of patients with a KL ≥2 with the two X-ray combined (right knee: p<0.0001; left knee: p<0.0003). In contrast, a finer analysis taking into account JSN (respectively p=0.8 and 0.07), osteophytes (0.8 and 0.3), and bone condensation (0.6 and 0.6) didn't show any significant differences. Our data suggested a less value of Schuss X-ray alone when BMI is high. A comparison of Schuss versus standard AP X-rays alone showed a Schuss superiority to detect JSN and osteophytes (p=0.0001 and p=0.0001).
Conclusions Combined procedure detect more radiological OA than Schuss X ray alone. However, when assessing separately the two main features of OA (JSN and osteophytes), no significant difference appeared in spite of a trend favouring the combined procedure. The partly subjective global KL scoring system is probably more robust to detect OA than separated assessment of JSN and osteophytes alone.Finally, regarding higher cost and irradiation of both radiographs compared to schuss alone, the choice of the procedure will depend on the aim of the study: in epidemiological studies only schuss may be realised, while in a clinical diagnosis perspective both views should be recommended.
Disclosure of Interest : None declared
No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Objectives Rheumatoid arthritis (RA) patients are at an increased risk of developing comorbid conditions. A close monitoring of the disease targeting a status of low disease activity is associated with a better outcome. The aim of this trial was to evaluate the impact of a nurse-led programme on comorbidities and the impact of patient self-assessment of disease activity on the management of RA.
Methods We enrolled 970 patients (mean age 58 years, 79% women) in a prospective, randomised, controlled, open-label, 6-month trial. In the comorbidity group (n=482), the nurse checked comorbidities and sent the programme results to the attending physicians. In the self-assessment group (n=488), the nurse taught the patient how to calculate his/her Disease Activity Score which had to be reported on a booklet to be shared with the treating rheumatologist. The number of measures taken for comorbidities and the percentage of patients recording a change (initiation, switch or increased dose) in disease-modifying antirheumatic drugs (DMARDs) in the 6 months follow-up period of the study defined the outcomes of the trial.
Results The number of measures taken per patient was statistically higher in the comorbidity group: 4.54±2.08 versus 2.65±1.57 (p<0.001); incidence rate ratio: 1.78 (1.61–1.96) and DMARD therapy was changed more frequently in the self-assessment group: 17.2% versus 10.9% (OR=1.70 (1.17; 2.49), p=0.006).
Conclusions This study demonstrates the short-term benefit of a nurse-led programme on RA comorbidity management and the impact of patient self-assessment of disease activity on RA treatment intensification.
Trial registration number NCT #01315652.
Full-text · Article · May 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Background Patients with RA are at an increased risk of developing a number of co-morbid conditions which have a major influence on both mortality and the outcome of RA.
Objectives To evaluate the impact of a nurse led program on the management of comorbidities (cardiovascular diseases (CVD), infection, cancer and osteoporosis) in RA.
Methods Study design: Prospective, randomized controlled open, 6-month trial (NCT #0131652). Patients: RA (ACR 1987 criteria). Study treatment: Collection of data by the nurse at a specific out-patient clinic for the four studied RA comorbidities according to the recommendations of the French Society of Rheumatology. In the event of non-agreement with the recommendation the patient was informed. A report summarizing the results of this program prepared by the nurse was sent to the patient’s attending physician and rheumatologist. Treatment allocation: After written informed consent, the study treatment was allocated randomly (i.e. either this evaluation of comorbidities or an evaluation of a self assessment program (not reported here). Outcome variables: number of actions undertaken against comorbidities according to the recommendations during the 6 months following this program. Actions taken into account for CVD were : introduction of lipid-lowering therapy or anti-platelet therapy, smoking cessation, taking of blood pressure, purchase of a sphygmomanometer, weight loss; for infections: pneumococcal, influenza, hepatitis and meningococcal vaccinations ; for cancers : mammography, Pap smears, consultation with an urologist, fecal occult blood testing, colonoscopy, consultation with a dermatologist; for osteoporosis: dual-Energy X-ray absorptiometry, increased alimentary calcium uptake, introduction of calcium and/or vitamin D supplementation and/or an osteoporotic medication.
