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ID PMID Title PublicationDate abstract
25494482 Might there be a link between intron 3 VNTR polymorphism in the XRCC4 DNA repair gene and 2015 Jan DNA repair genes are involved in several diseases such as cancers and autoimmune diseases. Previous studies indicated that a DNA repair system was involved in the development of rheumatoid arthritis (RA). In this study, we aimed to examine whether four polymorphisms in the DNA repair genes (xeroderma pigmentosum complementation group D [XPD], X-ray repair cross-complementing group 1 [XRCC1], and X-ray repair cross-complementing group 4 [XRCC4]) were associated with RA. Sixty-five patients with RA and 70 healthy controls (HCs) were examined for XPD (A-751G), XRCC1 (A399G), and XRCC4 (intron 3 VNTR and G-1394T) polymorphisms. All polymorphisms were genotyped by PCR and/or PCR-RFLP. The association between the polymorphisms and RA was analyzed using the chi-square test and de Finetti program. The intron 3 VNTR polymorphism in the XRCC4 gene showed an association with RA patients. The DI genotype was found lower in RA patients (χ(2)=8.227; p=0.0021), while the II genotype was higher in RA patients (χ(2)=5.285; p=0.010). There were deviations from the Hardy-Weinberg Equilibrium (HWE) in both intron 3 VNTR and G-1394T polymorphisms in the XRCC4 gene and in the polymorphism in the XRCC1 gene, and the observed genotype counts deviated from those expected according to the HWE (p=0.027, 0.004, and 0.002, respectively); however, there was no deviation in the other gene polymorphisms. There is no statistical difference between the RA patients and HCs for XPD (A-751G), XRCC1 (A399G), and XRCC4 (G-1394T) gene polymorphisms (p>0.05). Although XPD (A-751G), XRCC1 (A399G), and XRCC4 (G-1394T) gene polymorphisms have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of RA in Turkish patients. In conclusion, we suggested that the intron 3 VNTR polymorphism in the XRCC4 gene may be associated with the etiopathogenesis of RA as a marker of immune aging.
25065918 Construct validity, reliability, response rate, and association with disease activity of t 2015 Mar OBJECTIVE: First objective is to validate the Disabilities of the Arm, Shoulder and Hand (DASH) and Quick DASH (QuickDASH) questionnaire in rheumatoid arthritis (RA) patients with functional upper extremity impairment. Next is to clarify which clinical factor is associating with QuickDASH using a large cohort of RA. METHODS: The QuickDASH and DASH were applied to our 94 RA patients who underwent surgery for functional upper extremity impairment. Next, the QuickDASH was applied to our cohort of 5191 Japanese patients with RA. RESULTS: In the first cohort of 94 RA patients, both QuickDASH and DASH displayed excellent reliability and validity. The response rate of patients < 65 and ≥ 65 years of age showed significant difference in the DASH but not in the QuickDASH. In the second cohort with 5191 RA patients, QuickDASH showed a high response rate (93%) and good to moderate correlation with Japanese version of the Health Assessment Questionnaire (r = 0.88) and disease activity score of 28 (DAS28, r = 0.53). Change in QuickDASH score and DAS28-based European League Against Rheumatism response showed significant correlation. CONCLUSION: QuickDASH seems suitable for evaluating upper extremity impairment, disability index, and disease control in a large cohort of RA patients including elderly patients.
