Browse

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

ID PMID Title PublicationDate abstract
26082436 Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in 2015 Jun 16 Oxidative stress produced in response to infection or sterile injury activates the innate immune response. We found that extracellular vesicles (EVs) isolated from the plasma of patients with rheumatoid arthritis or secreted from cells subjected to oxidative stress contained oxidized phospholipids that stimulated cells expressing Toll-like receptor 4 (TLR4) in a manner dependent on its co-receptor MD-2. EVs from healthy subjects or reconstituted synthetic EVs subjected to limited oxidation gained the ability to stimulate TLR4-expressing cells, whereas prolonged oxidation abrogated this property. Furthermore, we found that 15-lipoxygenase generated hydro(pero)xylated phospholipids that stimulated TLR4-expressing cells. Molecular modeling suggested that the mechanism of activation of TLR4 by oxidized phospholipids in EVs was structurally similar to that of the TLR4 ligand lipopolysaccharide (LPS). This was supported by experiments showing that EV-mediated stimulation of cells required MD-2, that mutations that block LPS binding to TLR4 abrogated the stimulatory effect of EVs, and that EVs induced TLR4 dimerization. On the other hand, analysis of gene expression profiles showed that genes encoding factors that resolve inflammation were more abundantly expressed in responses to EVs than in response to LPS. Together, these data suggest that EVs act as an oxidative stress-induced endogenous danger signal that underlies the pervasive role of TLR4 in inflammatory diseases.
26391522 Milk Fat Globule-Epidermal Growth Factor 8 (MFG-E8) Is a Novel Anti-inflammatory Factor in 2016 Mar Milk fat globule-epidermal growth factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates the clearance of apoptotic cells and is implicated in the pathogenesis of autoimmune and inflammatory diseases. Because MFG-E8 also controls bone metabolism, we investigated its role in rheumatoid arthritis (RA), focusing on inflammation and joint destruction. The regulation of MFG-E8 by inflammation was assessed in vitro using osteoblasts, in arthritic mice and in patients with RA. K/BxN serum transfer arthritis (STA) was applied to MFG-E8 knock-out mice to assess its role in the pathogenesis of arthritis. Stimulation of osteoblasts with lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α downregulated the expression of MFG-E8 by 30% to 35%. MFG-E8-deficient osteoblasts responded to LPS with a stronger production of pro-inflammatory cytokines. In vivo, MFG-E8 mRNA levels were 52% lower in the paws of collagen-induced arthritic (CIA) mice and 24% to 42% lower in the serum of arthritic mice using two different arthritis models (CIA and STA). Similarly, patients with RA (n = 93) had lower serum concentrations of MFG-E8 (-17%) compared with healthy controls (n = 140). In a subgroup of patients who had a moderate to high disease activity (n = 21), serum concentrations of MFG-E8 rose after complete or partial remission had been achieved (+67%). Finally, MFG-E8-deficient mice subjected to STA exhibited a stronger disease burden, an increased number of neutrophils in the joints, and a more extensive local and systemic bone loss. This was accompanied by an increased activation of osteoclasts and a suppression of osteoblast function in MFG-E8-deficient mice. Thus, MFG-E8 is a protective factor in the pathogenesis of RA and subsequent bone loss. Whether MFG-E8 qualifies as a novel biomarker or therapeutic target for the treatment of RA is worth addressing in further studies.
26014481 Anti-arthritic agents: progress and potential. 2015 Jul 1 Osteoarthritis and rheumatoid arthritis are the two most common types of arthritis. Cartilage breakdown is a key feature of both diseases which contributes to the pain and joint deformity experienced by patients. Therefore, anti-arthritis drugs are of great importance. The aim of this review is to present recent progress in studies of various agents against osteoarthritis and rheumatoid arthritis. The structures and activities of anti-arthritic agents, which used in medical practice or are in development, are presented and discussed. The effects and mechanisms of action of opioids, glucocorticoids, non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, natural products derived from plants, nutraceuticals, and a number of new and perspective agents are considered. Various perspective targets for the treatment of osteoarthritis and rheumatoid arthritis are also discussed. Trials of good quality are needed to draw solid conclusions regarding efficacy of many of the studied agents. Unfortunately, to date, there is no pharmacologic agent proven to prevent the progression of both diseases, and there is an urgent need for further development of better anti-arthritic agents.
