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ID PMID Title PublicationDate abstract
21467568 Increasing power of genome-wide association studies by collecting additional single-nucleo 2011 Jun Genome-wide association studies (GWASs) have been effectively identifying the genomic regions associated with a disease trait. In a typical GWAS, an informative subset of the single-nucleotide polymorphisms (SNPs), called tag SNPs, is genotyped in case/control individuals. Once the tag SNP statistics are computed, the genomic regions that are in linkage disequilibrium (LD) with the most significantly associated tag SNPs are believed to contain the causal polymorphisms. However, such LD regions are often large and contain many additional polymorphisms. Following up all the SNPs included in these regions is costly and infeasible for biological validation. In this article we address how to characterize these regions cost effectively with the goal of providing investigators a clear direction for biological validation. We introduce a follow-up study approach for identifying all untyped associated SNPs by selecting additional SNPs, called follow-up SNPs, from the associated regions and genotyping them in the original case/control individuals. We introduce a novel SNP selection method with the goal of maximizing the number of associated SNPs among the chosen follow-up SNPs. We show how the observed statistics of the original tag SNPs and human genetic variation reference data such as the HapMap Project can be utilized to identify the follow-up SNPs. We use simulated and real association studies based on the HapMap data and the Wellcome Trust Case Control Consortium to demonstrate that our method shows superior performance to the correlation- and distance-based traditional follow-up SNP selection approaches. Our method is publicly available at http://genetics.cs.ucla.edu/followupSNPs.
21253758 Retinal functional changes measured by frequency-doubling technology in patients treated w 2011 May BACKGROUND: Antimalarial drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) are mainly used in the treatment of rheumatologic diseases, and their use may be associated with irreversible retinal toxicity. Previous studies indicate early paracentral visual field loss (Humphrey 10-2) in patients taking HCQ". These paracentral defects appear before changes in other clinical parameters as visual acuity and fundoscopy. The mechanism of CQ toxicity remains unclear. It was reported that toxic doses of CQ administered for as long as 4.5 years to Rhesus monkeys caused an initial dramatic effect on ganglion cells, followed later by photoreceptors and RPE degeneration. The purpose of this study is to explore early retinal functional changes measured by frequency-doubling technology (FDT) in patients treated with hydroxychloroquine (HCQ). METHODS: Forty-eight eyes of 48 subjects treated with hydroxychloroquine (HCQ), with no signs of retinal toxicity, and 36 eyes of 36 age and sex-matched healthy subjects were enrolled in this cross-sectional, prospective, observational, case control study. Functional testing included frequency-doubling Humphrey-matrix perimetry (FDP), white-on-white Humphrey visual field perimetry (HFA), using the 24-2 and 10-2 threshold programs, multifocal electroretinogram (mfERG, Veris 4.9) and low contrast sensitivity (CS) measurement. RESULTS: FDP mean deviation (MD) was found to be significantly reduced in HCQ-treated patients compared to controls both in the 24-2 (-1.38 ± 2.41 dB vs 0.21 ± 1.83 dB, p < 0.01) and in the 10-2 program (-0.97 ± 2.88 dB vs 0.15 ± 1.72 dB, p < 0.01). FDP pattern standard deviation (PSD) was found to be significantly worse in HCQ-treated patients compared to controls both in the 24-2 (2.70 ± 0.65 dB vs 2.41 ± 0.31 dB, p < 0.01 and in the 10-2 program (2.86 ± 0.48 dB vs 2.48 ± 0.39 dB, p < 0.01). HFA PSD and CS was also significantly reduced in HCQ patients, while response amplitude densities (RAD) were similar between patients and controls. A statistically significant difference in the ratio of the 5°-10° RAD and the 0°-2.5° RAD (0.31 ± 0.08 vs 0.36 ± 0.07 respectively, p < 0.05) was found between groups. CONCLUSION: Frequency doubling perimetry could be useful to detect early retinal impairment in patients treated with hydroxychloroquine.
