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

ID PMID Title PublicationDate abstract
26546562 Higher education is associated with a better rheumatoid arthritis outcome concerning for p 2015 Nov 6 INTRODUCTION: Whether low socioeconomic status (SES) is associated with worse rheumatoid arthritis (RA) outcomes in countries with general tax-financed healthcare systems (such as Sweden) remains to be elucidated. Our aim was to investigate the influence of educational background (achieving university/college degree (high) or not (low)) on the outcomes of early RA, in terms of disease activity (DAS28), pain (VAS-pain), and functional impairment (HAQ). METHODS: We evaluated DMARD-naïve RA patients recruited in the Epidemiological Investigation of RA (EIRA) study with outcomes followed in the Swedish Rheumatology Quality (SRQ) register (N = 3021). Outcomes were categorized in three ways: (1) scores equal to/above median vs. below median; (2) DAS28-based low disease activity, good response, remission; (3) scores decreased over the median vs. less than median. Associations between educational background and outcomes were calculated by modified Poisson regressions, at diagnosis and at each of the three standard (3, 6, 12 months) follow-up visits. RESULTS: Patients with different educational background had similar symptom durations (195 days) and anti-rheumatic therapies at baseline, and comparable treatment patterns during follow-up. Patients with a high education level had significantly less pain and less functional disability at baseline and throughout the whole follow-up period (VAS-pain: baseline: 49 (28-67) vs. 53 (33-71), p <0.0001; 1-year visit: RR = 0.81 (95% CI 0.73-0.90). HAQ: baseline: 0.88 (0.50-1.38) vs. 1.00 (0.63-1.50), p = 0.001; 1-year visit: 0.84 (0.77-0.92)). They also had greater chances to achieve pain remission (VAS-pain ≤20) after one year (1.17 (1.07-1.28)). Adjustments for smoking and BMI altered the results only marginally. Educational background did not influence DAS28-based outcomes. CONCLUSION: In Sweden, with tax-financed, generally accessible healthcare system, RA patients with a high education level experienced less pain and less functional disability. Further, these patients achieved pain remission more often during the first year receiving standard care. Importantly, education background affected neither time to referral to rheumatologists, disease activity nor anti-rheumatic treatments.
27756265 Motivational counselling and SMS-reminders for reduction of daily sitting time in patients 2016 Oct 18 BACKGROUND: Patients with rheumatoid arthritis (RA) spend a high proportion of their waking time in sedentary behaviour (SB) and have an increased risk of cardiovascular disease. Reduction of SB and increase in light intensity physical activity has been suggested as a means of improvement of health in patients with mobility problems. Short-term intervention studies have demonstrated that SB can be reduced by behavioural interventions in sedentary populations. To evaluate descriptively the feasibility of recruitment, randomisation, outcome assessments, retention and the acceptability of an individually tailored, theory-based behavioural intervention targeting reduction in daily sitting time in patients with RA. METHODS: A randomised, controlled trial with two parallel groups. RA patients >18 years of age and Health Assessment Questionnaire (HAQ) score < 2.5 were consecutively invited and screened for daily leisure time sitting > 4 h. The 16-week intervention included 1) three individual motivational counselling sessions and 2) individual text message reminders aimed at reducing daily sitting time. The control group was encouraged to maintain their usual lifestyles. Outcomes were assessed at baseline and after the 16 week intervention. Daily sitting time was measured using an ActivPAL3(TM) activity monitor. The study was not powered to show superiority; rather the objective was to focus on acceptability among patients and clinical health professionals. RESULTS: In total, 107 patients were invited and screened before 20 met eligibility criteria and consented; reasons for declining study participation were mostly flares, lack of time and co-morbidities. One patient from the control group dropped out before end of intervention (due to a RA flare). Intervention participants completed all counselling sessions. All procedures regarding implementation of the trial protocol were feasible. The daily sitting time was reduced on average by 0.30 h in the intervention group unlike the control group that tended to increase it by 0.15 h after 16 weeks. CONCLUSIONS: This study shows that an individually tailored behavioural intervention targeting reduction of SB was feasible and acceptable to patients with RA. TRIAL REGISTRATION: The Danish Data Protection Agency (ref.nb. 711-1-08 - 20 March 2011), the Ethics Committee of the Capital Region of Denmark (ref.nb. H-2-2012-112- 17 October 2012), clinicaltrials.gov ( NCT01969604 - October 17 2013, retrospectively registered).
