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ID PMID Title PublicationDate abstract
26455214 [MEDIUM- AND LONG-TERM EFFECTIVENESS OF THIRD-GENERATION CERAMIC-ON-CERAMIC TOTAL HIP ARTH 2014 Jun OBJECTIVE: To evaluate the medium- and long-term effectiveness of the 3rd-generation ceramic-on-ceramic total hip arthroplasty (THA) for end-stage hip disease. METHODS: A retrospective analysis was made on the clinical data of 142 patients (148 hips) who underwent the 3rd-generation ceramic-on-ceramic THA between May 2001 and May 2005. There were 78 males and 64 females, aged 57.2 years on average (range, 23-81 years). Preoperative diagnosis was avascular necrosis of femoral head in 73 patients (77 hips), degenerative osteoarthritis in 35 patients (36 hips), femoral neck fracture in 18 patients (18 hips), rheumatoid arthritis in 14 patients (15 hips), and septic hip sequelae in 2 patients (2 hips). The preoperative Harris hip score was 58.3 ± 12.9. RESULTS: All incisions healed by first intention without complication. All patients were followed up 8.8 years on average (range, 7-12 years). At the last follow-up, the Harris hip score (92.5 ± 10.2) was significantly higher than that at pre-operation (t = -25.29, P = 0.00). At the last follow-up, there were 4 hips with groin pain, 6 hips with thigh pain. Complications occurred in 6 cases (6 hips), including loosening cups in 2 hips, hip dislocation in 2 hips, ceramic head fracture in 1 hip, and squeaking in 1 hip. The revision rate was 1.35% (3/148). X-ray film showed that acetabular cup loosening in 2 hips, discontinuous radiolucent line in 4 hips, and new bone formation in 88 hips; discontinuous radiolucent line around femoral component was observed in 25 hips, endosteal new bone formation in 95 hips, cortical bone hypertrophy in 2 hips, and femoral component subsidence in 9 hips (less than 2 mm). CONCLUSION: Third-generation ceramic-on-ceramic THA is an effective treatment for end-stage hip disease, and can achieve satisfactory medium- and long-term effectiveness and a high implant survival rate.
24642022 Level of agreement between 2002 American-European Consensus Group and 2012 American Colleg 2014 Mar 19 INTRODUCTION: The aims of this study were to assess agreement between the currently used 2002 American-European Consensus Group (AECG) classification criteria and the new 2012 American College of Rheumatology (ACR) criteria for Sjögren's syndrome (SS) and to identify potential sources of disagreement. METHODS: We studied 105 patients between 2006 and 2013 from the Brittany cohort of patients with suspected SS. AECG criteria were applied using only Schimer's test and unstimulated whole salivary flow (UWSF) to assess objective ocular and oral involvement, since these are the tests most physicians use in clinical practice. Agreement between the two sets of criteria was assessed using Cohen's κ coefficient. RESULTS: Of those studied, 42 patients fulfilled AECG and 35 ACR criteria. Agreement between the two sets was moderate (κ = 0.53). Patients fulfilling ACR but not AECG criteria (n = 8) were significantly younger and had shorter symptom durations, but only three of them had SS in the opinion of the evaluating physician. Xerostomia and xerophthalmia (AECG set only) did not discriminate between patients with and without SS. The use of UWSF in the AECG but not the ACR criteria explained part of the disagreement. The serological item in the ACR set (positive rheumatoid factor and antinuclear antibody ≥1:320 or anti-SSA/SSB positivity) did not result in classification differences compared to anti-SSA/SSB antibody alone (AECG set). Agreement between ocular staining score ≥3 (ACR set) and Schirmer's test ≤5 mm/5 min (AECG set) was very low (κ = 0.14). CONCLUSIONS: Agreement was only moderate between ACR and AECG criteria, suggesting these two sets would not select comparable patient populations. An international consensus about which classification criteria should be used in clinical studies is needed.
