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ID PMID Title PublicationDate abstract
29529488 Amelioration of collagen antibody induced arthritis in mice by an antibody directed agains 2018 May Tenascin-C (TN-C) levels are elevated in the synovial tissue and fluid, as well as cartilage of rheumatoid arthritis (RA) patients. In addition, the presence of TN-C fragments has also been documented in arthritic cartilage. We have previously shown that a single chain variable fragment antibody (TN64), directed against the fibronectin type III repeats 1-5 (TNfnIII 1-5) of TN-C, effectively inhibits fibrotic pathology. Given that fibrosis results from chronic inflammation, and the fact that increased levels of TN-C in the synovial fluid of patients with RA contributes to synovial inflammation and joint destruction, we aimed to investigate the role of TNfnIII 1-5 region of TN-C in RA pathogenesis. Using either the wild type or variants of the two integrin-binding motifs (RGD and AEIDGIEL) present within the TNfnIII 1-5 polypeptide, we demonstrate that the adhesion and migration of synovial fibroblasts is RGD-dependent. The antibody TN64 is effective in inhibiting migration of cells in response to TnfnIII 1-5, and prevents fibroblast-mediated destruction of cartilage. The TN64 antibody was further tested in collagen antibody induced arthritic (CAIA) mice. Our data shows the efficacy of TN64 in preventing induction of arthritis, with significant downregulation of RA-associated cytokines. This suggests that components of the extracellular matrix such as the TNfnIII 1-5 region of TN-C could be exploited to develop therapies to suppress inflammation seen in RA. The TN64 antibody is one such promising candidate in the development of novel treatments for RA.
29879032 Inhibition of NF-κB signaling pathway induces apoptosis and suppresses proliferation and 2018 Jun BACKGROUND: Rheumatoid arthritis (RA) is the most common inflammatory arthritis and is a major cause of disability. The nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway has been reported to be involved in the pathogenesis of RA with unclear mechanisms. Therefore, this study aims to explore the effect of NF-κB pathway on proliferation, apoptosis, and angiogenesis of human fibroblast-like synovial cells (HFLS) in RA. METHODS: Normal HFLS and RA-HFLS were selected as the normal and control groups, respectively. RA-HFLS were treated by BAY11-7082 (an inhibitor of NF-κB) in different concentrations, namely 2.5 μmol/L BAY11-7082, 5 μmol/LBAY11-7082 and 10 μmol/L BAY11-7082. MTT assay was employed to detect cell proliferation. Cell apoptosis was determined by flow cytometry at 24, 48, and 72 hours after culture. Western blot analysis was employed to detect the expressions of NF-κB, angiogenesis-related factors (VEGF, Ang1, and Ang2). RESULTS: Initially, we found that BAY11-7082 inhibited NF-κB expression in a concentration-dependent manner. According to the findings of MTT assay and flow cytometry, we understood that RA-HFLS treated by BAY11-7082 (an inhibitor of NF-κB), the inhibition of NF-κB pathway, suppressed RA-HFLS proliferation and induced RA-HFLS apoptosis in a concentration and time-dependent manner. Furthermore, RA-HFLS treated by BAY11-7082 presented decreased VEGF, Ang1 and Ang2 expressions in a concentration-dependent manner. CONCLUSION: The study concluded that inhibition of NF-κB pathway induced cell apoptosis and suppressed proliferation and angiogenesis of RA-HFLS, which could serve as a novel target in the treatment of RA.
29652202 Effect of sulfasalazine use on the presence of Pneumocystis organisms in the lung among pa 2019 May OBJECTIVE: To evaluate the effect of sulfasalazine (SSZ) on the presence of Pneumocystis jirovecii (P. jirovecii) in the lungs of rheumatoid arthritis (RA) patients. METHODS: We retrospectively studied episodes of suspected P. jirovecii pneumonia (PJP) which were examined for P. jirovecii with polymerase chain reaction (PCR). We employed a test negative design case-control study; the cases were episodes of suspected PJP that were positive for PCR, and the controls were episodes of suspected PJP that were negative for PCR. The odds ratio for the positive PCR result associated with SSZ use was estimated by Firth's logistic regression. RESULTS: Between 2003 and 2017, 36 cases and 83 controls were identified. While none of the cases received SSZ before the episode, 18 of the controls received the drug. In the primary analysis involving all the episodes, SSZ use was negatively associated with PCR positivity (adjusted odds ratio, 0.087; confidence interval, <0.001-0.789). The sensitivity analysis, excluding those who received PJP prophylaxis, showed the same association as the primary analysis (adjusted odds ratio 0.085, 95% CI <0.001-0.790). CONCLUSION: This study demonstrated that SSZ use is associated with the absence of P. jirovecii in the lung, suggesting the preventive efficacy of the drug against PJP.