26106958 The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis. 2015 Jun OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions.
25684771 The OMERACT MRI in Arthritis Working Group - Update on Status and Future Research Prioriti 2015 Dec OBJECTIVE: To provide an update on the status and future research priorities of the Outcome Measures in Rheumatology (OMERACT) magnetic resonance imaging (MRI) in arthritis working group. METHODS: A summary is provided of the activities of the group within rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and its research priorities. RESULTS: The OMERACT RA MRI score (RAMRIS) evaluating bone erosion, bone edema (osteitis), and synovitis is now the standard method of quantifying articular pathology in RA trials. Cartilage loss is another important part of joint damage, and at the OMERACT 12 conference, we provided longitudinal data demonstrating reliability and sensitivity to change of the RAMRIS JSN component score, supporting its use in future clinical trials. The MRI group has previously developed a PsA MRI score (PsAMRIS). At OMERACT 12, PsAMRIS was evaluated in a randomized placebo-controlled trial of patients with PsA, demonstrating the responsiveness and discriminatory ability of applying the PsAMRIS to hands and feet. A hand OA MRI score (HOAMRIS) was introduced at OMERACT 11, and has subsequently been further validated. At OMERACT 12, good cross-sectional interreader reliability, but variable reliability of change scores, were reported. Potential future research areas were identified at the MRI session at OMERACT 12 including assessment of tenosynovitis in RA and enthesitis in PsA and focusing on alternative MRI techniques. CONCLUSION: MRI has been further developed and validated as an outcome measure in RA, PsA, and OA. The group will continue its efforts to optimize the value of MRI as a robust biomarker in rheumatology clinical trials.
25900105 Coverage for high-cost specialty drugs for rheumatoid arthritis in Medicare Part D. 2015 Jun OBJECTIVE: More than 1 in 4 Medicare beneficiaries with rheumatoid arthritis use high-cost biologic disease-modifying antirheumatic drugs (DMARDs), and spending for these drugs has risen sharply for Medicare Part D. Our aim was to conduct the first systematic, national investigation of how Part D plans cover biologic DMARDs and to determine patients' financial burden under current cost-sharing structures. METHODS: We performed a cross-sectional analysis of Part D plan formularies (n = 2,737) in 50 states and Washington, DC using the January 2013 Centers for Medicare and Medicaid Services Prescription Drug Plan Formulary and Pharmacy Network Files. We calculated the percentage of plans covering each DMARD as well as the percentage requiring prior authorization and/or coinsurance. We also compared biologic drug coverage in Medicare Advantage prescription drug plans to that in Medicare Part D stand-alone plans. RESULTS: All plans covered at least 1 biologic DMARD, but the vast majority required prior authorizations (95%). Nearly all plans (81-100%) required patients to pay a coinsurance percentage (averaging 29.6% of drug costs) rather than a fixed dollar copayment. This translated into mean out-of-pocket costs of $2,712-$2,774 before reaching the catastrophic phase of coverage, during which beneficiaries pay 5% of drug costs. Medicare Advantage prescription drug plans covered more individual biologic DMARDs (55-100%) than did Medicare Part D stand-alone plans (22-100%), but Medicare Advantage prescription drug plans required higher average coinsurance (31.1% versus 29.0%). In contrast, 6 of 9 nonbiologic DMARDs were covered by nearly all plans without prior authorizations at fixed copayments averaging $5-$10/month. CONCLUSION: Nationally, nearly all Part D plans cover at least 1 biologic DMARD, but the vast majority require cost sharing sufficiently high to risk significant financial burden to patients.
