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ID PMID Title PublicationDate abstract
25603279 The importance of sonographer experience and machine quality with regards to the role of m 2015 Jan OBJECTIVES: Regarding recent progress, musculoskeletal ultrasound (US) will probably soon be integrated in standard care of patient with rheumatoid arthritis (RA). However, in daily care, quality of US machines and level of experience of sonographers are varied. We conducted a study to assess reproducibility and feasibility of an US scoring for RA, including US devices of different quality and rheumatologist with various levels of expertise in US as it would be in daily care. METHODS: The Swiss Sonography in Arthritis and Rheumatism (SONAR) group has developed a semi-quantitative score using OMERACT criteria for synovitis and erosion in RA. The score was taught to 108 rheumatologists trained in US. One year after the last workshop, 19 rheumatologists participated in the study. Scans were performed on 6 US machines ranging from low to high quality, each with a different patient. Weighted kappa was calculated for each pair of readers. RESULTS: Overall, the agreement was fair to moderate. Quality of device, experience of the sonographers and practice of the score before the study improved substantially the agreement. Agreement assessed on higher quality machine, among sonographers with good experience in US increased to substantial (median kappa for B-mode and Doppler: 0.64 and 0.41 for erosion). CONCLUSIONS: This study demonstrated feasibility and reproducibility of the Swiss US SONAR score for RA. Our results confirmed importance of the quality of US machine and the training of sonographers for the implementation of US scoring in the routine daily care of RA.
26526676 Interleukin-6 promoter haplotypes are associated with etanercept response in patients with 2015 Dec Indices prognosticating anti-tumor necrosis factor (TNF) response in patients with rheumatoid arthritis are a matter of interest. Differential outcome under anti-TNF and anti-interleukin-6 (IL-6) therapy raises the question whether genetic polymorphisms that have previously been linked to IL-6 production are associated with response to anti-TNF therapy. Fifty (50) rheumatoid arthritis (RA) patients were treated with etanercept (median 36 weeks, range 4-52). In terms of the EULAR response criteria, 25 patients responded well, 17 patients moderately and 8 patients not. By direct sequencing, the patients and 91 matched healthy controls were genotyped for the IL-6 promoter SNPs -597G > A (rs1800797), -572G > C (rs1800796) and -174G > C (rs1800795) and for an AnTn microsatellite tract at -373. Alleles and haplotypes were tested for association with disease susceptibility and therapy response. No significant difference was seen in the genotype distribution between patients and healthy controls. Confirming the results of previous studies, we observed a trend of -174G being more frequent in patients with a good or moderate therapy response. Beyond that, carriage of the A9T11 microsatellite allele within the -174G haplotype was associated most closely with a favourable response (relative risk 1.31; 95 % confidence interval 1.02-1.68). A subtle analysis of the IL-6 promoter giving respect to its complex haplotypic structure results in more precise information as to the association of genotypes with the long-term etanercept response. Despite a conclusive hypothesis that a genetically determined IL-6-dominated RA responds less well to anti-TNF, more work has to be done to provide us with reliable information regarding the functional aspects of these genetic polymorphisms.
27460818 Health-selective migration among patients with rheumatoid arthritis in Québec: a cohort s 2016 Sep Little is known about how rheumatoid arthritis (RA) affects an individual's ability to relocate. The current literature suggests the relationship between health and migration is often disease-specific. We sought to estimate the impact of RA diagnosis on migration within a Canadian province, comparing migration rates in residents before and after RA diagnosis. We identified a cohort of 81,181 individuals diagnosed with RA between 1998 and 2009 using Québec administrative databases. A migration was defined as a change in the first three characters of the postal code. We categorized migrations as urban or rural depending upon an individual's origin and destination. We estimated the association between RA diagnosis and migration by fitting marginal models using a generalized estimating equations approach, adjusting for age, sex, and population level socioeconomic status indicators. The vast majority of moves after RA diagnosis were within urban areas. RA diagnosis was associated with increased migration except for people around age 50 moving within urban areas. Although RA was associated with increased inter-urban migration in many demographic groups, the net result did not translate to higher rates of rural-to-urban migration after RA diagnosis. Our results suggest fairly complex associations between RA diagnosis and migration. Both age and location (urban or rural) modify this effect. Overall, we did not see a greater movement from rural-to-urban areas after RA diagnosis. This is of interest for studies of regional environmental effects on chronic disease patterns.