29392761 Clinical diagnosis of temporomandibular joint arthritis. 2018 Apr Evidence-based clinical diagnostic criteria for temporomandibular joint (TMJ) arthritis are not available. To establish (i) criteria for clinical diagnosis of TMJ arthritis and (ii) clinical variables useful to determine inflammatory activity in TMJ arthritis using synovial fluid levels of inflammatory mediators as the reference standard. A calibrated examiner assessed TMJ pain, function, noise and occlusal changes in 219 TMJs (141 patients, 15 healthy individuals). TMJ synovial fluid samples were obtained with a push-pull technique using the hydroxycobalamin method and analysed for TNF, TNFsRII, IL-1β, IL-1ra, IL-1sRII, IL-6 and serotonin. If any inflammatory mediator concentration exceeded normal, the TMJ was considered as arthritic. In the patient group, 71% of the joints were arthritic. Of those, 93% were painful. About 66% of the non-arthritic TMJs were painful to some degree. Intensity of TMJ resting pain and TMJ maximum opening pain, number of jaw movements causing TMJ pain and laterotrusive movement to the contralateral side significantly explained presence of arthritis (AUC 0.72, P < .001). Based on these findings, criteria for possible, probable and definite TMJ arthritis were determined. Arthritic TMJs with high inflammatory activity showed higher pain intensity on maximum mouth opening (P < .001) and higher number of painful mandibular movements (P = .004) than TMJs with low inflammatory activity. The combination TMJ pain on maximum mouth opening and Contralateral laterotrusion <8 mm appears to have diagnostic value for TMJ arthritis. Among arthritic TMJs, higher TMJ pain intensity on maximum mouth opening and number of mandibular movements causing TMJ pain indicates higher inflammatory activity.
29854787 Area of Residence and Socioeconomic Factors Reduce Access to Biologics for Rheumatoid Arth 2018 INTRODUCTION: The study aimed to evaluate the influence of socioeconomic factors on rheumatoid arthritis (RA) patients' access to biologics in Romania. METHOD: Cross-sectional data were collected in January 2014 from the Romanian Registry of Rheumatic Diseases (RRRD) comprising all RA patients on biologics from 42 Romanian counties. "Territorial" access to biologics was defined by patients receiving biologics in their home county. A county was "equitable" if <25% of RA patients received biologics outside it. RESULTS: The RRRD included 4507 RA patients aged 56.7 ± 12.1 years, with a disease duration of 12.1 ± 8.3 years. Urban dwellers (67.8%) had a significantly higher prevalence of territorial biologic access than rural dwellers (83.1% compared to 74.1%; p < 0.001). Gross domestic product (GDP) in 1000 €/capita/county (odds ratio (OR) = 1.224) and number of physicians/1000 inhabitants/county (OR = 2.198) predict territorial access to biologics and also predict the number of territorially treated RA patients. Inequitable counties exhibited significantly lower socioeconomic indicators than equitable counties. CONCLUSION: In Romania, RA patients' access to biologics varies significantly between counties. Urban dwellers and patients living in counties/regions with high living standards are more likely to receive biologics locally than those living in more deprived areas.
