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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
23494522 Tumor necrosis factor receptor type I expression of CD4+ T cells in rheumatoid arthritis e 2013 Jun OBJECTIVE: The cytokine tumor necrosis factor (TNF) plays a central role in the pathogenesis of rheumatoid arthritis (RA), but its disease-specific effector mechanisms have not been fully elucidated. This study was undertaken to investigate the role of TNF in T cell accumulation and migration in the synovitic joints of RA patients. METHODS: Vital tissue sections from rheumatoid synovium were generated using a horizontally oscillating microtome and were coincubated with fluorescence-labeled CD4+ T cells. Migration was detected by fluorescence and confocal microscopy. Migrating T cells were recovered from the tissue and analyzed for phenotype. Chemotaxis of CD4+ T cells from RA patients in response to increasing concentrations of TNF was analyzed in Transwell experiments. RESULTS: CD4+ T cells from RA patients migrated into the tissue sections in significantly higher numbers than T cells from healthy controls. Migrating CD4+ T cells differed from nonmigrating ones in their increased expression of TNF receptor type I (TNFRI), which was expressed on a fraction of circulating CD4+ T cells from RA patients, but not from controls. CD4+ T cells from the peripheral blood of RA patients were also found to migrate along TNF concentration gradients ex vivo. Accordingly, blockade of either TNF or TNFRI nearly abrogated in vitro T cell migration in synovial tissue. CONCLUSION: Our findings indicate that the interaction of TNF with TNFRI is pivotal for T cell migration in synovial tissue in vitro, and thereby suggest a relevant role of the cytokine for in vivo T cell trafficking to synovitic joints.
24032649 Antigen-specific B lymphocytes acquire proteoglycan aggrecan from cartilage extracellular 2014 Jan The majority of studies examining antigen-presenting cell (APC) function have focused on the capture and presentation of antigens released from pathogens or damaged cells. However, antigen-specific B cells are also capable of efficiently extracting antigens that are either tethered to, or integrally part of the plasma membrane of various target cells. In this study we show that B cells are also highly efficient at extracting integral components of the extracellular matrix (ECM) for subsequent presentation. In particular we demonstrate that B cells specific for aggrecan, an integral component of cartilage ECM, acquire this rheumatoid arthritis candidate autoantigen in both a B-cell-receptor-dependent and a contact-dependent manner. We also demonstrate that the subsequent presentation of aggregan from ECM leads to CD4(+) T-cell activation and effector cell formation. Recent studies have identified B-cell-mediated antigen presentation as essential for the development of autoimmunity, but a unique role for B cells compared with other APC has yet to be defined. Our findings lead us to propose that the acquisition of ECM-derived autoantigens represents a mechanism that defines the APC requirement for B cells in the development of autoimmunity.
23520036 EULAR recommendations for the use of imaging of the joints in the clinical management of r 2013 Jun OBJECTIVE: To develop evidence-based recommendations on the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA). METHODS: The task force comprised an expert group of rheumatologists, radiologists, methodologists and experienced rheumatology practitioners from 13 countries. Thirteen key questions on the role of imaging in RA were generated using a process of discussion and consensus. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, dual-emission x-ray absorptiometry, digital x-ray radiogrammetry, scintigraphy and positron emission tomography. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. The experts used the evidence obtained from the relevant studies to develop a set of 10 recommendations. The strength of recommendation was assessed using a visual analogue scale. RESULTS: A total of 6888 references was identified from the search process, from which 199 studies were included in the systematic review. Ten recommendations were produced encompassing the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. The strength of recommendation for each proposition varied according to both the research evidence and expert opinion. CONCLUSIONS: Ten key recommendations for the role of imaging in the management of RA were developed using research-based evidence and expert opinion.