27037016 A prospective cohort study of 14-3-3η in ACPA and/or RF-positive patients with arthralgia 2016 Apr 1 BACKGROUND: 14-3-3η (eta) is a novel serum/plasma protein biomarker involved in the upregulation of inflammatory and joint damage factors. We analysed the association of 14-3-3η with the development of clinically apparent arthritis in a cohort of subjects with arthralgia and positivity for at least one serologic marker: rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA). METHODS: Measurement of 14-3-3η in plasma collected on entry into the cohort. For this study, 144 subjects with a minimum of 2.5 (median and maximum 5) years of follow-up were available. The relationship between presence and levels of 14-3-3η and development of arthritis was investigated. RESULTS: Arthritis occurred in 43 (30 %) of the 144 subjects after a median of 15 months. 14-3-3η was detectable up to 5 years before onset of clinical arthritis and was present significantly more often (36 % versus 14 %; relative risk 2.5, 95 % confidence interval 1.2-5.6; p = 0.02) and at significantly higher levels (median 0.95 versus 0.28 ng/ml; p = 0.02) in subjects developing arthritis compared with those who did not. 14-3-3η levels/positivity and ACPA, but not RF, were univariately associated with the development of arthritis while generalized linear model analysis with RF and ACPA as obligatory factors could not return an incremental benefit with 14-3-3η. CONCLUSIONS: 14-3-3η was detectable prior to the onset of arthritis and was associated with arthritis development in arthralgia subjects pre-selected for positivity of RF or ACPA. Its power to predict onset of arthritis independent of ACPA and RF requires a new study in which patients are not pre-selected based on ACPA and/or RF seropositivity.
26545701 When Patients Write the Guidelines: Patient Panel Recommendations for the Treatment of Rhe 2016 Jan OBJECTIVE: How best to involve patients in the development of clinical practice guideline (CPG) recommendations is not known. We sought to determine the feasibility and value of developing CPG recommendations based on a voting panel composed entirely of patients, with the ultimate goal of comparing the patients' recommendations to ones developed by a physician-dominated voting panel on the same clinical questions. METHODS: Ten patients with rheumatoid arthritis completed 8 hours of training on evidence-based medicine and guideline development. They constituted a voting panel and, with 2 American College of Rheumatology staff with expertise in CPG development and a physician facilitator, subsequently met at a face-to-face meeting to develop recommendations. They applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology to formulate recommendations on 18 questions for which there was evidence warranting moderate or high confidence. RESULTS: The patient panel developed recommendations for 16 of the 18 questions; for the other 2, the panel thought there were insufficient data to support a recommendation. For 13 of the 16 questions, the patient panel recommended the same course of action as did the physician-dominated panel. Differences were due to how the 2 panels valued the balance between benefits and harms. CONCLUSION: Patient and physician-dominated panels developed the same recommendations for most questions for which there was evidence warranting moderate to high confidence. Additional experiences are necessary to advance the evidence necessary to determine what panel composition is optimal to produce the best guidelines.
26850109 [Operative therapy for rheumatoid arthritis of the hand]. 2016 Feb The need for operative treatment of severe rheumatic deformities of the hand and wrist is decreasing due to the increased use of disease-modifying drugs; however, some patients do not tolerate or do not sufficiently respond to these drugs, which often results in the hands being affected and in advanced stages to severe deformity and loss of function. In these cases operative surgery can help to slow the progression of rheumatic destruction and restore the function of the patient's hand. This article describes the principles of surgery for rheumatoid arthritis of the hand. A meticulous synovectomy or tenosynovectomy is the first stage of treatment. With progression of rheumatic destruction various salvage procedures are necessary to preserve the best possible functional state.