29889832 Periodontal disease influences osteoclastogenic bone markers in subjects with and without 2018 BACKGROUND: Periodontal disease (PD) and rheumatoid arthritis (RA) are bone pathologies mediated through immuno-inflammatory mechanisms. The aim of this study was to investigate the serum markers osteopontin (OPN), tumor necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) receptor activator of nuclear factor-kappa B ligand (RANKL) and RANKL/ osteoprotegerin (OPG) ratio and compare them in PD and RA groups. MATERIALS & METHODS: RA (with PD = 19 and without PD = 19), PD (n = 38) and 14 healthy subjects underwent bleeding on probing (BOP) and probing pocket depth (PPD) measurement. PD was defined as PPD measuring ≥5mm registered in ≥3 sites. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. Serum samples were collected from all subjects. OPN, TNFR1, TNFR2 and RANKL were measured by enzyme-linked immunosorbent assays (ELISAs). OPG was measured as part of a multiplex proximity extension assay (PEA). RESULTS: OPN, TNFR1, TNFR2 and RANKL serum levels were the highest in the RA group with PD, while the RA group without PD were comparable to PD subjects only. The RANKL/OPG ratios were comparable between PD group and both RA groups with (p = 0.051) and without PD (p = 0.37). Serum RANKL levels were associated with MBL (p = 0.008) and PPD ≥ 5mm (p = 0.01). CONCLUSION: Peripheral osteoclastogenesis is a feature of periodontal disease with systemic levels of osteoclastogenic markers comparable to the effects observed in rheumatoid arthritis.
29844591 Cystathionine-γ-lyase ameliorates the histone demethylase JMJD3-mediated autoimmune respo 2019 Aug Cystathionine-γ-lyase (CSE), an enzyme associated with hydrogen sulfide (H(2)S) production, is an important endogenous regulator of inflammation. Jumonji domain-containing protein 3 (JMJD3) is implicated in the immune response and inflammation. Here, we investigated the potential contribution of JMJD3 to endogenous CSE-mediated inflammation in rheumatoid arthritis (RA). Upregulated CSE and JMJD3 were identified in synovial fibroblasts (SFs) from RA patients as well as in the joints of arthritic mice. Knocking down CSE augmented inflammation in IL-1β-induced SFs by increasing JMJD3 expression. In addition, CSE(-/-) mice with collagen-induced arthritis (CIA) developed severe joint inflammation and bone erosion. Conversely, overexpressing CSE inhibited JMJD3 expression by the transcription factor Sp-1 and was accompanied by reduced inflammation in IL-1β-treated SFs. Furthermore, JMJD3 silencing or the administration of the JMJD3 inhibitor GSK-J4 significantly decreased the inflammatory response in IL-1β-treated SFs, mainly by controlling the methylation status of H3K27me3 at the promoter of its target genes. GSK-J4 markedly attenuated the severity of arthritis in CIA mice. In conclusion, suppressing JMJD3 expression by the transcription factor Sp-1 is likely responsible for the ability of CSE to negatively modulate the inflammatory response and reduce the progression of RA.
30235736 Clinical and radiologic analysis of on-demand use of etanercept for disease flares in pati 2018 Sep To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we evaluated the efficacy of repeated etanercept (ETN) discontinuation and restarting in rheumatoid arthritis (RA) patients in a case-control study.Thirty-one bDMARD-naive RA patients with moderate to high disease activity received ETN until low disease activity (LDA) was achieved, after which ETN was discontinued. Upon flaring, ETN was readministered with observation every 2 months for 2 years, and radiographically evaluated in comparison with a historical control group treated continuously with ETN. Statistical methods including Fisher exact test, analysis of variance (ANOVA), Kruskal-Wallis test, multiple regression analysis, and Student t test were conducted as appropriate.Thirteen patients with inadequate response to ETN were withdrawn from the study, and 5 had no flare-up after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand to maintain LDA. Multivariate analysis revealed that MTX was significantly correlated with ETN. All 13 patients achieved LDA at final follow-up. Although joint damage progressed in patients using ETN on-demand, structural damage progression in the on-demand group was not significantly different from that in controls.On-demand use of ETN for flaring reduced disease activity but not structural damage in 50% of patients (though not significantly). However, inhibition of joint damage was achieved in 50% of patients after 2 years, supporting on-demand use of ETN as a treatment option for patients with RA who cannot afford bDMARD or targeted synthetic DMARD therapy.