25239880 Red cell distribution width is associated with cardiovascular risk and disease parameters 2015 Apr OBJECTIVE: Since red cell distribution width (RDW) has been associated with cardiovascular (CV) disease and inflammation in several conditions, the main aim of this study was to evaluate its prognostic value in RA patients and its potential associations with clinical features. METHODS: The history of CV events was retrospectively reviewed in 160 RA patients and RDW was recorded at disease onset and 6 and 12 months after diagnosis to calculate the accumulated value [area under the curve (AUC) RDW] and change during the first year (ΔRDW). In addition, RDW was analysed in 110 patients with established disease in relation to clinical features. RESULTS: Increased RDW at diagnosis and AUC RDW were able to predict the occurrence of CV events in RA patients [hazard ratio (HR) 1.247 (95% CI 1.079, 1.441), P = 0.003 and HR 1.038 (95% CI 1.018, 1.059), P = 0.0001, respectively] after adjusting by potential confounding factors. Receiver operating characteristic curve analyses revealed a better power of discrimination for the AUC RDW (P = 3.394 × 10(-5)). In addition, an increase in RDW during the first year was associated with poor CV outcome (P = 0.010). On the other hand, RDW in patients with established RA was significantly associated with disease activity, acute phase reactants and severity. CONCLUSION: RDW at disease onset may be used as an early marker of CV risk in RA, whereas in patients with established disease it was related to the activity of the disease. These findings suggest that RDW can be considered as a surrogate marker of inflammation and, consequently, CV risk in RA patients.
24431396 Chronicity of rheumatoid arthritis affects the responsiveness of physical function, but no 2015 Mar BACKGROUND: In previous studies it has been indicated that functional measures are less responsive in patients with established or late rheumatoid arthritis (RA) as compared with early RA, potentially because chronic irreversible functional damage is present. Therefore, they may not be useful as disease activity measures. We aimed to investigate whether this is specific to functional measures, or if it similarly also relates to other typical RA disease activity measures. METHODS: We performed a pooled analysis of patient level clinical trial data of patients with RA. We investigated the effects of duration of RA on the responsiveness of all RA core set measures by using logistic regression analysis. We performed a number of sensitivity analyses to support our findings. RESULTS: The probability of response in functional scores decreased from ~60% in early disease to ~30% in established/late disease (p=0.0023). No other core set variable or composite index behaved in this way. The effect of chronicity solely on functional responses was confirmed in all sensitivity analyses, particularly also when joint damage was used as a surrogate of chronicity, responsiveness decreased from >60% in patients with little structural damage to <20% in patients with severe joint damage (p<0.001). CONCLUSIONS: Physical function is among the most important outcomes of RA, but in contrast with other core set measures it is not a reliable measure for disease activity.
24185762 Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK popula 2014 Feb OBJECTIVE: The objective of this study was to evaluate the incidence of diabetes among patients with PsA and RA in the general population. METHODS: We conducted a cohort study using an electronic medical records database representative of the UK general population (1986-2010). We estimated hazard ratios (HRs) for incident diabetes in PsA, psoriasis and RA cohorts compared with age- and sex-matched comparison cohorts without the corresponding conditions, adjusting for BMI, smoking, alcohol use, co-morbidities and glucocorticoids at baseline. RESULTS: Cohorts included 4196 persons with PsA, 59 281 with psoriasis and 11 158 with RA, with mean follow-up times of 5.9, 5.8 and 5.5 years, respectively. Incidence rates for diabetes were 7.3, 6.4 and 6.3 cases per 1000 person-years among individuals with PsA, psoriasis and RA, respectively. Age- and sex-matched HRs for diabetes were 1.72 (95% CI 1.46, 2.02) in PsA, 1.39 (95% CI 1.32, 1.45) in psoriasis and 1.12 (95% CI 1.01, 1.25) in RA. After adjustment for BMI, smoking and alcohol, the HRs were attenuated substantially (1.43, 1.24 and 1.00, respectively). With further adjustment for baseline glucocorticoid use and co-morbidities, the HRs were 1.33 (1.09, 1.61) in PsA, 1.21 (1.15, 1.27) in psoriasis and 0.94 (0.84, 1.06) in RA. CONCLUSION: This general population study suggests an increased incidence of diabetes in PsA and RA, which is substantially explained by obesity and lifestyle factors. These findings support the importance of managing such factors in PsA and RA patients.