27813548 CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients fr 2016 Oct 24 The CD40 pathway is involved in the development and pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). Two single nucleotide polymorphisms (SNPs) in the CD40 gene, rs1883832 and rs4810485, are associated with susceptibility to inflammatory and autoimmune diseases and are thought to alter CD40 expression at the mRNA and protein level. This study assessed for the first time the association of these SNPs with RA and CD40 mRNA levels in a western Mexican population. A total of 278 RA patients and 318 control subjects were included. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and CD40 mRNA expression was determined by real-time quantitative PCR. No significant differences in genotype and allele frequencies were identified between the RA patients and controls. When stratified by genotype, these SNPs were not found to be associated with the presence of autoantibodies or the clinical activity of the disease. CD40 mRNA levels were elevated 1.5-fold in RA patients compared to control subjects; however, no clear tendencies were observed following stratification by genotype. These results suggest that the CD40 SNPs rs1883832 and rs4810485 are not RA susceptibility markers in the western Mexican population. Further studies are needed to clarify their roles in CD40 mRNA expression.
27322646 Interleukin-6 (IL-6) Receptor Antagonist Protects Against Rheumatoid Arthritis. 2016 Jun 20 BACKGROUND The aim of this study was to investigate the protective effect of interleukin-6 (IL-6) receptor antagonist tocilizumab (TCZ) on rheumatoid arthritis (RA) and its related mechanism. MATERIAL AND METHODS Thirty RA patients receiving long-term methotrexate therapy at moderate and severe active stages were selected and treated with TCZ 8 mg/kg/time iv gtt intravenously guttae every 4 weeks. Peripheral blood was extracted before and 24 weeks after TCZ treatment. Peripheral blood mononuclear cells (PBMC) were collected by density gradient centrifugation. Flow cytometry was used to detect the ratio of CD4 naïve T cells and CD4 memory T cells, Th17 cells, and Treg cells in PBMC. DAS28 score, CRP, RF, and CCP levels in patients were evaluated. RESULTS Compared with before treatment, IL-6 receptor antagonist TCZ significantly improved patients' condition, including DAS28 score, CRP, RF, and CCP levels (P<0.01). Furthermore, TCZ obviously upregulated CD4 naïve T cells proportion and decreased CD4 memory T cells ratio (P<0.01). TCZ also markedly reduced the proportion of Th17 cells and increased the proportion of Treg cells (P<0.01). CONCLUSIONS TCZ can treat RA patients through regulating the ratio of CD4 naïve T cells, CD4 memory T cells, Th17 cells, and Treg cells in PBMC.
27749229 Improvement of fatigue in patients with rheumatoid arthritis treated with biologics: relat 2017 Jan OBJECTIVES: To assess predictive factors of improvement in related fatigue in rheumatoid arthritis (RA) patients newly receiving biologic therapy, and specifically the influence of the improvement of the quality of sleep. METHODS: We conducted a multicentre prospective study in RA patients requiring initiation or change of biologic therapy. The improvement in fatigue, sleep disorders and depression was assessed respectively by the FACIT fatigue scale, Spiegel scale and Beck Depression Inventory at inclusion (M0) and 3 months (M3) after the beginning of treatment. Potential confounders were assessed and adjusted for. The association between evolution of fatigue and other characteristics were evaluated by univariate (χ2) then multivariate (logistic regression) analyses. RESULTS: We followed-up 99 patients. FACIT scores at M0 revealed frequently reported fatigue: 89%, high prevalence of sleep disorders: 95% and depression: 67%. Improvement of fatigue, sleep quality and depression was observed in 58.6%, 26.3% and 34.3% of cases, respectively. Significant factors associated with an improvement in fatigue at M3 were an elevated sedimentation rate at M0 (OR=5.7[2.0-16.0], p=0.001) and a favourable EULAR response at M3 (OR=4.8[1.6-14.8], p=0.006). Furthermore, a number of swollen joints > 5 at baseline (OR=0.3 [0.1-0.8]) and the use of psychotropic drugs (OR=0.2[0.04-0.9]) were predictive of an absence of improvement in fatigue. No significant association with the improvement in sleep disorders could be demonstrated. CONCLUSIONS: Fatigue in RA is improved by effective treatment, via decreasing disease activity. Improvement of sleep disorders is more likely a surrogate of therapeutic efficiency rather than an independent outcome.