24301077 Biowaiver monographs for immediate release solid oral dosage forms: piroxicam. 2014 Feb Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo.
25269884 Determination of Anticyclic Citrullinated Peptide Based on Biotin-Streptavidin-Amplified T 2015 Nov BACKGROUND: A rapid and sensitive time-resolved fluoroimmunoassay (TRFIA) based on the biotin-streptavidin amplification system was developed for the determination of anticyclic citrullinated peptide (anti-CCP). METHODS: Europium-labeled streptavidin derivatives combined with europium and anhydride of diethylene triamine pentaacetic acid were used to label streptavidin, biotin was coupled with rabbit anti-human IgG to form a biotin-anti-human IgG bridge between streptavidin-europium and the anti-CCP antibody in the immunoassay. The anti-CCP assay was carried out by measuring the fluorescence of Eu(3+) -streptavidin at 615 nm. RESULTS: The presented method produced a wide linear range from 0.58 to 9,463 U/ml, while it was only 591.4-18.48 U/ml when using an ELISA kit, and featured a detection limit up to 0.5 U/ml for anti-CCP. The values determined by the biotin-streptavidin-TRFIA and ELISA correlated well (R(2) = 0.8927). The method was applied to determine anti-CCP in serum samples with satisfied recoveries of 96.45-104.63%. CONCLUSION: The assay results obtained by the present method showed that biotin-streptavidin-amplified TRFIA improve the traditional ELISA kit for anti-CCP detection. Therefore, it offers a better alternative immunoassay in rheumatoid arthritis management.
25264908 Down-titration and discontinuation strategies of tumor necrosis factor-blocking agents for 2014 Sep 29 BACKGROUND: Anti-tumor necrosis factor (TNF) agents are effective in treating patients with rheumatoid arthritis (RA), but they are associated with (dose-dependent) adverse effects and high costs. To prevent overtreatment, several trials have assessed the effectiveness of down-titration compared with continuation of the standard dose. OBJECTIVES: To evaluate the benefits and harms of down-titration (dose reduction, discontinuation or disease activity guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) on disease activity, functioning, costs, safety and radiographic damage compared with usual care in patients with RA and low disease activity. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 8, 2013; Ovid MEDLINE (1946 to 8 September 2013); EMBASE (1947 to 8 September 2013); Science Citation Index (Web of Science); and conference proceedings of the American College of Rheumatology (2005 to 2012) and European League against Rheumatism (2005 to 2013). We contacted authors of the seven included studies to ask for additional information on their study; five responded. SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing down-titration (dose reduction, discontinuation, disease activity-guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) to usual care/no down-titration in patients with RA and a low disease activity state. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. MAIN RESULTS: Six RCTs and one CCT (total 1203 participants), reporting anti-TNF down-titration, were included. Three studies (559 participants) reported anti-TNF dose reduction compared with anti-TNF continuation. Five studies (732 participants) reported anti-TNF discontinuation compared with anti-TNF continuation (two studies assessed both anti-TNF discontinuation and dose reduction), and one study assessed disease activity-guided anti-TNF dose tapering (137 participants). These studies include only adalimumab and etanercept; controlled data on other anti-TNF agents are absent. Two studies were available in full text; one was assessed as having low risk of bias and the other high risk. Five studies were available only as one or more abstracts. Because data provided in these abstracts were limited, risk of bias was unclear. Clinical heterogeneity between the trials was high.Dose reduction of anti-TNF (etanercept data only) showed no statistically significant or clinical relevant difference in disease activity score in 28 joints (DAS28) (mean difference (MD) 0.10, 95% confidence interval (CI) -0.11 to 0.31) (scale 0.9 to 8; higher score indicates worse disease activity). The proportion of participants who maintained low disease activity was slightly lower among participants given reduced doses of the anti-TNF agent (risk ratio (RR) 0.87, 95% CI 0.78 to 0.98, absolute risk difference (ARD) 9%). Radiographic outcome was slightly worse, but this was not clinically meaningful, compared with continuation of anti-TNF (MD 0.11, 95% CI 0.08 to 0.14) (scale 0 to 448; higher score indicates greater joint damage). Function was not statistically different between anti-TNF dose reduction and continuation (MD 0.10, 95% CI 0.00 to 0.20) (scale 0 to 3; higher score indicates worse functioning). Reinstalment of anti-TNF after failure of dose reduction showed a 5% risk of persistent flare. Data on numbers of serious adverse events (SAEs) (RR 0.58, 95% CI 0.23 to 1.45, ARD -2%) and withdrawals due to adverse events (AEs) (RR 0.57, 95% CI 0.17 to 1,92, ARD -1%) were inconclusive. Most outcomes were based on moderate quality evidence.Participants who discontinued anti-TNF (adalimumab and etanercept data) had higher mean DAS28 (DAS28-erythrocyte sedimentation rate (ESR): MD 1.10, 95% CI 0.86 to 1.34) and DAS28-C-reactive protein (CRP): MD 0.57 95% CI -0.09 to 1.23) and were less likely to maintain a low disease activity state (RR 0.43, 95% CI 0.27 to 0.68, ARD 40%). Also, radiographic and functional outcomes are worse after anti-TNF discontinuation (MD 0.66, 95% CI 0.63 to 0.69, and MD 0.30, 95% CI 0.19 to 0.41, respectively). Data on numbers of SAEs (RR 1.26, 95% CI 0.61 to 2.63, ARD 2%) and withdrawals due to AEs (RR 0.72, 95% CI 0.23 to 2.24, ARD -1%) were inconclusive. Most outcomes were based on moderate quality evidence.The one study comparing disease activity-guided anti-TNF dose tapering (adalimumab and etanercept data) reported no statistically significant differences in functional outcomes (MD 0.20, 95% CI -0.02 to 0.42). Significantly higher mean disease activity was found among participants with tapered anti-TNF at study end (MD 0.50, 95% CI 0.11 to 0.89). No full text of this trial was available for this review. No other major outcomes were reported. All outcomes were based on low quality evidence. AUTHORS' CONCLUSIONS: We can conclude, mostly based on moderate quality evidence, that non-disease activity guided dose reduction of etanercept 50 mg weekly to 25 mg weekly, after at least three to 12 months of low disease activity, seems as effective as continuing the standard dose with respect to disease activity and functional outcomes, although dose reduction significantly induces minimal and not clinically meaningful differences in radiological progression. Discontinuation (also without disease activity-guided adaptation) of adalimumab and etanercept is inferior to continuation of treatment with respect to disease activity and radiological outcomes and function. Disease activity-guided dose tapering of adalimumab and etanercept seems slightly inferior to continuation of treatment with respect to disease activity, with no difference in function. However the only study investigating this comparison included lower than projected numbers of participants.Caveats of this review are that available data are limited. Also, the heterogeneity between studies and the suboptimal design choices (including absence of disease activity-guided dose reduction and discontinuation and use of superiority designs) limit definitive conclusions. None of the included studies assessed long-term safety and costs, although these factors are specific reasons why clinicians consider lowering the dose or stopping the administration of anti-TNF agents.Future research should include other anti-TNF agents; assessment of disease activity, function and radiographic outcomes after longer follow-up; and assessment of long-term safety, cost-effectiveness and predictors for successful down-titration. Also use of a validated flare criterion, non-inferiority designs and disease activity-guided instead of fixed-dose tapering or stopping would allow researchers to better interpret study findings and generalise the information to clinical practice.