21703545 TNF alpha antagonist therapy and safety monitoring. 2011 May OBJECTIVES: To develop and/or update fact sheets about TNFα antagonists treatments, in order to assist physicians in the management of patients with inflammatory joint disease. METHODS: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several experts and the overall process was coordinated by three experts. RESULTS: Several topics of major interest were selected: contraindications of TNFα antagonists treatments, the management of adverse effects and concomitant diseases that may develop during these therapies, and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA and SpA, initiation and monitoring of TNFα antagonists treatments, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information. CONCLUSION: These TNFα antagonists treatments fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on these therapies. They will be available continuously at www.cri-net.com and updated at appropriate intervals.
22401676 The Exeter femoral stem continues to migrate during its first decade after implantation: 1 2012 Apr BACKGROUND: Due to its collarless, double-tapered polished design, the Exeter femoral stem is known to migrate distally in the first 5 years after implantation. However, its long-term migration pattern has not been investigated. PATIENTS AND METHODS: 39 consecutive patients (41 total hip arthroplasties) received a cemented Exeter stem and had prospective clinical and RSA follow-up. Patients were evaluated postoperatively at 6, 12, 26, and 52 weeks, and annually thereafter. Short-term results have been reported. In this study, the mean length of follow-up was 9.4 years (SD 3.2 years). No patients were lost to follow-up. 15 patients died during follow-up. RESULTS: No stems were revised. In 4 stems, fractures of the cement mantle were noted within the first 3 postoperative years. In 3 stems, this resulted in a complete circumferential cement mantle discontinuity. For the 37 well-performing stems, continuous but small migration was measured between 2 and 12 years of follow-up. Continued subsidence of 0.08 mm/year (95% CI: 0.05-0.12, p < 0.001) was seen in combination with continued rotation in retroversion of 0.07°/year (95% CI: 0.02-0.12, p = 0.01). At 10 years of follow-up, mean subsidence was 2.1 (SD 1.2) mm and mean retroversion was 1.8° (SD 2.0). Two-thirds of this occurred during the first 2 postoperative years. In the 3 stems with a complete circumferential cement fracture, a sudden and disproportionately high increase in subsidence was measured in the time period of occurrence. INTERPRETATION: The Exeter femoral stem continues to migrate during the first decade after implantation. Absolute stability is not required for good long-term survival if this is compatible with the design of the implant.
23216663 Increased incidence of squamous cell carcinoma of the skin after long-term treatment with 2014 Jan BACKGROUND: Auto-immune inflammatory rheumatic diseases (AIRD) are often successfully treated with the immunosuppressant azathioprine for years. Treatment with azathioprine has been proven to increase the risk of non-melanoma skin cancer (NMSC) in transplant patients and possibly in patients with inflammatory bowel disease as well. Little is known about the risk of NMSC in AIRD patients treated with azathioprine. OBJECTIVES: The aim of this study is to determine the incidence of NMSC in patients with AIRD treated with azathioprine for at least 1 year, as compared with the general Dutch population. METHODS: Data were extracted from a historical cohort of patients with AIRD in a tertiary care centre. We compared the incidence to an age-matched control population and analysed risk factors for NMSC with univariate logistic regression. RESULTS: Fifty-nine patients were analysed. No patients were diagnosed with basal cell carcinoma and four patients with a single squamous cell carcinoma (SCC). Patients with SCC had a higher cumulative dose of azathioprine (≥ 500 g: OR 30.0 [95% CI 2.6-345.1]) and longer treatment duration (≥ 11 years: OR 13.5 [95% CI 1.3-143.6]). The risk of SCC compared with the general Dutch population was increased (standardized incidence ratio of 16.0 [95% CI 0.3-31.7]). CONCLUSIONS: In this cohort of patients with AIRD treated with azathioprine for at least 1 year, the risk of SCC was increased, as compared with the general population. An individual cumulative dose of at least 500 g azathioprine and a treatment duration of at least 11 years were quantified as risk factors.