Results There was no difference in the baseline characteristics of the 970 recruited patients (488 and 482 in the active and control groups, respectively): Age: 58±11 years, female gender: 79%, disease duration: 11[6.2-19.1] y, history or current biotherapy, DAS28: 3.1 ± 1.3., mHAQ: 0.25 (0.00-0.62). During the 6-month follow-up period, the number of actions per patient was statistically higher in the group comorbidities : 4.54 ± 2.08 vs 2.65 ± 1.57 (p< 0.001); Incidence Rate Ratio(IRR): 1.78 [1.60 -1.83]. This increase concerned CVD (IRR: 1.44 [1.30-1.61]), infections (IRR 1.78 [1.45 – 2.19]), cancer (IRR: 1.65 [1.42 – 1.92]) and osteoporosis (IRR 3.43 [2.88 – 4.13]).
Conclusions This study demonstrates the short-term benefit of a nurse led program on the management of comorbidities. Longer term follow-up of patients is required to better evaluate the sustainability of this benefit.
Acknowledgements This study was conducted thanks to a grant from the French National Research Program (PHRC) and thanks to an unrestricted grant from Roche Ltd France
Disclosure of Interest None Declared
No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Oxytocin (OT), a neurohypophysial hormone regulated by estrogen and leptin, may play a role in bone metabolism in humans as suggested by animal studies. This study assessed the relationship between OT and bone status in a large population of postmenopausal women.
Subjects and methods:
Subjects were included in the Osteoporosis and Ultrasound study, a 6-year prospective study in a population-based cohort. Final visit data were used for this cross-sectional study. OT, leptin, and estradiol serum levels were measured in 1097 postmenopausal women and compared with bone mineral density (BMD), fractures, and the bone turnover markers (BTMs) procollagen type 1 N-terminal propeptide, bone alkaline phosphatase, and C-telopeptide of type 1 collagen.
The median age was 70.8 years, 16% were osteoporotic, 48% were osteopenic, and 29% had at least one fracture. The OT serum level was related to spine (r = +0.12, P = .0002) and total hip BMD (r = +0.21, P < .0001) and with BTM (procollagen type 1 N-terminal propeptide: r = -0.13, P < .0001, bone alkaline phosphatase: r = -0.07, P = .02, C-telopeptide of type 1 collagen: r = -0.18, P < .0001). The relationship of OT with BMD was independent of BTM. After adjustment for confounding factors, the correlation between OT serum level and BMD remains significant at the hip in women with unmeasurable estradiol or leptin above the median value. There was no significant relationship between OT serum levels and fractures.
High OT levels are associated with high BMD, especially at the hip in women with low estradiol or high leptin serum levels. The mechanism may be explained by the effect of OT on bone turnover.
No preview · Article · Jan 2014 · The Journal of Clinical Endocrinology and Metabolism
[Show abstract][Hide abstract] ABSTRACT: Chondrogenesis has been widely investigated in vitro using bone marrow-derived mesenchymal stromal cells (BM-MSCs) or primary chondrocytes. However, their use raises some issues partially circumvented by the availability of Adipose tissue-derived MSCs. Herein; we characterized the chondrogenic potential of human Multipotent Adipose-Derived Stem (hMADS) cells, and their potential use as pharmacological tool. hMADS cells are able to synthesize matrix proteins including COMP, Aggrecan and type II Collagen. Furthermore, hMADS cells express BMP receptors in a similar manner to BM-MSC, and BMP6 treatment of differentiated cells prevents expression of the hypertrophic marker type X Collagen. We tested whether IL-1β and nicotine could impact chondrocyte differentiation. As expected, IL-1β induced ADAMTS-4 gene expression and modulated negatively chondrogenesis while these effects were reverted in the presence of the IL-1 receptor antagonist. Nicotine, at concentrations similar to those observed in blood of smokers, exhibited a dose dependent increase of Aggrecan expression, suggesting an unexpected protective effect of the drug under these conditions. Therefore, hMADS cells represent a valuable tool for the analysis of in vitro chondrocyte differentiation and to screen for potentially interesting pharmacological drugs.
Full-text · Article · Oct 2013 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: Several markers of comorbidities and cardiovascular (CV) risk are disturbed in moderate to severe psoriasis (PsO). The effect of systemic treatments of psoriasis on these markers remains poorly understood.
To study the frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk associated with moderate to severe PsO and psoriatic arthritis (PsA), and to assess their evolution under systemic treatments.
Monocentric prospective study on patients with PsO and PsA starting a systemic treatment for their psoriasis. The following markers were evaluated at baseline (M0), 3 months (M3) and 6 months (M6); weight, fasting blood glucose, blood pressure, uric acid, hepatic steatosis, smoking, lipid, metabolic and inflammatory parameters.