25581074 Cost-effectiveness analysis of two rituximab retreatment regimens for longstanding rheumat 2015 Jul OBJECTIVE: Rituximab (RTX) is licensed for second-line treatment of rheumatoid arthritis (RA) after first tumor necrosis factor (TNF) inhibitor failure. RTX is generally administered intravenously at 1 gm 2 weeks apart, and the retreatment is scheduled at the time of clinical relapse (regimen 1). A more intensive regimen is proposed with a fixed full cycle after 6 months (regimen 2) if remission is not reached. A cost-effectiveness analysis (CEA) compared these 2 regimens of RTX administration in patients with longstanding RA based on data provided by an observational study. METHODS: An observational retrospective study was conducted on 102 patients, enrolled in 3 hospitals and followed for ≥12 months. Forty-seven patients followed regimen 1, while 55 patients followed regimen 2. A CEA based on a Markov model was conducted. A lifelong and social perspective was adopted. CEA was conducted for the entire cohort and for the 2 subgroups separately (patients with positive rheumatoid factor and/or anti-cyclic citrullinated peptide and failures to TNF inhibitors). RESULTS: Results for the overall sample show at 10, 20, and 30 years that regimen 1 is less costly and associated with a higher quality of life compared to regimen 2. Probabilistic sensitivity analysis at 10 years estimated a probability of 95.1% for regimen 1 to be cost effective given a willingness to pay of €35,000/quality-adjusted life year, while for seropositive patients and for TNF failures it was estimated to be 92% and 92.7%, respectively. CONCLUSION: In longstanding RA, cost effectiveness of RTX retreatment at clinical relapse was found to be at least equivalent to the more intensive regimen proposed.
26927442 MRI and ultrasound in rheumatoid arthritis. 2016 May PURPOSE OF REVIEW: To overview the recent literature on the use of MRI and musculoskeletal ultrasonography (MSUS) in rheumatoid arthritis. RECENT FINDINGS: Subclinical inflammation has been widely confirmed, even in the earliest phases of rheumatoid arthritis. The presence of osteitis has added benefits to modern diagnostic criteria, and anticitrullinated peptide antibody positive patients have demonstrated higher osteitis scores. A model for prediction of rheumatoid arthritis onset employing usual clinical data and power Doppler ultrasonography has been reported. The presence of tenosynovitis may also be an early finding in rheumatoid arthritis. Modern imaging continues to inform our concept of pathogenesis with reports on the direct relationship of synovitis to cartilage proteoglycan loss using compositional MRI measures. Growing data on the validity of MRI as an important predictor of clinical and radiographic damage endpoints has been reported and reflected in the growing use of this outcome in many contemporary biologic therapy trials. Much work has been presented on improved and validated MSUS scores with reduced and feasible joint counts. The role of ultrasonography in making sensible decisions when monitoring biologic use, and in tapering, has been reported. SUMMARY: The recent literature demonstrates improved validity and utility for both MRI and MSUS in diagnosis, prognosis and monitoring of rheumatoid arthritis.
26879355 Early Remission Is a Realistic Target in a Majority of Patients with DMARD-naive Rheumatoi 2016 Apr OBJECTIVE: We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA). METHODS: Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care. RESULTS: Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36). CONCLUSION: Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.
29624033 EFFECT OF DISEASE-MODIFYING ANTIRHEUMATIC DRUGS ON THE VALUES OF APOLIPOPROTEIN A-1 AND AC 2016 In this observational study we examined the impact of disease-modifying antirheumatic drugs (DMARDS) on the disease activity as well as the values of acute phase reactants and the apolipoprotein A1 (Apo A1) in patients with active rheumatoid arthritis (RA). Eighty patients with active RA and newly discovered RA patients who meet the American Rheumatology Association (ARA) 1987 revised criteria were treated with disease modifying anti-rheumatic drugs – DMARDs according to the standard protocol of everyday clinical practice. At 6 and 12 months of treatment the patients achieved a signifi cant decrease in the disease activity score 28 (DAS28), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values. On the other hand, the levels of Apo A-1, which were low at baseline, were signifi - cantly higher. In conclusion, the use of DMARDs in patients with RA reduced disease activity and infl ammation, but also had a benefi cial eff ect in increasing the levels of atheroprotective Apo A-1 lipoprotein, which can reduce CV risks in these patients.
25668139 Genetics of rheumatoid arthritis in Asia--present and future. 2015 Jun Genome-wide association studies (GWAS) have uncovered numerous susceptibility genes for rheumatoid arthritis (RA) in patients of European, Asian and other ethnic ancestries. Although previous transethnic GWAS meta-analyses enabled the identification of several novel loci, the genetic heterogeneity observed in the PADI4 and PTPN22 genes suggests that ethnic variation should be considered. In addition, the effects of genetic polymorphisms on gene expression profiles are important when assessing the association of genetic information with disease pathogenesis and will influence the development of personalized medicine. Gene expression is controlled by epigenetic modifications, which in turn can be affected by environmental stimuli. Altogether, genetic and epigenetic information of Asian populations will contribute considerably to future rheumatology research.
