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ID PMID Title PublicationDate abstract
25422168 Patients and nursing staff views of using the education needs assessment tool in rheumatol 2015 Apr AIMS AND OBJECTIVES: To evaluate the usability of the educational needs assessment tool in clinical practice, from a practitioner and patient perspective and to establish whether patients perceive that they are getting an equally good or equally inadequate education service for their needs. BACKGROUND: The educational needs assessment tool was developed to enable patients with Rheumatoid Arthritis to assess their education needs prior to a consultation with a health professional. The educational needs assessment tool has been translated into nine languages and measurement properties have been established, however, its usability in clinical practice has not been studied. DESIGN: A qualitative study embedded into a multicentre RCT in which patients had been randomised into either educational needs assessment tool-focused education (Experimental Group) or usual care (control group). METHODS: Both groups were seen by a clinical nurse specialist. Sixteen patients and four clinical nurse specialists were recruited from the Rheumatology Outpatient Departments of three Acute Hospitals within the U K. Data were collected by interviews with patients and clinical nurse specialist. Analysis followed the Framework approach. RESULTS: Patients and clinical nurse specialist found completion of the educational needs assessment tool straightforward, comprehensive and easy to use. Completing the educational needs assessment tool helped patients to focus on what they needed to know from the clinical nurse specialist. Patients in both the control group and the experimental group felt supported and reassured by their clinical nurse specialist and perceived that they received a good and adequate education provision. CONCLUSION: This study provides useful insights into the ability of the educational needs assessment tool to assess the educational needs of patients with rheumatoid arthritis in routine clinical practice. RELEVANCE TO CLINICAL PRACTICE: The educational needs assessment tool would be useful as a structured guide for nurses when assessing and meeting individual patient educational needs. This has the potential to improve patient-centred care, involve patients more actively in their care and enhance the long-term effects of patient education provision.
24742142 CD4⁺CD25⁺/highCD127low/⁻ regulatory T cells are enriched in rheumatoid arthritis and 2014 Apr 17 INTRODUCTION: CD4⁺CD25⁺/highCD127low/⁻ regulatory T cells (Tregs) play a crucial role in maintaining peripheral tolerance. Data about the frequency of Tregs in rheumatoid arthritis (RA) are contradictory and based on the analysis of peripheral blood (PB) and synovial fluid (SF). Because Tregs exert their anti-inflammatory activity in a contact-dependent manner, the analysis of synovial membrane (SM) is crucial. Published reports regarding this matter are lacking, so we investigated the distribution and phenotype of Tregs in concurrent samples of SM, SF and PB of RA patients in comparison to those of osteoarthritis (OA) patients. METHODS: Treg frequency in a total of 40 patients (18 RA and 22 OA) matched for age and sex was assessed by flow cytometry. Functional status was assessed by analysis of cell surface markers representative of activation, memory and regulation. RESULTS: CD4⁺ T cells infiltrate the SM to higher frequencies in RA joints than in OA joints (P = 0.0336). In both groups, Tregs accumulate more within the SF and SM than concurrently in PB (P < 0.0001). Relative Treg frequencies were comparable in all compartments of RA and OA, but Treg concentration was significantly higher in the SM of RA patients (P = 0.025). Both PB and SM Tregs displayed a memory phenotype (CD45RO⁺RA⁻), but significantly differed in activation status (CD69 and CD62L) and markers associated with Treg function (CD152, CD154, CD274, CD279 and GITR) with only minor differences between RA and OA. CONCLUSIONS: Treg enrichment into the joint compartment is not specific to inflammatory arthritis, as we found that it was similarly enriched in OA. RA pathophysiology might not be due to a Treg deficiency, because Treg concentration in SM was significantly higher in RA. Synovial Tregs represent a distinct phenotype and are activated effector memory cells (CD62L⁻CD69⁺), whereas peripheral Tregs are resting central memory cells (CD62L⁺CD69⁻).