Forty-three patients, 31 PsO and 12 PsA, were included. Forty completed the study. Response to treatment was good, with 71% of the population obtaining a Psoriasis Area and Severity Index (PASI) of 75. All patients had at least one comorbidity, and 45% had two or more. A statistically significant decrease was observed only for inflammatory parameters (C-reactive protein [CRP], P = 0.004) and erythrocyte sedimentation rate (ESR, P = 0.002). We did not observe any correlation between the PASI and CRP (correlation coefficient 0.128, P = 0.438) or ESR (correlation coefficient 0.294, P = 0.069) for responding patients.
We observed a high frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk in a population with moderate to severe PsO and PsA, most of which were not detected before. A significant decrease in inflammatory parameters was noted after the introduction of systemic therapy, while other parameters remained unaffected by the treatment, except the weight that increased under biologics therapies.
Full-text · Article · Aug 2013 · Journal of the European Academy of Dermatology and Venereology
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is particularly frequent in subjects suffering from chronic obstructive pulmonary disease (COPD) and asthma, because they share numerous common risk factors: aging (for COPD), smoking, vitamin D deficiency, inactivity, muscular weakness, systemic inflammation, are an integral part of the physiopathology of COPD and asthma. Oral corticosteroid used in the severe forms of COPD and asthma contribute to the risk of osteoporosis in these frail patients and the application of the guidelines for steroid-induced osteoporosis is crucial. Inhaled corticosteroid, basis of asthma treatment and also used in some forms of COPD, has a less clear impact on bone status; however recent publications are in favour of a moderate effect, but long-term studies are necessary at these patients with long term treatments. Finally, severe kyphosis related to multiple vertebral ribs and sternal fractures can contribute to an alteration of respiratory function. The management of these patients is based on a global evaluation of fracture risk including the risk factors of osteoporosis and the measure bone mineral density, the non pharmacological measures of the osteoporosis treatment, vitamin D supplementation often required and, if needed, specific drugs of osteoporosis. This review emphasizes the need to increase vigilance of practitioners about the risk of osteoporosis in COPD and asthma.
No preview · Article · Apr 2013 · Revue du Rhumatisme Monographies
[Show abstract][Hide abstract] ABSTRACT: Objectifs
Cette étude visait à décrire la prévalence de l’arthrose du genou ou de la hanche, l’histoire naturelle de la maladie, ainsi que les facteurs pronostiques de son développement et les éléments déterminant le coût et l’accès aux soins pour une cohorte de patients en France.
Les sujets âgés de 40 à 75 ans, souffrant d’arthrose symptomatique du genou et/ou de la hanche uni- ou bilatérales (confirmées par les critères de l’ACR), au stade 2 ou supérieur dans la classification de Kellgren & Lawrence (KL), ont été recrutés à partir d’une enquête de prévalence en population générale pour constituer la cohorte multicentrique KHOALA. Les données de base collectées incluaient les données sociodémographiques et cliniques ; les scores WOMAC, IKS et Harris pour la douleur et la fonction ; le score MAQ pour l’activité physique ; l’index de comorbidité fonctionnelle ; le score GHQ28 pour le statut psychologique ; et les scores SF-36 (générique) et OAKHQOL (spécifique) pour l’évaluation de la qualité de vie. Des échantillons de sang et d’urine ont été collectés.
Huit-cent-soixante-dix-huit personnes ont été incluses, 222 atteintes d’arthrose de la hanche (âge moyen 61,2 ± 8,8 ans), 607 atteintes d’arthrose du genou (âge moyen 62,0 ± 8,5 ans) et 49 atteintes d’arthrose de la hanche et du genou (âge moyen 64,9 ± 7,9 ans). L’indice de masse corporelle (IMC) moyen était de 26,9 ± 4,5 pour les arthroses de la hanche et de 30,3 ± 6,3 pour les arthroses du genou. Les patients souffrant d’arthrose de la hanche et du genou avaient respectivement des index de comorbidité moyens de 1,99 et 2,06. La sévérité radiographique de la maladie pour des stades 2, 3 et 4 dans la classification de KL étaient, respectivement, de 69,8 %, 26,1 % et 4,1 % pour les arthroses de la hanche, et de 44,5 %, 30,3 %, et 25,2 % pour les arthroses du genou. En comparaison avec la population générale, les scores SF-36 standardisés selon l’âge et le sexe étaient fortement diminués pour les arthroses du genou et de la hanche dans toutes ses dimensions, particulièrement dans les dimensions physiques et émotionnelles.
Les patients vont être suivis annuellement, tour à tour par courrier et par une visite clinique. Cette cohorte, représentative de patients souffrant d’arthrose du genou et de la hanche, va être une opportunité pour de futures recherches collaboratives.
No preview · Article · Jan 2013 · Revue du Rhumatisme