21830840 Randomized controlled trials of COX-2 inhibitors: an analysis of doses used and trends ove 2011 Sep 1 BACKGROUND: Naproxen, ibuprofen and diclofenac are frequently used as comparators in randomized controlled trials (RCTs) on the safety and efficacy of cyclooxygenase (COX)-2 inhibitors. Different comparator doses may influence the results of RCTs. It has been hypothesized that RCTs of COX-2 inhibitors where different doses were administered resulted in different conclusions about the cardiovascular safety of COX-2 inhibitors. High comparator doses may let COX-2 inhibitors look better in terms of safety, while low comparator doses may result in the opposite. OBJECTIVE: The aim of the study was to compare doses of COX-2 inhibitors and comparator drugs used in RCTs, and to investigate dose changes over time. STUDY DESIGN AND METHODS: We searched the Cochrane Central Register of Controlled Trials, The Cochrane Library for published Cochrane reviews, Clinicaltrials.gov and PubMed, for RCTs between 1995 and 2009 in which celecoxib or rofecoxib were compared with naproxen, ibuprofen or diclofenac. All articles labelled as RCTs mentioning rofecoxib or celecoxib and one or more of the comparator drugs in the title and/or abstract were included. We extracted information on doses of both non-selective NSAIDs and selective COX-2 inhibitors used in the RCTs, and study year. The Mann-Whitney test was used to compare the difference in median dose in rofecoxib and celecoxib RCTs. Linear regression was performed to evaluate trends in dosage over time. For comparisons between COX-2-inhibitors, celecoxib trials after the 2004 market withdrawal of rofecoxib were excluded. RESULTS: Median defined daily dose (DDD) of celecoxib (2.00) was higher than the median DDD of rofecoxib (1.00; p < 0.001), whereas non-selective NSAID doses were comparable in rofecoxib (2.00) and celecoxib (2.00; p = 0.988) studies. In both groups, the non-selective NSAID doses decreased over time (B [regression coefficient] = -0.07; p = 0.28, and B = -0.054; p = 0.09, respectively). In contrast, the DDDs of rofecoxib increased slightly over time (B = 0.037; p = 0.28), whereas the celecoxib DDDs decreased over time (B = -0.081; p = 0.09). In due course, the contrasts between DDDs of COX-2 inhibitors and non-selective NSAIDs converged, both in rofecoxib and celecoxib RCTs; therefore, doses have become more comparable in recent years because of differences in steepness of two decreasing dose trends in the case of celecoxib, and opposing dose trends in the case of rofecoxib. CONCLUSIONS: Although the dose trends over time differed for RCTs comparing rofecoxib and celecoxib with diclofenac, ibuprofen or naproxen, the results of our study do not support the hypothesis that dose trends influenced the decision to continue marketing celecoxib after the withdrawal of rofecoxib because the overall median DDD of celecoxib was substantially higher than the median DDD of rofecoxib, while non-selective NSAID DDDs were comparable.
21029771 Extracts of Arisaema rhizomatum C.E.C. Fischer attenuate inflammatory response on collagen 2011 Jan 27 AIM OF THE STUDY: Arisaema rhizomatum C.E.C. Fischer (ARCF), called as "Xuelijian", a local herb just growing in China, has been used as a traditional ethnic Chinese medicine for long because of its remarkable activity to alleviate pain and inflammation for patients suffering from rheumatism among the people with weak side-effect. However, rare study on the anti-arthritic activity of ARCF has been reported in vivo. The aim of this study is to investigate the protective effect of the herb on collagen-induced arthritis in mice and explore the potential immunological mechanisms. MATERIALS AND METHODS: CIA was induced in male BALB/c mice by been subcutaneously injected type II bovine collagen (CII) for twice. The combined MeOH extract (ME) of ARCF rhizome was successively partitioned into four fractions with petroleum ether (PE), ethyl acetate (EE), n-butyl alcohol (n-BE) and water (WE). After the second collagen immunization, mice were administered orally with different doses of ME, EE and n-BE (ME 130, 261, 522 mg kg(-1); EE 10.2, 20.4, 40.8 mg kg(-1); n-BE 52, 104, 208 mg kg(-1)) every other day for 3 weeks. The progression of edema of paws and knee joints was inspected by using a vernier calliper every 3 days from the 10th day after the first injection to the end of the experiment. The spleen index was measured and the knee joint destruction was observed by pathological sections. Levels of inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-33 (IL-33 or IL-1F11) and rheumatoid factor (RF) in serum were measured by ELISA. RESULTS: Administration of ME, EE and n-BE significantly suppressed paws and joints swelling and reduced the spleen indexes. Pathological examination demonstrated that ARCF effectively protected anklebone and cartilage from being eroded versus vehicle-treated mice. Moreover, the serum levels of inflammatory cytokines TNF-α, IL-1β, IL-6, IL-33 and RF were markedly lowered in ARCF treated groups compared with the control group (p<0.05). CONCLUSION: Our studies demonstrate that administration of ARCF is obviously suppressed the progression of CIA. The anti-arthritic effectiveness of ARCF will make the herb a strong candidate for further clinical trials on RA patients.