23942247 Reproductive history and postmenopausal rheumatoid arthritis among women 60 years or older 2013 Sep OBJECTIVE: Rheumatoid arthritis, a condition of unknown etiology, has been associated with considerable costs to society. The purpose of this study is to determine whether selected reproductive history characteristics are associated with postmenopausal rheumatoid arthritis diagnosis. METHODS: Secondary analyses were performed using cross-sectional data from the Third National Health and Nutrition Examination Survey. Of 1,892 eligible participants, 182 fulfilled the criteria for postmenopausal rheumatoid arthritis, based on self-report and the 1987 American College of Rheumatology criteria. Logistic regression models were constructed, and odds ratios (ORs) with their 95% CIs were calculated for selected reproductive history characteristics as predictors of postmenopausal rheumatoid arthritis, after adjustment for potential confounders. RESULTS: Multivariate logistic models suggested that age at menopause was the only reproductive characteristic that was significantly associated with the outcome of interest (OR, 0.96; 95% CI, 0.93-0.99). Compared with women experiencing menopause at 50 years of age or later, those who experienced menopause before 40 years of age (OR, 2.53; 95% CI, 1.41-4.53) had increased odds of postmenopausal rheumatoid arthritis. CONCLUSIONS: Women who experience menopause before 40 years of age seem to be at increased risk for postmenopausal rheumatoid arthritis. Conversely, age at menarche and pregnancy history may not predict rheumatoid arthritis after menopause. Further research is needed to confirm and elucidate these epidemiological findings.
23561068 Rheumatoid arthritis in upper limbs benefits from moderate pressure massage therapy. 2013 May METHODS: Forty-two adults with rheumatoid arthritis in the upper limbs were randomly assigned to a moderate pressure or a light pressure massage therapy group. A therapist massaged the affected arm and shoulder once a week for a 4-week period and also taught the participant self-massage to be done once daily. RESULTS: The moderate pressure vs. the light pressure massage therapy group had less pain and perceived greater grip strength following the first and last massage sessions. By the end of the one month period the moderate pressure massage group had less pain, greater grip strength and greater range of motion in their wrist and large upper joints (elbows and shoulders).
25141578 [Adherence to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis] 2014 A close collaboration between doctor and patient is essential for optimization of treatment outcomes in patients with chronic disease. Nonadherence to disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may contribute to treatment failure and result in loss of joint function. The aim of the study was to evaluate adherence to prescribed drug therapy by patients with RA 6 months after hospital discharge. The influence of age, sex, level of education and DAS28 score on compliance with treatment regimen was also evaluated. MATERIALS AND METHODS. A telephone survey was conducted using a questionnaire. The survey involved 146 randomly selected patients who were previously treated at the Department of Rheumatology for worsening of rheumatoid arthritis. RESULTS: Most of the patients gave their consent for participation in the survey. 113 (82.5%) of the respondents reported good compliance /adherence with the DMARD treatment regimen. 24 (17.5%) of the patients did not take prescribed medications, primarily due to adverse side effects and, less commonly, due to ineffective treatment or lack of clinical symptoms, and also for financial reasons. Age, sex, level of education and DAS28 score did not significantly influence medication adherence. CONCLUSIONS: Most of the patients treated for RA are followed up at rheumatology outpatient clinics and they continue treatment with DMARDs after discharge from hospital. Adverse side effects are the main cause of a change or discontinuation of the treatment.
23926057 Rheumatoid arthritis increases the risk of deep vein thrombosis and pulmonary thromboembol 2014 Oct OBJECTIVE: Studies on the association between rheumatoid arthritis (RA) and deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) are scarce. This study identifies the effects of RA on the risks of developing DVT and PE in a nationwide prospective cohort study. METHODS: We studied the entire Taiwan population from 1998 to 2008, with a follow-up period extending to the end of 2010. We identified patients with RA using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD). We also selected a comparison cohort that was randomly frequency-matched by age (each 5-year span), sex and index year from the general population. We analysed the risks of DVT and PE using Cox proportional hazards regression models, including sex, age and comorbidities. RESULTS: From 23.74 million people in the cohort, 29 238 RA patients (77% women, mean age of 52.4 years) and 1 16 952 controls were followed 1 93 753 and 7 92 941 person-years, respectively. The risk of developing DVT and PE was 3.36-fold and 2.07-fold, respectively, in patients with RA compared with patients without RA, after adjusting for age, sex and comorbidities. The multiplicative increased risks of DVT and PE were also significant in patients with RA with any comorbidity. CONCLUSIONS: This nationwide prospective cohort study demonstrates that DVT and PE risks significantly increased in patients with RA compared with those of the general population.