24665571 Cost-effectiveness analysis of tocilizumab in combination with methotrexate for rheumatoid 2014 Feb BACKGROUND/AIM: Recent studies have shown that biological treatments for rheumatoid arthritis can change the course of rheumatoid arthritis and improve functional ability of patients with rheumatoid arthritis. In spite of this fact, use of biological therapy is still limited by high prices of these medicines, especially in countries in socioeconomic transition. The aim of our study was to compare cost-effectiveness of a combination of tocilizumab and methotrexate with methotrexate alone for rheumatoid arthritis in Serbia, a country in socioeconomic transition. METHODS: For the purpose of our study we designed a Markov model using data on therapy efficacy from the available literature, and data on the costs of health states calculated from records of actual patients treated in the Clinical Center Kragujevac, Serbia. The duration of one cycle in our model was set at one month, and the time horizon was 480 months (40 years). The study was done from the social perspective, and all the costs and outcomes were discounted for 3% per year. RESULTS: Treating rheumatoid arthritis with disease-modifying antirheumatic drugs (DMARDs) alone was more cost-effective in comparison with a combination of biologic treatment with tocilizumab and DMARDs. The total costs for treating a patient with DMARDs for one year were on average 261,945.42 RSD, or 2,497.70 Euro and the total costs for treatment with tocilizimab plus DMARDs were on average 1,959,217.44 RSD, or 18,659.20 Euro. However, these results are susceptible to changes in costs and treatment effects of tocilizumab in patients with more severe forms of rheumatoid arthritis. CONCLUSION: Our results show that the use of tocilizumab for rheumatoid arthrits in economic environment of Serbia is not cost-effective. Use of tocilizumab for treating rheumatoid arthritis can become affordable, if costs of its use become lower. In order to start using expensive biologic medicines in patients in transitional countries, special strategy and pricing policy of international pharmaceutical companies are necessary, which would include calculation of prices of biologic medicines on the basis of local pharmacoeconomic studies.
23508131 New methods for determining comparative effectiveness in rheumatoid arthritis. 2013 May PURPOSE OF REVIEW: To provide an overview of recently published articles describing or applying newer methods for evaluating comparative effectiveness research (CER) in rheumatoid arthritis (RA). RECENT FINDINGS: Historically, clinical trials in RA have compared newer therapies against placebo. Newer trials designed to increase the relevance of trial results to real-world settings include head-to-head comparisons, some that incorporate noninferiority, factorial and crossover designs. Extensions of traditional meta-analysis through network meta-analysis can combine direct and indirect evidence together and can compare multiple treatments with each other.Observational data used to support CER include disease registries, administrative claims data and electronic medical records. Pooling and linking across these data sources and applying newer epidemiologic methods to analyse such data can provide more valid inferences regarding optimal treatment regimens for RA. SUMMARY: CER methods in RA include head-to-head clinical trials, advanced techniques to summarize and aggregate data across studies, enrich the data available in observational settings and enhance the methods used for analysis. Efforts to continue to apply and improve these methodologies will address key needs of clinicians, patients and health policy decision-makers to generate evidence regarding real-world risks and benefits.
25546788 7th International Immunoglobulin Conference: Immunomodulation. 2014 Dec Rheumatoid arthritis (RA) is a debilitating autoimmune disease that is usually treated aggressively to slow the rate of joint destruction. The therapeutic strategy used at the French centre, described here, is to use the non-biological disease-modifying drug, methotrexate, as first-line therapy and to add biological agents as second-line treatment. The two other autoimmune diseases discussed in this session were immunobullous skin diseases, and secondary recurrent miscarriage (RM). In the former conditions, low levels of pathogenic autoantibodies can be achieved with adjuvant intravenous immunoglobulin (IVIg) therapy, usually in combination with an immunosuppressant. Secondary RM has an autoimmune basis, as shown by high tumour necrosis factor (TNF)-α levels and specific human leucocyte antigen (HLA) polymorphisms. Although the mechanism is not yet known, IVIg may also be an effective treatment, despite the generally low doses used in published studies.
24296720 T-cell aging in rheumatoid arthritis. 2014 Jan PURPOSE OF REVIEW: With progressive age, the immune system and the propensity for abnormal immunity change fundamentally. Individuals greater than 50 years of age are not only more susceptible to infection and cancer, but also at higher risk for chronic inflammation and immune-mediated tissue damage. The process of immunosenescence is accelerated in rheumatoid arthritis (RA). RECENT FINDINGS: Premature T-cell senescence occurs not only in RA, but also has been involved in morbidity and mortality of chronic HIV infection. Senescent cells acquire the 'senescence-associated secretory phenotype', which promotes and sustains tissue inflammation. Molecular mechanisms underlying T-cell aging are beginning to be understood. In addition to the contraction of T-cell diversity because of uneven clonal expansion, senescent T cells have defects in balancing cytoplasmic kinase and phosphatase activities, changing their activation thresholds. Also, leakiness in repairing DNA lesions and uncapped telomeres imposes genomic stress. Age-induced changes in the tissue microenvironment may alter the T-cell responses. SUMMARY: Gain-of-function and loss-of-function in senescent T cells undermine protective immunity and create the conditions for chronic tissue inflammation, a combination typically encountered in RA. Genetic programs involved in T-cell signaling and DNA repair are of high interest in the search for underlying molecular defects.