29523837 Association of nocturnal blood pressure patterns with inflammation and central and periphe 2018 Apr Predictors of adverse cardiovascular outcomes include elevated nighttime systolic blood pressure (SBP) and a non-dipping pattern. We investigated whether these factors correlate with systemic inflammation, cardiovascular risk, and markers of central and peripheral vascular damage in rheumatoid arthritis (RA), a disease characterized by excess cardiovascular risk. Twenty-four-hour ambulatory blood pressure monitoring was applied in patients and controls. Vascular assessments included measurement of arterial stiffness (pulse wave velocity) and carotid atherosclerosis (carotid intima-media thickness). Peripheral vascular resistance was estimated from impedance cardiography. Cardiovascular risk was calculated from the Framingham Heart Study. RA patients exhibited a higher prevalence of non-dipping pattern, elevated nighttime SBP and blunted dipping, compared to controls without cardiovascular comorbidities. Among RA patients, dipping levels correlated with arterial stiffness, and nighttime SBP with all vascular markers and cardiovascular risk. After adjustment for inflammation, the above associations with vascular measures were no longer significant. Plain categorization to dippers and non-dippers did not reveal any differences regarding inflammation, vascular measurements, and cardiovascular risk. However, the combination of a non-dipping profile with high nighttime SBP was accompanied by significantly higher levels of arterial stiffness and cardiovascular risk, compared to non-dippers with normal nighttime SBP; these parameters were similar between the latter group and dippers. Inflammation appears to mediate the observed associations of nighttime SBP and dipping levels with markers of subclinical vascular damage in RA patients. In these patients, the combination of a non-dipping profile with elevated nighttime SBP is accompanied by prominent subclinical vascular impairment and confers the highest cardiovascular risk.
30504445 Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the P 2019 Feb OBJECTIVES: We explored the effects of B-cell directed therapy in subjects at risk of developing autoantibodypositive rheumatoid arthritis (RA), who never experienced inflammatory arthritis before, and explored biomarkers predictive of arthritis development. METHODS: Individuals positive for both anti-citrullinated peptide antibodies and rheumatoid factor but without arthritis were included in a randomised, double-blind, placebo-controlled study to receive a single infusion of 1000 mg rituximab or placebo. RESULTS: Eighty-one individuals received treatment and were followed up for a mean of 29.0 (0-54) months, during which 30/81 (37%) individuals developed arthritis. The observed risk of developing arthritis in the placebo-treated group was 40%, which was decreased by 55% (HR 0.45, 95% CI 0.154 to 1.322) in the rituximab-treated group at 12 months. Rituximab treatment caused a delay in arthritis development of 12 months compared with placebo treatment at the point when 25% of the subjects had developed arthritis (p<0.0001). Erythrocyte sedimentation rate and the presence of anti-citrullinated α-enolase peptide 1 at baseline were significant predictors of arthritis development. CONCLUSIONS: A single infusion of 1000 mg rituximab significantly delays the development of arthritis in subjects at risk of developing RA, providing evidence for the pathogenetic role of B cells in the earliest, prearthritis stage of autoantibody positive RA.
29790294 JAK/STAT Blockade Alters Synovial Bioenergetics, Mitochondrial Function, and Proinflammato 2018 Dec OBJECTIVE: To examine the effects of tofacitinib on metabolic activity, mitochondrial function, and proinflammatory mechanisms in rheumatoid arthritis (RA). METHODS: Ex vivo RA synovial explants and primary RA synovial fibroblasts (RASFs) were cultured with 1 μM tofacitinib. RASF bioenergetics were assessed using an XF24 analyzer, and key metabolic genes were assessed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Mitochondrial function was assessed using specific cell fluorescent probes and by mitochondrial gene arrays. Mitochondrial mutagenesis was quantified using a mitochondrial random mutation capture assay, and lipid peroxidation was quantified by enzyme-linked immunosorbent assay (ELISA). The effect of tofacitinib on spontaneous release of proinflammatory mediators from RA whole tissue synovial explants was quantified by ELISAs/MSD multiplex assays, and metabolic markers were quantified by RT-PCR. Finally, RASF invasion, matrix degradation, and synovial outgrowths were assessed by transwell invasion/Matrigel outgrowth assays and ELISA. RESULTS: Tofacitinib significantly decreased mitochondrial membrane potential, mitochondrial mass, and reactive oxygen species production by RASFs and differentially regulated key mitochondrial genes. Tofacitinib significantly increased oxidative phosphorylation, ATP production, and the maximal respiratory capacity and the respiratory reserve in RASFs, an effect paralleled by a decrease in glycolysis and the genes for the key glycolytic enzymes hexokinase 2 (HK2), glycogen synthase kinase 3α (GSK-3α), lactate dehydrogenase A, and hypoxia-inducible factor 1α. Tofacitinib inhibited the effect of oncostatin M (OSM) on interleukin-6 (IL-6) and monocyte chemotactic protein 1 and reversed the effects of OSM on RASF cellular metabolism. Using RA whole tissue synovial explants, we found that tofacitinib inhibited the key metabolic genes for glucose transporter 1, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, 3'-phosphoinositide-dependent protein kinase 1, HK2, and GSK-3α, the proinflammatory mediators IL-6, IL-8, IL-1β, intercellular adhesion molecule 1, vascular endothelial growth factor, and TIE-2, and RASF outgrowth from synovial explants, RASF invasion, and matrix metalloproteinase 1 activity. CONCLUSION: This study demonstrates that JAK/STAT signaling mediates the complex interplay between inflammation and cellular metabolism in RA pathogenesis.