24729427 Alcohol consumption and risk of incident rheumatoid arthritis in women: a prospective stud 2014 Aug OBJECTIVE: To evaluate the association of alcohol consumption with the risk of rheumatoid arthritis (RA) in 2 large prospective cohorts, the Nurses' Health Study (NHS) and NHSII. METHODS: The NHS was established in 1976 and enrolled 121,701 female registered nurses in the US. The NHSII began in 1989, enrolling 116,430 female nurses. Lifestyle and environmental exposures were collected through biennial questionnaires. Alcohol consumption was assessed with a food frequency questionnaire, which was completed every 4 years. Incident RA cases were identified using a connective tissue disease screening questionnaire and a medical record review. Separate Cox proportional hazards models were used to estimate hazard ratios (HRs) after adjusting for potential confounders in the NHS and NHSII. The pooled HR from 2 cohorts was estimated using a DerSimonian and Laird random-effects model. RESULTS: Among 1.90 million person-years from 1980 to 2008, 580 incident cases of RA were diagnosed in the NHS cohort, and among 1.78 million person-years from 1989 to 2009, 323 incident cases of RA were diagnosed in the NHSII cohort. Compared to no use, the pooled multivariable adjusted HR for alcohol use of 5.0-9.9 gm/day was 0.78 (95% confidence interval [95% CI] 0.61-1.00). For seropositive RA cases, the association appeared stronger (HR 0.69 [95% CI 0.50-0.95]). In addition, women who drank beer 2-4 times a week had a 31% decreased risk compared to women who never drank beer. CONCLUSION: We found a modest association between long-term moderate alcohol drinking and reduced risk of RA. Future studies are needed to confirm our findings in other populations.
23165424 Silencing the expression of connexin 43 decreases inflammation and joint destruction in ex 2013 Apr The objective of the present study was to determine whether the expression of connexin 43 (Cx43) effected on inflammatory conditions in rat fibroblast-like synoviocytes (FLS) and on rat model of rheumatoid arthritis (RA). The expression of Cx43 in rat FLS stimulated with lipopolysaccharide (LPS) was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effects of small-interfering RNA targeting Cx43 (siCx43) on pro-inflammatory cytokines and chemokine were assessed by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). The therapeutic and side effects of siCx43 in a rat model of collagen-induced arthritis (CIA) were examined by in vivo electroporation method. LPS markedly enhanced Cx43 gene expression in rat FLS, with transfection of siCx43 suppressing the over-expression of pro-inflammatory cytokines and the chemokine. Treatment of CIA rats with siCx43 significantly ameliorated paw swelling, and significantly reduced histological arthritis scores and radiographic scores. In histological appearance of rat ankle joints, siCx43 treatment significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive (osteoclast-like) cells. These findings indicated that siCx43 had anti-inflammatory effects in rat FLS and efficiently inhibited the development of CIA. Cx43 may play an important role in the pathophysiology of RA, and may be a potential target molecule for novel RA therapies.
24971313 Commercial bovine proteoglycan is highly arthritogenic and can be used as an alternative a 2014 Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies.