26188585 Alterations of the thrombin generation profile in rheumatoid arthritis. 2016 Apr Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder resulting in the erosion of the cartilage and bone. Systemic involvement including the cardiovascular system with the risk of atherosclerosis may also occur. Calibrated automated thrombogram (CAT), a commercially available thrombin generation assay is suitable for the general assessment of the functionality of coagulation system. In this study we performed CAT assay in RA patients and in non-affected control subjects (matched for age, sex and comorbidities). Among the CAT parameters Velocity Index increased (from 60 to 83 nM/min), Lag Time and Time to Peak decreased (from 3.47 to 2.83 min and from 6.98 to 5.58 min respectively) in RA. On the other hand, Endogenous Thrombin Potential values decreased (from 1242 to 1108 nM min). The observed alterations were not associated with the applied therapy. These results indicate that the velocity of thrombin formation is increased, while the thrombin generating capability is reduced in RA.
27444780 Focus group interviews reveal reasons for differences in the perception of disease activit 2017 Feb OBJECTIVE: Doctors frequently see patients who have difficulties coping with their disease and rate their disease activity high, despite the fact that according to the doctors, the disease activity is low. This study explored the patients' perspectives on this discordance that may help to understand why for some patients, usual care seems to be insufficient. METHODS: In our qualitative study we conducted focus group interviews where questions were used as a guideline. Transcripts were analyzed using inductive thematic analysis. FINDINGS: Twenty-nine patients participated in four focus groups. Participants could not put their finger exactly on why doctors estimated that their disease activity was low, while they experienced high levels of disease activity. During the in-depth focus interviews, seven themes emerged that appeared related to high experienced disease activity: (1) perceived stress, (2) balancing activities and rest, (3) medication intake, (4) social stress, (5) relationship with professionals, (6) comorbidity, and (7) physical fitness. CONCLUSION: When patients were asked why their view of their disease activity was different from that of their physician, seven themes emerged. The way participants coped with these themes seemed to be the predominant concept. Specific interventions that focus on one or more of the reported themes and on coping may improve not only the quality of life of these patients but also the satisfaction with the patient-doctor relationship for both parties.
26414775 Poverty, Depression, or Lost in Translation? Ethnic and Language Variation in Patient-Repo 2016 May OBJECTIVE: Despite advances in therapies, disparities in outcomes have been documented for rheumatoid arthritis (RA) patients for both ethnicity and English language proficiency. The goals of these analyses were to compare differences in RA patient-reported outcomes, by both self-identification of ethnicity and English language proficiency, and to identify factors that might explain differences among groups. METHODS: Data were collected through structured telephone interviews of a longitudinal cohort with physician-diagnosed RA (n = 438); only women were included (n = 335). Three groups were defined based on self-reported ethnicity and English proficiency: white/English (n = 219), Hispanic/English (n = 39), and Hispanic/Spanish (n = 77). Outcomes examined were patient-reported physical functioning, pain, and presence of moderate or severe fatigue. Multivariate regression analyses compared outcomes among groups, adjusting for sociodemographic characteristics, health and disease factors, and depression. RESULTS: Hispanic/Spanish women had worse function, pain, and fatigue than either English-proficient group. Depression was associated with all outcomes (P < 0.0001), and accounted for greater differentials in scores than ethnicity/language proficiency. In interaction analyses, differences between women who were and were not depressed were greater for Hispanic/English than for Hispanic/Spanish. Nondepressed Hispanic/Spanish scores were significantly worse than nondepressed Hispanic/English, i.e., the impact of depression was less for Hispanic/Spanish women because both depressed and nondepressed women in this group reported worse outcomes. After adjustment for sociodemographic factors and depression, language remained significantly associated with outcomes. CONCLUSION: Disparities in patient-reported outcomes may be driven less by ethnicity than by sociodemographic or psychological factors. Measurement instruments that are not culturally appropriate and equivalent may also hamper meaningful analyses of disparities.