25684762 Sustained Remission in Tumor Necrosis Factor Inhibitor-treated Patients with Rheumatoid Ar 2015 May OBJECTIVE: To study frequency, possible baseline predictors, timing, and duration of sustained remission [SR; defined as 28-joint Disease Activity Score (DAS28) < 2.6 for at least 6 mos] in patients with established rheumatoid arthritis (RA) treated with different tumor necrosis factor (TNF) inhibitors [etanercept (ETN), infliximab (IFX), adalimumab (ADA)]. In addition, the aim was to compare (head-to-head) the effectiveness of individual drugs in patients receiving their first anti-TNF treatment. METHODS: All anti-TNF-treated patients with RA included in the observational South Swedish Arthritis Group register were eligible. We identified the patients' first SR periods (time between first visit after treatment initiation with DAS28 < 2.6 and subsequent visit with DAS28 ≥ 2.6). Baseline predictors of SR in biologic-naive patients were studied using multivariate regression models. Remission duration and timing of remission start was estimated with Kaplan-Meier curves. RESULTS: Of the 2416 patients included, 382 (15.8%) fulfilled the criteria for SR. Median estimated duration of SR was 5.25 years. Predictors for SR were male sex, low Health Assessment Questionnaire, low DAS28, methotrexate (MTX) treatment, and the calendar year of treatment start. OR for achieving SR within the first 12 months of treatment were 1.86 for ETN (95% CI 1.33-2.61) compared to IFX. HR for 4 years of SR were 1.32 for ETN (95% CI 1.01-1.74) and 1.84 for ADA (95% CI 1.23-2.78), with IFX as the reference drug. CONCLUSION: SR was uncommon in patients with RA treated with anti-TNF in clinical practice. However, patients remained in SR for a substantial period of time. Concomitant MTX treatment predicts remission. ETN and ADA were more likely in reaching SR.
26016638 [Risk of serious infection in patients with rheumatoid arthritis]. 2015 Studies in the pre-biologics era described elevated risk of infection in patients with rheumatoid arthritis (RA). Recently biologics have been popularized and glucocorticoids used still now in RA patients, which can lead to various infections. Incidence rates of infection in RA patients are reported to be higher than that in the general population. Several factors such as higher age, comorbidities including chronic lung disease and diabetes mellitus, and glucocorticoids are known to increase risk of serious infection. Significant correlation between methotrexate and infection is not established. Whether biologics, especially inhibitors of tumor necrosis factor alpha, increase the risk for infection is still controversial even with randomized control studies and the meta-analyses; however, time-dependent decrease of the risk was revealed. Our three-year analysis of RA patients for infections requiring hospitalization included 5441 patient-years (PY) in total and detected an incidence rate of 3.4/100 PY, of which the risk factors were higher age (70 years of age or older), male sex, progressed stage of arthritis, functional disorders, and use of glucocorticoids or biologics. Such risk factors should be kept in mind for therapeutic decisions in individual patients with RA.