23135613 Induced psoriasis after rituximab therapy for rheumatoid arthritis: a case report and revi 2013 Nov Rituximab is a human/murine monoclonal antibody targeting the CD20 antigen on B-lymphocytes surface. Although it has been licensed for treatment of non-Hodgkin's lymphoma, nowadays it is also a novel therapy for autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Despite the increasing evidence regarding the safety and efficacy of rituximab in these conditions, many cutaneous adverse events have been reported. Here, we describe the case of a 69-year-old patient, affected by rheumatoid arthritis, who developed psoriatic lesions on her trunk and arms, three months after the second course of rituximab. Similar cases appearing in the literature will also be briefly mentioned.
23322458 Cost-related medication nonadherence in older patients with rheumatoid arthritis. 2013 Feb OBJECTIVE: Economic access to costly medications including biologic agents can be challenging. Our objective was to examine whether patients with rheumatoid arthritis (RA) are at particular risk for cost-related medication nonadherence (CRN) and spending less on basic needs. METHODS: We identified a nationally representative sample of older adults with RA (n = 1100) in the Medicare Current Beneficiary Survey (2004-2008) and compared them to older adults with other morbidities categorized by chronic disease count: 0 (n = 5898), 1-2 (n = 30,538), and ≥ 3 (n = 34,837). We compared annual rates of self-reported CRN (skipping or reducing medication doses or not obtaining prescriptions because of cost) as well as spending less on basic needs to afford medications and tested for differences using survey-weighted logistic regression analyses adjusted for demographic characteristics, health status, and prescription drug coverage. RESULTS: In the RA sample, the unadjusted weighted prevalence of CRN ranged from 20.7% in 2004 to 18.4% in 2008 as compared to 18.5% and 11.9%, respectively, in patients with 3 or more non-RA conditions. In adjusted analyses, having RA was associated with a 3.5-fold increase in the risk of CRN (OR 3.52, 95% CI 2.63-4.71) and almost a 2.5-fold risk of spending less on basic needs (OR 2.41, 95% CI 1.78-3.25) as compared to those without a chronic condition. CONCLUSION: Patients with RA experience a high prevalence of CRN and forgoing of basic needs, more than do older adults with multiple other chronic conditions. The situation did not improve during a period of policy change aimed at alleviating high drug costs.
25260765 [Evaluation of a technical modification to Mannerfelt's total wrist fusion technique in a 2014 Oct We studied a technical modification of Mannerfelt's total wrist fusion technique in a series of 19 wrists. A fully intramedullary technique without dorsal carpal fixation was used to protect the extensor tendons. Two intramedullary Rush pins without dorsal staples were used during the arthrodesis procedure. Nineteen rheumatoid arthritis wrists (2 bilateral cases) were reviewed with a mean follow-up of 4.9 years (range 2-10 years). Clinical outcomes were assessed using the VAS pain scale, DASH-score and wrist strength measurements. Wrist fusion was assessed on AP and lateral X-rays of the wrist. The position of the carpal Rush pin entry points and distal hook orientation were also assessed. Pain was 8.9 preoperatively and 1.1 at the last follow-up with 95% patients satisfied. Mean DASH-score was 46.9 points. The pinch strength was 79% and the grip strength was 68% of the contralateral wrist. Carpal height, carpal anterior subluxation and ulnar deviation were stable at the last follow-up. All of the wrists were in straight position and no extensor tendon ruptures were noted. Fusion was complete in all cases within 6 to 12 weeks, except in one case. The technical modification proposed in the current study -intraosseous fixation only- appears to be a good alternative to Mannerfelt's original technique. Every case treated with this modified technique had good functional results and none required pin removal.