22923752 Use of adalimumab in refractory non-infectious childhood chronic uveitis: efficacy in ocul 2012 Dec OBJECTIVE: To assess the use of adalimumab in the treatment of refractory non-infectious childhood chronic uveitis. METHODS: A case cohort interventional study was performed on patients with uveitis, who were treated with adalimumab after failure of treatment with a combination of corticosteroids and another immunosuppressant drug. Main outcome measures were (i) stability of vision, (ii) stability of inflammation and (iii) reduction of immunosuppressive load. Adverse events and reasons for stopping adalimumab were noted. RESULTS: Seventeen patients from a single regional centre were included in the study. Nine patients had previously received an anti-TNF agent, and because of inefficacy, all were changed to adalimumab. At 12 months, fewer patients had visual acuity worse than LogMAR 0.4 (18% vs 32% at baseline). Using standardized uveitis nomenclature criteria, at 3 months, 50% of the patients eyes (n = 32) had improved, 16% had stable inflammation and 3% had worsened, whereas 31% were maintained with no anterior chamber cells. Six patients required courses of oral steroids for uveitis. Seven patients received intra- or periocular injections of steroids. Adalimumab treatment was interrupted in one patient because of varicella zoster infection. It was stopped in three patients. Seven (41%) patients reported injection site reactions. CONCLUSION: In this group of children with refractory uveitis, use of adalimumab was associated with improvement in visual acuity and improving or stable ocular inflammation. However, it did not completely obviate the need for systemic or periocular steroid treatment. Prospective randomized controlled trials are required to help determine which subset of patients may benefit from adalimumab and the duration of treatment.
22883323 Avoiding and managing temporomandibular joint total joint replacement surgical site infect 2012 Oct PURPOSE: Surgical site infections (SSIs) are rare complications after total joint replacement (TJR); however, should an SSI occur, the clinical and economic consequences can be significant. A Medicare 5% national sample administrative dataset was used to identify and longitudinally observe patients undergoing total knee TJR for deep infections and revision surgery. In 69,663 patients undergoing elective total knee TJR, 1,400 infections (2%) were identified. The infection incidence within 2 years of implantation was 1.55%. A recent retrospective survey of 2,476 temporomandibular joint (TMJ) alloplastic TJR cases involving 3,368 joints reported that a 1.51% SSI rate occurred over a mean of 6 months postoperatively, with a range of 2 weeks to 12 years. This article discusses approaches to avoid and minimize TMJ TJR SSIs and recommends management options should early or late SSIs occur. MATERIALS AND METHODS: On the basis of a review of the orthopedic SSI literature, this article will discuss TMJ TJR SSI risk, prevention, and management from a number of perspectives, including preoperative patient risk assessment, preincision antibiotic prophylaxis, anesthesia and skin preparation protocols, intraoperative surgical technique and duration of surgery, and postoperative antibiotic and follow-up regimens. RESULT: Ways to avoid and manage potential risks for SSI in TMJ TJR cases are recommended. The diagnostic criteria and management protocols for both early- and late-occurring SSIs after TMJ TJR are recommended. CONCLUSIONS: The risk of SSI after TMJ TJR can be decreased with appropriate consideration to preoperative patient risk assessment; properly timed antibiotic prophylaxis; and intraoperative, postoperative, and postdischarge attention to detail.