27640805 Association of TNFRSF1B +676 gene polymorphism with the risk of rheumatoid arthritis in Ha 2016 Sep 28 OBJECTIVE: To study the association of TNFRSF1B +676 gene (rs1061622) polymorphism with the risk of rheumatoid arthritis (RA ) in Han Chinese population of Hunan. METHODS: A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNFRSF1B +676 (rs1061622) gene polymorphisms were examined by PCR-RFLP. Serum levels of soluble TNFR II were analyzed by ELISA. RESULTS: RA patients displayed a similar TNFRSF1B +676 genotype to controls (GG/TG/TT: 5/62/45 vs 9/56/64, P=0.167), but signifi cant diff erence was found between female RA patients and female controls (GG/TG/TT: 3/49/24 vs 8/28/48, P<0.001). No significant difference was found in the frequency of TNFRSF1B +676 T or G allele between RA patients and controls (P>0.05). RA patients showed a signifi cantly higher level of serum soluble tumor necrosis factor receptor II (sTNFR II) than controls [(7.83±2.61) ng/mL vs (4.32±1.67) ng/mL, P<0.001], but there was no diff erence among the three genotypes (P>0.05). No association was found between TNFRSF1B+676 gene polymorphism and RA clinical characteristics. CONCLUSION: In Han Chinese population of Hunan province, TNFRSF1B+676 gene polymorphisms are not associated with the genetic risk of RA .
26154773 The Influence of Polymorphisms of Interleukin-17A and -17F Genes on Susceptibility and Act 2015 Aug BACKGROUND: The roles of interleukin (IL)-17A and IL-17F in the pathogenesis of rheumatoid arthritis (RA) have been previously studied. However, the relationships between polymorphisms (IL-17A G197A, the IL-17F 7488A/G, and the IL-17F 7383A/G) of these genes with RA have not been clarified yet. AIMS: To investigate the impacts of these polymorphisms on the severity and susceptibility of RA in a Turkish population. METHODS: One hundred sixty-one patients with RA and 88 healthy sex-, age-, and ethnicity-matched controls were enrolled in this study. The erythrocyte sedimentation rate, C-reactive protein (CRP), and disease activity scores 28 (DAS28) of all participants were recorded. The IL-17A G197A, the IL-17F 7488A/G, and 7383A/G polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: We found no significant difference regarding genotypes or allelic frequency distributions of the IL-17A G197A, the IL-17F 7383A/G, and 7488A/G polymorphisms between patients and healthy controls (p>0.05). There were slight, but not significant, differences in terms of CRP levels associated with the distribution of the genotypes of the IL-17F 7488A/G, and regarding DAS28 levels according to the genotype distribution of the IL-17A G197A polymorphism (p=0.062, 0.087, 0.052, respectively). CONCLUSIONS: These findings suggest that future larger scale studies with increased power should be performed to determine if the IL-17F 7488A/G and the IL-17A G197A polymorphisms are associated with the disease activity in patients with RA.
27141621 [Effect of Electroacupuncture on Serum TNF-α, IL-1β and Intercellular adhesion molecule 2016 Feb OBJECTIVE: To observe the influence of electroacupuncture (EA) on serum TNF-α, IL-1β and Intercellular adhesion molecule 1 (ICAM-1) levels in rheumatoid arthritis (RA) rats so as to explore its mechanism in relieving RA. METHODS: Eight Wistar rats were used as the normal control group in this study. The RA model was established by injecting mixture solution of incomplete Freund's adjuvant and type II chicken collagen into the left paw. The 24 successful RA rats were randomly divided into model, medication (Prednisolone) and EA groups (n = 8 in each group). EA(2 Hz /100 Hz,1-2 mA)was applied to "Zusanli"(ST 36) and "Kunlun" (BL 60) for 30 min, once daily for 10 days. For rats of the medication group, Prednisolone acetate (0. 1 mL/10 g) was intragastric infused daily. The rats' left ankle diameter was measured before and after the treatment, and the contents of serum TNF-α, IL-1β and ICAM-1 were assayed by ELISA. RESULTS: In comparison with the normal control group, the rats' ankle diameter, serum TNF-α, IL-1β and ICAM-1 contents were remarkably increased in the model group (P < 0.05); while compared with the model group, the increased ankle diameter, and serum TNF-α, IL-1β and ICAM-1 contents were obviously reversed in both medication and EA groups ( P < 0.05), without significant differences between the medication and EA groups (P > 0.05). CONCLUSION: EA intervention is effective in relieving RA rats' inflammatory reactions by down-regulating the levels of serum TNF-α, IL-1β and ICAM-1.