26340234 Non-invasive assessment of arterial stiffness in patients with rheumatoid arthritis: a sys 2015 INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) morbidity and mortality. Pulse-wave velocity (PWV) and augmentation index (AIx) are non-invasive methods to assess arterial stiffness, a marker of CV risk. We performed a meta-analysis evaluating the impact of RA on aortic-PWV, brachial-PWV, brachial-ankle (ba-) PWV, AIx, and AIx normalized to a 75 beats/minute heart rate (AIx@75). MATERIALS AND METHODS: Studies evaluating the relationship between RA and aortic-PWV, brachial-PWV, ba-PWV, AIx, and AIx@75 were systematically searched. A total of 25 studies (1,472 RA patients, 1,583 controls) were included. RESULTS: Compared to controls, RA patients showed a significantly higher aortic-PWV (mean difference 1.32 m/s; 95% CI 0.77, 1.88; P < 0.00001), ba-PWV (MD 198.42 cm/s; 95% CI 45.79, 342.76; P = 0.01), AIx (MD 11.50%; 95% CI 5.15, 17.86; P = 0.0004), and AIx@75 (MD 6.99%; 95% CI 4.92, 9.06; P < 0.00001), with a trend toward a higher brachial-PWV (MD 0.34 m/s; 95% CI -0.03, 0.70; P = 0.07). When analyzing studies on early RA, the difference in aortic-PWV among RA patients and controls was even higher (MD 2.30 m/s; 95% CI 1.15, 3.45; P < 0.0001). CONCLUSION: Meta-regression showed that a more severe inflammatory status impacted on aortic-PWV, AIx, and AIx@75. Arterial stiffness, a recognized marker of CV risk, is increased in RA patients. This alteration is associated with the severity of the inflammatory status and is present even in early-stage disease.
25799914 Activation of NALP1 inflammasomes in rats with adjuvant arthritis; a novel therapeutic tar 2015 Jul BACKGROUND AND PURPOSE: Pro-inflammatory cytokines are important in rheumatoid arthritis (RA) and their production is mainly regulated by NF-κB and inflammasomes. Carboxyamidotriazole (CAI) exhibits potent anti-inflammatory activities by decreasing cytokines. Here, we have investigated NACHT, LRR and PYD domains-containing protein (NALP) inflammasomes in a rat model of RA and explored the therapeutic effects of CAI in this model and the involvement of NF-κB and inflammasomes in the actions of CAI. EXPERIMENTAL APPROACH: The anti-arthritic effects of CAI were assessed in the adjuvant arthritis (AA) model in rats, using radiological and histological techniques. NALP1 and NALP3 inflammasomes, NF-κB pathway and pro-inflammatory cytokines levels were measured with Western blots, immunohistochemistry and ELISA. KEY RESULTS: CAI decreased the arthritis index, improved radiological and histological changes, and reduced synovial IL-1β, IL-6, IL-18 and TNF-α levels in rats with AA. Compared with normal rats, the 70 kDa NALP1 isoform was up-regulated, NALP3 was down-regulated, and levels of the 165 kDa NALP1 isoform and the adaptor protein ASC were unchanged in synovial tissue from AA rats. CAI reduced the 70 kDa NALP1 isoform and restored NALP3 levels in AA rats; CAI inhibited caspase-1 activation in AA synovial tissue, but not its enzymic activity in vitro. In addition, CAI reduced expression of p65 NF-κB subunit and IκBα phosphorylation and degradation in AA rats. CONCLUSION AND IMPLICATIONS: NALP1 inflammasomes were activated in synovial tissues from AA rats and appeared to be a novel therapeutic target for RA. CAI could have therapeutic value in RA by inhibiting activation of NF-κB and NALP1 inflammasomes and by decreasing pro-inflammatory cytokines.