26599798 Associations between asymmetric dimethylarginine, homocysteine, and the methylenetetrahydr 2016 Jul OBJECTIVES: The aim of our study was to determine whether asymmetric dimethylarginine (ADMA) levels are associated with homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene variants in patients with rheumatoid arthritis (RA). METHOD: Serum ADMA and Hcy levels were measured in 201 RA individuals [155 (77.1%) females, median age 67 years (interquartile range 59-73)]. The MTHFR C677T polymorphism was assessed by using the LightCyclerTM System. Initially, ADMA was compared across the categories of MTHFR using a one-way analysis of variance (ANOVA), followed by a multivariate model, which accounted for Hcy, age, erythrocyte sedimentation rate (ESR), and homeostatic model assessment (HOMA). RESULTS: In univariable analysis, ADMA differed significantly across the categories of MTHFR (p = 0.037). Patients with the MTHFR 677TT genotype had the highest ADMA levels, with a mean of 0.62 (SE = 0.03), significantly higher than either those patients carrying the MTHFR 677CT (0.55, SE = 0.01) or the MTHFR 677CC (0.55, SE = 0.01) genotype (p = 0.042) in both cases. In the multivariable model, Hcy (p = 0.022) and ESR (p < 0.001) were found to have significant positive associations with ADMA but the relationship between MTHFR gene variants and ADMA was found to be non-significant (p = 0.102). CONCLUSIONS: Hcy and ADMA are significantly associated in RA. It is plausible that abnormal Hcy metabolism plays an important role in premature atherosclerosis in RA by promoting ADMA accumulation and leading to the derangement of vascular haemostasis.
25773655 Patterns of use and dosing of tocilizumab in the treatment of patients with rheumatoid art 2015 Sep The aim of the study was to identify and describe the patterns of use of tocilizumab in clinical practice to ensure safety and optimal management of rheumatoid arthritis (RA). This is a 12-month prospective observational study in patients with moderate or severe RA of ≥6 months' duration who have started tocilizumab after failure of at least one previous disease-modifying antirheumatic drug (DMARD) including TNF inhibitors. For some analyses, patients were categorized by the use of tocilizumab as monotherapy or in combination, and by previous use of biological therapy. Overall, 379 were evaluable (84.4 % received tocilizumab after prior biologics and 78.4 % in combination with classic DMARDs). Tocilizumab was discontinued in 68/379 (17.9 %) patients after a median of 6.7 (3.7-10.4) months, mainly due to a lack of efficacy (24/379, 6.3 %) and adverse events (23/379, 6.1 %). Of 131 temporary interruptions of tocilizumab required in 101/379 (26.6 %) patients, 81/131 (61.8 %) were related to adverse events, and in 120/131 (91.6 %) cases, tocilizumab was reintroduced at 8 mg/kg. Thirty-six tocilizumab dose reductions occurred in 34/379 (9 %) patients due to abnormal laboratory values in 20/34 (55.6 %) cases. DAS28-ESR scores decreased from baseline (5.6 ± 1.0) to week 24 (3.0 ± 1.4) and week 52 (2.7 ± 1.3). DAS28 response differed between biologics-naive and biologics-experienced patients, both at weeks 24 and 52. In clinical practice, tocilizumab is effective in RA while retaining the expected safety and tolerability profile. Tocilizumab seems to be more effective for biologics-naive patients than for biologics-experienced patients, while it proves to be similarly effective when used in combination or monotherapy.
25313148 Patients receiving anti-TNF therapies experience clinically important improvements in RA-r 2015 Jun OBJECTIVES: Pro-inflammatory cytokines such as TNF-α are important in the pathogenesis of fatigue in conditions such as RA. This study aimed to determine whether fatigue improved in a cohort of RA patients with clinically relevant fatigue commencing anti-TNF-α therapy and, if so, to identify predictors of improvement. METHODS: Participants recruited to a long-term observational cohort study (the British Society for Rheumatology Biologics Register for RA) provided information on fatigue using the 36-item Short Form Health Survey (SF-36) vitality subscale. The prevalence of severe baseline fatigue (SF-36 vitality ≤12.5) was calculated and improvements, considered as (i) absolute values and (ii) improvement from severe to non-severe fatigue (SF-36 vitality >12.5), were examined 6 months subsequently. A comprehensive set of putative predictors of fatigue improvement were evaluated using multivariable logistic regression. RESULTS: In 6835 participants the prevalence of severe baseline fatigue was 38.8%. Of those with severe fatigue, 70% reported clinically relevant improvement and 66% moved to the non-severe fatigue category (i.e. improvers). The mean change for improvers was three times the minimum clinically important difference for improvement (33.0 U). Independent baseline predictors of improvement were female sex [odds ratio (OR) 1.3 (95% CI 1.1, 1.7)], not being unemployed due to ill health [OR 1.5 (95% CI 1.2, 1.7)], low disability [OR 1.2 (95% CI 1.001, 1.5)], seropositivity [OR 1.2 (95% CI 0.98, 1.4)], not using steroids [OR 1.2 (95% CI 1.03, 1.5)], no history of hypertension [OR 1.4 (95% CI 1.1, 1.6)] or depression [OR 1.3 (95% CI 1.1, 1.5)] and good mental health [SF-36 mental health subscale >35; OR 1.4 (95% CI 1.2, 1.7)]. CONCLUSION: Fatigued RA patients reported substantial improvement in their fatigue after commencing anti-TNF-α therapy. Further, a number of clinical and psychosocial baseline factors identified those most likely to improve, supporting future stratified approaches to RA fatigue management.