26300590 Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune Responses 2015 Microparticles (MPs) are induced during apoptosis, cell activation, and even "spontaneous" release. Initially MPs were considered to be inert cellular products with no biological function. However, an extensive research and functional characterization have shown that the molecular composition and the effects of MPs depend upon the cellular background and the mechanism inducing them. They possess a wide spectrum of biological effects on intercellular communication by transferring different molecules able to modulate other cells. MPs interact with their target cells through different mechanisms: membrane fusion, macropinocytosis, and receptor-mediated endocytosis. However, when MPs remain in the extracellular milieu, they undergo modifications such as citrullination, glycosylation, and partial proteolysis, among others, becoming a source of neoantigens. In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), reports indicated elevated levels of MPs with different composition, content, and effects compared with those isolated from healthy individuals. MPs can also form immune complexes amplifying the proinflammatory response and tissue damage. Their early detection and characterization could facilitate an appropriate diagnosis optimizing the pharmacological strategies, in different diseases including cancer, infection, and autoimmunity. This review focuses on the current knowledge about MPs and their involvement in the immunopathogenesis of SLE and RA.
26938757 Severe Thrombocytopenia Induced by First Infliximab Administration for Rheumatoid Arthriti 2016 Nov/Dec Thrombocytopenia due to antitumor necrosis factorα agents is very rare. A 68-year-old woman with rheumatoid arthritis on methotorexate received infliximab (IFX). Three days after the first IFX infusion, she developed gingival bleeding, petechia, and gross hematuria. Her platelet count fell to 2000/μL. We administered a platelet transfusion and intravenous methylprednisolone. Three days after admission, her platelet count was 7000/μL and her bleeding persisted. After double filtration plasmapheresis, her bleeding stopped and her platelet count recovered over 2 weeks. Thrombocytopenia is a rare but severe complication of IFX. Double filtration plasmapheresis may be useful for removing IFX or possible antibodies against platelets when IFX remaining in the patient's blood interferes with improvement of the patient's condition.
26950573 Suture Trabeculotomy Ab Interno for Secondary Glaucoma Combined With Scleromalacia. 2016 Jul PURPOSE: To report 2 cases of secondary glaucoma combined with scleromalacia that were successfully treated with trabeculotomy ab interno. DESIGN: Retrospective case report METHODS: : Trabeculotomy ab interno was used to treat secondary glaucoma combined with scleromalacia, which occurred due to refractory scleritis, in 2 cases. In case 2, goniosynechialysis was performed before the trabeculotomy to identify the trabecular meshwork. The sclera and conjunctiva were not incised in either case. RESULTS: The patients' postoperative intraocular pressure (IOP) levels (which were achieved without medication) were lower than their preoperative IOP levels (which were recorded during the administration of the maximum tolerable medication dosage); that is, they had dropped from 24 to 12 mm Hg in case 1 and from 33 to 11 mm Hg in case 2 by 12 postoperative months. No recurrent scleritis or postoperative worsening of the patient's scleromalacia was seen in either case. CONCLUSIONS: Trabeculotomy ab interno is a very valuable treatment for secondary glaucoma combined with scleromalacia.
26540618 Clinical efficacy of a new CD28-targeting antagonist of T cell co-stimulation in a non-hum 2016 Mar T cells have a central pathogenic role in the aetiopathogenesis of rheumatoid arthritis (RA), and are therefore a favoured target of immunotherapy aiming at physical or functional elimination. Here we report an efficacy test of FR104, a new co-stimulation inhibitor directly targeting CD28 on T cells, in a translationally relevant model, the rhesus monkey model of collagen-induced arthritis (CIA). As a relevant comparator we used abatacept [cytotoxic T lymphocyte antigen immunoglobulin (CTLA Ig)], an antagonist of CTLA-4 binding to CD80/86 clinically approved for treatment of RA. Treatment with either compound was started at the day of CIA induction. Although FR104 previously demonstrated a higher control of T cell responses in vitro than abatacept, both compounds were equally potent in the suppression of CIA symptoms and biomarkers, such as the production of C-reactive protein (CRP) and interleukin (IL)-6 and anti-collagen type II (CII) serum antibody (IgM/IgG). However, in contrast to abatacept, FR104 showed effective suppression of CII-induced peripheral blood mononuclear cell (PBMC) proliferation. The current study demonstrates a strong potential of the new selective CD28 antagonist FR104 for treatment of RA.