30559453 Extracellular vesicles are associated with the systemic inflammation of patients with sero 2018 Dec 17 Patients with rheumatoid arthritis (RA) and autoantibodies, such as rheumatoid factor and those against cyclic citrullinated peptides, are designated as seropositive and have a more severe disease with worse prognosis than seronegative RA patients. Understanding the factors that participate in systemic inflammation, in addition to articular commitment, would allow better treatment approaches for prevention of RA comorbidities and disease reactivation. We evaluated whether monocyte subsets and extracellular vesicles (EVs) could contribute to this phenomenon. Seropositive patients had higher levels of proinflammatory cytokines than those of seronegative patients and healthy controls (HCs); however, this systemic inflammatory profile was unrelated to disease activity. High frequencies of circulating EVs positive for IgG, IgM, CD41a, and citrulline, together with altered counts and receptor expression of intermediate monocytes, were associated with systemic inflammation in seropositive patients; these alterations were not observed in seronegative patients, which seem to be more similar to HCs. Additionally, the EVs from seropositive patients were able to activate mononuclear phagocytes in vitro, and induced proinflammatory cytokines that were comparable to the inflammatory response observed at the systemic level in seropositive RA patients; therefore, all of these factors may contribute to the greater disease severity that has been described in these patients.
30129776 Systematic review and network meta-analysis: effect of biologics on radiographic progressi 2018 Oct AIM: To evaluate the comparative effectiveness of biologics in inhibiting radiographic progression among rheumatoid arthritis (RA) patients. MATERIALS & METHODS: Bayesian network meta-analysis of published trials investigating the USA FDA approved biologics treatment in RA patients, using methotrexate (MTX) as the reference comparator. RESULTS: Nine trials met the inclusion criteria for base case analysis. Compared with MTX, most biologics (except golimumab) + MTX had significantly lower rates of radiographic progression at 1 year. Mean difference in radiographic progression rates between MTX monotherapy and biologics + MTX was highest for adalimumab + MTX (-3.8) and lowest for tocilizumab + MTX (-0.7). Inhibition of radiographic progression was sustained. CONCLUSION: Biologics inhibit radiographic progression in patients with RA at 1 year; however, published evidence beyond 1 year is limited.
30342611 Head and Neck Manifestations of Systemic Disease. 2018 Nov Systemic diseases commonly managed by the Internist may have presentations within the head and neck. Awareness of these manifestations, sometimes as the presenting signs or symptoms of systemic disease, may aid the Internist in diagnosis and management. The Otolaryngologist may be helpful in assisting in the evaluation of these patients and in some cases providing targeted symptomatic therapy. Some systemic processes can generate emergent airway events, and early engagement of the otolaryngologist is of value.