24967519 Medication effectiveness with the use of tumor necrosis factor inhibitors among Texas Medi 2014 Jul BACKGROUND: Adalimumab (Humira [ADA]), etanercept (Enbrel [ETN]), and infliximab (Remicade [IFX]) are tumor necrosis factor (TNF) inhibitors indicated for the treatment of a variety of disorders. While their effectiveness has not been directly compared in a clinical trial, results from the majority of the indirect treatment comparisons suggest comparable efficacy and safety profiles. However, these TNF inhibitor agents differ in administration method and dosing flexibility, which may result in differences in medication use profiles (e.g., adherence, persistence, discontinuation, dose escalation, and switching to a new biologic rheumatoid arthritis drug) and effectiveness in clinical practice.  OBJECTIVE: To estimate the effectiveness of ADA, ETN, and IFX in patients with rheumatoid arthritis (RA) using a validated, claims-based algorithm designed for large retrospective databases. METHODS: Adult (aged 18-63 years) patients diagnosed with RA, and receiving ADA, ETN, or IFX, and insured by Texas Medicaid were included. The index date was the date of the first prescription claim for ADA or ETN or infusion record for IFX with no claim or infusion record of a biologic drug in the preceding 6 months (i.e., biologic naïve). The study time frame was from July 2003 to August 2011, and prescription and medical claims for each subject were analyzed over an 18-month period (6 months pre- and 12 months post-index). Based on a RA medication effectiveness algorithm (Curtis et al. 2011), a RA medication was classified as effective if each of the following 6 criteria were met: (1) high medication adherence (i.e., medication possession ratio [MPR] ≥ 80%, defined as the sum of days' supply for all fills or infusions divided by the number of days in the study period); (2) no switching to (or addition of) new biologic RA drugs; (3) no addition of new nonbiologic RA drugs; (4) no increase in dose or frequency of administration of the RA medication currently evaluated; (5) no more than 1 glucocorticoid (GC) joint injection; and (6) no increase in dose of a concurrent oral GC. Propensity score (PS) matching was employed, and paired tests (i.e., McNemar's) and multivariate conditional logistic regression analysis were used to compare groups. Demographic (i.e., age, gender, race) and clinical (i.e., use of nonbiologic disease-modifying antirheumatic drugs [DMARDs], pain medication use, GC medication use, RA-related and non-RA-related health care visits [i.e., ambulatory and inpatient visits], number of nonstudy RA medications, and comorbidity index) characteristics, including total health care utilization cost at baseline, served as study covariates. RESULTS: After PS matching, 822 patients (n = 274 per group) were included. The majority of the sample (69.2%) was between 45-63 years, female (88%), and Hispanic (53.7%). Results for each TNF inhibitor differed significantly for 2 of the 6 effectiveness criteria (i.e., medication adherence and dose escalation). A significantly higher proportion of patients on IFX were adherent compared with patients on ETN or ADA (38.3% vs. 16.4% and 21.2%, P  less than  0.0001 for both). Adherence rates between ETN and ADA were not significantly different. A significantly higher (P  less than  0.0001) proportion of patients on ETN had no dose escalation compared with patients on ADA or IFX (98.2% vs. 88.7% and 80.3%, P  less than  0.0001). Dose escalation rate was also significantly lower (P = 0.0106) for ADA compared with IFX. The multivariate conditional logistic regression analysis indicated no significant difference in overall effectiveness using the claims-based algorithm among the 3 TNF inhibitors nor any significant relationship between effectiveness and the study covariates.  CONCLUSION: The study results suggest that when using a medication effectiveness algorithm, IFX, ETN, and ADA have comparable effectiveness in patients with RA. Patient adherence to therapy may be higher if given IFX, and patients who receive ETN are less likely to have a dose escalation.
25225673 Mucosal-associated invariant T cell deficiency in systemic lupus erythematosus. 2014 Oct 15 Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. In this study, we examined the level and function of MAIT cells in patients with rheumatic diseases. MAIT cell, cytokine, and programmed death-1 (PD-1) levels were measured by flow cytometry. Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis patients. In particular, this MAIT cell deficiency was more prominent in CD8(+) and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index and 28-joint disease activity score. Interestingly, MAIT cell frequency was significantly correlated with NKT cell frequency in SLE patients. IFN-γ production in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca(2+)/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by α-galactosylceramide-stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In rheumatoid arthritis patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.