22575069 Subgroups of Sjögren syndrome patients according to serological profiles. 2012 Aug Sjögren Syndrome (SS) is a systemic, autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands. Different clinical associations have been described for each of the diverse autoantibodies found in SS patients. Antibodies directed against the Ro/La ribonucleoprotein complexes have been correlated with younger age, more severe dysfunction of the exocrine glands and a higher prevalence of extraglandular manifestations. Anti-nuclear antibodies and rheumatoid factors have been associated to extraglandular manifestations and an active immunological profile, while cryoglobulins are markers of more severe disease and correlate to lymphoma development and death. Antibodies to cyclic citrullinated peptides are scarce in SS and have been linked in some cases to the development of non-erosive arthritis. Furthermore, the presence of anti-mitochondrial antibodies and anti-smooth muscle antibodies in the sera of primary SS patients is considered indicative of primary biliary cirrhosis and autoimmune hepatitis, respectively. In addition, anti-centromere antibodies have been associated with a clinical phenotype intermediate between primary SS and systemic sclerosis, while antibodies against carbonic anhydrase have been related to renal tubular acidosis. Finally, an association of anti-muscarinic antibodies with cytopenias and a higher disease activity has also been described in primary SS. In conclusion, although not all of the above mentioned antibodies are useful for predicting distinct patient subgroups in SS, knowledge of the clinical associations of the different autoantibody specificities encountered in SS can advance our understanding of the disease and improve patient management.
22908198 PlGF: a multitasking cytokine with disease-restricted activity. 2012 Aug 1 Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family that also comprises VEGF-A (VEGF), VEGF-B, VEGF-C, and VEGF-D. Unlike VEGF, PlGF is dispensable for development and health but has diverse nonredundant roles in tissue ischemia, malignancy, inflammation, and multiple other diseases. Genetic and pharmacological gain-of-function and loss-of-function studies have identified molecular mechanisms of this multitasking cytokine and characterized the therapeutic potential of delivering or blocking PlGF for various disorders.
22833479 Use of a disease risk score to compare serious infections associated with anti-tumor necro 2012 Oct OBJECTIVE: To evaluate whether rates of serious infection with anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients differ in magnitude by specific drugs and patient characteristics. METHODS: Among new nonbiologic disease-modifying antirheumatic drug users enrolled in Medicare and Medicaid or a large US commercial health plan, we created and validated a person-specific infection risk score based on age, demographics, insurance type, glucocorticoid dose, and comorbidities to identify patients at high risk for hospitalized infections. We then applied this risk score to new users of infliximab, etanercept, and adalimumab and compared the observed 1-year rates of infection to one another and to the predicted infection risk score estimated in the absence of anti-TNF exposure. RESULTS: Among 11,657 RA patients initiating anti-TNF therapy, the observed 1-year rate of infection was 14.2 infections per 100 person-years in older patients (age ≥65 years) and 4.8 in younger patients (age <65 years). There was a relatively constant rate difference of ~1-4 infections per 100 person-years associated with anti-TNF therapy across the range of the infection risk score. Infliximab had a significantly greater adjusted rate of infection compared to etanercept and adalimumab in both high- and lower-risk RA patients. CONCLUSION: The rate of serious infections for anti-TNF agents was incrementally increased by a fixed absolute difference irrespective of age, comorbidities, and other factors that contributed to infections. Older patients and those with high comorbidity burdens should be reassured that the magnitude of their incremental risk with anti-TNF agents is not greater than for lower-risk patients.