27067226 Majoon ushba, a polyherbal compound, suppresses pro-inflammatory mediators and RANKL expre 2016 Aug Fibroblast-like synoviocytes (FLS) are inhabitant mesenchymal cells of synovial joints and have been recognized to play an imperative role in the immunopathogenesis of rheumatoid arthritis (RA). Blocking these pathological roles of FLS provides a potentially important therapeutic strategy for the treatment for RA. A recent study had confirmed that majoon ushba (MU), a polyherbal unani compound, possesses anti-arthritic effects in in vivo. Toward this direction, an effort has been made to understand the effect of MU on FLS derived from adjuvant-induced arthritis (AIA) rats. Here, we observed that MU administration (100-300 µg/ml) significantly inhibited the expression and phosphorylation of NFкB-p65 protein similar to that of the Bay 11-7082 (NFкB inhibitor) in NFкB signaling pathway and suppressed the protein expression of ERK1/2 and JNK1/2 in MAPKs signaling pathway in AIA-FLS. In addition, the protein expression of TNF-α, IL-17, RANKL, and iNOS was also found reduced. MU treatment significantly inhibited the mRNA expression of pro-inflammatory mediators (TNF-α, IL-1β, IL-6, MCP-1, IL-17, iNOS, and COX-2), transcription factors (NFкB-p65 and AP-1), and RANKL and attenuated the overproduction of TNF-α, IL-1β, IL-6, and MCP-1 (ELISA) in AIA-FLS. Furthermore, MU treatment significantly inhibited the level of lipid peroxidation, lysosomal enzymes release, and glycoproteins and increased antioxidant status (superoxide dismutase and catalase) in AIA-FLS. In conclusion, the results of this study provide evidence that MU possesses anti-inflammatory effect against AIA-FLS through the decrease in pro-inflammatory mediators expression by suppressing NFкB and MAPKs signaling pathways.
26407995 Preserved skeletal muscle protein anabolic response to acute exercise and protein intake i 2015 Sep 25 INTRODUCTION: Rheumatoid arthritis (RA) is often associated with diminished muscle mass, reflecting an imbalance between protein synthesis and protein breakdown. To investigate the anabolic potential of both exercise and nutritional protein intake we investigated the muscle protein synthesis rate and anabolic signaling response in patients with RA compared to healthy controls. METHODS: Thirteen RA patients (age range 34-84 years; diagnosed for 1-32 years, median 8 years) were individually matched with 13 healthy controls for gender, age, BMI and activity level (CON). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay (ELISA) in resting blood samples obtained on two separate days. Skeletal muscle myofibrillar and connective tissue protein fractional synthesis rate (FSR) was measured by incorporation of the amino acid (13)C6-phenylalanine tracer in the overnight fasted state for 3 hours (BASAL) and 3 hours after intake of whey protein (0.5 g/kg lean body mass) alone (PROT, 3 hrs) and in combination with knee-extensor exercise (EX) with one leg (8 × 10 reps at 70 % of 1RM; PROT + EX, 3 hrs). Expression of genes related to inflammatory signaling, myogenesis and muscle growth/atrophy were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: CRP was significantly higher in the RA patients (2.25 (0.50) mg/l) than in controls (1.07 (0.25) mg/l; p = 0.038) and so was TNF-α (RA 1.18 (0.30) pg/ml vs. CON 0.64 (0.07) pg/ml; p = 0.008). Muscle myofibrillar protein synthesis in both RA patients and CON increased in response to PROT and PROT + EX, and even more with PROT + EX (p < 0.001), with no difference between groups (p > 0.05). The gene expression response was largely similar in RA vs. CON, however, expression of the genes coding for TNF-α, myogenin and HGF1 were more responsive to exercise in RA patients than in CON. CONCLUSIONS: The study demonstrates that muscle protein synthesis rate and muscle gene expression can be stimulated by protein intake alone and in combination with physical exercise in patients with well-treated RA to a similar extent as in healthy individuals. This indicates that moderately inflamed RA patients have maintained their muscle anabolic responsiveness to physical activity and protein intake.