24595319 Preclinical impairment of myocardial function in rheumatoid arthritis patients. Detection 2015 Jun OBJECTIVES: The incidence of heart failure is higher in patients with rheumatoid arthritis (RA) than in the general population and contributes to elevated cardiovascular mortality and morbidity rates. Impaired myocardial function can be detected by a novel echocardiographic method, speckle tracking echocardiography (STE), when conventional methods have yielded normal findings. The aim of our study was to investigate the effect of disease duration on myocardial strain and strain rate parameters in patients with RA. METHODS: This cross-sectional study included 37 RA patients [n=16, female gender n=16, mean age, 45.7 ± 9 years in the early-stage disease (ESD); n= 21, female gender n=19, 45.7 ± 16.8 years in the advanced-stage disease (ASD) group] who were compared according to early disease duration and advanced-stage disease (2.8 ± 1.2 vs. 14.6 ± 6.8 years, respectively). Hypertension, diabetes mellitus, and other cardiovascular risk factors were excluded. Offline analysis of STE was performed and data between the two groups were compared. RESULTS: RS, RSR-E, and RSR-E/A values were statistically significantly lower in patients with ASD. Circumferential strain and strain rate were similar between the two groups. Except for LSR-E/A values, LS, LSR-S, LSR-E, and LSR-A values were decreased in patients with ASD. CONCLUSION: RA patients without clinical evidence of cardiovascular disease and in the absence of traditional cardiovascular risk factors can be followed up with STE. In this way, early impairment of myocardial deformation can be detected before the appearance of any clinical evidence of cardiac involvement.
26697773 Quality in rheumatoid arthritis care. 2015 Aug While most rheumatology practices are characterized by strong commitment to quality of care and continuous improvement to limit disability and optimize quality of life for patients and their families, the actual step toward improvement is often difficult. This is because there are still barriers to be addressed and facilitators to be captured before a satisfying and cost-effective practice management is installed. Therefore, this review aims to assist practicing rheumatologists with quality improvement of their daily practice, focusing on care for rheumatoid arthritis (RA) patients. First we define quality of care as "the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge". Often quality is determined by the interplay between structure, processes, and outcomes of care, which is also reflected in the corresponding indicators to measure quality of care. Next, a brief overview is given of the current treatment strategies used in RA, focusing on the tight control strategy, since this strategy forms the basis of international treatment guidelines. Adherence to tight control strategies leads, also in daily practice, to better outcomes in patients with regard to disease control, functional status, and work productivity. Despite evidence in favor of tight control strategies, adherence in daily practice is often challenging. Therefore, the next part of the review focuses on possible barriers and facilitators of adherence, and potential interventions to improve quality of care. Many different barriers and facilitators are known and targeting these can be effective in changing care, but these effects are rather small to moderate. With regard to RA, few studies have tried to improve care, such as a study aiming to increase the number of disease activity measures done by a combination of education and feedback. Two out of the three studies showed markedly positive effects of their interventions, suggesting that change is possible. Finally, a simple step-by-step plan is described, which could be used by rheumatologists in daily practice wanting to improve their RA patient care.
25974991 Anti-mutated citrullinated vimentin antibody and rheumatoid factor (prevalence and associa 2015 background: The aims of this study were to assess the prevalence of anti-mutated citrullinated vimentin (MCV) antibodies and rheumatoid factor (RF) and to evaluate their association in rheumatoid arthritis patients, both Saudi and non-Saudi. METHODS: Retrospectively, we studied 280 rheumatoid arthritis patients, at King Abdulaziz University Hospital. The antibodies were measured by enzyme linked immunosorbent assay and rheumatoid factor by nephelometry. RESULTS: The 280 patients included 196 Saudis and 84 non-Saudis, 88% females and 12% males, and the mean age was 45.3 years (SD = 14.3). Prevalence of rheumatoid factor was 141/280 (50%) divided as 93/196 (47.5%) Saudis and 48/84 (57%) non-Saudis, with no significant differences (p > 0.05). Prevalence of mutated citrullinated vimentin antibodies was 165/280 (58.2%) divided as 121/196 (61.7%) Saudis and 44/84 (52.4%) non-Saudis, with no significant differences (p > 0.05). Among RF -ve patients, considerable numbers were anti-MCV +ve, and vice versa. Also, among the anti-MCV -ve patients, considerable numbers were RF +ve, and vice versa. In all cohorts and in Saudi and non Saudi patients, anti-MCV positivity was significantly associated with RF positivity (odds ratio (OR) 3.15; 95% CI 1.9, 5.19/p = 0.000); ESR and CRP were high with significant correlation (p < 0.005) with each other, with RF positivity but not with anti-MC positivity. Anti-MC positivity showed no significant correlation with age and gender. CONCLUSIONS: In this cohort of patients, anti-MCV antibodies are a useful diagnostic tool for RA, but its combination with RF is essential. Both markers are significantly associated. Larger scale studies are recommended. Correlation of anti-MCV with treatment and with disease activity still has to be published.