26986782 Cistromic and genetic evidence that the vitamin D receptor mediates susceptibility to lati 2016 Jun The vitamin D receptor (VDR) is a ligand-activated transcription factor that regulates gene expression in many cell types, including immune cells. It requires binding of 1,25 dihydroxy vitamin D3 (1,25D3) for activation. Many autoimmune diseases show latitude-dependent prevalence and/or association with vitamin D deficiency, and vitamin D supplementation is commonly used in their clinical management. 1,25D3 is regulated by genes associated with the risk of autoimmune diseases and predominantly expressed in myeloid cells. We determined the VDR cistrome in monocytes and monocyte-derived inflammatory (DC1) and tolerogenic dendritic cells (DC2). VDR motifs were highly overrepresented in ChIP-Seq peaks in stimulated monocyte (40%), DC1 (21%) and DC2 (47%), P
28028156 Patients' preferences and economic considerations play an important role in treatment deci 2017 Jan OBJECTIVE: To evaluate to what extent rheumatologists consider economic aspects and patients' preferences when choosing drug treatments in patients with active RA. METHODS: In a discrete choice experiment, rheumatologists were asked to choose between two unlabelled drug treatment options for a hypothetical RA patient with moderate disease activity who failed two synthetic DMARDs. Attributes and levels of drug treatments were selected based on existing literature, rheumatologists' opinion and expert consensus. This resulted in five attributes each described by three levels: efficacy (level of improvement and achieved state on DAS28), safety (probability of a serious adverse event), patients' preference (level of agreement), annual medication costs and cost-effectiveness (incremental cost-effectiveness ratio). An efficient experimental design generated 14 treatment choices and a random parameter logit model estimated the relative importance of attributes. RESULTS: Sixty-three rheumatologists from the Netherlands contributed to the analysis; 44% were female and mean (sd) age was 49 (8) years. Drug efficacy had the strongest relative contribution to the drug choice (44%) followed by medication costs (24%), patients' preference (17%) and cost-effectiveness (14%). Patients' preferences were most relevant when patients disliked a proposed treatment. The risk of serious but uncommon or rare side effects only played a minor role in the treatment choice (1%). CONCLUSION: In addition to drug efficacy, rheumatologists account for economic aspects and for patients' preferences when deciding on drugs. Decisions are more influenced by absolute costs than relative cost-effectiveness and by patients' disliking as opposed to favouring the treatment.
26091715 Cutting Edge: Chronic NF-κB Activation in CD4+ T Cells in Rheumatoid Arthritis Is Genetic 2015 Aug 1 Of identified genetic variants, HLA polymorphisms confer the greatest risk for developing autoimmune diseases, including rheumatoid arthritis (HLA-DRB1*04). There are strong influences of HLA polymorphisms on cell type-specific gene expression in B cells and monocytes. Their influence on gene expression in CD4(+) T cells is not known. We determined transcript and proteins levels of target genes in lymphocyte/monocyte subsets in healthy controls and rheumatoid arthritis subjects as a function of HLA-DRB1*04 haplotype. We identified gene expression dependent on HLA-DRB1*04 genotype in CD4(+) T cells. NF-κB activity in CD4(+) T cells was also dependent on HLA-DRB1*04 genotype, and blocking HLA-DR inhibited NF-κB activity in CD4(+) T cells and normalized gene expression, as did pharmacologic inhibition of NF-κB. We conclude that interactions between TCR and MHC class II encoded by HLA-DRB1*04 create a proinflammatory "hum" altering CD4(+) T cell phenotype.