22705192 The effects of Kv1.3 and IKCa1 potassium channel inhibition on calcium influx of human per 2013 Mar OBJECTIVE: The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx during lymphocyte activation and present a possible target for selective immunomodulation. DESIGN: Case-control study. SUBJECTS AND METHODS: We took peripheral blood samples from 10 healthy individuals and 9 recently diagnosed rheumatoid arthritis (RA) patients receiving no anti-rheumatic treatment. We evaluated calcium influx kinetics following activation in CD4, Th1, Th2 and CD8 cells applying a novel flow cytometry approach. We also assessed the sensitivity of the above subsets to specific inhibition of the Kv1.3 and IKCa1 potassium channels. RESULTS: The peak of calcium influx in lymphocytes isolated from RA patients is reached more rapidly, indicating that they respond more quickly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. No difference was detected between Th1 and Th2 or CD4 and CD8 cells in the sensitivity to IKCa1 channel inhibition among lymphocytes of RA patients. However, specific inhibition of the Kv1.3 channel acts differentially on calcium influx kinetics in RA lymphocyte subsets. Th2 and particularly CD8 cells are inhibited more dominantly than Th1 and CD4 cells. CONCLUSION: The inhibition of Kv1.3 channels does not seem to be specific enough in peripheral RA lymphocytes, since anti-inflammatory Th2 cells are also affected to a noteworthy extent.
22328069 β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice. 2012 Jul OBJECTIVE: The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17-dependent inflammatory arthritis developed after dectin 1-mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process. METHODS: SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly, and organs were assessed for pathologic features. Anti-IL-23 monoclonal antibodies were injected into curdlan-treated SKG mice. CD4+ T cells were transferred from curdlan-treated mice to SCID mice, and sera were analyzed for autoantibodies. RESULTS: After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle, and sacroiliac joint arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell- and IL-23-dependent and were transferable to SCID recipients with CD4+ T cells. SpA was associated with collagen- and proteoglycan-specific autoantibodies. CONCLUSION: Our findings indicate that the SKG ZAP-70W163C mutation predisposes BALB/c mice to SpA, resulting from innate and adaptive autoimmunity, after systemic β-glucan or mannan exposure.
21234630 Prevalence of IgA class antibodies to cyclic citrullinated peptide (anti-CCP) in patients 2011 Mar This study aims to determine the prevalence and clinical significance of anti-CCP isotype IgA in a population of patients with primary Sjögren's syndrome (pSS). Sixty-two patients diagnosed according to the USA-European classification criteria for pSS were examined two to four times during a 60.4-month follow-up, and clinical and laboratory data were registered prospectively. Antibodies against cyclic citrullinated peptides (anti-CCP) isotype IgG and IgA were determined in serum samples by an immunofluorescence ELiA™ system. Healthy individuals and patients with rheumatoid arthritis (RA) with matching sex and age served as controls. The serum level of anti-CCP IgA was higher in pSS patients than healthy individuals (2.37 versus 1.37 EU/ml; p < 0.0001), and lower than matching patients with RA (2.37 versus 6.51 EU/ml; p < 0.0001). Using a cutoff for anti-CCP IgA at 4.12 EU/ml, 8.1 % pSS patients had a positive test compared to 26.7% of patients with RA. Positive test for anti-CCP IgG was demonstrated in 4.8% pSS patients. There were no significant differences between demographic and serological variables in pSS patients with positive versus negative anti-CCP IgA. There was significantly more pSS patients with cutaneous vasculitis in the anti-CCP IgA-positive population, however (40.0% versus 3.5%; p = 0.030), and there was a nonsignificant trend of lower unstimulated whole saliva collection (USWC) in the anti-CCP IgA-positive patients. There were no correlations between arthritis and anti-CCP IgG and IgA. This is the first study on the prevalence of anti-CCP isotype IgA in patients with pSS, demonstrating that anti-CCP isotype IgA is moderately increased in patients with pSS but lower than the prevalence in patients with RA. The presence of IgA and IgG anti-CCP isotypes were not associated with arthritis or other clinical manifestations in pSS patients. We demonstrated an association of anti-CCP IgA to cutaneous vasculitis.