24431903 Safe re-administration of tumor necrosis factor-alpha (TNFα) inhibitors in patients with 2014 Jan There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFα) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFα inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFα therapy in patients with TNFα-associated TB. We used data of 1,012 patients with RA or AS treated with TNFα inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-γ releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFα therapy. All patients discontinued TNFα inhibitors with starting the treatment of TB. Eight patients were re-administered TNFα inhibitors due to disease flares and promptly improved without recurrence of TB. TNFα inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.
22923002 Adenosine A2A receptor and TNF-α regulate the circadian machinery of the human monocytic 2013 Feb Morning stiffness and increased symptoms of inflammatory arthritis are among the most common manifestations of rheumatoid arthritis (RA). Tumor necrosis alpha (TNF-α), an important mediator of inflammation in RA, regulates the circadian expression of clock proteins, and adenosine A(2A) receptors (A(2A)R) mediate many of the anti-inflammatory and antirheumatic actions of methotrexate, the cornerstone drug in the treatment of RA. We found that A(2A)R activation and TNF-α activated the clock core loop of the human monocytic THP-1 cell line. We further observed that interleukin (IL)-10, but not IL-12, mRNA expression fluctuates in a circadian fashion and that TNF-α and A(2A)R stimulation combined increased IL-10 expression. Interestingly, TNF-α, but not CGS21680, dramatically inhibited IL-12 mRNA expression. The demonstration that A(2A)R and TNF-α regulate the intrinsic circadian clock in immune cells provides an explanation for both the pathologic changes in circadian rhythms in RA and for the adverse circadian effects of methotrexate, such as fatigue.
24823404 Atypical cutaneous features in adult onset Still's disease. 2014 May Adult onset Still's disease is a rare but potentially serious disease. We present five cases of adult-onset Still's disease seen by us over a period of one year. The patients were all females and 28-39 years of age. Symptoms had been present for 2-6 weeks in three patients. The other two had been on a few years' follow-up for rheumatoid arthritis before the onset of rashes and fever. The patients had persistent erythematous maculopapular eruptions on face, body and extremities, with moderate to severe pruritus and/or a burning sensation that decreased their quality of life. The typical evanescent rash was not observed. High ferritin values were detected in all the patients and total serum IgE was increased in two. All the patients were started on oral prednisolone (0.5-1.0 mg/kg/day), and methotrexate (10-15 mg/week) had to be added in three patients. One patient was started on tocilizumab due to recalcitrant disease and one was lost to follow-up. Further investigation and classification of the various atypical cutaneous findings in adult-onset Still's disease is necessary.
25444344 Subjective and objective screening tests for hydroxychloroquine toxicity. 2015 Feb OBJECTIVE: To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing. DESIGN: Prospective, single-center, case control study. PARTICIPANTS: Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration. METHODS: Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected. MAIN OUTCOME MEASURES: We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group. RESULTS: Fifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 μm) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing. CONCLUSIONS: Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests.