29744553 Changes in MiRNA-5196 Expression as a Potential Biomarker of Anti-TNF-α Therapy in Rheuma 2018 Oct In this study, we analysed the expression level of sera circulating miRNA-5196 in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients before and after tumor necrosis factor (TNF)-α therapy as biomarkers predicting positive treatment outcome. We enrolled 10 RA patients, 13 AS patients, and 12 healthy individuals in the study. The expression of miRNA-5196 was measured by real-time polymerase chain reaction before and after anti-TNF-α therapy. Disease activity of RA patients was assessed using disease activity score 28 (DAS28), whereas ankylosing spondylitis DAS (ASDAS) was used in AS patients. MiRNA-5196 expression was significantly higher in patients with RA and AS before TNF-α therapy than in those following anti-TNF-α therapy and healthy controls. Changes in miRNA-5196 expression positively correlated with delta DAS28 or delta ASDAS, respectively, following TNF-α therapy. In contrast, changes in C-reactive protein (CRP) levels in RA and AS patients did not positively correlate with DAS28 or ASDAS changes. Receiver-operating characteristic analysis showed better diagnostic accuracy of miRNA-5196 expression both in RA (area under curve (AUC) = 0.87, p = 0.055) and AS patients (AUC = 0.90, p = 0.050) compared to CRP levels in RA (AUC = 0.75, p = 0.201) and AS patients (AUC = 0.85, p = 0.086) upon biologic therapy treatment. Finding novel biomarkers, including miRNA-5196 which allow to predict and monitor anti-TNF-α response, would be of clinical value especially during the early phase of RA or AS development.
30279454 A novel antimicrobial peptide acting via formyl peptide receptor 2 shows therapeutic effec 2018 Oct 2 In oriental medicine, centipede Scolopendra subspinipes mutilans has long been used as a remedy for rheumatoid arthritis (RA), a well-known chronic autoimmune disorder. However, the molecular identities of its bioactive components have not yet been extensively investigated. We sought to identify bioactive molecules that control RA with a centipede. A novel antimicrobial peptide (AMP) (scolopendrasin IX) was identified from Scolopendra subspinipes mutilans. Scolopendrasin IX markedly activated mouse neutrophils, by enhancing cytosolic calcium increase, chemotactic cellular migration, and generation of superoxide anion in neutrophils. As a target receptor for scolopendrasin IX, formyl peptide receptor (FPR)2 mediates neutrophil activation induced by the AMP. Furthermore, scolopendrasin IX administration strongly blocked the clinical phenotype of RA in an autoantibody-injected model. Mechanistically, the novel AMP inhibited inflammatory cytokine synthesis from the joints and neutrophil recruitment into the joint area. Collectively, we suggest that scolopendrasin IX is a novel potential therapeutic agent for the control of RA via FPR2.
30587175 RHAMM induces progression of rheumatoid arthritis by enhancing the functions of fibroblast 2018 Dec 26 BACKGROUND: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune joint disease. Fibroblast-like synoviocytes (FLS) produce inflammatory cytokines and are involved in the migration and invasion of panuus tissue, which leads to the destruction of joints in RA. Receptor for hyaluronan mediated motility (RHAMM), is known to be one of the important receptors for hyaluronic acid. It has the ability to regulate migration of fibrocytes and infiltration of inflammatory cells. Here,we explored the mechanisms of RHAMM in RAFs. METHODS: Quantitative PCR and western blot were performed to test the expression of RHAMM in synoviocytes of RA patients and osteoarthritis (OA) controls. Collagen antibody-induced arthritis (CAIA) was used to investigate the RHAMM expression in mouse synovial issues. RHAMM siRNA was used to detect the function of RHAMM in FLS. RESULTS: RA-FLS has a significantly higher expression of RHAMM than OA-FLS. Expression of RHAMM in joint synovial tissue was markedly increased in the CAIA mice compared with the controls. RHAMM silencing using SiRNA was not only decreased the production of IL-6 and IL-8, but also inhibited the migration and invasion of RA-FLS. CONCLUSIONS: RHAMM has an important role in the FLS induced modulation of inflammation and destruction of joints in RA.