27479870 Bioequivalence of Biosimilar Tumor Necrosis Factor-α Inhibitors Compared With Their Refer 2016 Oct 18 BACKGROUND: Biosimilars are of growing clinical, regulatory, and commercial importance. PURPOSE: To summarize evidence about the bioequivalence between biosimilar and reference tumor necrosis factor-α (TNF-α) inhibitors. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and LILACS from inception through 13 April 2016 and ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, EU Clinical Trials Register, U.S. Food and Drug Administration, and European Medicines Agency from inception through 30 April 2016. STUDY SELECTION: Published English-language studies of any size or design that compared the pharmacokinetics, clinical efficacy, adverse events, or immunogenicity of a biosimilar TNF-α inhibitor with a reference biologic in humans. DATA EXTRACTION: Two reviewers independently screened titles and abstracts, extracted data from selected studies, and assessed study quality. DATA SYNTHESIS: Of 19 eligible studies, 8 were phase 1 randomized trials, 5 were phase 3 randomized trials, and 6 were observational studies. Most phase 1 trials (n = 7) involved healthy volunteers, phase 3 trials involved patients with rheumatoid arthritis, and observational studies involved those with rheumatoid arthritis or inflammatory bowel disease. All phase 1 trials showed that pharmacokinetic parameters of the biosimilar and respective biologic were within the prespecified equivalence margin of 80% to 125%. Phase 3 trials suggested similar clinical responses and adverse events. Adverse events were usually of mild to moderate severity. Two cross-sectional observational studies showed cross-reactivity between products, whereas 4 cohort studies of patients switched from reference to biosimilar products suggested similar efficacy and safety outcomes. LIMITATION: Possible publication bias, small sample sizes of many studies, and lack of published studies for several biosimilars. CONCLUSION: Preliminary evidence supports the biosimilarity and interchangeability of biosimilar and reference TNF-α inhibitors. PRIMARY FUNDING SOURCE: Johns Hopkins Center of Excellence in Regulatory Science and Innovation. (PROSPERO: CRD42015025262).
25881902 Assessments of Immunomodulatory and Inflammatory effects against Induction of Entamoeba hi 2015 Today it is well known about mechanisms of cell communication, how the cells that mediate immune response and tissue injury accumulate in tissues but the aetiology of rheumatoid arthritis (RA) is still unknown. This study was to evaluate immunomodulatory effects of crude Entamoeba histolytica (HM1 IMS strain) antigen in complete freund's adjuvant female wistar rats by studying the alterations in humoral and cell mediated immune responses and also the inflammatory effects by evaluating the changes in body weight, paw thickness, biochemical, serological, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) and histopathology activities. Animals were randomly divided into six groups (n=6). CFA was induced in arthritic, drug and AA+CFA group whereas, 0.5ml amoebic antigen was induced subplantal in AA group while 0.5ml dose of amoebic antigen was given orally to AA+CFA group for 7-28th days. Indomethacin was used as a standard drug. Effects of amoebic antigen were associated with increased paw thickness and decreased body weight when compared to healthy control showed a significant difference. Oral administration of amoebic antigen has showed increased severe symptoms of arthritis in AA+CFA on comparison to healthy control rats. Significant increase in serum level of IL-6 and α TNF were found in AA group followed by AA+CFA group whereas, decrease in concentration of IL-10 was appear in AA+CFA group on comparison to arthritic and healthy control group (P<0.05). Histopathology of AA group showed severe signs of necrotic and degenerative changes on comparison to healthy control group. Thus the results demonstrated that E. histolytica alone or in combination with CFA increased bone damage, with alterations in antioxidant level in liver and kidney tissue homogenates as well as showed immunomodulatory arthritogenic properties which may contribute and raise joint inflammation.