25054606 Articular ultrasonography: interobserver reliability in rheumatoid arthritis. 2014 May INTRODUCTION: Ultrasonography (US) has a recent use in Rheumatology, and the reliability of the method in rheumatoid arthritis (RA) patients has yet to be clarified. OBJECTIVE: To test, in a RA survey, the reproducibility of musculoskeletal US performed by rheumatologists with one-year training through re-analysis by a Rheumatologist experienced in the method. PATIENTS AND METHODS: This cross-sectional study included consecutive RA patients from our tertiary center. US exam was performed in metacarpophalangeal joints, proximal interphalangeal joints, and wrists. Presence of synovitis, power Doppler (PD) signal, bone erosions, and cartilage changes comprised the US parameters evaluated. A kappa value in-between 0.20 and 0.40 was considered fair; in-between 0.41 and 0.60 was moderate; in-between 0.61 and 0.80 was good; and above 0.81 was excellent. RESULTS: We analyzed 1,380 joints of 60 RA patients (78% females, 78% caucasoids). Mean age was 58 ± 11.56 years, mean disease duration was 9.98 ± 7.79 years, mean DAS28 was 3.82 ± 1.53, and mean HAQ was 0.91 ± 0.67. Kappa agreement for synovitis ranged from 0.30 to 0.70; for PD signal, from 0.53 to absolute agreement; for erosions, from 0.70 to 0.97; for cartilage changes, from 0.28 to 0.63. CONCLUSION: Although good, moderate and excellent interobserver agreement were obtained for erosions and PD, concordance for synovitis and cartilage changes were less impressive in our patients with active RA. Further studies on standardization of scanning technique are necessary to improve musculoskeletal US reproducibility.
25246736 Usefulness of serum leucine-rich alpha-2 glycoprotein as a disease activity biomarker in p 2014 Sep Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-α and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8 ± 14.4 vs. 22.2 ± 6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (γ=0.671; γ=0.612; and γ=0.601, P<0.001, respectively), but not with serum TNF-α levels. Serum LRG levels in patients with an active disease status (DAS28≥2.6) were significantly higher than those in remission (DAS28<2.6) (36.45 ± 14.36 vs. 24.63 ± 8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-α and it may be a novel biomarker for assessing inflammatory activity in patients with RA.
23832166 Outcome after total ankle arthroplasty-results and findings from worldwide arthroplasty re 2013 Sep PURPOSE: The data currently available concerning total ankle arthroplasty (TAA) does not allow valid conclusions in several clinically relevant areas. Total ankle arthroplasty imposes special requirements on the methodology of data collection, evaluation, publication and the assessment of register data. METHODS: We undertook a structured and descriptive analysis of all outcome data available from high-quality national arthroplasty registers worldwide. Register data from Sweden, Finland, Norway, New Zealand and Australia were included in the analysis. RESULTS: There are marked differences between Europe and Oceania with respect to indications. All data sets show revision rates of approximately 10 % at five years, of which about 40 % of cases are for aseptic loosening. Inlay fractures are relatively common, which indicates potential for the improvement of implants. The documentation of intraoperative surgical errors leading to revision surgery varies significantly among registers. A relevant number of complications are treated without an implant component being exchanged and therefore not covered by a register. CONCLUSIONS: The results of TAA are promising, but the revision rate is higher than for total hip or knee arthroplasty. TAA outcome measurement by means of registers has several specific requirements necessitating additional documentation beyond the basic data set. For methodological reasons the evaluation of results is more complex than for hip or knee arthroplasty. It will therefore be essential to standardise data collection and evaluation and develop a methodology addressing the specific needs of TAA.
25138370 Non-HLA genes PTPN22, CDK6 and PADI4 are associated with specific autoantibodies in HLA-de 2014 Aug 20 INTRODUCTION: Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti-citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04. METHODS: We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen. RESULTS: Our data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P = 0.0001, P corrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel-Haenszel test P = 0.0004, P corrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02). CONCLUSION: These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA.
24440691 Involvement of transient receptor potential melastatin-8 (TRPM8) in menthol-induced calciu 2014 Feb 15 Rheumatoid arthritis is most prominently characterized by synoviocyte hyperplasia which therefore serves as an important target for clinical therapy. In the present study, it was observed that menthol, the specific agonist of transient receptor potential melastatin subtype 8 (TRPM8), could induce sustained increases of cytosolic calcium concentration ([Ca(2+)]c) in synoviocytes isolated from collagen-induced arthritis rats in dose-dependent manner, which was evidently blocked by applying an extracellular Ca(2+)-free buffer. Menthol-induced [Ca(2+)]c increase was also significantly inhibited by potent TRPM8 antagonist capsazepine (CZP), indicating that this [Ca(2+)]c elevation was mostly attributed to TRPM8-mediated Ca(2+) entry. Besides, RT-PCR indeed demonstrated presence of TRPM8 in the synoviocytes. Meanwhile, it was found that menthol evoked production of intracellular reactive oxygen species, which could be abolished by Ca(2+) free solutions or CZP. Further experiments showed that menthol reduced the cell numbers and survival of synoviocytes. This reduction was associated with apoptosis as suggested by mitochondrial membrane depolarization, nuclear condensation and a caspase 3/7 apoptotic assay. Menthol-induced death and apoptosis of synoviocytes both were obviously inhibited by CZP, intracellular calcium chelator BAPTA-AM, and reactive oxygen species inhibitor diphenylene iodonium, respectively. Taken together, our data indicated that menthol resulted in synoviocyte death associated with apoptosis via calcium entry and reactive oxygen species production depending on TRPM8 activation.