25294249 Isotretinoin-induced arthritis mimicking both rheumatoid arthritis and axial spondyloarthr 2015 May Isotretinoin is used for the treatment of various acne lesions that are resistant to other treatments. The most frequent rheumatologic side effect of isotretinoin is transient muscle and/or joint pains. Here, we report a case with bilateral wrist and metacarpophalangeal joint arthritis and unilateral sacroiliitis associated with isotretinoin usage to attract attention, particularly from physiatrists, rheumatologists and dermatologists, to this rare adverse effect of isotretinoin.
25433021 Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premat 2015 Feb 21 A variety of systemic inflammatory rheumatic diseases associate with an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Although this recognition has stimulated intense basic science and clinical research, the precise nature of the relationship between local and systemic inflammation, their interactions with traditional CV risk factors, and their role in accelerating atherogenesis remains unresolved. The individual rheumatic diseases have both shared and unique attributes that might impact CV events. Understanding of the positive and negative influences of individual anti-inflammatory therapies remains rudimentary. Clinicians need to adopt an evidence-based approach to develop diagnostic techniques to identify those rheumatologic patients most at risk of CV disease and to develop effective treatment protocols. Development of optimal preventative and disease-modifying approaches for atherosclerosis in these patients will require close collaboration between basic scientists, CV specialists, and rheumatologists. This interface presents a complex, important, and exciting challenge.
26921739 Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmun 2016 Apr BACKGROUND: Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA). OBJECTIVES: Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients. STUDY DESIGN: Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls. RESULTS: Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA. DISCUSSION: CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients.
26033386 Effect of Systemic Inflammation on the Function of Insulin and Glucose Metabolism in Rheum 2015 Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology characterized by chronic inflammation of the synovial membranes and articular structures of the joints. The concomitant comorbidities are important in the management and treatment of patients with RA, because they decrease their life quality and expectancy - with cardiovascular diseases being the most common comorbidities and primary cause of death in RA. Traditional cardiovascular risk factors, such as diabetes mellitus (DM) and insulin resistance (IR) are prevalent in these patients. The prevalence of DM in RA patients has not been well established and the association between these diseases is controversial. On the other hand, several epidemiological studies support the association between RA and IR, with the latter being linked to systemic inflammatory markers, including C reactive protein and erythrocyte sedimentation rate. Patients with RA who underwent glucocorticoid therapy were also determined to have a defective insulin sensitivity and pancreatic β-cell dysfunction. It has been proposed that systemic inflammation due to RA may result in insulin resistance - moreover, studies have examined the effect of inflammatory cytokines such as TNF-α, IL-6 and IL-1 on insulin sensitivity and glucose metabolism. Likewise, the association between RA and IR, and its role on the different characteristics of the disease, such as duration, activity, and treatment with glucocorticoids has not been well defined. A gap in the current understanding regarding the role that the systemic inflammation and the different RA characteristics have on the insulin function and glucose metabolism of RA patients suggest that more studies are required to elucidate these mechanisms.
25794145 Enrichment of Genetic Variants for Rheumatoid Arthritis within T-Cell and NK-Cell Enhancer 2015 Mar 16 To identify disease-causative variants, we intersected the published results of a metaanalysis of genome-wide association studies (GWAS) for rheumatoid arthritis (RA) with the set of enhancer regions for 71 primary cell types that was provided by the FANTOM consortium. We first retrieved all single nucleotide polymorphisms (SNPs) that are associated (P < 5 × 10(8)) with RA in the GWAS meta-analysis and that are located in any of these enhancer regions. After excluding the major histocompatibility complex (MHC) region, we identified 50 such RA-associated SNPs that are located in enhancer regions. Enhancer sets from different cell types were then compared with each other for their number of RA-associated SNPs by permutation analysis. This analysis showed that RA-associated SNPs are preferentially located in enhancers from several immunological cell types. In particular, we see a strong relative enrichment in enhancer regions that are active in T cells (P < 0.001) and NK cells (P < 0.001). Several loci display multiple RA-associated SNPs in tight linkage disequilibrium that are located within the same or neighboring enhancers. These haplotypes may have a greater likelihood to influence enhancer activity than any SNP on its own. Taken together, these results support the hypothesis that RA-causative variants often act through altering the activity of immune cell enhancers. The enrichment in T-cell and NK-cell enhancer regions indicates that expression changes in these cell types are particularly relevant for the pathogenesis of RA. The specific SNPs that account for this enrichment can be used as a basis for focused genotype-phenotype studies of these cell types.