24635564 Insomnia as a risk factor for ill health: results from the large population-based prospect 2014 Apr Insomnia co-occurs with many health problems, but less is known about the prospective associations. The aim of the current study was to investigate if insomnia predicts cumulative incidence of mental and physical conditions. Prospective population-based data from the two last Nord-Trøndelag Health Studies (HUNT2 in 1995–97 and HUNT3 in 2006–08), comprising 24 715 people in the working population, were used to study insomnia as a risk factor for incidence of physical and mental conditions. Insomnia was defined according to the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Insomnia at HUNT2 was a significant risk factor for incidence of a range of both mental and physical conditions at HUNT3 11 years later. Most effects were only slightly attenuated when adjusting for confounding factors, and insomnia remained a significant risk factor for the following conditions in the adjusted analyses: depression [odds ratio (OR): 2.38, 95% confidence interval (CI): 1.91–2.98], anxiety (OR: 2.08, 95% CI: 1.63–2.64), fibromyalgia (OR: 2.05, 95% CI: 1.51–2.79), rheumatoidarthritis (OR: 1.87, 95% CI: 1.29–2.52), whiplash (OR: 1.71, 95% CI: 1.21–2.41), arthrosis (OR: 1.68, 95% CI: 1.43–1.98), osteoporosis (OR:1.52, 95% CI: 1.14–2.01, headache (OR: 1.50, 95% CI: 1.16–1.95,asthma (OR: 1.47, 95% CI: 1.16–1.86 and myocardial infarction (OR:1.46, 95% CI: 1.06–2.00). Insomnia was also associated significantly with incidence of angina, hypertension, obesity and stroke in the crude analyses, but not after adjusting for confounders. We conclude that insomnia predicts cumulative incidence of several physical and mental conditions. These results may have important clinical implications, and whether or not treatment of insomnia would have a preventive value for both physical and mental conditions should be studied further.
23489234 Assessment of interleukin-6 receptor inhibition therapy on periodontal condition in patien 2014 Jan BACKGROUND: Overproduction of interleukin (IL)-6 may play a pathologic role in rheumatoid arthritis (RA) and chronic periodontitis (CP). The present study assesses IL-6 receptor (IL-6R) inhibition therapy on the periodontal condition of patients with RA and CP. METHODS: The study participants were 28 patients with RA and CP during treatment with IL-6R inhibitor, and 27 patients with RA and CP during treatment without IL-6R inhibitor. Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers and immunoglobulin G against periodontopathic bacteria were examined after medication with IL-6R inhibitor for 20.3 months on average (T1) and again 8 weeks later (T2). RESULTS: No differences were observed between the groups in any parameter values at T1, except for serum IL-6 levels. The anti-IL-6R group showed a significantly greater decrease in gingival index, bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and serum levels of IL-6 and matrix metalloproteinase (MMP)-3 from T1 to T2 than the control group (P <0.05). A significant correlation was found between changes in serum anticyclic citrullinated peptide levels and those in PD and CAL in the anti-IL-6R group (P <0.05), whereas both groups exhibited a significant association between changes in serum MMP-3 levels and those in BOP (P <0.05). CONCLUSION: Changes in periodontal and serum parameter values were different between the patients with RA and CP during treatment with and without IL-6R inhibitor.
23632606 Anaesthesia management for acute appendicitis in cases with Sjogren's syndrome accompanyin 2013 Apr 30 Characterised by lymphocytic infiltration of exocrine glands, Sjögren's syndrome (SS) is a chronic autoimmune disease. Symptoms belonging to the involved systems may occur owing to the fact that it affects multiple systems. While rheumatoid arthritis is observed concomitantly, its co-occurrence with autoimmune hepatitis is astonishingly common. Through this case report, we intended to review issues that should be attended to while administering anaesthesia to a patient with SS accompanying autoimmune hepatitis. In the light of literature, we aimed to discuss anaesthesia management to the patient with SS and issues stemming from the clinical features of SS. In SS, the expected issues are liver problems related autoimmune hepatitis and respiratory problems related pulmonary fibrosis. A careful preoperative evaluation, a comprehensive preparation against difficulty in intubation, a selective anaesthesia management in terms of autoimmune hepatitis and close monitoring of postoperative respiration may prevent or decrease possible complications.