27599586 Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signalin 2016 Oct Cytokines play a key role in the bone destruction of rheumatoid arthritis (RA). Interleukin-21 (IL-21) promotes osteoclastogenesis in RA in a receptor activator of nuclear factor-κB ligand (RANKL)-dependent way. Whether IL-21 is capable of promoting osteoclastogenesis directly in the absence of RANKL remains unknown. In the present study, we examined the osteoclastogenic activity of IL-21 in RAW264.7 cells in the absence of RANKL. We found that IL-21 enhanced osteoclastogenesis and this was demonstrated by increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive stained, multinucleated cells compared with the negative control. Western blot analysis and immunocytochemistry showed the positive expression of calcitonin receptor (CTR) in the IL-21 group. RT-PCR and RT-qPCR also verified the increased mRNA expression of CTR and cathepsin K in the IL-21 group compared with the negative control. The scanning electronic microscope images showed a few resorption pits on the bone slices cultured with IL-21. The phosphoinositide 3-kinase (PI3K)/AKT pathway inhibitor LY294002 significantly suppressed IL-21-induced osteoclastogenesis. Taken together, these findings suggest that IL-21 has direct osteoclastogenic potential independently of RANKL. IL-21 may promote osteoclastogenesis through the PI3K/AKT signaling pathway. Therapy targeting IL-21 may be of value in preventing bone erosions in patients with RA.
26866506 Brief Report: Intensification to Triple Therapy After Treatment With Nonbiologic Disease-M 2016 Jul OBJECTIVE: Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (DMARDs) have similar efficacy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate intensification to triple therapy after initial nonbiologic prescription among patients with RA. METHODS: The use of triple therapy among patients with RA in 2009-2014 was evaluated using US insurance claims data. Patients with a health care visit for RA and an initial nonbiologic DMARD prescription were included. Frequencies of intensification to triple therapy or a biologic DMARD and rates of intensification per 6-month time period were calculated. Using Cox regression, we evaluated whether sociodemographic, temporal, geographic, clinical, and health care utilization factors were associated with intensification to triple therapy. Among those patients whose therapy was intensified, we investigated factors associated with triple therapy use by logistic regression. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for intensification to triple therapy in relation to various clinical and demographic factors were calculated. RESULTS: There were 24,576 patients with a mean ± SD age of 50.3 ± 12.3 years, and 78% were female. During the study period, treatment was intensified to biologic DMARDs in 2,739 patients (11.1%) compared to 181 patients (0.7%) whose treatment was intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients whose treatment was intensified to triple therapy were more likely to receive glucocorticoids (HR 1.91 [95% CI 1.41-2.60]) compared to patients who did not use glucocorticoids and were more likely to use nonsteroidal antiinflammatory drugs (NSAIDs) (HR 1.48, 95% CI 1.10-1.99 versus no NSAID use). Among those patients whose treatment was intensified to triple therapy or biologic DMARDs, factors significantly associated with triple therapy use included older age, US region (with the highest odds for triple therapy use in the West and lowest odds for triple therapy use in the Northeast), glucocorticoid use, and lower number of outpatient visits within 180 days of initial nonbiologic DMARD prescription. CONCLUSION: Despite reports published during the study period suggesting equivalent efficacy of triple therapy and biologic DMARDs for RA, the use of triple therapy was infrequent and did not increase over time in this large nationwide study.
27549343 Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment re 2016 Aug 23 Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2)=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.