27283868 Stability of clinical outcome measures in rheumatoid arthritis patients with stable diseas 2016 Oct Natural variation also known as measurement error is assessed in individuals in "steady state." The study aimed to examine inter-visit variations in clinical outcome measures in rheumatoid arthritis (RA) patients with stable disease defined on the basis of the EULAR response criteria. Two hundred thirty-three RA patients with stable disease defined as a change in Disease Activity Score (DAS28-CRP) ≤0.6 between two consecutive visits were identified in the Danish rheumatology registry for biological treatment (DANBIO). Clinical data from a single set of such two visits were extracted for each patient. Using the Bland-Altman method, lower and upper 95 % limits of agreement (LLoA; ULoA) between the consecutive assessments and the bias were calculated for each measure. Associations were characterized by Pearson's r-values and standard errors of estimation (SEE). The mean change in DAS28-CRP was 0.0 ± 0.3. Agreements between the assessments were close on the group level but poor on the individual level. For example, LLoA; ULoA [bias] for patient global assessment (0-100) was -28.3; 29.7 [0.7], for fatigue (0-100) -38.1; 36.3 [-0.9] and for 28 swollen joint count -3.3; 3.3 [0.0]. Inter-visit differences were poorly explained by the baseline values (r [SEE] ranging from 0.15 [12.6] for fatigue to 0.58 [1.4] for 28 tender joint count) and by changes in other outcome variables. In conclusion, outcome measures fluctuated substantially and unpredictably in individual RA patients considered in steady state. The observed between-visit differences may be interpreted to reflect natural variation or measurement error that should be taken into account when monitoring patients in the daily clinic.
25941102 Optimizing perioperative outcomes for older patients with rheumatoid arthritis undergoing 2015 May Patients with rheumatoid arthritis continue to undergo arthroplasty despite widespread use of potent disease-modifying drugs (DMARDs), including the biologic tumor necrosis-α inhibitors. In fact, over 80 % of RA patients are taking DMARDs or biologics at the time of arthroplasty. While many RA-specific factors including disease activity and disability may contribute to the increase in infection in RA patients undergoing arthroplasty, immunosuppressant medications may also play a role. As the age of patients with RA undergoing arthroplasty is rising, and the incidence of arthroplasty among the older population is increasing, optimal perioperative management of DMARDs and biologics in older patients with RA is an increasing challenge. Although evidence is sparse, most evidence supports withholding tumor necrosis-α inhibitors and other biologics prior to surgery based on the dosing interval, and continuing methotrexate and hydroxychloroquine through the perioperative period. There is no consensus regarding leflunomide, and rituximab risk does not appear related to the interval between infusion and surgery. This paper reviews arthroplasty outcomes including complications in patients with RA, and discusses the rationale for strategies for the optimal medication management of DMARDs and biologics in the perioperative period to minimize complications and improve outcomes.
26743072 Prevalence of monosodium urate deposits in a population of rheumatoid arthritis patients w 2016 Jun OBJECTIVES: To investigate the prevalence of monosodium urate (MSU) crystal deposits, indicative for gout, in a population of rheumatoid arthritis (RA) patients with concomitant hyperuricemia and to analyze the clinical and disease-specific characteristics of RA patients who exhibit MSU crystal deposits. METHODS: Overall, 100 consecutive patients with the diagnosis of RA and a serum urate level above 6mg/dl underwent dual energy computed tomography (DECT) of both feet and hands to search for MSU crystals in a prospective study between October 2011 and July 2013. Presence and extent of MSU crystal deposits on DECT was assessed by automated volume measurement. Demographic and disease-specific characteristics were recorded and included into two logistic regression models to test for the factors associated with MSU crystal deposits in RA. RESULTS: Hyperuricemic RA patients were mostly male (55%), over 60 years of age (63 ± 11 years), had established disease (8.7 ± 10.5 years) and a mean disease activity score 28 (DAS 28) of 3.2. In total, 20 out of 100 patients displayed MSU crystal deposits in DECT. Interestingly, the majority (70%) of the RA patients positive for MSU crystal deposits were seronegative RA patients. Hence, every third seronegative RA patient had MSU crystal deposits. According to logistic regression model analysis, seronegative status correlated positively with presence of urate deposits (p = 0.019). CONCLUSIONS: These data show that a considerable number of RA patients display periarticular MSU crystal deposits. Seronegative patients were shown to be predominantly affected with every third patient being positive for urate deposits.