23415142 Determination of methotrexate and folic acid by ion chromatography with electrochemical de 2013 Mar 29 A simple and sensitive method was developed for simultaneous determination of methotrexate (MTX) and folic acid (FA) by ion chromatography with electrochemical detection (IC-ECD). Quaternary amine functionalized multi-wall carbon nanotubes (q-MWNTs) modified glassy carbon electrode (GCE) was used as an amperometric sensor to determine MTX and FA. The electrochemical behaviors of MTX and FA at the q-MWNTs/GCE were studied by cyclic voltammetry (CV). Results indicated that this modified electrode exhibited electrocatalytic oxidation toward MTX and FA with high sensitivity, stability and long life. Good separation of MTX and FA was demonstrated by IC on an anion-exchange column with phosphate buffer solution (PBS) as eluent. Under the optimal conditions, the linear ranges were from 0.01 to 20mg/L for both MTX and FA with correlation coefficients r ≥ 0.9994. The obtained detection limits (LODs) for MTX and FA were 0.2 and 0.4 μg/L (S/N=3), respectively. The method has been successfully applied to the determination of MTX and FA in plasma and urine of patients of rheumatoid arthritis.
25117655 Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory cytokines 2015 Jan BACKGROUND: Thrombopoietin (TPO) is a liver-produced protein that drives megakaryocyte maturation. TPO regulates platelet production and can increase platelet and endothelial reactivity. We investigated the relationship between TPO and the occurrence of thrombocytopenia and thrombosis in patients with systemic lupus erythematosus (SLE). METHODS: We undertook a cohort study of SLE patients (n = 98) with clinical data collected simultaneously with sampling for TPO, inflammatory cytokines and autoantibody detection. TPO levels were measured by sandwich ELISA with patients with rheumatoid arthritis (RA) (n = 100) and controls (n = 79) as comparators. Disease associations were evaluated using non-parametric methods. RESULTS: TPO levels in SLE (median 8 pg/ml, mean 326, range 8992) were moderately increased compared with RA (median 8 pg/ml, mean 100, range 1659, p = 0.07) and controls (median 8, mean 94, range 2088, p = 0.1). Among SLE patients, TPO levels did not correlate with platelet count or levels of antiphospholipid antibodies. The prevalence of thrombocytopenic episodes, thrombotic events or active disease was not increased in patients with high TPO levels. TPO levels correlated with MIP-1α (Rs 0.56, p < 0.001), IL6 (Rs 0.26, p = 0.02) and IL4 (Rs 0.29, p = 0.01), and inversely correlated to C4 (Rs -0.23, p = 0.04). MIP-1α was the strongest independent predictor of increased TPO levels. CONCLUSION: TPO levels are elevated in 20% of patients, but are not closely related to the occurrence of thrombocytopenia or thrombosis in SLE. MIP1-alpha is the main factor driving higher TPO levels among patients with SLE, likely through its inhibitory effect on megakaryocyte function.
23903583 Bisphosphonate-related osteonecrosis of jaw (BRONJ) in Japanese population: a case series 2013 Bisphosphonate-related osteonecrosis of the jaw (BRONJ) affects quality of life and is an important problem for dentists. A Japanese position paper on BRONJ was published in 2010. The purpose of this study was to review clinical data on the treatment of BRONJ obtained at the Clinic of Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba Hospital to further our understanding of this disease. A total of 13 patients (6 men and 7 women) were included. All the patients included in this study had received Bisphosphonate (BP) therapy and had BRONJ. Five of them (38.5%) had received oral BP therapy for osteoporosis, while the remaining 8 (61.5%) had received parenteral BP therapy for bone metastases from breast or prostate cancer. Osteoporosis patients were treated with risedronate or alendronate. Breast or prostate cancer patients were treated with zoledronate. Two patients with rheumatoid arthritis were treated with corticosteroid. Three patients had diabetes mellitus. Eleven patients were treated with antibiotics, while 5 underwent surgical treatment. Discontinuation of BP was recorded in 7 patients during dental treatment. Sequestration was observed in 6 patients during an 11-month follow-up. Eventually, healing and improvement of the oral mucosa were observed in 3 patients. The current standard treatment for BRONJ does not always provide good results. It is necessary to accumulate further clinical data to establish more effective treatment strategies for BRONJ.