24182347 Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radio 2014 OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought to be implicated in disease activity in chronic rheumatoid arthritis (RA). METHOD: We measured sPD-1 at baseline and 9 months after treatment initiation in plasma from early RA patients (n = 34). We tested for correlations with the Disease Activity Score using 28 joint counts (DAS28), the Health Assessment Questionnaire (HAQ) score, immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers (HV) (n = 20) and in plasma and synovial fluid (SF) from patients with chronic RA (> 8 years of disease, n = 30). We further investigated the cellular expression of PD-1 and its ligand PD-L1. RESULTS: sPD-1 concentrations in early [median 0.421 ng/mL, interquartile range (IQR) 0.04-2.560 ng/mL] and chronic (median 0.239 ng/mL, IQR 0.184-0.584 ng/mL) RA were increased compared with HV (median 0.04 ng/mL, IQR 0.04-0.04 ng/mL) (all p < 0.005). In early RA the change in sPD-1 was associated with DAS28 (r = 0.363, p < 0.05) and HAQ score (r = 0.554, p < 0.05) and inversely with TSS at 3-5 years (r = -0.468, p < 0.05). sPD-1 concentration correlated with IgM-RF, anti-CCP antibodies, and IL-21 (all p < 0.05). PD-1 was primarily expressed by synovial memory T cells whereas PD-L1 was mainly expressed by synovial monocytes. CONCLUSIONS: The significantly elevated plasma levels of sPD-1 in early RA, the association with core disease parameters, and the inverse correlation with TSS suggest that sPD-1 is an important mediator in inflammatory and radiographic disease progression.
23183906 Hypoxia-induced endogenous prostaglandin E2 negatively regulates hypoxia-enhanced aberrant 2013 Nov OBJECTIVE: During isometric exercise, the synovial joint tissue is prone to hypoxia, which is further enhanced in the presence of synovial inflammation. Hypoxia is also known to induce inflammatory cascades, suggesting that periodic hypoxia perpetuates synovitis in rheumatoid arthritis. We previously established an ex vivo cellular model of rheumatoid arthritis using the synovial tissue-derived inflammatory cells, which reproduced aberrant synovial overgrowth and pannus-like tissue development in vitro. Using this model, we investigated the regulatory mechanism of synovial cells against hypoxia in rheumatoid arthritis. METHODS: Inflammatory cells that infiltrated synovial tissue from patients with rheumatoid arthritis were collected without enzyme digestion, and designated as synovial tissue-derived inflammatory cells. Under normoxia or periodic hypoxia twice a week, their single-cell suspension was cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue in vitro. Cytokines produced in the culture supernatants were measured by enzyme-linked immunosorbent assay kits. RESULTS: Primary culture of the synovial tissue-derived inflammatory cells under periodic hypoxia resulted in the attenuation of the spontaneous growth of inflammatory tissue in vitro compared to the culture under normoxia. Endogenous prostaglandin E2 (PGE2) production was enhanced under periodic hypoxia. When endogenous PGE2 was blocked by indomethacin, the aberrant tissue overgrowth was more enhanced under hypoxia than normoxia. Indomethacin also enhanced the production of tumor necrosis factor-α (TNF-α), macrophage colony-stimulating factor (M-CSF), and matrix metalloproteinase-9 (MMP-9) under periodic hypoxia compared to normoxia. The EP4-specific antagonist reproduced the effect of indomethacin. Exogenous PGE1 and EP4-specific agonist effectively inhibited the aberrant overgrowth and the production of the inflammatory mediators under periodic hypoxia as well as normoxia. CONCLUSIONS: The enhancing effect of periodic hypoxia on the aberrant overgrowth of rheumatoid synovial tissue was effectively down-regulated by the simultaneously induced endogenous PGE2.
23982986 Is swollen to tender joint count ratio a new and useful clinical marker for biologic drug 2014 Feb OBJECTIVE: To study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients. METHODS: Patients with RA initiating their first course of anti-TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR <0.5), moderate (0.5 ≤ STR ≤ 1.0), or high (STR >1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010. RESULTS: A total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18-29%) with low, 39% (95% CI 35-43%) with moderate, and 40% (95% CI 36-44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively. CONCLUSION: STR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2- to 3-fold increased likelihood of responding according to ACR50 criteria.