27093159 Sustained Improvement of Arterial Stiffness and Blood Pressure after Long-Term Rosuvastati 2016 OBJECTIVE: Patients with inflammatory joint diseases (IJD) have a high prevalence of hypertension and increased arterial stiffness. The aim of the present study was to evaluate the effect of long-term rosuvastatin treatment on arterial stiffness, measured by augmentation index (AIx) and aortic pulse wave velocity (aPWV), and blood pressure (BP) in IJD patients with established atherosclerosis. METHODS: Eighty-nine statin naïve IJD patients with carotid atherosclerotic plaque(s) (rheumatoid arthritis n = 55, ankylosing spondylitis n = 23, psoriatic arthritis n = 11) received rosuvastatin for 18 months to achieve low-density lipoprotein cholesterol goal ≤1.8 mmol/L. Change in AIx (ΔAIx), aPWV (ΔaPWV), systolic BP (ΔsBP) and diastolic BP (ΔdBP) from baseline to study end was assessed by paired samples t-tests. Linear regression was applied to evaluate associations between cardiovascular disease (CVD) risk factors, rheumatic disease specific variables and medication, and ΔAIx, ΔaPWV, ΔsBP and ΔdBP. RESULTS: AIx, aPWV, sBP and dBP were significantly reduced from baseline to study end. The mean (95%CI) changes were: ΔAIx: -0.34 (-0.03, -0.65)% (p = 0.03), ΔaPWV: -1.69 (-0.21, -3.17) m/s2 (p = 0.03), ΔsBP: -5.27 (-1.61, -8.93) mmHg (p = 0.004) and ΔdBP -2.93 (-0.86, -5.00) mmHg (p = 0.01). In linear regression models, ∆aPWV was significantly correlated with ΔsBP and ΔdBP (for all: p<0.001). CONCLUSIONS: There is an unmet need of studies evaluating CVD prevention in IJD patients. We have shown for the first time that long-term intensive lipid lowering with rosuvastatin improved arterial stiffness and induced a clinically significant BP reduction in patients with IJD. These improvements were linearly correlated and may represent novel insight into the pleiotropic effects by statins. TRIAL REGISTRATION: ClinicalTrials.gov NCT01389388.
27870761 Disease Activity Score on 28 Joints and Polypharmacy Are Independent Predictors for Health 2016 Dec OBJECTIVE: The aim of this study was to investigate the main factors associated to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA (Health-Related Quality of Life Inventory for Latin American Patients) in patients with rheumatoid arthritis (RA). METHODS: Female, 18 years or older, RA (American College of Rheumatology 1987 criteria and American College of Rheumatology/European League against Rheumatism 2010 criteria) patients who attended the outpatient rheumatology department of the Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Mexico, matched with healthy controls were included. Patients with any known comorbidities or treatment with antidepressive drugs were excluded. Trained physicians performed the RA clinical evaluation and INCAVISA. All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05 was considered statistically significant. RESULTS: Patients with polypharmacy (≥3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy were independent predictors for a negative perception of HRQoL evaluated by INCAVISA in RA patients. CONCLUSIONS: Disease activity and disability secondary to RA have a negative impact in the HRQoL. Other factors such as the number of drugs prescribed to these patients have been shown to be important for the negative perception of their HRQoL evaluated by INCAVISA.
26883487 Computationally expanding infinium HumanMethylation450 BeadChip array data to reveal disti 2016 Jun 15 MOTIVATION: DNA methylation signatures in rheumatoid arthritis (RA) have been identified in fibroblast-like synoviocytes (FLS) with Illumina HumanMethylation450 array. Since <2% of CpG sites are covered by the Illumina 450K array and whole genome bisulfite sequencing is still too expensive for many samples, computationally predicting DNA methylation levels based on 450K data would be valuable to discover more RA-related genes. RESULTS: We developed a computational model that is trained on 14 tissues with both whole genome bisulfite sequencing and 450K array data. This model integrates information derived from the similarity of local methylation pattern between tissues, the methylation information of flanking CpG sites and the methylation tendency of flanking DNA sequences. The predicted and measured methylation values were highly correlated with a Pearson correlation coefficient of 0.9 in leave-one-tissue-out cross-validations. Importantly, the majority (76%) of the top 10% differentially methylated loci among the 14 tissues was correctly detected using the predicted methylation values. Applying this model to 450K data of RA, osteoarthritis and normal FLS, we successfully expanded the coverage of CpG sites 18.5-fold and accounts for about 30% of all the CpGs in the human genome. By integrative omics study, we identified genes and pathways tightly related to RA pathogenesis, among which 12 genes were supported by triple evidences, including 6 genes already known to perform specific roles in RA and 6 genes as new potential therapeutic targets. AVAILABILITY AND IMPLEMENTATION: The source code, required data for prediction, and demo data for test are freely available at: http://wanglab.ucsd.edu/star/LR450K/ CONTACT: wei-wang@ucsd.edu or gfirestein@ucsd.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.