24368727 Impact of concomitant low-dose aspirin on the safety and tolerability of naproxen and esom 2014 Jul Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤ 325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9%, respectively, for LDA users, 6.4 vs 22.4%, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8% for LDA users, 0.6 vs 5.3% for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5%, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5%, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1%; EC naproxen, 31.7%; celecoxib, 22.1%; placebo, 23.2%. Among LDA non-users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 20. %; EC naproxen, 36.6%; celecoxib, 18.5%; placebo, 18.9%. For LDA users, incidences of cardiovascular AEs were: NAP/ESO, 3.0%; EC naproxen, 1.0%; celecoxib, 0%; placebo, 0%. For LDA non-users, incidences of cardiovascular AEs were: NAP/ESO, 1.0%; EC naproxen, 0.6%; celecoxib, 0.3%; placebo, 0%. NAP/ESO appears to be well-tolerated in patients receiving concomitant LDA. For LDA users, AE incidence was less than that observed for EC naproxen. For most AE categories, incidences were similar among NAP/ESO, celecoxib and placebo groups. The safety of NAP/ESO appeared similar regardless of LDA use.
25650856 Intake of antioxidants in patients with rheumatoid arthritis. 2014 Nov OBJECTIVE: to investigate dietary intake of antioxidants in patients with rheumatoid arthritis. METHODS: this is a cross-sectional case series study with 53 women accompanied at the Rheumatology Outpatient Clinic, Hospital das Clínicas/UFPE, from January to October 2012. Demographic and anthropometric parameters (weight, height, body mass index, weight change) were collected by means of a form. The assessment of food consumption was conducted using a semi-quantitative food frequency survey, analyzed according to a food composition table. Database construction and statistical analysis were performed using Excel and SPSS version 18.0, using chi-squared test, Anova, and Student's t-test, at a confidence level of 5%. RESULTS: the sample was composed of 53 women with a mean age of 54.51 ± 4.24 years and BMI of 25.97 ± 5.94 kg/m². In the sociodemographic variables, statistically significant differences in origin, occupation, and income were observed. Daily consumption showed significance for vitamins A, C, and zinc. In adults, vitamins A and C were in accordance with recommendations, while in the elderly a low intake of vitamin E and selenium was observed. The relation between vitamin E and origin was significant. CONCLUSION: the sample was composed of 53 women with a mean age of 54.51 ± 4.24 years and BMI of 25.97 ± 5.94 kg/m². In the sociodemographic variables, statistically significant differences in origin, occupation, and income were observed. Daily consumption showed significance for vitamins A, C, and zinc. In adults, vitamins A and C were in accordance with recommendations, while in the elderly a low intake of vitamin E and selenium was observed. The relation between vitamin E and origin was significant.
24315997 Intracellular complement activation sustains T cell homeostasis and mediates effector diff 2013 Dec 12 Complement is viewed as a critical serum-operative component of innate immunity, with processing of its key component, C3, into activation fragments C3a and C3b confined to the extracellular space. We report here that C3 activation also occurred intracellularly. We found that the T cell-expressed protease cathepsin L (CTSL) processed C3 into biologically active C3a and C3b. Resting T cells contained stores of endosomal and lysosomal C3 and CTSL and substantial amounts of CTSL-generated C3a. While "tonic" intracellular C3a generation was required for homeostatic T cell survival, shuttling of this intracellular C3-activation-system to the cell surface upon T cell stimulation induced autocrine proinflammatory cytokine production. Furthermore, T cells from patients with autoimmune arthritis demonstrated hyperactive intracellular complement activation and interferon-γ production and CTSL inhibition corrected this deregulated phenotype. Importantly, intracellular C3a was observed in all examined cell populations, suggesting that intracellular complement activation might be of broad physiological significance.