23529475 Testosterone is protective in the sexually dimorphic development of arthritis and lung dis 2013 Jun OBJECTIVE: Rheumatoid arthritis (RA) is a sexually dimorphic inflammatory autoimmune disease with both articular and extraarticular disease manifestations, including RA-associated interstitial lung disease. Low levels of testosterone have been linked to disease severity in men with RA, and supplemental testosterone has been shown to improve RA symptoms in both postmenopausal women and men with low levels of testosterone. The mechanisms by which sex and sex steroids affect the immune system and autoimmunity are poorly understood. The purpose of this study was to examine the protective effects of testicular-derived sex hormones on the development of joint and lung disease in an autoimmune mouse model. METHODS: Arthritis prevalence and severity were assessed in orchiectomized, sham-orchiectomized, and intact male SKG mice as well as in female SKG mice over a 12-week period after intraperitoneal injection of zymosan. Lung tissues were evaluated by quantifying cellular accumulation in bronchoalveolar lavage fluid, collagen levels, and histologic changes. An antigen microarray was used to evaluate autoantibody generation under each experimental condition. RESULTS: Female SKG mice developed arthritis and lung disease at increased prevalence and severity as compared to intact male mice. The absence of testosterone after orchiectomy led to increased arthritis, lung disease, and autoantibody generation in orchiectomized male mice as compared to intact male mice. CONCLUSION: SKG mice represent an authentic sexually dimorphic mouse model of both the joint and lung disease seen in humans with RA. Testosterone protects against the development of joint and lung disease in male SKG mice.
23819623 Serum metabolic signatures of four types of human arthritis. 2013 Aug 2 Similar symptoms of the different types of arthritis have continued to confound the clinical diagnosis and represent a clinical dilemma making treatment choices with a more personalized or generalized approach. Here we report a mass spectrometry-based metabolic phenotyping study to identify the global metabolic defects associated with arthritis as well as metabolic signatures of four major types of arthritis--rheumatoid arthritis (n = 27), osteoarthritis (n = 27), ankylosing spondylitis (n = 27), and gout (n = 33)--compared with healthy control subjects (n = 60). A total of 196 metabolites were identified from serum samples using a combined gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF MS) and ultraperformance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-QTOF MS). A global metabolic profile is identified from all arthritic patients, suggesting that there are common metabolic defects resulting from joint inflammation and lesion. Meanwhile, differentially expressed serum metabolites are identified constituting an unique metabolic signature of each type of arthritis that can be used as biomarkers for diagnosis and patient stratification. The results highlight the applicability of metabonomic phenotyping as a novel diagnostic tool for arthritis complementary to existing clinical modalities.
23689232 Musculoskeletal ultrasonography in patients with rheumatoid arthritis. 2013 Jul In the current paradigm for management of patients with rheumatoid arthritis (RA), obtaining clinical remission of symptoms remains the most important aim, but achieving radiographic remission is another key goal of treatment. Several parameters detectable by musculoskeletal ultrasonography can predict the development of severe RA, as well as monitor patients' responses to treatment; thus, musculoskeletal ultrasonography is widely used for evaluating patients with RA, both in clinical trials and in clinical practice. This Review describes the applications of musculoskeletal ultrasonography in patients with RA, focusing on the identification of ultrasonographic features that predict the development of erosions. Such predictive markers include high vascularity of synovitis, persistent synovitis, tenosynovitis of the extensor carpi ulnaris tendon, and erosive changes in the distal ulna. This article also describes ultrasonographic scores that could feasibly be integrated into daily rheumatology practice for the evaluation of patients with RA.
25579963 Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for developme 2015 Mar The present study clarifies co-therapy action of deliveries from their textural changes point of view. Methotrexate (MTX) was immobilized onto biodegradable lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected into albino rats at doses of 0.25 and 0.5mg/kg/week for 2.5months, after which spleen, liver, testes and knee joint tissues were collected for tests. IFN-γ and IL-17A mRNA gene expressions in spleen in all biological samples were determined by RT-PCR. Physicochemical features of drug carriers were monitored by XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be closely related to the physico-features of deliverers. The interlayered lignin of micro- and meso-pore channels directed MTX toward concealed infected cells in liver and testes tissues, while meso-structured silica flacks satisfied by gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX toward spleen tissue, which is considered as a lively factory for the production of electron rich compounds.