27242206 New therapeutic approaches in rheumatoid arthritis. 2016 Jun The treatment of rheumatoid arthritis (RA) has changed dramatically over the past two decades. The combination of better insights into the pathophysiological and immunological mechanisms of RA and the possibilities offered by biotechnology led to the development and introduction into clinical practice of a new class of antirheumatic biologic therapies, which along with earlier and more aggressive treatment contributed to dramatically better outcomes for patients with RA. To date, nine biologic agents have been approved for the treatment for RA, and a first Janus kinase (JAK) inhibitor has also been approved in the United States and various other countries in the world (but not by the European Medicines Agency [EMA]). Many additional molecules with distinct mechanisms of action are currently being tested in laboratories and in clinical trials. In addition, considerable improvements have been made in the optimal use of all these agents through treatment strategies such as treating-to-target, induction-maintenance, and dose individualization.
29933531 Effect of Sanhuangyilong decoction plus methotrexate on tumor necrosis factor alpha and in 2016 Oct OBJECTIVE: To investigate the effect of Sanhuangyilong decoction plus methotrexate (MTX) on Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in the serum and synovial fluid of rheumatoid arthritis (RA) patients with damp-heat-obstruction symptom pattern, Sanhuangyilong decoction and the role of TNF-α and IFN-γ in the development of RA. METHODS: RA inpatients with damp-heat-obstruction symptom pattern (partly with knee joint effusion) were selected as the research subjects. Before the treatment, healthy subjects and osteoarthritis (OA) patients with knee joint effusion were assigned to the serum control group and the synovial fluid control group, respectively; during the treatment, RA patients with damp-heat-obstruction symptom pattern were divided into two groups: one is combined group that was administered Sanhuangyilong decoction plus MTX; the other group was MTX group that received MTX only. The expression levels of TNF-α and IFN-γ in the serum and synovial fluid were measured with enzyme-linked immunosorbent assay (ELISA) before and after the treatment, and the peripheral blood levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score in 28 joints (DAS28) were determined. RESULTS: Before treatment, the serum levels of TNF-α and IFN-γ in the RA patients with dampheat- obstruction symptom pattern were higher than those in healthy control group (P < 0.05).The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those in the serum of the RA patients (P < 0.05). The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those of the synovial fluid of the osteoarthritis patients (P < 0.05). The expression of TNF-α and IFN-γ in the serum and synovial fluid of the RA patients had no correlation with the inflammatory activity index ESR, CRP, or DAS28 (P > 0.05). After 2 weeks of treatment, the expression level of TNF-α and IFN-γ in the combined group had increased, although the difference was not statistically significant (P > 0.05); in contrast, ESR, CRP, and DAS28 decreased, and the difference was statistically significant (P < 0.01). After 4 weeks of therapy, TNF-alpha and IFN-γ, ESR, CRP, and DAS28 in the combined group decreased compared with the before-treatment levels (P < 0.01). After 2 w of treatment, the differences in the TNF-α and IFN-γ expression levels in the combined group were not statistically significant (P > 0.05) compared with that in the MTX group, although there were statistically significant differences in the ESR, CRP, and DAS28 (P < 0.05). After 4 weeks of treatment, differences in TNF-α, IFN-γ, ESR, CRP, and DAS28 in the combined group compared with MTX group were statistically significant (P < 0.01). CONCLUSION: TNF-α and IFN-γ might be involved in the development of RA. The RA patients with damp-heat-obstruction symptom pattern show better benefits from the treatment of Sanhuangyilong decoction plus MTX, and the treatment is superior to that of using MTX only.