27246346 Morbimortality in adult patients with septic arthritis: a three-year hospital-based study. 2016 Jun 1 BACKGROUND: The objective of this ambispective study was to determine outcomes and associated factors for adult patients with confirmed septic arthritis (SA). METHODS: All adult patients admitted to Amiens University Hospital between November 2010 and December 2013 with confirmed SA were included in the study. Patients with prosthetic joint infections were excluded. A statistical analysis was performed in order to identify risk factors associated with a poor outcome (including mortality directly attributable to SA). RESULTS: A total of 109 patients (mean ± SD age: 60.1 ± 20.1; 74 male/35 females) were diagnosed with SA during the study period. The most commonly involved sites were the small joints (n = 34, 31.2 %) and the knee (n = 25, 22.9 %). The most frequent concomitant conditions were cardiovascular disease (n = 45, 41.3 %) and rheumatic disease (n = 39, 35.8 %). One hundred patients (91.7 %) had a positive microbiological culture test, with Staphylococcus aureus as the most commonly detected pathogen (n = 59, 54.1 %). Mortality directly attributable to SA was relatively infrequent (n = 6, 5.6 %) and occurred soon after the onset of SA (median [range]: 24 days [1-42]). Major risk factors associated with death directly attributable to SA were older age (p = 0.023), high C-reactive protein levels (p = 0.002), diabetes mellitus (p = 0.028), rheumatoid arthritis and other inflammatory rheumatic diseases (p = 0.021), confusion on admission (p = 0.012), bacteraemia (p = 0.015), a low creatinine clearance rate (p = 0.009) and the presence of leg ulcers/eschars (p = 0.003). The median duration of follow-up (in patients who survived for more than 6 months) was 17 months [6-43]. The proportion of poor functional outcomes was high (31.8 %). Major risk factors associated with a poor functional outcome were older age (0.049), hip joint involvement (p = 0.003), the presence of leg ulcers/eschars (p = 0.012), longer time to presentation (0.034) and a low creatinine clearance rate (p = 0.013). CONCLUSIONS: In a university hospital setting, SA is still associated with high morbidity and mortality rates.
27320945 Use of ultrasound in treatment decisions for patients with rheumatoid arthritis: an observ 2016 Aug In rheumatoid arthritis (RA), treatment response is generally assessed using standard clinical disease activity measures. However, ultrasound has become increasingly popular among rheumatologists to monitor disease activity and response. The purpose of this analysis of ECOgraphic evaluation for STaging ARthritis (ECOSTAR) study data was to determine how ultrasound affects clinicians' decisions about changing treatment in RA. ECOSTAR was an observational, cohort study conducted between March 2010 and December 2012 at nine clinical centers in Italy in RA patients being considered for treatment change. After clinical evaluation of each patient, patients underwent diagnostic ultrasound (US) investigations and each patient was given a total echography score using a combination of scores for joint effusion, synovial hypertrophy, and power Doppler. The US results were provided to the clinicians and the influence of US on the clinicians' treatment choices were recorded. Ninety-five patients screened for study inclusion had confirmed RA (mean age 53.9 years; mean disease duration 8.9 years). Therapy changes were made by clinicians according to the hand and wrist joint US scores: score 0 appeared to have no influence on clinicians' decision to modify treatment, scores >0-3 were associated with a numerically higher estimated probability of not changing therapy than changing therapy, and scores >3 had a greater influence on the clinician to modify therapy and an increased probability of the clinician changing therapy versus not changing therapy. Ultrasonography scores appear to influence treatment decisions in patients with RA, with clinicians appearing less likely to alter treatment regimens in patients with low ultrasound scores and more likely to change treatment regimens when higher scores are obtained. Further research is warranted.