22236091 Disability outcomes and dose escalation with etanercept, adalimumab, and infliximab in rhe 2012 Apr INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease that if left untreated may substantially impair physical functioning. Etanercept, infliximab, and adalimumab are tumor necrosis factor (TNF) blockers whose FDA-approved indications in the US include moderate to severe RA. TNF-blocker dose escalation has been well documented in the literature; however, the comparative effectiveness of these agents remains uncertain. OBJECTIVE: To compare the effectiveness and dose escalation rates of etanercept, adalimumab, and infliximab in US community settings. We hypothesized that etanercept would be equivalent to infliximab and adalimumab in patient-reported disability 9-15 months after therapy initiation, and that fewer etanercept patients would experience dose escalation. METHODS: This is a retrospective analysis of the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). Adult patients with no biologic use 6 months before TNF-blocker initiation (index) and with Health Assessment Questionnaire Disability Index (HAQ-DI) scores at index and 9-15 months after index were analyzed (218 etanercept, 93 infliximab, and 40 adalimumab). RESULTS: HAQ-DI change scores at 9-15 months did not differ by treatment (-0.12, -0.10, and -0.08 points for etanercept, infliximab, and adalimumab, respectively; p = 0.52). Dose increases were observed in 1.4% of etanercept, 10.8% of infliximab (p < 0.001), and 12.5% of adalimumab patients (p = 0.004). HAQ-DI change was associated with pre-index HAQ-DI score (p < 0.0001) and disease duration (p = 0.001). CONCLUSIONS: Fewer etanercept patients escalated dose than infliximab or adalimumab patients, but improvements in functional disability were similar. These differences may have been influenced by package labeling, mode of administration, or other factors. RA treatment with infliximab and adalimumab in community settings, characterized by dose escalation, did not yield greater disability improvements compared to etanercept, which remained at a relatively stable dose. Uncontrolled treatment selection in this observational design may have influenced outcomes, and prior methotrexate treatment may partly explain disability improvements smaller than typically observed in clinical trials.
21298696 Risk factors for lower extremity fatigue among assembly plant workers. 2011 Mar BACKGROUND: Work-related fatigue of the lower extremities is a known cause of lost productivity and significant employer costs. Common workplace solutions to reduce fatigue levels include anti-fatigue matting, shoe orthoses, or sit/stand work stations. However, assessment of these anti-fatigue measures within the workplace has been limited. METHODS: This was a cross sectional study in an automotive assembly plant on employees with at least 6 months tenure. Subject data were collected via questionnaires including Likert-scale questions to define fatigue severity. Jobs were evaluated for lower extremity ergonomic exposures via videotaping, pedometers, interviews, and industrial engineering records. RESULTS: Lower extremity fatigue at the end of the work day was associated with a higher prevalence of smoking, rheumatoid arthritis, job dissatisfaction, use of shoes with firmer outsoles, and increased time on the job spent standing or walking. Supervisor support and increased time spent on carpet were protective. Lower extremity fatigue that interfered with activities outside of work had additional risk factors including higher BMI, prior diagnosis of osteoarthritis, and increased hours per week spent working. CONCLUSIONS: While these results identify carpet as being protective against lower extremity fatigue, no similar relationship was identified for anti-fatigue mats. No adverse relationship was found between hard surfaces such as concrete and lower extremity fatigue. Given the high costs associated with work-related fatigue, future areas for potential intervention include smoking cessation, specific shoe recommendations, and enhancing psychosocial aspects of work such as supervisor support.