23370751 Familial Mediterranean fever occurring in an elderly Japanese woman with recent-onset rheu 2013 A 60-year-old woman with a two-year history of rheumatoid arthritis (RA) developed recurrent two- to three-day attacks of fever (>38 °C) accompanied by monoarthritis of the right hip joint. The first attack occurred two months after beginning anti-tumor necrosis factor-α therapy. Since a diagnosis of infectious arthritis was suspected, the therapy was discontinued. Thereafter, the patient repeated similar episodes; however, oral colchicine effectively controlled the attacks. The patient was diagnosed to have familial Mediterranean fever (FMF). The clinical manifestations of FMF mimic infectious complications during anti-RA therapy. Clinicians should therefore consider the possibility of FMF development in RA patients exhibiting recurrent febrile attacks.
22949726 Early consultation with a rheumatologist for RA: does it reduce subsequent use of orthopae 2013 Mar OBJECTIVE: Optimal care in RA includes early use of DMARDs to prevent joint damage and hopefully decrease the need for costly surgical interventions. Our objective was to determine whether a reduced rate of orthopaedic surgery was evident for persons with RA who saw a rheumatologist early in the disease course. METHODS: We studied persons who had a diagnosis of RA based on billing code data in the province of Quebec in 1995, and for whom the initial date of RA diagnosis by a non-rheumatologist could be established before the confirmatory diagnosis by the rheumatologist. We followed these patients until 2007. Patients were classified as early consulters or late consulters depending on whether they were seen by a rheumatologist within or beyond 3 months of being diagnosed with RA by their referring physician. The outcome, orthopaedic surgery, was defined using International Classification of Diseases (ICD) procedure codes ICD9 and ICD10. Multivariate Cox regression with time-dependent covariates estimated the effect of early consultation on the time to orthopaedic surgery. RESULTS: Our cohort consisted of 1051 persons; mean age at diagnosis was 55.7 years, 68.2% were female and 50.7% were early consulters. Among all patients, 20.5% (215) had an orthopaedic surgery during the observation interval. Early consulters were less likely to undergo orthopaedic surgery during the 12-year follow-up period (adjusted hazard ratio 0.60, 95% CI 0.44, 0.82). CONCLUSION: Persons with RA who consult a rheumatologist later in the disease course have a worse outcome in terms of eventual requirement for orthopaedic surgery.
25264193 Substance P ameliorates collagen II-induced arthritis in mice via suppression of the infla 2014 Oct 10 Current rheumatoid arthritis (RA) therapies such as biologics inhibiting pathogenic cytokines substantially delay RA progression. However, patient responses to these agents are not always complete and long lasting. This study explored whether substance P (SP), an 11 amino acids long endogenous neuropeptide with the novel ability to mobilize mesenchymal stem cells (MSC) and modulate injury-mediated inflammation, can inhibit RA progression. SP efficacy was evaluated by paw swelling, clinical arthritis scoring, radiological analysis, histological analysis of cartilage destruction, and blood levels of tumor necrosis factor-alpha (TNF-α) interleukin (IL)-10, and IL-17 in vivo. SP treatment significantly reduced local inflammatory signs, mean arthritis scores, degradation of joint cartilage, and invasion of inflammatory cells into the synovial tissues. Moreover, the SP treatment markedly reduced the size of spleens enlarged by excessive inflammation in CIA, increased IL-10 levels, and decreased TNF-α and IL-17 levels. Mobilization of stem cells and induction of T(reg) and M2 type macrophages in the circulation were also increased by the SP treatment. These effect of SP might be associated with the suppression of inflammatory responses in RA and, furthermore, blockade of RA progression. Our results propose SP as a potential therapeutic for autoimmune-related inflammatory diseases.
24766912 Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis a 2014 Apr 25 INTRODUCTION: We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. METHODS: Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman's correlation analysis were utilized to determine relationships between variables. RESULTS: In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. CONCLUSION: Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production.