27302847 Air pollution exposure increases the risk of rheumatoid arthritis: A longitudinal and nati 2016 Sep OBJECTIVE: Rheumatoid arthritis (RA) has been associated with inhaled pollutants in several studies, and it is a disease of chronic inflammation. The association between air pollution and the risk of RA remains unclear. Therefore, we conducted this nationwide, retrospective, sex-stratification study to evaluate this association. METHODS: We collected data from the Longitudinal Health Insurance Database (LHID), maintained by the Taiwan Bureau of National Health Insurance, and the Taiwan Air Quality-Monitoring Database (TAQMD), released by the Taiwan Environmental Protection Agency. The TAQMD provides the daily concentrations of particulate matter with the aerodynamic diameter <2.5μm (PM2.5) and nitrogen dioxide (NO2) from 74 ambient air quality-monitoring stations distributed all over Taiwan during 1998-2010. The LHID and TAQMD were linked according to the residential areas of insurants and the areas where the air quality-monitoring stations were located. A residential area was defined according to the location of the clinic and hospital that treated acute upper respiratory tract infections. The yearly average air pollutant concentrations were categorized into 4 levels based on quartiles. We evaluated the risk of RA in residents exposed to 4 levels of PM2.5 and NO2 concentrations. RESULTS: We detected an increased risk of RA in participants exposed to PM2.5 and NO2. Among four quartiles of NO2 concentration, namely Q1, Q2, Q3, and Q4, the adjusted hazard ratios (aHRs) in Q2, Q3, and Q4 compared with that in Q1 were 1.07 (95% confidence interval [CI]=0.76-1.50), 1.63 (95% CI=1.16-2.31),and 1.49 (95% CI=1.05-2.12), respectively. Regarding the PM2.5 concentrations, the aHRs after exposure to the Q2, Q3, and Q4 levels were 1.22 (95% CI=0.85-1.74), 1.15 (95% CI=0.82-1.62), and 0.79 (95% CI=0.53-1.16), respectively. CONCLUSION: The results of this nationwide study suggest an increased risk of RA in residents exposed to NO2.
27711025 Methotrexate and lung disease in rheumatoid arthritis. 2017 Mar Rheumatoid arthritis (RA) is a common chronic inflammatory disease affecting many tissues and resulting in substantial morbidity and increased mortality. Arthritis is the most notable clinical feature, but extra-articular features can have devastating consequences. Pulmonary manifestations are common in RA, with high rates of disease related lung disease and a propensity to pulmonary infections. Respiratory illness remains a leading cause of death among RA populations. Modern medicine greatly reduces the illness burden among patients with RA, particularly through the use of disease-modifying medications. Methotrexate is recommended as the first-line treatment of RA as it effectively reduces disease activity, morbidity and mortality. However, it has long been implicated as a causative agent in lung disease. The evidence for a cause and effect relationship in modern populations is contentious, but critically important. Increasing recognition of the importance and prevalence of interstitial lung disease in RA, and recent studies on the incidence of lung disease among RA and non-RA populations have cast doubt on the role of methotrexate as a causative agent. A correct understanding of the complex pulmonary disease processes in RA is crucial if we are to improve outcomes in this patient group. In this article we will discuss the epidemiology and characteristics of lung disease in rheumatoid arthritis and its possible relationship to methotrexate use.