30511229 Validity and interpretability of the QuickDASH in the assessment of hand disability in rhe 2019 May Objective of this study is to evaluate the construct validity and the interpretability of the shortened Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) in the assessment of rheumatoid arthritis (RA) hand disability. Consecutive RA patients were assessed through the QuickDASH and other function and disease activity indices, respectively, the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Recent-Onset Arthritis Disability questionnaire (ROAD). For each patient were evaluated the tender and swollen 28-joints counts. Interpretability was defined determining cut-off points of impairment in accordance to the Simplified Disease Activity Index (SDAI) definition of disease activity states. A total of 440 patients (89 men and 351 women, mean age of 57.0 ± 12.7 years) were enrolled. Following the SDAI definition, 98 patients (22.3%) resulted in REM, 115 subjects (26.1%) in LDA, 74 patients (16.8%) in MDA, and 153 subjects (34.8%) in HDA. Mean QuickDASH differed significantly between patients classified as remission (REM), low disease activity (LDA), moderate disease activity (MDA), or high disease activity (HDA) (p < 0.001). High correlations were found comparing QuickDASH to composite indices of disease activity and of physical health function: of special interest are the correlations between the comparable dimension of the QuickDASH and the ROAD Upper Extremity Function (rho = 0.876; p < 0.001). The cut-off points for functional categories (SDAI categories as external criterion) resulted: no impairment ≤ 13, 13 < low impairment ≤ 18.5, 18.5 < moderate impairment ≤ 31.5, and high impairment > 31.5. QuickDASH is useful in clinical practice, for its ease of administration, and positively correlates with the disease activity. It may be a surrogate for evaluating upper extremity impairment, disability index and disease control in RA patients.
30466715 Applicability of trials in rheumatoid arthritis and osteoarthritis: A systematic review an 2019 Jun OBJECTIVES: To evaluate whether elderly people and women are adequately represented in randomized controlled trials (RCT) in rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Four systematic searches in MEDLINE yielded RCT in RA and OA on any intervention published in 2016 and 2017 and population-based studies (PBS) in RA and OA published between 2013 and 2017. Random effects meta-analyses estimated the pooled proportion of elderly people (defined as being ≥ 65 years old), the mean age, its standard deviation (SD), and the proportion of women stratified by disease (RA and OA) and study type (RCT and PBS). Stratified estimates were subsequently compared. RESULTS: 265 RCT comprising 51,240 participants and 53 PBS comprising 523,630 participants were included. In both RA and OA, RCT included lower proportions of elderly people than PBS: RA -0.18 (95% confidence interval -0.22 to -0.13); OA -0.20 (-0.30 to -0.09); had lower mean ages: RA -5.2 years (-6.8 to -3.5); OA -4.7 years (-7.5 to -2.0); and smaller SD: RA -1.9 years (-2.6 to -1.3); OA -2.7 years (-4.2 to -1.2); (all comparisons: p ≤ 0.001). Proportions of women were comparable in RCT compared to PBS in both RA and OA. CONCLUSIONS: While women are adequately represented in RA and OA trials, the elderly are underrepresented, probably limiting applicability of current evidence to this growing subgroup. It is urgent to improve the inclusion of elderly people in clinical trials and study age as a determinant for outcome.
30148443 Reduced quality of life impacts knowledge and type of informed consent in rheumatoid arthr 2019 Mar OBJECTIVES: Informed consent (IC) is an ethical process required in human subject research. Primary objective was to determine factors associated to poor knowledge of IC content (PK) in patients from an early rheumatoid arthritis cohort. METHODS: The cohort initiated in 2004, had assistant and research purposes (NCT03389711). At inclusion, each patient selected 1 of 4 options of the IC form; options ranged from broad consent (patient's data could be used for research) to patient denied to have his/her data used. Once enrolled, patients had regular assessments. Up to May 2017, the cohort had 146 patients with (median, range) follow-up of 8.8 years, (4.3-11.9) and 143 agreed to participate in a cross-sectional study; patients had scheduled rheumatic evaluations; additionally, a social worker applied a questionnaire that addressed objective described. PK was established by the borderline performance method. Multiple regression models were applied to investigate factors associated to PK. RESULTS: At cohort inclusion, patients were primarily middle-aged (38.3±13.1 years) females (88.9%), with high disease activity (DAS28: 5.8 [4.6-6.8)] and poor quality of life (SF-36: 42 [29-59]). All the patients gave broad IC. At study entry, 35-41.3% of them had PK; longer follow-up and lower SF-36 scores at cohort inclusion, were associated to PK. In addition, 79.7% of the patients had DAS28-remission and 67.1% had SF-36 scores within normal range; interestingly, only 49% of the patients considered broad re-consent and these patients had poorer SF-36 emotional subscore than their counterpart (79±23 vs. 87±1, p=0.02). CONCLUSIONS: Poor quality of life impacts the autonomy of RA patients.