21558138 Elevated circulating CD4+ ICOS+ Foxp3+ T cells contribute to overproduction of IL-10 and a 2011 May In this work, we aimed to investigate the frequency, possible categories and clinical significance of circulating CD4+ ICOS+ FoxP3+ T cells in patients with systemic lupus erythematosus (SLE). The frequency of circulating CD4+ ICOS+ FoxP3+ T cells was analysed by flow-cytometric analysis in 32 SLE patients, 10 rheumatoid arthritis patients and 32 healthy controls. Production of IL-10 and mTGF-β by different CD4+ T-cell populations was determined by intracellular cytokine staining. Plasma levels of IL-10 and TGF-β were determined by enzyme-linked immunosorbent assay (ELISA). The frequency of circulating CD4+ ICOS+ FoxP3+ T cells was significantly increased in SLE patients as compared with control groups. The elevated frequency of CD4+ ICOS+ FoxP3+ T cells had a positive correlation with SLE Disease Activity Index (SLEDAI) scores and serum anti-dsDNA but a negative correlation with serum C3. Additionally, the CD4+ ICOS+ Foxp3+ T cells contained significantly higher percentages of IL-10-producing cells than CD4+ ICOS- Foxp3+ T cells. A significant positive correlation was also observed between the frequency of CD4+ ICOS+ Foxp3+ T cells and the plasma level of IL-10 in SLE patients. In conclusion, an increased frequency of circulating CD4+ ICOS+ Foxp3+ T cells was observed in patients with SLE, suggesting its potential importance in the immunopathogenesis of SLE. Analysis of the CD4+ ICOS+ FoxP3+ T-cell population may be useful for the evaluation of lupus disease severity.
23274440 Hyposalivation in autoimmune diseases. 2013 Dec We have investigated the prevalence of dry mouth among patients with autoimmune diseases other than Sjögren's syndrome. One hundred and forty-four patients, excluding patients with primary Sjögren's syndrome, were enrolled in this study. The volume of saliva secreted was measured with the screening technique for estimation of salivary flow, which uses a filter paper for diagnosing dry mouth. Disturbed salivary secretion was observed in 84 (58.3 %) of the 144 patients. In the case of patients free of Sjögren's syndrome, the prevalence of disturbed salivary secretion differed significantly among the disease groups (P < 0.05), with the prevalence being over 50 % in all disease groups other than the rheumatoid arthritis group and the highest in the systemic sclerosis group. There was significant positive correlation between the number of colored spots and oral visual analog scale score (r = 0.45, P < 0.0001). Autoimmune diseases can be accompanied by salivary gland dysfunction, regardless of the presence/absence of complication by Sjögren's syndrome. In the present study, the screening technique for estimation of salivary flow, which uses a filter paper for diagnosing dry mouth, was shown to be a useful means of detecting salivary gland dysfunction.
21839493 Predictive blood coagulation markers for early diagnosis of venous thromboembolism after t 2011 Dec Pulmonary embolism development may be prevented if asymptomatic venous thromboembolism (VTE) can be predicted and treated preoperatively or soon after total knee arthroplasty (TKA). The purpose of this study was to evaluate whether asymptomatic VTE can be predicted by blood coagulation markers preoperatively or early after TKA. This prospective single-centre study enrolled 68 patients (6 men, 62 women; mean age: 71 years) who underwent TKA between September 2004 and August 2009. Sixteen-row multidetector computed tomography was performed 4 days before and after surgery for diagnosis of asymptomatic VTE. Blood samples were taken to measure the plasma levels of soluble fibrin monomer complex (SFMC), D-dimer and cross-linked fibrin degradation products by leukocyte elastase (e-XDP) at 4 days preoperatively, and at 1 hour, 1 day and 4 days postoperatively. The preoperative SFMC, D-dimer and e-XDP levels did not differ significantly between the thrombus (n=36) and no-thrombus (n=32) groups. D-dimer and e-XDP levels showed the most significant increases at days 4 and 1, respectively, after surgery in the thrombus group. With cut-off points of 7.5 μg/ml for D-dimer and 8.2 U/ml for e-XDP, the sensitivities were 75% and 75%, and the specificities were 63% and 59%, respectively. By multiple logistic regression analysis, D-dimer at day 4 and e-XDP at day 1 postoperatively were independent markers for early diagnosis of VTE (odds ratio=1.61 and 1.19, P=0.01 and 0.04, respectively). The postoperative occurrence of new asymptomatic VTE may be predicted by D-dimer at day 4 and e-XDP at day 1 after TKA.