26576422 Effects of Whole-Body Cryotherapy in Comparison with Other Physical Modalities Used with K 2015 Whole-body cryotherapy (WBC) has been frequently used to supplement the rehabilitation of patients with rheumatoid arthritis (RA). The aim of this study was to compare the effect of WBC and traditional rehabilitation (TR) on clinical parameters and systemic levels of IL-6, TNF-α in patients with RA. The study group comprised 25 patients who were subjected to WBC (-110 °C) and 19 patients who underwent a traditional rehabilitation program. Some clinical variables and levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were used to assess the outcomes. After therapy both groups exhibited similar improvement in pain, disease activity, fatigue, time of walking, and the number of steps over a distance of 50 m. Only significantly better results were observed in HAQ in TR group (p < 0.05). However, similar significant reduction in IL-6 and TNF-α level was observed. The results showed positive effects of a 2-week rehabilitation program for patients with RA regardless of the kind of the applied physical procedure.
27943573 Circulating cell free DNA: a marker to predict the therapeutic response for biological DMA 2017 Jun AIM: To evaluate the correlation between circulating cell-free DNA (ccfDNA) in plasma and clinical disease activities in patients with rheumatoid arthritis (RA). METHOD: The study group included 30 patients with RA who started biological disease-modifying anti-rheumatic drugs (DMARDs) therapy. The concentration of ccfDNA in plasma was measured by quantitative real-time polymerase chain reaction at baseline to 24 weeks in every 4-week period from 30 patients and 21 healthy individuals. We also evaluated the correlation between ccfDNA and the clinical activity or the therapeutic response for biological DMARDs, using the simplified disease activity index (SDAI), Disease Activity Score of 28 joints (erythrocyte sedimentation rate) and the European League Against Rheumatism (EULAR) response criteria. Synovial fluid samples of knee joints were collected from 13 patients with RA and 12 with osteoarthritis (OA) to measure ccfDNA. RESULT: The concentration of ccfDNA in RA patients at baseline was higher than healthy controls (P = 0.016). After introducing biological DMARDs, ccfDNA was increased until 8 weeks from the baseline, and decreased after 12 weeks. The average of SDAI was improved in all patients enrolled. At 12 weeks after treatment, 15 patients were good responders to the EULAR response criteria, nine showed moderate response and six showed no response. ccfDNA in good responders was increased until 8 weeks, while those of moderate or no response were not (P = 0.042). In joint fluid of RA patients, ccfDNA was remarkably increased as compared to those from OA (P = 0.00011). CONCLUSION: After introducing biological DMARDs, increase of ccfDNA at 8 weeks was associated with improvement of disease activities. Compared with biomarkers reported, ccfDNA is able to predict the early therapeutic effects of biological DMARDs in RA patients.