24364534 Disabilities of importance for patients to improve--using a patient preference tool in rhe 2014 PURPOSE: To investigate, using the McMaster Toronto Arthritis patient preference disability questionnaire (MACTAR), disabilities most important to improve in Swedish patients with rheumatoid arthritis (RA) and to compare these with the pre-defined activities in the International Classification of Functioning (ICF) comprehensive core set for RA and the Stanford Health Assessment Questionnaire (HAQ). Also to categorize patient preference selected disabilities using the ICF, to correlate the MACTAR score to RA core set measures and to evaluate the MACTAR's test-retest reliability. METHODS: 45 patients with RA (median (md) age 59 years, diagnosis duration md 10 years) were included. Assessments included disease activity score (DAS28), timed-stands test (TST), shoulder function assessment (SFA), visual analogue scale for pain (VAS), HAQ, patients' global assessment of well-being (PGA) and the MACTAR. RESULTS: 58 disabilities were identified of which 17 were identified by at least 5 patients. 47% of them were represented in the Comprehensive ICF RA core set and 53% in the HAQ. 16/17 were categorized in the ICF activities and participation component. Correlations between the MACTAR and other measures were: DAS28 (rs -0.65), TST (rs -0.19), SFA (rs 0.38), VAS (rs -0.61), HAQ (rs -0.51) and PGA (rs -0.61). Weighted κ was 0.59. CONCLUSIONS: Half of the disabilities patients with RA identified by use of the MACTAR are not evaluated in the Comprehensive ICF core set for RA or the HAQ. MACTAR has moderate test-retest reliability. MACTAR can be considered to be used in addition to traditional RA outcomes and may potentially improve clinical assessment of patients with RA. IMPLICATIONS FOR REHABILITATION: RA has an impact on personal life areas. The MACTAR helps identify individual disease-related disabilities of importance to improve. The MACTAR provides an opportunity for individualized goal-setting in rehabilitation and can thus promote adherence in rehabilitation. MACTAR may potentially improve clinical assessment for patients with RA.
24703402 Prevalence and concordance of early and sustained remission assessed by various validated 2014 Oct OBJECTIVES: To assess the prevalence of remission in early arthritis, to evaluate the concordance across different criteria sets in defining this state, and to look for predictive factors for early and sustained remission. METHODS: Patients from the ESPOIR cohort were followed-up every 6months. We analysed early remission and sustained remission in 3 groups of patients: patients having rheumatoid arthritis (RA) according to 2010 ACR/EULAR criteria, undifferentiated arthritis (UA), and the whole cohort. Remission was defined according to ACR/EULAR criteria, 28 Joint Disease Activity Score (DAS28<2.6), and Simplified Disease Activity Index (SDAI≤3.3). Agreement was evaluated by k-coefficient. Predictive factors for sustained remission at 1, 3 and 5year in RA patients were analyzed. RESULTS: Eight hundred and nineteen patients were included. Early remission rates in the RA/UA/ESPOIR groups were observed in respectively 29.2% (181/682), 51.4% (55/123) and 32.7% (239/813) of patients by DAS28; 15.7%, 29.1% and 18% by SDAI; and 11.2%, 29.1% and 12.8% by ACR/EULAR criteria. Agreement between classifications of remission was low for DAS28 vs. ACR/EULAR (k=0.44), high for SDAI vs. ACR/EULAR (k=0.78), and moderate for SDAI vs. DAS28 (k=0.54). Lower baseline disease activity scores, non-menopausal status and younger age were the best predictive factors for sustained remission, with consistent results across the 3 definitions of remission. CONCLUSION: Our study showed that the rate of early and sustained remission in early arthritis is dependent on the definition used, with a variable degree of agreement across criteria sets, but with consistent predictive factors of favourable outcome in patients finally diagnosed with RA.