26426533 Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide, Population 2015 BACKGROUND: The risk of periodontitis (PD) is increased in the patient group of rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The aim of this study is to investigate the risk of RA associated with PD exposure. METHODS AND FINDINGS: This study identified 3 mutually exclusive cohorts using the 1999-2010 Taiwanese National Health Insurance Research Database (NHIRD) to investigate the association between PD and the risk of incident RA. All patients with PD in 2000 were identified from the database of all enrollees as the PD cohort. From the representative database of 1,000,000 enrollees randomly selected in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999-2010 were selected as the non-PO cohort. Individuals who were not included in the non-PO cohort and received dental scaling (DS) no more than two times per year during 1999-2010 were selected as the DS cohort from LHID2010. Using cox proportional regression analysis, hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated to quantify the association between PD exposure and RA development. In the three-group comparison using the non-PO cohort as reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs, 1.89 and 1.43; 95% CIs, 1.56-2.29 and 1.09-1.87, respectively). For comparisons between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57-2.30 and 1.09-1.67, respectively). CONCLUSION: PD was associated with an increased risk of RA development.
28027916 Vitamin D in Saudi Arabia: Prevalence,distribution and disease associations. 2018 Jan More than 33 years have passed since the first paper highlighting vitamin D deficiency as a public health concern in Saudi Arabia was published in 1983. Despite "early" detection,it wasn't until the year 2010 where the interest in vitamin D research grew exponentially worldwide and was finally visible in Saudi clinical and academic areas. Since then,many landmark studies have been generated with regards to the physiologic functions of vitamin D,both skeletal and extra-skeletal. This review is limited to the prevalence,distribution A systematic review on the prevalence studies done in KSA from 2011 to 2016 was done and revealed that the prevalence of vitamin D deficiency (<50nmol/l) in Saudi Arabia among different populations (adults,children and adolescents,newborns and pregnant/lactating women) is 81.0% (Confidence Interval 95% 68.0-90.0),in line with most neighboring Gulf countries. Vitamin D deficiency in KSA has been mostly associated with bone and insulin-resistant diseases but limited data are available to prove causality. In conclusion,there is a need to develop local consensus guidelines that will identify candidates for screening,monitoring and treating those who are at most risk for vitamin D deficiency complications.
27241253 Nanofacilitated synergistic treatment for rheumatoid arthritis: A 'three-pronged' approach 2016 Jul Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease of unidentified etiology that affects the joints and causes pain, swelling, stiffness and redness in the joints. The exact cause of rheumatoid arthritis has not yet been discovered and, consequently, treatment methods have not been optimally effective. It has long been treated with anti-inflammatory and immunosupressants including modern biologics either alone or in combination but all of the drugs have severe life threatening consequences with impaired immune function due to nonspecific targeting. Therefore, a three-pronged approach of local, active and synergistic targeting can be used to optimize delivery of therapeutic agents to reduce toxicity and patient outcome without compromising patient's immunity.
26936261 Second-line therapy with biological drugs in rheumatoid arthritis patients in German rheum 2016 Aug The aim of the study was to assess the proportion of German patients with rheumatoid arthritis (RA) who received biological disease-modifying antirheumatic drugs (DMARDs) after initiation of conventional DMARD therapy. Patients aged 18 years or over who had initiated therapy with a conventional DMARD in a rheumatic care practice between 2009 and 2013 were included (IMS LRx database). The main outcome was the first prescription of a biological DMARD within 5 years following the index date. A multivariate Cox regression model was adopted to predict the prescription of biological DMARDs on the basis of patient characteristics. The mean age of the 137,673 patients with RA was 57.8 years (SD = 15.0). 68.3 % of the subjects were women. Most patients started their conventional DMARD therapy with methotrexate (62 %), sulfasalazine (13 %), and hydroxychloroquine (12 %). 20.7 % of the RA patients were given a biological DMARD within 5 years following the index date. Male gender was linked with a 10 % higher likelihood of biologic use whereas age decreased the odds of biological DMARD prescription by 3 % per year. Finally, leflunomide use was associated with increased odds of biologic prescription, whereas sulfasalazine and hydroxychloroquine decreased the chances of receiving biologics, as compared to methotrexate. Around 20 % of patients were being treated with biologics 5 years after prescription of conventional DMARDs. Gender, age, and initial treatment impacted the proportion of subjects treated with biological DMARDs.