25253504 Adjusting for comorbidities in cost of illness studies. 2015 Jan MOTIVATION: Differences in cost of illness (COI) methodological approaches have led to disparate results. This analysis examines two sources of this variation: specification of comorbidities in the estimated cost models and assumed prevalence rates used for generating aggregate costs. The study provides guidance in determining which comorbidities are important to include and how to handle uncertainty in optimal model specification and prevalence rate assumptions. METHODS: Comorbidities are categorized into four types. Type I comorbidities are those that increase the risk of the disease of interest; Type II comorbidities have no causal link to the disease of interest but are, nonetheless, highly correlated with that disease; Type III comorbidities are illnesses that the disease of interest may cause, and Type IV are comorbidities that have no causal link to the disease of interest and are only weakly correlated with that disease. Two-part models are used to estimate the direct costs of rheumatoid arthritis and diabetes mellitus using 2000-2007 Medical Expenditure Panel Survey data. RESULTS: COI estimates are sensitive to the specification of comorbidities. The odds of incurring any expenses varies by 71% for diabetes mellitus and by 27% for rheumatoid arthritis, while conditional expenditures (e.g., expenditures among subjects incurring at least some expenditures) vary by 62% and 45%, respectively. Uncertainty in prevalence rates cause costs to vary. A sensitivity analysis estimated the COI for diabetes ranges from $131.7-$172.0 billion, while rheumatoid arthritis varies from $12.8-$26.2 billion. CONCLUSIONS: The decision to include Type II and Type III comorbidities is crucial in COI studies. Alternative models should be included with and without the Type III comorbidities to gauge the range of cost effects of the disease. In generating costs, alternative values for prevalence rates should be used and a sensitivity analysis should be performed.
25483781 Early prediction of rheumatoid arthritis by magnetic resonance imaging in the absence of a 2015 Nov OBJECTIVE: To assess the practicability of magnetic resonance imaging (MRI) in confirming the diagnosis of clinically suspected rheumatoid arthritis (RA), when anti-cyclic citrullinated peptide antibody and radiographic erosions are absent. METHODS: We prospectively involved 31 treatment-naive patients with early inflammatory arthritis. At the initial visit, X-rays and gadolinium-enhanced MRI of both hands, as well as serological examinations and acute phase reactants were performed. The scores of synovitis, bone edema, bone erosion and tenosynovitis of metacarpophalangeal and wrist joints were evaluated using the RA-MRI scoring system. For all the patients, radiographs at baseline were normal and anti-cyclic citrullinated peptide antibodies were negative. RESULTS: At the end of follow-up(median 15 months, range 12-20 months), 22 patients were diagnosed as having RA according to 1987 American College of Rheumatology criteria. Bone edema, erosions, synovitis and tenosynovitis were observed in all the patients. However, the frequency of symmetric synovitis in wrists was significantly higher in the RA group. Moreover this group turned out to have significantly higher MRI bone erosion score in wrists. Further, receiver operating characteristic curve analysis revealed a positive wrist bone erosion score at 5, with a specificity of 78% and a sensitivity of 68%. There was no significant difference between the two groups with respect to metacarpophalangeal synovitis, metacarpophalangeal bone erosion, bone edema or tenosynovitis. CONCLUSION: MRI evidence of symmetric synovitis at wrist and a high bone erosion score at that site may assist in making an early diagnosis of RA in those patients who are negative for anti-cyclic citrullinated peptide antibody.
29911599 Sinomenine alleviates mechanical hypersensitivity in mice with experimentally induced rheu 2015 Apr 1 Background and aims We have previously reported that sinomenine, an alkaloid isolated from the root of the plant Sinomenium acutum, had antinociceptive effect in rodent models of acute inflammatory or neuropathic pain. As a traditional medicine, sinomenine is used in China to treat rheumatoid arthritis (RA). Methods In the present study, we evaluated the potential antinociceptive effect of sinomenine in a mouse model of RA, collagen type II antibody (CII Ab) induced arthritis (CAIA) after acute and chronic administration. Results As single administration, sinomenine at 40 or 80 mg/kg significantly reduced mechanical hypersensitivity both at the time of peak joint inflammation (days 11-19 after CII Ab injection) or during the post-inflammatory phase (days 35-54). No tolerance to the effect of 80 mg/kg sinomenine was observed during repeated injection twice a day for 5 days from day 11 to day 19 or from day 49 to day 53 after CII Ab injection in CAIA mice. Conclusions We have shown that sinomenine is effective in alleviating localized and spread hypersensitivities in CAIA mice both during acute inflammation and in post-inflammatory phase. Further, repeated sinomenine administration has elevated the baseline mechanical threshold without producing tolerance. Implications Sinomenine may be clinically useful to treat chronic pain in RA, including wide-spread pain which appears to be a difficult clinical problem despite the improvement in the acute treatment of RA by disease modifying agents.